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Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women.

ABSTRACT: Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression.To test whether long-term B-vitamin/folate supplementation reduces depression risk.Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women's Antioxidant and Folic Acid Cardiovascular Study - a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms.There were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86-1.21, P = 0.81), despite significant homocysteine level reduction.Long-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women.

SUBMITTER: Okereke OI

PROVIDER: S-EPMC4381191 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women.

Okereke Olivia I OI Cook Nancy R NR Albert Christine M CM Van Denburgh Martin M Buring Julie E JE Manson JoAnn E JE

The British journal of psychiatry : the journal of mental science 20150108 4

<h4>Background</h4>Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression.<h4>Aims</h4>To test whether long-term B-vitamin/folate supplementation reduces depression risk.<h4>Method</h4>Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women's Antioxidant and Folic Acid Cardiovascular Study - a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combin ...[more]

PMID: 25573400

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Project description:BACKGROUND:It has been proposed that maternal folic-acid supplement use may alter the DNA-methylation patterns of the offspring during the in-utero period, which could influence development and later-life health outcomes. Evidence from human studies suggests a role for prenatal folate levels in influencing DNA methylation in early life, but this has not been extended to consider persistent effects into adulthood. METHODS:To better elucidate the long-term impact of maternal folic acid in pregnancy on DNA methylation in offspring, we carried out an epigenome-wide association study (EWAS) nested within the Aberdeen Folic Acid Supplementation Trial (AFAST-a trial of two different doses: 0.2 and 5?mg, folic acid vs placebo). Offspring of the AFAST participants were recruited at a mean age of 47?years and saliva samples were profiled on the Illumina Infinium Human Methylation450 array. Both single-site and differentially methylated region analyses were performed. RESULTS:We found an association at cg09112514 (p?=?4.03×10-9), a CpG located in the 5' untranslated region of PDGFRA, in the main analysis comparing the intervention arms [low- (0.2?mg) and high-dose (5?mg) folic acid combined (N?=?43)] vs placebo (N?=?43). Furthermore, a dose-response reduction in methylation at this site was identified in relation to the intervention. In the regional approach, we identified 46 regions of the genome that were differentially methylated in response to the intervention (Sidak p-value <0.05), including HLA-DPB2, HLA-DPB1, PAX8 and VTRNA2-1. Whereas cg09112514 did not replicate in an independent EWAS of maternal plasma folate, there was suggested replication of differential methylation in PAX8. CONCLUSIONS:The results of this study suggest that maternal folic-acid supplement use is associated with changes in the DNA methylation of the offspring that persist for many years after exposure in utero. These methylation changes are located in genes implicated in embryonic development, immune response and cellular proliferation. Further work to investigate whether these epigenetic changes translate into detectable phenotypic differences is required.

Project description:BackgroundThe Aspirin/Folate Polyp Prevention Study previously found folic acid increased risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 y after randomization.ObjectiveWe conducted secondary analyses to evaluate folic acid effects with additional follow-up after treatment was stopped.MethodsIn total, 1021 participants recently diagnosed with colorectal adenomas were randomly assigned to 1 mg/d of folic acid (n = 516) or placebo (n = 505), with or without aspirin, beginning 6 July 1994. The original 3-y treatment period was extended into a subsequent colonoscopy interval, but eventually stopped prematurely on 1 October 2004. With additional post-treatment follow-up, a total of 663 participants who extended treatment completed a second colonoscopic surveillance interval after the initial 3-y follow-up. In addition, 490 participants provided information regarding a subsequent surveillance colonoscopy occurring before completion of follow-up on 31 May 2012, including 325 who had agreed to extended treatment. Study endpoints included conventional adenomas, sessile serrated adenomas/polyps (SSA/Ps), or colorectal cancer, and RRs with 95% CIs were adjusted for baseline characteristics associated with availability of follow-up.ResultsAmong those who extended treatment, any colorectal neoplasia was found in 118 (36%) participants assigned to placebo and 146 (43%) assigned to folic acid during the second surveillance interval (RR: 1.21; 95% CI: 0.99, 1.47; P = 0.06). Increased risk of SSA/P with extended folic acid supplementation was statistically significant during the second surveillance interval (RR: 1.94; 95% CI: 1.02, 3.68; P = 0.04). There was no evidence of post-treatment effects for any colorectal neoplasia (RR: 1.01; 95% CI: 0.80, 1.28; P = 0.94), and the post-treatment effect for SSA/P was no longer statistically significant (RR: 1.38; 95% CI: 0.59, 3.19; P = 0.46).ConclusionsDelayed treatment effects were not observed, but folic acid may increase SSA/P risk. This trial was registered at clinicaltrials.gov as NCT00272324.

Dataset Information

Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women.

Publications

Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women.

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