Effect of Homocysteine-Lowering Treatment With Folic Acid and B Vitamins on Risk of Type 2 Diabetes in Women

Abstract

OBJECTIVEHomocysteinemia 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.RESEARCH DESIGN AND METHODSThe Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged ≥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.RESULTSDuring 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).CONCLUSIONSLowering 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.

The Impact of Supplementation with Folic Acid on Homocysteine Concentration and Selected Lipoprotein Parameters in Patients with Primary Hypertension

“…As a result, the number of patients suffering from primary hypertension and hyperhomocysteinaemia dropped from 35.7% to 7.1%. Similarly, the reduction of homocysteine concentration after the administration of folic acid was also observed by Mierzecki et al, Sultan et al, and others (8)(9)(10)(11). The administration of folic acid seems to be beneficial as a consequence of the reduction of homocysteine concentration.…”

“…The results of the first population cohort studies showed that a lowering of the homocysteine concentration by 3 mmol/L (through the intake of folic acid) mitigates the risk of development of cardiovascular diseases by 11-16%, and cerebral stroke by 19-24% (22). Recent intervention studies, such as HOPE-2, NORVIT, WAFAC and VISP, however, have not discovered any benefits of the supplementation with folic acid combined with the intake of vitamin B12 and B6, with the exception of a decrease in the number of cerebral strokes (11,(23)(24)(25). Therefore, some researchers hypothesise that homocysteine is not a risk factor of cardiovascular diseases but only a signal of disturbances related to atherosclerotic processes in the vessel wall (26,27).…”

Dietary methyl-consuming compounds and metabolic syndrome

“…20,21 However, increasing evidence from clinical trials indicates that although folic acid and vitamin B 12 supplementation could reduce plasma homocysteine levels, they have no effect on T2D and cardiovascular events. [22][23][24][25] This implies that the increased prevalence of CVD may not be a simple matter of folate deficiency. Moreover, excessive folic acid may lead to a waste of labile methyl-group donors.…”

“…In fact, studies have demonstrated that folic acid supplementation neither lowers SAH, nor increases SAM, nor alters SAM/SAH ratio. 76 This may explain why folic acid supplementation has generally failed to reduce vascular events in clinical trials, [22][23][24][25] or even has potential harmful effect on individuals with high homocysteine at baseline. 24 It should be pointed out that in most case, the reverse association between low vegetable intake and metabolic syndrome-related diseases is attributed to folate deficiency.…”

The Management of Peripheral Arterial Disease (PAD) in Primary Care

“…Supplementation with Bvitamins, especially folate, reduces plasma homocysteine levels. Multiple trials based on the hypothesis that folate supplementation would reduce homocysteine levels and lead to a reduction in cardiovascular risk have failed to show any beneficial results (Lonn, 2008, Toole et al, 2004, Song et al, 2009. Therefore, B-vitamin supplementation cannot currently be recommended for the prevention of CVD events and there is no role for the routine screening for elevated homocysteine levels.…”