vitamin-b-12 and Cardiovascular-Diseases

The evidence of relationship between dietary intake of folate, vitamin B6 and vitamin B12 and cardiovascular diseases (CVD) in UK populations is limited. We aimed to analyze the association of dietary intake of folate, vitamin B6, and vitamin B12 with CVD events [stroke, myocardial infarction (MI)] and CVD mortality.. We included 115,664 participants, aged 40-70 years, with no CVD events or cancer at baseline, enrolled between 2006 and 2010 and followed up to the end of 2018. Dietary intake was measured with an online 24-h dietary assessment. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations.. After multivariate adjustment, higher dietary folate intake was inversely associated with CVDs with hazard ratios of 0.99, 0.92, and 0.88 in groups 2-4 compared with group 1 (the lowest group); inversely associated with stroke with hazard ratios of 0.94, 0.90, and 0.86 groups 2-4 compared to group 1 (lowest group); inversely associated with MI with hazard ratios of 1.01, 0.90 and 0.86 groups 2-4 compared to group 1 (lowest group); inversely associated with CVD mortality with hazard ratios of 0.95, 0.80 and 0.74 Groups 2-4 compared to group 1 (lowest group). Each tablespoon/day higher intake of raw vegetable intake, pieces/day higher intake of fresh fruit intake bowls/week higher intake of cereal intake, and g/day higher intake of dietary fiber were associated with higher intakes of folate every 0.02,0.06,0.05, and 0.08 SD, respectively. E-value analysis suggested robustness to unmeasured confounding.. Each increase in folate intakes was related to 5% lower risks of total CVD events and 10% lower risks of CVD mortality. Our findings support that strengthening dietary folate intake as a primary prevention strategy for CVD events and CVD mortality.

Topics: Cardiovascular Diseases; Folic Acid; Humans; Myocardial Infarction; Prospective Studies; Risk Factors; Stroke; United Kingdom; Vitamin B 12; Vitamin B 6

Thromboembolic manifestations are relatively frequent in patients with intermediate/severe hyperhomocysteinemia (>30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15-30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice.Homocysteine-lowering trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half of the cases and related to B12 and/or folate deficiency and Addison/Biermer disease in 55% of these cases.In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for B vitamin deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the effect of lowering homocysteine according to hyperhomocysteinemia categories at baseline.

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12

Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn, leads to cardiovascular injury and increases morbidity. Different studies have shown alterations in the levels of homocysteine with respect to multiple disease states. Whether this non-traditional marker is associated with cardiovascular injury or not is subject to conflicting results. The purpose of this systematic review is to evaluate the role of homocysteine in the formation of atherosclerotic cardiovascular disease in young adults and children.. This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). A search was done using specific keywords, including "homocysteine", "coronary artery disease", and "atherosclerosis", amongst several others, from the databases of PubMed, COCHRANE, and EBSCO. The data items included the diseased sample population along with the intervention used, or investigations carried out and the findings of the studies. Finally, 35 eligible studies were included.. Young patients with atherosclerotic cardiovascular disease were more likely to have elevated levels of homocysteine compared to elderly patients. Elevated levels of homocysteine have been observed with several genetic, nutritional deficiencies, and autoimmune states such as rheumatoid arthritis. On the other hand, decreased levels of homocysteine have been observed after certain intervention treatments, such as oral contraceptive pills, L-thyroxine, and even the adoption of certain diets. In the majority of studies, whenever homocysteine levels were higher than normal, this was reflected by an increased carotid intima-media thickness.. Homocysteine has a high correlation with atherosclerotic cardiovascular disease in young and overweight patients. In addition, the relationship of homocysteine with smoking, genetic polymorphism, specific hormonal and renal disorders, nutritional deficiencies (vitamin B12 and folic acid), and the use of specific medicines are among the other recurring findings. Given that many of these studies focus only on women, the relationship between homocysteine and atherosclerotic cardiovascular diseases in males is still unclear. Whether males are more prone to hyperhomocysteinemia needs to be assessed. Still, precise processes underlying variations in homocysteine in relation to all influencing factors are unclear and need further studies.

Topics: Aged; Atherosclerosis; Cardiovascular Diseases; Carotid Intima-Media Thickness; Child; Endothelial Cells; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Prognosis; Risk Factors; Vitamin B 12

Hyperhomocysteinemia is an independent risk factor for atherosclerosis, even in early childhood. A mutation in genes that code homocysteine metabolism enzymes or deficiency of specific vitamin cofactors may cause hyperhomocysteinemia. Vitamin B complex has been correlated with serum homocysteine levels. Any abnormality in its metabolism or nutritional deficiency may lead to hyperhomocysteinemia. Both vitamin B complex and homocysteine levels are partly genetically determined. Specifically, the most studied polymorphism is 677T-C in exon 5 of the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene, which plays an important role in folate's metabolism. This polymorphism has been shown to be correlated with hypertension and cardiovascular disease. Polymorphisms in methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene have also been correlated with increased risk for coronary artery disease. Other common serious polymorphisms regard the area with high linkage disequilibrium, including the neuroblastoma breakpoint family, NBPF3 gene, and ~ 12-50 kb upstream of the tissue nonspecific alkaline phosphatase gene. Finally, the polymorphisms which have been mostly associated with vitamin B12 concentration are the rs11254363 polymorphism at intron 52 of the intrinsic factor vitamin B12 receptor of the CUBN and the rs526934 polymorphism at intron 8 of transcobalamin I. To sum up, several polymorphisms have already been associated with vitamin B complexes and therefore homocysteine level, highlighting the complex nature of vitamin B genetics.

Topics: Aminohydrolases; Cardiovascular Diseases; Folic Acid; Formate-Tetrahydrofolate Ligase; Homocysteine; Humans; Hyperhomocysteinemia; Methylenetetrahydrofolate Dehydrogenase (NADP); Methylenetetrahydrofolate Reductase (NADPH2); Multienzyme Complexes; Neoplasm Proteins; Polymorphism, Genetic; Receptors, Cell Surface; Vitamin B 12; Vitamin B Complex

Plasma homocysteine (HCY) is an established risk factor for cardiovascular disease CVD and stroke. However, more than two decades of intensive research activities has failed to demonstrate that Hcy lowering through B-vitamin supplementation results in a reduction in CVD risk. Therefore, doubts about a causal involvement of hyperhomocysteinemia (HHcy) and B-vitamin deficiencies in atherosclerosis persist. Existing evidence indicates that HHcy increases oxidative stress, causes endoplasmatic reticulum (ER) stress, alters DNA methylation and, thus, modulates the expression of numerous pathogenic and protective genes. Moreover, Hcy can bind directly to proteins, which can change protein function and impact the intracellular redox state. As most mechanistic evidence is derived from experimental studies with rather artificial settings, the relevance of these results in humans remains a matter of debate. Recently, it has also been proposed that HHcy and B-vitamin deficiencies may promote CVD through accelerated telomere shortening and telomere dysfunction. This review provides a critical overview of the existing literature regarding the role of HHcy and B-vitamin deficiencies in CVD. At present, the CVD risk associated with HHcy and B vitamins is not effectively actionable. Therefore, routine screening for HHcy in CVD patients is of limited value. However, B-vitamin depletion is rather common among the elderly, and in such cases existing deficiencies should be corrected. While Hcy-lowering with high doses of B vitamins has no beneficial effects in secondary CVD prevention, the role of Hcy in primary disease prevention is insufficiently studied. Therefore, more intervention and experimental studies are needed to address existing gaps in knowledge.

Topics: Aged; Cardiovascular Diseases; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B Complex; Vitamin B Deficiency

We reviewed reasons for the high cardiovascular risk (CVD) of patients with chronic kidney disease (CKD), and explored alternatives to treatment of traditional risk factors to reduce CVD in CKD.. Besides traditional risk factors, patients with CKD are exposed to uremic toxins of two kinds: systemically derived toxins include asymmetric dimethylarginine (ADMA), total homocysteine (tHcy), thiocyanate, tumor necrosis factor alpha, and interleukin 6. Gut-derived uremic toxins (GDUT), products of the intestinal microbiome, include hippuric acid, indoxyl sulfate, p-cresyl sulfate, p-cresyl glucuronide, phenylacetylglutamine, and trimethylamine N-oxide (TMAO). Cyanocobalamin is toxic in patients with CKD. Approaches to reducing plasma levels of these uremic toxins would include diet to reduce GDUT, kidney transplantation, more intensive dialysis, and vitamin therapy to lower tHcy with methylcobalamin rather than cyanocobalamin. The high CVD risk in CKD requires consideration of therapies beyond treatment of traditional risk factors.

Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Humans; Renal Insufficiency, Chronic; Toxins, Biological; Vitamin B 12

The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the

Topics: Carbon Cycle; Cardiovascular Diseases; Diabetes Mellitus; Epigenesis, Genetic; Female; Folic Acid; Heart Disease Risk Factors; Homocysteine; Humans; Inflammation; Male; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Vascular Diseases; Vitamin B 12

Diabetes mellitus (DM) can lead to the development of macro- and microvascular complications. Homocysteine (Hcy) may play a role in the development of cardiovascular (CV) diseases (CVDs). The role of Hcy in the development of the vascular complications associated with DM is not clearly defined. Despite a strong initial assumption regarding the importance of Hcy in DM and its complications, over time "enthusiasm has waned" because several studies showed unconvincing and occasionally contradictory results. A universal conclusion is not easy to draw given the diversity of studies (e.g. number of patients, design, folic acid and vitamin B status, ethnic differences, genetic background). For some complications, most results encourages further investigation. Impaired renal function is a major independent determinant of high total Hcy (tHcy) levels. However, the role of hyperhomocysteinaemia (HHcy) in the development of diabetic kidney disease (DKD) has yet to be determined. Hcy-lowering therapies can significantly decrease Hcy levels but their effects on CVD risk reduction are conflicting. Further studies are needed to determine the influence of Hcy-lowering therapy on CVD risk reduction, especially in patients with DM.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Diabetic Nephropathies; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B 12

To discuss the overall and latest observations of the effect of diet, lifestyle, supplements, and some prescription heart healthy medications for prostate cancer prevention.. The concept of maximizing heart health to prevent aggressive prostate cancer continues to be solidified with the addition of more prospective observational and randomized controlled trial data. Heart healthy is prostate healthy, and heart unhealthy is prostate unhealthy. The primary goal of reducing the risk of all-cause and cardiovascular disease (CVD) morbidity and mortality also coincides with maximizing prostate cancer prevention. The obesity epidemic in children and adults along with recent diverse research has only strengthened the nexus between heart and prostate health. Greater dietary adherence toward a variety of healthy foods is associated with a graded improved probability of CVD and potentially aggressive cancer risk reduction. Preventing prostate cancer via dietary supplements should encourage a "first do no harm," or less is more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer. Supplements to reduce side effects of some cancer treatments appear to have more encouraging data. A discussion of quality (QC) before utilizing any pill also requires attention. Medications or interventions that potentially improve heart health including statins, aspirin, and metformin (S.A.M.), specific beta-blocker medications, and even preventive vaccines are in general generic, low-cost, "natural," and should continue to garner research interest. A watershed moment in medical education has arrived where the past perception of a diverse number of trees seemingly separated by vast distances, in reality, now appear to exist within the same forest.

Topics: Cardiovascular Diseases; Diet; Dietary Supplements; Fish Oils; Folic Acid; Food; Health Status; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Male; Prescription Drugs; Prostatic Neoplasms; Quality Control; Risk Reduction Behavior; Vitamin B 12

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.

Topics: Betaine; Cardiovascular Diseases; Choline; Dietary Supplements; DNA Methylation; Eating; Epigenesis, Genetic; Folic Acid; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Methionine; Nutritional Physiological Phenomena; Renal Insufficiency, Chronic; Uremia; Vitamin B 12; Vitamin B 6

Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to tetrahydrofolate, which is required for DNA and RNA synthesis. Deficiency of either of the cobalamin (Cbl) and/or folate cofactors results in elevated Hcy and megaloblastic anemia. Elevated Hcy is a sensitive biomarker of Cbl and/or folate status and more specific than serum vitamin assays. Elevated Hcy normalizes when the correct vitamin is given. Elevated Hcy is associated with alcohol use disorder and drugs that target folate or Cbl metabolism, and is a risk factor for thrombotic vascular disease. Elevated methionine and cystathionine are associated with liver disease. Elevated Hcy, cystathionine, and cysteine, but not methionine, are common in patients with chronic renal failure. Higher cysteine predicts obesity and future weight gain. Serum S-adenosylhomocysteine (AdoHcy) is elevated in Cbl deficiency and chronic renal failure. Drugs that require methylation for catabolism may deplete liver S-adenosylmethionine and raise AdoHcy and Hcy. Deficiency of Cbl or folate or perturbations of their metabolism cause major changes in sulfur amino acids.

Topics: Alcoholism; Amino Acids, Sulfur; Anemia, Megaloblastic; Biomarkers; Cardiovascular Diseases; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Liver Diseases; Nutritional Status; Obesity; S-Adenosylhomocysteine; Vitamin B 12; Vitamin B 12 Deficiency

Patients with psoriasis are at increased risk for cardiovascular comorbidities. Previous studies examined the possible contribution of serum homocysteine, folate and vitamin B. To perform a systematic review and meta-analysis of studies on serum homocysteine, folate and vitamin B. Online databases were searched on 15 February 2018 to include studies comparing serum homocysteine, folate and vitamin B. A comprehensive literature search identified 24 studies eligible for inclusion. Compared with controls, patients with psoriasis had a significantly higher serum homocysteine level [SMD 0·41, 95% confidence interval (CI) 0·21-0·61; I. Patients with psoriasis might have higher serum homocysteine and lower folate levels than control patients without psoriasis. However, due to significant heterogeneity and other limitations, the associations require further examinations in more studies.

Topics: Biomarkers; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Psoriasis; Vitamin B 12

Epidemiological studies established that elevated homocysteine, an important intermediate in folate, vitamin B

Topics: Animals; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12

Patients affected by chronic kidney disease (CKD) or end-stage renal disease (ESRD) experience a huge cardiovascular risk and cardiovascular events represent the leading causes of death. Since traditional risk factors cannot fully explain such increased cardiovascular risk, interest in non-traditional risk factors, such as hyperhomocysteinemia and folic acid and vitamin B12 metabolism impairment, is growing. Although elevated homocysteine blood levels are often seen in patients with CKD and ESRD, whether hyperhomocysteinemia represents a reliable cardiovascular and mortality risk marker or a therapeutic target in this population is still unclear. In addition, folic acid and vitamin B12 could not only be mere cofactors in the homocysteine metabolism; they may have a direct action in determining tissue damage and cardiovascular risk. The purpose of this review was to highlight homocysteine, folic acid and vitamin B12 metabolism impairment in CKD and ESRD and to summarize available evidences on hyperhomocysteinemia, folic acid and vitamin B12 as cardiovascular risk markers, therapeutic target and risk factors for CKD progression.

Topics: Biomarkers; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Risk Factors; Vitamin B 12

Meat is an important food for human nutrition, by especially providing high-quality protein and also some essential micronutrients, in front iron, zinc, and vitamin B

Topics: Animals; Cardiovascular Diseases; Cattle; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Diet, Healthy; Dietary Proteins; Evidence-Based Medicine; Food, Preserved; Humans; Iron, Dietary; Meat; Meat Products; Meta-Analysis as Topic; Mortality; Nutritive Value; Risk Factors; Sheep, Domestic; Sus scrofa; Vitamin B 12; Zinc

Cardiovascular disease, which includes coronary artery disease, stroke and peripheral vascular disease, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor for cardiovascular disease is an elevated circulating total homocysteine level. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events has been investigated. This is an update of a review previously published in 2009, 2013, and 2015.. To determine whether homocysteine-lowering interventions, provided to patients with and without pre-existing cardiovascular disease are effective in preventing cardiovascular events, as well as reducing all-cause mortality, and to evaluate their safety.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to 1 June 2017), Embase (1980 to 2017 week 22) and LILACS (1986 to 1 June 2017). We also searched Web of Science (1970 to 1 June 2017). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.. We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.. We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB). We measured statistical heterogeneity using the I. In this third update, we identified three new randomised controlled trials, for a total of 15 randomised controlled trials involving 71,422 participants. Nine trials (60%) had low risk of bias, length of follow-up ranged from one to 7.3 years. Compared with placebo, there were no differences in effects of homocysteine-lowering interventions on myocardial infarction (homocysteine-lowering = 7.1% versus placebo = 6.0%; RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I. In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo.There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial.Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.

Topics: Angina Pectoris; Cardiovascular Diseases; Cause of Death; Folic Acid; Humans; Hyperhomocysteinemia; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex

People with end-stage kidney disease (ESKD) have high rates of cardiovascular events. Randomised controlled trials (RCTs) of homocysteine-lowering therapies have not shown reductions in cardiovascular event rates in the general population. However, people with kidney disease have higher levels of homocysteine and may have different mechanisms of cardiovascular disease. We performed a systematic review of the effect of homocysteine-lowering therapies in people with ESKD.. To evaluate the benefits and harms of established homocysteine lowering therapy (folic acid, vitamin B6, vitamin B12) on all-cause mortality and cardiovascular event rates in patients with ESKD.. We searched Cochrane Kidney and Transplant's Specialised Register to 25 January 2016 through contact with the Information Specialist using search terms relevant to this review.. Studies conducted in people with ESKD that reported at least 100 patient-years of follow-up and assessed the effect of therapies that are known to have homocysteine-lowering properties were included.. Two authors independently extracted data using a standardised form. The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, incident cardiovascular disease (fatal and nonfatal myocardial infarction and coronary revascularisation), cerebrovascular disease (stroke and cerebrovascular revascularisation), peripheral vascular disease (lower limb amputation), venous thromboembolic disease (deep vein thrombosis and pulmonary embolism), thrombosis of dialysis access, and adverse events. The effects of homocysteine-lowering therapies on outcomes were assessed with meta-analyses using random-effects models. Prespecified subgroup and sensitivity analyses were conducted.. We included six studies that reported data on 2452 participants with ESKD. Interventions investigated were folic acid with or without other vitamins (vitamin B6, vitamin B12). Participants' mean age was 48 to 65 years, and proportions of male participants ranged from 50% to 98%.Homocysteine-lowering therapy probably leads to little or no effect on cardiovascular mortality (4 studies, 1186 participants: RR 0.93, 95% CI 0.70 to 1.22). There was no evidence of heterogeneity among the included studies (I² = 0%). Homocysteine-lowering therapy had little or no effect on all-cause mortality or any other of this review's secondary outcomes. All prespecified subgroup and sensitivity analyses demonstrated little or no difference. Reported adverse events were mild and there was no increase in the incidence of adverse events from homocysteine-lowering therapies (3 studies, 1248 participants: RR 1.12, 95% CI 0.51 to 2.47; I(2) = 0%). Overall, studies were assessed as being at low risk of bias and there was no evidence of publication bias.. Homocysteine-lowering therapies were not found to reduce mortality (cardiovascular and all-cause) or cardiovascular events among people with ESKD.

Topics: Aged; Cardiovascular Diseases; Cause of Death; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Stroke; Venous Thrombosis; Vitamin B 12; Vitamin B 6; Vitamin B Complex

To evaluate the effect of the combined supplementation of folic acid, vitamin B12 and B6 on the risk of cardio-cerebrovascular diseases.. The literatures of randomized control trials about the relationship between the combined supplementation of folic acid, vitamin B12 and B6 and risk of cardio-cerebrovascular diseases from 1980 to 2014 were retrieved, and the eligible studies were screened for a Meta-analysis. The study indicators were the incidences of cardiovascular disease events, myocardial infarction and stroke. The cffect indicators were relative risk(RR)and 95% confidence interval(CI). Jadad score was used for the quality evaluation of the trials used in the study.. The literatures of 11 randomized control trials, involving 26 395 patients, were used in the Meta-analysis. The combined supplementation of B vitamins had no effect on the incidence of cardiovascular disease events(RR=1.00, 95% CI: 0.94-1.07)based on 8 studies. The combined supplementation of B vitamins had no effect on the incidence of myocardial infarction(RR= 1.03, 95% CI: 0.94-1.13)based on 9 studies. The combined supplementation of B vitamins could reduce the incidence of stroke by 14%(RR=0.86, 95%CI: 0.78-0.95)based on 9 studies. Compared with the control group, Taking folic acid combined with vitamin B12 and B6 could reduce the level of homocysteine by 2.53 μmol/L(95%CI:-3.93--1.12). Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events. But the subgroup analysis for stroke showed that with the extension of follow-up time, the supplementation of B vitamins could reduce the risk of stroke. The effect of folic acid and B12 in small dosage seemed more significant in the prevention of stroke, while the preventive effect of B6 increased with increasing dosage. The preventive effect of combined supplementation of B vitamins was more significant for the patients with a history of cardio-cerebrovascular diseases.. Taking folic acid combined with vitamin B6 and B12 might have no significant effect on the incidences of cardio-cerebrovascular disease events and myocardial infarction, but could lower the risk of stroke and the level of homocysteine.

Topics: Adult; Aged; Cardiovascular Diseases; Dietary Supplements; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Incidence; Middle Aged; Randomized Controlled Trials as Topic; Risk; Vitamin B 12; Vitamin B 6; Vitamin B Complex

To evaluate the effects of folic acid, vitamin B(6) and B(12) supplementation on plasma homocysteine level and risk of cardiovascular disease.. The databases, including Embase, Pubmed, Ovid, Biosis, China National Knowledge Infra-structure (CNKI), Wanfang Data, VIP Database for Chinese Technical Periodical (VIP), Chinese Biomedical Literature Database (CMB), were searched to identify random control trials between February 1994 to February 2014 on the effect of folic acid, vitamin B(6) and B(12) supplementation on plasma homocysteine level and risk of cardiovascular disease. The screening, data extraction and quality assessment were conducted in accordance with the inclusion and exclusion criteria by two reviewers independently. The software Review Manager 5.2 was used. Funnel plots and Egger's regression test were applied to evaluate the publication bias.. Data from 12 studies including 34 481 patients were analyzed using a fixed-effects model. Funnel plot and Egger's test (P > 0.10) confirmed the absence of publication bias. No statistically significant heterogeneity was detected on testing after excluding the sources of heterogeneity (chi-square test, I < 2 < 50%). Baseline homocysteine levels were similar between the placebo and folic acid, vitamin B(6) and B(12) groups (all P > 0.05). Mean homocysteine levels were significantly lower with folic acid, vitamin B(6) and B(12) therapy compared with placebo during follow-up (all P < 0.05). The pooled relative risks with 95% confidence intervals of outcomes for patients treated with folic acid, vitamin B(6) and B(12) supplementation compared with placebo were 0.98 (0.93-1.03) for cardiovascular event, 0.97 (0.87-1.07) for coronary artery disease, 1.00 (0.92-1.08) for myocardial infarction and 0.92 (0.82-1.03) for cardiovascular death.. Folic aicd combined with vitamin B(6) and B(12) treatment significantly reduced plasma homocysteine level, but did not affect the risk of cardiovascular disease. Thus, folic acid combined with vitamin B(6) and B(12) should not be recommended as secondary prevention of cardiovascular diseases.

Topics: Asian People; Cardiovascular Diseases; China; Clinical Trials as Topic; Folic Acid; Humans; Myocardial Infarction; Secondary Prevention; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Homocysteine (Hcy) is an endogenous, non-structural protein, a sulfur-containing amino acid emerging on the pathway of methionine and cysteine, actively involved in numerous biochemical reactions. Total concentration of homocysteine in plasma of healthy humans is low and its level is between 5.0 and 15.0 mmol/l, assessed with the use of HPLC, or 5.0-12.0 mmol/l, using immunoassay methods. Higher concentration of this amino acid in blood is called hyperhomocysteinemia. Hyperhomocysteinemia is significantly correlated with cardiovascular disease and its complications: heart attacks and strokes. It is believed that hyperhomocysteinemia damages endothelial cells, reduces the flexibility of vessels, and adversely affects the process of hemostasis. In addition, hyperhomocysteinemia enhances the adverse effects of risk factors such as hypertension, smoking, and impaired glucose, lipid and lipoprotein metabolism, as well as promoting the development of inflammation. The concentration of homocysteine can be effectively lowered by supplementation with folic acid and vitamins B12 and B6. However, intervention studies conducted in the past decade did not confirm the clinical benefit of vitamin therapy lowering the level of homocysteine in blood of patients with cardiovascular disease. Moreover, there is not clear evidence from genetic studies that the presence of the gene for MTFHR polymorphism 677C>T, which is one of the most common causes of hyperhomocysteinemia, is also associated with the development of cardiovascular disease. These results led the researchers to discuss the role of homocysteine in the development and treatment of cardiovascular disease as well as the need for further research on this issue.

Topics: Cardiovascular Diseases; Causality; Comorbidity; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Myocardial Infarction; Risk Factors; Vitamin B 12

Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases.

Topics: Cardiovascular Diseases; China; Diet, Vegetarian; Dietary Supplements; Food, Fortified; Humans; India; Nutritional Status; Prevalence; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency

to determine whether the administration of folic acid, vitamin B6 and vitamin B12 would lead to reduction of cardiovascular complication and mortality among CKD patients.. a search was conducted on PubMed and Google. The selection of title and abstract was conducted using inclusion and exclusion criterias, which led to six relevant articles. The selected studies were critically appraised for its validity, importance and applicability.. the administration of folic acid and vitamin B reduce homocysteine level among CKD patients. Despite homocysteine level reduction, all six studies reported similar findings that folic acid and vitamin B supplementation did not significantly reduce cardiovascular complication and mortality.. treatment with folic acid, vitamin B6 and vitamin B12 did not reduce cardiovascular complication and mortality among CKD patients.

Topics: Cardiovascular Diseases; Evidence-Based Medicine; Folic Acid; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

It is now 30 years since the first publications stating that supplementation with folate could prevent neural tube defects appeared and 20 years since the definitive data, including prevention of other birth defects. Since then epidemiological studies and animal experiments have identified folate as a molecule at the crossroads of neural development. Fortification of food has greatly reduced the incidence of spina bifida. Much interest has focussed on long-term sequelae in children born to mothers severely deprived of folate (and other nutrients) such as during the Dutch Hunger Winter of 1944 and in poor parts of the world. In addition, deficiency in folate and B12 are increasingly discussed as a possible contributing factor in dementia and congenital orofacial and heart malformations. The year 2011 saw the publication of a study that implicated low folate intake in poorer school performance of adolescents as judged by school marks. This has enormous social implications but needs confirmation from other settings. This review assesses the current state of evidence and sets the data in context of whether folate has a role in the development and plasticity of the nervous system even after birth, with particular emphasis on childhood and adolescence.

Topics: Adolescent; Cardiovascular Diseases; Child; Child, Preschool; Cognition Disorders; Educational Status; Embryonic Development; Folic Acid; Folic Acid Deficiency; Humans; Nervous System; Neural Tube Defects; Socioeconomic Factors; Vitamin B 12

Peripheral arterial disease (PAD) has not been as extensively investigated as other cardiovascular diseases. However, the available data suggest that nutrition-based treatment strategies have the potential to reduce the cost-economic burden of PAD substantially. Abdominal obesity is associated with PAD and prospective and cross-sectional studies have shown that a low dietary intake of folate and reduced synthesis of vitamin D are associated with an increased risk of PAD and severe walking impairment in patients who have the disease. However, dietary patterns that are associated with decreased cardiovascular risk might protect against PAD. A small number of clinical trials have provided evidence that increased intakes of niacin and insoluble fiber might be associated with decreased levels of LDL cholesterol and thrombogenic biomarkers, as well as increased serum levels of HDL cholesterol in patients with PAD. However, little evidence that antioxidants, vitamins B(6) and B(12), or essential fatty acid supplements improve clinical outcomes in these patients exists. Overall, data on the effects of nutrition, body composition, and nutritional supplementation on the risk, progression, and prognosis of PAD are scarce. Further research into these areas is required to allow the development of evidence-based nutritional guidelines for the prevention and treatment of the disease.

Topics: Body Composition; Cardiovascular Diseases; Dietary Supplements; Disease Progression; Ethnicity; Folic Acid; Humans; Nutritional Status; Obesity, Abdominal; Peripheral Arterial Disease; Prognosis; Risk Factors; Vitamin B 12; Vitamin D

To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria.. A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events.. Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis--a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16-2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02-2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00-1.00 and HR = 1.15; 95% CI = 1.08-1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00-1.00). No association between study outcomes and vitamin B12 levels was found in four other studies.. Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Meta-Analysis as Topic; Risk Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine is a sulfur-containing aminoacid produced during metabolism of methionine. Since 1969 the relationship between altered homocysteine metabolism and both coronary and peripheral atherotrombosis has been known; in recent years experimental evidences have shown that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Several mechanisms by which elevated homocysteine impairs vascular function have been proposed, including impairment of endothelial function, production of Reactive Oxygen Species (ROS) and consequent oxidation of low-density lipids. Folic acid and B vitamins, required for remethylation of homocysteine to methionine, are the most important dietary determinants of homocysteinemia and daily supplementation typically lowers plasma homocysteine levels. Recently, large-scale intervention trials have been conducted to determine whether lowering homocysteine concentrations through B vitamins supplementation can decrease cardiovascular risk in healthy subjects or improve survival in patients with coronary heart disease. Some of these trials found no significant beneficial effects of combined treatment with folate and vitamin B(12), with or without vitamin B(6), in spite of adequate homocysteine lowering. In conclusion, it is still unclear whether decreasing plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk.

Topics: Animals; Cardiovascular Diseases; Folic Acid; Humans; Hyperhomocysteinemia; Risk Factors; Risk Reduction Behavior; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Vitamin B(12) is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B(12), and to evaluate the causes and consequences of sub-clinical vitamin B(12) deficiency. Vitamin B(12) deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B(12) deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B(12) is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health.

Topics: Absorption; Biomarkers; Cardiovascular Diseases; Cognition Disorders; Female; Food; Humans; Male; Neural Tube Defects; Nutritional Requirements; Osteoporosis; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin B 12 Deficiency

There has been a great interest in the last decades about the clinical significance of elevated total plasma homocysteine (tHcy), and especially its possible association with an increased cardiovascular risk. Measurement of tHcy is clearly indicated when homocystinuria is suspected in young or adult patients (in the presence of a severe, atypical or progressive myopia with ectopia lentis and/or venous thromboembolism and/or severe, premature or atypical atherosclerotic vascular disease) and in the evaluation of vitamin B12 and/or folic acid deficiencies. The current evidence does not support either the screening measurement of tHcy or the treatment with vitamin B12 and/or folic acid supplementation in patients with cardiovascular disease. It is important to remember that it remains to be proved whether the long-term administration of folic acid at pharmacological doses is safe.

Topics: Adolescent; Adult; Cardiovascular Diseases; Child; Child, Preschool; Ectopia Lentis; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Homocystinuria; Humans; Hyperhomocysteinemia; Infant; Infant, Newborn; Life Style; Male; Middle Aged; Myopia; Pregnancy; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. However, it is not known whether this also applies to patients with end-stage renal disease.. Meta-analysis of retrospective (11 studies including 1,506 individuals), prospective observational studies (12 studies including 1,975 individuals), and intervention trials (5 studies including 1,642 dialysis patients). Analyses were carried out separately, according to the study design.. Studies of patients with end-stage renal disease treated by means of hemodialysis or peritoneal dialysis.. Studies investigating the association between total homocysteine level and cardiovascular disease or total mortality or the influence of vitamin supplementation on cardiovascular or mortality risk.. In intervention studies, vitamin preparations with folic acid alone or in combination with other vitamins, such as vitamin B(12) and B(6), were used.. In retrospective studies, cases are patients with cardiovascular diseases. Outcomes for prospective observational and intervention studies are cardiovascular events and total mortality.. In retrospective studies, there was no significant overall difference in homocysteine concentrations between cases and controls (weighted mean difference in homocysteine, 2.82 micromol/L; 95% confidence interval [CI], -2.22 to 7.86; P = 0.3). The pooled overall risk estimate for prospective observational studies suggests no association between homocysteine level (5-micromol/L increase) and total mortality (hazard ratio [HR], 1.02; 95% CI, 0.93 to 1.12; P = 0.7), but there was an association with cardiovascular events (HR, 1.09; 95% CI, 1.03 to 1.14; P = 0.001). In subgroup analysis of patients not receiving vitamins, an increase in homocysteine level was associated with increased mortality (HR, 1.07; 95% CI, 1.02 to 1.13; P = 0.01). For intervention trials with B vitamins, there was a significant risk reduction for cardiovascular disease (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = 0.02), but no risk reduction for total mortality or the composite end point including total mortality (relative risk, 1.01; 95% CI, 0.88 to 1.15; P = 0.9).. Many studies are small, which may lead to the observed heterogeneity. Some intervention trials are neither placebo controlled nor randomized. Separate analyses for specific end points and patients treated by means of hemodialysis or peritoneal dialysis were not possible.. Total homocysteine level may be a risk factor for cardiovascular events and total mortality in patients with end-stage renal disease not receiving vitamin supplementation or folic acid food fortification. There may be a potential for reducing cardiovascular disease in this population by folic acid supplementation.

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis; Retrospective Studies; Risk Factors; Vitamin B 12

Cobalamin deficiency can lead to several adverse health consequences: folate trapping in the methylation cycle and subsequent impaired DNA biosynthesis; pernicious anemia hematologically, similar to that caused by folate deficiency; elevated blood homocysteine (tHcy) (risk factor for cardiovascular disease and adverse pregnancy outcomes); and neural tube defects (NTDs). Population-wide folate status is expected to improve where folic acid fortification policies for reducing NTD occurrence are established. However, there is concern that cobalamin deficiency and its characteristic neuropathy could be masked when hematological abnormalities in risk groups such as the elderly and vegetarians are reversed through folic acid supplementation. Folate-cobalamin interactions and their impact on health are reviewed here.

Topics: Adult; Aged; Cardiovascular Diseases; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Homocysteine; Humans; Neural Tube Defects; Nutritional Requirements; Nutritional Status; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Hyperhomocysteinemia, when considered as a causal factor of vascular diseases, has been subject of much discussion. Case-control, retrospective and prospective studies have identified a relationship between high plasma concentrations of homocysteine and vascular disease. The aim of the present review was to better understand the interrelation between plasma concentrations of homocysteine and vascular diseases, as well as the involvement of classical risk factors for the disease: genetic factors, such as mutations in the genes that codify the enzymes involved in the metabolism of homocysteine, and nutritional factors, such as complex B vitamin deficiency. The publications of the main databases in health were consulted for the period 1962 to 2009. The mechanism by which hyperhomocysteinemia acts as a risk factor for vascular diseases still has not been fully clarified, but involvement of endothelial dysfunction and lipid peroxidation is suggested. The treatment of hyperhomocysteinemia is based on food supplements and medication, with folic acid and vitamins B6 and B12.

Topics: Biomarkers; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Deficiency; Vitamins

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence ofa common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Dementia; Diet; Female; Folic Acid; Fractures, Bone; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Neural Tube Defects; Pregnancy; Public Health; Risk Factors; Vitamin B 12; Vitamin B 6

During the last years, many epidemiologic studies have identified homocysteine as an independent risk factor for cardiovascular diseases like coronary events, stroke, and venous thromboembolism. Supplementation with oral folate and vitamins B6 and B12 (mainly folate) reduce plasma homocysteine levels to a significant degree. Recent clinical trials showed that vitamin supplementation leads to slower progression or even regression of atherosclerotic lesions in the carotid arteries, as confirmed by ultrasonographic measurement of carotid intima media thickness. However, the recent Vitamin Intervention for Stroke Prevention (VISP) study failed to show any clinical effect on stroke prevention. It is unclear if homocysteine-lowering therapy really has a role in the prevention of cardiovascular diseases. Large trials, which are already conducted, will probably give the definitive answer. In this review, we try to keep pace with the data that make the homocysteine hypothesis still doubtful.

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Dietary Supplements; Folic Acid; Homocysteine; Humans; Intracranial Arteriosclerosis; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6

To review recent evidence that suggests vitamin B12 is associated with risk reduction for some chronic diseases and birth defects.. A MEDLINE search from 1999 to 2007 was performed using the key word vitamin B12. The most relevant articles (129) dealt with cardiovascular disease, cancer, mental health, and birth outcomes;most studies presented level II evidence.. Vitamin B12 might confer health benefits; however, such benefits are difficult to ascertain because of the complementary functions of vitamin B12 and folic acid. Vitamin B12 might lower high homocysteine levels below a threshold level achieved by folic acid alone. Furthermore, the interactions between the nutritional environment and genotype might have an important influence on vitamin B12, chronic disease risk, and risk of neural tube defects.. Vitamin B12 might help protect against chronic disease and neural tube defects, but more research, particularly in the area of nutritional genomics, is needed to determine how vitamin B12 might augment the benefits of folic acid. Some consideration should be given to the potential value of fortifying foods with vitamin B12 in addition to the current mandatory folic acid fortification of grains.

Topics: Cardiovascular Diseases; Congenital Abnormalities; Humans; Mental Disorders; Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Dietary supplementation with folic acid and vitamin B12 lowers blood homocysteine concentrations, but it is not known if this reduces the risk of coronary heart disease and stroke.. Recent evidence suggests that the maximum reduction in plasma homocysteine concentrations is obtained with 0.8 mg of folic acid and doses of 0.2 mg and 0.4 mg of folic acid are associated with about 60 and 90%, respectively, of this maximal effect. Among 12 large trials (involving a total of 52,000 participants) that are currently assessing the effects of B-vitamins on risk of coronary heart disease and stroke, results are available for four trials involving 14 000 participants. A meta-analysis of these four trials demonstrates no beneficial effects of B-vitamins on coronary heart disease (OR 0.99; 95% CI 0.88-1.10) or stroke (OR 89; 95% CI 0.76-1.05) or the combination of coronary heart disease and stroke (OR 0.98; 95% CI 0.90-1.08). The confidence intervals around the odds ratios for these completed trials are compatible with a 10% difference in risk for coronary heart disease and 20% difference for stroke associated with a 25% lower homocysteine predicted by the observational epidemiological studies.. The results of the ongoing homocysteine-lowering trials are required before making recommendations on the use of B-vitamins for prevention of vascular disease.

Topics: Cardiovascular Diseases; Confidence Intervals; Dementia; Dose-Response Relationship, Drug; Folic Acid; Homocysteine; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B Complex

Cardiovascular diseases are commonly related to classical risk factors, but other risk markers have been identified, including homocysteine. Homocysteine is a sulphurated amino acid which derives from methionine. The causes of hyperhomocysteinemia are multifactorial, such as genetic defects, pathophysiological conditions, lifestyle and drugs-related. Hyperhomocysteinemia favors atherothrombosis through endothelial dysfunction, enhancement of inflammation and thrombophilic profile. A number of clinical and laboratory trials exist regarding the association between homocysteine levels and an increased risk of cardiovascular disease. However, the lack of homogeneity in the data, together with the high number of factors capable of influencing homocysteine plasma levels, and the disappointing results of therapeutic trials do not permit us at present to consider homocysteine as an independent and major risk factor for cardiovascular disease.

Topics: Cardiovascular Diseases; Folic Acid; Follow-Up Studies; Homocysteine; Homocystinuria; Humans; Hyperhomocysteinemia; Methionine; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Vitamin B 12; Vitamin B 6

High levels of homocysteine are associated with cerebrovascular disease, monoamine neurotransmitters, and depression of mood. A plausible hypothesis for these associations is that high homocysteine levels cause cerebral vascular disease and neurotransmitter deficiency, which cause depression of mood. The homocysteine depression hypothesis, if true, would mandate inclusions of imaging studies for cerebrovascular disease and measures of homocysteine, folate, and B12 and B6 vitamins in the clinical evaluation of older depressed patients. Longitudinal studies and clinical trials should be designed to challenge the hypothesis.

