vitamin-b-12 and Vascular-Diseases

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

The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.

Topics: Diabetes Mellitus; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Infertility; Mental Disorders; Methylenetetrahydrofolate Reductase (NADPH2); Neoplasms; Nervous System Diseases; Polymorphism, Genetic; Psoriasis; Vascular Diseases; Vitamin B 12

In mid-20th century United States, deaths from vascular disease reached a peak incidence in 1955, but little was known about the underlying causes of this epidemic of disease. The significance of homocysteine in human disease was unknown until 1962, when cases of homocystinuria were first associated with vascular disease. Analysis of an archival case of homocystinuria from 1933 and a case of cobalamin C disease from 1968 led to the conclusion that homocysteine causes vascular disease by a direct effect of the amino acid on arterial cells and tissues. The homocysteine theory of arteriosclerosis attributes one of the underlying causes of vascular disease to elevation of blood homocysteine concentrations as the result of dietary, genetic, metabolic, hormonal, or toxic factors. Dietary deficiency of vitamin B-6 and folic acid and absorptive deficiency of vitamin B-12, which result from traditional food processing or abnormal absorption of B vitamins, are important factors in causing elevations in blood homocysteine. Numerous clinical and epidemiologic studies have established elevated blood homocysteine as a potent independent risk factor for vascular disease in the general population. Dietary improvement, providing abundant vitamin B-6, folic acid, and cobalamin, may prevent vascular disease by lowering blood homocysteine. The dramatic decline in cardiovascular mortality in the United States since 1950 may possibly be attributable in part to voluntary fortification of the food supply with vitamin B-6 and folic acid. Fortification of the US food supply with folic acid in 1998, as mandated by the US Food and Drug Administration, was associated with a further decline in mortality from vascular disease, presumably because of increased blood folate and decreased blood homocysteine in the population.

Topics: Aged; Atherosclerosis; Dietary Supplements; Folic Acid; Homocysteine; Humans; Vascular Diseases; Vitamin B 12; Vitamin B 6

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

Three topics affecting cobalamin, folate, and homocysteine that have generated interest, activity, and advances in recent years are discussed. These are: (I). the application of an expanded variety of tools to the diagnosis of cobalamin deficiency, and how these affect and are affected by our current understanding of deficiency; (II). the nature of the interaction between homocysteine and vascular disease, and how the relationship is affected by vitamins; and (III). the improved understanding of relevant genetic disorders and common genetic polymorphisms, and how these interact with environmental influences. The diagnostic approach to cobalamin deficiency now allows better diagnosis of difficult and atypical cases and more confident rejection of the diagnosis when deficiency does not exist. However, the process has also become a complex and sometimes vexing undertaking. Part of the difficulty derives from the lack of a diagnostic gold standard among the many available tests, part from the overwhelming numerical preponderance of patients with subclinical deficiency (in which isolated biochemical findings exist without clinical signs or symptoms) among the cobalamin deficiency states, and part from the decreased availability of reliable tests to identify the causes of a patient's cobalamin deficiency and thus a growing deemphasis of that important part of the diagnostic process. In Section I, Dr. Carmel discusses the tests, the diagnostic issues, and possible approaches to the clinical evaluation. It is suggested no single algorithm fits all cases, some of which require more biochemical proof than others, and that differentiating between subclinical and clinical deficiency, despite their overlap, may be a helpful and practical point of departure in the evaluation of patients encountered in clinical practice. The arguments for and against a suggested expansion of the cobalamin reference range are also weighed. The epidemiologic data suggest that homocysteine elevation is a risk factor for vascular and thrombotic disease. In Section II, Dr. Green notes that the interactions of metabolism and clinical risk are not well understood and a causative relationship remains unproven despite new reports that lowering homocysteine levels may reduce vascular complications. Genetic and acquired influences may interact in important ways that are still being sorted out. The use of vitamins, especially folate, often reduces homocysteine levels but also carries potential disa

Topics: Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Metabolism, Inborn Errors; Polymorphism, Genetic; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Classically, deficiency of folic acid (folate) or vitamin B12 (cobalamin) was recognized by the presence of a macrocytic anemia resulting from megaloblastic changes in the bone marrow. A markedly changing paradigm has identified both new mechanisms for altered folate and cobalamin status and new sequelae and clinical interrelationships that include altered mechanisms of absorption, a changing pattern of neurologic deficits, an increased risk of vascular occlusive lesions, and an important relationship with the mechanisms of neoplastic transformation. Several of these newer characterizations relate to issues of neoplasia in the nonpregnant woman and to issues in pregnancy, such as the potential for developmental abnormalities of the fetal nervous system.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Female; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Neoplasms; Neural Tube Defects; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency leads to severe hyperhomocysteinemia (HHcy). Vascular events (VE) remain the major cause of morbidity and mortality in the untreated patients with HCU. The study on the natural history of untreated HCU disclosed that, at the time of maximal risk, in other words beyond 10 years old, there was one event per 25 years. Recent studies from Australia (n = 32), The Netherlands (n = 28), and Ireland (n = 24) have documented the effects of long-term treatment on the vascular outcome of a total of 84 patients with 1314 patient-years of treatment for HCU. The mean (range) age was 27.8 (2.5 to 70) years. Five VE were recorded during treatment; one pulmonary embolism, two myocardial infarctions, and two abdominal aneurysms. All five VE occurred in B6-responsive patients at a mean (range) age of 48.8 (30 to 60) years. In 1314 patient-years of treatment, 53 VE would have been expected if they remained untreated; instead only 5 were documented, relative risk = 0.091 (95% confidence interval [CI] 0.043 to 0.190; p < 0.001). Appropriate homocysteine-lowering therapy for severe HHcy significantly reduced the vascular risk in patients with HCU. VE were rare with treatment despite the fact that the post-treatment homocysteine levels were several times higher than the cutoff point for homocysteine in the normal population. The present findings may have relevance to the current concept of "mild HHcy" as a risk factor for vascular disease, with elevated plasma homocysteine levels considerably lower than that of the post-treatment levels in this group of reported patients.

Topics: Adolescent; Adult; Aged; Australia; Child; Child, Preschool; Cohort Studies; Cystine; Drug Resistance; Female; Folic Acid; Follow-Up Studies; Genetic Predisposition to Disease; Homocysteine; Homocystinuria; Humans; Hyperhomocysteinemia; Infant; Ireland; Male; Methionine; Middle Aged; Netherlands; Pyridoxine; Risk; Risk Factors; Thrombophilia; Vascular Diseases; Vitamin B 12

Over the last 10 years, there has been an explosion of interest in homocysteine, a sulfur-containing amino acid that occupies a central location in the metabolic pathways of thiol compounds. This interest is primarily because of the realization that hyperhomocysteinemia is an important risk factor for vascular disease, including stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Since elevated homocysteine levels can often be normalized by supplementing the diet with folic acid (folate), pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)), these observations raise the exciting possibility that this inexpensive and well-tolerated therapy may be effective in decreasing the incidence of vascular disease. In addition to its association with cerebrovascular disease, homocysteine may play a role in neurodegenerative disorders, even if only as a marker of functional vitamin B(12) deficiency. Homocysteine is also important to neurologists since most anticonvulsants raise homocysteine levels, an effect that may explain the teratogenic effects of these drugs. Practical knowledge concerning some details of homocysteine metabolism, the diagnosis of hyperhomocysteinemia, and the use of polyvitamin therapy to lower homocysteine levels will be increasingly important in the treatment of patients with neurologic disease. Arch Neurol. 2000;57:1422-1428

