vitamin-b-12 and Stroke

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

Ischemic stroke is the most prevalent form of stroke and has a high incidence in older adults, characterized by high morbidity, mortality, disability, and recurrence rate. Vitamin B

Topics: Aged; Humans; Ischemic Stroke; Stroke; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

In this article, we discuss a problem in the most recent American Heart Association guideline on secondary stroke prevention that apparently arose from the rules of evidence imposed on the guideline panel. We are told by the cochair of the panel that American Heart Association rules about guidelines for secondary prevention prohibited consideration of primary prevention studies and secondary analyses of secondary prevention studies. However, evidence-based medicine should consider all the best external evidence available and also clinical judgement. The most important problem in the guideline was the recommendation that B vitamins to lower homocysteine do not prevent recurrent stroke. When considering all the best external evidence, it is clear that B vitamins do prevent stroke, but in the early secondary stroke prevention studies, the benefit of B vitamins in participants with good renal function was apparently offset by harm from cyanocobalamin among participants with renal failure (level B-R evidence). We review the evidence that B vitamins should be used to prevent stroke, both in primary and secondary stroke prevention (class 2a recommendation). We also review issues in folate metabolism that require further study, with regard to the form of folate to be used for stroke prevention. We recommend that the guideline be revised to say that B vitamins to lower homocysteine prevent stroke and that methylcobalamin or hydroxycobalamin should be used instead of cyanocobalamin.

Topics: American Heart Association; Folic Acid; Homocysteine; Humans; Stroke; Vitamin B 12; Vitamin B Complex

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated `Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Further observations indicate that proper dietary supplementation with B-vitamins decreases total plasma Hcy concentrations and may be an effective intervention for stroke prevention. Metabolic vitamin B

Topics: Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Stroke; Vitamin B 12; Vitamin B Complex

Patients with renal failure have extremely high cardiovascular risk; in dialysis patients the risk of stroke is increased approximately 10-fold over that in the general population. Reasons include not only a high prevalence of traditional risk factors such as diabetes, hypertension and dyslipidemia, but also the accumulation of toxic substances that are eliminated by the kidneys, so have very high levels in patients with renal failure. These include plasma total homocysteine, asymmetric dimethylarginine, thiocyanate, and toxic products of the intestinal microbiome (Gut-Derived Uremic Toxins; GDUT), which include trimethylamine N- oxide (TMAO), produced from phosphatidylcholine (largely from egg yolk) and carnitine (largely from red meat). Other GDUT are produced from amino acids, largely from meat consumption. Deficiency of vitamin B12 is very common, raises plasma tHcy, and is easily treated. However, cyanocobalamin is toxic in patients with renal failure. To reduce the risk of stroke in renal failure it is important to limit the intake of meat, avoid egg yolk, and use methylcobalamin instead of cyanocobalamin, in addition to folic acid.

Topics: Bacteria; Biomarkers; Comorbidity; Diet; Dietary Supplements; Gastrointestinal Microbiome; Homocysteine; Humans; Kidney; Nutritional Status; Protective Factors; Renal Insufficiency; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Uremia; Vitamin B 12; Vitamin B 12 Deficiency

Sexual dysfunction following stroke is common but often is poorly managed. As awareness of sexual dysfunction following stroke increases as an important issue, a clearer evidence base for interventions for sexual dysfunction is needed to optimise management.. To evaluate the effectiveness of interventions to reduce sexual dysfunction following stroke, and to assess adverse events associated with interventions for sexual dysfunction following stroke.. We conducted the search on 27 November 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; from June 2014), in the Cochrane Library; MEDLINE (from 1950); Embase (from 1980); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982); the Allied and Complementary Medicine Database (AMED; from 1985); PsycINFO (from 1806); the Physiotherapy Evidence Database (PEDro; from 1999); and 10 additional bibliographic databases and ongoing trial registers.. We included randomised controlled trials (RCTs) that compared pharmacological treatments, mechanical devices, or complementary medicine interventions versus placebo. We also included other non-pharmacological interventions (such as education or therapy), which were compared against usual care or different forms of intervention (such as different intensities) for treating sexual dysfunction in stroke survivors.. Two review authors independently selected eligible studies, extracted data, and assessed study quality. We determined the risk of bias for each study and performed a 'best evidence' synthesis using the GRADE approach.. We identified three RCTs with a total of 212 participants. We noted significant heterogeneity in interventions (one pharmacological, one physiotherapy-based, and one psycho-educational), and all RCTs were small and of 'low' or 'very low' quality. Based on these RCTs, data are insufficient to provide any reliable indication of benefit or risk to guide clinical practice in terms of the use of sertraline, specific pelvic floor muscle training, or individualised sexual rehabilitation.. Use of sertraline to treat premature ejaculation needs to be tested in further RCTs. The lack of benefit with structured sexual rehabilitation and pelvic floor physiotherapy should not be interpreted as proof of ineffectiveness. Well-designed, randomised, double-blinded, placebo-controlled trials of long-term duration are needed to determine the effectiveness of various types of interventions for sexual dysfunction. It should be noted, however, that it may not be possible to double-blind trials of complex interventions.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Female; Humans; Male; Middle Aged; Orgasm; Pelvic Floor; Premature Ejaculation; Quality of Life; Randomized Controlled Trials as Topic; Resistance Training; Sertraline; Sex Education; Sexual Dysfunction, Physiological; Sexual Partners; Stroke; Vitamin B 12; Vitamin B Complex; Young Adult

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

The purpose of this narrative review is to highlight insights into the importance and frequency of metabolic vitamin B12 (B12) deficiency, reasons why it is commonly missed, and reasons for the widespread but mistaken belief that treatment of B12 deficiency does not prevent stroke or improve cognitive function. Metabolic B12 deficiency is common, being present in 10%-40% of the population; is frequently missed; is easily treated; and contributes importantly to cognitive decline and stroke in older people. Measuring serum B12 alone is not sufficient for diagnosis; it is necessary to measure holotranscobalamin or functional markers of B12 adequacy such as methylmalonic acid or plasma total homocysteine. B-vitamin therapy with cyanocobalamin reduces the risk of stroke in patients with normal renal function but is harmful (perhaps because of thiocyanate accumulation from cyanide in cyanocobalamin) in patients with renal impairment. Methylcobalamin may be preferable in renal impairment. B12 therapy slowed gray matter atrophy and cognitive decline in the Homocysteine and B Vitamins in Cognitive Impairment Trial. Undiagnosed metabolic B12 deficiency may be an important missed opportunity for prevention of dementia and stroke; in patients with metabolic B12 deficiency, it would be prudent to offer inexpensive and nontoxic supplements of oral B12, preferably methylcobalamin or hydroxycobalamin. Future research is needed to distinguish the effects of thiocyanate from cyanocobalamin on hydrogen sulfide, and effects of treatment with methylcobalamin on cognitive function and stroke, particularly in patients with renal failure.

Topics: Animals; Biomarkers; Delayed Diagnosis; Dementia; Dietary Supplements; Humans; Hydroxocobalamin; Prevalence; Risk; Stroke; Vitamin B 12; Vitamin B 12 Deficiency; 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

Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk.. Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk.. The meta-analysis included fourteen randomized controlled trials,. A total of 39 420 patients.. Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification.. Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.

Topics: Databases, Factual; Folic Acid; Food, Fortified; Homocysteine; Humans; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Vitamin B 12

Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke.. A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions.. B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12.. B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.

Topics: Bayes Theorem; Dietary Supplements; Humans; Randomized Controlled Trials as Topic; Risk; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Circulating homocysteine levels (tHcy), a product of the folate one carbon metabolism pathway (FOCM) through the demethylation of methionine, are heritable and are associated with an increased risk of common diseases such as stroke, cardiovascular disease (CVD), cancer and dementia. The FOCM is the sole source of de novo methyl group synthesis, impacting many biological and epigenetic pathways. However, the genetic determinants of elevated tHcy (hyperhomocysteinemia), dysregulation of methionine metabolism and the underlying biological processes remain unclear. We conducted independent genome-wide association studies and a meta-analysis of methionine metabolism, characterized by post-methionine load test tHcy, in 2,710 participants from the Framingham Heart Study (FHS) and 2,100 participants from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, and then examined the association of the identified loci with incident stroke in FHS. Five genes in the FOCM pathway (GNMT [p = 1.60 × 10(-63)], CBS [p = 3.15 × 10(-26)], CPS1 [p = 9.10 × 10(-13)], ALDH1L1 [p = 7.3 × 10(-13)] and PSPH [p = 1.17 × 10(-16)]) were strongly associated with the difference between pre- and post-methionine load test tHcy levels (ΔPOST). Of these, one variant in the ALDH1L1 locus, rs2364368, was associated with incident ischemic stroke. Promoter analyses reveal genetic and epigenetic differences that may explain a direct effect on GNMT transcription and a downstream affect on methionine metabolism. Additionally, a genetic-score consisting of the five significant loci explains 13% of the variance of ΔPOST in FHS and 6% of the variance in VISP. Association between variants in FOCM genes with ΔPOST suggest novel mechanisms that lead to differences in methionine metabolism, and possibly the epigenome, impacting disease risk. These data emphasize the importance of a concerted effort to understand regulators of one carbon metabolism as potential therapeutic targets.

Topics: Aldehyde Dehydrogenase; Carbon; Folic Acid; Genome-Wide Association Study; Genotype; Homocysteine; Humans; Methionine; Oxidoreductases Acting on CH-NH Group Donors; Stroke; Vitamin B 12

High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously.. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.. A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855).. Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

Topics: Aged; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Homocysteine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Placebos; Recurrence; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Topics: Clinical Trials as Topic; Drug Combinations; Folic Acid; Humans; Randomized Controlled Trials as Topic; Stroke; Vitamin B 12; Vitamin B 6

Although a lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized, controlled trials have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of randomized, controlled trials to assess the efficacy of folic acid supplementation in the prevention of stroke.. Salient trials were identified by formal literature search. Relative risk (RR) with 95% CI was used as a measure of the association between folic acid supplementation and risk of stroke, after pooling data across trials in a fixed-effects model.. The search identified 13 randomized, controlled trials that had enrolled 39 005 participants for folic acid therapy to reduce homocysteine in which stroke was reported as an outcome measure. Across all trials, folic acid supplementation was associated with a trend toward mild benefit that did not reach statistical significance in reducing the risk of stroke (RR=0.93; 95% CI, 0.85-1.03; P=0.16). The RR for nonsecondary prevention trials was 0.89 (95% CI, 0.79-0.99; P=0.03). In stratified analyses, a greater beneficial effect was seen in the trials testing combination therapy of folic acid plus vitamins B6 and B12 (RR=0.83; 95% CI, 0.71-0.97; P=0.02) and in the trials that disproportionately enrolled male patients (men:women >2; RR=0.84; 95% CI, 0.74-0.94; P=0.003).. Folic acid supplementation did not demonstrate a major effect in averting stroke. However, potential mild benefits in primary stroke prevention, especially when folate is combined with B vitamins and in male patients, merit further investigation.

Topics: Female; Folic Acid; Homocysteine; Humans; Male; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex

In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes.. Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008.. Thirty-six hospitals in Norway.. 6837 patients with ischaemic heart disease.. One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo.. Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up.. Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs.. We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.

Topics: Capsules; Double-Blind Method; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Patient Compliance; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.. We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.. After a mean treatment period of 3.9 +/- 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 micromol/L, 95% CI 7.5 to 8.4 versus 11.8 micromol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 +/- 0.17 mm vitamins versus 0.83 +/- 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.. Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.

Topics: Aged; Carotid Arteries; Dietary Supplements; Double-Blind Method; Down-Regulation; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Regional Blood Flow; Stroke; Time Factors; Treatment Outcome; Tunica Intima; Tunica Media; Vasodilation; Vitamin B 12; Vitamin B 6; Vitamin B Complex

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

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

On the basis of the results of several recent clinical trials, many researchers have concluded that vitamin therapy designed to lower total homocysteine concentrations is not effective in reducing the risk of cardiovascular events. However, whereas almost all myocardial infarctions are due to plaque rupture, stroke has many more pathophysiological mechanisms, and thrombosis-which is increased by raised total homocysteine concentrations-has an important role in many of these processes. Thus, stroke and myocardial infarction could respond differently to vitamin therapy. A detailed assessment of the results of the recent HOPE-2 trial and a reanalysis of the VISP trial restricted to patients capable of responding to vitamin therapy suggest that higher doses of vitamin B12 and perhaps new approaches to lowering total homocysteine besides routine vitamin therapy with folate, vitamin B6, and vitamin B12 could reduce the risk of stroke. Thus, therapy to lower homocysteine could still help to prevent stroke, if not other vascular outcomes.

Topics: Animals; Clinical Trials as Topic; Homocysteine; Humans; Myocardial Infarction; Risk; Stroke; Vitamin B 12; Vitamin B 6

Two-thirds of stroke deaths worldwide occur in developing countries. The higher prevalence of undernutritional states and parasitic infestations in many of these countries could lead to vitamin B(12) and folate deficiencies. Hyperhomocysteinemia, a proxy measure for the nutritional status of B vitamins, has been reported in many developing countries and is found to be associated with nutrition-related low plasma folate and vitamin B(12). Several epidemiological observations have linked hyperhomocysteinemia to increased risk for stroke. The exact molecular mechanism by which homocysteine promotes atherothrombosis is not clear, although several possible roles have been suggested. Homocysteine is believed to cause atherogenesis and thrombogenesis via endothelial damage, focal vascular smooth muscle proliferation probably causing irregular vascular contraction, and coagulation abnormalities. Supplementation with the nutrient cofactors required for optimal functioning of the homocysteine metabolic pathways significantly impacts plasma homocysteine levels, and offers a new integrated possibility for prevention of stroke in the underdeveloped and rapidly developing countries.

Topics: Developing Countries; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Metabolic Networks and Pathways; Nutritional Status; Stroke; 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

In the present article we discuss the most recent data regarding the role of homocysteine, its cyclic thioester--homocysteine thiolactone and the process of protein N-homocysteinylation in human disease. The protective role of thiolactonase/paraoxonase enzyme, carried on high density lipoproteins (HDL) in human blood, as well as the influence of structural modifications on HDL function are discussed. We also describe the effect of vitamin therapy (folic acid, vitamins: B6, B12) used for lowering the homocysteine level in humans as well.

