Moderate Amounts of Vitamin D3 in Supplements Are Effective in Raising Serum 25-hydroxyvitamin D from Low Baseline Levels in Adults: a Systematic Review

There is controversy surrounding the designation of vitamin D adequacy as defined by circulating levels of the metabolite 25-hydroxyvitamin D (25(OH)D). Depending on the cutoff level chosen, dietary intakes of vitamin D may or may not provide sufficient impact upon vitamin D status measured as improvement in serum levels of 25(OH)D. We sought to examine whether modest daily doses (5-20 μg) as found in fortified foods or multivitamin supplements had a measureable impact on vitamin D status, defined as moving from below to above 50 nmol/L, or from less than 30 nmol/L to above 30 nmol/L. Published literature was searched for relevant articles describing randomized controlled trials. Exclusion criteria were: studies not involving humans; review articles; studies lacking blood level data pre- and post-treatment; no control group; bolus treatments (weekly, monthly, yearly); vitamin D < 5 μg or > 20 μg; baseline 25(OH)D ≥ 75 nmol/L; subjects not defined as healthy; studies < 8 weeks; and age < 19 years. Of the 127 studies retrieved, 18 publications with 25 separate comparisons met criteria. The mean rate constant, defined as change in 25(OH)D in nmol/L per μg vitamin D administered, was calculated as 2.19 ± 0.97 nmol/L per μg. There was a significant negative correlation (r = -0.65, p = 0.0004) between rate constant and administered dose. To determine impact of the dose reflecting the Estimated Average Requirement (EAR) of 10 μg administered in nine studies (10 comparisons), in every case mean 25(OH)D status rose either from "insufficient" (30-50 nmol/L) to "sufficient" (> 50 nmol/L) or from "deficient" (< 30 nmol/L) to "insufficient" (> 30 but < 50 nmol/L). Our study shows that when baseline levels of groups were < 75 nmol/L, for every microgram of vitamin D provided, 25(OH)D levels can be raised by 2 nmol/L; and further, when groups were deficient or insufficient in vitamin D, there was significant value in providing additional 10 μg per day of vitamin D.