A 2-year randomized controlled trial with low-dose B-vitamin supplementation shows benefits on bone mineral density in adults with lower B12 status

Michelle Clements, Maria Heffernan, Mary Ward, Leane Hoey, Leanne C Doherty, Roberta Hack Mendes, Michelle M Clarke, Catherine F Hughes, Ingrid Love, Shauna Murphy, Eilish McDermott, Jennifer Grehan, Adrian McCann, Liadhan B McAnena, JJ Strain, Lorraine Brennan, Helene McNulty

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Abstract

Folate, vitamins B12, B6, and riboflavin are required for one-carbon metabolism and may affect bone health, but no previous randomized trial has investigated all four nutrients in this context. We investigated the effect of low-dose B-vitamins for 2 years on bone mineral density (BMD) in a dual-centered, 2-year randomized controlled trial (RCT) in adults aged ≥50 years. Eligible participants not consuming B-vitamin supplements or fortified foods >4 times weekly were randomized to receive daily either combined folic acid (200 μg), vitamin B12 (10 μg), vitamin B6 (10 mg), and riboflavin (5 mg), or “active” placebo, whereby both the intervention and placebo groups received vitamin D (10 μg). BMD was assessed before and after intervention using dual-energy X-ray absorptiometry (DXA) scanning of the total hip, femoral neck, and lumbar spine (L1 to L4). Of 205 eligible participants randomized, 167 completed the trial in full. B-vitamin intervention resulted in increases in serum folate (p < 0.001), serum B12 (p < 0.001), and plasma pyridoxal-5-phosphate (p < 0.001) and decreases in functional biomarkers of B-vitamin status, erythrocyte glutathione reductase activation coefficient (p < 0.001), serum methylmalonic acid (MMA; p < 0.001), and serum total homocysteine (p < 0.001). B-vitamin intervention had no overall effect on BMD, which declined in both treatment groups by approximately 1% (ranging from −0.7% to −1.4%). However, in participants with lower baseline B12 status (serum B12 <246 pmol/L or MMA ≥0.22 μmol/L), B-vitamin intervention reduced the 2-year BMD decline versus placebo: adjusted mean (95% confidence interval [CI]) change of −0.003 (−0.008, 0.002) versus −0.015 (−0.021, −0.010) g/cm 2 at the total hip and −0.004 (−0.010, 0.001) versus −0.013 (−0.018, −0.007) g/cm 2 at the femoral neck. In conclusion, the findings indicate that although low-dose B-vitamin intervention for 2 years had no overall effect on BMD, improving B-vitamin status appears to have specific benefits for bone health in adults with lower B12 status.

Original languageEnglish
Pages (from-to)2443-2455
Number of pages13
JournalJournal of Bone and Mineral Research
Volume37
Issue number12
Early online date21 Sept 2022
DOIs
Publication statusPublished (in print/issue) - 31 Dec 2022

Bibliographical note

Funding Information:
This article was supported by governmental funding from the Department of Agriculture, Environment and Rural Affairs (DAERA) in Northern Ireland and the Department of Agriculture, Food and the Marine in the Republic of Ireland.

Funding Information:
The authors thank all the study participants for taking part in this research. We acknowledge the contributions of Advanced Orthomolecular Research (AOR; https://aor.ca/about/), Alberta, Canada, for providing the study supplements. This article was supported by governmental funding from the Department of Agriculture, Environment and Rural Affairs (DAERA) in Northern Ireland and the Department of Agriculture, Food and the Marine in the Republic of Ireland. Authors’ roles: HMN, LB, MW, MMC, and JJS designed the research. MC, MH, LCD, and RHM contributed equally to the recruitment of participants, execution of the trial, and collection of data across study centers in Northern Ireland and Republic of Ireland. IL, SM, EMD, and JG supported DXA scanning. AMC, LBM, and MC conducted laboratory analysis. MC analyzed the data. MC, CFH, MW, LH, and HMN drafted the manuscript. LB, JJS, MH, LCD, RHM, LBM, AMC, and MMC provided critical feedback to improve the intellectual content. HMN had primary responsibility for the final content. All authors approved the final manuscript.

Publisher Copyright:
© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Keywords

  • B-vitamins
  • One-carbon metabolism
  • Bone mineral density
  • Osteoporosis
  • Aging
  • BONE MINERAL DENSITY
  • AGING
  • B-VITAMINS
  • ONE-CARBON METABOLISM
  • OSTEOPOROSIS

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