Topics: Animals; Aryldialkylphosphatase; Atherosclerosis; Biomarkers; Fibrinogen; Folic Acid; Homocysteine; Humans; Lipoproteins, HDL; Rabbits; Stroke; Vitamin B 12; Vitamin B 6

The author presents an overview of the current literature on homocysteine as a risk factor for neuropsychiatric disorders. The databases MEDLINE, Current Contents and EMBASE were searched (between 1966 and 2002) for English language publications with the key words 'Homocysteine' and 'Stroke'; 'Alzheimer Disease'; 'Cognitive Impairment'; 'Epilepsy'; 'Depression'; or 'Parkinson's disease'. Individual articles were hand searched for relevant cross-references. It is biologically plausible that high homocysteine levels may cause brain injury and neuropsychiatric disorders. Homocysteine is proatherogenic and prothrombotic, thereby increasing the risk of cerebrovascular disease, and may have a direct neurotoxic effect. Evidence for homocysteine as a risk factor for cerebral microvascular disease is conflicting but warrants further study. Cross-sectional and some longitudinal studies support increased prevalence of stroke and vascular dementia in hyperhomocysteinemic individuals. The evidence of increased neurodegeneration is accumulating. The relationship with depression is still tentative, as it is with epilepsy. Currently, treatment studies are necessary to place the evidence on a stronger footing, and maybe high-risk patients should be screened for hyperhomocysteinemia and this should be treated with folic acid. More research evidence is necessary before population screening can be recommended.

Topics: Alzheimer Disease; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Mental Disorders; Parkinson Disease; Risk Factors; Stroke; Vitamin B 12; Vitamin B 6

Topics: Chile; Colonic Neoplasms; Congenital Abnormalities; Controlled Clinical Trials as Topic; Folic Acid; Food, Fortified; Myocardial Infarction; Netherlands; Public Health; Randomized Controlled Trials as Topic; Stroke; United Kingdom; United States; Vitamin B 12; Vitamin B 12 Deficiency

To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension.. From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months.. After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05).. Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Prognosis; Stroke; Treatment Outcome; Vitamin B 12

Topics: Aged; Cognitive Dysfunction; Double-Blind Method; Female; Folic Acid; Homocystine; Humans; Male; Middle Aged; Neuropsychological Tests; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex

To observe the clinical therapeutic effect of acupoint injection of medicine in the treatment of patients with acute cerebral ischemia stroke (ACIS).. Ninety ACIS patients were randomized into control, Cobalamin and Gangliosides groups (. After the treatment, of the three 30 cases in the control, Cobalamin and Gangliosides groups, 0, 4 and 2 were cured, 9, 15 and 14 experienced marked improvement in their symptoms, 12, 8 and 10 were improved, 9, 3 and 4 invalid, with the effective rates being 70.0%(21/30), 90.0%(27/30) and 86.7%(26/30), respectively. In comparison with pre-treatment, the CNDS of the three groups were all significantly decreased and the ADLS notably increased (. Acupoint injection of both Cobalamin and Gangliosides can effectively improve acute ischemic stroke patients' neurological function and daily life living ability.

Topics: Acupuncture Points; Acute Disease; Adult; Aged; Aged, 80 and over; Female; Gangliosides; Humans; Male; Middle Aged; Stroke; Treatment Outcome; Vitamin B 12

Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial.. The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B6 and B12 reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions.. This is a multicenter, randomized, double-blinded, placebo-controlled trial. Patients (n = 8000, α = 0.05, β = 0.10) within one-month of ischemic stroke (large-artery atherosclerosis or small-vessel occlusion) or hypertensive intracerebral haemorrhage with plasma homocysteine level ≥ 15 μmol/l will be enrolled. Eligible patients will be randomized by a web-based, random allocation system to receive multivitamins (folic acid 0.8 mg, vitamin B6 10 mg, and vitamin B12 500 μg) or matching placebo daily with a median follow-up of three-years.. Patients will be evaluated at six monthly intervals. The primary outcome event is the composite event 'stroke, myocardial infarction, or death from any vascular cause', whichever occurs first. Secondary outcome measures include nonvascular death, transient ischemic attack, depression, dementia, unstable angina, revascularization procedures of the coronary, and cerebral and peripheral circulations.. This is the first multicenter randomized trial of secondary prevention for ischemic stroke in a Chinese population with a higher homocysteine level but without folate food fortification.

Topics: Adult; Aged; Brain Ischemia; China; Double-Blind Method; Folic Acid; Homocysteine; Humans; Intracranial Hemorrhage, Hypertensive; Middle Aged; Myocardial Infarction; Protective Agents; Research Design; Secondary Prevention; Stroke; Vitamin B 12; Vitamin B 6

Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 μg twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (p<0.05) in patients with acute ischemic stroke. With supplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (p<0.05). The present study reconfirmed that ADMA can be regarded as a risk biomarker for acute ischemic stroke. We observed that with supplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.

Topics: Aged; Arginine; Blood Chemical Analysis; Brain Ischemia; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Stroke; Time Factors; Treatment Outcome; Vitamin B 12

To observe the effect differences on post-stroke dysphagia among acupoint injection combined with neural electrical stimulation, acupoint injection, neural electrical stimulation, and swallowing training respectively, so eligible intervention can be applied to this kind of disease.. One hundred and eight-three patients of post-stroke dysphagia were randomized into a comprehensive treatment group (42 cases), an acupoint injection group (44 cases), a neural electrical stimulation group (49 cases) and a swallow training group (48 cases) and were treated with the comprehensive therapy of acupoint injection and neural electrical stimulation, acupoint injection, neural electrical stimulation and swallowing training separately. The treatments for 10 days made one session. There were 3 days at the interval among treatment sessions and 3 sessions were required totally. The cases in those treatment groups were blankly controlled with the other 47 patients of post-stroke dysphagia. All the patients received basic rehabilitation treatment. The modified water swallowing test was conducted to assess the efficacy before treatment, 10 days after treatment and 30 days after treatment in each group separately. The clinical efficacy, score of water swallowing test and improvement in water swallow test were compared among the groups.. After 10-day treatment, the differences in efficacy and score of water swallow test were not significant in each group (all P > 0.05). After 30-day treatment, the effective rate (94.29%, 33/35) in the comprehensive treatment group was apparently better than 68.75% (22/32) in the acupoint injection group, 80.00% (32/40) in the neural electrical stimulation group, 67.50% (27/40) in the swallowing training group and 42.86% (12/28) in the blank group separately. The score in water swallow test in the comprehensive treatment group was lower than that in each of the other groups (1.37 ± 0.60 vs 2.03 ± 1.00, 1.90 ± 0.90, 2.20 ± 0.72, 2.71 ± 0.90, all P < 0.05). The differences in the effective rate and score in water swallow test were not significant among the acupoint injection group, neural electrical stimulation group and swallowing training group (all P > 0.05), which indicated that the improvement in swallowing function in the comprehensive treatment group was significantly superior to the other groups (all P < 0.05).. The comprehensive therapy of acupoint injection and neural electrical stimulation achieves the much better efficacy on post-stroke dysphagia.

Topics: Acupuncture Points; Adult; Aged; Combined Modality Therapy; Deglutition; Deglutition Disorders; Electric Stimulation Therapy; Female; Humans; Male; Middle Aged; Stroke; Treatment Outcome; Vitamin B 12; Young Adult

High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously.. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.. A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855).. Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

Topics: Aged; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Homocysteine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Placebos; Recurrence; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Previous studies have suggested that any benefits of folic acid-based therapy to lower serum homocysteine in prevention of cardiovascular events might be offset by concomitant use of antiplatelet therapy. We aimed to establish whether there is an interaction between antiplatelet therapy and the effects of folic acid-based homocysteine-lowering therapy on major vascular events in patients with stroke or transient ischaemic attack enrolled in the vitamins to prevent stroke (VITATOPS) trial.. In the VITATOPS trial, 8164 patients with recent stroke or transient ischaemic attack were randomly allocated to double-blind treatment with one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B(6), and 500 μg vitamin B(12)) and followed up for a median 3·4 years (IQR 2·0-5·5) for the primary composite outcome of stroke, myocardial infarction, or death from vascular causes. In our post-hoc analysis of the interaction between antiplatelet therapy and the effects of treatment with B vitamins on the primary outcome, we used Cox proportional hazards regression before and after adjusting for imbalances in baseline prognostic factors in participants who were and were not taking antiplatelet drugs at baseline and in participants assigned to receive B vitamins or placebo. We also assessed the interaction in different subgroups of patients and different secondary outcomes. The VITATOPS trial is registered with ClinicalTrials.gov, number NCT00097669, and Current Controlled Trials, number ISRCTN74743444.. At baseline, 6609 patients were taking antiplatelet therapy and 1463 were not. Patients not receiving antiplatelet therapy were more likely to be younger, east Asian, and disabled, to have a haemorrhagic stroke or cardioembolic ischaemic stroke, and to have a history of hypertension or atrial fibrillation. They were less likely to be smokers and to have a history of peripheral artery disease, hypercholesterolaemia, diabetes, ischaemic heart disease, and a revascularisation procedure. Of the participants taking antiplatelet drugs at baseline, B vitamins had no significant effect on the primary outcome (488 patients in the B-vitamins group [15%] vs 519 in the placebo group [16%]; hazard ratio [HR] 0·94, 95% CI 0·83-1·07). By contrast, of the participants not taking antiplatelet drugs at baseline, B vitamins had a significant effect on the primary outcome (123 in the B-vitamins group [17%] vs 153 in the placebo group [21%]; HR 0·76, 0·60-0·96). The interaction between antiplatelet therapy and the effect of B vitamins on the primary outcome was significant after adjusting for imbalance in the baseline variables (adjusted p for interaction=0·0204).. Our findings support the hypothesis that antiplatelet therapy modifies the potential benefits of lowering homocysteine with B-vitamin supplementation in the secondary prevention of major vascular events. If validated, B vitamins might have a role in the prevention of ischaemic events in high-risk individuals with an allergy, intolerance, or lack of indication for antiplatelet therapy.. Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, and Singapore National Medical Research Council.

Topics: Aged; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH.. We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini-Mental State Examination, Mattis dementia rating scale--initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters.. Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale--initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer's disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline.. Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer's pathology.

Topics: Aged; Atrophy; Brain; Cognition Disorders; Double-Blind Method; Female; Folic Acid; Humans; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Secondary Prevention; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Rapid aging of the population worldwide necessitates a heightened concern about preventing cognitive decline.. We investigated the effects of B vitamins and omega-3 (n-3) fatty acid supplementation on cognition in a high-risk population.. This was an ancillary study of the SU.FOL.OM3 (SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids) secondary prevention trial conducted in France between 2003 and 2009. The present sample included 1748 men and women aged 45-80 y with a history of myocardial infarction, unstable angina, or ischemic stroke and who were recruited via a network of 417 physicians. With the use of block randomization with stratification by sex, age, prior cardiovascular disease, and city of residence, participants were assigned in a 2 × 2 factorial design to 1 of 4 groups: 1) 5-methyltetrahydrofolate (folate, 0.56 mg) and vitamins B-6 (3 mg) and B-12 (0.02 mg), 2) eicosapentaenoic and docosahexaenoic acids (600 mg) in a 2:1 ratio, 3) B vitamins and omega-3 fatty acids, or 4) placebo. Cognitive function after 4 y of supplementation was assessed with the French version of the modified Telephone Interview for Cognitive Status.. No significant main effects of group assignment on cognitive function were found; however, we found some evidence of disease history- and age-specific effects. In the subgroup with prior stroke, for example, participants assigned to receive B vitamins plus omega-3 fatty acids were significantly less likely to have a decreased score on the temporal orientation task than were those assigned to receive placebo (odds ratio: 0.43; 95% CI: 0.21, 0.86).. If present, dietary effects on cognition are likely group-specific. These results could be useful in interventions aimed at preventing cognitive decline in high-risk individuals. This trial is registered at controlled-trials.com as ISRCTN41926726.

Topics: Aged; Aged, 80 and over; Cognition; Dementia; Dietary Supplements; Fatty Acids, Omega-3; Female; Folic Acid; Humans; Male; Middle Aged; Stroke; Vitamin B 12; Vitamin B 6

Homocysteine (Hcy) is an independent predictor of stroke. Coupling factor 6 (CF6) is regulated by nuclear factor kappa B (NF-kappaB) signaling which is activated by Hcy. We tested the hypothesis that CF6 is elevated with Hcy in stroke. We also examined the effect of vitamin treatment on CF6 and Hcy levels.. The 59 Japanese patients with a recent history of stroke were randomly assigned to a group without vitamin treatment (Group 1, n = 29) and to a group with treatment with both folic acid and vitamin B(12) for 2 months (Group 2, n = 30). The CF6 level was elevated in the patients with stroke compared with that in controls (n = 64) at admission. In a multiple regression model, the plasma CF6 level was weakly correlated to the total Hcy (tHcy) level. In Group 1, the plasma tHcy and CF6 levels were unchanged. In Group 2, however, they were both decreased, and there was a weak positive correlation between the decreases in plasma levels of CF6 and tHcy.. CF6 is elevated in patients with stroke independently of risk factors. Since Hcy and vitamin treatment affect CF6 levels in stroke, CF6 appears to be a novel molecule for the pathogenesis and treatment of stroke.

Topics: Aged; Female; Folic Acid; Homocysteine; Humans; Japan; Male; Middle Aged; Mitochondrial Proton-Translocating ATPases; Oxidative Phosphorylation Coupling Factors; Stroke; Vitamin B 12; Vitamin B Complex

Amyloid-beta protein (Abeta) plays a key role in Alzheimer disease (AD) and is also implicated in cerebral small vessel disease. Serum total homocysteine (tHcy) is a risk factor for small vessel disease and cognitive impairment and correlates with plasma Abeta levels. To determine whether this association results from a common pathophysiologic mechanism, we investigated whether vitamin supplementation-induced reduction of tHcy influences plasma Abeta levels in the Vitamin Intervention in Stroke Prevention (VISP) study.. Two groups of 150 patients treated with either the high-dose or low-dose formulation of pyridoxine, cobalamin, and folic acid in a randomized, double-blind fashion were selected among the participants in the VISP study without recurrent stroke during follow-up and in the highest 10% of the distribution for baseline tHcy levels. Concentrations of plasma Abeta with 40 (Abeta40) and 42 (Abeta42) amino acids were measured at baseline and at the 2-year visit.. tHcy levels significantly decreased with vitamin supplementation in both groups. tHcy were strongly correlated with Abeta40 but not Abeta42 concentrations. There was no difference in the change in Abeta40, Abeta42 (p = 0.40, p = 0.35), or the Abeta42/Abeta40 ratio over time (p = 0.86) between treatment groups. Abeta measures were not associated with cognitive change.. This double-blind randomized controlled trial of vitamin therapy demonstrates a strong correlation between serum tHcy and plasma Abeta40 concentrations in subjects with ischemic stroke. Treatment with high dose vitamins does not, however, influence plasma levels of Abeta, despite their effect on lowering tHcy. Our results suggest that although tHcy is associated with plasma Abeta40, they may be regulated by independent mechanisms.