Topics: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Child; Comorbidity; Depressive Disorder; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Mutation; Neurotransmitter Agents; Stroke; Vitamin B 12; Vitamin B 6

Topics: Cardiovascular Diseases; Diet; Evidence-Based Medicine; Fatty Acids, Omega-3; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Practice Guidelines as Topic; Primary Prevention; Risk Assessment; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Studies of the general population have suggested that high homocysteine levels are associated with cardiovascular morbidity and mortality. In chronic kidney disease, homocysteine levels rise, and cardiovascular risk increases with declining kidney function. While some studies in this population have found an association between elevated homocysteine and cardiovascular risk, others have noted that this association is largely attenuated by adjustment for kidney function, and several studies of patients with kidney failure have found that lower homocysteine levels predict mortality. Homocysteine levels can be lowered with folate, vitamin B6 and vitamin B12. Three large, randomized, controlled trials of patients with pre-existing cardiovascular disease and two smaller, randomized, controlled trials of patients with kidney failure failed to detect any cardiovascular benefit from homocysteine-lowering vitamins. Several more interventional trials are ongoing, but the available data thus far do not support screening for or treatment of hyperhomocysteinemia.

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Risk Factors; Survival Rate; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Elevated homocysteine (HCY) levels can be caused by a number of factors, including folate and B-vitamin deficiency, pre-existing atherosclerotic disease, diabetes and various drugs. Epidemiological evidence, as well as data from retrospective and prospective studies, supports an association between elevated HCY levels and increased risk of cardiovascular disease (CVD). However, whether lowering HCY levels by administration of folate and vitamins B6 and B12 is associated with any significant decrease in vascular risk remains the subject of ongoing debate. Although the major studies that have reported to date show that vitamin supplementation was associated with a decrease in HCY levels, this failed to have any significant effect on cardiovascular risk. Furthermore, although some lipid-modifying treatments have been shown to increase HCY levels, there is no evidence that this attenuates or compromises the beneficial effects of such treatments on cardiovascular risk. Taken together, these data suggest that HCY is a marker, rather than a cause, of CVD and therefore do not provide support for routine screening for and treatment of elevated HCY to prevent CVD. Data from ongoing clinical trials are awaited to clarify this issue.

Topics: Biomarkers; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Hypolipidemic Agents; Risk Assessment; Risk Factors; Treatment Outcome; Up-Regulation; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Homocysteine, a sulfur amino acid, is an intermediate metabolite of methionine. In 1969, McCully reported autopsy evidence of extensive arterial thrombosis and atherosclerosis in children with elevated plasma homocysteine concentrations and homocystinuria. On the basis of this observation, he proposed that elevated plasma homocysteine (hyperhomocysteinemia) can cause atherosclerotic vascular disease. Hyperhomocysteinemia is now well established as an independent risk factor for atherosclerotic vascular disease. Mild hyperhomocysteinemia is quite prevalent in the general population. It can be caused by genetic defects in the enzymes involved in homocysteine metabolism or nutritional deficiencies in vitamin cofactors, certain medications or renal disease. An increase of 5 micromol per liter in the plasma homocysteine concentration raises the risk of coronary artery disease by as much as an increase of 20 mg per deciliter in the cholesterol concentration. In this article, we review the biochemical, experimental and clinical studies on hyperhomocysteinemia, with emphasis on the metabolism and pharmacokinetics of homocysteine.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Animals; Betaine-Homocysteine S-Methyltransferase; Cardiovascular Diseases; Deuterium; Gas Chromatography-Mass Spectrometry; Gout; Homocysteine; Humans; Hyperhomocysteinemia; Isotope Labeling; Methionine; Oxidation-Reduction; Risk Factors; Serum Albumin; Vitamin B 12

Multifunctional systems must maintain homeostasis. Man is an ideal example of a system that constantly aspires to attain optimal regulation, even under the stress of severe disease. We assume that there are universal, interchangeable (as required) biologically active substances that regulate the system and try to keep it in balance. We propose that one of these substances is vitamin B12. Why vitamin B12? The list of organs and body systems in which vitamin B12 plays a functional role is constantly being added to. Vitamin B12 affects the normal growth of children, the peripheral and central nervous systems, bone marrow, skin, mucous membranes, bones, and vessels. It is possible that even when the serum cobalamin level is normal, treatment with vitamin B12 could correct defects caused by other biologically active substances. We call this phenomenon the "Master Key" effect. We suggest that this "Master Key" concept can be tested by treating diseases, such as recurrent stomatitis, various forms of hyperpigmentation, trophic ulcers, and burns, with vitamin B12, even if the B12 serum level is normal.

Topics: Animals; Avitaminosis; Cardiovascular Diseases; Dogs; Growth; Humans; Infant; Male; Nervous System Diseases; Skin Diseases; Vitamin B 12

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of 2 pathways: remethylation, which requires folic acid and B-12 coenzymes, and transsulfuration, which requires pyridoxal-5'-phosphate, the B-6 coenzyme. Data from several studies suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies we have shown that plasma total homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B-6 as well as vitamin B-12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid artery stenosis of at least 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and CVD mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. This multitude of relationships between elevated plasma total homocysteine and diseases that afflict the elderly point to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is homocysteine itself or whether homocysteine is merely a marker remains to be determined.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cardiovascular Diseases; Carotid Stenosis; Cohort Studies; Dementia; Diet; Female; Folic Acid; Fractures, Bone; Heart Failure; Homocysteine; Humans; Hyperhomocysteinemia; Male; Massachusetts; Middle Aged; Risk Factors; Stroke; Vascular Diseases; Vitamin B 12; Vitamin B 6

Many studies have suggested that elevated homocysteine levels are an independent risk factor for cardiovascular disease, stroke and Alzheimer's disease. Lower levels of the three water-soluble vitamins--folate (folic acid), vitamin B6 and vitamin B12--are primary determinants of high blood homocysteine levels. In the fourth of an occasional series on vitamins, minerals and supplements, June Thompson looks at the role folate, in particular, may play in reducing homocysteine in the body and in protecting the body from some other diseases.

Topics: Alzheimer Disease; Cardiovascular Diseases; Chemoprevention; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Neoplasms; Primary Prevention; Risk Factors; Risk Reduction Behavior; Vitamin B 12; Vitamin B 6

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.

Topics: Animals; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Models, Chemical; Oxidative Stress; Smoking; Thrombosis; Vitamin B 12; Vitamin B 6

During the last decade, scientific evidence is mounting that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Despite this evidence, however, there are still concerns about the mechanisms(s) by which homocysteine exerts its pro-atherogenic effect, and it is unclear whether the decreased plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk. Experimental studies have shown that many possible mechanisms are implicated in the pro-atherogenic effect of homocysteine. Endothelial function is altered in subjects with hyperhomocysteinemia, and endothelial dysfunction is correlated with plasma levels of homocysteine. Exercise training reduces plasma levels of homocysteine and improves endothelial function, however without evidence of a better outcome. Larger studies are needed in order to demonstrate that the reduction of plasma levels of homocysteine by oral supplementation with folates and vitamins B6 and B12 translates into a decreased incidence of ischemic events, in particular in patients with documented coronary artery disease and ischemic encephalopathy.

Topics: Atherosclerosis; Cardiovascular Diseases; Drug Therapy, Combination; Endothelium; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

The nutritional status and plasma concentrations of some group B vitamins, namely vitamin B6, vitamin B12 and folic acid, have recently emerged as inverse correlates of cardiovascular risk, and several experimental and clinical studies, these latter mostly retrospective and case-control studies, indicate a defect of such vitamins as capable of promoting the progression of atherosclerosis. Since all these vitamins are implicated in homocysteine metabolism, and since homocysteine has a well-recognized relationship with cardiovascular risk, the simplest hypothesis to explain the relationship of vitamin B6, vitamin B12 and folic acid on the one hand, and cardiovascular risk on the other is that this relationship is mediated by plasma levels of homocysteine. The most convincing literature data for the existence of a relationship with cardiovascular risk are for vitamin B6 and folic acid. These vitamins, however, have also a series of in vitro effects indicating a direct antiatherogenic action, and the results of several clinical studies, especially for vitamin B6, indicate an inverse relationship with cardiovascular risk at least in part independent of homocysteinemia. A further confirmation of these data is important to devise future intervention strategies in primary and secondary prophylaxis of atherosclerotic vascular disease.

Topics: Adult; Aged; Arteriosclerosis; Cardiovascular Diseases; Case-Control Studies; Clinical Trials as Topic; Cross-Over Studies; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Primary Prevention; Prospective Studies; Retrospective Studies; Risk; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Homocysteine is a methionine-derived amino acid and its metabolism depends on B12, B6 and B2 vitamins and folic acid. The total homocysteine plasmatic concentration can be measured in most laboratories by means of enzymeimmunoassays. Hyperhomocysteinemia may be caused by genetic defects of the enzymes involved in its metabolism, nutritional deficiencies or absorption deficiencies of the vitamin cofactors of these enzymes, chronic diseases or administration of some drugs. An increase in the total plasmatic concentration of homocysteine represents a sensitive marker of folate and cobalamin deficiencies as well as an independent risk factor of cardiovascular disease. Furthermore, total plasmatic concentrations of homocysteine are related to the development of congenital malformations, pregnancy complications, psychiatric diseases and to cognitive impairment in the elderly. Therefore, the measurement of the concentration of homocysteine has a notable clinical interest, which may increase in future if it is confirmed that the association with these disorders is causal and that they can be prevented by treating hyperhomocysteinemia.

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12

The results of dietary intervention trials favor the hypothesis that higher intakes of B-vitamins (folate, vitamin B(6) and B(12)), and subsequently lower total homocysteine (tHcy) concentrations, are causally associated with a decreased risk of vascular disease in patients with cardiovascular diseases (CVD). The same is true for a higher intake of omega-3 fish fatty acids. Yet, the lack of hard end points and/or appropriate study designs precludes a definitive conclusion about causality. In the future, intervention trials with hard end points and randomized double-blind placebo-controlled designs should be able to elucidate the causality problem. There are several pathways by which B-vitamins and omega-3 fatty acids may exert their protective effect on CVD, a common pathway is a beneficial effect on the endothelial function and hemostasis. With respect to synergy between B-vitamins and omega-3 fatty acids, there is no evidence that fish oils have a tHcy-lowering effect beyond the effect of the B-vitamins. Nevertheless, animal studies clearly illustrate that vitamin B(6)- as well as folate-metabolism are linked with those of long-chain omega-3 fatty acids. Furthermore, a human study indicated synergistic effects of folic acid (synthetic form of folate) and vitamin B(6) together with omega-3 fatty acids on the atherogenic index and the fibrinogen concentration. Although these results are promising, they were produced in very small selective study populations. Thus, confirmation in large well-designed intervention trials is warranted.

Topics: Cardiovascular Diseases; Dietary Supplements; Drug Synergism; Fatty Acids, Omega-3; Folic Acid; Homocysteine; Humans; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 6

Oral supplements of synthetic folic acid and vitamin B12 are very effective in increasing blood levels of the vitamins and are known to prevent birth defects and cardiovascular diseases.

Topics: Cardiovascular Diseases; Congenital Abnormalities; Dietary Supplements; Folic Acid; Humans; Vitamin B 12

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Tests; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Marfan Syndrome; Multicenter Studies as Topic; Mutation; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Risk Factors; Thrombophilia; Time Factors; Venous Thrombosis; Vitamin B 12; Vitamin B 6

Since the identification of homocysteine (Hcy) as a risk factor for cardiovascular disease, it has been the subject of much research. As with other cardiovascular risk factors, a gender difference exists for Hcy. Plasma levels are lower in women of reproductive age than in men and postmenopausal women. This has led to the hypothesis that the increased risk of cardiovascular disease documented in postmenopausal women may be related to the increase in Hcy levels. Factors affecting total plasma levels of Hcy include genetic factors, nutritional factors, and lifestyle. Many studies appear to support the ability of estrogen replacement therapy to significantly lower both basal levels of Hcy and levels following methionine loading. A mean reduction of 10-15% in Hcy levels after 6 months of hormone therapy has been reported. Similarly, raloxifene and tamoxifen and low-dose folic acid administration induce reductions in plasma Hcy levels of the same degree observed for hormone therapy. The reduction occurs after a few months of therapy and is sustained, suggesting the potential for cardioprotective effects. Although there is a positive effect of estrogen therapy and hormone therapy on Hcy levels, recent studies do not recommend the use of estrogen or hormone replacement therapy for the primary or secondary prevention of cardiovascular disease. Further research is therefore needed to identify strategies to maximize the efficacy of hormone replacement therapy, while minimizing the risks.

Topics: Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Folic Acid; Homocysteine; Humans; Menopause; Risk Factors; Vitamin B 12; Vitamin B 6

Homocysteine is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar, even moderate hyperhomocysteinemia is associated with increased incidence of cardiovascular disease and Alzheimer's disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. Pyridoxal, folic acid, riboflavin, and Vitamin B(12) are all required for methionine metabolism, and deficiency of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15 %, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable lifestyle factors, in affecting methionone metabolism and in determining plasma homocysteine levels is discussed.

Topics: Avitaminosis; Cardiovascular Diseases; Creatinine; Folic Acid; Homocysteine; Humans; Incidence; Kidney Diseases; Life Style; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Nutritional Physiological Phenomena; Polymorphism, Genetic; Pyridoxal; Riboflavin; Vitamin B 12

Inadequate folate status is associated with an increased risk for chronic diseases that may have a negative impact on the health of the aging population. Folate, a water-soluble vitamin, includes naturally occurring food folate and synthetic folic acid in supplements and fortified foods. Inadequate folate status may result in hyperhomocysteinemia, a significant risk factor for atherosclerotic vascular disease, changes in DNA that may result in pro-carcinogenic effects and increased risk for cognitive dysfunction. Folate status may be negatively influenced by inadequate intake, genetic polymorphisms and interactions with various drugs. In the US, folic acid is now added to enriched grain products and continues to be included in the majority of ready-to-eat breakfast cereals. Recent data indicate that the folate status in the US population has improved significantly, presumably due to the effects of fortification. Folic acid (not food folate) intake in excess of the Tolerable Upper Intake Level may mask the diagnosis of a vitamin B(12) deficiency, which is more prevalent in the elderly than younger individuals. When folic acid supplements are recommended, a multivitamin that includes vitamin B(12) should also be advised. To safely and effectively increase folate intake in the elderly, naturally occurring folate-rich food sources should be promoted. Folate-rich foods include orange juice, dark green leafy vegetables, asparagus, strawberries and legumes. These foods are also excellent sources of other health-promoting nutrients associated with chronic disease risk reduction.

Topics: Aged; Biological Availability; Cardiovascular Diseases; Cognition Disorders; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Humans; Male; Neoplasms; Nutrition Policy; Risk Factors; United States; Vegetables; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine, and exists at a critical biochemical intersection in the methionine cycle - between S-adenosylmethionine, the indispensable ubiquitous methyl donor, and vitamins B12 and folic acid. High blood levels of homocysteine signal a breakdown in this vital process, resulting in far-reaching biochemical and life consequences. The link between homocysteine and cardiovascular disease is well established, and decreasing plasma total homocysteine by providing nutritional cofactors for its metabolism has been shown to reduce the risk of cardiovascular events. Information has been emerging regarding a connection between homocysteine metabolism and cognitive function, from mild cognitive decline (age-related memory loss) to vascular dementia and Alzheimer's disease. Significant deficiencies in the homocysteine re-methylation cofactors cobalamin (B12) and folate, as well as the trans-sulfuration cofactor vitamin B6, are commonly seen in the elderly population, with a resultant increase in homocysteine with advancing age. Hyperhomocysteinemia has been shown to be an independent risk factor for cognitive dysfunction. Indirect and direct vascular damage can be caused by homocysteine, which has been implicated in vascular dementia, with an increased risk of multiple brain infarcts and dementia as homocysteine levels rise. A significant correlation has been found between risk of Alzheimer's disease and high plasma levels of homocysteine, as well as low levels of folic acid, and vitamins B6 and B12. All of these disease associations are thought to be interrelated via increased homocysteine and S-adenosylhomocysteine and subsequent hypomethylation of numerous substances, including DNA and proteins, that render vascular structures and neurons more susceptible to damage and apoptosis. Providing the nutritional cofactors for proper functioning of the methionine cycle may improve methylation and protect the brain from damage. Further studies need to be performed to assess whether this will also reduce the risk of cognitive diseases and/or improve cognitive functioning.

Topics: Alzheimer Disease; Cardiovascular Diseases; Cognition Disorders; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Memory Disorders; Methionine; Methionine Adenosyltransferase; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6

In the latest Dutch national food consumption survey (1998) just over 1% of subjects (about 150,000 persons) claimed to be vegetarians; however, a much larger group (6% or approximately 1 million persons) ate meat < or = once a week. Vegetarianism can be subdivided into lacto-vegetarianism (a diet without meat and fish) and veganism (a diet without any animal foods whatsoever, including dairy products and eggs). A recent meta-analysis showed that vegetarians had a lower mortality from ischaemic heart disease than omniovorous subjects; however, cancer mortality and total mortality did not differ. Although a high consumption of red meat, which is rich in haeme iron and saturated fat, may increase the risk of cardiovascular disease and some types of cancer, this does not apply to white meat and fish. In fact, the most important protective effect would seem to be derived from the consumption of unrefined vegetable products (whole-grain cereals, vegetables, fruits, nuts and legumes) and fish. In other words, a prudent, omnivorous diet with moderate amounts of animal products, in which red meat is partly replaced by white meat and fish (especially fatty fish), together with the consumption of ample amounts of unrefined vegetable products, is thought to be just as protective as a vegetarian diet. On the other hand, the omission of meat and fish from the diet increases the risk of nutritional deficiencies. A vegan diet, in particular, leads to a strongly increased risk of deficiencies of vitamin B12, vitamin B2 and several minerals, such as calcium, iron and zinc. However, even a lacto-vegetarian diet produces an increased risk of deficiencies of vitamin B12 and possibly certain minerals, such as iron. Data from the latest Dutch food consumption survey suggest that 5-10% of all inhabitants of the Netherlands (up to 1 million persons) actually have a vitamin B12 intake below recommended daily levels. In medical practice, the possibility of vitamin B12 deficiency in subjects consuming meat or fish < or = once a week deserves serious consideration. In case of doubt, evaluation is indicated using sensitive and specific deficiency markers such as the levels of methylmalonic acid in plasma or urine. Alternative dietary sources of vitamin B12 instead of meat are fish (especially fatty fish is a good source of vitamin B12), or a vitamin-B12-supplement.

Topics: Cardiovascular Diseases; Dairy Products; Diet Surveys; Diet, Vegetarian; Female; Humans; Iron, Dietary; Male; Meat; Netherlands; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

In the results numerouses clinical and epidemiological trials have shown that high level of blood homocysteine is a marker of increased risk of coronary, cerebral and peripheral atherosclerosis. Close relation between high level of homocysteine and enhanced platelet aggregation, its prooxidant action, ability to inhibit growth of endothelial cells constituted basis for proposal of homocysteine theory of atherosclerosis. In this review use soy, products its processing, folate and vitamins B6 and B12 as homocysteine reducing therapy has been also suggested in the treatment of the patients with cardiovascular diseases.

Topics: Alcoholic Beverages; Arteriosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Coronary Disease; Diet; Female; Folic Acid; Glycine max; Homocysteine; Humans; Hyperhomocysteinemia; Male; Platelet Aggregation; Risk Factors; Vitamin B 12; Vitamin B 6

About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and getting larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B12, and vitamin B6 deficiencies and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10% of total risk. Elevated plasma homocysteine levels (>12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10% of the general population and in up to 40% of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence over-proportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial anti-thrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stress. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and lifestyle factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine leve

Topics: Austria; Cardiovascular Diseases; Female; Folic Acid; Germany; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Switzerland; Thrombosis; Vitamin B 12; Vitamin B 6

The importance of sulfur amino acid metabolism has become increasingly apparent in recent years. Methionine and cysteine are precursors of glutathione, which plays an important role in intracellular antioxidant/free radical defenses. Homocysteine is a non-protein-bound sulfur amino acid strongly implicated in the pathogenesis of several diseases. Both glutathione and homocysteine are affected by abnormalities in sulfur amino acid metabolism that occur in the clinical setting.. The Storch-Young model, which determines methionine turnover and homocysteine remethylation by means of a tracer methionine infusion, has been improved by using plasma homocysteine (rather than methionine) enrichment in the model. A complex new tracer method involving the use of tracer serine, methionine, and leucine has been described to determine the effects of folate or pyridoxine deficiency on sulfur amino acid-methyl transfer reactions in humans. The etiology of hyperhomocysteinemia in chronic renal failure is controversial; new concepts in this area are described. There is new interest in the subspecies of homocysteine in the circulation. A new method is described for measuring the extremely low plasma concentrations of reduced homocysteine, using gas chromatography-mass spectrometry. Plasma S-adenosylhomocysteine, measured by fluorescence high-performance liquid chromatography, has been suggested as being superior to homocysteine as a predictor of the risk of vascular disease.. This review highlights and critiques the above recent developments, and points out some of the complexities and pitfalls in designing and interpreting human metabolic studies involving the sulfur amino acids.

Topics: Amino Acids, Sulfur; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Glutathione; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kinetics; Methionine; Methylation; Models, Biological; Radioisotope Dilution Technique; Vitamin B 12

A raised plasma level of the amino acid homocysteine is associated with increased risk of cardiovascular disease. This association may be causal-it is biologically plausible, fairly strong, graded, and an increase in plasma homocysteine preceeds the onset of vascular disease. Plasma homocysteine levels are controlled by genetic and nutritional factors, notably folate, vitamin B12 and vitamin B6 intakes. Folic acid in particular lowers plasma homocysteine levels by about 25%. It is not known if this cheap and safe treatment reduces vascular disease risk. Current randomized control trials are addressing this issue, and proof or otherwise of causality must await their results. Homocysteine may also interact with conventional risk factors such as smoking to substantially increase their effect on risk. Thus meticulous risk factor control may be particularly important in subjects at high total cardiovascular risk who also have a raised plasma homocysteine level, and folic acid supplementation may be considered in such individuals.

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamins

Homocysteine is an independent, modifiable risk factor for cardiovascular disease. It is an intermediate amino acid formed during the metabolism of methionine. Plasma homocysteine is normally < or = 12 micromol/L, but when elevated has many deleterious cardiovascular effects. This review explains homocysteine metabolism, the effects of elevated homocysteine, factors contributing to high homocysteine, and its measurement. Risk factors for elevated homocysteine and intervention with B vitamins are discussed. Cardiovascular nurses are encouraged to facilitate homocysteine awareness through a variety of educational means.

Topics: Blood Chemical Analysis; Cardiovascular Diseases; Folic Acid; Health Education; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Risk Factors; Vitamin B 12; Vitamin B 6

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Pyridoxine; Risk Factors; Vitamin B 12

Topics: Biomarkers; Cardiovascular Diseases; Dietary Supplements; Folic Acid; Homocysteine; Humans; Nutrition Policy; Pyridoxine; Risk Factors; Vitamin B 12

An elevated blood level of homocysteine (Hcy), a sulfur amino acid, is associated with increased cardiovascular risk. Hcy is generated from S-adenosylhomocysteine (AdoHcy), the demethylated product of S-adenosylmethionine (AdoMet) in transmethylation reactions. AdoHcy is a competitive inhibitor of AdoMet-dependent methyltransferases. AdoHcy accumulation is prevented by rapid metabolism of its products. Chronic renal failure (CRF) is almost constantly associated with hyperhomocysteinemia. It has been shown that: (1) AdoHcy concentration is significantly increased and the AdoMet-AdoHcy ratio is reduced in erythrocytes of patients with CRF; (2) erythrocyte membrane protein methyl esterification, catalyzed by the enzyme protein L-isoaspartyl O-methyltransferase (PCMT; EC 2.1.1.77), is reduced in CRF; PCMT catalyzes a repair reaction involved in the conversion of an isopeptide bond (detrimental to protein structure and function) into a normal peptide bond; (3) D-aspartate residues, a side product of protein methylation and repair, are significantly reduced in erythrocyte membrane proteins of patients with CRF; and (4) folate treatment significantly reduces plasma Hcy levels and improves AdoMet-AdoHcy ratios. Stable isotope studies recently confirmed that the rate of methyl transfer reactions is significantly reduced in uremia. Additional evidence, obtained by independent groups, is consistent with this interpretation. We recently found increased isoaspartyl content of circulating plasma protein levels, particularly albumin, which was only partially reduced after folate treatment, in uremia. This kind of molecular damage possibly is caused by protein increased intrinsic instability as a result of interference with the uremic milieu. In conclusion, Hcy is an uremic toxin involved in protein molecular damage through the inhibition of methylation reactions and protein PCMT-mediated repair.

Topics: Cardiovascular Diseases; Female; Glomerular Filtration Rate; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylation; Renal Dialysis; Risk Factors; Sex Factors; Uremia; Vitamin B 12; Vitamin B 6

In the past, recommended vitamin or micronutrient intakes have often been based on levels that were adequate to prevent clinical deficiencies from developing. Once these levels were reached, clinicians and nutrition scientists generally attributed little value to higher vitamin intake from supplements or food sources. Evidence has continued to mount showing that the intake and serum concentration of certain vitamins above those necessary to prevent clinical deficiencies, might importantly influence health status. This paper discusses the association of anti-oxidant vitamins and cardiovascular disease, and the association of low intake or serum concentrations of folate, vitamin B6 and vitamin B12, and elevated serum homocysteine, resulting in an increase in vascular disease risk.

Topics: Aged; Antioxidants; Asia; Avitaminosis; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Pacific Islands; Risk Factors; Vitamin B 12; Vitamin B 6

Elevated plasma total homocysteine concentrations are a marker of vitamin deficiency and a risk factor for cardiovascular disease. It is possible that vitamin supplementation with folic acid and other B vitamins, which lower plasma homocysteine concentrations, may reduce the risk of cardiovascular disease. Large-scale clinical trials are currently underway to assess the homocysteine hypothesis of cardiovascular disease. Pending the outcome of such trials, measurement of plasma homocysteine concentrations in people at high risk of cardiovascular disease may help to identify patients who could benefit from more intensive treatment of classical cardiovascular risk factors. The introduction of immunoassays for homocysteine determination has made assessment of homocysteine status accessible to most routine hospital laboratories, and this review summarizes the evidence on why and how to assess homocysteine as a risk factor for cardiovascular disease in clinical practice.

Topics: Biomarkers; Blood Chemical Analysis; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Immunoassay; Mutation; Risk Factors; Vitamin B 12

Hyperhomocysteinemia refers to an elevated circulating level of the sulfur-containing amino acid homocysteine and has been shown to be a risk factor for vascular disease in the general population. In patients with renal failure, hyperhomocysteinemia is a common feature. The underlying pathophysiological mechanism for this phenomenon is unknown. Proposed mechanisms include reduced renal elimination of homocysteine and impaired nonrenal disposal, possibly because of inhibition of crucial enzymes in the methionine-homocysteine metabolism by the uremic milieu. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Several case-control and prospective studies have now indicated that hyperhomocystenemia is an independent risk factor for atherothrombotic disease in patients with predialysis and end-stage renal disease. In renal patients, plasma homocysteine concentration can be reduced by administration of folic acid in doses ranging from 1 to 15 mg per day. In more than 50% of the cases, however, the homocysteine concentration remains above 15 micromol/L. The effects of vitamin B12 or vitamin B6 are unclear. Large intervention trials are now needed to establish whether homocysteine-lowering therapy will reduce atherothrombotic events in patients with renal failure. These studies are now planned or are ongoing.

Topics: Adult; Arteriosclerosis; Cardiovascular Diseases; Case-Control Studies; Child; Endothelium, Vascular; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Life Tables; Male; Methionine; Peritoneal Dialysis; Prospective Studies; Pyridoxine; Renal Dialysis; Survival Analysis; Thrombophilia; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

Epidemiological studies have shown that higher blood homocysteine levels appear to be associated with higher risks of coronary, cerebral, and peripheral vascular disease and are inversely related to blood levels of folate and of vitamin B12 and vitamin B6. However, observational studies cannot exclude the possibility that elevated homocysteine levels may be associated with some other factor, rather than being causally related to vascular disease. Large-scale clinical trials of sufficient dose and duration of treatment are required to test this hypothesis, but there was substantial uncertainty about the optimal vitamin regimen to test in such trials. A meta-analysis of 12 randomized trials of vitamin supplements to lower homocysteine levels was carried out to determine the optimal dose of folic acid required to lower homocysteine levels and to assess whether vitamin B12 or vitamin B6 had additive effects. This meta-analysis demonstrated that reductions in blood homocysteine levels were greater at higher pretreatment blood homocysteine levels and at lower pretreatment folate concentrations. After standardization for a pretreatment homocysteine concentration of 12 micromol/L and folate concentration of 12 nmol/L (approximate average concentrations for western populations), dietary folic acid reduced homocysteine levels by 25% (95% confidence interval [CI]: 23 to 28%) with similar effects in a daily dosage range of 0.5 to 5 mg. Vitamin B12 (mean 0.5 mg) produced an additional reduction in blood homocysteine of 7%, whereas vitamin B6 (mean 16.5 mg) did not have any significant effect. Hence, in typical populations, daily supplementation with both 0.5 to 5 mg folic acid and about 0.5 mg vitamin B12 would be expected to reduce homocysteine levels by one quarter to one third (from about 12 micromol/L to about 8 to 9 micromol/L). Large-scale randomized trials of such regimens are now required to determine whether lowering homocysteine levels by folic acid and vitamin B12, with or without added vitamin B6, reduces the risk of vascular disease.

Topics: Adult; Aged; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Double-Blind Method; Drug Synergism; Europe; Female; Folic Acid; Forecasting; Genetic Variation; Homocysteine; Humans; Hyperhomocysteinemia; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; North America; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Treatment Outcome; Vitamin B 12

An elevated total homocysteine (tHcy) plasma concentration is associated with increased morbidity and mortality due to cardiovascular disease in the general population and in patients with impaired renal function. The prevalence of hyperhomocysteinaemia (plasma levels above 15 micromol/l) in the general population is less than 5% and can be as high as 50% in patients with vascular disease. In patients with renal insufficiency, elevated tHcy plasma levels are detected in 50 - 100% of the patients. Total homocysteine plasma levels can be lowered or normalised by folic acid and/or vitamin B(6) and vitamin B(12) supplementation. In patients with advanced chronic renal insufficiency or end-stage renal disease, hyperhomocysteinaemia is partially resistant to folic acid or vitamin therapy. However, higher tHcy plasma levels may also reflect tissue damage and the increase in Hcy after an acute incident such as stroke or myocardial infarction may be necessary for tissue repair mechanisms. This implies, that lowering tHcy may even be harmful to some patients. Currently, prospective studies are underway to clarify whether folate supplementation, with or without additional other vitamins, improves cardiovascular disease morbidity and mortality in the general population, as well as in renal failure patients. While population-wide screening for and treatment of hyperhomocysteinaemia is generally not recommended, treatment of high risk patients may be considered.

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kidney Transplantation; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Pyridoxine; Renal Dialysis; Risk Factors; Vitamin B 12

In recent years there has been growing evidence that high levels of plasmatic homocysteine constitute an independent risk factor for early cardiovascular disease. In this article we review the main theories of atherosclerosis which take into account the proteins, namely homocysteine, homocysteine metabolism, the cause that may be responsible for high levels of homocysteinemia, the pathophysiologic mechanisms of vascular lesion induced by hyperhomocysteinemia, the clinical evidence that homocysteinemia constitutes a vascular risk factor and finally, the evidence that it is possible to control homocysteinemia with supplementation of co-factors of homocysteine metabolism, namely vitamin B6, B12 or folic acid.

Topics: Arteriosclerosis; Cardiovascular Diseases; Folic Acid; Humans; Hyperhomocysteinemia; Pyridoxine; Risk Factors; Vitamin B 12

Homocystinuria is an uncommon genetic disease characterized by a marked increase of serum homocysteine (HCY), an intermediate of methionine metabolism. In patients with homocystinuria, hyperhomocysteinemia promotes the development of atherosclerotic lesions and is responsible for premature coronary artery disease. Recently, several studies have also demonstrated that moderate hyperhomocysteinemia--not necessarily linked to an inborn metabolic defect--may also be considered as an independant risk factor for cardiovascular disease. The main mechanisms of HCY atherogenic action are thought to be LDL oxydation, inhibition of vascular endothelium growth combined with stimulation of smooth muscular cells proliferation, and interference with the coagulation and fibrinolytic systems. Cofactors of key enzymes in HCY metabolism, folic acid, vitamin B12 and vitamin B6, may be given, alone or in combination, for the treatment of hyperhomocysteinemia. Homocysteinemia can be assessed by basal plasma HCY concentration and/or by HCY levels measured after a methionine loading test. Mainly measured till now in specialized laboratories using rather complex techniques (HPLC, GCMS, amino acid analyser ...), HCY determination is today spreading widely owing to the development of automated immunoassays.

Topics: Arteriosclerosis; Cardiovascular Diseases; Folic Acid; Homocystinuria; Humans; Hyperhomocysteinemia; Pyridoxine; Risk Factors; Vitamin B 12

Elevated plasma total homocysteine may be causally related to the risk of atherosclerotic cardio-vascular diseases. Many significant studies indicate an effect by elevated homocysteine on cardiovascular disease occurrence, progression, and recurrence that is independent of traditional risk factors. However, recent data have cast doubt on the veracity of the relationship between elevated plasma total homocysteine and the incidence of cardiovascular disease. In general, a stronger relationship has been found in cross-sectional and retrospective case-control studies than in nested case-control or prospective studies. The issues of study design, bias, and confounding are critical to an analysis of this putative relationship, and their effects can only be avoided by randomized controlled trials of homocysteine-lowering therapy (folic acid). While awaiting the outcome of these trials, there may already be sufficient evidence to prescribe homocysteine-lowering therapy in subjects deemed to be at high risk of cardiovascular disease.

Topics: Aged; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Incidence; Male; Meta-Analysis as Topic; Prospective Studies; Pyridoxine; Retrospective Studies; Risk; Risk Factors; Smoking; Vitamin B 12

An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.

Topics: Arteriosclerosis; Cardiovascular Diseases; Coronary Artery Disease; Female; Folic Acid; Folic Acid Deficiency; Forecasting; Homocysteine; Humans; Intracranial Arteriosclerosis; Male; Peripheral Vascular Diseases; Prevalence; Risk Factors; Safety; Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cardiovascular Diseases; Dietary Supplements; Folic Acid; Folic Acid Deficiency; Hematinics; Homocysteine; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pyridoxine; Renal Dialysis; Vitamin B 12

Topics: Animals; Cardiovascular Diseases; Homocysteine; Humans; Pyridoxine; Vitamin B 12

Topics: Cardiovascular Diseases; Dietary Supplements; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Pyridoxine; Randomized Controlled Trials as Topic; Research Design; Vitamin B 12

The sulfur-containing amino acid, homocysteine, is formed from the essential amino acid methionine, and a number of B vitamins are involved in methionine metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine beta synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the transsulfuration pathway and the urinary excretion of sulfur. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocyst(e)ine elevation, as does diminished renal function, both of which are common in the elderly. It is also established that homocyst(e)ine elevation of this order is associated with increased cardiovascular risk but is also associated with most established risk factors, although it is thought to be an independent contributor. In the inborn error of metabolism homocystinuria due to cystathionine beta synthase deficiency there is greatly increased circulating homocyst(e)ine and a clear association with precocious vascular disease. In about 50% of these patients there is a vascular event before the age of 30 years. The homocysteine-induced adverse vascular changes appear to result from endothelial and smooth muscle cell effects and increased thrombogenesis. We have documented a highly significant reduction in the occurrence of vascular events during 539 patient years of treatment in 32 patients with cystathionine beta synthase deficiency (mean age 30 years, range 9-66 years) by aggressive homocyst(e)ine lowering with pyridoxine, folic acid, and B12 (p = 0.0001). The 15 pyridoxine nonresponsive patients also received oral betaine. Although a cause and effect relationship is postulated for the increased cardiovascular risk associated with mild homocysteine elevation, a common cause of this elevation is the methylenetetrahydrofolate reductase C677T mutation. Homozygotes occur in about 11% of Caucasian populations. However, the mutation is not associated with increased coronary risk. Since mild homocysteine elevation is easily normalized by B vitamin supplementation, usually with folic acid, it remains for controlled clinical trials of this inexpensive therapy to determine whether normalizing mild homocyst(e)ine elevation reduces cardiovascular risk.

Topics: Aging; Cardiovascular Diseases; Diet; Folic Acid; Folic Acid Deficiency; Homocysteine; Homocystinuria; Humans; Pyridoxine; Risk Factors; Vitamin B 12; Vitamin B Deficiency

Research during the last 5 years has made it clear that people who do not take folic acid supplements are at increased risk for functional folate deficiency, which has been proven to cause spina bifida and anencephaly and also has been associated with an increased risk for occlusive cardiovascular disease. The overriding folate policy issue is how to increase dramatically the folate consumption of 75% of the population who are now consuming 0.4 mg of folic acid in a supplement. The most expeditious way to increase consumption is through fortification of a food staple. Public health programs are also needed to educate people about the vital importance of increased consumption of folic acid vitamin supplements and of food rich in natural folates. It is urgent that fortification of cereal-grain products be implemented now. The level proposes by FDA would accomplish some prevention, but much more prevention would occur if the fortification were 2.5 times that level. Fortification at the higher level would prevent about 1000 spina bifida and anencephaly birth defects each year and perhaps as many as 50,000 premature deaths each year from coronary disease. Available data have not demonstrated that increasing consumption of folic acid by 0.1 to 0.25 mg of folic acid a day is harmful. If a policy needs to be established on the assumption that people who take vitamin supplements could be harmed, a good policy option ia available; require that all folic acid vitamin supplements also contain 0.4 mg of vitamin B-12.

Topics: Adult; Aged; Anencephaly; Cardiovascular Diseases; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Homocysteine; Humans; Infant, Newborn; Male; Pregnancy; Risk Factors; Spinal Dysraphism; United States; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adenoma, Islet Cell; Carbohydrates; Cardiovascular Diseases; Celiac Disease; Diabetes Mellitus; Fatty Acids; Gastrectomy; Gastroenteritis; Glutens; Hematinics; Humans; Liver Diseases; Radiation Injuries; Vitamin B 12

A growing body of research evidence suggests that elevated homocysteine level (hyperhomocysteinemia) is an independent risk factor for cardiovascular diseases. The current study aimed to investigate the prevalence and associated risk factors for hyperhomocysteinemia among adolescent Afghan refugees aged 10−19 years. In total, 206 healthy adolescent boys and girls were randomly recruited from a refugee village in Peshawar, Pakistan, in 2020. Socio-demographic data, anthropometric assessment, and blood sample collection were performed following standard methods. Serum homocysteine was assessed using a chemiluminescent microparticle immunoassay, with hyperhomocysteinemia defined as levels ≥ 15 µmol/L. The overall prevalence of hyperhomocysteinemia was 25%, with mean homocysteine levels significantly (p = 0.004) higher among boys (14.1 µmol/L) than girls (11.8 µmol/L). Multivariate logistic regression analysis revealed a significant association between hyperhomocysteineimia and serum levels of vitamin B12 (OR 0.29; 95% CI of 0.14 to 0.62; p < 0.01) and folate (OR 0.1; 95% CI of 0.03 to 0.27; p < 0.001). Overall, our study findings indicate high prevalence of hyperhomocysteinemia among adolescent Afghan refugees who are potentially at high risk of developing cardiovascular diseases in future. There is a dire need to develop and implement nutritional and public health strategies to control hyperhomocysteinemia, protect against related diseases and complications in future, and ensure healthy lives and well-being among these vulnerable populations.

Topics: Adolescent; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Malnutrition; Micronutrients; Prevalence; Refugees; Vitamin B 12

In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk.. Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease.. A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present.. This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.

