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

Abstract

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 (n 102), 2000 IU vitamin D3 (n 102) or matching placebo (n 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 v. placebo for hepcidin (20·7 [se 0·90] v. 20·5 [1·21] ng/ml), sTfR (0·69 [0·010] v. 0·70 [0·015] µg/ml), ferritin (97·1 [2·81] v. 97·8 [4·10] µg/l) and sTfR-ferritin ratio (0·36 [0·006] v. 0·36 [0·009]), respectively, while arithmetic mean levels were similar for Fe (16·7 [0·38] v. 17·3 [0·54] µmol/l), transferrin (2·56 [0·014] v. 2·60 [0·021] g/dl) and TSAT% (26·5 [0·60] v. 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.

Keywords: Erythropoiesis; Healthy older population; Iron; Randomised Controlled Trial; Vitamin D supplementation.

Figure 1.

Median levels of parameters measured at baseline to define Fe deficiency in healthy male and female participants in the BEST-D study. Box and whisker plots show the median of each parameter with individual outliers shown above and below the inter-quintile range for (a) Fe, (b) transferrin (Tf), (c) transferrin saturation (TSAT%), (d) Hepcidin and (e) correlation of hepcidin with TSAT% (below dashed line may be deficient in Fe).

Figure 2.

Measurements of Fe availability for erythropoiesis at baseline and their relationship with hepcidin levels in the BEST-D cohort of healthy male and female participants. (a) sTfR, (b) ferritin, (c) sTfR-ferritin index (sTfR-F index) is shown at baseline before randomisation. Horizontal bars of box and whisker plots represent medians with individual outliers above and below the inter-quintile range. (d) Correlation of hepcidin with sTfR-F index (above dashed line may have reduced erythropoiesis).