Topics: Brain Diseases; Epilepsy; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Neurodegenerative Diseases; Pyridoxine; Vascular Diseases; Vitamin B 12

Folate fortification of bread and grains has been directed to prevent neural tube birth defects. Research has also challenged previous concepts of folate nutritional status and suggested that folate may play a role in reducing the risk of vascular disease. Although folate status of many elderly people is adequate according to traditional, hematologic criteria, some elderly persons have elevated blood concentrations of the metabolite homocysteine, which indicates subclinical deficiency of folate or vitamin B-12. Higher homocysteine concentrations, even within the normal range, are associated with increased risk of vascular disease. Elderly people with better folate and vitamin B-12 status have lower homocysteine concentrations and may have lower risk for vascular disease. Although the new folate fortification rules provide the benefit of increasing folate in the food supply, they could be a risk for the elderly because excess folate intake can mask vitamin B-12 deficiency, thereby delaying diagnosis. Elderly people have a higher prevalence of vitamin B-12 deficiency as a result of absorption problems. Those deficient in vitamin B-12 should be treated to prevent irreversible neurologic damage. Modern approaches to screening the elderly include using higher cutoff points for serum vitamin B-12 and obtaining blood concentrations of the metabolite methylmalonic acid, which is elevated in deficiency of vitamin B-12 but not folate. To examine current folate intake and food sources, food frequency questionnaires were administered to 308 elderly volunteers aged 65 to 94 years. Mean (+/-standard error) folate intake from food was 299.6+/-5.8 microg/day. Supplements (median dose=400 microg/day) were consumed by 47% of participants. Only 3.2% of the sample had total folate intake greater than 1,000 microg/day, the recommended upper limit, and these were taking high-dose folate supplements (> or = 800 microg/day). Breakfast cereals provided 25.6% of folate intake; vegetables, 23.2%; fruit, 20.8%; refined breads/grains, 6.7%; dark bread, 5.0%; legumes/nuts, 5.9%; dairy products, 5.8%; meat/poultry/fish/eggs, 5.1%; other, 1.9%. Mean folate intake would increase 16.5% if enriched bread and grains were fortified. Such fortification could help some persons to lower serum homocysteine concentration and vascular disease risk. Dietitians should be aware of modern protocols for screening the elderly for vitamin B-12 deficiency.

Topics: Aged; Aged, 80 and over; Aging; Female; Folic Acid; Food, Fortified; Homocysteine; Homocystinuria; Humans; Male; Nutritional Status; Risk Factors; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

In summary, we have shown that there is a high prevalence of Cbl deficiency in the elderly. This observation is based on an increase in the number of low and low normal serum Cbl levels, an increase in elevated serum total homocysteine levels that correct with Cbl therapy, and an increase in elevated serum methylmalonic acid levels that also correct with Cbl therapy. These observations may be of great clinical importance since Cbl deficiency may be a common and treatable cause of vascular disease.

Topics: Aged; Hematologic Diseases; Homocysteine; Humans; Mental Disorders; Methylmalonic Acid; Nervous System Diseases; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Blood Coagulation Factors; Blood Platelets; Child; Cystathionine beta-Synthase; Endothelium, Vascular; Fibrinolytic Agents; Folic Acid Deficiency; Homocysteine; Humans; Incidence; Male; Methionine; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Penicillamine; Risk Factors; Thrombosis; Vascular Diseases; Vitamin B 12; Vitamin B 6 Deficiency; Vitamins

Reduction of circulating homocysteine levels by folic acid suggests an additional approach to the prophylaxis of certain forms of vascular disease related to atherogenic amino acids.

Topics: Arterial Occlusive Diseases; Arteriosclerosis; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Metabolism, Inborn Errors; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Chromium Isotopes; Cobalt Isotopes; Female; Humans; Iron Isotopes; Male; Radioisotopes; Vascular Diseases; Vitamin B 12

The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment.. The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67-90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study.. MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score between the study and control groups (P = 0.06). No adverse events were recorded.. In this study, citicoline was effective and well tolerated in patients with mild vascular cognitive impairment. Citicoline activates biosynthesis of phospholipids in neuronal membranes, increases brain metabolism as well as norepinephrine and dopamine levels in the central nervous system, and has neuroprotective effects during hypoxia and ischemia. Therefore, citicoline may be recommended for patients with mild vascular cognitive impairment.

Topics: Activities of Daily Living; Administration, Oral; Aged; Aged, 80 and over; Cognitive Dysfunction; Cytidine Diphosphate Choline; Depression; Female; Folic Acid; Geriatric Assessment; Humans; Magnetic Resonance Imaging; Male; Mental Disorders; Nootropic Agents; Thyroid Hormones; Tomography, X-Ray Computed; Vascular Diseases; Vitamin B 12

Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease but lowering tHcy with B-vitamins, including folate, has generally not reduced vascular events in secondary prevention trials. Elevated plasma S-adenosylhomocysteine (AdoHcy) concentration may be a more sensitive indicator of vascular disease than plasma tHcy. However, unlike tHcy, plasma AdoHcy did not correlate with folate concentration in one study indicating that folate supplementation may not lower AdoHcy. Our aim was to determine whether providing B-vitamin supplements to healthy older people with elevated tHcy (>13 micromol/l) affects plasma AdoHcy and S-adenosylmethionine (AdoMet) concentrations. Healthy older participants (n 276; > or = 65 years) were randomised to receive a daily supplement containing folate (1 mg), vitamin B12 (500 microg) and vitamin B6 (10 mg), or placebo, for 2 years. Of these participants, we selected the first fifty participants in each treatment group and measured plasma AdoHcy and AdoMet. Plasma tHcy was 4.4 (95 % CI 3.2, 5.6; P < 0.001) micromol/l lower at 2 years in the vitamins group compared with the placebo group. At 2 years, there were no significant differences in plasma AdoMet (+4 % (95 % CI - 2, 11); P = 0.19), AdoHcy ( - 1 % (95 % CI - 10, 8); P = 0.61) or the AdoMet:AdoHcy ratio (0.22 (95 % CI - 0.04, 0.49); P = 0.10) between the two groups. In conclusion, B-vitamin supplementation of older people lowered plasma tHcy but had no effect on plasma AdoMet or AdoHcy concentration. If elevated plasma AdoHcy is detrimental, this may explain why B-vitamins have generally failed to reduce vascular events in clinical trials.

Topics: Aged; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Placebos; S-Adenosylhomocysteine; S-Adenosylmethionine; Vascular Diseases; Vitamin B 12; Vitamin B 6; Vitamins

We studied the efficacy of B vitamins as a treatment for hyperhomocysteinemia and endothelial dysfunction in renal transplant recipients in the Chinese population.. A total of 36 stable renal transplant recipients with hyperhomocysteinemia were randomly assigned to folate treatment (5 mg folic acid per day, 50 mg vitamin B6 per day and 1,000 microg vitamin B12 per day) or to the control group (placebo only) for 6 months. All subjects underwent tests for creatinine, creatinine clearance rate, average blood pressure, total cholesterol, triglyceride and fasting homocysteine. Endothelial function was evaluated using high resolution vascular ultrasound.. Homocysteine significantly decreased in those with folate treatment after intervention compared with baseline (12.6 +/- 3.9 vs 20.1 +/- 5.4 micromol/l, t = 5.3, p <0.01), whereas no significant changes were observed in controls. In the folate treatment group endothelium dependent and independent vasodilatation responses significantly increased after intervention (12.2% +/- 4.6% vs 8.8% +/- 5.2%, t = 2.9, p <0.01 and 17.6% +/- 3.9% vs 12.2% +/- 4.7%, t = 3.4, p <0.01, respectively). However, no significant changes were observed in controls. Endothelium dependent and independent vasodilatation responses were significantly lower in controls compared to levels in the folate group after treatment (8.7% +/- 6.3%, t = 2.8, p <0.01 and 12.2% +/- 5.3%, t = 3.5, p <0.01, respectively).. Based on these data B vitamin supplementation may decrease blood homocysteine and improve endothelial function in renal transplant recipients with hyperhomocysteinemia.

