TY - JOUR
T1 - Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease
T2 - Extended follow-up of the B-PROOF trial
AU - Oliai Araghi, Sadaf
AU - Kiefte-de Jong, Jessica C.
AU - van Dijk, Suzanne C.
AU - Swart, Karin M.A.
AU - Ploegmakers, Kim J.
AU - Zillikens, M. Carola
AU - van Schoor, Natasja M.
AU - de Groot, Lisette C.P.G.M.
AU - Lips, Paul
AU - Stricker, Bruno H.
AU - Uitterlinden, André G.
AU - van der Velde, Nathalie
N1 - Funding Information:
The initial B-PROOF study has received funding so far by The Netherlands Organization for Health Research and Development (ZonMw, Grant 6130.0031 ), the Hague; unrestricted grant from NZO , Zoetermeer ; Orthica , Almere ; NCHA (Netherlands Consortium Healthy Ageing) Leiden/Rotterdam; Ministry of Economic Affairs, Agriculture and Innovation (project KB-15-004-003 ), the Hague; Wageningen University , Wageningen; VUmc,Amsterdam; Erasmus Medical Center , Rotterdam.
Publisher Copyright:
© 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - B-vitamins
KW - Cardiovascular disease
KW - Fracture
KW - Long-term follow-up
UR - http://www.scopus.com/inward/record.url?scp=85089356180&partnerID=8YFLogxK
U2 - 10.1016/j.clnu.2020.07.033
DO - 10.1016/j.clnu.2020.07.033
M3 - Article
C2 - 32800386
AN - SCOPUS:85089356180
SN - 0261-5614
VL - 40
SP - 1199
EP - 1206
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 3
ER -