Topics: Aged; Cardiovascular Diseases; Cerebrovascular Disorders; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Fractures, Bone; Homocysteine; Humans; Male; Odds Ratio; Osteoporotic Fractures; Placebos; Risk Factors; Vitamin B 12

Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B

Topics: Adult; Biomarkers; Cardiovascular Diseases; Cholesterol; Diet, Vegan; Fatty Acids; Female; Healthy Volunteers; Homocysteine; Humans; Inflammation; Male; Methylmalonic Acid; Micronutrients; Nutritional Status; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to determine whether reducing plasma homocysteine concentrations with long-term, combined treatment with folic acid, vitamin B. These findings indicate that long-term, combined treatment with folic acid, vitamin B. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000541.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Double-Blind Method; Drug Combinations; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Inflammation; Inflammation Mediators; Middle Aged; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamins

Obesity is a major public health problem and great risk for not only cardiovascular diseases but also cancer, musculoskeletal, and gynecological diseases. This study was aimed to investigate the association between serum Vitamin B12 (vitB12), body mass index (BMI), and nutritional status among obese women.. This cross-sectional study enrolled consecutive female subjects. The consumptions of red meat, fish, bovine liver, egg, and mushroom were recorded. According to the Dietary Reference Intakes, the patients were categorized as insufficiency and sufficiency. Three cutoff points were defined for vitB12 status: (1) Deficiency if vitB12 is <200 pg/mL; (2) insufficiency if vitB12 is 250-350 pg/mL, and (3) sufficient if vitB12 is ≥350 pg/mL. According to BMI, the patients were assigned to nonobese and obese groups. BMI, serum vitB12 level, consumptions of red meat, fish, bovine liver, egg, and mushroom were evaluated and compared between two groups.. Mean level of vitB12 was 247.8 ± 10.4 pg/mL and significantly associated with consumption of egg (P = 0.031), bovine liver (P = 0.004), mushroom (P = 0.040), and red meat (P = 0.003). VitB12 was significantly higher in nonobese than obese group (282.5 ± 106.8 vs. 242.5 ± 107.5 pg/mL, P = 0.001). The ratio of vitB12 deficiency was significantly higher in obese than nonobese group (37.6% vs. 24.7%; P = 0.019). VitB12 level was negatively correlated with BMI (r = -0.155; P< 0.001), but not insulin resistance (r = -0.172; P = 0.062).. Obesity was associated with low level of vitB12 in obese women, and more likely to be vitB12 deficient. Consumption of certain types of food contributes to increase vitB12 level.

Topics: Adult; Animals; Body Mass Index; Cardiovascular Diseases; Cattle; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Middle Aged; Nutritional Status; Obesity; Turkey; Vitamin B 12

To examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12.. In a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial.. During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04).. In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.

Topics: Adult; Aged; Cardiovascular Diseases; Cataract; Cataract Extraction; Double-Blind Method; Drug Combinations; Female; Folic Acid; Health Personnel; Humans; Incidence; Middle Aged; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

We investigated whether daily supplementation with low-dose B vitamins in the healthy elderly population improves the Framingham risk score (FRS), a predictor of cardiovascular disease risk.. Between 2007 and 2012, a double-blind randomized controlled trial was conducted in a rural area of North China. In all, 390 healthy participants aged 60-74 were randomly allocated to receive daily vitamin C (50 mg; control group) or vitamin C plus B vitamins (400 µg folic acid, 2 mg B6, and 10 µg B12; treatment group) for 12 months. FRSs were calculated for all 390 subjects.. Folate and vitamin B12 plasma concentrations in the treatment group increased by 253 and 80%, respectively, after 6 months, stopped increasing with continued supplementation after 12 months and returned to baseline levels 6 months after supplementation cessation. Compared with the control group, there was no significant effect of B vitamin supplementation on FRSs after 6 months (mean difference -0.38; 95% CI -1.06, 0.31; p = 0.279), whereas a significant effect of supplementation was evident after 12 months (reduced magnitude 7.6%; -0.77; 95% CI -1.47, -0.06; p = 0.033). However, this reduction disappeared 6 months after supplementation stopped (-0.07; 95% CI -0.80, 0.66; p = 0.855). The reduction in FRS 12 months after supplementation was more pronounced in individuals with a folate deficiency (10.4%; -1.30; 95% CI -2.54, -0.07; p = 0.039) than in those without (4.1%; -0.38; 95% CI -1.12, 0.36; p = 0.313). B vitamins increased high-density lipoprotein cholesterol by 3.4% after 6 months (0.04; 95% CI -0.02, 0.10; p = 0.155) and by 9.2% after 12 months (0.11; 95 % CI 0.04, 0.18; p = 0.003). Compared with the control group, this change in magnitude decreased to 3.3% (0.04; 95 % CI -0.02, 0.10; p = 0.194) 6 months after supplementation cessation.. Daily supplementation with a low-dose of B vitamins for 12 months reduced FRS, particularly in healthy elderly subjects with a folate deficiency. These reduced effects declined after supplementation cessation, indicating a need for persistent supplementation to maintain the associated benefits.

Topics: Aged; Asian People; Blood Pressure; Body Mass Index; Cardiovascular Diseases; China; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Triglycerides; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients.. The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50  μmol/l), treated with B-vitamins (500  μg vitamin B12 and 400  μg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima-media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured.. Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6  μmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed.. Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Blood Pressure; Cardiovascular Diseases; Carotid Intima-Media Thickness; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Pulse Wave Analysis; Risk Factors; Treatment Outcome; Vascular Stiffness; Vitamin B 12

Vitamin B-12 and n-3 polyunsaturated fatty acids (PUFA) decrease blood homocysteine (Hcy) concentrations. However, the combined effect of these nutrients on Hcy and ferritin, and C-reactive protein is limited and inconclusive. The objective was to examine the synergistic effect of vitamin B-12 in combination of n-3 PUFA on plasma Hcy, ferritin, and other biochemical markers.. In a randomized controlled trial, thirty eligible subjects were randomly divided into three groups, and assigned to receive 1000 μg of vitamin B-12, 2 g fish oil, or 1000 μg vitamin B-12 and 2 g fish oil, respectively, for 8 weeks. Plasma phospholipids (PL) fatty acids and biochemical markers were determined. This study was registered under ClinicalTrials.gov Identifier: NCT01762072.. Plasma PL 20:5n-3, 22:6n-3 and n-3 PUFA was increased after 4 and 8 week supplementation of fish oil, and vitamin B-12+fish oil. Plasma concentrations of triacylglycerol, uric acid, C-reactive protein, and ferritin were significantly decreased after 4 and 8 week supplementation of fish oil, and vitamin B-12+fish oil. In all groups, significant changes in plasma Hcy were observed during the study period. Vitamin B-12, fish oil, and vitamin B-12+fish oil supplementation lowered plasma Hcy concentrations by 22%, 19%, and 39%, respectively.. The combination of vitamin B-12 and fish oil has a synergistic effect on lowering plasma concentrations of Hcy.. 目的：维生素B-12 和欧米伽3 多不饱和脂肪酸能够降低血液同型半胱氨酸浓 度。但是，这两种营养元素是否对同型半胱氨酸、铁蛋白、C 反应蛋白有协 同效应仍不清楚。方法：为进一步解决该问题，我们开展了一项随机对照实 验，38 位参与者随机分为三组，每天分别食用1000 μg 维生素B-12、2 g 鱼 油、1000 μg 维生素B-12+2 g 鱼油。八周以后，收集受试者血样，测定血浆磷 脂脂肪酸组成，生物标志物等。结果：四周或者八周干预以后，鱼油组和鱼 油+维生素B-12 组的血浆磷脂20:5n-3、22:6n-3 和总欧米伽3 脂肪酸显著升 高，然而，血浆甘油三酯、尿酸、C 反应蛋白以及铁蛋白显著降低。维生素 B-12 组、鱼油组、维生素B-12+鱼油组，血浆同型半胱氨酸分别降低22%、19% 和39%。结论：维生素B-12 和鱼油在调节同型半胱氨酸代谢过程中存在协同 效应。.

Topics: Adult; C-Reactive Protein; Cardiovascular Diseases; China; Dietary Supplements; Fatty Acids, Omega-3; Female; Ferritins; Fish Oils; Homocysteine; Humans; Male; Risk Factors; Vitamin B 12; Vitamin B Complex; Young Adult

Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile.. Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention.. Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention.. These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages. www.isrctn.org: ISRCTN88720134.

Topics: Adipokines; Aged; Apolipoproteins; Blood Glucose; Cardiovascular Diseases; Cholesterol; Cross-Over Studies; Diet; Ethanol; Fasting; Folic Acid; Glucose; Homeostasis; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Polyphenols; Risk Factors; Triglycerides; Vitamin B 12; Wine

Recent studies suggest increased cancer risk in patients with type 2 diabetes mellitus (T2DM) compared with healthy individuals. The present study aims to assess whether T2DM is associated with increased genome instability and whether a healthy diet with natural foods can improve genome stability in peripheral blood lymphocytes (PBLs). Seventy-six diabetic and 21 non-diabetic individuals were randomly assigned to either an 'intervention' or an 'information only' group. All participants received information about the beneficial effects of a healthy diet, while subjects of the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids per day for 8 weeks. Chromosomal damage was assessed using the cytokinesis-block micronucleus (MN) cytome assay. Levels of chromosomal damage did not differ between diabetic and non-diabetic individuals. However, diabetic individuals with MN frequency above the high 50th percentile had significantly higher levels of fasting plasma glucose, glycosylated haemoglobin and were at higher risk for cardiovascular disease (CVD), assessed by the Framingham general cardiovascular risk score. Non-diabetic individuals with MN frequency above the 50th percentile had significantly lower vitamin B12 levels. The intervention with vegetables and plant oil led to significant increases in folate, γ-tocopherol, α- and β-carotene while vitamin B12 was significantly reduced. Levels of chromosomal damage were not altered, only apoptosis was slightly increased. The results suggest interactions between glycaemic control, CVD risk and genome stability in individuals with T2DM. However, a healthy diet does not improve genome damage in PBLs.

Topics: Aged; Anthropometry; beta Carotene; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Carotenoids; Chromosome Aberrations; Diabetes Mellitus, Type 2; DNA Damage; Fatty Acids, Unsaturated; Female; Folic Acid; gamma-Tocopherol; Genome, Human; Genomic Instability; Glycated Hemoglobin; Humans; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Plant Oils; Risk Factors; Vegetables; Vitamin B 12

Dietary factors might affect depressive symptoms.. In secondary data analyses, we examined effects of supplementation with B vitamins or n-3 (omega-3) fatty acids on depressive symptoms in cardiovascular disease survivors.. The SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3) trial was a secondary prevention trial (2003-2009; n = 2501) in which individuals aged 45-80 y were randomly assigned, by using a 2 × 2 factorial design, to receive 0.56 mg 5-methyl-tetrahydrofolate and vitamins B-6 (3 mg) and B-12 (0.02 mg); EPA and DHA (600 mg) in a 2:1 ratio; B vitamins and n-3 fatty acids; or a placebo. Depressive symptoms were evaluated at years 3 and 5 with the 30-item Geriatric Depression Scale (GDS). Overall and sex-specific ORs and 95% CIs were estimated in 2000 participants by using factorial logistic regression.. After a median of 4.7 y of supplementation, there was no association between allocation to receive B vitamins and depressive symptoms. However, the allocation to receive n-3 fatty acids was positively associated with depressive symptoms (GDS >10) in men (adjusted OR: 1.28; 95% CI: 1.03, 1.61) but not in women.. We showed no beneficial effects of a long-term, low-dose supplementation with B vitamins or n-3 fatty acids on depressive symptoms in cardiovascular disease survivors. The adverse effects of n-3 fatty acids in men merit confirmation.

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Cardiovascular Diseases; Combined Modality Therapy; Depression; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Psychiatric Status Rating Scales; Secondary Prevention; Sex Characteristics; Tetrahydrofolates; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma.. The Women's Antioxidant and Folic Acid Cardiovascular Study was a randomized, double-blind, placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005. Participants were randomly assigned to receive a combination pill of folic acid (2.5mg), vitamin B(6) (50mg), and vitamin B(12) (1mg) or placebo. This study included 1470 participants who were followed up for as long as 9.2 years and underwent an endoscopy at any point during follow-up. We estimated relative risks using a generalized linear model with a natural logarithm link function and Poisson distributed errors. All statistical tests were two-sided.. The risk of colorectal adenoma was similar among participants receiving treatment (24.3%, 180 of 741 participants) vs placebo (24.0%, 175 of 729 participants) (multivariable adjusted relative risk = 1.00, 95% confidence interval = 0.83 to 1.20). Treatment was not associated with the risk of adenoma when data were analyzed by subsite, size, stage, and the number of adenomas. There was no statistically significant effect modification by alcohol intake, history of cancer or adenoma, or baseline plasma levels or intakes of folate, vitamin B(6), or vitamin B(12).. Our results indicate no statistically significant effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on colorectal adenoma among women at high risk for cardiovascular disease.

Topics: Adenoma; Adult; Aged; Anticarcinogenic Agents; Cardiovascular Diseases; Colorectal Neoplasms; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Linear Models; Male; Middle Aged; Poisson Distribution; Risk Assessment; Risk Factors; Vitamin B 12; Vitamin B 6

Serum asymmetric dimethylarginine (ADMA) levels are increased in maintenance hemodialysis patients, and this abnormality may increase cardiovascular risk. We investigated whether combined administration of oral folate and intravenous methylcobalamin in such patients is more beneficial than oral folate alone at decreasing circulating ADMA levels.. Randomized controlled trial.. Patients undergoing hemodialysis.. 40 patients were randomly assigned to 1 of 2 groups. For 3 weeks, they received supplementation with either folate alone (15 mg/d; n = 20; folate group) or coadministered folate (15 mg/d) and methylcobalamin (500 mug after each hemodialysis treatment 3 times weekly; n = 20; methylcobalamin group).. normalization of plasma homocysteine levels (<15 mumol/L), decrease in serum ADMA levels.. change in augmentation index in the carotid artery and ratios of S-adenosylmethionine to S-adenosylhomocysteine (as a transmethylation indicator) and dimethylamine to ADMA (as an indicator of ADMA hydrolysis).. Blood samples were collected under fasting conditions during the prehemodialysis procedure.. The proportion showing normalization of plasma homocysteine levels was much greater in the methylcobalamin group (18 of 20 patients; 90%) than in the folate group (6 of 20; 30%; P < 0.001). The percentage of decrease in ADMA levels was greater in the methylcobalamin than folate group (25.4% +/- 10.2% vs 13.2% +/- 11.2%; P < 0.001). The increase in ratio of S-adenosylmethionine to S-adenosylhomocysteine was not different between the 2 groups; however, the ratio of dimethylamine to ADMA was increased in only the methylcobalamin group (P = 0.04). Augmentation index was decreased in only the methylcobalamin group (P = 0.03).. This study had an open-label nature and did not examine long-term effects of homocysteine-normalizing therapy (no clinical end points).. Coadministration of intravenous methylcobalamin and oral folate in hemodialysis patients normalized hyperhomocysteinemia and decreased ADMA levels and arterial stiffness. We suggest that this regimen may have greater potential than folate alone to decrease cardiovascular risk in such patients.

Topics: Administration, Oral; Aged; Arginine; Cardiovascular Diseases; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Vitamin B 12; Vitamin B Complex

Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and the risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of therapy to lower homocysteine levels in AMD are lacking. Our objective was to examine the incidence of AMD in a trial of combined folic acid, pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)) therapy.. We conducted a randomized, double-blind, placebo-controlled trial including 5442 female health care professionals 40 years or older with preexisting cardiovascular disease or 3 or more cardiovascular disease risk factors. A total of 5205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), pyridoxine hydrochloride (50 mg/d), and cyanocobalamin (1 mg/d) or placebo. Our main outcome measures included total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition.. After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the combination treatment group and 82 in the placebo group (relative risk, 0.66; 95% confidence interval, 0.47-0.93 [P = .02]). For visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36-0.95 [P = .03]).. These randomized trial data from a large cohort of women at high risk of cardiovascular disease indicate that daily supplementation with folic acid, pyridoxine, and cyanocobalamin may reduce the risk of AMD.

Topics: Adult; Aged; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Endpoint Determination; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Macular Degeneration; Middle Aged; Proportional Hazards Models; Pyridoxine; Risk Factors; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes.. The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged > or = 40 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group.. During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79-1.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76-1.10]; P = 0.36).. Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Middle Aged; Placebos; Proportional Hazards Models; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin E

Diet and lifestyle are modifiable factors involved in the development and prevention of non-communicable diseases, including cardiovascular disease. Nut consumption, particularly walnut intake, has been inversely related to incident coronary heart disease (CHD) in observational studies and to improved lipid profiles in short-term feeding trials.. To assess the potential functional effect associated with the regular consumption of walnut-enriched restructured meat products in subjects at risk for cardiovascular disease (CVD).. A crossover single-dose bioavailability study (n = 3) using gamma-tocopherol as exposure marker and a crossover unblinded dietary intervention study (5 weeks) in subjects at risk (n = 25). Dietary intervention consisted of regular consumption of the meat product, with or without walnuts, five times per week for five weeks with a 1-month washout in between. Overnight fasting blood samples were collected on days 0, 12, 21, 28 and 35, coinciding with blood pressure and body weight recordings. Participants were asked to complete a diet record throughout the study. The functional effects were assessed using clinically relevant and related biomarkers of CHD: serum total, HDL and LDL cholesterol, triacylglycerols, homocysteine, vitamins B(6) and B(12), folic acid, alpha-tocopherol and platelet function test (obturation time).. The regular consumption of walnut-enriched meat products compared with that of the restructured meat products without added walnuts provokes a decrease in total cholesterol of 6.8 mg/dl (CI(95%): -12.8, -0.85). Compared to baseline (mixed diet), meat products with walnuts decreased total cholesterol (-10.7 mg/dl, CI(95%): -17.1, -4.2), LDL cholesterol (-7.6 mg/dl, CI(95%): -2.2, -13.0) and body weight (-0.5 kg, CI(95%): -0.1, -0.9) and increased gamma-tocopherol (8.9 mg/dl, CI(95%): 1.0, 16.8).. The restructured meat products with added walnuts supplied in this study can be considered functional foods for subjects at high risk for CVD, as their regular consumption provokes a reduction in total cholesterol of 4.5% with respect to baseline values (mixed diet) and 3% with respect to the restructured meat without walnuts.

Topics: Aged; Animals; Cardiovascular Diseases; Cattle; Cholesterol; Cross-Over Studies; Female; Folic Acid; gamma-Tocopherol; Homocysteine; Humans; Juglans; Lipoproteins, HDL; Lipoproteins, LDL; Male; Meat Products; Middle Aged; Platelet Function Tests; Postprandial Period; Triglycerides; Vitamin B 12; Vitamin B 6

Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels.. To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.. Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.. Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780).. The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.. Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).. This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.. clinicaltrials.gov Identifier: NCT00354081.

Topics: Aged; Aortic Valve Stenosis; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Homocysteine has been proposed as a risk factor for atherosclerosis. The association between plasma total homocysteine (tHcy) concentration and carotid atherosclerosis has not been thoroughly studied in high-risk populations with vascular disease. For this study, carotid atherosclerosis was assessed by measurements of carotid intima-media thickness (IMT) and plaque calcification in 923 patients with vascular disease or diabetes. Associations with tHcy and plasma folate concentrations were examined. The mean and single maximum carotid IMT were 1.27 +/- 0.34 mm and 2.41 +/- 0.83 mm, respectively. The mean segment plaque calcification score was 27.8%. tHcy correlated with mean (r = 0.13; p < 0.001) and single maximum (r = 0.12; p < 0.001) carotid IMT. There was a progressive increase in mean and single maximum carotid IMT across quartiles of tHcy (p < 0.0001 for trend). These associations were no longer significant after adjusting for other CV risk factors. A trend towards an inverse association between plasma folate and mean max carotid IMT was found in both univariate and multivariable analyses. However, the plaque calcification score increased across quartiles of tHcy (p < 0.01) and decreased across quartiles of plasma folate concentrations (p < 0.05) after multiple adjustments. In conclusion, in high-risk individuals, tHcy and low folate concentrations were only weakly associated with carotid IMT. In contrast, we found an independent association with the plaque calcification score, a measure of more advanced atherosclerosis. The effect of tHcy lowering on carotid atherosclerosis and stroke prevention warrants further investigation.

Topics: Aged; Biomarkers; Calcinosis; Canada; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Artery, Common; Disease Progression; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Tunica Intima; Tunica Media; Ultrasonography; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Folate, vitamin B(6), and vitamin B(12) are thought to play an important role in cancer prevention.. To evaluate the effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on cancer risk in women at high risk for cardiovascular disease.. In the Women's Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older, with preexisting cardiovascular disease or 3 or more coronary risk factors, were randomly assigned to receive either a daily combination of folic acid, vitamin B(6), and vitamin B(12) or a matching placebo. They were treated for 7.3 years from April 1998 through July 31, 2005.. Daily supplementation of a combination of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) (n = 2721) or placebo (n = 2721).. Confirmed newly diagnosed total invasive cancer or breast cancer.. A total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group). Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer (101.1/10,000 person-years for the active treatment group vs 104.3/10,000 person-years for placebo group; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.79-1.18; P = .75), breast cancer (37.8/10,000 person-years vs 45.6/10,000 person-years, respectively; HR, 0.83; 95% CI, 0.60-1.14; P = .24), or any cancer death (24.6/10,000 person-years vs 30.1/10,000 person-years, respectively; HR, 0.82; 95% CI, 0.56-1.21; P = .32).. Combined folic acid, vitamin B(6), and vitamin B(12) treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era.. clinicaltrials.gov Identifier: NCT00000541.

Topics: Adult; Aged; Antioxidants; Breast Neoplasms; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Humans; Middle Aged; Neoplasms; Risk; Vitamin B 12; Vitamin B 6; Vitamin B Complex

High homocysteine concentrations may be neurotoxic and contribute to cognitive decline in older persons.. The objective was to examine the effect of supplementation with folic acid, vitamin B-12, and vitamin B-6 on cognitive change in women with cardiovascular disease (CVD) or CVD risk factors.. The Women's Antioxidant and Folic Acid Cardiovascular Study is a randomized placebo-controlled trial designed to test the effect of a combination of B vitamins (2.5 mg folic acid/d, 50 mg vitamin B-6/d, and 1 mg vitamin B-12/d) on secondary prevention of CVD. Female health professionals aged >or=40 y (n = 5442) with CVD or >or=3 coronary risk factors in 1998 (after folic acid fortification began in the United States) were randomly assigned to treatment. Shortly after randomization (mean: 1.2 y), a substudy of cognitive function was initiated among 2009 participants aged >or=65 y. Telephone cognitive function testing was administered up to 4 times over 5.4 y with 5 tests of general cognition, verbal memory, and category fluency. Repeated-measures analyses were conducted, and the primary outcome was a global composite score averaging all test results.. Mean cognitive change from baseline did not differ between the B vitamin and placebo groups (difference in change in global score: 0.03; 95% CI: -0.03, 0.08; P = 0.30). However, supplementation appeared to preserve cognition among women with a low baseline dietary intake of B vitamins.. Combined B vitamin supplementation did not delay cognitive decline among women with CVD or CVD risk factors. The possible cognitive benefits of supplementation among women with a low dietary intake of B vitamins warrant further study.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Chi-Square Distribution; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Psychometrics; Risk Factors; Statistics, Nonparametric; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.. To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.. Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.. Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12.. A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.. Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L).. After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.. clinicaltrials.gov Identifier: NCT00000541.

Topics: Adult; Aged; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Middle Aged; Risk; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Aged; Cardiovascular Diseases; Drug Therapy, Combination; Female; Folic Acid; Fractures, Bone; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Male; Middle Aged; Proportional Hazards Models; Pyridoxine; Risk Factors; Treatment Outcome; Vitamin B 12

Epidemiological studies suggest that mild to moderate elevation in plasma homocysteine concentration is associated with increased risk of atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine levels by approximately 25% to 30% and may reduce CV events. Therefore, a large, randomized clinical trial--the Heart Outcomes Prevention Evaluation (HOPE)-2 study--is being conducted to evaluate this therapy in patients at high risk for CV events.. To evaluate whether long-term therapy with folic acid and vitamins B6 and B12 reduces the risk of major CV events in a high-risk population. The primary study outcome is the composite of death from CV causes, myocardial infarction and stroke.. A total of 5522 patients aged 55 years or older with pre-existing CV disease or with diabetes and additional risk factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to placebo. Follow-up will average five years, to be completed by the end of 2005.. The patients' baseline characteristics confirmed their high-risk status. Baseline homocysteine levels varied between countries and regions. HOPE-2 is one of the largest trials of folate and vitamins B6 and B12 and is expected to significantly contribute to the evaluation of the role of homocysteine lowering in CV prevention.

Topics: Aged; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Follow-Up Studies; Global Health; Homocysteine; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease.. We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke.. Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49).. Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Follow-Up Studies; Humans; Hyperhomocysteinemia; Male; Middle Aged; Myocardial Infarction; Risk Factors; Stroke; Vascular Diseases; Vitamin B 12; Vitamin B 6

Deficiency of folic acid, vitamin B(6) and/or vitamin B(12) can result in elevated total plasma homocysteine concentrations (tHcy), which are considered to be a risk factor for vascular disease. Studies have shown that supplementation of the three vitamins can lower tHcy even in subjects with tHcy in the normal range.. The aim of this study was to evaluate the effect of a 6 month supplementation with vitamin B(6), B(12) and folate on the concentrations of total plasma homocysteine and serum methylmalonic acid (MMA) of elderly women.. The study was designed as a randomized placebo controlled double-blind trial, and 220 healthy women (aged 60-91 years) were involved. The vitamin and mineral capsule contained pyridoxine (3.4 mg), folic acid (400 microg) and cobalamin (9 microg) in addition to other micronutrients. Blood concentrations of folate, cobalamin, tHcy, MMA and the activity coefficient of erythrocyte alpha-aspartic aminotransferase (alpha-EAST) were measured at baseline and after 6 months of supplementation. Dietary intake was evaluated at the beginning and the end of the intervention by two 3-day diet records.. Median concentrations of serum cobalamin, serum folate and erythrocyte folate increased significantly and tHcy and alpha-EAST activity (indicative of improved status of vitamin B(6)) coefficient decreased significantly in the supplemented group. Median MMA concentration of the supplemented group was significantly lower than that of the placebo group after the intervention. The vitamin supplementation had a greater decreasing effect on the tHcy concentration of volunteers with lower vitamin and higher tHcy initial concentrations. In a linear regression model, baseline tHcy, serum folate, age and alpha-EAST activity coefficient were significantly correlated with the change in tHcy. The change in MMA in the supplement group was significantly associated to the baseline MMA values.. Our results show that a 6 month supplementation including physiological dosages of B vitamins improves the status of these nutrients and reduces tHcy in presumed healthy elderly women.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Geriatric Assessment; Homocysteine; Humans; Methylmalonic Acid; Middle Aged; Minerals; Risk Assessment; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamins

Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability.. We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability.. At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1 [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy).. Lowering tHcy by 3.7 micromol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.

Topics: Biomarkers; Blood Coagulation; Cardiovascular Diseases; Endothelium, Vascular; Folic Acid; Homocysteine; Humans; Inflammation; Ischemic Attack, Transient; Pyridoxine; Risk Factors; Stroke; Vitamin B 12; Vitamin B Complex

To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.. In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.. In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Topics: Aged; Brachial Artery; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Nitroglycerin; Regional Blood Flow; Risk Factors; S-Adenosylmethionine; Tetrahydrofolates; Ultrasonography; Vasodilation; Vasodilator Agents; Vitamin B 12; Vitamin B 6

In apparently healthy people, the relation between blood pressure and risk of subsequent cardiovascular disease (CVD) is linear. In persons with CVD, the relation is uncertain.. We conducted a prospective study of 5218 older women with CVD who reported their blood pressure at baseline in the Women's Antioxidant Cardiovascular Study (WACS), an ongoing double-blind, placebo-controlled secondary prevention trial of the benefits and risks of antioxidant vitamins, folic acid, vitamin B6, and vitamin B12 among women with CVD or > or =3 coronary risk factors. A total of 661 confirmed CVD events (nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass graft procedure, percutaneous coronary angioplasty, or CVD death) occurred during a median follow-up of 6.5 years. After controlling for age, randomized treatment assignment, antihypertensive medication use, and coronary risk factors, we found that systolic blood pressure (SBP) was a strong predictor of CVD events and that the relation between SBP and CVD risk was positive, continuous, and linear (P for linear trend=0.001). For each 10-mm Hg increment in SBP, there was a 9% (95% CI 4% to 15%) increase in risk of secondary CVD events. Diastolic blood pressure, mean arterial pressure, and pulse pressure were weaker predictors of CVD risk in this cohort, and joint consideration of SBP and diastolic blood pressure found that only SBP significantly predicted risk. Use of antihypertensive medication did not modify the relationship of SBP with CVD events.. In this population of women with CVD, we observed a strong, continuous, and linear association between SBP and risk of secondary CVD events. SBP was the blood pressure measure most strongly related to CVD risk.

Topics: Adult; Aged; Antihypertensive Agents; Antioxidants; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Humans; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Factors; Systole; Vitamin B 12; Vitamin B 6

High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults.. We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocysteine status.. A randomized, double-blind trial was conducted in 189 volunteers aged 50-85 y. The subjects had no history of hypertension, anemia, asthma, cancer, or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal. Subjects were randomly assigned to consume 1 cup (0.24 L) breakfast cereal fortified with 440 microg folic acid, 1.8 mg vitamin B-6, and 4.8 microg vitamin B-12 or placebo cereal for 12 wk. Blood was drawn at 0, 2, 12, and 14 wk. Methionine-loading tests were conducted at baseline and week 14.. Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group (P < 0.001). The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2% to 0%, with vitamin B-12 concentrations < 185 pmol/L from 9% to 3%, with vitamin B-6 concentrations < 20 nmol/L from 6% to 2%, and with homocysteine concentrations > 10.4 micromol/L (women) or > 11.4 micromol/L (men) from 6.4% to 1.6%. The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased.. In this relatively healthy group of volunteers, consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations, including post-methionine-load homocysteine concentrations.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Double-Blind Method; Edible Grain; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Methionine; Middle Aged; Vitamin B 12; Vitamin B 6

The relationship between cardiovascular disease and high plasma levels of homocysteine is known; it is therefore necessary to keep the concentrations of this amino acid, considered an independent risk factor for these pathologies, within the physiological range. The objective of this study is to evaluate the efficacy of the medicinal product STRESSEN on homocysteinemia in patients with current cardiovascular disease.. The study was carried out on 40 patients with homocysteinemia higher than 14 micromol/l. Patients were divided into 2 groups of 20: one was treated with STRESSEN for 30 days and the other did not receive any specific therapy. Homocysteinemia was evaluated at t = 0 and t = 30 days in both groups.. STRESSEN determined a significative mean reduction of 39.2% (P < 0.0001) of plasma levels of the considered amino acid, which on the contrary did not change in non treated patients.. The results of this study show the efficacy of STRESSEN in reducing homocysteinemia and, consequently, the risk of coronary disease.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Drug Combinations; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Middle Aged; Vitamin B 12

Vitamin B-6 is necessary for the metabolism of homocysteine and is often used in combination with folic acid and vitamin B-12 in clinical trials that investigate whether the lowering of plasma total homocysteine (tHcy) can prevent vascular disease.. We compared the effects of vitamin B-6 with the effects of folic acid and vitamin B-12, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on basal and postmethionine load (PML) tHcy and cystathionine concentrations.. Ninety patients with suspected coronary artery disease were randomly assigned to 1 of 4 groups to receive daily oral treatment with 1) 0.8 mg folic acid, 0.4 mg vitamin B-12, and 40 mg vitamin B-6 (group A); 2) 0.8 mg folic acid and 0.4 mg vitamin B-12 (group B); 3) 40 mg vitamin B-6 (group C); or 4) placebo (group D). For the first 2 wk, groups A and B received additional folic acid (5 mg/d). A methionine-loading test was performed at baseline and after 3 mo.. Treatment with folic acid and vitamin B-12 caused a rapid and significant lowering of basal (31%) and PML tHcy concentrations (22%), with no effect on cystathionine. Vitamin B-6 did not change basal tHcy and had a significant but limited effect on PML tHcy concentrations. However, vitamin B-6 treatment markedly lowered basal and PML cystathionine by 31% and 42%, respectively.. The folic acid and vitamin B-12 combination applied in WENBIT provides rapid, substantial, and long-term tHcy-lowering effects, whereas the effect of vitamin B-6 on tHcy was relatively small and confined to PML tHcy. However, vitamin B-6 treatment caused a marked reduction in plasma cystathionine. Cystathionine could be a useful marker for assessment of the vitamin B-6 effect and should, together with tHcy, be related to clinical outcome in ongoing trials.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Analysis of Variance; Cardiovascular Diseases; Cystathionine; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methionine; Middle Aged; Norway; Prospective Studies; Vitamin B 12; Vitamin B 6

Thiazides and angiotensin-converting enzyme (ACE) inhibitors are first-choice drugs for lowering elevated blood pressure and hence risk of cardiovascular disease. Homocysteine (tHcy) is another and independent cardiovascular risk factor and has been reported to be elevated in patients on antihypertensive therapy. As these studies reported only associations, a preliminary, randomized, prospective treatment study was performed in 40 hypertensive patients. We investigated the major determinants of tHcy concentrations after treatment with hydrochlorothiazide (HCT) or captopril: vitamins B6, B12, folic acid, and creatinine and cystatin C as parameters of renal function. A total of 21 Patients were treated with HCT and 19 with captopril, for, respectively, 31 and 29 days. HCT, but not captopril, raised tHcy by 16% (P =.003) and also creatinine and cystatin C (P =.025 and P =.004, respectively). This tHcy increase may offset the desired cardioprotection conferred by lowering the blood pressure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cardiovascular Diseases; Creatinine; Cystatin C; Cystatins; Female; Folic Acid; Homocysteine; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Prospective Studies; Risk Factors; Vitamin B 12; Vitamin B 6

Fortification of food with folic acid to prevent neural-tube defects in babies also lowers plasma total homocysteine, which is a risk factor for vascular disease. We investigated the effect of folate and vitamin B12 on homocysteine concentrations. 30 men and 23 women received sequential supplementation with increasing doses of folic acid. After supplementation, the usual dependency of homocysteine on folate diminished, and vitamin B12 became the main determinant of plasma homocysteine concentration. This finding suggests that a fortification policy based on folic acid and vitamin B12, rather than folic acid alone, is likely to be much more effective at lowering of homocysteine concentrations, with potential benefits for reduction of risk of vascular disease.

Topics: Adult; Aged; Cardiovascular Diseases; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Vitamin B 12

In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d.. We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples.. In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order.. Total homocysteine in plasma collected 4-5 h after supplement intake was 12% (1.2 micromol/L; 95% CI: 0.6, 1.7) higher after chlorogenic acid and 11% (1.1 micromol/L; 95% CI: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4% (0.4 micromol/L; 95% CI: 0.0, 0.8) higher after chlorogenic acid and 5% (0.5 micromol/L; 95% CI: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations.. Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established.

Topics: Adult; Cardiovascular Diseases; Chlorogenic Acid; Coffee; Cross-Over Studies; Fasting; Female; Flavonoids; Folic Acid; Glucosides; Homocysteine; Humans; Male; Phenols; Polymers; Postprandial Period; Pyridoxine; Quercetin; Risk Factors; Tea; Vitamin B 12

It is unclear whether total serum homocysteine (tHcy) and the C677T mutation of methylenetetrahydrofolate reductase (MTHFR) are associated with cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD).. A cross-sectional sample of 459 patients with ESRD on chronic dialysis was assessed to determine whether tHcy and the C677T mutation are associated with CVD prevalence in multiple logistic regression. As CVD mortality is high, we examined the relationship between homozygosity and duration of dialysis.. Mean tHcy was higher in patients without a history of CVD (35.2 micromol/L vs. 30.4 micromol/L, P = 0.02). In multivariate models, CVD was negatively associated with tHcy and positively associated with TT genotype, male gender, and body mass index. Mean tHcy levels were higher among those with the TT genotype compared with those with the CC genotype when adjusted for age, folate, creatinine, and albumin (37.9 micromol/L vs. 31.9 micromol/L, P = 0.005). Among whites, the prevalence of the TT genotype was higher in those having undergone less than one year of dialysis (P = 0.002).. The C677T genotype of MTHFR is associated with CVD in ESRD and may be a more meaningful marker than tHcy for abnormal homocysteine metabolism in ESRD. Prospective data from ongoing clinical trials are needed to improve our understanding of these findings. Screening for this polymorphism may help guide prevention measures.

Topics: Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Ethnicity; Female; Folic Acid; Genotype; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Peritoneal Dialysis; Pyridoxine; Renal Dialysis; Risk Factors; Sex Factors; Vitamin B 12

Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Cerebrovascular Disorders; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Middle Aged; Minerals; Nutritional Status; Pyridoxal Phosphate; Risk Factors; Vitamin B 12; Vitamin B Complex; Vitamins

Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater.. Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease.. This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate.. Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD.. The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Topics: Adult; Aged; Analysis of Variance; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Pyridoxine; Risk Factors; Vitamin B 12

Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.. A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.. Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.. Patients were randomized into two groups at week 0. The folate group received 0.25 mg day-1 of folate in addition to 60 mg day-1 of Fe2+, while the placebo group received only 60 mg day-1 of Fe2+.. Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.. Folate administration reduced serum levels of total homocysteine in the folate group as compared with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo group serum levels of vitamin B12 increased by 9.9% (P = 0.010) and 9.6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively.. The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Female; Folic Acid; Hematinics; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12

We measured the vitamin B-6, vitamin B-12, and folic acid nutritional status in a group of apparently healthy men (n = 44) with moderate hyperhomocysteinemia (plasma homocysteine concentration > 16.3 mumol/L). Compared with control subjects (n = 274) with normal plasma homocysteine (< or = 16.3 mumol/L) concentrations, significantly lower plasma concentrations of pyridoxal-5'-phosphate (P < 0.001), cobalamin (P < 0.001), and folic acid (P = 0.004) were demonstrated in hyperhomocysteinemic men. The prevalence of suboptimal vitamin B-6, B-12, and folate status in men with hyperhomocysteinemia was 25.0%, 56.8%, and 59.1%, respectively. In a placebo-controlled follow-up study, a daily vitamin supplement (10 mg pyridoxal, 1.0 mg folic acid, 0.4 mg cyanocobalamin) normalized elevated plasma homocysteine concentrations within 6 wk. Because hyperhomocysteinemia is implicated as a risk factor for premature occlusive vascular disease, appropriate vitamin therapy may be both efficient and cost-effective to control elevated plasma homocysteine concentrations.

Topics: Adult; Aged; Cardiovascular Diseases; Cystathionine beta-Synthase; Dose-Response Relationship, Drug; Double-Blind Method; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Pyridoxine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

The influence of a monophasic sub-50 oral contraceptive (OC), Marvelon, on fasting total homocysteine levels was investigated in OC users and controls. Homocysteine levels in serum of OC users were significantly higher (P less than .01) than in controls during the low-hormonal phase of the cycles and comparable with levels determined in heterozygotes for homocystinuria. Blood levels of pyridoxal phosphate (PLP) were significantly lower (P less than .05) in OC users both in the low and high hormonal phase. However, there were no significant differences in the levels of homocysteine nor in folate and vitamin B12 between both groups in the high-hormonal phase. In contrast to the control group, the homocysteine levels in OC users in the high-hormonal phase of the cycle were significantly decreased compared with those on a low-hormonal day (P less than .05). These data suggest that cyclically recurrent periods of hyperhomocysteinemia do occur during sub-50 OC use in normal women and might be considered a predisposition to the occurrence of vascular complications.. Serum level of the amino acid homocysteine, and vitamins folate, B12 and pyridoxal phosphate, and red blood cell folate levels were determined on Cycle days 3 and 21 in 26 women using the oral contraceptive Marvelon (30 mcg ethinyl estradiol and 150 mcg desogestrel), compared with 15 menstruating women. The 26 pill users had taken Marvelon for mean 3.7 years. Fasting homocysteine was assayed with an amino acid autoanalyzer; folate and B12 by radioimmunoassay; pyridoxal by high-performance liquid chromatography. The pill users had significantly higher homocysteine on Day 3 than controls (p0.01), levels comparable to those in heterozygote carriers of homocystinuria. Homocysteine levels were significantly lower in pill users on Day 21 compared to their levels on Day 3. Pyridoxal levels were significantly lower in Marvelon users on both days tested (p0.05). Homocysteine, folate and B12 were not significantly different in pill users and non-users on Day 21. The data indicate a cycle of high and low homocysteine levels in users of Marvelon. High homocysteine has been implicated in vascular disease, and may be a causative factor in the risk for thrombosis in pill users.

