Effect of supplementation with vitamin D on biochemical markers of iron status and erythropoiesis in older people: BEST-D trial

Previous observational studies suggested that vitamin D may control the absorption of iron (Fe) by inhibition of hepcidin, but the causal relevance of these associations is uncertain. Using placebo-controlled randomisation, we assessed the effects of supplementation with vitamin D on biochemical markers of Fe status and erythropoiesis in community-dwelling older people living in the UK. The BEST-D trial, designed to establish the optimum dose of vitamin D3 for future trials, had 305 participants, aged 65 years or older, randomly allocated to 4000 IU vitamin D3 (<i>n</i> 102), 2000 IU vitamin D3 (<i>n</i> 102) or matching placebo (<i>n</i> 101). We estimated the effect of vitamin D allocation on plasma levels of hepcidin, soluble transferrin receptor (sTfR), ferritin, Fe, transferrin, saturated transferrin (TSAT%) and the sTfR-ferritin index. Despite increases in 25-hydroxy-vitamin D, neither dose had significant effects on biochemical markers of Fe status or erythropoiesis. Geometric mean concentrations were similar in vitamin D3 arms <i>v</i>. placebo for hepcidin (20·7 [se 0·90] <i>v</i>. 20·5 [1·21] ng/ml), sTfR (0·69 [0·010] <i>v</i>. 0·70 [0·015] µg/ml), ferritin (97·1 [2·81] <i>v</i>. 97·8 [4·10] µg/l) and sTfR-ferritin ratio (0·36 [0·006] <i>v</i>. 0·36 [0·009]), respectively, while arithmetic mean levels were similar for Fe (16·7 [0·38] <i>v</i>. 17·3 [0·54] µmol/l), transferrin (2·56 [0·014] <i>v</i>. 2·60 [0·021] g/dl) and TSAT% (26·5 [0·60] <i>v</i>. 27·5 [0·85]). The proportions of participants with ferritin < 15 µg/l and TSAT < 16 % were unaltered by vitamin D3 suggesting that 12 months of daily supplementation with moderately high doses of vitamin D3 are unlikely to alter the Fe status of older adults.