title: Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.
abstract: OBJECTIVE
  We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12supplementation 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 B12and 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 B12supplementation will be beneficial above and beyond normal dietary intake for brain health.
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. nikitavanderzwaluw@gmail.com.
authors.forename: Nikita L
authors.initials: NL
authors.lastname: van der Zwaluw
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. Elske.brouwer-brolsma@wur.nl.
authors.forename: Elske M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. ondine.vanderest@wur.nl.
authors.forename: Ondine
authors.initials: O
authors.lastname: van de Rest
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. PHjanneke.vanwijngaarden@gmail.com.
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. paulette.intveld@gmail.com.
authors.forename: Paulette H
authors.initials: PH
authors.lastname: In 't Veld
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. daniella_kourie@hotmail.com.
authors.forename: Daniella I
authors.initials: DI
authors.lastname: Kourie
authors.affiliation: 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. k.swart@vumc.nl.
authors.forename: Karin M A
authors.initials: KM
authors.lastname: Swart
authors.affiliation: Division of Internal Medicine, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. anke_enneman@hotmail.com.
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.affiliation: Division of Internal Medicine, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. s.c.vandijk@erasmusmc.nl.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Dijk
authors.affiliation: Division of Internal Medicine, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. n.vandervelde@erasmusmc.nl.|Department of Internal Medicine, Section Geriatric Medicine, Academic Medical Centre, Postbus 22660, 1100 DD Amsterdam, The Netherlands. n.vandervelde@erasmusmc.nl.
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
authors.affiliation: Department of Medical Psychology, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands. Roy.Kessels@radboudumc.nl.|Radboud Alzheimer Centre, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands. Roy.Kessels@radboudumc.nl.|Donders Institute for Brain, Cognition and Behavior, Radboud University, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Roy.Kessels@radboudumc.nl.
authors.forename: Roy P C
authors.initials: RP
authors.lastname: Kessels
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. Paul.smeets@wur.nl.|Image Sciences Institute, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Paul.smeets@wur.nl.
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Smeets
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. frans.kok@wur.nl.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Kok
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. rosalie.dhonukshe-rutten@wur.nl.
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.affiliation: Division of Human Nutrition, Wageningen University, Box 8129, 6700 EV Wageningen, The Netherlands. lisette.degroot@wur.nl.
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001921:Brain / Q000033:anatomy & histology*; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D009752:Nutritional Status; D009929:Organ Size; D053719:Tandem Mass Spectrometry; D014155:Transcobalamins / Q000032:analysis; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D015415:Biomarkers; D014155:Transcobalamins; D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12
keywords: brain volume; folate; grey matter; holotranscobalamin; homocysteine; methylmalonic acid; vitamin B12; white matter