Strategies for Repletion of Vitamin D Nutritional Deficiency: A Comparative Effectiveness Trial of High-quality Vitamin D3 Nutritional Supplements to Replete Serum Vitamin D

Abstract

Background: Vitamin insufficiency and deficiency may be associated with increased risk for cardiovascular disease, diabetes, some cancers and all cause mortality. Practice guidelines define sufficient vitamin D status as a serum 25-hydroxycholecalciferol (25-OHD) concentration >30 ng/mL (70 nmol/L). Supplementation strategies to safely achieve vitamin D sufficiency are needed. Objective: We evaluated the change in serum 25-OHD concentrations after supplementation with three commercially available vitamin D3 products with different vehicles of delivery: a chewable tablet; a liquid drop; and a encapsulated powder. Methods: The clinical trial design was a prospective, randomized, pragmatic, comparative effectiveness study of vitamin D3 supplementation. We conducted third-party analysis of the three commercially available vitamin D3 supplements used in this trial. Subjects were provisioned informed consent and randomized to one of the three vitamin D3 supplements, dosed at 10,000 IU per day for 12 weeks, per label claim. Results: Eligible subjects (n=66) were enrolled in the study, of which 11 subjects were lost to follow up (17%). 100% of the subjects in the tablet and capsule allocation arms attained sufficient vitamin D status, compared to 80% in the oil drop arm. The mean (±SD) change in 25-OHD (ng/mL) from baseline to week 12 reached the level of statistical significance (p<0.001) for each of the three allocation groups: tablet (n=18); 31.8 (7.6); oil drop (n=20); 32.2 (8.0); and capsule (n=17); 48.1 (8.1). Between group changes in serum 25-OHD were also significant (ANOVA; p<0.05). While pairwise-comparisons of changes in serum 25-OHD showed a statistically significant difference, distinguishing Group C from Groups A and B (Tukey's Test; p<0.05). Three non-serious adverse events occurred during the study, without observed hypercalcemia or hypervitaminosis D. Discussion: We observed variability in vitamin D3 concentration in the three supplements, with the tablet and capsule showing increased D3 concentration, compared to label claim. The majority of subjects (93%) achieved sufficient 25-OHD status at the end of the study. We conclude that 10,000 IU vitamin D3 per day for 12-weeks may be a safe and effective strategy for vitamin D supplementation to correct nutritional deficiency in 25-OHD insufficient populations. This trial was registered at clinicaltrials.gov as NCT01524874.