Topics: Adult; Asian People; Case-Control Studies; Endothelium, Vascular; Female; Folic Acid; Humans; Hyperhomocysteinemia; Kidney Transplantation; Male; Middle Aged; Treatment Outcome; Ultrasonography, Interventional; Vascular Diseases; Vasodilation; Vitamin B 12; Vitamin B 6; Vitamin B Complex

High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.. To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.. Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L).. Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo.. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients.. Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups.. Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.. clinicaltrials.gov Identifier: NCT00032435.

Topics: Aged; Cause of Death; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Pyridoxine; Renal Insufficiency, Chronic; Vascular Diseases; Vitamin B 12; 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

Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function.. We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function.. This was a factorial 2 x 2 x 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 microg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged >or=65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y.. The mean (+/-SD) baseline plasma homocysteine concentration was 16.5 +/- 6.4 micromol/L. This value was 5.0 (95% CI: 3.8, 6.2) micromol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7, 0.4).. Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.

Topics: Aged; Analysis of Variance; Cognition; Double-Blind Method; Drug Synergism; Female; Fibrinogen; Folic Acid; Homocysteine; Humans; Male; Riboflavin; Treatment Outcome; Vascular Diseases; Vitamin B 12; Vitamin B 6; Vitamin B Complex; von Willebrand Factor

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals.

Topics: Adult; Alcohol Drinking; Arterioles; Bariatric Surgery; Brachial Artery; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Male; Nitric Oxide; Nutritional Status; Obesity, Morbid; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Environmental and genetic factors influence serum total homocysteine (tHcy), a risk factor for vascular diseases. The gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) is reported to be a genetic factor for influencing tHcy. However, it is not clear whether MTHFR polymorphism influences tHcy in the younger generation. To investigate the influence of MTHFR polymorphism on vascular disease risks in young Japanese females, we determined dietary intakes, serum folate and tHcy, and examined the influence of MTHFR 677C>T polymorphism in healthy junior and high school students (n=192, 12-18y). The relationships between MTHFR polymorphism and folate intake, serum folate or tHcy were investigated by dividing participants into CC, CT and TT types. Among individuals with the TT genotype, folate and tHcy levels were significantly lower (p<0.05) or higher (p<0.0001), respectively, than in those with the other genotypes; although there were no significant differences in the intake of folate among genotypes. In addition, a significant inverse correlation between folate and tHcy (p<0.05) was noted in all genotypes, even in young females, so far not examined in Asian populations. Therefore, MTHFR genotypes were proven to be a significant determinant for folate and tHcy concentrations. However, the association of increased folate intake with lower tHcy concentration, even in cases of the mutation TT type, indicates the importance of folate intake in young Japanese females for early detection of risk, as well as the prevention of vascular diseases.

Topics: Adolescent; Amplified Fragment Length Polymorphism Analysis; Child; Diet; Female; Folic Acid; Genetic Association Studies; Genetic Predisposition to Disease; Health Surveys; Homocysteine; Homozygote; Humans; Hyperhomocysteinemia; Japan; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Vascular Diseases; Vitamin B 12; Vitamin B 6

A moderate elevation of plasma total homocysteine (tHcy) is considered a potential risk factor for Alzheimer's disease (AD).. We have investigated the main determinants (age, renal impairment, cobalamin/folate status and the presence of vascular disease) of plasma tHcy in 326 patients with AD, and also in 281 patients with mild cognitive impairment (MCI), since about half of these patients develop AD during the first 5 years.. Elevated plasma tHcy in patients with AD could mainly be attributed to cobalamin/folate deficiency or renal impairment. Younger patients (below 75 years) with AD and patients with MCI without cobalamin/folate deficiency or renal impairment showed normal levels of plasma tHcy.. Our findings suggest that plasma tHcy is not primarily involved in the pathogenesis of AD but rather a reflection of changes of the main determinants of plasma tHcy in AD patients.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Case-Control Studies; Cognitive Dysfunction; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Renal Insufficiency; Risk Factors; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Thirty-three inpatients (22 females, 11 males, aged 79.4 ± 9.5 years) were investigated in this prospective cohort study to study the prevalence of polyneuropathy (PNP) and dementia in geriatric inpatients. Clinical and electrodiagnostic investigations, routine laboratory, including thyroid parameters, folic acid, vitamin B(12), homocysteine, neopterin, fibrinogen and glycosylated hemoglobin were measured in serum, the mini-mental state examination and computed tomographic scanning were performed in each patient. PNP was found clinically and electrodiagnostically in 96% of patients. Age was the most precipitating factor for PNP, and was significantly correlated to electrodiagnostic changes in the nerves investigated in both, upper and lower extremities, while clinical symptoms were confined only to the feet. Correlation was seen between homocysteine and the amplitude of the sural nerve (surAmpl) (rs = -0.406, p = 0.029) as well as the sural nerve conduction velocity (surNCV) (rs = -0.389, p = 0.037), and between neopterin and the grade of denervation (rs = 0.445, p = 0.014) in our patients. Neopterin and fibrinogen did not correlate significantly, but there was a trend to higher fibrinogen concentrations in patients with higher neopterin levels (rs = 0.344, p = 0.062). A trend of a correlation was seen between higher homocysteine concentrations and the number of changes in electrodiagnostic measurements (rs = 0.354, p = 0.055). Twenty-one of the 33 patients (64%) were demented, 9 (27%) presented clinically as mild cognitive impairment, 3 (9%) were not demented. Vascular risk factors were found in 83%: hypertension in 58%, hypercholesterinemia in 39%, cardiac disease in 36%, diabetes mellitus (DM) in 21%, peripheral arterial disease (PAD) in 9%. A significant correlation was found between homocysteine and folic acid concentrations (rs = -0.401, p = 0.028). Falls were reported in 48% of cases, indicating PNP as a risk factor in this group of patients. In conclusion, PNP was found very common with a high coincidence with dementia and a female preponderance, suggesting an influence on daily life (falls) in our subjects studied. PNP correlated significantly with markers for vascular disease as well as immune activation (homocysteine and neopterin) similar to earlier findings in patients with neurodegenerative disorders, suggesting common therapeutic options in patients with PNP and dementia.

