Folate and vitamin B12-related biomarkers in relation to brain volumes

Nikita L. van der Zwaluw, Elske M. Brouwer-Brolsma, Ondine van de Rest, Janneke P. van Wijngaarden, Paulette H. In ’t Veld, Daniella I. Kourie, Karin M.A. Swart, Anke W. Enneman, Suzanne C. van Dijk, Nathalie van der Velde, Roy P.C. Kessels, Paul A.M. Smeets, Frans J. Kok, Rosalie A.M. Dhonukshe-Rutten, Lisette C.P.G.M. de Groot

Research output: Contribution to journalArticleAcademicpeer-review

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 articipants 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.

Original languageEnglish
Article number8
JournalNutrients
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

Cite this

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., ... de Groot, L. C. P. G. M. (2017). Folate and vitamin B12-related biomarkers in relation to brain volumes. Nutrients, 9(1), [8]. https://doi.org/10.3390/nu9010008
van der Zwaluw, Nikita L. ; Brouwer-Brolsma, Elske M. ; van de Rest, Ondine ; van Wijngaarden, Janneke P. ; In ’t Veld, Paulette H. ; Kourie, Daniella I. ; Swart, Karin M.A. ; Enneman, Anke W. ; van Dijk, Suzanne C. ; van der Velde, Nathalie ; Kessels, Roy P.C. ; Smeets, Paul A.M. ; Kok, Frans J. ; Dhonukshe-Rutten, Rosalie A.M. ; de Groot, Lisette C.P.G.M. / Folate and vitamin B12-related biomarkers in relation to brain volumes. In: Nutrients. 2017 ; Vol. 9, No. 1.
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title = "Folate and vitamin B12-related biomarkers in relation to brain volumes",
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 articipants 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.",
keywords = "Brain volume, Folate, Grey matter, Holotranscobalamin, Homocysteine, Methylmalonic acid, Vitamin B, White matter",
author = "{van der Zwaluw}, {Nikita L.} and Brouwer-Brolsma, {Elske M.} and {van de Rest}, Ondine and {van Wijngaarden}, {Janneke P.} and {In ’t Veld}, {Paulette H.} and Kourie, {Daniella I.} and Swart, {Karin M.A.} and Enneman, {Anke W.} and {van Dijk}, {Suzanne C.} and {van der Velde}, Nathalie and Kessels, {Roy P.C.} and Smeets, {Paul A.M.} and Kok, {Frans J.} and Dhonukshe-Rutten, {Rosalie A.M.} and {de Groot}, {Lisette C.P.G.M.}",
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van der Zwaluw, NL, Brouwer-Brolsma, EM, van de Rest, O, van Wijngaarden, JP, In ’t Veld, PH, Kourie, DI, Swart, KMA, Enneman, AW, van Dijk, SC, van der Velde, N, Kessels, RPC, Smeets, PAM, Kok, FJ, Dhonukshe-Rutten, RAM & de Groot, LCPGM 2017, 'Folate and vitamin B12-related biomarkers in relation to brain volumes' Nutrients, vol. 9, no. 1, 8. https://doi.org/10.3390/nu9010008

Folate and vitamin B12-related biomarkers in relation to brain volumes. / van der Zwaluw, Nikita L.; Brouwer-Brolsma, Elske M.; van de Rest, Ondine; van Wijngaarden, Janneke P.; In ’t Veld, Paulette H.; Kourie, Daniella I.; Swart, Karin M.A.; Enneman, Anke W.; van Dijk, Suzanne C.; van der Velde, Nathalie; Kessels, Roy P.C.; Smeets, Paul A.M.; Kok, Frans J.; Dhonukshe-Rutten, Rosalie A.M.; de Groot, Lisette C.P.G.M.

In: Nutrients, Vol. 9, No. 1, 8, 01.01.2017.

Research output: Contribution to journalArticleAcademicpeer-review

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.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of articipants 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.

AB - Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of articipants 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.

KW - Brain volume

KW - Folate

KW - Grey matter

KW - Holotranscobalamin

KW - Homocysteine

KW - Methylmalonic acid

KW - Vitamin B

KW - White matter

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U2 - 10.3390/nu9010008

DO - 10.3390/nu9010008

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JO - Nutrients

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van der Zwaluw NL, Brouwer-Brolsma EM, van de Rest O, van Wijngaarden JP, In ’t Veld PH, Kourie DI et al. Folate and vitamin B12-related biomarkers in relation to brain volumes. Nutrients. 2017 Jan 1;9(1). 8. https://doi.org/10.3390/nu9010008