Topics: Adult; Cardiovascular Diseases; Causality; Contraceptives, Oral; Desogestrel; Fasting; Female; Homocysteine; Humans; Norpregnenes; Pyridoxal Phosphate; Vitamin B 12

The aim of this study was to evaluate the variation of homocysteine (Hcy) levels in patients with rheumatoid arthritis (RA) and to analyze the relationship to inflammatory parameters, cardiovascular risk, and methotrexate (MTX).. This cross-sectional study assessed disease activity and treatment in RA patients. The European League Against Rheumatism (EULAR) 2015 HeartSCORE was performed for cardiovascular (CV) risk estimation and levels of plasma Hcy, serum folate concentrations, vitamin B12, and erythrocyte sedimentation rate (ESR) were measured.. A total of 103 participants with mean age 53 ± 10 years and mean disease duration 10.55 ± 7.34 years were included. Patients were treated with MTX in 69.9% of cases and corticosteroid in 80.5% of cases. Of all patients, 13% had a cardiovascular inheritance, 25% were hypertensive, and 18% had diabetes. The EULAR 2015 HeartSCORE was high and very high (≥5%) in 35% of cases. Mean Hcy level was 12.54 ± 4.2 µmol/L [6.89-32.92] and hyperhomocysteinemia was noted in 20.4% of patients. Analytic study demonstrated that hyperhomocysteinemia was associated with male gender (p = 0.01), MTX use (p = 0.01), smoking (p = 0.008), renal failure (p = 0.04), and high disease activity (p = 0.05), but there was no association with the HeartSCORE (p = 0.23). Hcy level was negatively correlated with folate (p = 0.009) and vitamin B12 level (p = 0.02) and positively with age (p = 0.01), C‑reactive protein (CRP; p = 0.05), and Simplified Disease Activity Index (SDAI; p = 0.03). In multivariate logistic regression analysis, current MTX use, levels of vitamin B12 and creatine, and Clinical Disease Activity Index (CDAI) appeared to be independent factors associated with hyperhomocysteinemia.. MTX use, CDAI, and the levels of vitamin B12 and creatine are independent factors associated with hyperhomocysteinemia.. HINTERGRUND: Ziel der vorliegenden Studie war es, Unterschiede in den Werten für Homocystein (Hcy) bei Patienten mit rheumatoider Arthritis (RA) und den Zusammenhang mit Entzündungsparametern, Herz-Kreislauf-Risiko und Methotrexat (MTX) zu untersuchen.. In dieser Querschnittstudie wurden Krankheitsaktivität und Therapie von RA-Patienten analysiert. Zur Abschätzung des kardiovaskulären Risikos wurde The European League Against Rheumatism (EULAR) 2015 HeartSCORE eingesetzt und die Werte für Plasma-Hcy, Folsäurekonzentration im Serum, Vitamin B12 und Blutsenkungsgeschwindigkeit (BSG) bestimmt.. Es wurden 103 Teilnehmer mit einem mittleren Alter von 53 ± 10 Jahren und einer mittleren Krankheitsdauer von 10,55 ± 7,34 Jahren in die Studie einbezogen. In 69,9% der Fälle wurden die Patienten mit MTX und in 80,5% mit Kortikosteroiden behandelt. Bei 13% der Patienten bestanden familiär kardiovaskuläre Erkrankungen, bei 25% Hypertonie und bei 18% Diabetes mellitus. In 35% der Fälle war der EULAR 2015 HeartSCORE hoch oder sehr hoch (>5%). Im Mittel betrug der Hcy-Wert 12,54 ± 4,2 µmol/l [6,89–32,92], und eine Hyperhomocysteinämie lag bei 20,4% der Patienten vor. Die Auswertung ergab, dass eine Hyperhomocysteinämie mit männlichem Geschlecht (p = 0,01), MTX-Therapie (p = 0,01), Rauchen (p = 0,008), Niereninsuffizienz (p = 0,04) und hoher Krankheitsaktivität (p = 0,05) assoziiert war, aber es gab keinen Zusammenhang mit dem HeartSCORE (p = 0,23). Der Hcy-Wert war negativ mit den Werten für Folsäure (p = 0,009) und Vitamin B12 (p = 0,02) korreliert und positiv mit dem Alter (p = 0,01), C‑reaktivem Protein (CRP; p = 0,05) und dem Simplified Disease Activity Index (SDAI; p = 0,03). In der multivariaten logistischen Regressionsanalyse schienen eine derzeitige MTX-Therapie, Werte für Vitamin B12 und Kreatin sowie der Clinical Disease Activity Index (CDAI) unabhängige Faktoren zu sein, die mit Hyperhomocysteinämie assoziiert waren.. MTX-Therapie, CDAI und die Werte für Vitamin B12 und Kreatin sind unabhängige, mit Hyperhomocysteinämie assoziierte Faktoren.

Topics: Adult; Arthritis, Rheumatoid; Cardiovascular Diseases; Creatine; Cross-Sectional Studies; Folic Acid; Heart Disease Risk Factors; Homocysteine; Humans; Inflammation; Male; Methotrexate; Middle Aged; Risk Factors; Vitamin B 12

Emerging evidence suggests that dietary one-carbon metabolism-related B-vitamins are associated with the reduced risk of cardiovascular disease (CVD) in the general population. However, only a few studies have assessed their associations in patients with type 2 diabetes (T2D).. This study aimed to assess the associations between the intake of three one-carbon metabolism-related B-vitamins (folate, vitamin B6, and vitamin B12) and CVD risk in Chinese patients with T2D.. A hospital-based case-control study of 419 patients with T2D and newly diagnosed CVD and 419 age- (±5 years) and sex-matched T2D-only controls was carried out in China. A validated 79-item semi-quantitative food-frequency questionnaire administered in face-to-face interviews was used to measure dietary B-vitamin intake. Conditional logistic regression was used to assess associations, which were tested by estimating odds ratios (ORs) with 95% confidence intervals (CIs).. Compared with the lowest quartile, the multivariable-adjusted ORs and 95% CIs for highest quartile were 0.32 (95% CI: 0.20, 0.52; p trend <0.001) for folate, 0.47 (95% CI: 0.30, 0.76; p trend = 0.002) for vitamin B6, and 1.02 (95% CI: 0.67, 1.55; p trend = 0.841) for vitamin B12. Consistent inverse associations were found for folate intake from eggs, vegetables, fruits, soy, and other foods but not for folate intake from grains.. Findings suggest that the high consumption of folate and vitamin B6, but not that of vitamin B12, might be associated with the low risk of CVD in patients with T2D. This study suggests that dietary folate and vitamin B6 protect against CVD in patients with T2D.

Topics: Carbon; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Folic Acid; Humans; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamins

Cobalamin is an essential molecule for humans; it is exceptionally important for various body functions, including deoxyribonucleic acid synthesis and cellular energy production. Vegans are more vulnerable to vitamin B12 deficiency than natives with moderate consumption of animal dietary supplements or people with inadequate nutritional patterns. However, the long-term effects of sub-medical deficiency have not been thoroughly studied, but they may have a negative impact on the cardiovascular system, pregnancy outcomes, and vascular, renal, cognitive, bone, and eye health. Alongside the statin remedy, that is a powerful approach for CVD prevention. Another approach is related to the B nutrition substitution remedy with folic acid, and vitamins B6 and B12 are extensively practised nowadays. There is a tremendous interest in plasma homocysteine (tHcy) as a cardiovascular hazard factor. However, current research in the field of its prevention is more inclined toward confirming the benefit of tHcy-reducing remedy with vitamin B12. Thus, while folic acid fortification is primarily aimed at reducing neural-tube defects, it may also play a significant role in the primary prevention of CVD by lowering tHcy. Folate and B-vitamins play important roles in CVD prevention and nutrition policy implementation. Patients affected with Chronic Kidney Disease (CKD) or end-stage Stage Renal Disease (ESRD) experience a tremendous cardiovascular threat that may also further lead to death. As a result, routine monitoring of vitamin B12 levels is likely to be beneficial for the early detection and treatment of metabolic vitamin B12 deficiency, as well as the prevention of heart-related diseases.

Topics: Cardiovascular Diseases; Folic Acid; Humans; Kidney; Kidney Failure, Chronic; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Our study aims to evaluate the associations between the serum cobalamin (vitamin B12) and related biomarkers with mortality in hypertensive adults. Data on serum cobalamin from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2014 were included. Mortality status was linked to National Death Index mortality data through 31 December, 2019. Cox regression and restricted cubic spline (RCS) analyses were used to determine the hazard ratios (HRs) and 95% CIs for mortality risk. A total of 9934 hypertensive adults were included in the analysis (mean age, 58.1 ± 17.5 years; 4899 [49.3%] men). At 11.0 years of mean follow-up, 935 cardiovascular deaths and 3096 all-cause deaths were identified. Compared to the third quartiles, the first and fourth quartiles of serum cobalamin were associated with risk of cardiovascular mortality, with multivariable-adjusted HRs of 1.26 (1.05-1.53) and 1.40 (1.17-1.68). Similar results were observed in the relationship between serum cobalamin and all-cause mortality. These results were supported by the RCS analysis. The inflection points for the nonlinear associations of serum cobalamin with cardiovascular and all-cause mortality were 649.9 pg/mL and 577.2 pg/mL, respectively. In addition, compared with the second quartile of circulating methylmalonic acid (MMA, a cobalamin-deficiency marker), this association with the fourth quartile was evident for an increased rate of cardiovascular and all-cause mortality, with 111% (HR = 2.11, 1.71-2.61) and 73% (HR = 1.73, 1.55-1.93) increase. Findings suggest that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults. This study was a prospective cohort study that included serum cobalamin data from 9934 hypertensive adults from the NHANES from 1999-2006 and 20011-2014. Findings suggested that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults.

Topics: Adult; Aged; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Nutrition Surveys; Prospective Studies; Vitamin B 12

The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD.. The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk.. Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31-2.20) for all-cause mortality, and 2.00 (1.39-2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001).. MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.

Topics: Adult; Aged; Cardiovascular Diseases; Humans; Male; Methylmalonic Acid; Nutrition Surveys; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

The associations of serum folate and vitamin B12 levels with cardiovascular outcomes among patients with type 2 diabetes (T2D) remain unclear.. To investigate the associations of serum folate and vitamin B12 levels with risk of cardiovascular disease (CVD) mortality among individuals with T2D.. This prospective cohort study included 8067 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2014 and NHANES III (1988-1994). American Diabetes Association criteria were used to define T2D. Data were analyzed between October 1, 2020, and April 1, 2021.. Serum folate and vitamin B12 levels.. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of serum folate and vitamin B12 levels with risks of CVD and all-cause mortality. Two multivariable models were constructed. Restricted cubic spline analyses were used to examine the nonlinear association of serum folate levels and vitamin B12 levels with CVD mortality, and nonlinearity was assessed using the likelihood ratio test.. This cohort study included data from 7700 participants in the folate analysis (mean [SE] age, 57.8 [0.3] years; 3882 men [weighted, 50.5%]; median serum folate level, 12.1 ng/mL [IQR, 7.1-19.5 ng/mL]) and 4860 participants for the vitamin B12 analysis (mean [SE] age, 57.8 [0.3] years; 2390 men [weighted, 50.7%]; median serum vitamin B12 level, 506.1 pg/mL [IQR, 369.1-703.5 pg/mL]). During 72 031 person-years of follow-up, 799 CVD deaths were documented for the folate analysis, and during 43 855 person-years of follow-up, 467 CVD deaths were reported for the vitamin B12 analysis. Nonlinear associations were observed for serum levels of folate (P = .04 for nonlinearity) and vitamin B12 (P = .04 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the second quartile of serum folate levels (7.1-12.1 ng/mL), the hazard ratios for CVD mortality were 1.43 (95% CI, 1.04-1.98) for participants in the lowest serum folate level quartile (<7.1 ng/mL) and 1.03 (95% CI, 0.74-1.44) for participants in the highest quartile (≥19.5 ng/mL). In addition, compared with participants in the second quartile of serum vitamin B12 levels (369.1-506.0 pg/mL), the hazard ratios for CVD mortality were 1.74 (95% CI, 1.20-2.52) for participants in the lowest quartile (<369.1 pg/mL) and 2.32 (95% CI, 1.60-3.35) for participants in the highest quartile (≥703.5 pg/mL). Similar patterns of association were observed for all-cause mortality (nonlinearity: P = .01 for folate and P = .02 for vitamin B12).. This cohort study found that both low and high serum levels of vitamin B12 as well as low serum levels of folate were significantly associated with higher risk of CVD mortality among individuals with T2D.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Folic Acid; Humans; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Proportional Hazards Models; Prospective Studies; Vitamin B 12

The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71-0.85) and 0.79 (0.71-0.86) for all-cause mortality, 0.59 (0.48-0.72) and 0.69 (0.56-0.85) for CVD mortality, and 0.68 (0.56-0.84) and 0.73 (0.60-0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78-0.95) and 0.88 (0.80-0.97) for all-cause mortality and 0.53 (0.41-0.69) and 0.56 (0.44-0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults.

Topics: Adult; Cardiovascular Diseases; Cause of Death; Female; Folic Acid; Humans; Male; Nutrition Surveys; Pyridoxine; Vitamin B 12; Vitamin B 6

Vitamin B 12 (cobalamin) deficiency may be a significant cause of hyperhomocysteinemia, and high homocysteine (Hcy) levels are associated with an increased risk of cardiovascular disease. Endothelium-derived microparticles (EMPs) are a new marker in endothelial dysfunction and atherosclerosis, which play a role in cardiovascular diseases' pathogenesis. This study aimed to evaluate the EMPs, the markers of endothelial dysfunction and atherosclerosis, and lipid profile in teenagers with cobalamin deficiency.. This prospective study included 143 teenagers, 75 vitamin B 12 deficient patients and 68 healthy controls between 11 and 18 years of age. Routine laboratory tests, hemogram, vitamin B 12 , folic acid, ferritin, Hcy, lipid profile and EMPs were examined and compared. EMP subgroups were analyzed by flow cytometry method according to the expression of membrane-specific antigens. The microparticles released from the endothelium studied were VE-cadherin (CD144), S-endo1 (CD146), and Endoglin (CD105).. The present study demonstrates that circulating CD105+ EMP, CD144+ EMP, CD146+ EMPs, and Hcy were increased, and high-density lipoprotein (HDL) cholesterol was reduced in teenagers with cobalamin deficiency. Vitamin B 12 showed a negative correlation with EMPs and Hcy, positive correlation with folate and HDL. All EMPs showed a significant positive correlation with triglyceride, vitamin B 12 , and HDL.. Vitamin B 12 deficiency may predispose to endothelial damage and atherosclerosis by increasing EMPs and harms lipid metabolism in the long term.

Topics: Adolescent; Atherosclerosis; Biomarkers; Cardiovascular Diseases; CD146 Antigen; Endothelium; Endothelium, Vascular; Humans; Lipids; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Humans; Monocytes; Vitamin B 12; Vitamin B 12 Deficiency

The association of moderate hyperhomocysteinemia (HHcy) (15-30 μmol/L) with cardiovascular diseases (CVD) has been challenged by the lack of benefit of vitamin supplementation to lowering homocysteine. Consequently, the results of interventional studies have confused the debate regarding the management of patients with intermediate/severe HHcy.. We sought to evaluate the association of intermediate (30-100 μmol/L) and severe (>100 μmol/L) HHcy related to vitamin deficiencies and/or inherited disorders with CVD outcomes.. We performed a retrospective cross-sectional study on consecutive patients who underwent a homocysteine assay in a French University Regional Hospital Center. Patients with CVD outcomes were assessed for vitamin B12, folate, Hcy, methylmalonic acid, and next-generation clinical exome sequencing.. We evaluated 165 patients hospitalized for thromboembolic and other cardiovascular (CV) manifestations among 1006 patients consecutively recruited. Among them, 84% (138/165) had Hcy >30 μmol/L, 27% Hcy >50 μmol/L (44/165) and 3% Hcy >100 μmol/L (5/165). HHcy was related to vitamin B12 and/or folate deficiency in 55% (87/165), mutations in one or more genes of one-carbon and/or vitamin B12 metabolisms in 11% (19/165), and severe renal failure in 15% (21/141) of the studied patients. HHcy was the single vascular risk retrieved in almost 9% (15/165) of patients. Sixty % (101/165) of patients received a supplementation to treat HHcy, with a significant decrease in median Hcy from 41 to 17 µmol/L (IQR: 33.6-60.4 compared with 12.1-28). No recurrence of thromboembolic manifestations was observed after supplementation and antithrombotic treatment of patients who had HHcy as a single risk, after ∼4 y of follow-up.. The high frequency of intermediate/severe HHcy differs from the frequent moderate HHcy reported in previous observational studies of patients with pre-existing CVD. Our study points out the importance of diagnosing and treating nutritional deficiencies and inherited disorders to reverse intermediate/severe HHcy associated with CVD outcomes.

Topics: Adult; Cardiovascular Diseases; Child, Preschool; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Male; Metabolism, Inborn Errors; Methylmalonic Acid; Middle Aged; Retrospective Studies; Vitamin B 12

Higher circulating folate and vitamin B-12 concentrations and lower circulating homocysteine concentrations during pregnancy seem to be associated with fetal development. These micronutrients may also be associated with cardiometabolic health.. We examined the associations of circulating folate, vitamin B-12, and homocysteine concentrations during pregnancy and in neonates with childhood cardiometabolic outcomes.. This study was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onward. We sampled blood in early pregnancy and cord blood. We measured cardiometabolic outcomes in the children at school age. Among 4449 children aged 10 y (median: 9.7; 95% range: 9.3, 10.7), we examined associations of plasma folate, serum vitamin B-12, and plasma homocysteine concentrations in early pregnancy and at birth with BMI, body fat distribution, heart rate, blood pressure, and insulin, glucose, and lipid concentrations, using linear regression models. Using logistic models, we examined the associations of these micronutrients with risks of overweight/obesity and clustering of cardiovascular risk factors.. One standard deviation score (SDS) higher maternal plasma folate concentration was associated with lower BMI (-0.04 SDS; 95% CI: -0.08, -0.01), android-to-gynoid fat ratio (-0.04 SDS; 95% CI: -0.07, -0.01), systolic blood pressure (-0.06 SDS; 95% CI: -0.10, -0.03), risk of overweight (OR: 0.87; 95% CI: 0.78, 0.96), and clustering of cardiovascular risk factors (OR: 0.79; 95% CI: 0.68, 0.91). One SDS higher maternal serum total B-12 concentration was associated with lower glucose (-0.06 SDS; 95% CI: -0.10, -0.02) and higher HDL cholesterol concentrations (0.04 SDS; 95% CI: 0.00, 0.08). Cord blood folate, vitamin B-12, and homocysteine concentrations were not consistently associated with cardiometabolic outcomes.. Subtle differences in circulating folate and vitamin B-12 concentrations in early pregnancy may be associated with child cardiometabolic health at age 10 y. The causality and mechanisms underlying these associations need further study.

Topics: Cardiometabolic Risk Factors; Cardiovascular Diseases; Child; Female; Folic Acid; Glucose; Homocysteine; Humans; Infant, Newborn; Micronutrients; Overweight; Pregnancy; Prospective Studies; Risk Factors; Vitamin B 12; Vitamins

Whether a modestly elevated homocysteine level is causally associated with an increased risk of cardiovascular disease remains unestablished. We conducted a Mendelian randomization study to assess the associations of circulating total homocysteine (tHcy) and B vitamin levels with cardiovascular diseases in the general population.. Independent single nucleotide polymorphisms associated with tHcy (n = 14), folate (n = 2), vitamin B6 (n = 1), and vitamin B12 (n = 14) at the genome-wide significance level were selected as instrumental variables. Summary-level data for 12 cardiovascular endpoints were obtained from genetic consortia, the UK Biobank study, and the FinnGen consortium.. Higher genetically predicted circulating tHcy levels were associated with an increased risk of stroke. For each one standard deviation (SD) increase in genetically predicted tHcy levels, the odds ratio (OR) was 1.11 (95% confidence interval (CI), 1.03, 1.21; p = 0.008) for any stroke, 1.26 (95% CI, 1.05, 1.51; p = 0.013) for subarachnoid hemorrhage, and 1.11 (95% CI, 1.03, 1.21; p = 0.011) for ischemic stroke. Higher genetically predicted folate levels were associated with decreased risk of coronary artery disease (OR. This study reveals suggestive evidence that B vitamin therapy and lowering of tHcy may reduce the risk of stroke, particularly subarachnoid hemorrhage and ischemic stroke.

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Mendelian Randomization Analysis; Risk Factors; Vitamin B 12; Vitamin B Complex

An abnormal lipid profile is an independent risk factor for cardiovascular diseases. The relationship between vitamin B12 deficiency and lipid profile is inconclusive, with most studies conducted in unhealthy populations. In this study, we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women, aged 19-30 years, from different colleges at King Saud University, Saudi Arabia. Sociodemographic, anthropometric, biochemical, and lifestyle data were collected, including diet and physical activity. Serum vitamin B12 deficiency was defined as serum B12 level of <148 pmol/L. The prevalence of vitamin B12 deficiency was approximately 0.6%. Using multivariable linear regression models, serum vitamin B12 levels were found to be inversely associated with total cholesterol (B = -0.26;

Topics: Adult; Age Factors; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Female; Healthy Volunteers; Humans; Lipid Metabolism; Obesity; Risk Factors; Saudi Arabia; Sex Factors; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Topics: Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Female; Humans; Male; Risk Factors; Survival Rate; United Kingdom; Vitamin B 12; Vitamin B 12 Deficiency

Folate and vitamin B12 are keys to the correct functioning of one-carbon (1-C) metabolism. The current evidence on associations between 1-C metabolism biomarkers and mortality is inconclusive and generally based on younger or institutionalized populations. This study aimed to determine the associations between biomarkers of 1-C metabolism and all-cause and cardiovascular (CVD) mortality in the very old.. The Newcastle 85+ Study is a prospective longitudinal study of participants aged 85 at recruitment living in Northeast England. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were available for 752-766 participants. Associations between biomarkers of 1-C metabolism and all-cause and CVD mortality for up to 9 years were assessed by Cox proportional hazard models and confirmed by restricted cubic splines.. Participants with higher tHcy concentrations had higher risk of death from any cause (hazard ratio [HR] [×10 μmol/L]: 1.24, 95% confidence interval [CI]: 1.10-1.41) and cardiovascular diseases (HR [×10 μmol/L]: 1.23, 95% CI: 1.04-1.45) than those with lower concentrations; and women with higher plasma vitamin B12 concentrations had increased risk of all-cause and cardiovascular mortality (HR [×100 pmol/L]: 1.10, 95% CI: 1.04-1.16) after adjustment for key sociodemographic, lifestyle, and health confounders.. Higher concentrations of tHcy in all participants and plasma vitamin B12 in women were associated with increased risk of all-cause and CVD mortality in the very old. This confirms findings for tHcy in younger populations but the adverse relationships between elevated plasma vitamin B12 concentrations and mortality in this setting are novel and require further investigation.

Topics: Aged, 80 and over; Aging; Biomarkers; Cardiovascular Diseases; Correlation of Data; Demography; Erythrocytes; Female; Folic Acid; Health Status Disparities; Homocysteine; Humans; Male; Risk Assessment; Risk Factors; Sex Factors; Socioeconomic Factors; United Kingdom; Vitamin B 12

Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality.. The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2).. We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic.. We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol.. We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.

Topics: Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Genome-Wide Association Study; Humans; Insulin Resistance; Leptin; Lipids; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Vitamin B 12

BACKGROUND The purpose of this study was to assess the values of the mean platelet volume (MPV) in children with attention deficit hyperactivity disorder (ADHD) and with autism spectrum disorders (ASDs) to determine the risk of cardiovascular disease in these 2 disorder groups. MATERIAL AND METHODS The study included a total of 79 patients with ADHD or ASDs and controls in the Van region of Turkey. The control group included subjects of matching age and sex with no ADHD, ASDs, or chronic disease and taking no vitamins. The hematological parameters of the patients, including MPV, vitamin B12, and vitamin D, were assessed. RESULTS The study included a total of 79 children and adolescents aged 2-18 years (32 females and 47 males). Of the patients, 36 were in the ADHD group, 18 in the ASDs group, and 25 in the control group. There was no statistically significant difference in hematological parameters between the groups, but there were significant differences in terms of vitamin D and vitamin B12. The patient groups showed lower levels of vitamin B12 and vitamin D. In the ADHD group, there was a negative correlation between both vitamins and MPV (p<0.05). Partial correlation analysis of the ADHD group showed that MPV in particular was negatively correlated to vitamin D, and not to vitamin B12 (p: 0.03). CONCLUSIONS Both ADHD and ASDs may accompany increased risk for cardiovascular disease due to the presence of vitamin B12 and D deficiency and their own characteristics. Therefore, these disorders should be closely followed up.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Avitaminosis; Biomarkers; Cardiovascular Diseases; Child; Female; Humans; Male; Mean Platelet Volume; Risk Factors; Vitamin B 12; Vitamin D

B-vitamins involved in one-carbon metabolism (OCM) can affect arsenic metabolism efficiency in highly arsenic exposed, undernourished populations. We evaluated whether dietary intake of OCM nutrients (including vitamins B2, B6, folate (B9), and B12) was associated with arsenic metabolism in a more nourished population exposed to lower arsenic than previously studied. Dietary intake of OCM nutrients and urine arsenic was evaluated in 405 participants from the Strong Heart Study. Arsenic exposure was measured as the sum of iAs, monomethylarsonate (MMA) and dimethylarsenate (DMA) in urine. Arsenic metabolism was measured as the individual percentages of each metabolite over their sum (iAs%, MMA%, DMA%). In adjusted models, increasing intake of vitamins B2 and B6 was associated with modest but significant decreases in iAs% and MMA% and increases in DMA%. A significant interaction was found between high folate and B6 with enhanced arsenic metabolism efficiency. Our findings suggest OCM nutrients may influence arsenic metabolism in populations with moderate arsenic exposure. Stronger and independent associations were observed with B2 and B6, vitamins previously understudied in relation to arsenic. Research is needed to evaluate whether targeting B-vitamin intake can serve as a strategy for the prevention of arsenic-related health effects at low-moderate arsenic exposure.

Topics: Adult; Aged; Arsenic; Cardiovascular Diseases; Cohort Studies; Female; Folic Acid; Humans; Indians, North American; Male; Middle Aged; Riboflavin; South Dakota; Vitamin B 12; Vitamin B 6

Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk.. We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B. Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05).. Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels.

Topics: Adult; Anticonvulsants; Carbamazepine; Cardiovascular Diseases; Case-Control Studies; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Vitamin B 12

Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients.. 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices.. Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025).. Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

Topics: Antihypertensive Agents; Autonomic Nervous System Diseases; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Diabetic Neuropathies; Female; Heart Rate; Humans; Hypertension; Hypoglycemic Agents; Male; Mass Screening; Metformin; Middle Aged; Prevalence; Proton Pump Inhibitors; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Folate is involved in carbohydrate metabolism, a process that can have clinical implications regarding diabetes management. The aim of this study was to assess the relationship between serum folate and fatality among adults with diabetes.. A retrospective cohort study was conducted with 532 adults with diabetes who participated in Phase II of NHANES III (National Health and Nutrition Examination Survey III; 1991-1994). This study served as baseline and was linked to the National Death Index database for a 15-y (1991-2006) follow-up study. Estimates of hazard ratios (HRs) for all-cause and cancer-related deaths, cardiovascular disease (CVD), and diabetes for individuals with different serum folate levels were obtained from Cox proportional hazards regression.. The mean age of adults with diabetes and detected serum folate at baseline was 63.2 y (SD 13.8 y). During follow-up, diabetes was listed as a contributor for 138 of 299 deaths. For all-cause deaths, the fatality rate of the upper quartile (74.30/1000 person-years [PY]) was almost twofold higher than the lower quartile (41.75/1000 PY) of serum folate levels. After adjusting for several covariates, including serum vitamin B12, cotinine, homocysteine and CVD history at baseline; the HRs for all-cause fatalities were 1.00 (reference), 1.62 (95% confidence interval [CI], 1.06-2.47) and 1.76 (95% CI, 1.09-2.83) among adults with diabetes in the lower, intermediate, and upper quartiles of serum folate levels, respectively.. Results indicate that high serum folate concentrations are associated with an increased fatality risk among adults with diabetes. Further studies are warranted to determine the mechanism(s) of this phenomenon.

Topics: Aged; Cardiovascular Diseases; Cotinine; Diabetes Mellitus; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Proportional Hazards Models; Retrospective Studies; Risk Factors; Socioeconomic Factors; Vitamin B 12

Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM).We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50 ± 13.26 years) with T2DM (N = 839), hypertension (N = 490), or CVD (N = 7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged < 50, 50 to 64, 65 to 80, and ≥80 years. A subgroup analysis was also performed to identify correlations between the serum biochemical markers. Stratified chi-squared analyses were performed based on the levels of folic acid and total vitamin D.In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P < 0.05 for all). The linear regression and stratified analyses showed that the highest levels of folic acid and vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P < 0.05 for all), whereas the highest level of vitamin B12 correlated with a lowest level of homocysteine in CVD patients only (P < 0.05).Our results indicate that the contributions of both vitamin D2 and vitamin D3 should be considered in investigations of the effects of vitamin D supplements in T2DM, CVD, and hypertension patients. Our findings warrant future studies of the benefits of vitamin D and folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone.

Topics: Aged; Aged, 80 and over; Asian People; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Hypertension; Male; Vitamin B 12; Vitamin D

Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p < 0.01) during pregnancy, increased systolic (p < 0.05) and diastolic (p < 0.01) blood pressure, and lowered the levels of plasma/liver DHA (p < 0.05 for both) but did not affect the lipid profile. Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p < 0.05) the levels of plasma triglycerides. Omega-3 fatty acid supplementation to the vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial.

Topics: Animals; Cardiovascular Diseases; Deficiency Diseases; Dietary Supplements; Fatty Acids, Omega-3; Female; Fetal Development; Hypertriglyceridemia; Lactation; Liver; Male; Maternal Nutritional Physiological Phenomena; Organ Size; Overweight; Pregnancy; Rats, Wistar; Vitamin B 12; Vitamin B 12 Deficiency; Weaning; Weight Gain

This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population.. A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m² and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m²) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer.. Vitamin B12 was negatively associated with TNF-α (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r = -0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p < 0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = -0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r² = -0.17, p < 0.05) and in children (r² = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r² = -0.78, p < 0.05).. Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Resistin; Risk Factors; Saudi Arabia; Tumor Necrosis Factor-alpha; Vitamin B 12; Waist Circumference

Many studies have reported that serum total homocysteine (tHcy) levels in cystathionine-beta-synthase (CBS) carriers are usually normal and only elevated after a methionine load. However, the amount of methionine required for a loading test is non-physiological and is never reached with regular feeding. Therefore, CBS carriers do not seem to be at an increased risk of cardiovascular diseases. However, the risk of cardiovascular diseases of CBS carriers with folate deficiency has not been studied. We recently found an extraordinarily high carrier rate (1/7.78) of a novel CBS mutation (p.D47E, c.T141A) in an Austronesian Taiwanese Tao tribe who live in a geographic area with folate deficiency. We evaluated if the CBS carriers tend to have higher fasting serum tHcy concentrations than non-carriers in presence of folate deficiency.. The serum tHcy and folate levels before and after folate replacement were measured in 48 adult Tao carriers, 40 age-matched Tao non-carriers and 40 age-matched Han Taiwanese controls.. The serum tHcy level of the Tao CBS carriers (17.9 ± 3.8 μmol/l) was significantly higher than in Tao non-carriers (15.7 ± 3.5 μmol/l; p < 0.008) and Taiwanese controls (11.8 ± 2.9 μmol/l; p < 0.001). Furthermore, a high prevalence of folate deficiency in the Tao compared with the Taiwanese controls (4.9 ± 1.8 ng/ml vs. 10.6 ± 5.5 ng/ml; p < 0.001) was also noted. Of note, the difference in tHcy levels between the carriers and non-carriers was eliminated by folate supplementation. (carriers:13.65 ± 2.13 μmol/l; non-carriers:12.39 ± 3.25 μmol/l, p = 0.321).. CBS carriers tend to have a higher tHcy level in the presence of folate deficiency than non-carriers. Although many reports have indicated that CBS carriers are not associated with cardiovascular disease, the risk for CBS carriers with folate deficiency has not been well studied. Owing to a significantly elevated level of fasting tHcy without methionine loading, it is important to evaluate the risk of cardiovascular disease in CBS carriers with folate deficiency.

Topics: Aged; Cardiovascular Diseases; Case-Control Studies; Cystathionine beta-Synthase; Dietary Supplements; Fasting; Female; Folic Acid; Folic Acid Deficiency; Genotyping Techniques; Heterozygote; Homocysteine; Homocystinuria; Humans; Male; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Prevalence; Risk Factors; Taiwan; Vitamin B 12

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Critical Illness; Diabetes Mellitus; Female; Humans; Intensive Care Units; Iran; Male; Middle Aged; Severity of Illness Index; Surgical Procedures, Operative; Vitamin B 12; Young Adult

Topics: Animals; Cardiovascular Diseases; Disease Models, Animal; Folic Acid; Homocysteine; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Methylenetetrahydrofolate Reductase (NADPH2); Oxidative Stress; Risk Factors; Signal Transduction; Vitamin B 12

Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.. To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.. We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.. Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 μM among TT homozygotes as compared to 12.3 ± 5.6 μM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal ( 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).. Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency be tested for MTHFR polymorphism in order to identify potential vascular abnormalities and increased cardiovascular risk.

Topics: Adult; Cardiovascular Diseases; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Homozygote; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Physical Endurance; Polymorphism, Genetic; Prospective Studies; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD.

Topics: Adult; Cardiovascular Diseases; Comorbidity; Depressive Disorder, Major; Erythrocytes; Fatty Acids; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Oxidative Stress; Recurrence; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Meta-analyses have suggested an effect of MTHFR C677T genotype (rs1801133), a proxy for blood total homocysteine, on cardiovascular disease (CVD) in populations with low population dietary folate. The aim was to examine the association and effect modification by serum folate and vitamin B12 levels between MTHFR and CVD-related outcomes in a general population with no mandatory folic acid fortification policy.. The study population included 13,748 adults retrieved from pooling of four population-based studies conducted in Denmark. MTHFR genotype, serum folate (measured in approximately 9,356 individuals), and serum vitamin B12 (9,215 individuals), hypertension, and dyslipidemia were measured at baseline, and participants were followed for a mean of 10.5-11.7 years in central registries for diagnoses of stroke (623 incidents), ischaemic heart disease (IHD) (835 incidents), and all-cause mortality (1,272 incidents).. The MTHFR genotype (TT vs. CC/CT) was not associated with hypertension [OR (95% CI) 1.09 (0.95-1.25)], dyslipidemia [OR (95% CI) 0.97 (0.84-1.11)], stroke [HR (95% CI) 0.92 (0.69-1.23)], and all-cause mortality [HR (95% CI) 0.94 (0.77-1.14)], either overall, or in participants with low serum folate or B12 status (P values for interactions 0.15-0.94). Individuals with the MTHFR TT genotype had a higher risk of IHD (HR (95% CI) 1.38 (1.11-1.71)), but this association was not modified by folate status (P value for interaction 0.45).. Our results do not support a causal relationship between homocysteine and CVD. However, we cannot exclude a direct causal effect of MTHFR C677T genotype on IHD.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Denmark; Dyslipidemias; Female; Folic Acid; Follow-Up Studies; Genotype; Genotyping Techniques; Homocysteine; Humans; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Risk Factors; Stroke; Triglycerides; Vitamin B 12; Young Adult

Folate and vitamin B12 are essential components in the metabolism of homocysteine (Hcy). Hyperhomocysteinemia has been implicated in endothelial dysfunction and cardiovascular disease. However, the association of Hcy, vitamin B12, and folic acid with cardiovascular risk factors in patients with coronary artery disease (CAD) has not been studied in Indian patients. This study was conducted with the aim to evaluate the relationship of vitamin B12, folic acid, and Hcy levels with cardiovascular risk factors in subjects with known CAD.. Three hundred patients (216 men; 84 women; aged 25-92 years) who had CAD on angiography were included in this study consecutively. All patients were evaluated for anthropometry and cardiovascular risk factors, and blood samples were collected for biochemical, nutritional, and inflammatory markers.. Percentage of vitamin B12 and folate deficiency was 86.7% and 2.7%, respectively. Hyperhomocysteinemia was present in 95.3% patients. Vitamin B12 levels were significantly lower and Hcy levels were significantly higher in subjects with dyslipidemia, DM, and/or hypertension. Serum vitamin B12 was inversely associated with triglyceride and very low-density lipoprotein (VLDL) and positively with high-density lipoprotein (HDL). Hcy was positively associated with triglyceride and VLDL and negatively with HDL. Vitamin B12 was inversely correlated with inflammatory markers (high-sensitivity C-reactive protein and interleukin-6) directly related to insulin resistance whereas Hcy showed the opposite pattern.. Serum vitamin B12 deficiency and hyperhomocysteinemia are related with cardiovascular risk factors in Indian patients with CAD.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Coronary Artery Disease; Dyslipidemias; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; India; Male; Middle Aged; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Concerns have been raised on whether a gluten-free diet affects the cardiovascular risk profile of coeliac patients.. To assess changes of multiple cardiovascular risk factors in coeliac patients evaluated before and during a gluten-free diet.. Retrospective analysis of the effects of 1-5 years of gluten-free diet on indicators of cardiovascular risk and on distribution in cardiovascular risk categories in 715 coeliac patients.. Compared to baseline, significant increases were found in body mass index (21.4±3.4 vs. 22.5±3.5; p<0.0001), total cholesterol (171.2±37.4mg/dL vs. 181.4±35.1mg/dL; p<0.0001), and γ-glutamyl transpeptidase (16.5±14.9 vs. 19.5±19.2U/L; p<0.0001). Significant reductions were found in serum triglycerides (87.9±49.5 vs. 80.2±42.8mg/dL; p<0.0001) and homocysteine (16.9±9.6 vs. 13.3±8.0μmol/L; p=0.018) during gluten-free diet. The proportion of patients included in an arbitrarily defined category of "lowest cardiovascular risk profile" decreased from 58% at baseline to 47% during gluten-free diet.. A gluten-free diet significantly affects cardiovascular risk factors in coeliac patients, but changes do not consistently point towards worse or better risk profiles, thus suggesting that the diet is unlikely to be atherogenic.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Celiac Disease; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Gluten-Free; Female; Folic Acid; gamma-Glutamyltransferase; Homocysteine; Humans; Insulin Resistance; Male; Middle Aged; Retrospective Studies; Risk Factors; Triglycerides; Vitamin B 12; Young Adult

To explore the relationship between total plasma homocysteine (tHcy) concentration and central retinal vein occlusion (CRVO) in the acute phase in a Chinese population.. This was a matched case-control study, and participants were recruited between January 2008 and April 2012. The cohort included 68 consecutive patients with CRVO and 68 controls, matched for age and gender, aged 50 years and over. The total plasma homocysteine, vitamin B12 and folate levels and the presence of C677T MTHFR polymorphisms were analyzed in all patients and controls. Fasting venous blood samples were collected within three days after CRVO.. There were no significant differences (p = 0.134) in mean plasma tHcy between CRVO patients (10.73 ± 3.21 µmol/l) and controls (9.99 ± 2.57 µmol/l), nor were there any statistically significant differences when subjects were categorized by ischemic and nonischemic CRVO. However, six patients (27.3%) in the ischemic group and three patients (6.5%) in the nonischemic group were found to have hyperhomocysteinemia (p = 0.018). There were no statistically significant differences in serum folate (p = 0.503) or vitamin B12 levels (p = 0.419) between CRVO patients (folate, 5.97 ± 2.06 ng/ml; vitamin B12, 411 ± 122 pg/ml) and controls (folate, 6.18 ± 1.42 ng/ml; vitamin B12, 427 ± 115 pg/ml). The prevalence of the homozygous genotype of the MTHFR C677T mutation was not significantly different in patients than in controls.. We found no association between tHcy in the acute phase after CRVO and CRVO occurrence in a Chinese population, but hyperhomocysteinemia were associated with the development of CRVO.