Topics: Aged; Aged, 80 and over; Aging; Cognition Disorders; Cohort Studies; Dementia; Female; Folic Acid; Geriatrics; Homocysteine; Humans; Inflammation; Male; Mental Status Schedule; Neopterin; Neural Conduction; Polyneuropathies; Sural Nerve; Vascular Diseases; Vitamin B 12

Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness, and patients with vascular disease have higher plasma tHcy concentration than patients without vascular disease.. We investigated the influence of cobalamin/folate status and renal function on the association between plasma tHcy levels and vascular disease.. There was a similar degree of significant difference in plasma tHcy levels between patients with and without vascular disease in all enrolled patients and in a group of patients where all those with signs of cobalamin/folate deficiency and/or impaired renal function had been excluded. Furthermore, logistic regression analysis showed that the age-adjusted plasma tHcy was the main predictor of vascular disease in both groups of patients.. The findings suggest that the presence of vascular disease itself is associated with elevated levels of plasma tHcy. Plasma tHcy might be a marker of vascular disease in elderly patients with mental illness.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Female; Folic Acid; Homocysteine; Humans; Kidney; Logistic Models; Male; Mental Disorders; Middle Aged; Predictive Value of Tests; Vascular Diseases; Vitamin B 12

Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness, and patients with vascular disease have higher plasma tHcy concentrations than patients without vascular disease. Increasing evidence indicates that vascular risk factors play a role in the development of cognitive impairment.. We have investigated the relation between plasma tHcy, its determinants and cognition, measured as MMSE, in 448 consecutively enrolled patients with dementia or other psychogeriatric diseases.. Multiple regression analyses showed that plasma tHcy was related to cognitive function in all patients as well as in demented and non-demented patients. The apparent close relationship between plasma tHcy and cognition was mainly dependent on its determinant age, whereas the other determinants of plasma tHcy exhibited a limited influence on the relation between plasma tHcy and cognition. Plasma tHcy has its own, albeit modest, relationship to cognitive function (predictive value about 5%).. Plasma tHcy itself seems to play a minor role in cognitive impairment in patients with dementia or other psychogeriatric diseases. When investigating the relation between plasma tHcy and cognition, it is important to consider the distribution of the main determinants of plasma tHcy and to correct plasma tHcy for these variables.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Creatinine; Dementia; Diagnostic and Statistical Manual of Mental Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Regression Analysis; Tomography, X-Ray Computed; Vascular Diseases; Vitamin B 12

Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness. Plasma tHcy is known to be associated with cardiovascular disease, renal impairment and negative lifestyle factors, and has been shown to predict mortality in human subjects. Epidemiological data on this topic in elderly patients with mental illness are missing. We therefore investigated the association between plasma tHcy levels and mortality in these patients.. The group of deceased patients showed higher age, higher plasma tHcy, lower renal function and lower serum folate than patients who were still alive. Only age, plasma tHcy and the presence of vascular disease significantly influenced mortality.. The association between plasma tHcy level and mortality risk was probably explained in part by the two plasma tHcy determinants age and presence of vascular disease. The determination of plasma tHcy in elderly patients with mental illness may help to identify patients in need of more intensive treatment.

Topics: Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Female; Folic Acid; Homocysteine; Humans; Kaplan-Meier Estimate; Kidney Function Tests; Male; Mental Disorders; Middle Aged; Proportional Hazards Models; Regression Analysis; Survival Analysis; Vascular Diseases; Vitamin B 12

Plasma total homocysteine (tHcy) is often elevated in patients with mental illness. Since patients with mental illness and vascular disease exhibit a higher plasma tHcy concentration than patients without vascular disease, it is possible that elevated plasma tHcy in mental illness is mainly due to concomitant vascular disease.. We have investigated plasma tHcy, cobalamin/folate status, renal function and the presence of vascular disease in patients with vascular dementia (VaD, n = 501), Alzheimer's disease (AD, n = 300), depression (n = 259) and in healthy subjects (n = 144) stratified according to age (below and above 75 years).. Plasma tHcy concentration showed the highest increase in patients with VaD compared to patients with AD or depression. After the exclusion of patients with cobalamin/folate deficiencies and increased serum creatinine, patients with AD or depression above 75 years with vascular disease showed a similar elevation of plasma tHcy concentration as patients with VaD. Furthermore, patients with AD and depression without vascular disease showed a similar plasma tHcy concentration to healthy subjects.. The findings imply that elevated plasma tHcy concentration in elderly patients with mental illness is mainly associated with the presence of vascular disease and is not related to the specific psychogeriatric diagnosis.

Topics: Aged; Aged, 80 and over; Aging; Creatinine; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Kidney Function Tests; Male; Mental Disorders; Psychiatric Status Rating Scales; Vascular Diseases; 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

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

Topics: Aged; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Vascular Diseases; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Cobalamin/folate deficiency and vascular disease are prevalent in elderly subjects and may lead to mental symptoms, but may even more often influence the severity of other organic and non-organic mental diseases. In the present study, we have evaluated cobalamin-folate status and the presence of vascular disease in 1,982 psychogeriatric patients investigated and diagnosed in a psychogeriatric clinic. The objective of the present study is to obtain information on the role of cobalamin/folate status and vascular disease in different diagnoses of psychogeriatric patients and their association with plasma homocysteine (tHcy).. We have measured serum cobalamin, blood/serum folate, serum creatinine, plasma tHcy and evaluated the presence of vascular disease in 1,982 well-defined psychogeriatric patients.. The present study indicates that cobalamin/folate deficiencies do not play an important role in cognitive dysfunction in psychogeriatric patients, since only about 7% of the study population had metabolic cobalamin/folate deficiencies. Furthermore, cobalamin/folate deficiencies were rare in younger patients (below 70 years of age). We were also able to confirm our previous finding that there was no association between dementia of Alzheimer type (AD) and plasma tHcy level or metabolic cobalamin/folate deficiencies. Furthermore, we observed a low proportion of vascular disease in patients with AD, which does not give support for an association between well-defined AD and the presence of vascular disease. The presence of vascular disease was higher and of similar degree in patients with mild cognitive impairment and depression, which indicates an association between these diagnoses and the presence of vascular disease. The present study also shows that at plasma tHcy levels below 14 micromol/l, the likelihood of cobalamin/folate deficiency is small and further investigation of cobalamin/folate status could be omitted.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Depressive Disorder; Female; Folic Acid; Hematocrit; Homocysteine; Humans; Male; Mental Disorders; Middle Aged; Nutritional Status; Population; Sweden; Vascular Diseases; Vitamin B 12

There is a high frequency of elevated plasma total homocysteine (tHcy) concentrations in elderly patients with mental disorders. Psychogeriatric patients with a history of vascular disease exhibit a significantly higher plasma tHcy concentration than patients without vascular disease.. The main reason for the present study is to further investigate the association between plasma tHcy concentration and vascular disease in psychogeriatric patients. We therefore investigated 152 psychogeriatric patients and determined plasma tHcy and its most important determinants (serum folate and serum cobalamin, serum cystatin C and serum creatinine). The patients were divided into two groups according to the presence of vascular disease. Eighty-seven patients had concomitant vascular disease. We also analysed the natriuretic peptide N-terminal pro brain natriuretic peptide (NT-proBNP) and protein S-100B in serum. NT-proBNP is a marker for congestive heart failure, whereas protein S-100B is a marker for brain damage.. The plasma tHcy concentration is elevated in the presence of dementia or vascular disease in psychogeriatric patients. The presence of dementia or vascular disease is also associated with higher age, renal impairment and lower serum folate concentration than in patients without dementia or vascular disease. Furthermore, we observed elevated serum concentrations of NT-proBNP in patients with dementia or vascular disease as a sign of poorer cardiovascular status. Likewise, protein S-100B concentrations were elevated in patients with dementia or vascular disease, possibly indicating brain damage in these groups of patients.. The high frequency of comorbidity of vascular disease and mental illness indicates a possibility to prevent and treat psychogeriatric disease by actively counteracting vascular disease in patients with psychogeriatric symptoms. Routine determination of NT-proBNP is valuable for obtaining information about cardiovascular status.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Creatinine; Cystatin C; Cystatins; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein S; Vascular Diseases; Vitamin B 12

