Studies of vitamin B12, folate and the metabolically related B-vitamins, and their relationship with bone health, in older adults

Student thesis: Doctoral Thesis


Osteoporosis affects over 200 million people globally, with an estimated 1 in 2 women and 1 in 5 men aged > 50 years expected to experience an osteoporotic fracture. Therefore, there is an urgent need to identify public health strategies to support better bone health in ageing. Several non-modifiable (age, Caucasian ethnicity, female gender and loss of oestrogen) and modifiable (low body weight, physical inactivity, smoking, excessive alcohol) factors are associated with an increased risk of osteoporosis, while nutritional factors are recognised as playing important preventative roles. The essential roles of vitamin D and calcium have been well-documented, but emerging evidence suggests protective roles in bone for folate and related B-vitamins, namely, vitamin B12, vitamin B6 and riboflavin, and/or adverse effects of the related metabolite homocysteine, through a mechanism involving one-carbon metabolism. The overall aim of this thesis was to investigate the potential impacts of these B-vitamins and homocysteine on bone mineral density (BMD) and prevention of osteoporosis. A critical review of the literature was conducted which highlighted that folate-related B-vitamins, and vitamin B12 in particular, may be beneficial to bone health, albeit the evidence to date is predominantly observational and randomised controlled trials (RCTs) are lacking. The findings of this thesis build on the existing literature in this area and provide new evidence from three interrelated studies. The first, an observational study in older adults from the TUDA cohort, showed that atrophic gastritis (a common condition leading to vitamin B12 deficiency) is associated with greater vitamin B12 deficiency, lower BMD and higher risk of osteoporosis. The second, an RCT, was conducted as part of The Optimal Nutrition for Healthier Ageing (OptiAge) study and investigated the effects of low-dose combined B-vitamin intervention for 2 years on nutritional status and bone health in adults ≥ 50 years (n=240). The findings provide the first RCT evidence to show that low-dose B-vitamin intervention can reduce the rate of decline in BMD over time, specifically in older adults with sub-optimal vitamin B12 status. A final study addressed relevant practical considerations to achieve impacts by examining dietary intakes in relation to B-vitamin status, and identified fortified foods as important sources for achieving more optimal B-vitamin biomarkers in older adults, whilst those not regularly consuming fortified food or supplements were at greater risk of B-vitamin deficiency and elevated homocysteine concentrations. In conclusion, the findings of this thesis suggest that the achievement of optimal B-vitamin status in ageing is important for maintaining bone health and osteoporosis prevention, particularly in older adults at risk of low/deficient vitamin B12 status.
Date of AwardApr 2022
Original languageEnglish
SponsorsDepartment for the Economy
SupervisorHelene Mc Nulty (Supervisor), Leane Hoey (Supervisor), Mary Ward (Supervisor) & Catherine Hughes (Supervisor)


  • B-vitamins
  • Osteoporosis
  • Bone mineral density
  • Older adults
  • Randomised controlled trial
  • Atrophic gastritis
  • Dietary intake

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