Clinical and biomarker modifiers of vitamin D treatment response: the Multi-Ethnic Study of Atherosclerosis

Different 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown. The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation. A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations from baseline to 16 wk. Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was −3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: –5; 95% CI: –8, –2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D