Topics: Folic Acid; Humans; Hyperhomocysteinemia; Renal Dialysis; Vascular Diseases; Vitamin B 12

Peripheral arterial disease (PAD) causes morbidity and is associated with mortality. B vitamin intake has been inversely associated with coronary heart disease, but their effects on PAD are not known. We examined prospectively the relationships between dietary folate, vitamin B-6 and B-12 and PAD risk in 51529 male U.S. health professionals, aged 40 to 75 y, who answered a detailed 131-item questionnaire to assess diet and vitamin supplement use. The study population consisted of 46036 men free of PAD, cardiovascular disease and diabetes at baseline followed for 12 y during which we documented 308 incident PAD cases. For every 400 microg/d increment of folate intake, the multivariate adjusted PAD risk decreased by 21% [relative risk (RR) = 0.79, 95% CI 0.64-0.96]. Men in the top category of folate intake (median = 840 micro g) were at 33% lower risk of PAD than men in the bottom category (median = 244 microg) (RR = 0.67, 95% CI 0.45-0.96, P-value, test for trend = 0.03) after multivariate adjustment. There were weak inverse associations between intake of vitamin B-6 and PAD risk (RR = 0.70, 95% CI 0.48-1.02, P-value, test for trend = 0.06) and B-12 (RR = 0.77, 95% CI 0.54-1.11, P-value, test for trend = 0.12). These results suggest that higher consumption of folate may contribute to the prevention of PAD.

Topics: Adult; Aged; Arteries; Dietary Supplements; Folic Acid; Humans; Male; Middle Aged; Prospective Studies; Risk; Vascular Diseases; Vitamin B 12; Vitamin B 6

Hyperhomocysteinaemia has recently been identified as an important risk factor for atherosclerotic vascular disease. Screening for hyperhomocysteinaemia has been recommended, however, the incidence of hyperhomocysteinaemia in vascular patients is not known.. To determine the incidence of hyperhomocysteinaemia in vascular patients, to determine the relation of hyperhomocysteinaemia with folate, vitamin B12 levels and lipid profiles in vascular patients. To examine if there is a relationship between the degree of vascular injury and homocysteine concentration.. New vascular patients at The Queen Elizabeth Hospital were recruited and divided into peripheral, and aneurysmal presentations. Patients demographics were recorded, blood samples were taken for fasting lipid profile, and homocysteine concentration. Samples were also taken for vitamin B12, plasma and red cell folate levels. Sixty age and sex matched controls were included for comparison.. One hundred and twenty-six patients have been recruited, (95 men and 31 women) with a median age of 68 years (61-74 years). The incidence of elevated homocysteine, and cholesterol levels was 33, 47 and 24%. The levels of vitamin B12 and folate were normal in all patients. Homocysteine was elevated in 27% of claudicants, 50% of patients with rest pain and 53% of patients with an aortic aneurysm.. There is a high rate of hyperhomocysteinaemia in vascular patients with a higher incidence in patients with rest pain. There was also a high incidence of elevated homocysteine levels in patients with an abdominal aortic aneurysm. The rate of growth of these aneurysms is currently under review. Low folate or B12 concentrations is not the cause of raised homocysteine levels.

Topics: Aged; Aortic Aneurysm, Abdominal; Chronic Disease; Female; Folic Acid; Humans; Hyperhomocysteinemia; Intermittent Claudication; Ischemia; Leg; Lipids; Male; Middle Aged; Vascular Diseases; Vitamin B 12

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD). Intracellular vitamin B(12) deficiency may lead to increased plasma total homocysteine (tHcy) concentrations and because transcobalamin (TC) is the plasma transporter that delivers vitamin B(12) to cells, genetic variation in the TC gene may affect intracellular vitamin B(12) availability and, consequently, tHcy concentrations.. We examined five sequence variants, i.e., I23V, G94S, P259R, S348F, and R399Q, in the TC gene as possible determinants of tHcy and, concordantly, as possible risk factors for CVD in 190 vascular disease patients and 601 controls. We also studied potential effect-modification of vitamin B(12) by genotype.. In individuals with high vitamin B(12), 259PP individuals had lower tHcy concentrations than 259PR and 259RR individuals. Homozygous 23VV individuals had lower fasting tHcy concentrations than their 23IV and 23II peers. None of the genotypes defined by the three other sequence variants showed an association with tHcy concentrations, nor was any TC genotype associated with an increased CVD risk.. In individuals in the highest quartile of the vitamin B(12) distribution (>299 pmol/L), tHcy concentrations are lower in 259PP homozygotes than in 259PR and 259RR individuals. Therefore, 259PP individuals, who represent >25% of the general population, may be more susceptible to reduction of plasma tHcy concentrations by increasing the vitamin B(12) status.

Topics: Female; Homocysteine; Humans; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; Transcobalamins; Vascular Diseases; Vitamin B 12

Cobalamin (B12) and folate deficiency is related to both increased erythrocyte mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values. Furthermore, there are indications that B12 and folate serum values do not represent the tissue status of the two vitamins exactly. Therefore, a direct relationship between MCV and tHcy, if demonstrated, could support the hypothesis that tHcy is a better indicator for the cited vitamin status than the serum levels of B12 and folate. We studied MCV, gamma glutamyl transferase (GGT), serum B12, folate and tHcy values in 200 hospitalized patients. There was a significant correlation of MCV with GGT (r = 0.266, P < 0.001) and with tHcy (r = 0.248, P < 0.001), but not with serum B12 and folate. Stepwise multiple linear regression with MCV as dependent and GGT, B12, folate and tHcy as independent variables, respectively, revealed significant associations of MCV with GGT (B = 2.18, 95% CI 0.95-3.42, P = 0.001) and tHcy (B = 3.33, 95% CI 1.26-5.39, P = 0.002). By removing tHcy from this model, serum B12 became a significant predictor of MCV (B = -1.70, 95% CI -3.25 to -0.15, P = 0.032). Serum folate was not significantly associated with MCV in multivariate analysis. In conclusion, the present study confirms indications that serum B12 and folate values lack clinical sensitivity and specificity in diagnosing vitamin deficiency states by showing MCV was better associated to tHcy, than to B12 or folate serum levels. This observation demonstrates that tHcy may be useful in diagnosing patients with B12 and/or folate deficiency.

Topics: Cerebrovascular Disorders; Erythrocyte Volume; Female; Folic Acid; Hemodynamics; Hemoglobins; Homocysteine; Humans; Male; Middle Aged; Vascular Diseases; Vitamin B 12

Epidemiologic studies have identified the plasma homocysteine concentration as a risk factor for atherothrombotic vascular disease. There is little information on the distributions and determinants of homocysteine concentrations in Asian populations.. The present study was designed to examine the relations between genetic and lifestyle factors and plasma homocysteine concentrations among Chinese in Singapore.. Plasma total homocysteine, folate, vitamin B-12, and vitamin B-6 concentrations and genetic variation at the methylenetetrahydrofolate reductase (MTHFR) locus were measured in 486 Chinese men and women aged 45-74 y in Singapore. Data on dietary and other lifestyle factors were collected in face-to-face interviews.. Men had higher plasma concentrations of total homocysteine than women (P = 0.0001). Age was positively associated with plasma homocysteine in both sexes (P for trend = 0.0001). Plasma concentrations of folate, vitamin B-12, and vitamin B-6 were inversely associated with homocysteine concentrations. Among individuals with low plasma folate, those possessing 2 copies of MTHFR mutant alleles had significantly higher homocysteine concentrations than did those with > or = 1 copy of the wild-type allele. Cigarette smoking, daily coffee consumption, and physical inactivity were positively related to plasma homocysteine concentrations in both sexes (P < 0.05). However, these associations disappeared after adjustment for plasma folate concentrations.. Age, sex, plasma folate, vitamin B-12 and B-6 concentrations, and MTHFR genotype are independent determinants of plasma homocysteine in middle-aged and older Chinese in Singapore. These factors combined could account for up to 40% of the total variation in homocysteine concentrations in this Asian population.