Topics: Acute Disease; Aged; Asian People; Cardiovascular Diseases; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Hyperlipidemias; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Retinal Vein Occlusion; Risk Factors; Vitamin B 12

The burden of chronic noncommunicable diseases (NCDs) such as diabetes, obesity and cardiovascular disease is shifting rapidly to low- and middle-income countries. It calls for a review of the classic 'dogma' of genetic predisposition, precipitated by adult lifestyle. The paradigm of early life origins of chronic disease has focused attention on maternal health and nutrition as major determinants of the health of the offspring. India has high burden of maternal ill health and also of diabetes and cardiovascular disease, offering unique opportunities to study the links between the two. Pune studies showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal micronutrient status during pregnancy was a determinant of offspring size and body composition. Two thirds of the mothers had low vitamin B12 concentrations, while folate deficiency was rare. Higher circulating concentrations of homocysteine predicted smaller baby size. Follow-up studies revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance in the child at 6 years of age, and that low maternal vitamin B12 exaggerated the risk of insulin resistance. Low maternal vitamin B12 status is also associated with increased risk of neural tube defects and poor offspring cognitive functions. Our results suggest an important role for maternal one-carbon metabolism in offspring growth and programming of NCD risk. These ideas are supported by animal studies. Improvement of adolescent nutrition could effect intergenerational prevention of chronic diseases.

Topics: Adiposity; Adolescent; Adult; Animals; Body Weight; Carbon; Cardiovascular Diseases; Child; Chronic Disease; Diabetes Mellitus; Female; Folic Acid; Folic Acid Deficiency; Growth; Homocysteine; Humans; India; Infant; Infant, Newborn; Insulin Resistance; Maternal Nutritional Physiological Phenomena; Neural Tube Defects; Nutritional Status; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

To evaluate the presence of dyslipidemia and plasma concentrations of homocysteine (Hcy) and cysteine (Cys) in adolescents with juvenile systemic lupus erythematosus (SLE) and relate these findings to disease activity (Systemic Lupus Erythematosus Disease Activity Index, SLEDAI) and cardiovascular risk factors.. A cross-sectional controlled study including 26 female adolescents with SLE and 26 healthy controls was conducted. We evaluated SLEDAI, medications, anthropometric data, dietary intake, lipid profile, proteinuria, Hcy, Cys, folic acid, vitamin B12, and high-sensitivity C-reactive protein levels.. Dyslipidemia was observed in 46.2% of the patients and in 19.2% of the controls. The SLE group had a higher Cys concentration and a lower high-density lipoprotein cholesterol concentration compared with the controls. In the multivariate analysis only Hcy was significantly and independently associated with the presence of dyslipidemia in the juvenile SLE group; an increase of 1 μmol/l in the Hcy concentration doubled the chance of dyslipidemia (OR: 2.1; 95% CI: 1.1-4.9; p = 0.030). The Cys concentration was correlated with Hcy, total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations.. We observed the presence of cardiovascular risk factors in adolescents with juvenile SLE. The early identification of biochemical alterations allows the development of intervention strategies that may lower the risk of cardiovascular disease.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Child; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Cysteine; Dyslipidemias; Energy Intake; Female; Folic Acid; Homocysteine; Humans; Lupus Erythematosus, Systemic; Multivariate Analysis; Nutritional Status; Puberty; Risk Factors; Triglycerides; Vitamin B 12; Waist Circumference; Young Adult

Few modifiable risk factors are known to be associated with the presence and progression of diabetic polyneuropathy (DPN).. We have analyzed in 405 type 2 diabetic (T2DM) subjects (169 women) the association of plasma homocysteine with the presence of DPN measured with the Semmes-Weinstein (SW) monofilament test. A score below 4 was considered an altered SW monofilament test. Plasma homocysteine, vitamin B12 and folic acid were measured using standard procedures (ELISA).. Patients with T2DM with altered SW test have significantly higher age, evolution of disease, HbA1c and lower creatinine clearance values. In addition, plasma homocysteine values were independently and significantly higher in T2DM with DPN measured as altered SW test (13.64 ± 4.93 vs. 12.22 ± 4.48 μmol/l, P<.01) with similar vitamin B12 and folic acid values comparing the 2 groups.. Plasma homocysteine and HbA1c values are the 2 modifiable biological factors associated with the presence of DPN evaluated as an altered SW monofilament test in T2DM subjects.

Topics: Age Factors; Aged; Alcohol Drinking; Cardiovascular Diseases; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Progression; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Hyperhomocysteinemia; Hypesthesia; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Overweight; Physical Examination; Risk Factors; Severity of Illness Index; Smoking; Vitamin B 12

Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population.. Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B(12), and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured.. Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = -20.80, t = -2.9, df = 223, p = 0.004) and lower speed of processing (β = -0.38, t = -2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated.. In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level.

Topics: Age Factors; Aged; Asian People; Brain; Cardiovascular Diseases; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Fibers, Myelinated; Neuropsychological Tests; Organ Size; Singapore; Vitamin B 12

Elevated circulating fasting total homocysteine (tHcy) concentration is associated with an increased risk of occlusive vascular disease in adults. Important determinants of tHcy levels are folate, vitamin B(12) and vitamin B(6). This study aimed to investigate age, gender, and body mass as determinants of folate, vitamin B(12) and tHcy levels in Arab older children and adolescents and to propose population, gender and age-specific reference ranges for these biomarkers.. 774 (316 boys, 458 girls) healthy 10-19 yr olds attending secondary schools in Kuwait were assessed for anthropometry and fasting blood levels of Hcy, folate and vitamin B(12). The mean (95% CI) serum levels of tHcy, folate and vitamin B(12) were respectively 6.57 μmol/L (6.42-6.73), 16.0 ng/ml (15.6-16.3) and 354.3 pg/ml (343.0-365.7). Boys had significantly higher tHcy and folate concentrations than the girls, although vitamin B(12) levels were greater in the latter. Folate and vitamin B(12) levels decreased significantly with age, while correspondingly, tHcy levels increased, with mean values (μmol/L) for boys (6.71; 8.25) and girls (5.36; 6.67) aged 10-14 yr and 14-19 yr respectively. Bivariate and multivariate analyses with adjustment for confounders such as age, gender, need for dietary control and socio-demographic variables indicated that the independent determinants of levels of tHcy were age, gender and body mass.. There is an age-related increase in tHcy in adolescents reflecting decreased levels of folate and vitamin B(12), with the suggestion that age-related reference ranges for these biomarkers be used. These observations may have implications for prevention of future atherogenic disease.

Topics: Adolescent; Age Factors; Arabs; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Diet; Female; Folic Acid; Homocysteine; Humans; Kuwait; Logistic Models; Male; Motor Activity; Reference Values; Risk Factors; Sex Factors; Socioeconomic Factors; Vitamin B 12; Vitamin B Complex; Young Adult

Homocysteine (Hcy) is an intermediate in sulfur amino acid metabolism and may induce oxidative stress. Several studies have reported that elevated Hcy in end-stage renal failure may contribute to cardiovascular disease (CVD). The purpose of this study is to investigate whether the changes in Hcy levels correlate better with the CVD outcomes than baseline Hcy level.. A total of 187 patients on dialysis participated in the present prospective observational study and were followed up for 107 months. Baseline cross-sectional analysis of the relationship between Hcy and several factors related to its metabolism was performed, along with survival analysis for the occurrence of CVD. All subjects were divided into the Increase or Decrease of Hcy group on the basis of changes in Hcy from baseline to year 3.. The occurrence of CVD was higher in the Increase (30.1%) than in the Decrease group (9.0%). Greater change of Hcy was associated with risk of CVD (hazard ratio: 3.658) after adjusting basic factors and nutritional status. In stepwise multiple analyses, serum folate, vitamin B(12), cysteine, creatinine, and body mass index were considered to be independent predictors of Hcy.. These data show that increase in Hcy is a powerful predictor of the occurrence of CVD in patients on dialysis.

Topics: Body Mass Index; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Middle Aged; Prospective Studies; Renal Dialysis; Vitamin B 12

To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study.. Of 5192 African American Jackson Heart Study participants (21-94 years), 5064 (mean age, 55 ± 13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants' vitamin B12 (n = 1790) and folate (n = 1788) levels. Regression analyses were used to examine age, gender, vitamin B12 and folate with homocysteine levels.. Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (P < 0.001) and were higher for men of all ages.. The results show that, as with other populations, age, gender, vitamin B12 and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships that were observed between plasma homocysteine and serum B vitamin levels.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Black or African American; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Linear Models; Male; Middle Aged; Mississippi; Sex Factors; Vitamin B 12; Young Adult

A better understanding of the relationship of homocysteine with cardiovascular risk factors is needed. The objectives of this study were to assess the serum level of homocysteine in HIV-infected patients and to analyse the possible association of increased levels of the amino acid with cardiovascular risk factors, demographic and clinical characteristics of participants.. Cross-sectional study carried out as a supplementary task to the usual controls necessary in HIV-infected patients in the outpatient clinic of the Hospital General of Castellon, Spain. For two consecutive visits the demographic, clinical and HIV-related characteristics and blood analyses results were obtained for each participant. Homocysteine serum level was documented and the possible association of the amino acid with all the other study variables was assessed with a multiple linear regression analysis.. A total of 145 patients were included. The mean homocysteine serum level of all participants was 11.9 ± 5.9 µmol/L. A total of 54 patients (37%) presented homocysteine serum levels higher than the upper limit of normal. An association was found between higher homocysteine serum level and the following variables: family history of early coronary disease (P = 0.027), sexual HIV risk behaviour (P = 0.016), hepatitis C virus co-infection (P = 0.002), higher height (P = 0.002), higher diastolic blood pressure (P = 0.049), lower serum level of folic acid (P <0.001), and lower serum level of vitamin B12 (P = <0.001).. In the HIV population, increased homocysteine serum level is associated with sexual risk behaviour and hepatitis C virus coinfection.

Topics: Adult; Cardiovascular Diseases; Coinfection; Cross-Sectional Studies; Female; Folic Acid; Hepacivirus; Hepatitis C; HIV; HIV Infections; Homocysteine; Humans; Male; Risk Factors; Risk-Taking; Sexual Behavior; Vitamin B 12

The aim of this retrospective cohort study was to identify early risk factors of mortality and develop a mortality risk stratification instrument for severely anaemic Jehovah's Witness patients. It has been shown that Jehovah's Witness patients with the Auckland Anaemia Mortality Risk Score (Auckland AMRS) of 0 to 3 had 4% mortality, Auckland AMRS 4 to 5 32%, Auckland AMRS 6 to 7 50% and Auckland AMRS 8 and above 83%. It is concluded that the Auckland AMRS predicts mortality of severely anaemic Jehovah's Witness patients.

Topics: Adolescent; Adult; Aged; Anemia; Cardiovascular Diseases; Erythropoietin; Factor VIIa; Female; Filgrastim; Folic Acid; Granulocyte Colony-Stimulating Factor; Hemorrhage; Hospital Mortality; Hospitals, Public; Humans; Infections; Iron; Jehovah's Witnesses; Kidney Failure, Chronic; Male; Middle Aged; New Zealand; Plasma; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Vitamin B 12; Young Adult

Topics: Adenoma; Anticarcinogenic Agents; Cardiovascular Diseases; Colorectal Neoplasms; Female; Folic Acid; Humans; Male; Vitamin B 12; Vitamin B 6

Homocysteine (Hcy) is metabolized through two pathways, requiring folates and B6-12 vitamins as cofactors. Increased Hcy concentration is responsible for early atherosclerosis with possible acute cardiovascular events. Ample evidence has demonstrated that Hcy lowering with folic acid and B vitamin supplementation, even if reduces Hcy serum levels, is unable to lower cardiovascular risk. On the contrary, omega-3 fatty acids and some nutraceuticals, such as N-acetyl cysteine, taurine, or S-adenosyl-methionine, reduce both Hcy serum concentration and cardiovascular risk. Instead, antiplatelet drugs, such as aspirin and clopidogrel or ticlopidine and statins only antagonize vascular derangements. Finally, metformin, some lipid-lowering drugs, and some diuretics should be avoided because they can increase Hcy levels.

Topics: Acetylcysteine; Aspirin; Blood Vessels; Cardiovascular Diseases; Clopidogrel; Diuretics; Fatty Acids, Omega-3; Folic Acid; Homocysteine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Platelet Aggregation Inhibitors; S-Adenosylmethionine; Ticlopidine; Vitamin B 12; Vitamin B 6

Psoriasis is a hyperproliferative, cutaneous disorder with the potential to lower levels of folate. This may result in raised levels of homocysteine, an independent risk factor for the development of cardiovascular disease.. A study was conducted to compare levels of red-cell folate (RCF) and homocysteine in patients with psoriasis and in healthy controls. Levels of homocysteine were also examined in the context of other major cardiovascular risk factors.. In total, 20 patients with psoriasis and 20 controls had their RCF, homo-cysteine and other conventional cardiovascular risk factors assessed.. Patients with psoriasis had a trend towards lower levels of RCF. Significantly raised levels of homocysteine were found in patients with psoriasis compared with controls (P = 0.007). There was no correlation between homocysteine levels, RCF levels or disease activity as measured by the Psoriasis Area and Severity Index. Patients with psoriasis had higher body mass index (P < 0.004) and higher systolic blood pressure (P < 0.001) than controls. This may contribute to the excess cardiovascular mortality observed in patients with psoriasis.

Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Psoriasis; Risk Factors; Severity of Illness Index; Vitamin B 12

Folate is of prime interest among investigators in nutrition due to its multiple roles in maintaining health, especially in preventing neural tube defects and reducing the risk of cardiovascular diseases. We investigated the effect of dietary folate intake on blood folate, vitamin B(12), vitamin B(6), and homocysteine status. One hundred subjects consisting of Chinese and Malay subjects volunteered to participate in this cross-sectional study. Dietary folate intake was assessed by 24-h dietary recall and a food-frequency questionnaire (FFQ). Serum and red blood cell folate were analyzed using a microbiological assay, while serum vitamin B(12) was determined by electrochemiluminescence immunoassay (ECLIA), and high-performance liquid chromatography (HPLC) was used for the determination of serum vitamin B(6) and homocysteine. The mean folate intake, serum folate, RBC folate, serum vitamin B(12), and B(6), were higher in female subjects, with the exception of serum homocysteine. The Chinese tended to have higher folate intake, serum folate, RBC folate, and vitamin B(12). A positive association was found between folate intake and serum folate while a negative association was found between folate intake and serum homocysteine. Stepwise linear regression of serum folate showed a significant positive coefficient for folate intake whilst a significant negative coefficient was found for serum homocysteine when controlling for age, gender, and ethnicity. In conclusion, high dietary folate intake helps to increase serum folate and to lower the homocysteine levels.

Topics: Adult; Asian People; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Diet Records; Diet Surveys; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Linear Models; Malaysia; Male; Middle Aged; Neural Tube Defects; Nutritional Status; Sex Factors; Surveys and Questionnaires; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Young Adult

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Data Interpretation, Statistical; Homocysteine; Humans; Kidney; Meta-Analysis as Topic; Methylenetetrahydrofolate Dehydrogenase (NADP); Polymorphism, Genetic; Reproducibility of Results; Risk Assessment; Stroke; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed at assessing vitamin A, E, B12, and folic acid status in Tunisian ESRD patients and testing their predictive value for overall mortality and cardiovascular events (CVE).. We examined plasma vitamin A, E, B12, and folic acid in 115 ESRD patients and looked for any correlation with all-cause mortality and CVE after a six year follow-up. Vitamin A and E were determined by HPLC and vitamin B12 and folic acid were determined by enzyme immunoassay.. At enrolment, plasma vitamin A was higher in patients than controls, while plasma vitamin B12 was higher in HD patients. No significant differences were observed for plasma vitamin E and folic acid concentrations between patients and controls. Folic acid and vitamin B12 levels were higher in supplemented patients. During the follow-up period, 17 patients were lost, 15 died, and 36 presented a CVE. Survival analysis showed that mortality and/or CVE trend to be lower for high folic acid levels (Log Rank = 0.098). Cox's regression analysis showed that high levels of folic acid are inversely related to all-cause mortality and/or CVE [Hazard ratio (95% confidence interval), 0.255 (0.08 - 0.740); p = 0.012].. Plasma vitamins A, E, B12, and folic acid concentrations are usually normal in Tunisian ESRD patients. High folic acid levels are associated with fewer CVE and better survival. However, as uremia could be associated with functional vitamin deficiency, maintaining high plasma vitamin levels by adequate nutrition and tolerable supplementation would be beneficial in ESRD patients.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Cause of Death; Comorbidity; Female; Folic Acid; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Proportional Hazards Models; Smoking; Tunisia; Vitamin A; Vitamin B 12; Vitamin E; Young Adult

This study sought to determine nutrition-related cardiovascular risk factors in hemodialysis patients.. This was a cross-sectional study.. This study included outpatients from the Hemodialysis Unit of Baskent University Ankara Hospital.. This study was conducted on 93 endstage chronic renal-failure patients (50 male and 43 female) aged between 18 and 65 years. Patients undergoing hemodialysis three times weekly with 4 hours of standardized bicarbonate hemodialysis were included. Patients with cardiovascular disease were excluded.. A questionnaire was administered to patients regarding demographic and disease information. The nutritional status of patients was determined by a food-frequency questionnaire, a 3-day, 24-hour dietary record, and subjective global assessment. Several biochemical parameters were analyzed, and body weight was measured.. Percentages of patients' serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol/low-density lipoprotein cholesterol levels that were higher than National Kidney Foundation (NKF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) criteria amounted to 7.5%, 4.3%, 43%, and 10.8%, respectively. The percentage of patients' serum high-density lipoprotein cholesterol levels that were lower than NKF and NCEP/ATP III criteria reached 41.9%. According to serum albumin levels, 44.1% of patients were malnourished. In terms of patients' dietary total fat intake, 98.9% were higher than NKF and NCEP/ATP III criteria, and all patients' dietary saturated fatty acids intake were higher than recommended. For 87.1% of patients, the dietary polyunsaturated fatty acids/saturated fatty acids ratio was <1. Moreover, in terms of NKF recommendations, the percentages of patients with insufficient dietary folate and vitamin B(12) intake reached 100% and 61.3%, respectively.. Hemodialysis patients should be considered at high risk for developing cardiovascular disease. Therefore, when planning diets of endstage renal disease patients, it is important to consider nutrition-related cardiovascular-disease risk factors for the sake of quality of life and survival.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Diet; Dietary Fats; Female; Folic Acid; Humans; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Nutritional Status; Renal Dialysis; Risk Factors; Serum Albumin; Surveys and Questionnaires; Vitamin B 12

Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease.

Topics: Cardiovascular Diseases; Case-Control Studies; Demography; Folic Acid; Homocysteine; Humans; Inflammation; Interleukin-2; Interleukin-6; Middle Aged; ROC Curve; Vitamin B 12

Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations.. The objective was to examine whether choline and betaine intakes, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post-methionine-load conditions in both pre- and post-folic acid fortification periods in the United States.. We assessed the association between choline and betaine intakes and fasting and post-methionine-load homocysteine concentrations using the US Department of Agriculture revised food-composition tables and evaluated whether the associations varied by folic acid fortification periods in 1325 male and 1407 female participants in the sixth examination (1995-1998) of the Framingham Offspring Study.. A higher choline-plus-betaine intake was associated with lower concentrations of post-methionine-load homocysteine; the multivariate geometric means were 24.1 micromol/L (95% CI: 23.4, 24.9 micromol/L) in the top quintile of intake and 25.0 micromol/L (95% CI: 24.2, 25.7 micromol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 micromol/L (95% CI: 9.3, 9.9 micromol/L) in the top quintile and 10.1 micromol/L (95% CI: 9.8, 10.4 micromol/L) in the bottom quintile (P for trend < 0.001). When we stratified by plasma folate and vitamin B-12 concentrations, the inverse association was limited to participants with low plasma folate or vitamin B-12 concentrations. In the postfortification period, the inverse association between choline-plus-betaine intake and either fasting or post-methionine-load homocysteine was no longer present.. Choline and betaine intakes were associated with both fasting and post-methionine-load total homocysteine concentrations, especially in participants with low folate and vitamin B-12 status. The inverse association between choline and betaine intakes and homocysteine concentrations was no longer present in the postfortification period.

Topics: Betaine; Cardiovascular Diseases; Choline; Cognition Disorders; Diet; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Vitamin B 12; Vitamin B 6

The association of dietary folate and B vitamin intakes with risk of cardiovascular disease is controversial, and the evidence in Asian populations is limited.. A total of 23 119 men and 35 611 women, age 40 to 79 years, completed a food frequency questionnaire in the Japan Collaborative Cohort Study. During the median 14-year follow-up, there were 986 deaths from stroke, 424 from coronary heart disease, and 2087 from cardiovascular disease.. Dietary folate and vitamin B(6) intakes were inversely associated with mortality from heart failure for men and with mortality from stroke, coronary heart disease, and total cardiovascular disease for women. These inverse associations did not change materially after adjustment for cardiovascular risk factors. No association was found between vitamin B(12) intake and mortality risk.. High dietary intakes of folate and vitamin B(6) were associated with reduced risk of mortality from stroke, coronary heart disease, and heart failure among Japanese.

Topics: Adult; Aged; Asian People; Cardiovascular Diseases; Cohort Studies; Dietary Supplements; Female; Folic Acid; Humans; Japan; Male; Middle Aged; Retrospective Studies; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Biomarkers; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Risk Factors; Vitamin B 12; Vitamin B 6

Topics: Cardiovascular Diseases; Diabetic Nephropathies; Disease Progression; Down-Regulation; Folic Acid; Homocysteine; Humans; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 6; Vitamins

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12; Vitamin B Complex

Non-arteritic anterior ischemic optic neuropathy (NAION) is a multifactorial disease that is caused by an infarction of the vessels that supply the optic nerve head. This study aims at evaluating the role of traditional and emerging cardiovascular risk factors on the development of NAION.. A total of 85 newly diagnosed NAION patients and 107 age- and gender-matched healthy controls were studied. All participants underwent blood testing for homocysteine and lipoprotein(a). Plasma levels of vitamin B6 and B12, and folic acid were also determined. Plasma values of all these parameters were evaluated as continuous variables, by a logarithmic transformation. In addition, traditional cardiovascular risk factors were considered.. With univariate analysis, higher values of homocysteine and Lp(a) (OR 4.24, 95% CI 2.01-8.94, p < 0.0001; OR 1.32, 95% CI 1.04-1.67, p = 0.03, respectively) and lower values of vitamin B6 (OR 0.44, 95% CI 0.25-0.76, p = 0.003) were significantly associated with NAION. At multivariate analysis, adjusted for age, gender, smoking habit, hypertension, dyslipidemia, diabetes, sleep apnea, and thrombophilic risk factors, the higher homocysteine and Lp(a) values (OR 5.74, 95% CI 2.41-13.67, p = 0.0001; OR 1.27, 95% CI 1.01-1.63, p = 0.04) and lower vitamin B6 values (OR 0.42, 95% CI 0.23-0.77, p = 0.005) maintained their significant relationship with NAION.. This study demonstrated that elevated plasma homocysteine and lipoprotein(a) levels, as well as low vitamin B6 levels, may increase the risk of developing NAION. A screening for these thrombophilic markers could be useful in subjects experiencing NAION.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Case-Control Studies; Dyslipidemias; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Homocysteine; Humans; Hypertension; Lipoprotein(a); Male; Middle Aged; Optic Neuropathy, Ischemic; Risk Factors; Thrombophilia; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia is associated with an increased risk of cardiovascular diseases. We determine homocysteine levels (Hcy), paraoxonase (PON1) concentration and their relationship on cardiovascular complications in patients with chronic renal disease (CRD).. The study population included 100 CRD patients and 120 healthy controls. Renal function was assessed using the eGFR by the MDRD study equation. Patients were considered to have CRD when the eGFR was <60 mL/min/1.73 m(2). Hcy concentrations were determined by direct chemiluminescence assay. PON1 concentration was measured spectrophotometrically using phenylacetate as a substrate.. We found an increased Hcy levels and a decreased eGFR and PON1 concentration in CRD patients compared to the control group (P<0.001, P<0.001, P<0.01 respectively). Patients with cardiovascular complications showed an increased Hcy levels and a lower PON1 concentration than patients without cardiovascular complications (P<0.001, P<0.01 respectively).. We showed that hyperhomocysteinemia and low PON1 concentration are associated with CRD and markedly associated in patients with cardiovascular complications. Additional effects contribute to the severity of renal disease and increase the incidence of cardiovascular disease.

Topics: Adult; Aryldialkylphosphatase; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Female; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Multivariate Analysis; Radioimmunoassay; Triglycerides; Tunisia; Vitamin B 12

Evidence exists that well-planned vegetarian diets provide numerous health benefits and are appropriate for all stages of the life cycle. It is also known that animal foods provide micronutrients that are nonexistent or available only in limited amounts in plant foods. Restriction or exclusion of all animal foods may therefore result in low intake of certain micronutrients such as vitamin B-12, thereby affecting vitamin B-12 status and elevating plasma homocysteine concentrations. Overall, the studies we reviewed showed reduced mean vitamin B-12 status and elevated mean homocysteine concentrations in vegetarians, particularly among vegans. Low vitamin B-12 intake may lead to decreased bioavailability and functional deficiency of cobalamin. Although early noticeable symptoms of vitamin B-12 deficiency are nonspecific (unusual fatigue, digestion problems, frequent upper respiratory infections), the best-known clinical manifestations of cobalamin malabsorption are hematologic (pernicious anemia) and neurologic symptoms. Hyperhomocysteinemia is associated with an increased risk of atherosclerosis and cardiovascular disease. Given these health concerns, vegetarians, particularly vegans, must be advised to carefully plan their diets, to monitor their plasma vitamin B-12 on a regular basis to facilitate early detection of low cobalamin status, and to use vitamin B-12-fortified foods or take vitamin B-12 supplements if necessary.

Topics: Anemia, Pernicious; Atherosclerosis; Cardiovascular Diseases; Diet, Vegetarian; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to assess the relationship between total plasma homocysteine, cholesterol levels, vitamin B(12), folate, thyroid hormones, urea, ferritin, uric acid, C-reactive protein, cardiovascular risk factors and silent brain infarct (SBI) in patients without any neurological disorder. Whether the factors of interest were associated with SBI is investigated.. One hundred and forty-two subjects with a mean age of 52.1 +/- 13.1 years (21-87 years) without any history of stroke, transient ischaemic attack and neurological abnormality were enrolled in this cross-sectional study. The subjects underwent brain magnetic resonance imaging and blood chemistry determinations. Student's t-test was used to compare differences in means of laboratory results between the groups with and without SBI. The chi(2)-test was used for categorized variables. Multiple logistic regression analysis was used to determine the independent predictors of SBI.. The group comprised 56 men and 86 women. SBI were found in 40 patients (28%). The low-density lipoprotein levels were significantly higher in the infarct group (P = 0.019), homocysteine concentrations were significantly higher in the men-infarct group (P = 0,029) and total cholesterol levels were significantly higher in the women-infarct group than the women non-infarct group (P = 0.006).. Serum low-density lipoprotein, total cholesterol and homocysteine levels were associated with SBI.

Topics: Adult; Aged; Aged, 80 and over; Blood Chemical Analysis; Brain Infarction; Cardiovascular Diseases; Cholesterol; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Lipoproteins, LDL; Magnetic Resonance Imaging; Male; Middle Aged; Risk Factors; Sex Factors; Vitamin B 12; Young Adult

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 microg (n = 191) or 2 microg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of > or =15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 micromol/L in children and >15 micromol/L in adults). In the 10 microg group, the plasma holo-TC concentration increased by 4.8-fold from (mean +/- SD) 9.3 +/- 7.0 pmol/L to 53.8 +/- 25.9 pmol/L and in the 2 microg group by 2.2-fold from 11.1 +/- 8.5 pmol/L to 35.7 +/- 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.

Topics: Adult; Body Height; Body Weight; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Fathers; Female; Folic Acid; Hemoglobins; Homocysteine; Humans; Intestinal Absorption; Male; Maternal Nutritional Physiological Phenomena; Mother-Child Relations; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine is considered as independent predictor of cardiovascular risk. Patients treated with haemodialysis (HD) exhibit elevated homocysteine levels, even four times higher than the general population does. This study focuses on the determination of the vascular risk in patients treated with conventional HD and haemodiafiltration on-line (HDF). It was also considered important to determine whether there was a relationship between homocysteine and the variables given to the patient such as dialysis dose, obesity and treatment with folic acid, vitamin B6 and vitamin B12. A one-year cross-sectional observational study was conducted on patients initially treated with renal replacement therapy such as HDF on-line and conventional HD. Data collected included patient's age, sex, aetiology, duration of dialysis treatment and association with dialysis session, including data on body mass index, waist circumference, treatment with vitamin B6, B12 and folic acid. The results obtained conclusively indicate that patients treated with renal replacement therapy such as HDF on-line exhibit lower homocysteine levels than those treated with conventional HD. Therefore we can conclude that: homocysteine markers indicate that patients treated with HDF on-line are exposed to lower average vascular risk.

Topics: Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Female; Folic Acid; Hemodiafiltration; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Online Systems; Renal Dialysis; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin B 12

Folate and vitamin B12 have been suggested to play a role in chronic diseases like cardiovascular diseases. The objectives are to give an overview of the actual intake and status of folate and vitamin B12 in general populations in Europe, and to evaluate these in view of the current vitamin recommendations and the homocysteine concentration.. Searches in Medline with 'folic acid', 'folate' and 'vitamin B12', 'B12' or 'cobalamin' as key words were combined with the names of the European countries. Populations between 18 and 65 years were included.. Sixty-three articles reporting on studies from 15 European countries were selected. Low folate intakes were observed in Norway, Sweden, Denmark and the Netherlands. Low intakes of vitamin B12 were not common and only seen in one small Greek study. In the countries with a low intake of folate, the recommended levels were generally not achieved, which was also reflected in the folate status. Vitamin B12 intake was not strongly associated with the vitamin B12 status, which can explain why in the Netherlands and Germany the vitamin B12 status was inadequate, despite sufficient intake levels. In countries with a low folate intake in particular, the Hcy concentration was higher than ideal.. Populations from the Nordic countries, the Netherlands, Germany and Greece may need to improve their intakes of folic acid, B12 or both to either meet the recommendations or to optimize their statuses. This could be achieved via a food-based approach, food fortification or supplements.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Diet; Europe; Folic Acid; Homocysteine; Humans; Middle Aged; Nutritional Requirements; Vitamin B 12; Young Adult

Topics: Anemia; Cardiovascular Diseases; Female; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Nutritional Status; Pregnancy; Pregnancy Outcome; Public Health; Vitamin B 12; Vitamin B 12 Deficiency; World Health Organization

Topics: Aged; Aortic Valve Stenosis; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Survival Rate; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Although the health benefits of vegetarian diets have been well documented among Western population, there are geographic differences of vegetarian diets and the health benefits of the Taiwanese vegetarian diet have not been studied extensively. In addition to conventional risk factors, homocysteine and high-sensitivity C-reactive protein (hs-CRP) levels have been found to predict first atherothrombotic events. We undertook this study to examine the total risk profile of Taiwanese vegetarians.. A total of 198 healthy subjects (99 vegetarians and 99 omnivores) were recruited. Fasting blood samples were analyzed for glucose, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), white blood cell count, hs-CRP and homocysteine.. There was no significant difference in age, body mass index, blood glucose, white blood cell count, triglyceride and HDL-C between the two groups. The vegetarian group had significantly more females (65.7 vs 46.5%); lower body weight (58.66+/-11.13 vs 62.88+/-12.24 kg); shorter height (159.14+/-7.88 vs 162.53 +/-8.14 cm); lower total cholesterol (184.74+/-33.23 vs 202.01+/-41.05 mg/dl); and lower LDL-C (119.63+/-31.59 vs 135.89+/-39.50 mg/dl). Hs-CRP was significantly lower (0.14+/-0.23 vs 0.23+/-0.44 mg/dl, P=0.025), whereas homocysteine was significantly higher (10.97+/-6.69 vs 8.44+/-2.50 micromol/l, P=0.001) in vegetarians than omnivores.. Taiwanese vegetarians have lower total cholesterol, LDL-C and hs-CRP levels, and higher homocysteine levels than omnivores. Owing to different predictive value of each risk factor, the Taiwanese vegetarians had a better cardiovascular risk profile than omnivores. Whether the Taiwanese vegetarian diet should be supplemented with vitamin B(12) to lower serum homocysteine level remains to be addressed.

Topics: C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Diet, Vegetarian; Female; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Nutritional Status; Risk Assessment; Risk Factors; Taiwan; Vitamin B 12; Vitamin B 12 Deficiency

Elevated serum total homocysteine (tHcy) is associated with an increased risk of cardiovascular disease. Homocysteine levels may be influenced by dietary habits. The aim of the present study was to determine the effects of a vegetarian diet on some of the cardiovascular risk factors in Turkish females.. The study was conducted on 26 vegetarian and 26 omnivore females. Serum tHcy, folate, vitamin B(12) and lipids were determined and dietary data were assessed using a 4-day food intake record at two time points.. Compared with omnivores, vegetarians had higher plasma tHcy, 10.8 +/- 3.72 versus 12.6 +/- 5.97, (P < 0.05) and folate (P < 0.05) levels. The prevalence of hyperhomocysteinaemia was higher in vegetarians than in omnivores (34.6% versus 12.0%). In addition, serum vitamin B(12) levels were lower in vegetarians than in omnivores (P < 0.05). In vegetarians, significant inverse correlation was found between tHcy and serum vitamin B(12) levels (r = -0.969, P = 0.001).. The higher prevalence of mild hyperhomocysteinaemia in vegetarians indicated a diminished protective effect of vegetarian nutrition in cardiovascular disease prevention.

Topics: Adult; Cardiovascular Diseases; Diet; Diet Records; Diet, Vegetarian; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Lipids; Middle Aged; Nutritional Status; Risk Factors; Turkey; Vitamin B 12

Regular physical activity is associated with a reduction of cardiovascular morbidity and mortality; however, evidence of unfortunate cardiovascular events accompanying elite sport involvement continues to accumulate. To date, no information is available on possible peculiarities of the cardiovascular risk profile in athletes.. The aim of this study was to evaluate plasma homocysteine levels in a group of athletes and to search for relationship with vitamin status and other metabolic variables in order to confirm the existence of a "sport-related hyperhomocysteinaemia" and to explain its clinical significance. The study population was composed of 82 athletes (59 male and 23 female) practising different sports and 70 healthy age-matched subjects (40 male and 30 female) as a control group. Besides the general clinical and analytical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and high-density lipoprotein (HDL) cholesterol, lactate dehydrogenase (LDH), creatine kinase (CPK) and interleukin-6 (IL-6).. The prevalence of hyperhomocysteinaemia (>15 micromol/l) in athletes and controls was 47% and 15%, respectively. No correlation was found between homocysteine and any of the other investigated variables, in particular plasma folate, blood pressure, LDH, CPK, total and HDL cholesterol and IL-6.. The results of this study confirm the existence of a sport-related hyperhomocysteinaemia which appears linked neither to the same variables found in the general population, nor to specific training-related variables. We suggest that it would represent an adaptation to training but the possibility of a secondary vascular damage cannot be excluded.

Topics: Adult; Cardiovascular Diseases; Case-Control Studies; Cholesterol, HDL; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Interleukin-6; L-Lactate Dehydrogenase; Male; Muscle, Skeletal; Risk Factors; Sports; Vitamin B 12

The purpose of this study was to determine if nonsupplementing older women (aged >or=55 years) with rheumatoid arthritis had higher plasma homocysteine and lower B-vitamin status compared to healthy controls. Elevated plasma homocysteine, a risk factor for cardiovascular disease, may help explain why individuals with rheumatoid arthritis have an increased risk of cardiovascular disease.. Older, free-living women were classified as rheumatoid arthritis (n=18) or healthy control (n=33). Participants were not using B-vitamin supplements. Fasting blood samples were measured for pyridoxal 5'phosphate (PLP) (the metabolically active coenzyme form of vitamin B-6), folate, red blood cell folate, vitamin B-12, transcobalamin II, homocysteine, C-reactive protein, and lipid concentrations. Participants completed 7-day weighed food records, the Stanford Health Assessment Questionnaire (HAQ), and a visual analog pain scale.. PLP concentrations were lower in the rheumatoid arthritis vs healthy control participants (4.93+/-3.85 vs 11.35+/-7.11 ng/mL [20+/-16 vs 46+/-29 nmol/L]; P<0.01) whereas plasma homocysteine was higher in the rheumatoid arthritis group (1.63+/-0.74 vs 1.15+/-0.38 mg/L [12.1+/-5.5 vs 8.5+/-2.8 micromol/L]; P=0.02). Red blood cell folate concentrations were lower in the rheumatoid arthritis vs healthy control participants [414+/-141 vs 525+/-172 ng/mL [938+/-320 vs 1,190+/-390 nmol/L]; P=0.02). No significant differences were found for plasma folate, vitamin B-12, and transcobalamin II. An inverse correlation was found between PLP concentrations and the HAQ disability index (r=-0.37; P<0.01). A positive correlation was found between homocysteine concentrations and the HAQ disability index (r=0.36; P=0.01). Total cholesterol and low-density lipoprotein cholesterol levels were lower in the rheumatoid arthritis group (cholesterol 191+/-43 vs 218+/-33 mg/dL [4.95+/-1.11 vs 5.65+/-0.85 mmol/L]; P=0.02; low-density lipoprotein cholesterol 110+/-36 vs 137+/-29 mg/dL [2.85+/-0.93 vs 3.55+/-0.75 mmol/L]; P<0.01). No significant differences were seen between groups for protein (g/day), fat (g/day), cholesterol (mg/day), folate (microg/day), vitamin B-12 (microg/day), and vitamin B-6 (mg/day) dietary intakes.. Poor vitamin B-6 status and elevated plasma homocysteine concentrations were seen in older women with rheumatoid arthritis compared to healthy controls and may contribute to their increased risk of cardiovascular disease.

Topics: Aged; Arthritis, Rheumatoid; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Diet Records; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Lipids; Middle Aged; Nutritional Status; Pyridoxal Phosphate; Risk Factors; Transcobalamins; Vitamin B 12; Vitamin B 6; Vitamin B 6 Deficiency; Vitamin B Complex

The purpose of this study was to determine whether adjustment for renal function eliminates the relationship between total plasma homocysteine (tHcy) and vascular risk, assessed by carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery.. We used cross-sectional data from 173 stroke patients treated with B-vitamins (folic acid 2 mg, vitamin B(6) 25 mg, and vitamin B(12) 0.5 mg) or placebo in a randomized double-blinded trial to test the relationships between posttreatment tHcy, cystatin C (a marker of glomerular filtration rate), estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease equation) creatinine, CIMT, and FMD in stepwise and multivariable regression models. The strong linear relationship between tHcy and cystatin C was not altered by long-term B-vitamin treatment. tHcy lost significance as a predictor of the vascular measurements after adjustment for any single marker of renal function. Cystatin C, but not tHcy, was a significant independent predictor of FMD after adjustment for age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol, and treatment group.. Adjusting for renal function eliminates the relationship between tHcy and CIMT and FMD, supporting the hypothesis that elevated tHcy is a marker for renal impairment rather than an independent cardiovascular risk factor.

