TY - JOUR
T1 - Folate and vitamin B12-related biomarkers in relation to brain volumes
AU - van der Zwaluw, Nikita L.
AU - Brouwer-Brolsma, Elske M.
AU - van de Rest, Ondine
AU - van Wijngaarden, Janneke P.
AU - In ’t Veld, Paulette H.
AU - Kourie, Daniella I.
AU - Swart, Karin M A
AU - Enneman, Anke W.
AU - van Dijk, Suzanne C.
AU - van der Velde, Nathalie
AU - Kessels, Roy P C
AU - Smeets, Paul A M
AU - Kok, Frans J.
AU - Dhonukshe-Rutten, Rosalie A M
AU - de Groot, Lisette C P G M
N1 - Funding Information:
The authors gratefully acknowledge all study participants and our B-PROOF colleagues, with special thanks to Livia Ottenheijm, Annelies Ham, Natasja van Schoor, Paul Lips, and André Uitterlinden. We also gratefully thank Pauline Schaapsmeerders for her help with analyzing the MRI scans. The study was supported and funded by The Netherlands Organization for Health Research and Development (ZonMw, Grant 6130.0031), the Hague; unrestricted grant from NZO (Dutch Dairy Association), Zoetermeer; NCHA (Netherlands Consortium Healthy Ageing) Leiden/Rotterdam; MCO Health, Almere; Ministry of Economic Affairs, Agriculture and Innovation (project KB-15-004-003), the Hague; Wageningen University, Wageningen; VU University Medical Center, Amsterdam; Erasmus Medical Center, Rotterdam. All organizations are based in The Netherlands. The sponsors did not have any role in the design or implementation of the study, data collection, data management, data analysis, data interpretation, or in the preparation, review, or approval of the manuscript.
Publisher Copyright:
© 2016 by the author; licensee MDPI, Basel, Switzerland.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - AIM: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B
12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B
12 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 B
12, 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 B
12, 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 B
12 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 B
12 supplementation will be beneficial above and beyond normal dietary intake for brain health.
AB - AIM: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B
12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B
12 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 B
12, 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 B
12, 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 B
12 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 B
12 supplementation will be beneficial above and beyond normal dietary intake for brain health.
KW - Brain volume
KW - Folate
KW - Grey matter
KW - Holotranscobalamin
KW - Homocysteine
KW - Methylmalonic acid
KW - Vitamin B
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85008191240&partnerID=8YFLogxK
U2 - 10.3390/nu9010008
DO - 10.3390/nu9010008
M3 - Article
C2 - 28029114
AN - SCOPUS:85008191240
VL - 9
JO - Nutrients
JF - Nutrients
IS - 1
M1 - 8
ER -