Plasma Vitamin B12, Supplementation and Mortality

Research paper by Mendonça N, Jagger C, Granic A, et al.

Indexed on: 21 Dec '18Published on: 03 Oct '18Published in: The journals of gerontology. Series A, Biological sciences and medical sciences


We thank Professor J. David Spence for his comments on our manuscript “Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study” (1). In his letter to the editor “Harm with high levels of serum B12 in elderly persons,” Professor Spence proposes that the associations between elevated plasma vitamin B12 and cardiovascular mortality in the very old observed in the Newcastle 85+ Study are likely due to supplementation with cyanocobalamin (a form of vitamin B12). Although an interesting proposition, this is unlikely to be the cause for the observed associations that are reported in our manuscript. In the Newcastle 85+ Study, only 35 (4.6%) participants from the analytic sample (n = 753) took vitamin B12 supplements (for more details, see (2,3)), and although B12 concentrations were higher in the supplement-taking group (258 [186–400] pmol/L vs 231 [170–320] pmol/L), only two of these participants had plasma vitamin B12 concentration more than 500 pmol/L. Moreover, we further adjusted the final models in our manuscript for vitamin B12 supplement use, and no differences in the effect sizes were detected. Elevated plasma vitamin B12 concentrations have been found in patients with cancers and with liver, renal, autoimmune, and infectious diseases in other populations (4,5). For example, greater numbers of leukocytes in hematological malignancies increase haptocorrin production and release into the circulation (4), which subsequently binds to vitamin B12, increasing plasma concentrations. Moreover, increased hepatocyte turnover or damage may lead to greater leakage of vitamin B12 stored in the liver, also resulting in higher vitamin B12 concentration in plasma (6). Participants with these conditions at the time of blood collection could have had very high plasma vitamin B12 concentrations and this would drive the results though our models were adjusted for a number of chronic diseases. These are more likely explanations for the associations between higher plasma vitamin B12 and mortality that we reported (1). Importantly, the Newcastle 85+ Study is an observational study, and so, we cannot attribute causality to the observed relationships.