Topics: Aged; Aged, 80 and over; Biomarkers; Brachial Artery; Cardiovascular Diseases; Carotid Arteries; Cross-Sectional Studies; Cystatin C; Cystatins; Female; Folic Acid; Follow-Up Studies; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Regional Blood Flow; Regression Analysis; Risk Factors; Vitamin B 12; Vitamin B 6

To investigate the association of dietary folate, vitamin B(6) (VB(6)) and vitamin B(12) (VB(12)) with the risk of coronary heart disease among middle-aged persons.. A total of 40,803 subjects aged 40-59 years living in the community who were free of prior diagnoses of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed from 1990-1992 to the end of 2001 in the Japan Public Health Center-based Prospective Study.. After 468,472 person-years of follow-up, 251 coronary heart disease incidents were documented. Coronary heart disease and definite myocardial infarction were inversely associated with dietary intake of folate, VB(6) and VB(12) after adjustment for age and sex, but the associations were attenuated after further adjustment for smoking, dietary and other cardiovascular risk factors. However, among non-multivitamin supplement users, multivariable hazard ratios (95% confidence intervals) in the highest vs. lowest quintiles of VB(6) intake were 0.60 (0.37-0.97) for total coronary heart disease and 0.52 (0.29-0.91) for definite myocardial infarction, and the inverse associations with VB(12) were marginally significant. The combination of below-median intake of three vitamins or of only B(6) conferred a twice excess risk of total coronary heart disease.. Dietary intake of VB(6) was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users. Dietary folate and VB(12) were also suggested to be protective factors for coronary heart disease.

Topics: Adult; Cardiovascular Diseases; Cohort Studies; Confidence Intervals; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Multivariate Analysis; Nutrition Surveys; Odds Ratio; Prospective Studies; Risk Factors; Surveys and Questionnaires; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Cardiovascular Diseases; Dietary Supplements; Folic Acid; Homocysteine; Humans; Vitamin B 12; Vitamin B 6; Vitamin B Complex

There is uncertainty about the importance of plasma levels of homocysteine, vitamin B-12, and folate for all-cause and cardiovascular disease (CVD) mortality in older people. We examined the associations between plasma levels of folate, vitamin B-12, and homocysteine, and all-cause and CVD mortality among community-dwelling adults aged > or = 75 y living in the United Kingdom. In a population-based prospective cohort study, 853 men and women aged > or = 75 y were examined in 1995-98 as part of the Medical Research Council Trial of Assessment and Management of Older People in the Community. During a median follow-up of 7.6 y (5528 person-years of follow-up), 429 individuals (50.3%) died, including 185 from CVD. Individuals with plasma homocysteine levels in the top one-third compared with the bottom one-third had a 2-fold higher risk of all-cause mortality (hazard ratio, 2.20; 95% CI, 1.76, 2.75; P < 0.001) and CVD mortality (hazard ratio, 1.96; 95% CI, 1.39, 2.78; P < 0.001) after adjustment for age, sex, and other covariates. There was no association of plasma folate or vitamin B-12 levels with mortality. Our results extend previously reported associations of homocysteine with mortality, and the absence of associations of folate and vitamin B-12 with mortality, to the older population.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Folic Acid; Homocysteine; Humans; Male; Risk Factors; United Kingdom; Vitamin B 12

Topics: Animals; Arginine; Cardiovascular Diseases; Cystatin C; Cystatins; Disease Models, Animal; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Diseases; Risk Factors; Vitamin B 12; Vitamin B 6

To assess the role of homocysteine as a risk factor for mortality in diabetic subjects.. Homocysteine, vitamin B(12), and folate concentrations were measured in stored sera of 396 diabetic Pima Indians aged > or = 40 years when examined between 1982 and 1985. Vital status was assessed through 2001.. Over a median follow-up of 15.7 years, there were 221 deaths-76 were due to cardiovascular disease (CVD), 36 to diabetes/nephropathy and 34 to infections. Homocysteine was positively associated with mortality from all causes (hazard rate ratio (HRR) for highest versus lowest tertile of homocysteine = 1.70, 95% confidence interval (CI) 1.18-2.46), from diabetes/nephropathy (HRR = 2.39, 95% CI 0.94-6.11) and from infectious diseases (HRR = 3.39, 95% CI 1.19-9.70), but not from CVD (HRR = 1.16, 95% CI 0.62-2.17) after adjustment for age, sex and diabetes duration. Homocysteine correlated with serum creatinine (r = 0.50), and the relationships with mortality rates were not significant after adjustment for creatinine. Vitamin B(12) was positively associated with all-cause mortality (HRR for 100 pg/mL difference adjusted for age, sex and diabetes duration = 1.15, 95% CI 1.08-1.22) and death from diabetes/nephropathy (HRR = 1.27, 95% CI 1.10-1.46). The association between homocysteine and mortality in type 2 diabetes is not causal, but is confounded by renal disease in Pima Indians.

Topics: Adult; Aged; Aged, 80 and over; Arizona; Cardiovascular Diseases; Cause of Death; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Folic Acid; Homocysteine; Humans; Indians, North American; Infections; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Serum Albumin; Vitamin B 12

Since studies suggest that both hypoxia and sleep fragmentation are related to cardiovascular alterations induced by obstructive sleep apnea, the present study was designed to evaluate the effects of hypoxia, sleep deprivation, and their combination on biochemical blood parameters in rats. In subchronic experiments (4 days), rats were exposed to intermittent hypoxia (IH) during the light period (2min room air-2min 10% O(2) for 12h/day) and/or paradoxical sleep deprivation (PSD, 24h/day). Consequences of chronic intermittent hypoxia (CIH) exposure were examined after 21 consecutive days of hypoxia protocol from 10:00 to 16:00 followed by a sleep restriction (SR) period of 18h (16:00-10:00). Rats were randomly assigned to seven treatment groups: (1) control (2) IH (3) PSD (4) IH-PSD (5) SR (6) CIH and (7) CIH-SR. PSD reduced triglycerides and very low-density lipoprotein (VLDL) cholesterol concentrations and increased total cholesterol and high-density lipoprotein (HDL) cholesterol. IH did not alter any of these parameters. The combination of IH-PSD did not modify the values of total cholesterol and HDL compared to control group. In the chronic experiment, the animals exposed to CIH displayed a reduction of Vitamin B(6) and an increase of triglycerides and VLDL. Our findings show a duration-dependent effect of hypoxia on triglycerides. Rats in the SR and CIH-SR groups showed a diminished concentration of triglycerides and VLDL. SR rats showed a reduction in the concentration of homocysteine but the animals in the CIH-SR treatment condition did not display any alterations in this parameter. In this latter group, an augmentation of cysteine concentration was observed. These results suggest that sleep deprivation and hypoxia modify biochemical blood parameters in distinct ways.

Topics: Animals; Blood Gas Analysis; Body Weight; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Chronic Disease; Cysteine; Folic Acid; Homocysteine; Hypoxia; Male; Rats; Rats, Wistar; Risk Factors; Sleep Apnea Syndromes; Sleep Deprivation; Sleep, REM; Triglycerides; Vitamin B 12

Homocysteine is associated with age, folate and vitamin B(12). Our study investigated the functional and clinical characteristics of the elderly (aged 60-85 years) of San Teodoro, a village in Central Sicily, and evaluated associations with vitamin B(12), folate and homocysteine.. Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests.. A total of 19.3% of the population had a low blood level of folate (<7 nmol/L) and 3.2% had low vitamin B(12) concentration (<100 pmol/L). The level of dependency, determined by the Barthel index, influenced homocysteine blood levels (p<0.0001), independent of age (p<0.0001), folate (p=0.0028) and vitamin B(12) (p=0.0165). Homocysteine was significantly associated with stroke (p=0.0027) and peripheral arterial vascular disease (p=0.0001), but not with myocardial infarction, angina pectoris, venous thrombosis or cancer. Vitamin B(12) was lower in myocardial infarction and higher in diabetes and venous thrombosis compared to the other diseases.. The prevalence of deficits in folate and vitamin B(12) was paradoxically high in the mountainous northeastern area of Sicily. Our study also underlines the association of homocysteine with dependency of the elderly and with stroke and peripheral arteriopathy.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Diabetes Mellitus; Folic Acid; Homocysteine; Humans; Middle Aged; Neoplasms; Peripheral Vascular Diseases; Sicily; Stroke; Vitamin B 12

Brachial artery flow-mediated dilation (BAFMD) has been proposed as a measurement of the degree and severity of cardiovascular disease. The purpose of this study was to (1) evaluate the associations between BAFMD and homocysteine, folate, vitamin B(12), vitamin B(6); (2) examine the influence of 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes on homocysteine levels and BAFMD; and (3) evaluate the effect of homocysteine on the baseline diameter of the vessel vs BAFMD. A total of 174 healthy research subjects were examined for BAFMD, homocysteine, folate, vitamin B(12), vitamin B(6), and MTHFR genotype, nucleotide 677 C-->T. The data indicated a significant inverse correlation between homocysteine and BAFMD (r = -0.1763, P = .02). There was a significant difference in BAFMD between MTHFR genotype groups (P = .01) (T/T vs C/C, P = .042; C/C vs C/T, P = .13; T/T vs C/T, P = .003). Homocysteine was significantly associated with the baseline brachial artery diameter (r = 0.1878, P = .013). The data confirmed a significant inverse correlation between baseline diameter and BAFMD (r = -0.3321, P = .0001). Regression analysis indicated that the MTHFR genotype, homocysteine, and age were significant predictors of BAFMD (P = .0001, r(2) = 0.118). When the baseline brachial diameter was incorporated into the model, the effect of homocysteine on BAFMD disappeared. The present data indicate an association between homocysteine and BAFMD and reduced BAFMD in individuals with the MTHFR nucleotide 677 T/T genotype, despite similar blood values for folate and homocysteine. Finally, the data suggest that the effect of homocysteine on vascular reactivity is in part a consequence of its influence on baseline brachial artery diameter.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Aged; Brachial Artery; Cardiovascular Diseases; Dilatation, Pathologic; DNA; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Point Mutation; Polymerase Chain Reaction; Ultrasonography; Vitamin B 12; Vitamin B 6

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12

Elevation of plasma homocysteine (Hcy) level has been implicated in the pathogenesis of slow coronary flow (SCF) as it can severely disturb vascular endothelial function. Helicobacter pylori chronically infect the human stomach and causes malabsorption of vitamin B(12) and folate in food, leading ultimately to an increase in circulating Hcy levels.. Forty-three patients with angiographically proven SCF (group I) were enrolled in this study; 43 cases with normal coronary flow pattern (group II) served as controls. Fasting plasma levels of Hcy, vitamin B(12), and folate were measured in all subjects. Presence of H. pylori infection was defined as positive 14 C urea breath test. Coronary flow patterns for each major epicardial coronary artery were determined with the Thrombolysis in Myocardial Infarction (TIMI) frame count method.. Mean TIMI frame count was 46.3 +/- 8.7 in group I and 24.3 +/- 2.9 in Group II (p = .0001). Vitamin B(12) levels were similar, whereas folate levels were dramatically reduced in group I compared to group II (13.2 +/- 4.3 vs. 17.1 +/- 5.2, p = .0001). Plasma Hcy levels were significantly higher in group I compared to group II (13.4 +/- 5.6 vs. 7.9 +/- 2.5, p = .0001) as was the prevalence of H. pylori infection (90.7% in group I vs. 58.1% in group II, p = .001). Hcy levels were elevated (11.7 +/- 5.3 vs. 7.5 +/- 2.7, p = .0001) and folate levels were reduced (13.9 +/- 4.7 vs. 18.6 +/- 4.9, p = .0001) in patients with H. pylori infection, while vitamin B(12) levels were similar in patients with and without H. pylori infection. Correlation analysis revealed a significant negative correlation between plasma folate and Hcy levels and also between folate levels and mean TIMI frame counts (r = -.33, p = .002 vs. r = -.33, p = .003). Moreover, there was a significant positive correlation between plasma Hcy levels and mean TIMI frame counts (r = .66, p = .0001). In addition, the folate level was the only significant determinant of the variance of Hcy in multiple regression analysis (r = -.21, p = .03).. Our data showed that plasma folate levels were decreased and plasma Hcy levels were increased in patients with SCF compared to controls. Also, the prevalence of H. pylori infection was increased in patients with SCF. These findings suggest that elevated levels of plasma Hcy, possibly caused by H. pylori infection, and/or a possible disturbance in its metabolism may play a role in the pathogenesis of SCF.

Topics: Adult; Blood Flow Velocity; Cardiovascular Diseases; Coronary Circulation; Female; Folic Acid; Helicobacter Infections; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Vitamin B 12

Mandatory folic acid fortification of food is effective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse effects. Thus, it is virtually nonexistent in Europe, albeit many countries allow food fortification on a voluntary basis.. The objective of the study was to examine the effect of a voluntary but liberal food fortification policy on dietary intake and biomarker status of folate and other homocysteine-related B vitamins in a healthy population.. The study was a cross-sectional study. From a convenience sample of 662 adults in Northern Ireland, those who provided a fasting blood sample and dietary intake data were examined (n = 441, aged 18-92 y). Intakes of both natural food folate and folic acid from fortified foods were estimated; we used the latter to categorize participants by fortified food intake.. Fortified foods were associated with significantly higher dietary intakes and biomarker status of folate, vitamin B-12, vitamin B-6, and riboflavin than were unfortified foods. There was no difference in natural food folate intake (range: 179-197 microg/d) between the fortified food categories. Red blood cell folate concentrations were 387 nmol/L higher and plasma total homocysteine concentrations were 2 micromol/L lower in the group with the highest fortified food intake (median intake: 208 microg/d folic acid) than in the nonconsumers of fortified foods (0 microg/d folic acid).. These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Erythrocytes; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Middle Aged; Neural Tube Defects; Nutrition Policy; Nutritional Status; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia, an independent cardiovascular risk factor, is present in the majority of hemodialysis patients. Among the postulated mechanisms of toxicity, protein homocysteinylation is potentially able to cause significant alterations in protein function. Protein homocysteinylation occurs through various mechanisms, among which is the post-translational acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine (Hcy) thiolactone). Another type of protein homocysteinylation occurs through the formation of a covalent -S-S- bond, found primarily with cysteine residues (protein-S-homocysteinylation). Scant data are available in the literature regarding the extent to which alterations in protein homocysteinylation are present in uremic patients on hemodialysis, and the effects of folate treatment are not known. Protein homocysteinylation was measured in a group of hemodialysis patients (n=28) compared to controls (n=14), with a new method combining protein reduction, gel filtration and Hcy derivatization. Chemical hydrolysis was performed, followed by high-pressure liquid chromatography separation. The effects of folate treatment on protein homocysteinylation, as well as in vitro binding characteristics were evaluated. Plasma Hcy, protein-N-homocysteinylation and protein-S-homocysteinylation were significantly higher in patients vs controls. Plasma Hcy and protein-S-homocysteinylation were significantly correlated. After 2 months of oral folate treatment, protein-N-homocysteinylation was normalized, and protein-S-homocysteinylation was significantly reduced. Studies on albumin-binding capacity after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam-binding site. In conclusion, increased protein homocysteinylation is present in hemodialysis patients, with possible consequences in terms of protein function. This alteration can be partially reversed after folate treatment.

Topics: Adult; Aged; Blood Proteins; Cardiovascular Diseases; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; In Vitro Techniques; Male; Middle Aged; Models, Molecular; Protein Binding; Protein Processing, Post-Translational; Renal Dialysis; Serum Albumin; Uremia; Vitamin B 12; Vitamin B 6; Xenobiotics

Elevated plasma total homocysteine is an independent risk factor for cardiovascular disease and a sensitive marker of the inadequate vitamin B12 and folate insufficiency. Folate and vitamin B12 have a protective effect on cardiovascular disease. This population based study was conducted to evaluate the plasma total homocysteine, folate, and vitamin B12 in healthy Iranian individuals.. This study was a part of the Cardiovascular Risk Factors Survey in the Population Lab Region of Tehran University has been designed and conducted based on the methodology of MONICA/WHO Project. A total of 1214 people aged 25-64 years, were recruited and assessed regarding demographic characteristics, homocysteine, folate, and vitamin B12 levels with interview, questionnaires, examination and blood sampling. Blood samples were gathered and analyzed according to standard methods.. The variables were assessed in 1214 participants including 428 men (35.3%) and 786 women (64.7%). Age-adjusted prevalence of hyperhomocysteinemia (Hcy > or = 15 micromol/L) was 73.1% in men and 41.07% in women (P < 0.0001). Geometric mean of plasma homocysteine was 19.02 +/- 1.46 micromol/l in men and 14.05 +/- 1.45 micromol/l in women (P < 0.004) which increased by ageing. Age-adjusted prevalence of low serum folate level was 98.67% in men and 97.92% in women. Age-adjusted prevalence of low serum vitamin B12 level was 26.32% in men and 27.2% in women. Correlation coefficients (Pearson's r) between log tHcy and serum folate, and vitamin B12 indicated an inverse correlation (r = -0.27, r = -0.19, P < 0.0001, respectively).. These results revealed that the prevalence of hyperhomocysteinemia, low folate and vitamin B12 levels are considerably higher than other communities. Implementation of preventive interventions such as food fortification with folic acid is necessary.

Topics: Adult; Age Factors; Cardiovascular Diseases; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Iran; Male; Middle Aged; Nutrition Surveys; Prevalence; Sex Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cardiovascular Diseases; Diabetes Mellitus; Drug Therapy, Combination; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Methylation; Myocardial Infarction; Secondary Prevention; Vascular Diseases; Vitamin B 12; Vitamin B 6

Serum homocysteine levels, which increase with age, are now recognized as a vascular risk factor and are related to the development of heart failure and dementia in the elderly. However, relatively low serum homocysteine levels have also been reported to be an adverse prognostic factor in dialysis patients. The objective of the study was to analyze the prevalence, clinical significance, and prognostic value of serum homocysteine levels in patients older than 65 years, admitted to a general internal medicine hospitalization unit. We studied 337 hospitalized patients, 184 males and 153 females, aged 77.2+/-0.4 years, whose admission was not determined by an acute vascular event. We recorded past vascular events and vascular risk factors. We determined the body mass index (weight in kilograms divided by the square of height in meters), and cholesterol, triglyceride, folate, vitamin B12, and homocysteine levels. We also studied 36 control subjects (18 males and 18 females) of similar age. After discharge, we assessed the survival status of 301 patients by telephone recall. Survival curves were plotted by the method of Kaplan and Meier. Median survival was 1186 days. The 15th (9.6 micromol/L) and 50th (14.4 micromol/L) percentiles, as the lowest and highest cut-off points, were empirically defined as those related to a shorter survival. Serum homocysteine concentration was significantly positively correlated with age and serum creatinine and albumin concentrations, and negatively correlated with serum cobalamin and folate concentrations. The average serum homocysteine concentration for the patients group, as a whole, was 16.5+/-0.5 micromol/L, not significantly different from the control group, but with a much greater dispersion, as patients with congestive heart failure or cognitive impairment had higher serum homocysteine concentrations, and patients with sepsis, leukocytosis, and hypoalbuminemia had lower concentrations. Malnutrition was associated both with abnormally high and low homocysteine concentrations, and abnormally low and abnormally high homocysteine concentrations were both associated with higher mortality. In conclusion, low homocysteine levels in elderly non-vitamin-supplemented hospitalized patients should not be interpreted as a protective factor in some individuals. Instead, it may be considered as an effect of an inflammatory-malnutrition process associated with a poor prognosis.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Creatinine; Female; Hemoglobins; Homocysteine; Humans; Lymphocyte Count; Male; Neutrophils; Nutritional Status; Predictive Value of Tests; Risk Factors; Serum Albumin; Statistics, Nonparametric; Survival Analysis; Triazoles; Vitamin B 12

Topics: Cardiovascular Diseases; Folic Acid; Hematinics; Homocysteine; Humans; Randomized Controlled Trials as Topic; Stroke; Vitamin B 12; Vitamin B 6

Moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) even among children. The purpose of this study is to investigate for the first time the distribution and determinants of total serum homocysteine (tHcy) levels in healthy Greek children.. tHcy, folate, B12 were measured in 524 children (275 boys and 249 girls) aged 6-15 years old from different socioeconomic status in Northern Greece.. The geometric mean tHcy level for boys and girls was 7.8 (3.4-24.2) and 7.5 (3.9-29.0) micromol/L, respectively. Eighty one (15.4%) children had homocysteine levels above the upper reference limits (>10 micromol/L). The geometric mean serum tHcy level was significantly (P<0.001) increasing with age; 6.4 (3.4-11.2) micromol/L was found in the age group of 6-9 yr (group1), 7.2(4.1-22.1) micromol/L in the one of 10-12 yr (group 2) and 8.5 (3.9-29.0) micromol/L in the one of 13-15 yr (group 3). Serum folate levels were found to be statistically significant (P<0.001) between age group 1 and age group 3 [11.8 (4.66-20.00) vs. 7.5 (0.99-20.00)ng/mL) and between age group 2 and 3 [10.0 (1.82-20.0) vs. 7.5 (0.99-20.00)ng/mL]. Vitamin B12 levels were significantly (P<0.001) different in the three age groups [1048 (117-2000), 805 (296-2000), 700 (214-2000)pg/mL] respectively. Age, BMI, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively correlated with tHcy, whereas serum folate and vitamin B12 were negatively correlated. No association was found between tHcy levels and parental education status. In multiple linear regression analysis only age (Beta: 0.248, 95%, CI: (0.159-0.361), P<0.05) and folate (Beta: 0.347, 95%, CI: [(-0.206)-(-0.118)], P<0.05) were found significantly and independently associated with tHcy.. tHcy levels were increasing with age and boys were found to have slightly higher levels than girls. Age and folate levels were the most significantly and independently determinants associated with tHcy. Children with tHcy levels above the upper reference limits (>10 micromol/L) were found to be correlated with BMI, WC, SBP, serum folate and vitamin B12 levels. These children should be encouraged to include high folate food items in their diet and where necessary folate supplements should be recommended. In addition, more prospective studies are necessary in order to evaluate the relationship of tHcy and CVD risk factors in children of our region.

Topics: Adolescent; Adolescent Nutritional Physiological Phenomena; Age Factors; Aging; Blood Pressure; Cardiovascular Diseases; Child; Child Nutritional Physiological Phenomena; Female; Folic Acid; Greece; Health Surveys; Homocysteine; Humans; Hyperhomocysteinemia; Male; Reference Values; Risk Factors; Sex Factors; Social Class; Vitamin B 12; Vitamin B Complex

Homocysteine and asymmetric dimethylarginine (ADMA) affect nitric oxide (NO) concentration, thereby contributing to cardiovascular disease (CVD). Both amino acids can be reduced in vivo by estrogen. Variation in the estrogen receptor (ER) may influence homocysteine and ADMA, yet no information is available on associations with single nucleotide polymorphisms in the estrogen receptor genes ERalpha (PvuII and XbaI) and ERbeta (1730G-->A and cx + 56 G-->A).. To find relationships between common polymorphisms associated with cardiovascular disease and cardiovascular risk factors homocysteine and ADMA.. In a cross-sectional study with healthy postmenopausal women (n = 89), homocysteine, ADMA, nitric oxide metabolites (NOx), plasma folate and ERalpha and beta polymorphisms ERalpha PvuII, ERalpha XbaI; ERbeta 1730G-->A (AluI), ERbeta cx + 56 G-->A (Tsp509I) were analyzed.. Women who are homozygotic for ERbetacx + 56 G-->A A/A exhibited higher homocysteine (p = 0.012) and NOx (p = 0.056) levels than wildtype or heterozygotes. NOx concentration was also significantly affected by ERbeta 1730 G -->A polymorphism (p = 0.025). The ERbeta (p < 0.001) and ERalpha (p < 0.001) polymorphisms were in linkage disequilibrium.. Women who are homozygotic for ERbetacx + 56 G-->A A/A may be at increased risk for cardiovascular disease due to higher homocysteine levels.

Topics: Aged; Arginine; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Folic Acid; Genetic Variation; Genotype; Homocysteine; Humans; Linkage Disequilibrium; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Polymorphism, Single Nucleotide; Postmenopause; Risk Factors; Vitamin B 12

Topics: Cardiovascular Diseases; Dementia; Folic Acid; Humans; Hyperhomocysteinemia; Vascular Diseases; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Atherosclerosis; Cardiovascular Diseases; Folic Acid; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Data Interpretation, Statistical; Folic Acid; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Cardiovascular Diseases; Folic Acid; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Cardiovascular Diseases; Folic Acid; Humans; Hyperhomocysteinemia; India; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Data Interpretation, Statistical; Folic Acid; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6; Vitamin B Complex

There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases.. Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences.. From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis.. The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women.. It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.

Topics: Adult; Aged; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; COUP Transcription Factor II; Diabetes Mellitus, Type 2; Factor XIII; Female; Folic Acid; Homocysteine; Humans; Hungary; Hyperhomocysteinemia; Linear Models; Male; Middle Aged; Patient Selection; Polymorphism, Genetic; Retrospective Studies; Risk Factors; Vitamin B 12

To assess Homocysteine (Hcy), vitamin B12 and folic acid (FA) concentrations in resident Indian women and to study their correlation with traditional risk factors for coronary artery disease.. The study included 137 consecutive women who attended a health care program (HCP) for women at and above 40 years of age (MAITREYI's HCP). Fasting blood samples for Hcy, B12 and folate were collected on ice, centrifuged within 1/2 hour and stored at -70 degrees C till assayed using a chemiluminescence method. All women underwent a screening for their general health profile including cardiovascular health.. Of the 137 women screened 21 were excluded because of presence of factors known to affect Hcy levels (history of existing CAD had hypothyroidism or were on multivitamin supplements). The median Hcy, folic acid and vitamin B12 levels were 9 pmol/L (range 4.2-38.6), 8.8 ng/ml (2.3-31.6 range) and 214 pg/ml (100-2400 range) respectively. The prevalence of hyperhomocysteinemia (>15 pmol/L) was 24.2%. Correlation for continuous variables using spearman's test and for categorical variables with chi-square test showed a highly significant negative correlation with vitamin B12 (p < 0.001) and FA (p<0.002). Both systolic (p < 0.05) and diastolic (p < 0.02) and diastolic blood pressure also showed a significant correlation. However, no correlation was found between plasma Hcy and blood sugars, lipids, age, body mass index and menopausal status. The CAD risk was assessed using Framingham risk scores and this too did not show a correlation with plasma Hcy.. A large number of women from the present study had hyperhomocysteinemia and were deficient in vitamin B12. A significant negative correlation between vitamin B12 and plasma Hcy levels was foundin these older women. Most Indian studies including the present one do not show a positive correlation between elevated Hcy levels and CAD in spite of a large percentage of persons showing elevated homocysteine levels. Since high Hcy levels are recognized as an independent risk factor for CAD, these findings of absence of correlation between Hcy and CAD as reported in various Indian studies need to be explored and explained.

Topics: Adult; Aged; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; India; Middle Aged; Risk Assessment; Risk Factors; Vitamin B 12

The risk of cardio vascular disease (CVD) doubles after menopause. Plasma homocysteine (hCy) is a risk factor which is influenced by vitamins B12,B6 and folate. The present study was conducted to examine the relationship of plasma hCy to the three vitamins and other contributing variables in early natural menopause.. Participants were healthy, non smoking Caucasian women 3 to 5 years postmenopausal (n = 26) or premenopausal between 30 and 45 y(n = 30). Anthropometric data, dietary records and plasma concentrations of hCy, vitamin B6, vitamin B12 and folate were obtained.. The nutritional status of vitamins B6, B12 and folate as measured by dietary intake and blood concentrations was adequate in both groups. Mean fasting plasma total (t) hCy concentration of postmenopausal group was 2-fold higher than the value found for control group (P < 0.0001) without oral methionine loading. The difference between the two groups remained highly significant after adjustment for confounding variables by multivariate analysis, suggesting that the effect of estrogen deficiency was direct.. In addition to the loss of the protective effects of estrogen on their cardiovascular physiology and lipid metabolism, postmenopausal women are exposed to higher plasma hCy concentrations and deleterious cardiovascular effects. The exact mechanism is not known but does not seem to be related to coenzyme deficiency.

Topics: Adult; Cardiovascular Diseases; Coenzymes; Diet; Estrogens; Female; Folic Acid; Homocysteine; Humans; Menopause; Middle Aged; Risk Factors; Vitamin B 12; Vitamin B 6

Topics: Cardiovascular Diseases; Female; Folic Acid; Fractures, Bone; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6

Rates of renal and cardiovascular disease are high among Aboriginal Australians living in remote communities. Nutritional problems, in particular low folate levels, are also common. This suggests that increased homocysteine concentrations might be widespread, and a possible contributor to the high rates of cardiovascular disease.. To examine homocysteine concentrations, and their relationships to folate levels, and to markers of renal disease and cardiovascular disease in a remote Aboriginal Australian community. As part of a cross-sectional survey among adults in one community, homocysteine concentrations, concentrations of the crucial determinants (red blood cell (RBC) folate, vitamin B(12) and the C677T methylene tetrahydrofolate reductase polymorphism) and cardiovascular risk factors were examined.. Among 221 people, geometric mean homocysteine concentration was 11.8 micromol/L (range: 11.1-12.5 micromol/L), with 57/221 (26%) values > or =15.0 micromol/L. Higher concentrations were associated with older age, male gender, lower RBC folate and lower vitamin B(12) concentrations and homozygosity for C677T. Homocysteine concentrations were not related to the presence of albuminuria, other than over the overt albuminuria range. Homocysteine concentrations were inversely correlated with calculated glomerular filtration rate (GFR). Carotid intima-media thickness, however, was not related to homocysteine concentration. In multivariate analyses, age, male gender, lower RBC folate concentrations, lower vitamin B(12) concentrations, lower calculated GFR and the C677T polymorphism were all associated with homocysteine concentrations.. Homocysteine concentrations were consistent with previous limited reports in Aboriginal communities. Although superficially they are similar to reports from non-Aboriginal settings, the younger age of this cohort and the association of homocysteine concentrations with age suggest that age-specific concentrations are higher among Aboriginal Australians. In addition to dietary determinants, the high prevalence of apparently reduced renal function renal disease appears to be an important determinant of homocysteine concentrations in remote Aboriginal communities. The role of homocysteine concentrations as a potential mediator of the high rates of cardiovascular disease remains to be determined.

Topics: Adult; Albuminuria; Arteriosclerosis; Australia; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Native Hawaiian or Other Pacific Islander; Polymorphism, Genetic; Regression Analysis; Rural Population; Vitamin B 12

Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity.. The study was designed to evaluate the total homocysteine level and MTHFR C677T polymorphism frequency of 122, healthy, young adults who had increased risk for cardiovascular disease. The serum levels of folic acid and vitamin B12 were also measured.. Immunoassay, PCR-RFLP methods were used. The statistical analysis was performed by SPSS program.. The frequency of the gene-polymorphism was not different significantly in the study group compared to a Hungarian neonatal sample: although in the increased risk group the frequency of homozygous 677TT polymorphism was higher (14.8%), and heterozygosity was smaller (41%). There was no association between MTHFR gene polymorphism and homocysteine levels. A significant negative correlation was found between the folic acid and homocysteine, and between the vitamin B12 and homocysteine levels correlating with the literature. The mean serum total homocysteine level of the group without vitamin supplementation (n: 86) was 9.8 +/- 3.3 micromol/l, while in the other group with vitamin uptake (n: 36) this level was 7.5 +/- 3.0 micromol/l. There was a significant difference between the homocysteine levels of men and women.. The results of the study correlate with the literature. It would be useful to call the attention of the Hungarian population to the importance of vitamin supply.

Topics: Adult; Cardiovascular Diseases; Cytosine; Female; Folic Acid; Heterozygote; Homocysteine; Humans; Immunoassay; Male; Methylenetetrahydrofolate Reductase (NADPH2); Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Risk Factors; Thymine; Vitamin B 12

There is increased worldwide concern about the consequences of folic acid and vitamin B12 deficiencies on health, which include megaloblastic anemia, neural tube defects and cardiovascular disease.. This study intended to determine the prevalence of folic acid and vitamin B12 deficiencies in vulnerable groups in labor and poor socioeconomic strata of the Venezuelan population.. A total of 5658 serum samples were processed to determine folic acid and vitamin B12 concentrations. The study involved three surveys performed during 2001-2002 and included infants, children, adolescents and pregnant women from labor and poor socioeconomic strata of the population. The method used was a radio immunoassay designed for the simultaneous measurement of serum folic acid and vitamin B12.. The prevalence of folic acid deficiency was higher than 30% for all groups studied, reaching 81.79% in adolescents. Vitamin B12 deficiency was 11.4% in samples collected nationwide, but there was also a similar prevalence of high serum levels. The prevalence of folic acid and vitamin B12 deficiencies in pregnant women reached 36.32 and 61.34%, respectively.. This work shows that there is a high prevalence of folic acid deficiency, especially in women of reproductive age, pregnant adolescents and in the whole population studied in Vargas state. This situation requires immediate intervention as supplementation or food fortification programs.

Topics: Adolescent; Adult; Anemia, Megaloblastic; Cardiovascular Diseases; Child; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Male; Neural Tube Defects; Nutrition Surveys; Pregnancy; Radioimmunoassay; Seroepidemiologic Studies; Venezuela; Vitamin B 12; Vitamin B 12 Deficiency

To investigate the relationship between homocysteine (Hcy) and B vitamins status in the Taiwanese elderly population, an analysis was made of the plasma Hcy levels in elderly persons. The study sample was taken from the Elderly Nutrition and Health Survey in Taiwan (1999-2000) (Elderly NAHSIT) and included 1094 males and 1135 females aged 65-90 years. The results showed that average plasma Hcy was 13.3+/-0.6 micromol/ L for males and 10.6+/-0.7 micromol/L for females. The average plasma Hcy levels of males from all age groups were significantly higher than those of females, and significantly increased with age (P<0.0001). The overall prevalence of hyperhomocysteinemia (Hcy>15 micromol/L) was 23.4% for elderly males and 11.2% for elderly females, and this also increased with age (P<0.0001). In subjects with normal renal function, folate, vitamin B2, B6, and B12 status were significantly lower in males with hyperhomocysteinemia, while only folate and vitamin B12 were significantly lower in females with hyperhomocysteinemia. Further analysis suggested that folate, vitamin B6 or B12 insufficiency were associated with hyperhomocysteinemia in both sexes, while vitamin B2 insufficiency was significantly associated only in males. In elderly persons with adequate folate, vitamin B6, and B12 status, there was no significant association between vitamin B2 and hyperhomocysteinemia. This association occurred only in those who had concurrent poor folate, vitamin B6, or B12 status. The strength of the association between vitamin B12 insufficiency and hyperhomocysteinemia was not affected by simultaneous vitamin B2 or B6 insufficiency, but increased about 3-fold when combined with folate. This suggests that poor folate and vitamin B12 status has a synergistic effect on the risk of hyperhomocysteinema in the elderly, as did a poor folate and vitamin B6 status. Therefore, maintaining adequate vitamin B12 status and avoiding multiple B vitamin insufficiency, especially that of folate and vitamin B12 or B6, should be emphasized as an important measure for reducing plasma Hcy levels among elderly Taiwanese.

Topics: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Health Surveys; Homocysteine; Humans; Hyperhomocysteinemia; Male; Nutrition Surveys; Nutritional Status; Sex Factors; Taiwan; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency; Vitamin B Complex

Topics: Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Micronutrients; Nutritional Requirements; Risk Factors; Sex Factors; Vitamin B 12

High consumption of vegetables and fruits is associated with reduced risk for cardiovascular disease. However, little information is available about diets based predominantly on consumption of fruits and their health consequences. We investigated the effects of an extremely high dietary intake of raw vegetables and fruits (70-100% raw food) on serum lipids and plasma vitamin B-12, folate, and total homocysteine (tHcy). In a cross-sectional study, the lipid, folate, vitamin B-12, and tHcy status of 201 adherents to a raw food diet (94 men and 107 women) were examined. The participants consumed approximately 1500-1800 g raw food of plant origin/d mainly as vegetables or fruits. Of the participants, 14% had high serum LDL cholesterol concentrations, 46% had low serum HDL cholesterol, and none had high triglycerides. Of raw food consumers, 38% were vitamin B-12 deficient, whereas 12% had an increased mean corpuscular volume (MCV). Plasma tHcy concentrations were correlated with plasma vitamin B-12 concentrations (r = -0.450, P < 0.001), but not with plasma folate. Plasma tHcy and MCV concentrations were higher in those in the lowest quintile of consumption of food of animal origin (P(trend) < 0.001). This study indicates that consumption of a strict raw food diet lowers plasma total cholesterol and triglyceride concentrations, but also lowers serum HDL cholesterol and increases tHcy concentrations due to vitamin B-12 deficiency.

Topics: Adult; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diet, Vegetarian; Female; Folic Acid; Fruit; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Risk Factors; Triglycerides; Vegetables; Vitamin B 12

To examine the effect of hemodialysis on plasma homocysteine levels, and the relationship of these values to clinical cardiovascular events in patients with end-stage renal disease (ESRD).. Adults undergoing chronic hemodialysis were studied at baseline and at six months. Their clinical histories were obtained at the baseline visit, and measurements of plasma homocysteine concentration were made immediately prior to and following routine dialysis. The occurrence of clinical cardiovascular events was assessed over six months.. We enrolled 147 patients (85 men and 62 women, age 58 +/- 15 years) who required hemodialysis for 3.4 +/- 3.4 years (mean +/- SD). The median homocysteine level for this population (including both pre- and post-dialysis values) was 17.3 micromoles/L. Mean pre-dialysis plasma homocysteine levels of patients with clinical cardiovascular disease did not differ significantly from those without the disease (22.5 +/- 9.9 vs. 25.4 +/- 24.5 micromoles/L, respectively), nor did post-dialysis levels differ between these populations. During six months follow-up, rates of ischemic events were not related to hyperhomocysteinemia. The difference between mean pre- and post-dialysis homocysteine levels (26.3 +/- 19.7 and 15.6 +/- 11.4 micromoles/L, respectively) and the decline in homocysteine over the course of a single dialysis treatment session (10.3 +/- 10.2 micromoles/L) were highly significant (p<0.0005).. Plasma homocysteine levels were elevated in 82% of 147 patients with ESRD and fell to the normal range in a majority of patients during a single dialysis treatment session. Mean pre-dialysis levels did not change significantly over six months, however, and plasma homocysteine levels did not predict cardiovascular events in this population. There was also a trend towards worse outcomes in patients with lower homocysteine levels, which correlates to findings from recent studies. Further studies are needed to clarify the association between hyperhomocysteinemia and coronary risk in patients with ESRD.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Statistics, Nonparametric; Vitamin B 12

Patients with diabetic nephropathy are at elevated cardiovascular risk. C-reactive protein (CRP) has been used to successfully predict cardiovascular events.. We identified clinical and biochemical characteristics that correlate with CRP levels in diabetic nephropathy patients.. Baseline data obtained from 722 patients in the Irbesartan Diabetic Nephropathy Trial included age, sex, body mass index (BMI), systolic blood pressure (BP), serum creatinine, plasma low- and high-density cholesterol, triacylglycerol, serum albumin, hemoglobin A1C, 24h urinary protein excretion, plasma total homocysteine (tHcy), folate, B12, pyridoxal 5'-phosphate (PLP, active form of Vitamin B(6)), and plasma CRP levels.. In univariate analyses CRP was positively associated with female sex (r=0.08; P=0.04), BMI (r=0.34; P<0.01), serum creatinine (r=0.21; P<0.01), hemoglobin A1C (r=0.08; 0.04), and inversely associated with PLP (r=-0.17; P<0.01) and folate (r=-0.09; P=0.02). A stepwise multiple regression model found CRP directly correlated with BMI (P<0.01) and serum creatinine (P<0.01), and inversely correlated with PLP (P<0.01). The final model explained 16% of the total variance of CRP.. These results extend previous findings of an inverse relationship between Vitamin B(6) and CRP. The lack of association between CRP and certain established or emerging cardiovascular risk factors offers novel information regarding cardiovascular risk in this population.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Depsipeptides; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Folic Acid; Glycated Hemoglobin; Humans; Male; Middle Aged; Peptides, Cyclic; Proteinuria; Pyridoxal Phosphate; Risk Factors; Serum Albumin; Triglycerides; Vitamin B 12

Hyperhomocysteinemia is a risk factor for cardiovascular disease. C677T mutation at the MTHFR gene and deficiencies of folic acid and vitamin B-12 may account for elevation of total homocysteine (tHcy). Ninety Brazilian Parkatêjê Indians (90.0% of the population without admixture, aged > or = 20 years) were studied. Hyperhomocysteinemia was observed in 26.7% of the Indians. No case of vitamin B-12 deficiency was detected. Folic acid deficiency was found in 43.3% of the subjects. Rates of mutated allele 677T and TT genotype were 40.7% and 14.0%, respectively. Prevalence of hypertension, dyslipidemia, smoking, WHR > or = 0.9, BMI > or = 25 kg/m2 and chronic alcohol use were 4.4%, 44.4%, 25.6%, 72.2%, 67.8%, and 0.0%, respectively. All creatinine values were normal. Natural logarithmic (ln) tHcy showed no correlation with age, but was positively correlated with systolic (r = 0.22) and diastolic (r = 0.21) blood pressure and triglycerides (r = 0.39) and inversely correlated with folic acid (r = -0.40) adjusted for age and sex. Total homocysteine (tHcy) was higher among TT genotype (P < .001). The multiple linear regression model, containing variables for sex, folic acid, TT genotype, and triglycerides, explained 50.0% of the variation of the ln tHcy. In summary, high rates of cardiovascular risk factors were discovered. C667T mutation and folic acid deficiency can explain, at least in part, the observed hyperhomocysteinemia.