Topics: Aged; Aging; Asian People; Cohort Studies; Exercise; Female; Folic Acid; Genotype; Homocysteine; Humans; Interviews as Topic; Life Style; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Prospective Studies; Pyridoxine; Risk Factors; Sex Factors; Singapore; Smoking; Vascular Diseases; Vitamin B 12

Hyperhomocysteinemia is associated with increased risk of atherosclerotic and thrombotic vascular disease. In many patients, hyperhomocysteinemia can be treated or prevented by dietary supplementation with B vitamins, but the clinical benefit of B vitamins for the prevention of vascular disease has not been proven.. Using an atherogenic diet that produces both hyperhomocysteinemia and hypercholesterolemia, we tested the hypothesis that dietary supplementation with B vitamins (folic acid, vitamin B(12), and vitamin B(6)) would prevent hyperhomocysteinemia, vascular dysfunction, and atherosclerotic lesions in monkeys. After 17 months, plasma total homocysteine increased from 3.6+/-0.3 to 11.8+/-1.7 micromol/L in monkeys fed an unsupplemented atherogenic diet (P<0.01) but did not increase in monkeys fed an atherogenic diet supplemented with B vitamins (3.8+/-0.3 micromol/L). Serum cholesterol increased from 122+/-7 to 550+/-59 mg/dL in the unsupplemented group (P<0.001) and from 118+/-5 to 492+/-55 mg/dL in the supplemented group (P<0.001). Responses to endothelium-dependent vasodilators, both in resistance vessels in vivo and in the carotid artery ex vivo, were impaired to a similar extent in groups that did and did not receive vitamin supplements. Anticoagulant responses to the infusion of thrombin were also impaired to a similar extent in both groups. Vitamin supplementation failed to prevent intimal thickening in the carotid or iliac arteries.. These findings demonstrate that supplementation with B vitamins prevents hyperhomocysteinemia but is not sufficient to prevent the development of vascular dysfunction or atherosclerotic lesions in monkeys with marked hypercholesterolemia, even in the absence of preexisting atherosclerosis.

Topics: Animals; Arteriosclerosis; Blood Coagulation; Carotid Arteries; Cholesterol; Diet, Atherogenic; Dietary Supplements; Disease Models, Animal; Folic Acid; Hypercholesterolemia; Hyperhomocysteinemia; In Vitro Techniques; Macaca fascicularis; Partial Thromboplastin Time; Pyridoxine; Thrombin; Treatment Outcome; Vascular Diseases; Vasodilation; Vasodilator Agents; Vitamin B 12

The serum total homocysteine concentration (tHcy), an indicator of folate status and a possible risk factor for vascular disease, is elevated with impaired renal function and poor vitamin B-12 status, which are common in the elderly.. Our objective was to determine the association between tHcy, folate intake, alcohol consumption, and other lifestyle factors in elderly persons.. This cross-sectional study used linear regression to model changes in tHcy. Subjects were 278 men and women aged 66-94 y studied in 1993.. Total folate intake was negatively associated with tHcy in models adjusted for age, sex, serum creatinine, and serum albumin. We found an interaction between food folate intake and supplement use. Food folate intake had an inverse dose-response relation with tHcy that was limited to nonusers of supplements. Predicted tHcy was 1.5 micromol/L lower in users of supplements containing folate and vitamin B-12 than in nonusers and was independent of food folate intake. We found a positive dose-response relation of coffee and tea intake with tHcy, a positive association for alcohol intake of > or = 60 drinks/mo compared with low intake, and an interaction of alcohol use with folate intake and supplement use. Compared with alcohol users, nonusers had higher predicted tHcy and a lower inverse dose-response relation of food folate intake with tHcy.. The inverse association between folate intake and tHcy was strongest among nonusers of supplements and among alcohol drinkers. Identifying modifiable factors related to tHcy, a possible risk factor for vascular disease, is especially important in elderly persons.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Alcohol Drinking; Coffee; Cross-Sectional Studies; Dietary Supplements; Dose-Response Relationship, Drug; Female; Folic Acid; Homocysteine; Humans; Life Style; Linear Models; Male; Methylmalonic Acid; Risk Factors; Smoking; Tea; Vascular Diseases; Vitamin B 12

Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. Although cysteine is structurally similar and metabolically linked to tHcy, its relation to the risk of cardiovascular disease has received little attention. We studied the relation between plasma total cysteine (tCys) levels and the risk of vascular disease in the coronary, cerebral, and peripheral vessels.. This case-control study included 750 patients with vascular disease and 800 age- and sex-matched control subjects recruited from 19 centers in 9 European countries. Conventional risk factors for cardiovascular disease were recorded. In addition, plasma levels of tCys, tHcy, folate, B(6), B(12), and creatinine were measured. Overall, a U-shaped relationship was observed between tCys and risk of vascular disease. With the middle range of 250 to 275 micromol/L tCys used as the reference category, the adjusted risk of vascular disease at low (300 micromol/L) tCys levels was 1.6 (95% CI 1.1 to 2.3). Different shapes of the dose-response relationship were seen for the 3 vascular disease categories. The relation with peripheral vascular and cerebrovascular disease was U-shaped, whereas a weak positive relation was observed with coronary heart disease.. Our data show a significant U-shaped relationship between tCys and cardiovascular disease after adjustment for tHcy, creatinine, and other cardiovascular disease risk factors.

Topics: Adult; Case-Control Studies; Creatinine; Cysteine; Female; Folic Acid; Homocysteine; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Pyridoxine; Risk Factors; Vascular Diseases; Vitamin B 12

Hyperhomocysteinemia is considered as a risk factor for cardiovascular diseases. Usually, an inverse relationship exists between homocysteine and folate levels, and supplementation with folate lowers homocysteine concentrations in patients. Therefore, hyperhomocysteinemia is mainly ascribed to the insufficient dietary intake of folate. Hyperhomocysteinemia has also been observed in infections and inflammatory diseases. Oxidative stress appears to be involved in the pathogenesis of these disorders, and associations have been found between homocysteine and e.g., neopterin concentration. Increased neopterin concentration indicates immune system activation and also allows an estimate of thus elicited oxidative stress. It may be relevant that the active cofactor, tetrahydrofolate, is very susceptible to oxidation. Immunologically induced oxidative stress could lead to folate depletion resulting in hyperhomocysteinemia. Thus, hyperhomocysteinemia in patients can be considered as an indirect consequence of hyperconsumption of antioxidant vitamins during prolonged states of immune activation.

