The role of dose and frequency in vitamin D supplementation Original paper

In this meta-analysis of randomized controlled trials, supplementation with vitamin D increased circulating vitamin D levels, without significant differences between daily and intermittent supplementation schedules.

The relative efficacy of daily and intermittent vitamin D supplementation schedules and the association between specific dosages and the resulting serum vitamin D (25(OH)D) concentrations.

A total of 11,376 participants.

Studies that recruited children, pregnant women, and participants with severe liver or kidney-related diseases were excluded, but those that recruited participants with diabetes mellitus, obesity, and polycystic ovary syndrome were included.

This meta-analysis included 116 randomized controlled trials, ranging from 2 to 12 months in duration. The vitamin D dosages included daily supplementation at 400–8,000 IU, weekly supplementation at 5,000–50,000 IU, and monthly supplementation at 18,000–120,000 IU.

The majority of studies were placebo controlled, but some control groups received no intervention or alternate doses of vitamin D.

Data were pooled to assess the mean difference (MD) in serum 25(OH)D levels between the intervention and control groups for various average daily doses (IU/day) when supplemented on a daily, weekly, or monthly basis. The efficacy of various protocols was also ranked as a percentage using the Surface Under the Cumulative Ranking (SUCRA) curve.^[1]

In addition, meta-regression models were used to associate specific dosage protocols (such as 2,000 IU daily or 60,000 IU monthly) with the serum 25(OH)D concentrations achieved.

Both daily and intermittent dosing protocols increased serum concentrations of 25(OH)D, and no statistically significant differences in efficacy were observed between dosing frequencies. However, the authors of the study noted that SUCRA rankings were generally higher with daily dosing.

The highest average daily dose analyzed was 6,666 IU/day for 3 months, which also resulted in the greatest increase in serum concentrations (+74 nmol/L with daily dosing and +63 nmol/L with weekly dosing).

To achieve a serum concentration of greater than 75 nmol/L, the authors highlighted dosages of 2,000 IU daily and 60,000 monthly, which were associated with 25(OH)D concentrations of 87 and 85 nmol/L, respectively.