Abstract
Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. Methods: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = −0.91, 95% CI −1.85–0.03; p = 0.06) and between serum folate and TBV (β = −0.20, 95% CI −0.38, −0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058–1069 mL) than the non-supplemented group (1072, 95% CI 1067–1078 mL, p = 0.03). Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health.
Highlights
Elevated homocysteine (Hcy) levels have been associated with faster cognitive decline, cognitive impairment and dementia [1], by neurotoxicity or via other, probably vascular, pathways [2].Remethylation of Hcy into methionine is dependent of vitamin B12 and folate
The Netherlands; VU medical center, Erasmus Medical Centre, and Wageningen University. Primary objective of this randomized, double-blind, placebo-controlled intervention study was to assess the efficacy of lowering homocysteine levels, by two years oral supplementation with 400 μg folic acid and 500 μg vitamin B12, in the prevention of osteoporotic fractures
In the B-vitamin group, a trend was observed for Hcy and grey matter volume (β = −2.53, 95% confidence interval (95% CI) −5.24–0.19), but not for white matter volume
Summary
Remethylation of Hcy into methionine is dependent of vitamin B12 and folate. Low intake or low status of these vitamins can result in elevated Hcy levels, and as such, negatively affect cognitive health. A low vitamin B12 status is characterized by low levels of serum B12 and holotranscobalamin (holoTC), and high levels of methylmalonic acid (MMA) and Hcy [3]. Observational studies have shown associations between vitamin B12 and folate with cognitive performance. Most of the intervention studies, did not show an effect of supplementation with vitamin B12 and folic acid on cognitive performance, despite a lowering effect on Hcy concentrations [4]. Relatively new, method to investigate the role of vitamin B12 , folate and Hcy in brain health, is by studying brain volumes
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