Topics: Aged; Amyloid beta-Peptides; Cognition; Dose-Response Relationship, Drug; Double-Blind Method; Down-Regulation; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Osmolar Concentration; Peptide Fragments; Pyridoxine; Stroke; Treatment Failure; Vitamin B 12; Vitamin B Complex; Vitamins

Homocysteine may promote atherosclerosis by exacerbating inflammatory processes within the arterial wall. B-vitamin supplements reduce total plasma homocysteine concentrations (tHcy), but it is not known whether the treatment also reduces arterial wall inflammation. We used (18)F-fluorodeoxygluose positron emission tomography ((18)F-FDG PET) to investigate whether long-term homocysteine-lowering treatment alters arterial wall inflammation in patients with a history of ischemic stroke.. 30 stroke patients were randomly assigned to B-vitamin therapy (folic acid 2 mg, vitamin B(6) 25 mg and vitamin B(12) 0.5 mg) or placebo in a double-blind clinical trial. After a mean treatment period of 4.0 +/- 0.7 years, all subjects had tHcy, carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery measured and underwent an (18)F-FDG PET scan. Standardised uptake values (SUV) were measured at six sites in the carotid, femoral and aortic arteries. Areas of locally increased tracer uptake in the arterial wall ('hot spots') were also identified and counted.. Long-term B-vitamin treatment significantly reduced tHcy compared with placebo (8.4 micromol/l, 95% confidence interval, CI, 7.2-9.6 vs. 11.6 micromol/l, 95% CI 10.0-13.4, p = 0.002). The treatment did not affect mean arterial SUV (2.0 +/- 0.3 vitamins vs. 2.1 +/- 0.3 placebo, p = 0.65) or the number of hot spots (n = 1.1 +/- 1.0 vitamins vs. n = 1.2 +/- 1.0 placebo, p = 0.65). There was no significant correlation between mean arterial SUV and CIMT or FMD.. These results suggest that a long-term Hcy reduction with B vitamins does not affect arterial wall inflammation assessed by (18)F-FDG PET.

Topics: Aged; Aged, 80 and over; Aorta; Arteritis; Atherosclerosis; Brachial Artery; Carotid Arteries; Cross-Sectional Studies; Double-Blind Method; Drug Combinations; Female; Femoral Artery; Fluorodeoxyglucose F18; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Stroke; Time Factors; Treatment Outcome; Ultrasonography; Vasodilation; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Elevated total homocysteine is associated with a higher risk of cerebrovascular disease. It is not known whether lowering homocysteine impacts on stroke risk, both in terms of severity and ischemic vs hemorrhagic stroke subtypes. Our aim was to determine whether vitamin therapy reduces the risk of ischemic and hemorrhagic stroke, as well as stroke-related disability.. We analyzed stroke outcomes among participants of the Heart Outcomes Prevention Evaluation 2 (HOPE 2) trial that randomized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12, or matching placebo, for 5 years.. Among 5522 participants, stroke occurred in 258 (4.7%) individuals during a mean of 5 years of follow-up. The geometric mean homocysteine concentration decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. The incidence rate of stroke was 0.88 per 100 person-years in the vitamin therapy group and 1.15 per 100 person-years in the placebo group (hazard ratio [HR], 0.75; 95% CI, 0.59-0.97). Vitamin therapy also reduced the risk of nonfatal stroke (HR, 0.72; 95% CI, 0.54-0.95) but did not impact on neurological deficit at 24 hours (P=0.45) or functional dependence at discharge or at 7 days (OR, 0.95; 95% CI, 0.57-1.56). In subgroup analysis, patients aged younger than 69 years, from regions without folic acid food fortification, with higher baseline cholesterol and homocysteine levels, and those not receiving antiplatelet or lipid-lowering drugs at enrollment had a larger treatment benefit.. Lowering of homocysteine with folic acid and vitamins B6 and B12 did reduce the risk of overall stroke, but not stroke severity or disability.

Topics: Aged; Disability Evaluation; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Kaplan-Meier Estimate; Male; Middle Aged; Risk Factors; Severity of Illness Index; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamins

Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.. We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.. After a mean treatment period of 3.9 +/- 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 micromol/L, 95% CI 7.5 to 8.4 versus 11.8 micromol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 +/- 0.17 mm vitamins versus 0.83 +/- 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.. Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.

Topics: Aged; Carotid Arteries; Dietary Supplements; Double-Blind Method; Down-Regulation; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Regional Blood Flow; Stroke; Time Factors; Treatment Outcome; Tunica Intima; Tunica Media; Vasodilation; Vitamin B 12; Vitamin B 6; Vitamin B Complex

The associations of dietary folate, vitamin B(6), vitamin B(12), and methionine intakes with risk of stroke subtypes were examined among 26,556 male Finnish smokers, aged 50-69 years, enrolled in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Dietary intake was assessed at baseline by using a validated food frequency questionnaire. During a mean follow-up of 13.6 years, from 1985 through 2004, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were identified from national registers. In analyses adjusting for age and cardiovascular risk factors, a high folate intake was associated with a statistically significant lower risk of cerebral infarction but not intracerebral or subarachnoid hemorrhages. The multivariate relative risk of cerebral infarction was 0.80 (95% confidence interval: 0.70, 0.91; p(trend) = 0.001) for men in the highest versus lowest quintile of folate intake. Vitamin B(6), vitamin B(12), and methionine intakes were not significantly associated with any subtype of stroke. These findings in men suggest that a high dietary folate intake may reduce the risk of cerebral infarction.

Topics: Aged; Feeding Behavior; Finland; Folic Acid; Health Status; Humans; Male; Methionine; Middle Aged; Multivariate Analysis; Nutrition Surveys; Nutritional Status; Prospective Studies; Risk; Risk Assessment; Risk Factors; Smoking; Stroke; Vitamin B 12; Vitamin B 6

Increased plasma total homocysteine (tHcy) levels are a risk factor for stroke and can be reduced with vitamin therapy. However, data on the tHcy-lowering effects of vitamins are limited largely to white populations. Thus, we aimed to determine in Singaporean patients with recent stroke: (1) the efficacy of vitamin therapy (folic acid, vitamin B12, and B6) on lowering tHcy, and (2) whether efficacy is modified by Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism(s).. A total of 443 eligible patients were recruited after presenting with ischemic stroke within the past 7 months. Patients were randomized to receive either placebo or vitamins. Fasting blood samples collected at baseline and at 1 year were assayed for levels of plasma tHcy. Patients were genotyped for MTHFR C677T and A1298C polymorphisms.. Mean baseline tHcy was similar in the 2 groups (placebo 13.7 micromol/L; vitamins 14.0 micromol/L; P=0.70). At 1 year, mean tHcy was 14.5 micromol/L in the placebo group compared with 10.7 micromol/L in the vitamin group (difference 3.8 micromol/L; 95% CI, 2.8 to 4.8 micromol/L; P<0.0001). MTHFR C677T genotype was an independent determinant of tHcy levels at baseline (P=0.005), but A1298C was not (P=0.08). Neither polymorphism significantly influenced the effect of vitamin therapy on tHcy at 1 year. The magnitude of the reduction in tHcy levels at 1 year with vitamin therapy was similar, irrespective of MTHFR genotypes.. Vitamin therapy reduces mean tHcy levels by 3.8 micromol/L in the Singaporean stroke population studied. MTHFR C677T but not A1298C is independently associated with tHcy levels at baseline, and neither impacts the tHcy-lowering effect of vitamins used in this study.

Topics: Aged; Coronary Artery Disease; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Ischemic Attack, Transient; Male; Methylenetetrahydrofolate Dehydrogenase (NAD+); Middle Aged; Models, Statistical; Placebos; Polymorphism, Genetic; Regression Analysis; Risk Factors; Singapore; Stroke; Vitamin B 12; Vitamin B 6; Vitamins

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 a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction.. The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease.. The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05).. Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).

Topics: Adult; Aged; Aged, 80 and over; Death, Sudden, Cardiac; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Secondary Prevention; Stroke; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia has been identified as a risk factor for venous and arterial thrombosis especially in adult populations. Twenty-eight patients with an initial diagnosis of ischemic stroke and 100 controls, aged

Topics: Adolescent; Child; Child, Preschool; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Infant; Ischemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation, Missense; Polymorphism, Single Nucleotide; Retrospective Studies; Risk Factors; Stroke; Thailand; Thrombosis; Vitamin B 12

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

It is uncertain what impact increasing voluntary folate fortification may be having on the statistical power of randomized trials testing the homocysteine hypothesis of atherothrombosis. The objective of this study was to determine whether there has been a change in folate status between 1998 and 2002 in stroke patients randomized into the VITAmins TO Prevent Stroke (VITATOPS) Study at a single center in Perth, Australia, and what impact this may have had on the magnitude of the homocysteine-lowering effect achieved over time with folic acid-based multivitamin therapy.. We conducted a randomized, double-blind, placebo-controlled study involving 285 patients with stroke or transient ischemic attack who were recruited between 1998 and 2002 and randomized to long-term folic acid 2.0 mg/day, pyridoxine 25 mg/day and cobalamin 0.5 mg/day (active VITATOPS medication) or placebo. Fasting plasma total homocysteine, red cell folate, serum cobalamin and serum pyridoxine levels were measured at baseline and 6 months, and the change in blood levels over 4 time quartiles and differences in levels between the two randomized treatments were examined.. Between 1998 and 2002, there was a significant rise in baseline mean red cell folate levels over 4 time quartiles among the entire stroke cohort (723.3, 780.1, 922.6 and 1,023.7 nmol/l in the first, second, third and fourth quartiles, respectively; p < 0.0001), but this was not associated with a spontaneous reduction in mean baseline total homocysteine levels during the same time period (12.7, 14.3, 12.1 and 12.8 micromol/l in the first, second, third and fourth quartiles, respectively; p = 0.55). The homocysteine-lowering effect of the active VITATOPS trial medication at 6 months after randomization also did not change significantly between 1998 and 2002 (difference between randomized groups: -4.1, -4.1, -3.1 and -3.6 micromol/l in the first, second, third and fourth quartiles, respectively; p = 0.56).. The homocysteine-lowering effect of the active VITATOPS trial medication has not attenuated significantly in the past 5 years despite increasing voluntary fortification of foods with folic acid as reflected by a progressive rise in baseline folate status. These data suggest that in the continuing absence of a program of mandatory folate fortification of food in populations served by centers participating in the VITATOPS trial, the study will remain adequately powered to test the homocysteine-lowering hypothesis for which it was designed.

Topics: Aged; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Hematinics; Homocysteine; Humans; Male; Middle Aged; Pyridoxine; Stroke; Time Factors; Vitamin B 12

Stroke increases the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. Treatment with folate and mecobalamin (vitamin B12) may improve hyperhomocysteinemia.. To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke.. A double-blind, randomized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke, who were recruited from a single Japanese hospital from April 1, 2000, to May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate and 1500 microg of mecobalamin, or double placebo; 559 completed the 2-year follow-up.. Incidence of hip fractures in the 2 patient groups during the 2-year follow-up.. At baseline, patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group (P<.001). The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (P<.001). The adjusted relative risk, absolute risk reduction, and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI, 3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects were reported.. In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.

Topics: Aged; Bone Density; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Hemiplegia; Hip Fractures; Homocysteine; Humans; Male; Risk Factors; Stroke; Vitamin B 12

Our previous study showed that overuse of the nonparetic hand and wrist of the nonparetic side following stroke result in significantly more abnormal on the nonparetic side than on the hemiparetic side in terms of electrophysiologic indices of median nerve function. The purpose of this study was to evaluate the effects of the orally administered mecobalamin, an analogue of vitamin B12, for carpal tunnel syndrome (CTS) in the nonparetic side in patients following stroke. In a randomized open label and prospective study of stroke patients, 67 received of 1500 mug mecobalamin daily for 2 years, and the remaining 68 (untreated group) did not. At baseline, sensory nerve conduction velocity, motor nerve conduction velocity, sensory nerve action potentials (SNAP) at the wrist, palm-to-wrist distal sensory latency, palm-to-wrist SNAP, motor nerve conduction velocity compound motor action potentials, and distal motor latency of median nerve were significantly more abnormal on the nonparetic side than on the hemiparetic side or in controls. Before the treatment 21 patients (31%) of untreated and 20 patients (30%) of treated group met electrophysiologic criteria for CTS. Sensory impairment of the nonparetic side had lessened in the treated group. After 2 years, all electrophysiologic indices of nonparetic side were significantly improved in the treated group compared with those in the untreated group. The improvement from baseline of electrophysiologic parameters in sensory nerve in the treated group was greater than the improvement measured in motor nerve. There were no side effects. Oral mecobalamin treatment is a safe and potentially beneficial therapy for CTS in stroke patients.

Topics: Action Potentials; Administration, Oral; Aged; Carpal Tunnel Syndrome; Electric Stimulation; Extremities; Female; Functional Laterality; Humans; Male; Median Nerve; Neural Conduction; Prospective Studies; Reaction Time; Stroke; Vitamin B 12; Wrist

In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials.. To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins.. Double-blind randomized controlled trial (September 1996-May 2003).. 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland.. All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid.. Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes).. Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death.. In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Topics: Adult; Aged; Coronary Disease; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Myocardial Infarction; Recurrence; Risk; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6

Topics: Australia; Cohort Studies; Double-Blind Method; Edible Grain; Folic Acid; Food, Fortified; Humans; Hyperhomocysteinemia; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Sample Size; Secondary Prevention; Stroke; Thrombophilia; Treatment Outcome; Vitamin B 12; Vitamin B 6

Many new therapies are being developed that are anti-atherosclerotic, but which do not change clinical parameters such as blood pressure or cholesterol. In order to measure the effects of these therapies it will be necessary to measure atherosclerosis. Elevated levels of plasma total homocysteine (tHcy) are associated with increased risk of stroke and myocardial infarction. Measurement of the effect of vitamin therapy on atherosclerosis has therefore been used as an example of this approach.. 2-Dimensional measurement of carotid plaque cross-sectional area has been used to measure effects of vitamin therapy in patients whose plaque is progressing despite intensive treatment of traditional risk factors. In clinic patients, addition of vitamin therapy halted progression of atherosclerosis, in samples of 50 patients over 2.5 years. However, in patients randomized to high-dose vs. low-dose vitamins in the Vitamin Intervention for Stroke Prevention trial, no difference in plaque progression was seen between high-dose and low-dose vitamin therapy. New methods have been developed for the measurement of 3-dimensional plaque volume, and for the measurement of plaque surface roughness.. The accuracy and reliability of the measurement of plaque volume is 95%. This will permit measurement of effects of new anti-atherosclerotic therapies with much smaller sample sizes, in a much shorter time, than previously available methods such as intima-media thickness.. Measurement of atherosclerotic plaque volume and roughness will greatly enhance the study of new anti-atherosclerotic therapies.