Topics: Dementia, Vascular; Diet; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Models, Biological; Models, Chemical; Neopterin; Oxidative Stress; Oxygen; Vascular Diseases; Vitamin B 12

Thrombotic events are a well-recognized complication of homocystinuria. However, the mechanisms involved in the atherogenic and thrombotic effects of homocyst(e)ine remain incompletely understood. The objective of this study was to determine the role of endothelial cell activation/damage as indicated by levels of thrombomodulin, tissue factor and tissue factor pathway inhibitor, and factor VII activity in patients with homocystinuria. Six patients with homocystinuria, nonresponsive to pyridoxine, treated only with trimethylglycine (betaine) were injected with a bolus of 20 IU/kg body weight of unfractionated commercial heparin to induce the release of tissue factor pathway inhibitor from the vascular endothelium. Tissue factor, thrombomodulin, and factor VII activity were measured by enzyme-linked immunosorbent assay and clotting assay before heparin administration. Tissue factor pathway inhibitor antigen and activity were measured before and 5 minutes after the bolus of heparin. Levels of homocyst(e)ine were elevated (patients: 144.2+/-19.2 micromol/L; controls: 10.2+/-0.9 micromol/L); however, levels of thrombomodulin, tissue factor, and tissue factor pathway inhibitor antigen were not statistically different from the control group. In contrast, tissue factor pathway inhibitor activity showed a significantly increased level (patients: 2.09+/-0.34 U/L; controls: 1.14+/-0.20 U/L; p<0.05) that was correlated with homocyst(e)ine. Factor VII activity was significantly decreased (patients: 64.7+/-5.1%; controls: 91.4+/-4.7%; p<0.05) and inversely correlated with homocyst(e)ine. After heparin the patients released higher amounts of tissue factor pathway inhibitor antigen and activity compared with the control group; however, the difference was not statistically significant. Although not treated with antithrombotic drugs, none of the patients had any thromboembolic complications after starting betaine. In addition to betaine treatment, the enhanced factor pathway inhibitor antigen activity observed in this small series of patients suggests that factor pathway inhibitor antigen may play an additional, as yet unexplained, role in this genetic disorder.

Topics: Adult; Betaine; Biomarkers; Cystathionine beta-Synthase; Endothelium; Factor VII; Female; Fibrinolytic Agents; Heparin; Homocysteine; Homocystinuria; Homozygote; Humans; Lipoproteins; Male; Protein C; Pyridoxine; Serine Proteinase Inhibitors; Thrombomodulin; Thromboplastin; Vascular Diseases; Vitamin B 12

Topics: Folic Acid; Homocysteine; Humans; Pyridoxine; Sex Factors; Vascular Diseases; Vitamin B 12

Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitamins B(6)and B(12)affect tHcy levels. Objectives To study associations of gender and age with levels of plasma tHcy, and to examine the relationships of tHcy and circulating levels of folate, vitamins B(6)and B(12)with risk of vascular disease in men and women (pre- and post-menopausal).. In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the coronary, cerebral, or peripheral vessels and 800 control subjects (570 men, 230 women) were enrolled. Plasma tHcy levels (fasting and after methionine loading) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional adjustment for serum creatinine and vitamins for the tHcy comparisons between the sexes and between cases and controls. Risk analyses included adjustment for creatinine and traditional risk factors. Relationships between age, gender and tHcy were studied among control subjects only.. Fasting tHcy levels were lower in women than in men. Levels of tHcy showed a positive association with age, for both sexes. In the post-menopausal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before the menopause. For post-methionine load tHcy, there was a 40% stronger association with vascular disease in women than in men. In both sexes, but especially in pre-menopausal women, low circulating levels of vitamin B(6)conferred a two- to threefold increased risk of vascular disease, independent of tHcy. In men, but not in women, low (defined as <20th percentile of controls) circulating folate levels were associated with a 50% increased risk of vascular disease.. Elevation of tHcy appears to be at least as strong a risk for vascular disease in women as men, even before the menopause. Our data indicate that associations of the various tHcy measurements (and the vitamins that determine them), with risks of vascular disease may differ between the sexes. The tHcy-independent relationship of vitamin B(6)with vascular disease indicates that it will be advisable to test the effects of vitamin B(6)in clinical trials.

Topics: Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Male; Menopause; Pyridoxine; Risk Factors; Sex Factors; Vascular Diseases; Vitamin B 12

Topics: Dietary Supplements; Folic Acid; Homocysteine; Humans; Pyridoxine; Risk Factors; Vascular Diseases; Vitamin B 12

Topics: Anemia, Pernicious; Bread; Female; Folic Acid; Food, Fortified; Humans; Hungary; Neural Tube Defects; Pregnancy; Pyridoxine; Vascular Diseases; Vitamin B 12

Recent studies suggest that vascular disease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD.. To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12.. Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects.. Referral population to a hospital clinic between July 1988 and April 1996.. Serum tHcy, folate, and vitamin B12 levels in patients and controls at entry; the odds ratio of DAT or confirmed AD with elevated tHcy or low vitamin levels; and the rate of disease progression in relation to tHcy levels at entry.. Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third (> or = 14 micromol/L) compared with the bottom third (< or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2), after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. The corresponding odds ratio for the lower third compared with the upper third of serum folate distribution was 3.3 (95% confidence interval, 1.8-6.3) and of vitamin B12 distribution was 4.3 (95% confidence interval, 2.1-8.8). The mean tHcy levels were unaltered by duration of symptoms before enrollment and were stable for several years afterward. In a 3-year follow-up of patients with DAT, radiological evidence of disease progression was greater among those with higher tHcy levels at entry.. Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Case-Control Studies; Disease Progression; Female; Folic Acid; Homocysteine; Humans; Male; Memory Disorders; Middle Aged; Polymorphism, Genetic; Predictive Value of Tests; Risk Factors; Vascular Diseases; Vitamin B 12

Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disease remains a matter of debate. Testing for the 677C-T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interaction between the 677C-T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting homocysteine and plasma folate levels was found in all individuals homozygous for the 677C-T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C-T MTHFR polymorphism is not a major determinant of the vascular disease but contributes to increased plasma homocysteine concentration in conjunction with low plasma folate levels.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Adolescent; Adult; Aged; Aged, 80 and over; Erythrocytes; Female; Folic Acid; Genotype; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases; Polymorphism, Genetic; Risk Factors; Vascular Diseases; Vitamin B 12

To determine whether homocyst(e)ine, a relatively new risk factor for possible endothelial cell dysfunction and premature vascular disease, is elevated in nulliparous pregnant women with preeclampsia.. We measured plasma homocyst(e)ine, folic acid, and vitamin B12 levels in 40 nulliparas, 20 with and 20 without preeclampsia at the time of their delivery.. Mean (+/- standard deviation) plasma homocyst(e)ine levels in the 20 nulliparous women with preeclampsia were significantly higher than in the 20 nulliparous women without preeclampsia (8.66 +/- 3.05 versus 4.99 +/- 1.11 mumol/L, P < .001). Folic acid and vitamin B12 concentrations were not significantly different between the two groups.. Homocyst(e)ine levels are elevated in pregnant nulliparas with preeclampsia at the time of their delivery. Further studies are necessary to determine what role homocyst(e)ine may play in the etiology of preeclampsia.

