Modern insights on vitamin D metabolism and the effect of peroral vitamin D on fatigue in adults with low 25-hydroxy-vitamin D levels

Abstract

Background: Vitamin D deficiency is common and has been associated with fatigue in many uncontrolled trials. Material and Methods: This is a prospective, randomized, placebo-controlled, double-blind clinical trial observing the effect of vitamin D supplementation on fatigue in vitamin D deficient, otherwise healthy adults complaining of fatigue. 286 volunteers complaining of fatigue were screened for vitamin D deficiency and known causes of fatigue. We enrolled 133 adult volunteers (median age 27.5 years (range 19–51 y), 53.3% female) with low blood-levels of 25-OH-vitamin D (Serum 25-OH-vitamin D <20 μg/l). Participants were randomized and given either 100’000 IU vitamin D or placebo. The primary end-point was individual change in fatigue assessment scale (FAS) 4 weeks after treatment. Due to unforeseen adverse events potentially biasing results, two branches of data analysis were determined before unblinding, resulting in a full data set, i.e. per protocol and an adjusted data set. Results: Per protocol data analysis showed mild correlation (R=-0.199, p=0.026, Pearson) between ΔFAS and Δ25-OH-Vitamin D (Δ25-OH-VitD). Vitamin D supplementation improved fatigue in 42 (70.0%) of the patients in the vitamin D group vs. 36 (54.5%) taking the placebo (odds ratio (OR) 1.2833, confidence interval (CI) 0.73 – 2.26, p=0.3877). The adjusted data set enforced this mild correlation (R=-0.240, p=0.006). Vitamin D supplementation also improved fatigue in 39 (72.2%) cases vs 29 (53.7%) taking placebo (OR 1.35, CI 0.73 – 2.48, p=0.34). As expected, overall efficacy of cholecalciferol was very good Δ25-OH-VitD (R=0.858, p=0.000). Conclusion: In winter, vitamin D deficiency is common with an especially high prevalence of 46.5% (133 / 286) in people feeling fatigued. Vitamin D supplementation decreased fatigue in vitamin D deficient individuals. After excluding other causes for fatigue, vitamin D deficiency should be actively sought and treated. The oral administration of 100’000 IU cholecalciferol is a safe, convenient and quick way to raise vitamin D levels. Response to supplementation is not dependent on the extent of deficiency.