Topics: Aged; Carotid Stenosis; Dose-Response Relationship, Drug; Folic Acid; Homocysteine; Humans; Imaging, Three-Dimensional; Reproducibility of Results; Stroke; Ultrasonography; Vitamin B 12; Vitamin B 6; Vitamins

Hyperhomocysteinemia is considered to be a risk factor for vascular diseases including ischemic stroke. It has been shown that plasma homocysteine level can be lowered by folic acid supplementation. Vitamin B(12) may be also beneficial when included in the supplement regimen with folic acid. We have examined in Japanese patients with ischemic stroke the homocysteine-lowering potential of a combination therapy with folic acid and vitamin B(12). Patients with ischemic stroke were randomized into three groups and each group received vitamin B(12) (1500 microg/day, n = 63), folic acid (5 mg/day, n = 64), or both vitamin B(12) and folic acid (n = 64) for 8 weeks. Plasma levels of homocysteine and these vitamins were followed. Significant reduction in plasma homocysteine was observed in all three groups, and the combination therapy yielded the most remarkable result, i.e., plasma total homocysteine was reduced by 38.5% and this was significantly larger than the reduction in other two groups (22.4% and 10.9% in the groups received folic acid and vitamin B(12), respectively). Vitamin B(12) synergizes with folic acid in reducing plasma homocysteine in Japanese patients with ischemic stroke and the combined therapy may be particularly effective in the secondary prevention.

Topics: Aged; Chronic Disease; Drug Synergism; Drug Therapy, Combination; Female; Folic Acid; Hematinics; Homocystine; Humans; Hyperhomocysteinemia; Japan; Male; Middle Aged; Stroke; Treatment Outcome; Vitamin B 12

In a randomized, placebo-controlled double-blind trial a combination of lofepramine, phenylalanine and vitamin B(12) was found to be effective in relieving the symptoms of multiple sclerosis (MS). The effect occurred within 2-4 weeks, and improved all types of symptoms in all types of MS. The combination was also effective in relieving symptoms in patients with chronic pain and chronic fatigue. We hypothesize that the action of this combined therapy may relate to activation of the noradrenergic locus coeruleus/lateral tegmentum (LC/LT) system which has the potential to influence the functioning of large areas of the brain and spinal cord.

Topics: Adrenergic Fibers; Adrenergic Uptake Inhibitors; Antidepressive Agents; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Fatigue Syndrome, Chronic; Humans; Locus Coeruleus; Lofepramine; Methylation; Multiple Sclerosis; Norepinephrine; Pain; Phenylalanine; Severity of Illness Index; Stroke; Stroke Rehabilitation; Tegmentum Mesencephali; Treatment Outcome; Vitamin B 12

Vitamin Intervention for Stroke Prevention (VISP) is designed to determine whether the utilization of folic acid, vitamins B(6) and B(12), in addition to other risk factor reducing measures, have a demonstrable effect on prevention of recurrent stroke. The entry criteria are a first-ever nondisabling stroke, the patient signs informed consent with willingness to participate and randomization to a high- or low-dose vitamin intervention regimen. Case acquisition of 3,688 individuals has been completed, half in the high-dose and the other half in the low-dose intervention arm. Follow-up is in progress and the end results are expected within the year. The Vitamins to Prevent Stroke (VITATOPS) is a parallel study based in Australia with similar goals, and, hopefully, the data from the two will be comparable and supportive.

Topics: Aged; Diet; Double-Blind Method; Electrocardiography; Endpoint Determination; Female; Folic Acid; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Recurrence; Risk Factors; Stroke; Vitamin B 12; Vitamin B 6; Vitamins

Homocysteine is a proposed causal risk factor for atherosclerosis, but this remains controversial. We measured fasting plasma homocysteine concentrations immediately after atherothrombotic stroke and in the convalescent period to investigate this controversy.. One hundred six patients (59 men and 47 women, mean age 57.2 [25 to 70] and 56.5 [26 to 69] years, respectively) were recruited within 24 hours of admission, and 82 patients were resampled at least 3 months later. Fasting total plasma homocysteine (tHcy) concentrations were measured by high-performance liquid chromatography.. Median tHcy in the acute phase of stroke was not significantly higher than in matched control subjects (men 9.2 [range 4.4 to 22.8] versus 8.7 [4.9 to 20] micromol/L, P:=0.09, Mann-Whitney U: test; women 8.1 [4.8 to 32.3] versus 7.6 [3.3 to 14.4] micromol/L, P:=0.58). Median plasma concentrations increased significantly in the convalescent period (from 8.5 [4.8 to 19.2] to 10.1 [4.3 to 31.5] micromol/L, P:<0.001, Wilcoxon signed rank test) and were then significantly higher than in control subjects in both men and women (P:=0.03 and 0.05, respectively, Mann-Whitney U: test). This did not appear to be explained by alteration in the known covariates red-cell folate, serum B(12), or creatinine concentrations.. Homocysteine concentrations are not elevated after recent atherothrombotic stroke but rise in the convalescent period. These data do not support the hypothesis that raised plasma homocysteine concentrations predate atherothrombotic stroke. Instead, they offer an explanation for the discrepancies between prospective and retrospective studies and suggest that elevated tHcy levels may be caused by the disease process itself.

Topics: Acute Disease; Adult; Aged; Arteriosclerosis; Brain; Case-Control Studies; Chromatography, High Pressure Liquid; Convalescence; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Intracranial Thrombosis; Lipids; Male; Middle Aged; Regression Analysis; Risk Factors; Scotland; Stroke; Stroke Rehabilitation; Tomography, X-Ray Computed; Vitamin B 12

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Chromatography, High Pressure Liquid; Female; Folic Acid; Humans; Hyperhomocysteinemia; Lipid Peroxides; Male; Nitric Oxide; Oxidative Stress; Predictive Value of Tests; Stroke; Vitamin B 12

Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease and stroke. Metformin is an old, relatively safe, first line therapy for T2DM; however, it has been associated with stroke.. To study the effects of metformin use and vitamin B12 deficiency on stroke rate among patients with T2DM.. We conducted a prospective study of patients admitted with ischemic stroke within 12 months (starting March 2020). We studied the clinical impact of metformin on vitamin B12 deficiency and stroke evolution. Student's t-test and ANOVA were used to compare the groups of patients and to determine whether there was any direct or indirect effect of metformin use on vitamin B12 deficiency and stroke.. In total, 80 patients were admitted with ischemic stroke. Clinical status and biochemical data were collected and compared with healthy volunteers. There were 39 diabetic patients, 16 took metformin for at least 1 year. Among those who took metformin for at least 1 year, 9 had vitamin B12 level < 240 pg/ml (56.2%); 23 diabetic patients did not get metformin and only 4 had vitamin B12 level < 240 pg/ml (17.4%) (P = 0.014).. T2DM is a significant risk factor to the development of ischemic stroke. We found an association between metformin use and vitamin B12 deficiency and an association between vitamin B12 deficiency and stroke risk in patients with T2DM. Diabetic patients who are taking metformin should monitor their vitamin B12 level.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Ischemic Stroke; Metformin; Prospective Studies; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Autonomic dysfunction is common in patients with ischemic stroke. An ischemic stroke may induce abnormalities in autonomic tone, resulting in poor heart rate regulation and an increased risk of severe cardiac arrest and sudden death. Heart rate variability (HRV) is a reliable index for evaluating autonomic dysfunction. Vitamin B12 deficiency is frequent among older adults and is a known risk factor for ischemic stroke. As vitamin B12 deficiency affects the peripheral nerves and the central nervous system, it can lead to autonomic dysfunction. However, no study has been published on the correlation between HRV and vitamin B12 status in patients with ischemic stroke. This study aimed to investigate the relationship between HRV and vitamin B12 status and to determine whether the serum vitamin B12 level can be a predictor of HRV parameters. This retrospective study enrolled patients with ischemic stroke between January 2015 and December 2022. The patients underwent serum vitamin B12 level measurements and 24-h Holter monitoring. Pearson correlation analysis was used to investigate the correlation between serum vitamin B12 levels and HRV parameters. The impact of serum vitamin B12 status on HRV parameters was determined using multiple linear regression analysis. A total of 87 patients with ischemic stroke were included in this study. HRV parameters were significantly correlated with serum vitamin B12 status in the frequency domain. In multiple linear regression analysis, the serum vitamin B12 status was a significant predictor of HRV parameters. HRV parameters may be correlated with serum vitamin B12 status in patients with ischemic stroke. Therefore, the serum vitamin B12 status may be a significant predictor of autonomic dysfunction. Our results may provide objective evidence for the impact of serum vitamin B12 status on autonomic dysfunction in patients with ischemic stroke.

Topics: Aged; Heart Rate; Humans; Ischemic Stroke; Primary Dysautonomias; Retrospective Studies; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Severely elevated serum homocysteine is a rare cause of ischaemic stroke and extra-cranial arterial and venous thrombosis. Several factors can lead to mild elevation of homocysteine including dietary folate and B12 deficiency, and genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The use of Anabolic androgenic steroid (AAS) is under-reported, but increasingly linked to ischaemic stroke and can raise homocysteine levels.. We present a case of a man in his 40s with a large left middle cerebral artery (MCA) territory ischaemic stroke and combined multifocal, extracranial venous, and arterial thrombosis. His past medical history was significant for Crohn's disease and covert use of AAS. A young stroke screen was negative except for a severely elevated total homocysteine concentration, folate and B12 deficiencies. Further tests revealed he was homozygous for the methylenetetrahydrofolate reductase enzyme thermolabile variant (MTHFR c.667 C > T). The etiology of this stroke was a hypercoagulable state induced by raised plasma homocysteine. Raised homocysteine in this case was likely multifactorial and related to chronic AAS use in combination with the homozygous MTHFR c.677 C > T thermolabile variant, folate deficiency and, vitamin B12 deficiency.. In summary, hyperhomocysteinemia is an important potential cause of ischaemic stroke and may result from genetic, dietary, and social factors. Anabolic androgenic steroid use is an important risk factor for clinicians to consider, particularly in cases of young stroke with elevated serum homocysteine. Testing for MFTHR variants in stroke patients with raised homocysteine may be useful to guide secondary stroke prevention through adequate vitamin supplementation. Further studies looking into primary and secondary stroke prevention in the high-risk MTHFR variant cohort are necessary.

Topics: Anabolic Androgenic Steroids; Brain Ischemia; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Ischemic Stroke; Male; Methylenetetrahydrofolate Reductase (NADPH2); Risk Factors; Stroke; Thrombosis; Vitamin B 12

Stroke remains the second leading cause of death world wide after ischaemic heart disease. Stroke occurs mainly due to infarction which accpounts for 85% of etiological factors and 15% due to hemorrhage. Hyperhomocysteinemia is associated with premature atherosclerosis and vascular events and it is an important risk factor for cerebrovascular accidents.. Case will be selected from patients admitted to medical wards in Navodaya Medical College, Raichur. Duration based study with a minimum of 50 cases for a period of 18 months from august 2019. In all patients admitted with symptoms suggestive of stroke careful methodical examination of central nervous system carried out recording all physical signs in order. In all cases with the help of close relatives the preceding symptoms and risk factors were enquired all patients were subjected to CT scan brain, CBC, FBS, PPBS, lipid profile and serum homocysteine levels were done.. In our study we observed that the serum homocysteine levels were elevated in ischemic stroke significantly. The mean serum homocysteine levels were higher in non diabetics(29.57 micromole/ litre) than diabetics (20.75 micromole/litre) and difference was statistically significant (P<0.001). Mean serum Homocysteine levels were higher in age group <65 years(28.73 micromole/litre) than patient age >65 years (20.50 micromole/litre) and the difference was statistically significant (p<0.001). Mean serum heomocysteine levels were higher in hypertensives (26.73 micromole/litre) than normotensive (23.28 micromole/litre) however the difference was statistically not significant (p>0.001).The mean serum homocysteine levels were higher in patients with normal lipid profile(30.97 micromole/litre) than patients with dyslipidemia (21.92 micromole/litre) and the difference was statistically significant (p<0.001).. The present study revealed that hyperhomocysteinemia appears to be an important risk factor for ischemic stroke. It is therefore important to use serum homocysteine as an important tool to investigate all cases of ischemic stroke and if serum homocysteine is elevated patient should be put on multivitamins containing vitamin B12, folic acid and pyridoxine to reduce serum homocysteine levels.

Topics: Aged; Homocysteine; Humans; Hyperhomocysteinemia; Ischemia; Ischemic Stroke; Lipids; Risk Factors; Stroke; Vitamin B 12

A vitamin B12 deficiency (vit. B12 def.) is common in the elderly, because of changes in metabolism. Clinical studies have reported that a vit. B12 def. results in worse outcome after stroke, and the mechanisms through which a vit. B12 def. changes the brain requires further investigation. This study investigated the role of vit. B12 def. on stroke outcome and mechanisms using aged female mice. Eighteen-month-old females were put on a control or vit. B12 def. diet for 4 weeks, after which an ischemic stroke was induced in the sensorimotor cortex. After damage, motor function was measured, the animals were euthanized, and tissues were collected for analysis. Vit. B12 def. animals had increased levels of total homocysteine in plasma and liver, and choline levels were also increased in the liver. Vit. B12 def. animals had larger damage volume in brain tissue and more apoptosis. The cecum tissue pathway analysis showed dysfunction in B12 transport. The analysis of mitochondrial metabolomics in brain tissue showed reduced levels of metabolites involved in the TCA cycle in vit. B12 def. animals. Motor function after stroke was impaired in vit. B12 def. animals. A dietary vit. B12 def. impairs motor function through increased apoptosis and changes in mitochondrial metabolism in brain tissue.

Topics: Animals; Brain; Cecum; Diet; Female; Folic Acid; Homocysteine; Ischemic Stroke; Mice; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Brain Ischemia; Folic Acid; Homocysteine; Humans; Ischemic Stroke; Stroke; Vitamin B 12

To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B. Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B. Vegetarians had lower serum vitamin B. Taiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.

