Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial

Background & aims: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5–7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. Methods: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2–3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. Results: A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51–58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0–76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62–1.59 and HR: 0.77; 95% CI: 0.50–1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80–1.44 and OR: 0.85; 95%CI: 0.50–1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present. Conclusions: This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.

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Main Authors: Oliai Araghi, Sadaf, Kiefte-de Jong, Jessica C., van Dijk, Suzanne C., Swart, Karin M.A., Ploegmakers, Kim J., Zillikens, M.C., van Schoor, Natasja M., de Groot, Lisette C.P.G.M., Lips, Paul, Stricker, Bruno H., Uitterlinden, André G., van der Velde, Nathalie
Format: Article/Letter to editor biblioteca
Language:English
Subjects:B-vitamins, Cardiovascular disease, Fracture, Long-term follow-up,
Online Access:https://research.wur.nl/en/publications/long-term-effects-of-folic-acid-and-vitamin-b12-supplementation-o
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spelling dig-wur-nl-wurpubs-5690962024-10-30 Oliai Araghi, Sadaf Kiefte-de Jong, Jessica C. van Dijk, Suzanne C. Swart, Karin M.A. Ploegmakers, Kim J. Zillikens, M.C. van Schoor, Natasja M. de Groot, Lisette C.P.G.M. Lips, Paul Stricker, Bruno H. Uitterlinden, André G. van der Velde, Nathalie Article/Letter to editor Clinical Nutrition 40 (2021) 3 ISSN: 0261-5614 Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial 2021 Background & aims: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5–7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. Methods: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2–3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. Results: A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51–58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0–76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62–1.59 and HR: 0.77; 95% CI: 0.50–1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80–1.44 and OR: 0.85; 95%CI: 0.50–1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present. Conclusions: This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated. en application/pdf https://research.wur.nl/en/publications/long-term-effects-of-folic-acid-and-vitamin-b12-supplementation-o 10.1016/j.clnu.2020.07.033 https://edepot.wur.nl/530240 B-vitamins Cardiovascular disease Fracture Long-term follow-up https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ Wageningen University & Research
institution WUR NL
collection DSpace
country Países bajos
countrycode NL
component Bibliográfico
access En linea
databasecode dig-wur-nl
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region Europa del Oeste
libraryname WUR Library Netherlands
language English
topic B-vitamins
Cardiovascular disease
Fracture
Long-term follow-up
B-vitamins
Cardiovascular disease
Fracture
Long-term follow-up
spellingShingle B-vitamins
Cardiovascular disease
Fracture
Long-term follow-up
B-vitamins
Cardiovascular disease
Fracture
Long-term follow-up
Oliai Araghi, Sadaf
Kiefte-de Jong, Jessica C.
van Dijk, Suzanne C.
Swart, Karin M.A.
Ploegmakers, Kim J.
Zillikens, M.C.
van Schoor, Natasja M.
de Groot, Lisette C.P.G.M.
Lips, Paul
Stricker, Bruno H.
Uitterlinden, André G.
van der Velde, Nathalie
Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial
description Background & aims: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5–7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. Methods: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2–3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. Results: A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51–58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0–76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62–1.59 and HR: 0.77; 95% CI: 0.50–1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80–1.44 and OR: 0.85; 95%CI: 0.50–1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present. Conclusions: This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.
format Article/Letter to editor
topic_facet B-vitamins
Cardiovascular disease
Fracture
Long-term follow-up
author Oliai Araghi, Sadaf
Kiefte-de Jong, Jessica C.
van Dijk, Suzanne C.
Swart, Karin M.A.
Ploegmakers, Kim J.
Zillikens, M.C.
van Schoor, Natasja M.
de Groot, Lisette C.P.G.M.
Lips, Paul
Stricker, Bruno H.
Uitterlinden, André G.
van der Velde, Nathalie
author_facet Oliai Araghi, Sadaf
Kiefte-de Jong, Jessica C.
van Dijk, Suzanne C.
Swart, Karin M.A.
Ploegmakers, Kim J.
Zillikens, M.C.
van Schoor, Natasja M.
de Groot, Lisette C.P.G.M.
Lips, Paul
Stricker, Bruno H.
Uitterlinden, André G.
van der Velde, Nathalie
author_sort Oliai Araghi, Sadaf
title Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial
title_short Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial
title_full Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial
title_fullStr Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial
title_full_unstemmed Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease : Extended follow-up of the B-PROOF trial
title_sort long-term effects of folic acid and vitamin-b12 supplementation on fracture risk and cardiovascular disease : extended follow-up of the b-proof trial
url https://research.wur.nl/en/publications/long-term-effects-of-folic-acid-and-vitamin-b12-supplementation-o
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