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Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial.

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

SUBMITTER: Song Y

PROVIDER: S-EPMC2712772 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial.

Song Yiqing Y Cook Nancy R NR Albert Christine M CM Van Denburgh Martin M Manson JoAnn E JE

Diabetes 20090602 8

<h4>Objective</h4>Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes.<h4>Research design and methods</h4>The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals ...[more]

PMID: 19491213

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Project description:An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B(12) (0.5 mg/d) and vitamin B(6) (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P =? 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P =? 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.Controlled-Trials.com ISRCTN94410159.

Project description:ObjectiveTo systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011.Study selectionRandomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and assessing the effect of folic acid based homocysteine lowering therapy. No language restrictions were applied.Data extractionTwo reviewers independently extracted data on study setting, design, and outcomes using a standardised form. The primary endpoint was cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality, or as defined by study author). Secondary endpoints included the individual composite components, all cause mortality, access thrombosis, requirement for renal replacement therapy, and reported adverse events, including haematological and neurological events. The effect of folic acid based homocysteine lowering on outcomes was assessed with meta-analysis using random effects models.Results11 trials were identified that reported on 4389 people with chronic kidney disease, 2452 with end stage kidney disease, and 4110 with functioning kidney transplants (10,951 participants in total). Folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P = 0.326) or any of the secondary outcomes. There was no evidence of heterogeneity in subgroup analyses, including those of kidney disease category, background fortification, rates of pre-existing disease, or baseline homocysteine level. The definitions of chronic kidney disease varied widely between the studies. Non-cardiovascular events could not be analysed as few studies reported these outcomes.ConclusionsFolic acid based homocysteine lowering does not reduce cardiovascular events in people with kidney disease. Folic acid based regimens should not be used for the prevention of cardiovascular events in people with kidney disease.

Project description:BackgroundHomocysteine has been postulated as a novel, potentially reversible risk factor for osteoporosis and related fractures. We evaluated whether homocysteine-lowering therapy with B-vitamins in patients with symptomatic cerebrovascular disease reduced the incidence of osteoporotic fractures.MethodsVITAmins To Prevent Stroke (VITATOPS) was a prospective randomised double-blind placebo-controlled trial in which 8,164 patients with recent (within 7 months) stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of either placebo (n = 4,075) or B-vitamins (folic acid 2 mg, vitamin B6 25 mg, vitamin B12 500 μg; n = 4,089). Patients were reviewed every six months. Any osteoporotic fracture and osteoporotic hip fractures were secondary outcome events, and were reviewed by a masked adjudication committee. Analysis was by intention to treat. Logistic regression was used to identify independent predictors of fracture.ResultsParticipants had a mean age of 62.6 years (SD 12.5 years) and 64% were male, 42% of Western European descent and 75% were functionally independent (Oxford Handicap Scale of two or less). After a median duration of 2.8 years therapy and 3.4 years follow-up, there was no significant difference in the incidence of any osteoporotic fracture between participants assigned B-vitamins (67 [1.64%]) and placebo (78 [1.91%]; risk ratio [RR] 0.86, 95% confidence interval [CI] 0.62-1.18) or the incidence of hip fractures (34 [0.83%] B-vitamins vs. 36 [0.88%] placebo; RR 0.94, 95% CI 0.59-1.5). There was no significant impact of B-vitamin therapy on time to first fracture. Baseline homocysteine levels did not predict any osteoporotic fracture (p =0.43). Independent predictors of any osteoporotic fracture were female sex, age > 64 years, Western European ethnicity and use of anti-osteoporosis medication at randomization (all p < 0.01).ConclusionsOnce daily treatment with B-vitamins had no effect on incidence of osteoporotic fractures during a median of 3.4 years follow-up in patients with cerebrovascular disease. A modest effect of B-vitamin therapy is not excluded due to the low numbers of fracture outcome events.

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

Project description:PurposeTo test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification.MethodsOne hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 μg folic acid, 8 mg vitamin B6, 6.4 μg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis.ResultsStatistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (β = -1.680, P = 0.004) and betaine (β = -1.421, P = 0.020) after 12 weeks of supplementation.ConclusionsDaily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia.Trial registrationThis trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Dataset Information

Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial.

Publications

Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial.

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