Topics: Adult; Aged; Cohort Studies; Diet, Vegetarian; Female; Humans; Incidence; Male; Middle Aged; Stroke; Taiwan; Vitamin B 12

The prevalence of stroke increases with age and the ability to absorb all nutrients from our diets decreases with age. Nutrition is a modifiable risk factor for stroke, which is a leading cause of death and disability in world-wide. Deficiencies in one‑carbon metabolism, including in methyltetrahydrofolate reductase (MTHFR), have been linked to increased risk of stroke. The Mthfr

Topics: Aging; Animals; Brain; Choline; Dietary Supplements; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mice; Mice, Inbred C57BL; Recovery of Function; Stroke; Tetrahydrofolates; Vitamin B 12

Trials of B vitamin therapy to lower blood total homocysteine (tHcy) levels for prevention of stroke are inconclusive. Secondary analyses of trial data and epidemiological studies suggest that tHcy levels may be particularly associated with small vessel stroke (SVS). We assessed whether circulating tHcy and B vitamin levels are selectively associated with SVS, but not other stroke subtypes, using Mendelian randomization.. We used summary statistics data for single-nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B. Genetically predicted tHcy was associated with SVS, with an odds ratio of 1.34 (95% confidence interval [CI], 1.13-1.58; p = 6.7 × 10. These findings suggest that any effect of homocysteine-lowering treatment in preventing stroke will be confined to the SVS subtype. Whether genetic variants at or near the MTHFR and MUT genes influence SVS risk through pathways other than homocysteine levels and downstream effects require further investigation. Ann Neurol 2019;85:495-501.

Topics: Brain Ischemia; Homocysteine; Humans; Mendelian Randomization Analysis; Microvessels; Polymorphism, Single Nucleotide; Stroke; Vitamin B 12

The debated vascular risk potential of total homocysteine (tHcy), due to failed clinical trials designed on B vitamin supplementation, raises many possible explanations like the higher risk potential of the deleterious, free form of homocysteine (fHcy) or, the unchecked confounding effects of B-vitamins in tHcy-based association studies. Additionally, the cardiovascular risk probability of altered status of the homocysteine precursor, methionine (tMet) could shed light on the causality of association between tHcy and cardiovascular diseases. Hence, we aimed to evaluate the risk associations of elevated plasma levels of tHcy, fHcy and low levels of tMet with premature, ischemic stroke.. We recruited 171 young, ischemic stroke patients (aged ≤45 years) and 249 age- and gender-matched healthy controls. Plasma levels of fHcy, tHcy, tMet and vitamin B6 were estimated using HPLC coupled with coulometric electrochemical detection. Plasma levels of vitamin B12 and folate were estimated by radioimmunoassay.. Elevated fHcy (>2.9 μmol/L) was independently and strongly associated with the risk of premature, ischemic stroke (OR = 9.62, 95% CI = 3.51-26.40). On the contrary, association between premature ischemic stroke and elevated tHcy (>15.0 μmol/L) was found to attenuate when adjusted for vitamin B6 values (OR = 0.24, 95%, CI = 0.03-1.69). Interestingly, compromised B6-status (<59.2 nmol/l) was found to confer high risk of premature ischemic stroke (OR = 170.80, 95% CI = 58.22-501.06). We could not establish any significant correlation between fHcy and B-vitamin levels (P > 0.05). Low tMet (<13.86 μmol/L) was also not significantly associated with premature, ischemic stroke (OR = 2.53, 95% CI = 0.613-10.38).. Our results indicate significant but not-correlated, independent associations of fHcy and vitamin B6 with risk of premature, ischemic stroke. However, the causality of these associations need prospective and large scale validations. Further, our findings highlight the crucial confounding effects of B-vitamins on risk association between tHcy and premature ischemic stroke.

Topics: Adolescent; Adult; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Odds Ratio; Risk Factors; Stroke; Vitamin B 12; Vitamin B 6; Young Adult

Topics: China; Coronary Artery Disease; Folic Acid; Humans; Norway; Primary Prevention; Stroke; Uric Acid; Vitamin B 12; Vitamins

We explored the relationship between acute ischaemic stroke (IS) early functional outcome and serum levels of homocysteine, vitamin B12, and D in a noninterventional prospective clinical study. We enrolled 50 patients with first-ever IS and performed laboratory tests and functional assessment at three time points: on admission and three and six months after stroke. Modified Rankin Scale (mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all participants by trained examiner blinded to laboratory data. Patients did not receive treatment that might alter laboratory data. Admission NIHSS correlated with homocysteine levels (

Topics: Aged; Aged, 80 and over; Brain Ischemia; Female; Homocysteine; Humans; Male; Middle Aged; Recovery of Function; Stroke; Vitamin B 12; Vitamin D

This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051 ~ 1.206, P = 0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023 ~ 1.193, P = 0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081 ~ 1.334, 1.058 ~ 1.313, P = 0.001, P = 0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987 ~ 0.996, 0.991 ~ 0.999, P < 0.001, P = 0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels ma

Topics: Aged; Aged, 80 and over; Asian People; Case-Control Studies; Cerebrovascular Disorders; China; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Intracranial Arteriosclerosis; Kidney; Male; Middle Aged; Retrospective Studies; Stroke; Vitamin B 12

Both deficiency and, according to recent reports, excess of vitamin B12 (B12) are associated with increased mortality. Thus, it is difficult to estimate the effect of B12 on overall survival, which also depends on folate (FA) in homocysteine lowering. This study aimed to assess FA and B12 serum concentrations associated with long-term survival of vascular surgery patients by means of a prognostic index (PI).. This single-center, prospective cohort study comprised 485 consecutive carotid surgery patients. B-vitamin baseline concentrations of B12 and FA were used to compute a PI for postoperative overall survival from January 2003 to January 2012 (mean observation period 102.3 months).. Increasing B12 serum concentrations showed a nonlinear association with overall survival (P = .033). A B vitamin-based PI significantly predicted overall (hazard ratio [HR] per standard deviation = 1.97, confidence interval [CI] 1.37-2.82; P < .001), cardiovascular (HR = 3.03, CI 1.78-5.14; P < .001), and stroke-free survival (HR = 2.20, CI 1.22-3.98; P = .009), and revealed that the highest adverse event-free survival was predicted by high FA (16.3 ± 12.9 ng/mL) but only moderate B12 (360.3 ± 156.0 pmol/L) baseline concentrations.. Prediction of increased long-term overall, cardiovascular, and stroke-free survival is based on high FA but only moderate B12 serum concentrations. Excessive B12 concentrations might harbor a potential harm and are no requisite for low homocysteine concentrations. The association between B vitamins and survival might serve either as a tool for risk stratification or, if causative, as effective therapy, if optimal dosing of B vitamins is provided and on-treatment concentrations, including homocysteine and renal functions, are closely monitored.

Topics: Aged; Austria; Biomarkers; Carotid Stenosis; Disease-Free Survival; Endarterectomy, Carotid; Female; Folic Acid; Folic Acid Deficiency; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Nonlinear Dynamics; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.

Topics: Aged; Aged, 80 and over; Asian People; Brain Infarction; Female; Humans; Male; Middle Aged; Polymorphism, Genetic; Reduced Folate Carrier Protein; Republic of Korea; Stroke; Vitamin B 12

Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.

Topics: Case-Control Studies; CpG Islands; DNA Methylation; Epigenesis, Genetic; Female; Folic Acid; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Risk; Stroke; Vitamin B 12

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Stroke; Vitamin B 12; Vitamin B 12 Deficiency; Warfarin

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

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52 cm(3) vs 5.01 ± 6.00 cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Topics: Aged; Cerebral Cortex; Cerebral Small Vessel Diseases; Cognition Disorders; Disease Progression; Female; Folic Acid; Humans; Magnetic Resonance Imaging; Male; Stroke; Vitamin B 12; Vitamin B 6; White Matter

Clinical trials have failed to show a benefit of B vitamin therapy in reducing composite outcomes of cardiovascular death, myocardial infarction, and stroke among stroke survivors with elevated total serum homocysteine (tHcy) levels. Recent post hoc analyses have shown that numerous factors including age, baseline tHcy levels, folic acid fortification of grains, B12 status, renal function, comorbidities, and medications may modify the effect of B vitamin therapy on vascular risk in individuals with high tHcy. It remains possible that tHcy-lowering therapy may reduce cardiovascular risk in certain subgroups of stroke survivors. Post hoc subgroup analysis of the Heart Outcomes Prevention Evaluation-2 randomized controlled trial, which randomized participants with known cardiovascular disease to tHcy-lowering therapy or placebo, revealed larger treatment benefit for patients aged younger than 69 years; however, that analysis did not control for other factors. The aim of this study was to determine the effect of age on the impact of tHcy-lowering therapy for reducing vascular risk after stroke while controlling for other factors known to modify the effect of tHcy and tHcy-lowering therapy on vascular risk.. In this post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a randomized controlled trial of tHcy lowering for secondary stroke prevention, we excluded individuals who had poor renal function (glomerular filtration rate <47; the 10th percentile) or were treated with vitamin B12 injections. We assessed the effects of high-dose vitamin replacement on primary (stroke, myocardial infarction, or death) and secondary (stroke) outcomes, after stratifying by age (< vs. ≥ median age, 67 years) and adjusting for demographic and clinical factors.. This subgroup consisted of 2,993 individuals. Among individuals older than 67 years, high-dose vitamin therapy was associated with reduced risk of stroke, myocardial infarction or death (adjusted HR 0.76, 95% CI 0.58-0.99) and a trend towards reduced likelihood of stroke (adjusted HR 0.86, 95% CI 0.59-1.25). High-dose vitamin therapy did not impact outcomes among individuals younger than 67 years.. In this post hoc subgroup analysis of the VISP trial, age modified the association between B vitamin therapy and recurrent vascular risk among stroke survivors with elevated serum tHcy levels. Older individuals with stroke were more likely to benefit from B vitamin therapy than younger individuals. These findings can help inform the future design of clinical trials of tHcy-lowering therapy for cardiovascular risk reduction after stroke. © 2014 S. Karger AG, Basel.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Female; Homocysteine; Humans; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Stroke; Vitamin B 12; Vitamins

Recent studies have focussed on the association between elevated homocysteine levels with megaloblastic changes and thromboembolic events, but the relationship between occult megaloblastosis (with normal haemoglobin levels) and ischaemic stroke has not been widely explored. The objective of this study is to establish a simple and economical marker for the detection of occult megaloblastosis at the community health care level in developing countries. A hundred patients who met the inclusion criteria were studied. At the 5% level of significance, the levels of cobalamin and folate were significantly lower, while the number of hypersegmented neutrophils on the peripheral smear was higher in patients from Group A (70 patients with high homocysteine) compared with the patients in Group B (30 patients with normal homocysteine). Forty-five (64.2%) of the 70 patients in Group A showed hypersegmentation of neutrophils in the peripheral smear. The high cost and difficulty in performing the vitamin assays limit their use as early markers of megaloblastosis. Hence, we conclude that in developing countries, the detection of hypersegmented neutrophils can be used at the primary healthcare level for early diagnosis of occult megaloblastosis, so that early therapeutic interventions with vitamins can prevent attacks of hyperhomocysteinemia-induced ischaemic stroke.

Topics: Anemia, Megaloblastic; Biomarkers; Brain Ischemia; Early Diagnosis; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Neutrophils; Primary Health Care; Stroke; Vitamin B 12

Vascular cognitive impairment-no dementia (VCIND) refers to the early or mild cognitive impairment induced by cerebral vascular injury. Research shows that serum total homocysteine (tHcy) level is an independent risk factor for cerebral vascular disease and may be closely related to cognitive function.Current studies on the tHcy level in VCIND patients are limited, and the relationship of tHcy with cognitive function remains unclear. This study aims to investigate the tHcy levels in patients with VCIND and to determine their correlation with cognitive function, as well as to provide useful clues for preventing and treating VCIND.. The tHcy, folate, and vitamin B12 levels in 82 patients with VCIND were reviewed retrospectively and compared with those of 80 stroke patients without cognitive impairment and 69 healthy controls by using the Montreal Cognitive Assessment (MoCA) scale and the event-related potential P300 to evaluate cognitive function.. The tHcy levels in the VCIND group were higher than those in the other two groups, whereas the folate and Vitamin B12 levels in the VCIND group were lower than those of the other two groups. The tHcy levels in the stroke group were higher than those in the control group, and the folate and vitamin B12 levels in the stroke group were lower than those in the control group. The patients in the VCIND group with high tHcy exhibited lower MoCA scores and prolonged P300 latency than those in with normal tHcy. Correlation analysis showed that tHcy level is positively correlated with P300 latency period and negatively correlated with MoCA score.. The tHcy levels were significantly higher and the vitamin B12 and folate levels were significantly lower in the patients with VCIND than those in the other groups. The high tHcy levels in the VCIND patients may be correlated with impaired cognitive function.

Topics: Adult; Aged; Brain; Case-Control Studies; Cognition; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Stroke; Vitamin B 12

Therapy to lower homocysteine with B vitamins does reduce the risk of stroke, if not myocardial infarction. The apparent lack of efficacy of vitamin therapy in most of the large clinical trials was probably determined by the failure to take account of the metabolic deficiency of vitamin B12, which is very common and often missed, and by the failure to take account of impaired renal function. Metabolic B12 deficiency is present in 20% of people over 65 years of age, and in 30% of vascular patients above 70 years, so higher doses of B12 are needed in elderly patients. However, high-dose cyanocobalamin leads to accumulation of cyanide in patients with renal failure. B vitamin therapy is beneficial in patients with good renal function, but harmful in patients with significantly impaired renal function (a glomerular filtration rate <50). It seems likely that in patients with renal impairment, methylcobalamin should be used instead cyanocobalamin.

Topics: Aged; Clinical Trials as Topic; Glomerular Filtration Rate; Humans; Renal Insufficiency; Risk Factors; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Serum B12 concentrations, homocysteine plasma levels, the presence of retinopathy and history of macroangiopathy (stroke or coronary heart disease) were analyzed in patients without renal dysfunction (serum creatinine<115 μmol/L). Firstly, B12 status was analyzed in 62 consecutive metformin-treated patients. Secondly, the relationship between B12, homocysteine and vascular complications was analyzed in 46 metformin-treated and 38 age- and sex-matched non-metformin-treated patients. Among the 62 consecutive metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin dosage, the lower the B12 (P=0.02, Spearman's ρ=-0.30). There were independent correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12 lowering and elevation of homocysteine (P<0.01, r=-0.34). Elevation of homocysteine was a risk for retinopathy (P=0.02, OR 1.26, 95%CI 1.04-1.52). There was no significant relation between homocysteine and macroangiopathy. Correlation between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients. In ten B12 deficient patients, B12 supplementation (1,500 μg/day) for 2.2±1.0 months with continued use of metformin raised B12 levels: 152±42 and 299±97 pmol/L before and after treatment, respectively (P<0.01). Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy. Metformin-induced B12 deficiency was correctable with B12 supplementation.