Topics: Adult; Brazil; Cardiovascular Diseases; Female; Folic Acid Deficiency; Health Status Indicators; Homocysteine; Humans; Hyperhomocysteinemia; Indians, South American; Linear Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Risk Factors; Sex Factors; Smoking; Vitamin B 12

Topics: Brazil; Cardiovascular Diseases; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Indians, South American; Risk Factors; Vitamin B 12

Apolipoprotein E (APOE), vitamin B12, and folate were examined in relation to free recall among 167 community-based older adults. Cognitive support at encoding and retrieval was also taken into account. Participants were classified as APOE e4 or non-epsilon4 allele carriers and as either low or normal vitamin B12 or folate status. A significant association was identified between low vitamin B12 and the epsilon4 genotype in respect to free recall, but only in circumstances of low cognitive support. This result remained after removing dementia cases that occurred up to 6 years after testing. A similar, but nonsignificant, trend was evident in relation to folate. The research is discussed with reference to vulnerability models and genetic influences on brain reserves.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Attention; Cardiovascular Diseases; Cues; Female; Folic Acid; Genetic Carrier Screening; Genotype; Humans; Male; Mental Recall; Paired-Associate Learning; Reference Values; Risk Factors; Sweden; Verbal Learning; Vitamin B 12; Vitamin B 12 Deficiency

Cardiovascular disease is a major cause of morbidity and mortality in the United States and other developed countries; arterial lesions that are precursors of disease begin during childhood. Homocysteine levels have been associated with cardiovascular disease rates in adults, but information about levels in and impact on children is limited, particularly among various ethnic groups. This study examined the cardiovascular risk factors of a multi-ethnic sample of 100 9-15 year-old Native American, Hispanic, White, and mixed race children in rural central Washington. The mean fasting homocysteine level was 5.82 micromol/l (+/- 1.47), with no significant differences noted among ethnic groups. Mean dietary intake of folate, vitamin B6, and vitamin B12 exceeded current Recommended Dietary Allowances. Homocysteine levels did not show statistically significant correlations with cardiovascular risk factors. Homocysteine levels were not found to be a cardiovascular risk factor of importance, nor were significant ethnic differences found, in Native American, Hispanic and White children consuming adequate diets.

Topics: Adolescent; Cardiovascular Diseases; Child; Diet; Ethnicity; Fasting; Female; Folic Acid; Hispanic or Latino; Homocysteine; Humans; Indians, North American; Male; Nutrition Policy; School Health Services; Vitamin B 12; Vitamin B 6; White People

The effects of 96 h of paradoxical sleep deprivation (PSD) on blood parameters associated with cardiovascular risk were studied in young (3-month old) and aged (22-month old) rats. In general, aging was associated with an overall increase in most measures, irrespective of sleep deprivation condition. The latter manipulation also had significant effects on blood variables, but not in a consistent pattern. Thus, PSD significantly reduced triglyceride levels in both young and aged rats; it reduced blood viscosity in aged but not in young rats, and had no effect on the increased cholesterol levels observed in aged controls. Examinations of cholesterol fractions revealed significant increases in low density lipoprotein and high density lipoprotein in aged PSD rats compared to respective controls, whereas very low density lipoprotein was significant decreased after PSD in both young and aged animals. PSD increased vitamin B(12) levels in aged rats, and significantly decreased homocysteine levels in young but not in aged rats which in turn were already reduced. Folate levels were the only variable that was unaffected by aging and/or PSD. These results indicate that PSD has significant but heterogeneous physiological effects in aged rats and may intensify certain aging-related effects which contribute to cardiovascular disease risk while attenuating others.

Topics: Age Factors; Aging; Animals; Blood Viscosity; Cardiovascular Diseases; Cholesterol; Folic Acid; Homocysteine; Lipoproteins; Male; Rats; Rats, Wistar; Risk Factors; Sleep Deprivation; Triglycerides; Vitamin B 12

Low selenium levels in humans have been associated with several pathologies; however, an earlier animal investigation found a direct association between Se intake and total plasma homocysteine (tHcy) concentrations. To date, the importance of serum selenium levels in association with tHcy in humans has not been determined. We evaluated the cross-sectional association of blood selenium concentrations with plasma tHcy and other determinants of this cardiovascular disease risk factor. We estimated protein intake and measured the blood status of selenium, tHcy, and several other related factors in serum such as folate, vitamin B-12, and creatinine. Serum selenium was inversely associated with tHcy, explaining 5.8% of tHcy variance with respect to 2.2% accounted for by serum folate. Furthermore, there was a 63% decreased risk of higher tHcy concentrations (>14 micro mol/L) for subjects with serum selenium in the highest tertile (P = 0.013). We also found an inverse association of protein intake with tHcy in men (beta = -0.144; P = 0.036), which disappeared after controlling for serum Se concentrations (beta = -0.055; P = 0.003). In conclusion, selenium should be considered as a potential factor to lower tHcy. In addition, the described association between protein intake and homocysteine levels could be mediated by this trace element.

Topics: Aged; Aged, 80 and over; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Energy Intake; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Selenium; Vitamin B 12

We examined the prevalence of vitamin B(12) deficiency and its association with medication use and characteristics, including infection with Helicobacter pylori (H. pylori), in 255 patients hospitalized for cardiovascular disease. In almost half of the study population, vitamin B(12) deficiency was found; patients using acetylsalicylic acid were more frequently vitamin B(12) deficient in comparison to nonusers (p = 0.02). Fifty-one percent of the patients were infected with H. pylori, and fewer infected patients were vitamin B(12) deficient.

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Viral; Aspirin; Biomarkers; Cardiovascular Diseases; Female; Helicobacter Infections; Humans; Male; Middle Aged; Netherlands; Platelet Aggregation Inhibitors; Prevalence; Statistics as Topic; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA). The objective of this study was to examine the distribution of known CVD risk factors and biomarkers of CVD in women with and without RA.. This study included two components: an examination of clinical CVD risk factors among women participating in the Nurses' Health Study, a prospective longitudinal cohort, and an analysis of CVD biomarkers among a subgroup of women from this cohort who provided a blood specimen in 1989 (biospecimen cohort). Data regarding clinical risk factors for CVD were collected in 1990 by mailed questionnaire. The diagnosis of RA was confirmed through a structured medical record abstraction. We compared clinical risk factors for CVD and biomarkers of CVD between women with and without RA, adjusting for age, body mass index (BMI), smoking status, and menopause status.. Women with RA (n = 287) were significantly more likely than women without RA (n = 87,019) to report no alcohol use (48.2% versus 39.4%) and past cigarette smoking (47.8% versus 38.0%). No significant differences between these groups were observed for current smoker status, BMI, regular aspirin use, diabetes, hypertension, physical activity, and family history of early myocardial infarction. In the biospecimen cohort (69 RA cases and 491 controls), the levels of several inflammatory biomarkers linked to CVD were significantly elevated in women with RA, including CRP, fibrinogen, sICAM-1, sTNFRI, sTNFRII, and osteoprotegerin. Levels of total cholesterol, low-density lipoprotein, triglycerides, apolipoprotein B, and Lp(a) were similar between groups. Levels of homocysteine were similar, but vitamin B(12) was significantly higher among women with RA than among the controls.. In women participating in the Nurses' Health Study, most traditional CVD risk factors were similar between those who had RA and those who did not. However, as expected, biomarkers of inflammation associated with CVD were generally elevated in women with RA.

Topics: Adult; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Female; Humans; Longitudinal Studies; Middle Aged; Nurses; Prospective Studies; Risk Factors; Surveys and Questionnaires; Vitamin B 12; Women's Health

Over the last 30 years, cardiovascular diseases (CVDs), including stroke and myocardial infarction, have increased in developing countries. Serum lipids and diet of the Fulani, a rural Nigerian population, were previously studied. Despite their consumption of a diet rich in saturated fat, the overall blood lipid profiles of Fulani men and women are generally favourable. However, Fulani males in the same study had mean serum levels of homocysteine, an emerging risk factor for CVD, that exceeded the upper limit of the homocysteine reference range. The authors were interested in knowing if these findings in the Fulani nomads were representative of the biochemical parameters of CVD risk in other ethnic groups in the same region of Nigeria. To address this question, the nutrient content of diets of 55 men, aged 20-75 years, and 77 women, aged 20-70 years, who were inhabitants of a large urban centre in northern Nigeria, was assessed, and their serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and homocysteine were determined. These data were compared with those of the same rural Fulani population studied previously. Urban subjects consumed more calories than rural subjects (men: 2061 vs 1691 kcal; women: 1833 vs 1505 kcal) and had a significantly higher mean body mass index (BMI) and percentage of body fat than rural subjects. Both urban males and females had carbohydrate intakes that were greater than those of Fulani pastoralists (men: 56% vs 33% total calories; women: 51% vs 38% total calories), but had a significantly lower dietary intake of total fat and saturated fat (men: 36% vs 51% of total calories; women: 40% vs 51% of total calories). With the exception of HDL-cholesterol levels, which were significantly lower in the rural population, the blood lipid profiles of rural subjects were more favourable compared to those of urban subjects. Both urban and rural males had homocysteine levels above the upper limit of the reference range for healthy adults (urban males--12.7 micromol/L; rural males-15.2 micromol/L). The dietary intakes of folate and vitamin B12 were lower for rural Fulani subjects, and this was reflected in their significantly lower serum concentrations of these two vitamins. Results of this study suggest that, although the lipid profiles of urban and rural men and women in northern Nigeria indicate a relatively low risk for CVD, their elevated serum homocysteine levels are a cause for concern. The high homocy

Topics: Adult; Aged; Cardiovascular Diseases; Diet; Female; Folic Acid; Homocysteine; Humans; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Nigeria; Risk Factors; Rural Population; Triglycerides; Urban Population; Vitamin B 12

It is unclear whether homocysteine itself is causal in the pathogenesis of cardiovascular disease. Alternatively or additionally, the association between homocysteine and cardiovascular disease may be because of its metabolic precursor, S-adenosylhomocysteine, or of the ratio of S-adenosylmethionine to S-adenosylhomocysteine. Therefore, it is relevant to know how these moieties are interrelated, and whether, as is the case for homocysteine, they are influenced by blood levels of folate, cobalamin or vitamin B6.. We cross-sectionally studied a population-based cohort of 97 Caucasian subjects aged 60-85 years. Concentrations of homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, folate, cobalamin and vitamin B6 were measured in fasting blood samples.. In multiple regression analysis, homocysteine was associated with vitamin B12 (per 50 pmol L-1 increase of cobalamin, change in homocysteine, -0.70 mmol L-1; 95% CI, -1.30 to -0.10 mmol L-1) and folate (per 100 nmol L-1 increase in erythrocyte folate, change in homocysteine, -0.68 mmol L-1; 95% CI -1.28 to -0.08 mmol L-1). S-adenosylhomocysteine, S-adenosylmethionine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with serum folate, cobalamin or vitamin B6, nor with erythrocyte folate. Furthermore, plasma homocysteine showed a negative correlation with the ratio of S-adenosylmethionine to S-adenosylhomocysteine in plasma (r = -0.27; P < 0.01) but not in erythrocytes.. In contrast to homocysteine, the plasma concentrations of S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with the folate, cobalamin and vitamin B6 concentrations in the present study. If these precursors in part explain why homocysteine is associated with cardiovascular disease, homocysteine-lowering treatment with B vitamins may be less effective than currently expected, at least in an elderly population.

Topics: Aged; Aged, 80 and over; Body Constitution; Cardiovascular Diseases; Cross-Sectional Studies; Erythrocytes; Female; Folic Acid; Humans; Male; Middle Aged; Regression Analysis; S-Adenosylhomocysteine; S-Adenosylmethionine; Vitamin B 12; Vitamin B 6

To test the hypothesis that the incidence of fatal coronary heart disease and cardiovascular disease in a general population is related to serum and red cell folate and vitamin B-12 concentrations.. Cohort study with follow up of 29 years.. Busselton, Western Australia.. 1419 men and 1531 women aged 20 to 90 years, who were alive more than three years after their participation in the 1969 Busselton health survey. 2314 (78.4%) had no cardiovascular disease at the initial survey.. Hazard ratios for fatal coronary heart disease and cardiovascular disease in men and women according to baseline concentrations of serum and red cell folate and serum vitamin B-12.. 213 men and 159 women died from coronary heart disease, and 342 men and 302 women died from cardiovascular disease. Serum and red cell folate concentrations showed a moderate positive correlation (r=0.26, P<0.001) but otherwise serum and red cell folate and serum B-12 concentrations were not strongly correlated with each other or with other standard risk factors. After age and standard risk factors were adjusted for, there was no independent association between folate and B-12 concentrations and death from coronary heart disease or cardiovascular disease in the full cohort or the subcohort with no cardiovascular disease at baseline. The multivariate adjusted hazard ratio for death from cardiovascular disease in the lowest versus the highest category of red cell folate concentration was 1.05 (95% confidence interval 0.77 to 1.43) in men and 1.10 (0.81 to 1.51) in women.. These findings do not support the hypothesis that lower folate and B-12 concentrations increase the risk of fatal cardiovascular disease in a general population. The routine use of these vitamins for preventing cardiovascular disease should await evidence from clinical trials.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Erythrocytes; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Prognosis; Risk Factors; Survival Analysis; Vitamin B 12; Western Australia

Plasma total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease (CVD) even among children. The purpose of this study is to evaluate the determinants and distributions of plasma tHcy levels and the relationship between plasma tHcy, folate and vitamin B12 levels among school children in Taipei.. After multi-stage sampling, we randomly selected 1234 school children (609 boys and 625 girls) with the mean age of 13 years (from 12 to 15 years) in this study. Fasting plasma tHcy levels were measured using an ABBOTT IMx analyzer (Axis Biochemicals ASA, Oslo, Norway). Plasma folate and vitamin B12 levels were measured by ACS:180 automated chemiluminescence analyzer (Bayer, Tarrytown, NY, USA).. The distribution of plasma tHcy levels were skewed to the right with the mean values of 10.50 and 8.95 micromol/l and medians of 9.67 and 8.474 micromol/l for boys and girls, respectively. Plasma tHcy concentrations were lower in younger children and progressively increased with increasing age. Boys had significantly higher plasma tHcy levels than girls (10.50 +/- 4.134 vs. 8.95 +/- 2.61 micromol/l, p < 0.01) and lower plasma folate levels (6.05 +/- 2.85 vs. 6.39 +/- 2.58 nmol/l, p < 0.01), and vitamin B12 levels (444.8 +/- 158.4 vs. 495.0 +/- 181.5 pmol/l, p < 0.001). Plasma tHcy levels were significantly positively associated with anthropometric measures in boys; but these characteristics attenuated and became insignificant after adjusting for other potential confounders in girls. Plasma tHcy levels were negatively associated with plasma folate and vitamin B12 levels even after adjusting for BMI and other potential confounders in both genders.. From this study, the distributions of tHcy levels were skewed to the right and the boys had higher plasma tHcy levels than girls. Plasma tHcy levels were significantly positively associated with BMI among boys. Further studies are needed to evaluate the relationship between tHcy and CVD risk factors among children for the better prevention of heart disease in early life.

Topics: Adolescent; Age Factors; Anthropometry; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Health Surveys; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Schools; Sex Factors; Taiwan; Vitamin B 12; Vitamin B 12 Deficiency

We studied the association between total plasma homocysteine (tHcy) concentrations and folate, B(12), and B(6) status in the urban and rural areas of Costa Rica.. We determined plasma tHcy concentrations and assessed dietary folate, B(12) and B(6) intake by a food frequency questionnaire in 462 subjects selected by stratified random sampling in the urban and rural areas of Puriscal, Costa Rica. Plasma folate and vitamin B(12) concentrations were measured in women.. THcy concentrations were higher (p < 0.01) in the rural compared with the urban area: 12.0 micro mol/L vs. 8.9 micro mol/L in men, and women 7.3 micro mol/L vs. 5.5 micro mol/L in women, respectively. The prevalence of hyperhomocysteinemia (greater than 15.0 micro mol/L) was twice as high in rural compared with urban men (19.8% vs. 10.8%, p = 0.06) and women (6.6% vs. 3.4%, p = 0.26). Most study subjects (98%) had folate intakes that were less than the recommended 400 micro g/day. In women, 31% of those living in the urban area and 40% of those in the rural area had plasma folate concentrations of less than 6.8 nmol/L, an indicator of folate deficiency. In women, age-adjusted mean tHcy concentrations ( micro mol/L) were higher in the lowest compared with highest quintiles for dietary vitamin B(6) (9.9 vs. 5.4, p < 0.05), B(12) (9.2 vs. 4.9, p < 0.01), and folate (7.0 vs. 5.7, p = 0.87). Similar results were found for plasma B(12) (9.9 vs. 5.4, p < 0.01) and folate (10.5 vs. 5.0, p < 0.0001).. Residents of the rural area in Puriscal, Costa Rica have higher plasma concentrations of tHcy and lower intake of B vitamins, particularly in women. Because these characteristics are associated with high risk of cardiovascular disease, the efficacy of food fortification program in rural areas should be carefully addressed.

Topics: Adult; Aged; Alcohol Drinking; Blood Pressure; Body Constitution; Body Mass Index; Cardiovascular Diseases; Costa Rica; Diet; Educational Status; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Nutritional Status; Physical Fitness; Risk Factors; Rural Population; Sex Characteristics; Smoking; Urban Population; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Clinical Protocols; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Vitamin B 12

To investigate the effects of tobacco smoking on serum vitamin B12, folic acid and haematological parameters in healthy Thai smokers and non-smokers.. Cross-sectional study of smokers and non-smokers in a military unit in Bangkok, Thailand.. A military unit in Thailand.. One hundred and twenty-three male smokers from a military unit in Bangkok, who participated voluntarily in the study, were investigated. Sixty-six male non-smokers from the same unit were selected as controls. Fasting blood samples were collected for investigation of vitamin B12, folic acid and haematological variables.. The serum folic acid concentration of smokers was lower than that of non-smokers, but was not statistically significantly different. Haemoglobin was lower in smokers than in non-smokers; 16.3% of smokers were anaemic compared with only 3.0% of non-smokers. Anaemia was not related to folate deficiency. The white blood cell count was found to be higher in smokers than in non-smokers.. The results of this study suggest that there were low serum folic acid concentrations in smokers compared with non-smokers, which might contribute to the development of vascular and cardiovascular diseases. The higher white blood cell count might be indicative alterations in the immune functions of smokers.

Topics: Adult; Anemia; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Erythrocyte Indices; Folic Acid; Folic Acid Deficiency; Hematologic Tests; Humans; Leukocyte Count; Male; Middle Aged; Risk Factors; Smoking; Thailand; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Arteriosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B 12

Hyperhomocysteinemia is an independent cardiovascular risk factor that depends on folate and vitamin B12 nutrition.. To measure homocysteine, folic acid and vitamin B12 serum levels in healthy children with and without a family history of cardiovascular disease.. Forty children aged 6 to 15 years with a family history of cardiovascular disease, and 40 age and sex matched children without such history were studied. Serum homocysteine, folic acid and vitamin B12 were measured in a fasting blood sample. Homocysteine was measured by a fluorescence polarization immunoassay (FPIA), vitamin B12 by enzymatic microparticle assay, covered with intrinsic factor and folic acid by ionic capture, using commercial kits.. Children with family history of cardiovascular disease had higher homocysteine levels than their counterparts without family history (7.9 +/- 3 and 5.8 +/- 2 mumol/l respectively, p < 0.03), but similar folic acid (5.2 +/- 1.8 and 5.5 +/- 1.4 pg/ml respectively) and vitamin B12 levels (431 +/- 213 and 445 +/- 209 ng/ml respectively). There was a negative and significant correlation between homocysteine and folic acid and vitamin B12 levels.. Children with a family history of cardiovascular disease have higher levels of serum homocysteine than those without such history, despite having similar levels of folic acid and vitamin B12.

Topics: Adolescent; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Lipids; Lipoproteins; Male; Risk Factors; Vitamin B 12

To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents.. Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal.. Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents.. GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.

Topics: Adolescent; Cardiovascular Diseases; Child; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Eating; Fasting; Female; Fibrinogen; Folic Acid; Homocysteine; Hormone Replacement Therapy; Human Growth Hormone; Humans; Male; Plasminogen Activator Inhibitor 1; Postprandial Period; Risk Assessment; Time Factors; Triglycerides; Vitamin B 12

Atherosclerosis is the main cause of cardiovascular morbidity and mortality in many countries. It is believed that hyperhomocysteinemia is a risk factor for premature atherosclerosis and other cardiovascular diseases (CVD) in both men and women.. Plasma samples from 31 non-CVD and 51 CVD patients with diabetes were studied. Informed consent was obtained from all subjects. Blood samples were collected after overnight fasting. Total homocysteine (H [e]), the levels of high and low density lipoproteins (HDL, LDL), total cholesterol, urea and creatinine were determined with commercial kits.. The levels of homocysteine, vitamin B12, creatinine, and urea in CVD patients were significantly higher than those found in the normal subjects. On the other hand, the levels of folic acid, HDL and LDL were lower in CVD patients than in normal subjects. Interestingly, a linear relationship was found between the levels of homocysteine and total cholesterol in CVD samples, whereas no such linear relationship was present in normal subjects.. The level of homocysteine in plasma is known to be mainly dependent on the levels of folic acid and vitamin B12. However, in the present study the level of homocysteine in the plasma of CVD patients is dependent on the level of folic acid and not on the level of vitamin B12. Subjects with high homocysteine levels should be advised to consume a folic acid-fortified diet in order to reduce the homocysteine level in patients at high risk for cardiovascular disease.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Risk Factors; Vitamin B 12

The aim of the study was the analysis of the blood biochemical indices values depending on the nutrition model. The research was carried out in 1999 year among at random chosen 188 people 75-80 years old residing the neighbourhood of Olsztyn. The nutrients intake was assessed by means of the 24-hour recall method and, after having included loses, was compared with the recommended intake on the safe level. The blood biochemical indices were defined in the Central Analytical Laboratory of the City Hospital in Olsztyn according to the standard procedure. The analysis was assessed by Statistica v.6.0 program with the application of the factor and cluster analysis. Three nutrition models were separated: "low nutritive", "dairy" and "meat-vegetable-fruit". The comparison and distribution of the mean blood biochemical value was carried out using the variance analysis and the chi 2 test at p < or = 0.05. No differentiation in the levels of most blood biochemical indices depended on women and men nutrition model has been confirmed. Among 1-16% of women and 12-28% of men too low haematocrit and haemoglobin values were stated, among 34% of women and 23% of men--too low albumin values, and among 24% of women and 11% of men too high glucose values in the blood were found. About 32% of women and 35% of men showed too low HDL cholesterol ratio to total cholesterol content. Too low value of the vitamin B12 in the blood was revealed for 6% of women and 5% of men, and folic acid among 26% and 37%, for women and men, respectively. Regardless of realized nutrition model the significant percentage of elderly people has been characterized with the increased risk of cardiovascular diseases, diabetes or anaemia.

Topics: Aged; Aged, 80 and over; Aging; Albumins; Anemia; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Mellitus; Diet; Female; Folic Acid; Hematocrit; Hemoglobins; Humans; Male; Risk Factors; Vitamin B 12

The Fulani of northern Nigeria are indigenous semi-nomadic pastoralists whose diet consists largely of dairy products. Despite their consumption of relatively large amounts of saturated fats, an earlier study showed that their total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglyceride levels fall within the reference range of values for North Americans. Men in the cities of Jos and Abuja, two populations who also reside in northern Nigeria, differ from the Fulani with regard to diet and activity level. Males in both Jos and Abuja have diets consisting of high protein or carbohydrate and are more sedentary than the Fulani subjects. The main aims of the study were to measure the concentrations of various lipids in the blood serum of male urban dwellers in Jos and Abuja and to compare their blood lipid profiles with those of the rural Fulani (mean age 33.9 years). Blood serum samples from 118 men in Jos (mean age 37.9 years) and 77 men in Abuja (mean age 34.4 years) were analyzed for total cholesterol, triglycerides, LDL, HDL, homocysteine, folate, and vitamin B12. In addition to height and weight, systolic and diastolic blood pressures were measured. The mean total cholesterol, triglyceride, HDL and LDL values for the three groups of subjects fell within or close to the accepted range of values for North Americans. However, the Fulani males had HDL values (mean, 33.9 mg/dL) below the range of values prescribed for North Americans (>40 mg/dL). Moreover, the Fulani men and the men in Abuja had a total cholesterol/ HDL ratio of 4.2 and 4.0 respectively, which exceed the accepted value (< or =3.5) prescribed by the Columbia University. In all three populations, the incidence ofhomocysteinaemia (serum homocysteine > 12.4 micromol/L) was very high. Their mean homocysteine levels ranged from 14.7 to 16.7 pmol/L and could not be accounted for by folate or vitamin B12 status. The mean blood pressures of the Abuja (127/77 mm Hg) and the Fulani (120/74 mm Hg) men were within the normotensive range (<130/85 mm Hg). However, the mean blood pressures of the Jos males (131/85 mm Hg) indicated borderline hypertension. These data indicate that, with regard to serum lipids, urban and rural adult Nigerian males have generally favourable risk factors for cardiovascular disease when compared with healthy North Americans. All three sub-populations, however, have levels of homocysteine that are cause for concern vis-à-vis their overall

Topics: Adult; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Nigeria; Risk Factors; Triglycerides; Vitamin B 12

Elevated levels of total homocysteine and low folate in blood are independent and graded risk factors for arterial occlusive disease. An impairment of folate distribution can be an important cause of hyperhomocysteinemia. Glutamate carboxypeptidase II (GCPII) regulates the absorption of dietary folates. In the present study, we examined the relationship of a 1561C-->T variant in the GCPII gene with fasting, post-methionine load plasma homocysteine, folate and vitamin B(12) levels and the risk of cardiovascular disease (CVD) in 190 vascular disease patients and in 601 apparently healthy controls. Fasting as well as post-load homocysteine concentrations associated with the 1561TT genotype tended to be lower, whereas the homocysteine concentrations of the 1561CT individuals were not different from their 1561CC peers. The 1561C-->T polymorphism significantly increased both red blood cell folate and plasma folate concentrations (ANOVA P=0.013; test for linear trend P=0.03, respectively), but had no effect on vitamin B(12) levels (ANOVA P=0.35). Since not only homocysteine itself is considered to be positively associated with the risk of CVD, but also a decreased folate status, the results of this study indicate that the 1561C-->T polymorphism may affect the predisposition to CVD.

Topics: Adult; Analysis of Variance; Antigens, Surface; Carboxypeptidases; Cardiovascular Diseases; Case-Control Studies; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Glutamate Carboxypeptidase II; Homocysteine; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Vitamin B 12

Smoking is known to be associated with an increased plasma homocysteine level. Both are associated with an increased risk of cardiovascular disease. B-vitamins modulate plasma homocysteine levels.. To investigate the relationships between smoking, plasma homocysteine, nutrient levels and risk of cardiovascular disease.. The European Concerted Action Project case control study of 750 cases and 800 age- and sex-matched controls aged less than 60 years from 19 centres in 10 European countries.. Smokers were at increased risk of vascular disease. This risk was greatly increased in the presence of a raised plasma homocysteine; cigarette smokers with a plasma homocysteine above 12 micromol.l(-1) had a 12-fold increased risk of cardiovascular disease (OR 12.4 95% CI 7.3 to 21.2) compared with non-smokers with a normal plasma homocysteine. In both cases and controls the current smokers had a higher plasma homocysteine level than the never smokers (11.7 micromol.l(-1) vs 10.07 micromol.l(-1), P<0.05 cases; 9.90 micromol.l(-1) vs 9.53 micromol.l(-1)P value non significant controls). Current smokers tended to have lower levels of folate, and vitamin B6 and vitamin B12 than never smokers. The risk of cardiovascular disease associated with smoking was not significantly altered by adjustment for levels of B-vitamins using a conditional regression model (OR for current smoker >20.day(-1) 8.19, after adjustment for B6, B12, folate OR 7.09).. This case control study suggests that smokers with high plasma homocysteine are at greatly increased risk of cardiovascular disease and should therefore be offered intensive advice to help them cease smoking. They also have reduced levels of those B-vitamins (folate, vitamin B6 and vitamin B12) that modulate homocysteine metabolism. While this finding may reflect a direct effect of smoking or reduced B-vitamin intake, supplementation of these nutrients may be appropriate in smokers with high homocysteine levels.

Topics: Adult; Cardiovascular Diseases; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Smoking; Vitamin B 12; Vitamin B 6

The purpose of this study is to examine the association of plasma Hcy, folate and vitamin B(12) levels on CVD risk factors among children in Taiwan.. After multistage sampling, we selected randomly 1,235 children (609 boys and 626 girls) aged 12 to 15 yr. Plasma Hcy levels was measured using ABBOTT Imx analyzer, while plasma folate and vitamin B(12) were measured using ACS: 180 automated chemiluminescence analyzer. Anthropometric, blood pressure (BP) and other biochemical CVD risk factors including serum total cholesterol (CHOL), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1) and B (apoB) and lipoprotein(a) [Lp(a)]were measured using standard methods. We also calculated low density lipoprotein-cholesterol (LDL-C) and TCHR (total cholesterol to HDL-C ratio) as atherogenic indices.. Boys were taller and heavier, having higher body mass index (BMI), systolic blood pressure (SBP) and plasma glucose levels but lower diastolic blood pressure (DBP), heart rate (HR), cholesterol, TG, HDL-C, LDL-C, TCHR, and Lp(a) levels than girls. Boys also had higher plasma Hcy and lower folate, vitamin B(12), levels than girls (for plasma Hcy, mean +/- SD, 10.50 +/- 4.13 vs. 8.95 +/- 2.61 micromol/L for boys vs. girls, respectively). Plasma Hcy levels were significantly correlated positively with body height, body weight, SBP and DBP in both genders. Body height, body weight, BMI and SBP levels were found to increase with trend among different quintile plasma Hcy subgroups on boys but not on girls. Plasma folate and vitamin B(12) were decreased significantly along with the higher quintile plasma Hcy subgroup in both genders.. Boys had higher plasma Hcy levels than girls after adjusting for age. Furthermore, plasma Hcy levels were significantly associated with anthropometric parameters, such as body height and weight and blood pressure, but not related with lipid profiles among children in Taiwan.

Topics: Adolescent; Analysis of Variance; Anthropometry; Blood Pressure; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Male; Risk Factors; Sex Characteristics; Statistics, Nonparametric; Surveys and Questionnaires; Taiwan; Vitamin B 12

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Arteriosclerosis; Cardiovascular Diseases; Chlamydia Infections; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Folic Acid; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Hypertension; Hypolipidemic Agents; Infections; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B Complex

An elevated plasma total homocysteine (tHcy) concentration seems to increase the risk of cardiovascular disease.. We evaluated the determinants of tHcy in healthy French adults.. tHcy was measured by HPLC and fluorometric detection in 1139 women and 931 men aged 35-60 y. Subjects were participants of the Supplementation with Antioxidant Vitamins and Minerals Study, which investigates the effects of antioxidant supplementation on chronic diseases. Red blood cell folate (RBCF), plasma vitamins B-6 and B-12, and cardiovascular disease risk factors were also measured. The habitual diet was assessed in 616 subjects. Cross-sectional analyses were adjusted for age, smoking, energy intake, and concentration or intake of folate and vitamin B-6, where appropriate.. The mean (+/-SD) tHcy concentration was 8.74 +/- 2.71 micro mol/L in women and 10.82 +/- 3.49 micro mol/L in men. In women, tHcy was positively related to age (P = 0.001), apolipoprotein B (P < 0.01), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.02), and coffee and alcohol consumption (both P < 0.01) and inversely related to RBCF (P = 0.11) and plasma vitamin B-12 (P = 0.08) and vitamin B-6 (P = 0.01) intakes. In men, tHcy was positively associated with body mass index (P = 0.03), blood pressure (P < 0.02), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.01), and energy intake (P < 0.01) and inversely associated with physical activity (P = 0.04), RCBF (P = 0.02), plasma vitamin B-12 (P = 0.09), and dietary fiber (P < 0.01), folate (P = 0.03), and vitamin B-6 (P = 0.09) intakes.. To control tHcy, decreasing coffee and alcohol consumption may be important in women, whereas increasing physical activity, dietary fiber, and folate intake may be important in men.

Topics: Adult; Aging; Alcohol Drinking; Antioxidants; Apolipoproteins B; Blood Glucose; Body Constitution; Body Mass Index; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Coffee; Dietary Fiber; Dietary Supplements; Energy Intake; Erythrocytes; Exercise; Fasting; Female; Folic Acid; France; Homocysteine; Humans; Male; Middle Aged; Minerals; Risk Factors; Sex Characteristics; Triglycerides; Vitamin B 12; Vitamin B 6; Vitamins

Topics: Antioxidants; Biomarkers; Cardiovascular Diseases; Carotenoids; Female; Folic Acid; Fruit; Homocysteine; Humans; Male; Middle Aged; Morbidity; Neoplasms; Portugal; Risk Factors; Surveys and Questionnaires; Vegetables; Vitamin B 12; Vitamin B 6; Vitamin E

Elevated plasma total homocysteine (tHcy) levels have been established as a risk factor for occlusive cardiovascular disease. Also known is that plasma folate and vitamin B12 influence homocysteine metabolism as cosubstrate and cofactor, respectively. However, not much information is available describing plasma tHcy levels and their relationship to plasma folate and vitamin B12 status in Koreans. We measured the plasma levels of tHcy, folate, and vitamin B12 in 195 adults (99 males, 96 females; 23-72 y old in the lower middle class). The mean plasma tHcy levels of males, 11.18 +/- 3.88 micromol/L, was significantly higher (p < 0.001) than that of females, 9.20 +/- 2.65 micromol/L. The distribution of tHcy levels of males showed a wide range, 3-50 micromol/L, with a long tail toward higher values. Thus the incidence of hyperhomocysteinemia (> or = 5 micromol/L) in males, 10.1%, was significantly higher (< 0.02) than the 2.1% in females. As age increased, plasma tHcy levels tended to be higher in females. Therefore, sex differences in plasma tHcy levels disappeared in subjects over fifty. On the other hand, both plasma folate (6.47 +/- 3.06 vs 7.96 +/- 3.55 ng/mL, p < 0.01) and vitamin B12 levels (537.0 +/- 222.0 vs. 664.1 +/- 309.8 ng/mL, p < 0.01) were significantly lower in males than in females. A plasma folate deficiency (< 3.0 ng/mL) was found in 6.1% of males and 2.1% of females. And a vitamin B12 deficiency (< 150 pg/mL) was detected in 2.0% and 1.0%, respectively. Plasma tHcy levels were related with inversely plasma concentrations of folate (r = -0.37249, p < 0.001) as well as vitamin B12 (r = -0.22560, p < 0.01) in both sexes. Plasma levels of tHcy and the prevalence of hyperhomocysteinemia in Korean adults are similar to findings in the West. Our results indicate that male adults may be in worse condition for cardiovascular disease (CVD) than females. And improving folate and vitamin B12 status may reduce plasma tHcy level, which may be more important in males.

Topics: Adult; Age Factors; Aged; Area Under Curve; Cardiovascular Diseases; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Korea; Male; Middle Aged; Nutritional Status; Prevalence; Sex Factors; Vitamin B 12; Vitamin B 12 Deficiency

Cardiovascular disease (CVD) is the principle cause of death in patients with end-stage renal disease. Some gene polymorphisms and hyperhomocysteinemia have been implicated in the pathogenesis of CVD. The aim of this study was to assess the relationships between angiotensin-converting enzyme genotype, endothelial nitric oxide synthase genotype, and methylenetetrahydrofolate reductase (MTHFR) genotype and CVD in patients on hemodialysis and to clarify the determinants of plasma homocysteine level. One hundred and sixty-eight patients on hemodialysis (87 males and 81 females, mean age 60.7 +/- 13.1 years) were included. A history of CVD was present in 25% of the patients. There was a significant difference in the distributions of MTHFR non-VV genotype and MTHFR VV genotype between patients with a CVD history and patients without a CVD history, but no difference in the distributions of angiotensin-converting enzyme genotypes and endothelial nitric oxide synthase genotypes. The plasma homocysteine concentration was significantly higher in patients with MTHFR VV genotype than in patients with MTHFR non-VV genotype. The plasma homocysteine concentration was negatively correlated with plasma vitamin B12 concentration and plasma folate concentration. On stepwise multiple-regression analysis for the predictors of plasma homocysteine concentration, MTHFR VV genotype and gender were significant. In conclusion, MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Oxidoreductases Acting on CH-NH Group Donors; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renal Dialysis; Risk Factors; Statistics as Topic; Vitamin B 12

Mild hyperhomocysteinemia is an independent risk factor for cardiovascular disease and may result from a deficiency of folate, vitamin B-6 or vitamin B-12. Because vitamin B-12 deficiency is often associated with vegetarianism, this study was designed to examine the effect of Taiwanese vegetarian diets on B-vitamin status and plasma homocysteine levels. Female Buddhist lacto-vegetarians (n = 45; 31-45 y) and matched omnivores (n = 45) recruited in Hualien, Taiwan, were investigated. Taiwanese vegetarians consumed normal amount of folate, but only 21% of Taiwan Recommended Daily Nutrient Allowances (RDNA) values of vitamin B-12. Compared with the omnivores, the vegetarians had significantly higher levels of plasma folate (14.79 +/- 7.70 vs. 11.98 +/- 8.29 nmol/L), but lower levels of vitamin B-12 (207.7 +/- 127.1 vs. 403.5 +/- 138.9 pmol/L). Fasting plasma homocysteine levels were significantly higher in vegetarians than in omnivores (mean: 11.20 +/- 4.27 vs. 8.64 +/- 2.06 micromol/L; median: 10.5 vs. 8.5 micromol/L). Fasting plasma homocysteine was inversely correlated with plasma folate and vitamin B-12 in the vegetarian group. Multiple regression analysis revealed that plasma folate, vitamin B-12 and creatinine were independent determinants of homocysteine variation and contributed to 38.6% of homocysteine variation in the vegetarians. Compared with the omnivores, vegetarians also had significantly lower serum levels of valine, isoleucine, leucine, lysine, alanine and arginine, but higher levels of glycine. In the vegetarian group, fasting plasma homocysteine correlated negatively with serum threonine, lysine, histidine, arginine and cystine, and these amino acids contributed to 38.7% of homocysteine variation. In conclusion, the Buddhist nuns who consumed a lacto-vegetarian diet had mildly elevated fasting plasma homocysteine levels presumably due to lower levels of plasma vitamin B-12.