Topics: Adult; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Parity; Pre-Eclampsia; Pregnancy; Risk Factors; Vascular Diseases; Vitamin B 12

To provide a reference range for plasma total homocysteine (tHcy), an independent risk factor for vascular disease, and to explore relationships with nutritional indices for people aged 65 y and over, in the UK National Diet and Nutrition Survey (NDNS).. The survey procedures described in the National Diet and Nutrition Survey Report (1997) included a health-and-lifestyle interview, a four-day weighed diet record, anthropometric and blood pressure measurements and a fasting blood sample for biochemical indices, including tHcy.. Eighty randomly selected postcode sectors from mainland Britain during 1995-1996.. Of 2060 people interviewed, 1527 were visited by the nurse, 1276 gave a blood sample and 972 had tHcy measured. About 80% were in their own homes and the remainder were in nursing homes or similar institutions.. Significant cross-sectional relationships, both univariate and multivariate were found between tHcy and index concentrations of folate and vitamin B12 (P < 0.0001), and between tHcy and plasma creatinine, urea, calcium, zinc, alpha 1-antichymotrypsin, lutein and cysteine (P = 0.013 to < 0.0001). Dietary nutrient analyses showed an association with folate intake. tHcy was also correlated with age and with domicile (free-living or institution), with history of vascular disease and with use of four classes of drugs, two of which are prescribed for vascular diseases. There was a north-south gradient in tHcy (P = 0.005), and also in food choices, blood micronutrient indices and vascular disease prevalence.. The concentrations of tHcy found in this study provide a reference range for people aged 65 y and over, in mainland Britain. tHcy is a valuable functional index of micronutrient status and intakes for British people aged 65 y and over, which can assist the development of health-promotion strategies.

Topics: Aged; alpha 1-Antichymotrypsin; Calcium; Creatinine; England; Female; Folic Acid; Homocysteine; Humans; Lutein; Male; Nutritional Status; Random Allocation; Reference Values; Regression Analysis; Risk Factors; Urea; Vascular Diseases; Vitamin B 12; Zinc

Plasma homocysteine concentration is a sensitive marker for cobalamin and folate deficiency. The previously reported high incidence of increased plasma homocysteine in psychogeriatric patients and the association between reduced concentrations of cobalamin, folate and neuropsychiatric symptoms led to the present study on 741 consecutive psychogeriatric patients. The concentrations of plasma homocysteine correlated significantly with blood folate, serum cobalamin and serum creatinine both in demented (n = 295) and in non-demented patients with other psychiatric disorders (n = 215). Plasma homocysteine concentrations were significantly increased in both the demented and the non-demented patients, whereas only the demented patients had lower blood folate and serum creatinine concentrations than 163 control subjects. Almost all of the different diagnostic groups of demented and non-demented patients exhibited significantly increased plasma homocysteine concentrations compared with control subjects. Significantly decreased blood folate concentrations were mainly found in the different diagnosis groups of demented patients. Plasma homocysteine concentrations in both demented and non-demented patients with serum cobalamin and blood folate above the lower 20th percentile of these vitamins in the control subjects were also studied. Despite these vitamin concentrations, both groups of patients still exhibited significantly higher plasma homocysteine concentrations than the control subjects, which may indicate an increased frequency of impaired genetic capacity to metabolize homocysteine in these patients. Patients with either dementia of vascular cause or a history of other occlusive arterial disease had a significantly higher plasma homocysteine concentration than those without a history of vascular disease.

Topics: Aged; Aged, 80 and over; Dementia; Female; Folic Acid; Homocysteine; Humans; Male; Vascular Diseases; Vitamin B 12

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5, 10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Adult; Folic Acid; Genotype; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Neural Tube Defects; Oxidoreductases; Phenotype; Risk Factors; Vascular Diseases; Vitamin B 12

Homocysteine is a probably atherogenic amino acid, the fasting and post-methionine load serum concentrations of which have been reported to be much lower in premenopausal women than in men and postmenopausal women. This difference has been proposed to explain the reduced proneness of premenopausal women to vascular disease. We measured both free and total plasma homocysteine concentrations both fasting and post-methionine load, in 169 healthy subjects. Twelve subjects (7%) had distinctly abnormal plasma homocysteine values. Among the remaining 157 subjects, neither fasting nor post-load values of free or total homocysteine were lower in premenopausal women (n = 46) than in men of similar age (n = 41) or postmenopausal women (n = 37). Fasting but not post-load values were lower in postmenopausal women than in men of similar age (n = 33), and lower among the women as a whole (n = 83) than among the men (n = 74). In men, fasting values increased with age, and paralleled age-related decreases in the concentrations of homocysteine metabolism cofactors (serum vitamin B12, blood folate, and plasma pyridoxal 5-phosphate). Both in men and in women, fasting total plasma homocysteine values were significantly and negatively correlated to serum vitamin B12 and blood folate concentrations. Whether the small differences in plasma homocysteine values between the present men and women may be a contributory factor vis-à-vis their different proneness to vascular disease has yet to be settled.

Topics: Adult; Aged; Aging; Fasting; Female; Folic Acid; Homocysteine; Humans; Male; Menopause; Methionine; Middle Aged; Pyridoxal Phosphate; Sex Characteristics; Vascular Diseases; Vitamin B 12

Homocysteine is an amino acid considered to cause vascular injury, arteriosclerosis, and thromboembolism. Total plasma homocysteine (free and protein-bound) was found to be twice as high in asymptomatic vitamin B12-deficient subjects (23.8 +/- 3.8 mumol/L, means +/- SEM, n = 20) as in controls (11.5 +/- 0.9 mumol/L, P less than .0001, n = 21), and higher than in heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency (13.8 +/- 1.6 mumol/L, P less than .01, n = 14), who were recently shown to be much more common among patients with premature vascular disease than expected. Eight (40%) vitamin B12-deficient and two (14%) heterozygote subjects had significant homocysteinemia (greater than mean +2 SD for controls). After administration of hydroxycobalamin to vitamin B12-deficient subjects, homocysteine levels decreased to normal (-49%, 12.2 +/- 1.5 mumol/L, P less than .0001, n = 20). Thus, if homocysteine does cause vascular injury, theoretically vitamin B12-deficiency might be associated with an increased frequency of vascular disease.

Topics: Cystathionine beta-Synthase; Heterozygote; Homocysteine; Homocystinuria; Humans; Hydro-Lyases; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Arteriosclerosis Obliterans; Choline; Coronary Disease; Folic Acid; Gangrene; Heparin; Humans; Male; Middle Aged; Niacinamide; Sympathectomy; Thrombosis; Vascular Diseases; Vasodilator Agents; Vitamin B 12

Topics: Blood Proteins; Chemistry Techniques, Analytical; Chromatography; Cobalt Isotopes; Corrinoids; Humans; Intrinsic Factor; Leukemia; Leukemia, Myeloid; Metabolism; Schilling Test; Transcobalamins; Urine; Vascular Diseases; Vitamin B 12

Topics: Angiography; Arteriosclerosis Obliterans; Atherosclerosis; Barbiturates; Diagnosis, Differential; Drug Therapy; Humans; Ischemia; Leg; Salicylates; Thiamine; Thrombophlebitis; Vascular Diseases; Vascular Surgical Procedures; Vasodilator Agents; Vitamin B 12; Vitamin B Complex

Topics: Hematinics; Humans; Liver Diseases; Vascular Diseases; Vitamin B 12

Topics: Corrinoids; Diagnosis, Differential; Hematinics; Humans; Liver Diseases; Prognosis; Vascular Diseases; Vitamin B 12

Topics: Hematinics; Humans; Liver Diseases; Vascular Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Liver Diseases; Vascular Diseases; Vitamin B 12

Topics: Hematinics; Humans; Liver Diseases; Serum; Vascular Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Peripheral Vascular Diseases; Vascular Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Liver Diseases; Vascular Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Liver Diseases; Vascular Diseases; Vitamin B 12

Topics: Corrinoids; Hematinics; Hematologic Diseases; Humans; Vascular Diseases; Vitamin B 12