Topics: Aged; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Dietary Supplements; Dose-Response Relationship, Drug; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Japan; Male; Metformin; Middle Aged; Prevalence; Risk Factors; Severity of Illness Index; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Down-Regulation; Homocysteine; Humans; Recurrence; Stroke; Vitamin B 12; Vitamin B 6

The author describes a 13-year-old Thai boy who developed stroke caused by carotid dissection and found mild elevation of plasma homocysteine (tHcy). The patient improved after anticoagulation therapy and his plasma tHcy decreased after vitamin supplement. With long-term follow-up, he is having normal neurological condition. This case proposes that the pathogenesis of carotid dissection may associate with mild hyperhomocysteinemia.

Topics: Adolescent; Anticoagulants; Brain; Carotid Artery, Internal; Carotid Artery, Internal, Dissection; Folic Acid; Humans; Hyperhomocysteinemia; Male; Stroke; Ultrasonography; Vitamin B 12

The functional point mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, has been reported to contribute to hyperhomocysteinaemia which is a risk factor for atherothrombotic ischaemic strokes. This study evaluated the prevalence of the C677T polymorphism of the gene in Malaysian ischaemic stroke subjects of Malay, Chinese and Indian ethnicities, and its association with homocysteine levels (tHcy).. A total of 292 subjects were recruited, comprising 150 ischaemic stroke patients and 142 control subjects who were age and sex matched. Plasma homocysteine, serum folate and vitamin B12 were measured in all subjects. Genotyping was carried out using PCR-RFLP.. The homocysteine levels were significantly higher (P = 0.001) in the stroke group (11.35 ± 2.75 μmol/L) compared to the control group (10.38 ± 2.79 μmol/L). The MTHFR C677T genotype distribution for the stroke group was 46%, 40% and 14%, respectively for CC, CT and TT genotypes and 59.9%, 33.8% and 6.3%, respectively for the control group. The genotype and allelic frequencies were significantly different between the 2 groups, with P = 0.02 and P = 0.004 respectively. No significant difference was seen in the genotype distribution inter-ethnically. An increasing tHcy was seen with every additional T allele, and the differences in the tHcy for the different genotypes were significant in both the control (P <0.001) and stroke groups (P <0.001).. This study shows that TT genotype of the methylenetetrahydrofolate reductase C677T polymorphic gene is an important determinant for homocysteine levels in Malaysian ischaemic stroke patients.

Topics: China; Ethnicity; Female; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; India; Malaysia; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Point Mutation; Polymorphism, Genetic; Stroke; Vitamin B 12

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

Migration to the UK is associated with higher incidence of stroke in African populations. A low folate status has been associated with increased risk of stroke, likely to be mediated through raised plasma homocysteine concentrations. We conducted a cross-sectional study to compare blood folate and homocysteine concentrations in eighty healthy Ghanaian migrants living in London matched by sex, age and occupation to 160 individuals from an urban population in Accra, Ghana. Folate intake was determined using three 24 h recalls. Fasting blood samples were collected for the determination of serum and erythrocyte folate and plasma homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR) 677C --> T polymorphism. Reported mean folate intake was 20 % lower in London compared with Accra (P < 0.001). However, serum folate was 44 % higher, erythrocyte folate 30 % higher and plasma homocysteine was 26 % lower in subjects from London compared with those from Accra (P < 0.001). These differences persisted after adjusting for confounders including the MTHFR 677C --> T mutation, which was rare in both populations. Although there were no associations between dietary folate intake and blood folates (P>0.05), folic acid supplement use, which was more prevalent in London than Accra (25 and 10 %, respectively, P = 0.004) was associated with erythrocyte folate in both populations (P < 0.01). The main predictors of plasma homocysteine concentrations were erythrocyte folate and male sex (P < 0.001). Findings from the present study suggest that migration from Ghana to the UK results in improvement of biomarkers of folate status despite the fact that reported dietary intake of folate was apparently lower in subjects from London.

Topics: Adult; Black People; Educational Status; Erythrocytes; Fasting; Female; Folic Acid; Ghana; Guinea; Homocysteine; Humans; Incidence; Male; Methylenetetrahydrofolate Dehydrogenase (NAD+); Polymorphism, Single Nucleotide; Smoking; Stroke; Urban Population; Vitamin B 12

The aim of this study was to investigate blood folic acid and vitamin B12 levels in patients with ischemic and hemorrhagic stroke patients and correlate these levels with prognosis.. Patients presenting within 3 hours of onset of ischemic or hemorrhagic strokes were approached for participation in the study. Diagnosis was made by clinical examination and head computed tomography scan. Venous blood samples were taken for determination of blood folic acid and vitamin B12 levels. Parameters were evaluated with respect to stroke type and according to Glasgow coma scale (< or =8 or > or =9).. Eighty-seven patients with ischemic stroke (mean age: 65 +/- 10 years, 53% male) and 27 patients with hemorrhagic stroke (mean age: 60 +/- 10 years, 56% male) were included in the study. A significant direct correlation was found between Glasgow coma scale and mean plasma B12 levels in ischemic, but not hemorrhagic, stroke (r=112.75 and p=0.007, respectively). A significant direct correlation was found between Glasgow coma scale and mean plasma folic acid levels in hemorrhagic, but not ischemic, stroke (r=1.03 and p=0.017, respectively). In patients with Glasgow coma scale < or =8 (either hemorrhagic or ischemic stroke), a significant direct correlation was found between Glasgow coma scale and blood vitamin B12 levels. Vitamin B12 levels were significantly lower in patients with Glasgow coma scale < or =8 than in patients with Glasgow coma score > or =9 (p=0.04).. In patients with ischemic stroke, low vitamin B12 levels, and in patients with hemorrhagic stroke, low blood folic acid levels, are associated with lower Glasgow coma scale values and higher hospital mortality.

Topics: Acute Disease; Aged; Biomarkers; Brain Ischemia; Female; Folic Acid; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prognosis; Stroke; Time Factors; Vitamin B 12

We sought to evaluate the magnetic resonance (MR) angiography (MRA) findings in patients with ischemic stroke (IS) from North India and correlate the changes with various conventional and nonconventional risk factors.. The study took place at a tertiary care teaching hospital. The patients with IS were clinically evaluated including body mass index, dietary habits, and family history of stroke. MR imaging, MRA, and testing for blood sugar, lipid profile, B12, folic acid, and homocysteine were carried out. The MRA abnormalities were considered significant if stenosis was 50% or greater and these were categorized into extracranial (EC), intracranial (IC), or combined lesions. The location of infarct on MR imaging was also noted.. There were 151 patients whose median age was 60 (22-85) years. The EC MRA was abnormal in 56.3% and the IC MRA in 63.3% of patients, the internal carotid artery being the most common site. Corresponding infarct was present in 64.7% and noncorresponding in 45.3% of patients. The MRA abnormality positively correlated with hypertension and diabetes, and negatively with alcohol consumption. The EC MRA abnormality was more common in upper caste Hindus and Muslims and in the city dwellers.. In North Indian patients with IS, the frequency of EC and IC MRA abnormality lies between Whites and the Orientals.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Biomarkers; Blood Glucose; Body Mass Index; Brain Ischemia; Carotid Artery, External; Carotid Artery, Internal; Diabetes Mellitus; Feeding Behavior; Female; Folic Acid; Homocysteine; Humans; Hypertension; India; Lipids; Magnetic Resonance Angiography; Male; Middle Aged; Racial Groups; Risk Factors; Socioeconomic Factors; Stroke; Vitamin B 12; Young Adult

Homocysteine, folate, and some group B vitamins have been proposed as a cause of Cerebro-Vascular Accidents (CVA). We conducted a case-control study to compare the plasma levels of folate, vitamin B12 and homocysteine in Iranian subjects with and without cerebro-vascular accident.. We recruited 82 patients with ischemic stroke as cases and 60 subjects as controls (using simple nonrandom sampling). Homocysteine was measured by fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured by an ion-capture method.. Mean plasma level of vitamin B12 in cases and controls were 358.4 ± 290.3 Pg/ml and 369.8 ± 110.4 Pg/ml, respectively which did not show any significant difference. Mean plasma level of folate in cases was significantly lower than the controls (6.8 ± 4.5 ng/ml vs. 12.2 ± 3.0 ng/ml, p = 0.001). It was also shown that mean plasma level of total homocysteine in cases was significantly higher than the controls (21.1 ± 9.8 μM/L vs. 13.5 ± 3.2 μM/L, P=0.001). Homocysteine and folate but not plasma B12 had linear relation with age. Male cases had significantly lower Folate and B12 in contrast to women. In addition, male cases had significantly higher Homocysteine level in contrast to women.. Our data shows that the level of homocysteine was higher and the level of folate was significantly lower in patients with ischemic stroke in contrast to controls. Effectiveness of supplementary folate and B 12 in such patients needs further well-structured prospective placebo controlled studies.

Topics: Aged; Case-Control Studies; Chromatography, High Pressure Liquid; Female; Folic Acid; Homocysteine; Humans; Iran; Male; Middle Aged; Stroke; Vitamin B 12

Hyperhomocysteinemia (HH) is an emerging risk factor for ischemic stroke but its role in outcome is controversial. We compare the risk factors, nature of stroke and outcome of patients with and without hyperhomocysteinemia.. CT proven ischemic stroke patients were included. The conventional risk factors such as diabetes, hypertension, hyperlipidemia, obesity, smoking, and family history of stroke were recorded. Dietary history was noted. Fasting serum homocysteine (Hcy), B12 and folic acid were estimated after 1 month of stroke. Severity of stroke was assessed by Canadian Neurological Scale (CNS) and outcome at 3 months by Barthel Index (BI) score into good (BI > or = 12) and poor (BI < 12). Serum Hcy, B12 and folic acid were also estimated in 200 normal healthy volunteers.. There were 198 patients with ischemic stroke whose median age was 56 years and 36 were females. In the study group, 41.4% patients were vegetarian, 55.1% hypertensive, 24.7% diabetic, 30.8% smoker, 61.1% sedentary and 28.8% obese. 23.2% had past history of stroke and 21.7% had stroke in their first degree relative. Serum cholesterol was elevated in 11.7% and LDL in 10.8% patients. Serum Hcy was elevated in 60.6% and serum B12 low in 25.7% and folic acid in 42.1%. Hcy levels correlated with serum B12 and LDL. Patients with hyperhomocysteinemia had significantly better outcome at 3 months. Hcy levels in stroke patients did not significantly differ from controls.. Hyperhomocysteinemia is found in 60.6% stroke patients, which is related to low serum B12 level. Patients with hyperhomocysteinemia had a better 3-month outcome.

Topics: Adult; Aged; Brain Ischemia; Comorbidity; Diabetes Mellitus; Diet, Vegetarian; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Hyperlipidemias; Hypertension; India; Male; Middle Aged; Obesity; Risk Factors; Severity of Illness Index; Smoking; Stroke; Tomography, X-Ray Computed; Vitamin B 12

Vitamin B-12 and folate deficiency are common, especially in people aged 55 or over, and accompanied by elevated methylmalonic acid (MMA) and homocysteine concentrations. The aims of the study were to investigate the relationship between serum vitamin B-12, homocysteine, folate, erythrocyte folate and urinary MMA in patients with ischemic stroke, and to develop a simple screening HPLC method for the measurement of urinary MMA.. Twenty-eight patients aged 55 years and over with ischemic stroke and 23 age- and sex- matched healthy controls were included in the study. Serum vitamin B-12 and folate were measured by immunoassay; serum total homocysteine and urinary MMA concentrations by HPLC.. There was no significant difference in vitamin B-12, folate and homocysteine concentrations between the patient and control groups. Urinary MMA concentrations and erythrocyte folate levels were significantly higher in patients than controls. There was a significantly negative correlation between vitamin B-12 and MMA.. Increased urinary MMA excretion is associated with ischemic stroke and it may more robustly reflect vitamin B-12 deficiency in patients with ischemic stroke. The method used in this study is eligible for routine urinary MMA measurements.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Creatinine; Female; Folic Acid; Homocysteine; Humans; Male; Methylmalonic Acid; Middle Aged; Stroke; Vitamin B 12

Blood-brain barrier dysfunction may be an early phenomenon in the development of the small vessel disease, which underlies white matter lesions. Because vitamin B12 plays a role in maintaining the integrity of the blood-brain barrier, we studied serum vitamin B12 level in relation to such lesions.. In 124 patients with first lacunar stroke, we measured serum vitamin B12 level and rated the degree of white matter lesions on MRI.. Mean vitamin B12 level was 202 pmol/L (SD, 68.9). Thirty-nine patients (31.5%) had a vitamin B12 level less than the lower reference value of 150 pmol/L. Lower vitamin B12 level was (statistically significant) associated with more severe periventricular white matter lesions (odds ratio/100 pmol/L decrease, 1.773; 95% CI, 1.001-3.003), but not with deep white matter lesions (odds ratio/100 pmol/L decrease, 1.441; 95% CI, 0.881-2.358; ordered multivariate regression analysis).. More severe periventricular white matter lesions in lacunar stroke patients relate to lower vitamin B12 levels. A possible causal relationship should now be studied prospectively.

Topics: Aged; Blood Vessels; Cerebrovascular Circulation; Female; Humans; Infant, Newborn; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Male; Middle Aged; Reference Values; Stroke; Ultrasonography; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Blood levels of total homocysteine (tHcy), cysteine (Cys), total and reduced glutathione (tGSH and rGSH), folic acid (FA), and vitamin B12 (B12) change during ischemic stroke as accompaniment of the tissue damage. The relationship between these changes remains scantly investigated. We evaluated the variation of these molecules in the 48 h after acute large artery atherothrombotic stroke (LAAS) and searched for the presence of matched variation of them. The study involved 50 subjects affected by acute LAAS and 49 healthy controls. Plasma levels of tHcy and Cys were significantly higher and serum levels of FA and B12 and plasma levels of rGSH were significantly lower in the patients than in the control group. Acute LAAS was associated with increased Hcy-decreased tGSH and decreased FA/tGSH. Pathways involved in cellular stress and in tissue repair are activated during acute LAAS.