Topics: Adult; Amino Acids; Cardiovascular Diseases; Diet, Vegetarian; Fasting; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Middle Aged; Nutritional Status; Regression Analysis; Risk Factors; Taiwan; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency

Hyperhomocysteinemia is considered a risk factor for cardiovascular disease and is prevalent in the elderly. Supplementation with folic acid, vitamin B-6 and B-12 lowers homocysteine levels. In January 2000, the Chilean government initiated a flour folic acid fortification program to decrease the occurrence of neural tube defects. The aim of this study was to evaluate the effect of this program on serum homocysteine and folate levels in elderly subjects after 6 mo. A total of 108 elderly people were studied. We measured serum folate, homocysteine and vitamin B-12 levels before the fortification started and 6 mo later. At baseline, folate deficiency (<6.8 nmol/L) was present in 1.8%, vitamin B-12 deficiency (<165 pmol/L) in 27.6% and hyperhomocysteinemia (>14 micromol/L) in 31% of the sample. Six months later, serum folate levels increased from 16.2 +/- 6.2 to 32.7 +/- 7.1 nmol/L (P < 0.001), homocysteine levels decreased from 12.95 +/- 3.7 to 11.43 +/- 3.6 micromol/L (P < 0.001) and vitamin B-12 levels were unchanged. Flour fortification with folic acid had a moderate lowering effect on homocysteine levels. Given that vitamin B-12 deficiency was more common than folate deficiency, it may be more appropriate to add vitamin B-12 to food, at least in foods for this age group.

Topics: Aged; Cardiovascular Diseases; Chile; Cholesterol, HDL; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Hyperhomocysteinemia; Male; Nutritional Status; Prevalence; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cardiovascular Diseases; Folic Acid; Food, Fortified; Homocysteine; Humans; Ireland; United Kingdom; Vitamin B 12

Moderate alcohol consumption is associated with improved vascular risk profile and decreased mortality in the middle aged. An elevated homocysteine concentration is an independent risk factor for cardiovascular disease.. To examine the relationship between alcohol consumption and homocysteine concentrations in severely obese patients (body mass index (BMI)>35).. A careful alcohol history was obtained from 350 (male:female 1:5) consecutive patients as part of preoperative assessment for surgical treatment of obesity. Data were obtained concerning amount, frequency, timing and type of alcohol consumption. Fasting homocysteine, serum folate and vitamin B(12) concentrations were measured. Differences between groups were assessed using Student t-test, and ANOVA. Linear regression was used to assess factors influencing homocysteine concentration.. There is a U-shaped relationship between alcohol consumption and homocysteine concentrations, with light to moderate consumption being associated with lower concentrations. Those consuming <100 g/week (n=165) of alcohol had geometric mean (95% CI of mean) serum homocysteine concentrations of 8.5 (8.2-8.9) micromol/l compared with 9.5 (9.1-9.9) micromol/l for non or rare consumers (n=153; P=0.001). The lower concentrations of homocysteine in regular consumers were associated with higher folate concentrations of 9.4 (8.6-10.2) ng/ml when compared with non-consumers 7.5 (7.1-7.8) ng/ml (P=0.001). Red wine consumers (n=42) had lower fasting concentrations of homocysteine 7.8 (7.5-8.1) micromol/l compared with 153 non-consumers 9.4 (9.0-9.8) micromol/l (P<0.001), 82 beer and spirit consumers 9.0 (8.4-9.7) micromol/l (P=0.005) and 73 white wine consumers 8.8 (8.2-9.4 micromol/l (P=0.013). Red wine consumption was an independent predictor for lower homocysteine concentrations.. Mild to moderate alcohol consumption, especially red wine consumption, in obese subjects is associated with lower fasting homocysteine concentrations. This may reduce cardiovascular risk and help explain the 'French paradox'.

Topics: Adult; Alcohol Drinking; Alcoholic Beverages; Beer; Cardiovascular Diseases; Fasting; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Obesity, Morbid; Risk; Vitamin B 12; Wine

Topics: Aged; Cardiovascular Diseases; Dietary Supplements; Folic Acid; Food, Fortified; Homocysteine; Humans; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinaemia is a risk factor for premature atherosclerotic vascular disease and venous thrombosis. The aim of the present study was to assess plasma total homocysteine (tHCys) concentrations in hypo- as well as hyperthyroid patients before and after treatment, and to evaluate the role of potential determinants of plasma tHCys levels in these patients.. Prospective follow up study.. Fifty hypothyroid and 46 hyperthyroid patients were studied in the untreated state and again after restoration of euthyroidism.. Fasting plasma levels of tHCys and its putative determinants (plasma levels of free thyroxine (fT4), folate, vitamin B(12), renal function, sex, age, smoking status and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene were measured before and after treatment.. Restoration of the euthyroid state decreased both tHCys (17.6 +/- 10.2-13.0 +/- 4.7 micromol/l; P < 0.005) and creatinine (83.9 +/- 22.0-69.8 +/- 14.2 micromol/l; P < 0.005) in hypothyroid patients and increased both tHCys (10.7 +/- 2.5-13.4 +/- 3.3 micromol/l; P < 0.005) and creatinine (49.0 +/- 15.4-66.5 +/- 15.0 micromol/l; P < 0.005) in hyperthyroid patients (values as mean +/- SD). Folate levels were lower in the hypothyroid group compared to the hyperthyroid group (11.7 +/- 6.4 and 15.1 +/- 7.6 nmol/l; P < 0.05). Pretreatment tHCys levels correlated with log fT(4) (r = - 0.47), folate (r = - 0.21), plasma creatinine (r = 0.45) and age (r = 0.35) but not with C677T genotype. Multivariate analysis indicated that pretreatment log(fT(4)) levels and age accounted for 28% the variability of pre-treatment tHCys (tHCys = 14.2-5.50 log(fT(4)) + 0.14 age). After treatment the logarithm of the change (Delta) in fT(4) (expressed as the post-treatment fT(4)/pre-treatment fT(4) ratio) accounted for 45% of the variability in change of tHCys ( tHCys = - 0.07-4.94 log ( fT(4))); there was no independent contribution of changes in creatinine which was, however, strongly related to changes in tHCys (r = 0.61).. Plasma tHCys concentrations increased in hypothyroidism and decreased in hyperthyroidism. Plasma fT(4) is an independent determinant of tHCys concentrations. Lower folate levels and a lower creatinine clearance in hypo-thyroidism, and a higher creatinine clearance in hyperthyroidism only partially explain the changes in tHCys.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Biomarkers; Cardiovascular Diseases; Creatinine; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperthyroidism; Hypothyroidism; Linear Models; Male; Metabolic Clearance Rate; Methylenetetrahydrofolate Dehydrogenase (NADP); Middle Aged; Polymorphism, Genetic; Prospective Studies; Risk Factors; Sex Factors; Smoking; Thyroid Function Tests; Thyroxine; Vitamin B 12

Hyperhomocysteinemia is a cardiovascular disease (CVD) risk factor. We determined plasma homocysteine (Hcy) reference values at optimized vitamin status and investigated their influence on the prevalence of hyperhomocysteinemia in healthy adults. Results were compared with those obtained using European Concerted Action Project (ECAP) cutoff values.. Healthy adults (n = 101) received folic acid (5 mg/day) and vitamin B(12) (1 mg/day) for 2 weeks and the same dosages of folic acid and vitamin B(12) plus vitamin B(6) (1 mg. kg(-1). day(-1)) during the following 2 weeks. Hcy concentrations, both fasting and 6-h post-methionine load, were determined at baseline and after 4 weeks.. Baseline (4 weeks) fasting and 6-h postload Hcy reference values were 4.7-14.6 (4.1-9.3) and 18.8-49.7 (12.9-35.1) micromol/L, respectively. Mean fasting and 6-h postload Hcy decreased after 4 weeks of vitamin supplementation by 3.5 micromol/L (33.5%) and 8.5 micromol/L (26.3%), respectively. The percentages of subjects exhibiting significant decreases in fasting Hcy following vitamin supplementation were 88% (all subjects), 92% (non-vitamin users), and 72% (vitamin users). The prevalences of hyperhomocysteinemia with use of ECAP cutoff values were 29% for all groups, 29% for men, 27% for premenopausal women, and 53% for postmenopausal women. With vitamin-optimized cutoff values, prevalences were 58%, 58%, 76%, and 89%, respectively. Use of vitamin-optimized cutoff values increased the diagnostic value of fasting Hcy and decreased that of a 6-h postload Hcy compared with use of ECAP cutoff values.. Use of vitamin-optimized cutoff values gives rise to high hyperhomocysteinemia pretest probabilities in the general population and, therefore, precludes any meaningful role for Hcy testing. Future demonstration of a beneficial effect of decreasing Hcy on CVD risk would justify use of vitamin-optimized cutoff values for assessment of CVD risk.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prevalence; Pyridoxine; Vitamin B 12; Vitamins

In India, most people adhere to a vegetarian diet, which may lead to cobalamin deficiency.. The objective was to examine indicators of cobalamin status in Asian Indians.. The study population included 204 men and women aged 27-55 y from Pune, Maharashtra, India, categorized into 4 groups: patients with cardiovascular disease (CVD) and diabetes, patients with CVD but no diabetes, patients with diabetes but no CVD, and healthy subjects. Data on medical history, lifestyle, and diet were obtained by interviews and questionnaires. Blood samples were collected for measurement of serum or plasma total cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) and hemetologic indexes.. MMA, tHcy, total cobalamin, and holoTC did not differ significantly among the 4 groups; therefore, the data were pooled. Total cobalamin showed a strong inverse correlation with tHcy (r = -0.59) and MMA (r = -0.54). Forty-seven percent of the subjects had cobalamin deficiency (total cobalamin <150 pmol/L), 73% had low holoTC (<35 pmol/L), 77% had hyperhomocysteinemia (tHcy >15 micromol/L), and 73% had elevated serum MMA (>0.26 micromol/L). These indicators of impaired cobalamin status were observed in both vegetarians and nonvegetarians. Folate deficiency was rare and only 2.5% of the subjects were homozygous for the MTHFR 677C-->T polymorphism.. About 75% of the subjects had metabolic signs of cobalamin deficiency, which was only partly explained by the vegetarian diet. If impaired cobalamin status is confirmed in other parts of India, it may have important health implications.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Diet, Vegetarian; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; India; Male; Methylmalonic Acid; Middle Aged; Prevalence; Surveys and Questionnaires; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Pyridoxine; Risk Factors; Vitamin B 12

Topics: Cardiovascular Diseases; Dietary Supplements; Folic Acid; Gastric Bypass; Humans; Hyperhomocysteinemia; Risk Factors; Vitamin B 12; Weight Loss

Although plasma total homocysteine has been identified as an independent risk factor for vascular disease in a multitude of studies, there is a considerable overlap in values between patients at risk and control subjects. The difference in values can be used to distinguish statistically between the 2 groups, provided each group is large enough; however, discriminating between individual patients at risk and control subjects is difficult.. We investigated whether the precursor of homocysteine, S-adenosylhomocysteine, is a more sensitive indicator of risk.. We measured plasma total homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, creatinine, folate, and vitamin B-12 in 30 patients with proven cardiovascular disease and 29 age- and sex-matched control subjects.. The homocysteine values (+/-SD) were 12.8 +/- 4.9 (95% CI: 11.0, 14.7) micromol/L for patients and 11.0 +/- 3.2 (9.8, 12.2) micromol/L for control subjects. The S-adenosylhomocysteine values were 40.0 +/- 20.6 (32.3, 47.7) nmol/L for patients and 27.0 +/- 6.7 (24.5, 30.0) nmol/L for control subjects (P = 0.0021). The S-adenosylmethionine values were 121.8 +/- 42.9 (105.8, 137.8) nmol/L for patients and 103.9 +/- 21.8 (95.6, 112.2) nmol/L for control subjects (P = 0.0493). The creatinine values were 110 +/- 27 (97, 120) micromol/L for patients and 97 +/- 9 (80, 100) micromol/L for control subjects (P = 0.0025). Values for folate and vitamin B-12 did not differ significantly between groups.. Plasma S-adenosylhomocysteine appears to be a much more sensitive indicator of the difference between patients with cardiovascular disease and control subjects than is homocysteine. Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients.

Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Creatinine; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk Factors; S-Adenosylhomocysteine; S-Adenosylmethionine; Sensitivity and Specificity; Vitamin B 12

The Fulani of northern Nigeria are seminomadic pastoralists who consume a diet rich in saturated fats, do not use tobacco, are lean, and have an active lifestyle. Little is known about their serum lipid profiles and corresponding risk of cardiovascular disease.. We measured serum lipid, homocysteine, folate, and vitamin B-12 concentrations in Fulani men and women and assessed the nutrient content of their diet.. Blood samples from 42 men (18-64 y old) and 79 women (15-77 y old) living in the Jos Plateau of Nigeria were analyzed for cholesterol (total, HDL, and LDL), triacylglycerol, homocysteine, folate, and vitamin B-12 serum concentrations. Body composition was determined by bioelectrical impedance analysis. Dietary information was obtained with use of a 7-d dietary recall and a food-frequency questionnaire. Results were compared with US referent ranges.. The mean energy content of the Fulani diet was relatively low (men, 6980 kJ; women, 6213 kJ) and the mean protein content was high (men, 20% of energy; women, 16% of energy). Nearly one-half of energy was provided by fat, and one-half of that was derived from saturated fatty acids. The diet provided marginal to adequate amounts of vitamins B-12, B-6, and C but only one-third of the US recommended dietary allowance for folate. The mean total cholesterol, HDL-cholesterol, and triacylglycerol concentrations of Fulani adults were within the referent ranges; the mean LDL-cholesterol concentration of Fulani adults below the range; and the mean serum homocysteine concentration of Fulani men above the range. Homocysteine and folate concentrations were inversely correlated for both men and women.. Despite a diet high in saturated fat, Fulani adults have a lipid profile indicative of a low risk of cardiovascular disease. This finding is likely due to their high activity level and their low total energy intake.

Topics: Adolescent; Adult; Aged; Body Composition; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Diet; Dietary Fats; Electric Impedance; Energy Intake; Exercise; Female; Folic Acid; Food Analysis; Homocysteine; Humans; Lipids; Male; Mental Recall; Middle Aged; Nigeria; Risk Factors; Surveys and Questionnaires; Vitamin B 12

Several cardiovascular risk factors have been investigated in patients with adult growth hormone deficiency (GHD) to explain the observed increase in vascular mortality. Plasma homocysteine concentration has been identified recently as an independent risk factor for atherosclerosis. We wished to determine whether plasma homocysteine contributes to cardiovascular risk in adult GHD.. Plasma homocysteine was measured by fluorescence polarization immunoassay in 45 GH-deficient adults on stable conventional hormone replacement (25M, 20F), age range 23-76 years, and compared with 55 matched controls (30M, 25F), age range 21-77 years. All subjects were free from clinical hypertension, diabetes, ischaemic heart disease and peripheral vascular disease. Blood pressure, body mass index and waist hip ratio were recorded. Serum creatinine and fasting lipids were measured. Serum vitamin B12 and folate levels, important cofactors in the homocysteine metabolic pathways, were also measured.. Homocysteine levels were not different in patients and controls (9.75 [7.8-11.6] micromol/l vs. 9.65 [8.3-11.5] micromol/l, respectively, P = 0.88). Serum vitamin B12 was also not different (320.5 [262.0-427.5] pmol/l vs. 313.5 [277.0-460.5] pmol/l, respectively, P = 0.77). Serum folate levels were significantly lower in the patient group (7.05 [5.12-8.27] ng/ml vs. 7.80 [6.52-10.60] ng/ml, respectively, P = 0.03). When separated by gender, in males folate was not significantly different between patients and controls 7.05 [5.17-9.19] vs. 7.65 [6.15-10.22], P = 0.264, whereas in females, folate was significantly lower in patients at 7.05 [4.57-7.75] compared to controls at 8.4 [6.60-12.20], P = 0.01.. Plasma homocysteine levels are not significantly elevated in GH-deficient adults and are unlikely to be a major risk factor for vascular disease in these individuals.

Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Creatinine; Female; Folic Acid; Growth Hormone; Homocysteine; Humans; Lipids; Male; Middle Aged; Risk Factors; Statistics, Nonparametric; Vitamin B 12

Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly diagnosed T2D, and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 +/- 4.6; T2D, 12.8 +/- 4.0; NGT, 10.7 +/- 4.4 micromol/L) and PML-tHcy (IGT, 46.5 +/-17.39; T2D, 41.1 +/- 6.8; NGT, 38.0 +/- 9.7 micromol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association between tHcy and renal function in these subjects.

Topics: Blood Glucose; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Folic Acid; Homocysteine; Humans; Insulin; Male; Methionine; Middle Aged; Proinsulin; Risk Factors; Time Factors; Vitamin B 12

Study the determinants of plasma total homocysteine (tHcy) levels, such as fasting levels of serum creatinine (SCr), albumin, plasma tHcy, folate, B(12), and pyridoxal-5'-phosphate (PLP) in chronic Korean renal transplant recipients (RTR).. Cross-sectional study.. Nephrology & Transplant Service in Catholic University Kangnam St. Mary's Hospital, Seoul, Korea.. Ninety-one chronic Korean RTR with stable renal function who were > or =6 months post-transplant.. Used medical record review and anthropometric measurements, and overnight (10 to 14 hours) fasting blood samples were measured for plasma tHcy, PLP, folate, B(12), SCr, and albumin.. The prevalence of hyperhomocysteinemia (tHcy > 12 micromol/L) was 56%, and 47% had low plasma folate levels (<3 ng/mL). Linear modeling with analysis of covariance adjusted for age, sex, albumin, SCr, and plasma B-vitamin status revealed that only SCr (standard regression coefficient R = +0.663, P<.001), plasma folate (R = -0.276, P =.001), and B(12) (R = -0.149, marginal, P =.08) were independent determinants of fasting tHcy levels in this patient population.. Renal function is the major independent determinant of the fasting tHcy levels among chronic, stable Korean RTR, and that B-vitamin status plays a secondary role among such patients.

Topics: Adult; Aged; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Fasting; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kidney Transplantation; Korea; Male; Middle Aged; Prevalence; Pyridoxal Phosphate; Serum Albumin; Vitamin B 12

Hyperhomocysteinemia in association with vitamin B(12) deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B(12) normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 microg) in 18 individuals, serum vitamin B(12) increased from 149+/-63 pg/mL to 532+/-204 pg/mL (p<0.0001) and total tHcy dropped from 12.4+/-4.7 to 7.9+/-3.1 micromol/L (p<0. 0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B(12) and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.

Topics: Adult; Cardiovascular Diseases; Diet, Vegetarian; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Hyperhomocysteinemia; Injections, Intramuscular; Male; Middle Aged; Platelet Aggregation; Risk Factors; Vitamin B 12

Long-term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis-related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age- and sex-matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P < 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI-1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2-45.5) vs 7.9 IU/ml (4-18.0); P < 0.0001] with an odd ratio (OR) of 11.8 (4.9-28.5) in univariate analysis and of 5.8 (2.1-15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1-992) vs 100.5 mg/l (10-412); P < 0.005] with an OR of 5.9 (1.9-18.4) in univariate analysis and of 3.5 (0.9-13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 micromol/l (4.0-68) vs 8.1 micromol/l (2.0-24.0); P < 0.00001] with an OR of 40.4 (14.7-111) in univariate analysis and of 33.1 (11.1-115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95%). Finally, we found a significant correlation between tHcy and PAI-1 plasma levels (r = 0.76; P < 0.000001). Our results show a high prevalence of hemostasis-related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long-term survival and to tailor therapy.

Topics: Autoantibodies; Biomarkers; Cardiovascular Diseases; Female; Folic Acid; Glomerular Filtration Rate; Hemostasis; Homocysteine; Humans; Kidney Transplantation; Lipoprotein(a); Male; Middle Aged; Plasminogen Activator Inhibitor 1; Postoperative Complications; Reference Values; Risk Factors; Vitamin B 12

Increased plasma total homocysteine (tHcy) levels are a known risk factor for vascular disease and have been reported in association with cognitive impairment of old age. Alternatively, however, increased tHcy levels may simply be an indicator of B vitamin deficiency. We evaluated the relationship between plasma tHcy levels, serum vitamin B12 and folate levels, and the scores at a battery of neuropsychological tests in 54 healthy cognitively normal subjects aged 65 years and over. Hyperhomocysteinemia prevalence (plasma tHcy>15 micromol/L) was about 24%. In univariate analysis, vitamin B12 levels were associated with both verbal memory and visuo-spatial skills, whereas no association was found between psychometric test scores and folate levels or tHcy levels. However, none of the univariate associations of neuropsychological test scores and serum B12 vitamin levels was confirmed when adjusting for age, education and other confounding variables. In conclusion, although a relationship between homocysteine, B vitamins and poor cognitive skills in the elderly is plausible, this study does not suggests that such relationship is biologically important.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Cognition; Dementia; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Vitamin B 12

Topics: Biological Availability; Biomarkers; Cardiovascular Diseases; Choline; Congenital Abnormalities; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Homocysteine; Humans; Male; Neoplasms; Neural Tube Defects; Nutrition Policy; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown.. We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined.. The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the GFR (P = 0.0001), folate levels (P = 0.0001), age (P = 0.0001), body mass index (P = 0.0001), gender (P = 0.0005), and vitamin B12 levels (P = 0.004) on total homocysteine concentrations was observed. The donor MTHFR gene polymorphism had no influence on total homocysteine and folate levels. Geometric mean total homocysteine levels in patients homozygous for the mutant MTHFR allele were 18.6 micromol/liter compared with 14.6 micromol/liter and 14.9 micromol/liter in patients heterozygous for the MTHFR gene polymorphism and those with wild-type alleles (P < 0.05 for TT vs. CT and CC). Geometric mean folate levels were lower in CT and TT patients (11.2 and 10.2 nmol/liter) compared with CC patients (13.6 nmol/liter, P < 0.05 vs. CT and TT).. This study demonstrates that homozygosity for the C677T polymorphism in the MTHFR gene significantly increases total homocysteine concentrations and lowers folate levels in kidney graft recipients, even in patients with excellent renal function (GFR more than median). These findings have important implications for risk evaluation and vitamin intervention therapy in these patients who carry an increased risk for the development of cardiovascular disease.

Topics: Adult; Aged; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Homozygote; Humans; Kidney Transplantation; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Risk Factors; Tissue Donors; Vitamin B 12

Although evidence suggests that homocysteine is a risk factor for cardiovascular disease in adults, little information exists on homocysteine levels in children.. To describe the distribution of serum homocysteine concentrations among children and to examine the association between homocysteine levels and several characteristics, including serum levels of folic acid and vitamins B12 and B6.. Cross-sectional analysis.. School-based cohort from California, Louisiana, Minnesota, and Texas.. A total of 3524 US schoolchildren, aged 13 and 14 years, from the Child and Adolescent Trial for Cardiovascular Health (completed in 1994). Measurement was conducted in 1997.. Nonfasting serum total homocysteine concentration.. The distribution of homocysteine values ranged from 0.1 to 25.7 micromol/L (median, 4.9 micromol/L). Geometric mean homocysteine concentration was significantly higher in boys (5.22 micromol/L) than girls (4.84 micromol/L); blacks (5.51 micromol/L) than whites (4.96 micromol/L) or Hispanics (4.93 micromol/L); nonusers of multivitamins (5.09 micromol/L) than users (4.82 micromol/L); and smokers (5.19 micromol/L) than nonsmokers (5.00 micromol/ L). Serum homocysteine was significantly inversely correlated with serum levels of folic acid (r= -0.36; P = .001), vitamin B12 (r = -0.21; P = .001), and vitamin B6 (r = -0.18; P = .001). Serum homocysteine was not significantly associated with serum lipid levels or family history of cardiovascular disease and was only weakly related to body mass index and systolic blood pressure. After multivariate adjustment, homocysteine remained independently associated with sex, race, serum folic acid and vitamin B12 levels, and systolic blood pressure.. The distribution of homocysteine levels in children is substantially lower than that observed for adults; however, a small percentage of children are still potentially at elevated risk for future cardiovascular disease. Serum folic acid may be an important determinant of homocysteine levels in children.

Topics: Adolescent; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Health Surveys; Homocysteine; Humans; Male; Pyridoxine; Reference Values; Regression Analysis; Risk Factors; Vitamin B 12

The increased cardiovascular risk in subjects with NIDDM is partly explained by an association with established risk factors like hypertension, dyslipidemia, and obesity. Mild hyperhomocysteinemia has emerged as a new risk factor for cardiovascular disease. The purpose of this study was to assess its role in NIDDM.. We studied predictors of homocysteine levels and correlations between homocysteine and (micro-)albuminuria, retinopathy, and history of cardiovascular disease in normotensive NIDDM subjects under stable metabolic control. This was done in 85 NIDDM subjects by measuring fasting and post-methionine-loading homocysteine levels together with blood pressure, BMI, serum cholesterol, triglyceride, HDL cholesterol, folate, vitamin B12, pyridoxal-5-phosphate, HbA1c, and (micro-)albuminuria and creatinine clearance in triplicate 24-h urine samples. The relationship between micro- and macrovascular complications and fasting homocysteine only was studied in an additional 65 subjects, giving a total of 150 subjects.. In multiple regression analysis, significant (P < 0.05) predictors of fasting homocysteine were low-normal values of creatinine clearance (threshold effect at < 80 ml.min-1 .1.73 m-2), folate (< 20 nmol/l), and vitamin B12 (< 350 pmol/l), and postmenopausal status in women. Determinants of post-methionine homocysteine were pyridoxal-5-phosphate levels < 80 nmol/l, creatinine clearance, and sex (higher levels in women). Hyperhomocysteinemia did not cluster with other cardiovascular risk factors, like hypertension, obesity, or dyslipidemia. Regarding cardiovascular complications, fasting homocysteine, but not post-methionine homocysteine, was higher in subjects with a history of cardiovascular disease. There was a stepwise increase in the prevalence of subjects with cardiovascular disease with increasing fasting homocysteine. The prevalence of cardiovascular disease was 19.4% in the bottom quartile of fasting homocysteine, versus 55.0% in the top quartile (P for trend < 0.01). Neither fasting homocysteine nor post-methionine homocysteine correlated with (micro-)albuminuria or with retinopathy.. The findings suggest that homocysteine levels in NIDDM rise even with modest deterioration of renal function and when vitamin status is in the low to low-normal range. Fasting homocysteine correlates with macrovascular disease, but we found no evidence of a correlation with retinopathy or (micro-)albuminuria. Post-methionine homocysteine levels do not show a correlation with micro- or macrovascular complications.

Topics: Administration, Oral; Adult; Aged; Albuminuria; Analysis of Variance; Blood Pressure; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Fasting; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Middle Aged; Postmenopause; Premenopause; Pyridoxal Phosphate; Regression Analysis; Risk Factors; Vitamin B 12

Elevated homocyst(e)ine levels are associated with an increased risk of vascular disease, particularly aorto-iliac, coronary and cerebrovascular disease. In patients with confirmed disease, plasma homocyst(e)ine is a strong predictor of death. In addition to B vitamins, folic acid and certain genotypes, renal function is an independent determinant of plasma homocyst(e)ine level. There also may be a polygenic component contributing to elevated homocyst(e)ine levels in confirmed vascular disease. Possible mechanisms of homocyst(e)ine-induced vascular change include proliferation of vascular smooth muscle cells, endothelial cell dysfunction and a procoagulant state. The definition of hyperhomocyst(e)inemia is based on arbitrary cut-points (eg, the 90th percentile). In most populations, this is approximately 15 microM/L. Patients with hyperhomocyst(e)inemia should be treated with at least 400 micrograms of folic acid per day. Alternative treatments are vitamin B6 and B12 supplementation, although optimal doses have yet to be identified.

Topics: Animals; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Cricetinae; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Pyridoxine; Risk Factors; Vitamin B 12

We found a higher plasma concentration of total homocysteine (tHcy), an independent risk factor for cardiovascular disease, in patients with hypothyroidism (mean, 16.3 micromol/L; 95% confidence interval [CI], 14.7 to 17.9 micromol/L) than in healthy controls (mean, 10.5 micromol/L; 95% CI, 10.1 to 10.9 micromol/L). The tHcy level of hyperthyroid patients did not differ significantly from that of the controls. Serum creatinine was higher in hypothyroid patients and lower in hyperthyroid patients than in controls, whereas serum folate was higher in hyperthyroid patients compared with the two other groups. In multivariate analysis, these differences did not explain the higher tHcy concentration in hypothyroidism. We confirmed the observation of elevated serum cholesterol in hypothyroidism, which together with the hyperhomocysteinemia may contribute to an accelerated atherogenesis in these patients.

Topics: Adult; Aged; Arteriosclerosis; Cardiovascular Diseases; Cholesterol; Creatinine; Female; Folic Acid; Homocysteine; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Multivariate Analysis; Risk Factors; Thyroxine; Triiodothyronine; Vitamin B 12

The mechanisms leading to elevated total homocysteine concentrations in peritoneal dialysis patients are only partially understood. We show that a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition) results in increased total homocysteine levels in peritoneal dialysis patients compared to age- and sex-matched healthy individuals. The allelic frequency of the C677T transition in the MTHFR gene in peritoneal dialysis patients (0.29) was comparable to the frequency in healthy individuals (0.34). Separate comparison of the total homocysteine plasma levels between non-carriers of the MTHFR polymorphism (C/C), heterozygous (C/T) and homozygous (T/T) subjects was performed by analysis of covariance in the patient and the control group. In the patient group the mean total homocysteine level was 61.7 +/- 40.1 mumol/liter in individuals with the (T/T) genotype, which was significantly higher than the total homocysteine concentration of 23.1 +/- 15.8 mumol/liter in (C/T) patients and 22.2 +/- 11.1 mumol/liter for non-carriers (P = 0.0001). Vitamin B12 (P = 0.0001), folate (P = 0.0005), serum creatinine (P = 0.016), albumin (P = 0.0157) and dialysis center (P = 0.0173) significantly influenced total homocysteine plasma levels in peritoneal dialysis patients, whereas this was not the case for age, gender, weekly Kt/V, weekly creatinine clearance, residual renal function, duration of dialysis, mode of peritoneal dialysis and vitamin intake. Folate levels in peritoneal dialysis patients were significantly affected by the MTHFR genotype (P = 0.016). Elevated total homocysteine levels in diabetic patients with cardiovascular disease were associated with increased cardiovascular morbidity. In summary, the present study provides evidence that homozygosity for the C677T transition in the MTHFR gene, low vitamin B12 and low folate levels result in elevated total homocysteine levels in peritoneal dialysis patients.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Aged; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Osmolar Concentration; Oxidoreductases; Peritoneal Dialysis; Polymorphism, Genetic; Vitamin B 12

Recently, we reported a relation between plasma total homocysteine (tHcy) in children and cardiovascular disease (CVD) in their male relatives, suggesting that tHcy may partly explain the increased risk related to a family history of CVD. Because individuals with familial hyperlipidemias have an exceptionally high risk of premature CVD, we explored the relationship between tHcy and parental history of CVD in children with familial hypercholesterolemia (FH).. Study subjects were 91 boys and 64 girls (age range, 7 to 17 years) with FH who were treated with a standard lipid-lowering diet at a tertiary care lipid clinic. We conducted a cross-sectional analysis of demographics, the diet, tHcy level, presence of the C677T mutation in the methylenetetrahydrofolate reductase gene (a common genetic cause of elevated tHcy) in children, and the prevalence of parental CVD. tHcy increased after puberty and was inversely related to parental educational level. Intakes of folate, vitamin C, and fruits and vegetables were inversely associated with tHcy, as were serum folate and vitamin B12 (Spearman's rho, -0.2 to 0.4; P<.05). tHcy was increased in children whose parent with FH had experienced CVD compared with children without parental CVD (median [interquartile range], 6.6 [5.3, 8.0] micromol/L versus 5.6 [4.7, 6.8] micromol/L; P=.01). This difference remained significant in multivariate regression analysis. Homozygosity for the C677T mutation was associated with a higher tHcy level and tended to be more frequent in the group with than in the group without a parental history of CVD (18% versus 8%; P=.07).. These findings suggest that a moderately elevated tHcy level may partly account for the contribution of the family history to risk of CVD in FH. Dietary recommendations for FH should include nutrients that affect homocysteine metabolism.

Topics: Adolescent; Age Distribution; Cardiovascular Diseases; Child; Diet; Family Health; Female; Folic Acid; Heterozygote; Homocysteine; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Methylenetetrahydrofolate Reductase (NADPH2); Multivariate Analysis; Oxidoreductases Acting on CH-NH Group Donors; Parents; Point Mutation; Prevalence; Risk Factors; Sex Distribution; Vitamin B 12

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Pyridoxine; Vitamin B 12; Vitamins

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.

Topics: Adult; Aged; Arteriosclerosis; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Cohort Studies; Comorbidity; Diabetes Mellitus; Fasting; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Proportional Hazards Models; Prospective Studies; Pyridoxine; Renal Dialysis; Single-Blind Method; Smoking; Treatment Outcome; Vitamin B 12

The study sought to define the relation of plasma total homocysteine to biological and clinical variables and to serum vitamin concentrations in patients with primary hyperlipidaemia. Fasting plasma total homocysteine was measured in 219 men and 159 women; vitamin concentrations were available for about 60% of the sample. Men had significantly higher plasma total homocysteine than women [median (25th, 75th percentiles) 9.4 (8.2, 11.5) mumol L-1 vs. 8.5 (7.0, 10.2) mumol L-1; P = 0.0001]. Plasma total homocysteine was lower in women taking lipid-lowering drugs than in women who were not taking drugs. Serum folate and vitamin B12 concentrations were normal for all but one and four subjects respectively. Correlations (P < or = 0.06) were found between plasma total homocysteine and age, triglyceride concentration in women, uric acid concentration in men, serum folate, vitamin B12 and creatinine concentrations. In multiple regression analysis, the association between plasma total homocysteine and sex and between plasma total homocysteine and use of lipid-lowering drugs disappeared when creatinine concentration was entered into the analysis. This study shows that plasma total homocysteine is related to vitamin concentrations within the normal range, suggesting that plasma total homocysteine may be modifiable by diet in hyperlipidaemic subjects with normal vitamin nutrition. Sex-related differences appear to be related to men's higher creatinine concentration. Whether lipid-lowering drugs interact with total homocysteine concentration requires further study.

Topics: Adult; Age Factors; Aged; Cardiovascular Diseases; Female; Homocysteine; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Regression Analysis; Sex Factors; Vitamin B 12

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.

Topics: Adult; Aged; Amino Acid Sequence; Cardiovascular Diseases; Cholesterol, HDL; Comorbidity; Creatinine; DNA Mutational Analysis; Female; Folic Acid; Glucose Intolerance; Homocysteine; Humans; Hypertension; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Peritoneal Dialysis; Polymorphism, Restriction Fragment Length; Prevalence; Renal Dialysis; Risk Factors; Smoking; Vitamin B 12

Topics: Aged; Cardiovascular Diseases; Carotid Stenosis; Folic Acid; Homocysteine; Humans; Male; Risk Factors; Vitamin B 12

Topics: Cardiovascular Diseases; Humans; Pyridoxine; Vitamin B 12

Serum vitamin B12, folic acid and haematological data from 147 elderly people (55 males and 92 females) who visited the special clinic for the elderly at Rajvithi Hospital, Bangkok between July and November 1989 were investigated. The individuals studied came from a health-conscious group of the middle socio-economic class in Bangkok. All of them were fairly well except for minor ailments and typical diseases of elderly people such as hypertension, mild to moderate degree coronary heart diseases and non-insulin dependent diabetes mellitus. There was a statistically significant difference in haemoglobin concentrations between males and females. According to the standard haemoglobin cut-off point values of 13 g/dl for males and 12 g/dl for females, anaemia was detected in 22 (15%) of the 147 subjects. The percentage of folic acid deficiency was found to be 20.6 per cent (30 of the 147 cases). Vitamin B12 insufficiency was found in only 6.9 per cent (10 of the 147 cases). No statistically significant correlation between haemoglobin, folic acid and vitamin B12 was found. However, when the data were grouped according to different intervals of increasing haemoglobin concentrations, for females there was a tendency for serum vitamin B12 to decrease, and serum folic acid to increase in both males and females. The results of this study suggest that folate deficiency may play a role in the occurrence of anaemia in elderly people, and therefore, dietary counselling and supplementation of folic acid are recommended.

Topics: Aged; Blood Cell Count; Cardiovascular Diseases; Developing Countries; Diabetes Mellitus, Type 2; Erythrocyte Indices; Female; Folic Acid; Folic Acid Deficiency; Hematocrit; Hemoglobinometry; Humans; Hypertension; Male; Middle Aged; Thailand; Vitamin B 12; Vitamin B 12 Deficiency

The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Contraceptives, Oral, Hormonal; Estradiol Congeners; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Prostatic Neoplasms; Risk Factors; Vitamin B 12

A total of 1280 80-year-old men were invited to a medical examination to study common risk indicators for cardiovascular disease (CVD) in the elderly. From the pool of 811 responders (63.3%), all 122 individuals who fulfilled our inclusion criteria were assigned to one of four groups: (1) no CVD, non-smokers; (2) no CVD, smokers; (3) CVD, smokers; (4) CVD, non-smokers. A telephone interview with 75 non-responders suggested that this group contained more institutionalized subjects, but otherwise did not differ from the group of participants. Subjects with CVD had higher levels of plasma cholesterol and LDL cholesterol than those without CVD, whereas plasma HDL cholesterol and plasma triglyceride concentrations did not differ between the groups; thus the LDL/HDL ratio was higher in the CVD group. Lipoprotein concentrations did not differ between smokers and non-smokers. However, the mean cholesterol levels were low (5.19 +/- 1.01 mmol l-1), suggesting selective mortality. No differences between the groups were found with regard to Lp(a). The mean blood pressure for the whole group was 149/79 mmHg, and there were no differences between subgroups. Our study suggests that mechanisms such as selective mortality modify the risk factor pattern in the elderly. In 80-year-old individuals, elevated LDL cholesterol levels can still be identified as a risk indicator for CVD, whereas there does not appear to be any association between CVD or low HDL levels or elevated blood pressure in this age group.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Cardiovascular Diseases; Cholesterol; Creatinine; Cross-Sectional Studies; Glycated Hemoglobin; Humans; Hypertension; Lipoproteins; Male; Myocardial Infarction; Prevalence; Risk Factors; Smoking; Sweden; Vitamin B 12

Cardiovascular lesions were observed at necropsy in five of six sheep which were subjected to an experimentally induced cobalt-vitamin B12 deficiency during a period of 34 weeks. The classical symptoms of cobalt-vitamin B12 deficiency (anorexia, cachexia, anaemia) were seen in all six sheep at week 20 of the experiment. Histologically, lesions of the auricular epicardium and myocardium consisted of a high concentration of inflammatory cells dominated by polynuclear eosinophils as well as the haemorrhagic inflammation of blood vessels accompanied by necrosis of auricular tissue. The similarity between the lesions observed in the present experiment and those seen in arteriosclerosis, led to the suggestion that a deficiency of vitamin B12 may be implicated in the pathogenesis of arteriosclerosis. A hypothesis is advanced in this respect.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Cobalt; Myocardium; Necrosis; Sheep; Sheep Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adenine Nucleotides; Animals; Cardenolides; Cardiac Glycosides; Cardiovascular Diseases; Drug Therapy, Combination; Female; Glucosides; Glycosides; Male; Myocardium; Rats; Vitamin B 12

Topics: Adenosine Triphosphate; Age Factors; Aged; Blood Glucose; Blood Proteins; Cardiovascular Diseases; Cholesterol; Drug Combinations; Humans; Lipids; Niacinamide; Thiamine Pyrophosphate; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Hypochromic; Biliary Tract Diseases; Biometry; Cardiovascular Diseases; Erythrocyte Count; Erythrocytes; Erythrocytes, Abnormal; Female; Gastrointestinal Diseases; Hematologic Diseases; Hemophilia A; Humans; Leukemia; Liver Diseases; Lung Diseases; Male; Middle Aged; Neoplasms; Pancreatic Diseases; Splenectomy; Thalassemia; Thyroid Diseases; Urologic Diseases; Vitamin B 12

Topics: Aged; Brain; Cardiovascular Diseases; Dementia; Electroencephalography; Humans; Immunization, Passive; Methanol; Middle Aged; Picolines; Sulfides; Time Factors; Vitamin B 12

Topics: Adult; Aged; Cardiovascular Diseases; Coenzymes; Humans; Male; Middle Aged; Pyridoxine; Thiamine; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Blood Cell Count; Cardiovascular Diseases; Causality; Corrinoids; Drug Therapy; Geriatrics; Humans; Prothrombin Time; Reticulocytes; Thrombosis; Toxicology; Vitamin B 12