Effect of race, gender and age on intrinsic diurnal variation of serum calcifediol: Insights into vitamin D toxicity

Intrinsic diurnal variation of serum calcifediol (25-hydroxyvitamin D₃) was evaluated in healthy United States (US) adults by race, gender and age. Eligible participants (18-55 years old, body mass index 18-30 kg/m², body weight ≥ 50 kg) were enrolled with gender balance into two groups by race: first generation Japanese (n = 35) and non-Japanese (n = 32). "First generation Japanese" was defined as having Japanese parents and grandparents and residing outside Japan for < 5 years without major lifestyle or dietary changes. "Non-Japanese" were of non-Asian descent and included 14 African-Americans, 16 Caucasians and 2 of "Other" race. Vitamin D supplementation during the prior 28 days was an exclusion criterion. Participants were housed for two days in a phase 1 unit shielded from sunlight and fed timed standardized meals devoid of vitamin D. Serum calcifediol, measured by LC-MS/MS on Day 2 at 0, 2, 4, 6, 8, 10, 12, 14, 16, 20 and 24 h, had a minor circadian rhythm (p = 0.0081) having a midline statistic of rhythm (MESOR) of 21.5 ng/mL, an amplitude of 0.19 ng/mL and an acrophase at 5:24 a.m. Mean inter-participant variation was high (CV of 30.89 %) while intra-participant variation was low (5.54 %), only nominally exceeding the assay precision (4.10 %). No significant differences in rhythmicity were observed between subgroups based on race, gender or age. These data show that intrinsic diurnal variation of circulating calcifediol is low, suggesting that avoidance of abrupt iatrogenic changes in serum total 25-hydroxyvitamin D concentrations may be important for minimizing the risk of toxicity.