Topics: Acute Disease; Aged; Aged, 80 and over; Brain Ischemia; Cysteine; Female; Folic Acid; Glutathione; Homocysteine; Humans; Hyperhomocysteinemia; Intracranial Thrombosis; Male; Middle Aged; Risk Factors; Stroke; Vitamin B 12; Vitamins

Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism.. Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO.. Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI, 1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26-16.2; p=0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021).. A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.

Topics: Adult; Blood Coagulation Tests; Embolism, Paradoxical; Female; Foramen Ovale, Patent; Homocysteine; Humans; Logistic Models; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke; Ultrasonography, Doppler, Transcranial; Vitamin B 12

Topics: Cohort Studies; Controlled Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Meta-Analysis as Topic; Myocardial Infarction; Prospective Studies; Retrospective Studies; Risk Factors; Stroke; Time Factors; Vitamin B 12; Vitamin B 6

To study the relationship between smoking and hyperhomocysteinemia (HHe) in ischemic stroke patients.. The clinical data of 329 ischemic stroke patients with HHe and 306 age-matched ischemic stroke patients without HHe, including sex, symptoms, signs, history of smoking, and plasma homocysteine (Hcy), folate, and vitamin B(12) concentrations were compared. The ischemic stroke lesions were divided into 2 subtypes: large vessel disease group and small vessel disease group according to the TOAST system.. The number of cigarettes smoked per day, cumulative year of smoking, and smoking index (number of cigarettes smoked per day X cumulative year of smoking), and ratio of males of the HHe group were all significantly higher than those of the non-HHe group, and the plasma homocysteine, folate, and vitamin B(12) concentrations of the HHe group were all significantly lower than those of the non-HHe group (all P < 0.01). Smoking index was positively correlated with the Hcy concentrations and negatively correlated with the folate and vitamin B(12) concentrations (all P < 0.01). The smoking proportion and Hcy concentration of the male patients were significantly higher than those of the female patients (both P < 0.01), and the plasma folate and vitamin B(12) concentrations of the male patients were all significantly lower than those of the female patients (P < 0.01 and P < 0.05). The number of cigarettes smoked per day, cumulative year of smoking, smoking index, and Hcy concentration of the large vessel disease group were all significantly higher than those of the small vessel disease group (all P < 0.01).. Smoking and being male may be the risk factors of HHe in ischemic stroke patients. Smoking and HHe are prone to cause lesion in large vessel.

Topics: Aged; Brain Ischemia; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Sex Factors; Smoking; Stroke; Vitamin B 12

Topics: Endothelium, Vascular; Humans; Hyperhomocysteinemia; Kidney Diseases; Leucovorin; Renal Dialysis; Stroke; Tetrahydrofolates; Vitamin B 12; Vitamin B 6

In children, clinical recognition of stroke and determination of its exact etiology are extremely difficult. The authors described a case of cryptogenic stroke in a 14-year-old-boy with asymptomatic atrial septal defect and hypercoagulable state. Paradoxical embolism was hypothesized as the responsible etiopathological mechanism. It is crucial to increase clinician awareness of stroke in children.

Topics: Adolescent; Age of Onset; Anticoagulants; Blood Coagulation Disorders, Inherited; Cerebral Arteries; Diffusion Magnetic Resonance Imaging; Folic Acid; Genetic Predisposition to Disease; Heart Septal Defects, Atrial; Hemianopsia; Humans; Hyperhomocysteinemia; Infarction, Posterior Cerebral Artery; Intracranial Embolism; Male; Occipital Lobe; Stroke; Vitamin B 12

High concentrations of homocysteine have been linked to a greater risk of Alzheimer disease, dementia, and cognitive decline.. We evaluated the association between homocysteine and 4.5-y combined incidences of dementia and cognitive impairment without dementia (CIND) in a cohort of 1779 Mexican Americans aged 60-101 y.. Homocysteine, red blood cell (RBC) folate, and plasma vitamin B-12 were measured at baseline. New cases of dementia or CIND were ascertained by neuropsychological and clinical examinations and expert adjudication. We used proportional hazards models to estimate the risk of homocysteine-associated dementia or CIND and the influence of RBC folate and plasma vitamin B-12 on that association.. High homocysteine concentrations were associated with a greater risk of dementia or CIND: hazard ratio (HR): 2.39; 95% CI: 1.11, 5.16. Plasma vitamin B-12 modified the association between homocysteine and the outcome. The rates of dementia or CIND associated with homocysteine for those in the lowest and highest tertiles of vitamin B-12, respectively, were significantly higher (HR: 1.61, P = 0.04) and lower (HR: 0.94, P = 0.015) than the risk for those in the middle tertile.. Homocysteine is an independent risk factor for both dementia and CIND. Higher plasma vitamin B-12 may reduce the risk of homocysteine-associated dementia or CIND.

Topics: Aged; Aged, 80 and over; Aging; California; Cognition Disorders; Dementia; Disease Susceptibility; Female; Folic Acid; Health Surveys; Hispanic or Latino; Homocysteine; Humans; Incidence; Male; Middle Aged; Risk Factors; Stroke; 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

Topics: Cause of Death; Drug Therapy, Combination; Folic Acid; Humans; Hyperhomocysteinemia; Multicenter Studies as Topic; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke; Survival Analysis; Vitamin B 12; Vitamin B 6

To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology.. Cross-sectional study.. Department of Neurology, Cardinal Tien Hospital.. Eighty-nine elderly post-stroke patients were enrolled for dietary assessment and blood tests. Neuroradiological assessment was done in 62 of these patients.. Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall system using a semi-quantitative questionnaire. Circulating levels of folate, B12, and tHcy were measured. Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy.. Mean folate and B12 intakes of these post-stroke patients were 69% and 261% of the recommended dietary allowances (RDA), respectively. Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these patients. Hyperhomocysteinemia levels (tHcy >or=15 micromol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273). After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7-56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1-81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels. No significant association was noted between vitamin B12 levels and brain lesions.. Our data shows that folate deficiency and hyperhomocysteinemia are prevalent in elderly post-stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy.

Topics: Aged; Biomarkers; Brain; Brain Infarction; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Magnetic Resonance Imaging; Male; Mental Recall; Nutrition Assessment; Nutrition Policy; Stroke; Surveys and Questionnaires; Vitamin B 12; Vitamin B Complex

Hyperhomocysteinemia is associated with cerebral small vessel disease (SVD). We examined the relationship between homocysteine and 1) volumetric measure of white matter change (WMC), 2) silent brain infarcts, 3) cerebral atrophy on MRI and 4) cognition on a consecutive cohort of patients with stroke associated with SVD.. Fifty-seven patients consecutively admitted to the Acute Stroke Unit in a university hospital due to stroke associated with SVD were recruited and assessed three months after the stroke. Non-fasting homocysteine was obtained. Using MRI, the number of infarcts, volume of WMC and cerebral atrophy were measured. General cognitive functions were assessed using the Mini Mental State Examination and Alzheimer's disease Assessment Scale. Mattis Dementia Rating Scale - Initiation/Perseveration subset was used to assess executive cognitive functions.. Hyperhomocysteinemia (> or = 14.88 micromol/L) significantly accounted for the volume of WMC on MRI in a multivariate stepwise regression model (adjusted R(2)=0.058, p <0.05) after adjustment for age and folate level. Patients in the highest quartile of WMC volume had significantly higher levels of homocysteine than those in lowest quartile (p <0.001). No significant relationship was found between homocysteine and silent brain infarcts, cerebral atrophy and performance on psychometric tests.. Hyperhomocysteinemia is associated with volumetric measure of WMC among patients with SVD. The role of homocysteine in the development of silent brain infarcts and cerebral atrophy as previously reported cannot be ascertained in this study. No direct relationship was found between homocysteine and cognitive functions.

Topics: Aged; Brain; Cerebrovascular Disorders; Cognition Disorders; Cohort Studies; Creatinine; Female; Homocysteine; Humans; Hyperhomocysteinemia; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychometrics; Regression Analysis; Risk Factors; Stroke; Vitamin B 12

Topics: Coronary Artery Disease; Homocysteine; Humans; Hyperhomocysteinemia; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Stroke; Vitamin B 12

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

Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C(677)T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects.. To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C(677)T MTHFR mutation.. Mean age was 67.7 years, and tHcy 18.2 micromol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects.. The allelic frequency of C(677)T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C(677)T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.

Topics: Aged; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Folic Acid; Gene Frequency; Heterozygote; Homozygote; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Peripheral Vascular Diseases; Polymorphism, Genetic; Risk Factors; Stroke; Vitamin B 12

Topics: Aged, 80 and over; Bias; Dose-Response Relationship, Drug; Folic Acid; Homocysteine; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke; Vitamin B 12; Vitamin B 6

Topics: Folic Acid; Hip Fractures; Humans; Multicenter Studies as Topic; Stroke; Vitamin B 12

In view of the prevailing controversy about the role of Methylenetetrahydrofolate reductase (MTHFR) C677T mutation in stroke and paucity of studies from India, this study has been undertaken to evaluate MTHFR C677T gene polymorphism in consecutive ischemic stroke patients and correlate these with folic acid, homocysteine (Hcy) and conventional risk factors.. Ischemic stroke patients prospectively evaluated in a tertiary care teaching hospital.. Computerized tomography proven ischemic stroke patients were prospectively evaluated including clinical, family history of stroke, dietary habits and addictions. Their fasting and postprandial blood sugar, lipid profile, vitamin B12, folic acid and MTHFR gene analysis were done.. MTHFR gene polymorphism was correlated with serum folic acid, Vitamin B12 and Hcy levels; family history of stroke in first-degree relatives; and dietary habits; employing Chi-square test.. There were 58 patients with ischemic stroke, whose mean age was 50 (4-79) years; among them, 10 were females. MTHFR gene polymorphism was present in 19 (32.8%) patients, 3 were homozygous and 16 were heterozygous. Both serum folate and B12 levels were low in 29 (50%) patients and Hcy in 48 (83%). Hypertension was present in 28 (48%) patients, diabetes in 12 (21%), hyperlipidemia in 52 (90%), smoking in 17 (29%), obesity in 1 (1.7%) and family history of stroke in first-degree relatives in 13 (22.4%). There was no significant relationship of MTHFR gene polymorphism with folic acid, B12, Hcy levels, dietary habits and number of risk factors. Vitamin B12 level was low in vegetarians (P<0.003). In 3 patients with MTHFR TT alleles, Hcy was elevated in all 3, low folic acid in 2 and family history of stroke in 1 patient.. MTHFR gene polymorphism was found in one-third of patients with ischemic stroke and was insignificantly associated with higher frequency of elevated Hcy.

Topics: Adolescent; Adult; Aged; Blotting, Northern; Chi-Square Distribution; Child; Child, Preschool; DNA Mutational Analysis; Female; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; India; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; RNA, Messenger; Stroke; Vitamin B 12

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Abortion, Habitual; Brain; Female; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Hyperhomocysteinemia; Infarction, Middle Cerebral Artery; Middle Aged; Mutation; Platelet Aggregation Inhibitors; Pregnancy; Stroke; Treatment Outcome; Vitamin B 12

Topics: Dietary Supplements; Folic Acid; Hip Fractures; Homocysteine; Humans; Risk Factors; Stroke; Vitamin B 12

Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B12, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms.. Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort.. Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71; P for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40; P for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55; P for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23; P for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype.. The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.

Topics: Adult; Aged; Brain Ischemia; Case-Control Studies; Cohort Studies; Diet; Female; Folic Acid; Hemorrhage; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Nutritional Status; Odds Ratio; Polymorphism, Genetic; Prospective Studies; Registries; Risk; Stroke; Sweden; Vitamin B 12

Topics: Bone Density; Dietary Supplements; Folic Acid; Hemiplegia; Hip Fractures; Humans; Stroke; Vitamin B 12

Topics: Aged; Female; Folic Acid; Hip Fractures; Homocysteine; Humans; Male; Stroke; Vitamin B 12

The Vitamin Intervention for Stroke Prevention trial (VISP) intention-to-treat analysis did not show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke. Reasons for lack of efficacy may have included folate fortification of grain products, inclusion of the recommended daily intake for B12 in the low-dose arm, treatment with parenteral B12 in patients with low B12 levels in both study arms, a dose of B12 too low for patients with malabsorption, supplementation with nonstudy vitamins, and failure of patients with significant renal impairment to respond to vitamin therapy. We conducted an efficacy analysis limited to patients most likely to benefit from the treatment, based on hypotheses arising from evidence developed since VISP was initiated. The criteria for this subgroup were defined before any data analysis.. For this analysis, we excluded patients with low and very high B12 levels at baseline (<250 and >637 pmol/L, representing the 25th and 95th percentiles), to exclude those likely to have B12 malabsorption or to be taking B12 supplements outside the study and patients with significant renal impairment (glomerular filtration rate <46.18; the 10th percentile).. This subgroup represents 2155 patients (37% female), with a mean age of 66+/-10.7 years. For the combined end point of ischemic stroke, coronary disease, or death, there was a 21% reduction in the risk of events in the high-dose group compared with the low-dose group (unadjusted P=0.049; adjusted for age, sex, blood pressure, smoking, and B12 level P=0.056). In Kaplan-Meier survival analysis comparing 4 groups, patients with a baseline B12 level at the median or higher randomized to high-dose vitamin had the best overall outcome, and those with B12 less than the median assigned to low-dose vitamin had the worst (P=0.02 for combined stroke, death, and coronary events; P=0.03 for stroke and coronary events).. In the era of folate fortification, B12 plays a key role in vitamin therapy for total homocysteine. Higher doses of B12, and other treatments to lower total homocysteine may be needed for some patients.

Topics: Aged; Disease-Free Survival; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Ischemia; Male; Middle Aged; Models, Statistical; Randomized Controlled Trials as Topic; Stroke; Time Factors; Treatment Outcome; Vitamin B 12; Vitamins

Topics: Drug Therapy, Combination; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Stroke; Vitamin B 12; Vitamin B 6

Folate, vitamin B6, and B12 deficiency are related to elevated blood homocysteine level. However, the effects of intakes of these vitamins on risk of stroke are still uncertain. This study examines intakes of folate, vitamin B6, and B12 in relation to risk of ischemic and hemorrhagic stroke.. We enrolled 43 732 men, aged 40 to 75 years, who were free of cardiovascular diseases and diabetes at baseline. Participants were followed from 1986 to 2000. Dietary information was assessed every 4 years using a detailed and validated semiquantitative food frequency questionnaire. The main outcome measures were incident ischemic and hemorrhagic strokes.. A total of 725 incident strokes, including 455 ischemic, 125 hemorrhagic, and 145 unknown types of stroke, were documented during the 14-year follow-up. After adjustment for major lifestyle and dietary factors, intake of folate was associated with a significantly lower risk of ischemic but not hemorrhagic stroke. The multivariate relative risk of ischemic stroke was 0.71 (95% CI, 0.52 to 0.96; P for trend=0.05) for men in the highest quintile of intake compared with those who in the lowest quintile. Intake of vitamin B12, but not B6, was also inversely associated with risk of ischemic stroke.. Our findings suggest that increased folate intake is associated with decreased risk of ischemic stroke in men.

