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Nutrients 2017, 9(1), 8;

Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes

Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands
Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
Division of Internal Medicine, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
Department of Internal Medicine, Section Geriatric Medicine, Academic Medical Centre, Postbus 22660, 1100 DD Amsterdam, The Netherlands
Department of Medical Psychology, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
Radboud Alzheimer Centre, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
Donders Institute for Brain, Cognition and Behavior, Radboud University, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Image Sciences Institute, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
Author to whom correspondence should be addressed.
Received: 13 September 2016 / Revised: 26 November 2016 / Accepted: 14 December 2016 / Published: 24 December 2016
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism)
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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. View Full-Text
Keywords: homocysteine; vitamin B12; folate; holotranscobalamin; methylmalonic acid; brain volume; grey matter; white matter homocysteine; vitamin B12; folate; holotranscobalamin; methylmalonic acid; brain volume; grey matter; white matter

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van der Zwaluw, N.L.; Brouwer-Brolsma, E.M.; van de Rest, O.; van Wijngaarden, J.P.; In ’t Veld, P.H.; Kourie, D.I.; Swart, K.M.A.; Enneman, A.W.; van Dijk, S.C.; van der Velde, N.; Kessels, R.P.C.; Smeets, P.A.M.; Kok, F.J.; Dhonukshe-Rutten, R.A.M.; de Groot, L.C.P.G.M. Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes. Nutrients 2017, 9, 8.

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