LBSAT230 Daily Variation In Serum Calcifediol In Japanese And Non-japanese Adults

Abstract

Abstract Circadian rhythm and 24-hour intra-subject variation in serum calcifediol (25-hydroxyvitamin D3) in the absence of vitamin D supplementation or treatment are poorly studied in healthy adults of any race. To address this dearth of information, a single-center, open-label study was completed in the US to evaluate both of these parameters in 67 male and female (balanced for gender) first generation Japanese (n=35) and non-Japanese (n=32) subjects, aged between 18 and 55 years. "First generation" was defined as: born in Japan; had 2 Japanese biological parents and 4 Japanese biological grandparents; had lived outside of Japan for less than 5 years; and, had made no significant changes in lifestyle, including diet, since leaving Japan. "Non-Japanese" was defined as: not of Japanese or Asian descent; and, parents and grandparents were not born in Japan or in any Asian countries. Enrolled subjects had a body mass index within 18. 0 to 30. 0 kg/m2 (inclusive) and body weight not less than 50 kg. The body weight for non-Japanese subjects was 9% to 17% higher than that of Japanese subjects (60.3 to 92.9 kg versus 51.2 to 84.9 kg). Exclusion criteria included consumption of a vitamin D supplement within the previous 28 days, consumption of grapefruit or oranges, alcohol, medications or tobacco within the previous 72 hours, and participation in strenuous physical activity within the previous 72 hours. Subjects were housed in a Phase 1 unit for 2 days where they received only standardized diets. Blood samples were collected on the second day at 0, 2, 4, 6, 8, 10, 12, 16 and 24 hours for determination of serum calcifediol by LC/MS/MS (mean accuracy: 0.37%; mean precision: 3. 07%) at Syneos Laboratories (Quebec, Canada). For all subjects, mean serum calcifediol levels ranged from 20.90 to 22.24 ng/mL over the 24-hour collection period with an average inter-subject variation (SD) of 6.79 ng/mL. A circadian rhythm was not evident either in the total population or in the racial subgroups. Mean intra-subject variation over 24 hours was 1. 08 ng/mL (SD; range: 0.27-3.22) or 5. 05% (CV; range: 2.36-14.81). Differences in 24-hour intra-subject variation between races were not significant (P>0. 05). These data support the conclusions that: (1) clinically meaningful circadian rhythms in serum calcifediol are absent in healthy first generation Japanese and non-Japanese adults living in the US; (2) the mean diurnal variation in serum calcifediol is small (approximately 5%); and (3) vitamin D therapies may appropriately be considered "physiological" if they raise serum total 25-hydroxyvitamin D after each dose only within the bounds of normal diurnal variation thereby allowing gradual adaptation to repletion. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.