Topics: Adult; Aged; Cohort Studies; Diet; Dietary Supplements; Folic Acid; Follow-Up Studies; Humans; Incidence; Life Style; Male; Middle Aged; Multivariate Analysis; Risk; Risk Assessment; Risk Factors; Stroke; Surveys and Questionnaires; United States; Vitamin B 12; Vitamin B 6

Topics: Antibodies, Antiphospholipid; Folic Acid; Homocysteine; Humans; Risk Factors; Risk Reduction Behavior; Stroke; Vitamin B 12; Vitamin B 6

We conducted a case-control study to evaluate the relationship between ischemic stroke in young adults (<45 years of age) and plasma homocysteine (Hcy), plasma folate and vitamin B(12), after a methionine load. We studied 42 patients with a history of ischemic stroke and 29 controls with a negative clinical history of cardio- or cerebrovascular diseases, venous thrombosis and renal disease. A fasting blood sample was drawn from each participant; the second and third samples were collected, respectively, 120 and 240 min after the methionine load. Whilst there was no difference between controls and patients in basal total homocysteine (tHcy), we found a statistically significant difference in both the 120- and 240-min samples. We compared the basal and 240-min tHcy in patients and controls. We obtained a median value of 17.8 and 11.6 micromol/l in patients and controls, respectively. The difference between these two values was highly significant. The methionine loading test (MLT) reveals Hcy metabolism abnormalities that were not revealed by the basal sample. MLT may help identify and treat this new risk factor, which seems to be both atherogenic and prothrombotic, and is hypothesized to operate through various mechanisms.

Topics: Adult; Case-Control Studies; Cysteine; Fasting; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Methionine; Middle Aged; Stroke; Time Factors; Vitamin B 12

To explore the association between high homocysteine levels and risk of Alzheimer disease (AD) in the Washington Heights-Inwood Columbia Aging Project (WHICAP).. The authors obtained fasting plasma samples in 909 elderly subjects chosen at random from a cohort of Medicare recipients; there was longitudinal data in 679 subjects without dementia at baseline who were followed for 3,206 person-years. Prevalent and incident dementia and its subtypes were diagnosed using standard methods.. There were 128 persons with prevalent AD and 109 with incident AD in 3,206 person-years of follow-up. The adjusted OR of prevalent AD for the highest quartile of homocysteine compared to the lowest was 1.3 (95% CI = 0.7, 2.3; p for trend = 0.25). In longitudinal analyses, the authors found that the adjusted hazard ratio of AD for the highest quartile of homocysteine was 1.4 (95% CI = 0.8, 2.4; p for trend = 0.31). The authors also found that high homocysteine levels were not related to a decline in memory scores over time. Age was a significant confounder in all the analyses. The study had 80% power to detect a hazard ratio of 1.3 in the longitudinal analyses.. High homocysteine levels were not associated with AD and were not related to a decrease in memory scores over time.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoproteins E; Cohort Studies; Comorbidity; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Cysteine; Dementia; Diabetes Mellitus; Ethnicity; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Male; Memory; Neuropsychological Tests; New York City; Prevalence; Risk Factors; Sampling Studies; Stroke; Vitamin B 12; Vitamin B 6

While the incidence of infectious diseases has been on the decline in developing countries, the toll of cardiovascular diseases, including stroke and myocardial infarction, has been increasing. The impression of physicians in certain regions of the western Sahel, including the state of Gombe in northeastern Nigeria, is that macrovascular disease in the indigenous population is on the rise. This study was, therefore, undertaken to compare well-established risk factors for cardiovascular disease in a group of 53 men (n=34) and women (n=19) in the town of Gombe who had suffered a stroke or heart attack with the corresponding parameters in 48 age- and gender-matched healthy adults living in the same environment. The parameters of cardiovascular diseases considered were: overweight and obesity, blood pressure, lipid profiles, and homocysteine. While the male and female patients who had suffered stroke (n=48) or heart attack (n=5) were borderline hypertensive, their mean body mass index values were not different from the corresponding values of their control groups. Although the serum homocysteine levels of the patients and controls were not significantly different, 85% of the stroke patients had serum homocysteine levels greater than 10 microM. These high homocysteine levels could not be accounted for by sub-optimal folate or vitamin B 12 status. The serum levels of HDL-cholesterol and triglyceride were not significantly different between the male and female patients and their respective controls. However, the males, but not the females, with macrovascular disease had significantly higher levels of total cholesterol (161 vs 137 mg/dL, p=0.04) and LDL-cholesterol (91 vs 70 mg/dL, p=0.02). In addition, both female and male stroke/myocardial infarction patients exhibited an elevated LDL-cholesterol/HDL-cholesterol ratio. These results indicate that blood pressure and the LDL-cholesterol/HDL-cholesterol ratio are associated with stroke and myocardial infarction in adults in northern Nigeria, thereby creating potential opportunities for possible public-health interventions.

Topics: Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Female; Folic Acid; Homocysteine; Humans; Hypertension; Lipids; Male; Middle Aged; Myocardial Infarction; Nigeria; Risk Factors; Stroke; Triglycerides; Vitamin B 12

Topics: Adult; Age Factors; Aged; Arteriosclerosis; Clinical Trials as Topic; Dementia; Diet; Drug Therapy, Combination; Female; Folic Acid; Fruit; Homocysteine; Humans; Hyperhomocysteinemia; Male; Myocardial Infarction; Prospective Studies; Risk Factors; Sex Factors; Stroke; Vegetables; Vitamin B 12; Vitamin B 6

The introduction of cereal grain folic acid fortification in 1998 has reduced homocyst(e)ine (tHcy) concentrations in the US population. We performed a case-control study to determine the risk of stroke and transient ischemic attack (TIA) associated with tHcy and low vitamin status in a postfortification US sample.. Consecutive cases with new ischemic stroke/TIA were compared with matched controls. Fasting tHcy, folate, pyridoxal 5'-phosphate (PLP), B12, and MTHFR 677C-->T genotype were measured.. Mean PLP was significantly lower in cases than controls (39.97 versus 84.1 nmol/L, P<0.0001). After stroke risk factors were controlled for, a strong independent association was present between stroke/TIA and low PLP (adjusted odds ratio [OR], 4.6; 95% CI, 1.4 to 15.1; P<0.001) but not elevated tHcy (OR, 0.92; 95% CI, 0.4 to 2.1).. Low B6 but not tHcy was strongly associated with cerebrovascular disease in this postfortification, folate-replete sample.

Topics: Case-Control Studies; Comorbidity; Edible Grain; Female; Folic Acid; Food, Fortified; Homocysteine; Homocystine; Humans; Ischemic Attack, Transient; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Odds Ratio; Oxidoreductases Acting on CH-NH Group Donors; Pyridoxal Phosphate; Risk Assessment; Risk Factors; Serum Albumin; Stroke; United States; Vitamin B 12; Vitamin B 6

Topics: Adult; Arteriosclerosis; Aspirin; C-Reactive Protein; Case-Control Studies; Contraceptives, Oral; Female; Fibrinogen; Folic Acid; Humans; Hyperhomocysteinemia; Inflammation; Male; Meta-Analysis as Topic; Migraine Disorders; Risk Factors; Smoking; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Vitamin B 12; Vitamin B 6

Topics: Anticoagulants; Humans; Hyperhomocysteinemia; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Treatment Outcome; Vitamin B 12

Topics: Adult; Blood Coagulation Disorders; C-Reactive Protein; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Meta-Analysis as Topic; Middle Aged; Primary Prevention; Prognosis; Pyridoxine; Risk Factors; Sinus Thrombosis, Intracranial; Stroke; Time Factors; Vitamin B 12

Topics: Adult; Aged; Alzheimer Disease; Arteriosclerosis; Brain; Cerebral Infarction; Folic Acid; Humans; Hyperhomocysteinemia; Male; Risk Factors; Stroke; Vitamin B 12

The aim of this study is to evaluate whether any relationship between stroke and vitamin B12, folic acid concentration. We examined 50 patients with stroke (male: 26 and female: 24) aged between (mean +/- SD, year) 59 +/- 14 and 16 control subjects (male: 6 and female: 10) aged between (mean +/- SD, year) 53 +/- 11. Patients were classified into two groups as infarct and hemorrhagic by using Computerised Brain Tomography and Cranial Nuclear Magnetic Resonance Imaging techniques. The percentage of patients with infract was 47.5% in female and 52.5% in male while it was 40% in female and 60% in male with hemorrhagic. The vitamin B12 levels of patients with infarct, hemorrhagic and control group were found as mean +/- SEM, 355 +/- 47 pg/ml, 313 +/- 58 pg/ml, 1569 +/- 258 pg/ml and folic acid levels 13.4 +/- 2.6 ng/ml, 7.7 +/- 1.0 ng/ml, 14.8 +/- 4.0 ng/ml, respectively. The significant difference was found between subgroups of patients with stroke and control group in both folic acid and B12 vitamin levels (p < 0.001 and p < 0.0001, respectively). But, there was no significant difference between vitamin B12 and folic acid levels of patients with hemorrhagic and infarct. In order to well understand the effects of these vitamin in patients with stroke, more detailed follow up studies with long period are needed.

Topics: Cerebral Hemorrhage; Cerebral Infarction; Female; Folic Acid; Humans; Male; Middle Aged; Stroke; Vitamin B 12

The aim of this study was to investigate a possible association among the thermolabile polymorphism, nucleotide 677 cytosine to thymidine point mutation (677 C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene, hyperhomocysteinemia, serum folate, vitamins B12 and B6, and stroke in children. Allele and genotype frequencies for the 677 C-->T polymorphism in 21 children with stroke and 28 healthy children of the same age were studied. No differences in allelic frequency were detected between the two populations. However, the prevalence of homozygous 677 C-->T was doubled in the stroke population (28.6%) compared to the healthy group (14.3%). Total plasma homocysteine (tHcy) levels were significantly increased in children aged 2 months to 15 years with stroke compared to reference values. No association was observed between the homozygous genotype (T/T) and hyperhomocysteinemia, nor between the T/T genotype and low folate levels (below the 95th percentile) in this group of patients. Vitamin concentrations in patients were not significantly different from reference values. Significant negative correlations were found between tHcy and folate and between tHcy and cobalamin, but not between tHcy and B6 concentrations. In summary, a higher prevalence of hyperhomocysteinemia and the 677 C-->T polymorphism were observed in children with stroke, but were not always associated. The systematic study of both abnormalities in children with stroke is recommended, so that hyperhomocysteinemia of any genetic origin can be corrected with vitamin supplementation. Moreover, the 677 C-->T genotype is a strong factor for predisposition to hyperhomocysteinemia and recurrent risk of stroke that might also be prevented with folate supplementation.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Cytosine; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Humans; Hyperhomocysteinemia; Infant; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Polymorphism, Genetic; Pyridoxine; Secondary Prevention; Stroke; Thymidine; Vitamin B 12; Vitamins

High circulating total homocysteine (tHcy) concentration, which is influenced by folate and vitamin B-12 status, is a suspected cause of cardiovascular events. This relation has been investigated in both case-control and prospective studies but has not been evaluated for different sex x age subgroups of the general U.S. population. We used data on adult (i.e., aged > or =40 y) male (n = 1097) and female (n = 1107) participants in the third National Health and Nutrition Examination Survey, excluding diabetics and those supplemented with estrogen, vitamins or minerals, to evaluate the association between serum tHcy concentration and self-report of heart attack or stroke. After adjustment for age, race-ethnicity, smoking, blood pressure, blood pressure medication, body mass index and serum concentrations of creatinine and cholesterol, past events were reported 2.4 (95% confidence interval 1.0-5.5) times as often by men with tHcy concentration of >12 micromol/L as by men with lower values. The odds ratio for women was 2.6 (95% confidence interval 1.1-6.6) after adjustment for the same factors plus menopausal status. A stronger relation in men aged < or =60 y compared with older men may help reconcile conflicting results of earlier studies.

Topics: Adult; Age Factors; Aged; Female; Folic Acid; Heart Arrest; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Nutrition Surveys; Risk Factors; Self Disclosure; Sex Factors; Stroke; Vitamin B 12

Homocysteine (HC) at concentrations of from 0.05 to 1.0 mM caused dose-dependent loss of [Mg2+]i in cultured cerebral vascular smooth muscle cells (VSMC), whereas cysteine and methionine (its metabolic products) failed to interfere with changes in [Mg2+]i. HC, methionine and cysteine did not produce any changes in [Ca2+]i. Lowering [Mg2+]o to 0.3 mM resulted in elevation of [Ca2+]i and loss of [Mg2+]i. Depletion of [Mg2+]i, induced by HC, was potentiated by low Mg2+. Preincubation of these cells with vitamin B6, vitamin B12, folic acid, alone, did not alter [Ca2+]i or [Mg2+]i. Likewise, concomitant addition of vitamin B6, vitamin B12, or folic acid, together with HC (1 mM) did not change the reduction in [Mg2+]i induced by HC. However, concomitant addition of HC and the three vitamins inhibited completely the loss of [Mg2+]i. Exposure of these cells to each vitamin, alone, or combination of the three vitamins failed to interfere with reduction in [Mg2+]i induced by low [Mg2+]i, but it did suppress the rise in [Ca2+]i. Interestingly, in the presence of low [Mg2+]o, the vitamin combination did not retard depletion of [Mg2+]i. The present findings are compatible with the hypothesis that an increased serum HC concentration causes abnormal metabolism of Mg2+ in cerebral VSMC, thus priming these cells for HC-induced atherogenesis, cerebral vasospasm and stroke. Our results suggest the need for the three B-vitamins, together with normal physiological levels of Mg2+, in order to prevent [Mg2+]i depletion and occlusive cerebral vascular diseases induced by homocysteinemia.

Topics: Animals; Arteriosclerosis; Basilar Artery; Calcium; Cells, Cultured; Cerebral Arteries; Dogs; Folic Acid; Homocysteine; Hyperhomocysteinemia; Magnesium; Microscopy, Fluorescence; Muscle, Smooth, Vascular; Pyridoxine; Signal Transduction; Stroke; Vitamin B 12; Vitamins