Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial

BACKGROUND: Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. METHODS: This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ± 6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 g/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. RESULT: The mean age of the participants was 29 ± 6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (-3.3 ± 5.3; 95% confidence interval [CI] for change -14.1 to 4.1) compared with placebo (-0.8 ± 5.3; 95% CI for change -9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23-5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = -0.22, P = 0.02). CONCLUSION: Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency.This study was registered at the www.ClinicalTrials. gov Protocol ID NCT02022475. DOI: https://doi.org/10.1097/MD.0000000000005353 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-138798 Journal Article Published Version Originally published at: Nowak, Albina; Boesch, Lukas; Andres, Erik; Battegay, Edouard; Hornemann, Thorsten; Schmid, Christoph; Bischoff-Ferrari, Heike A; Suter, Paolo M; Krayenbuehl, Pierre-Alexandre (2016). Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine, 95(52):e5353. DOI: https://doi.org/10.1097/MD.0000000000005353 Effect of vitamin D3 on self-perceived fatigue A double-blind randomized placebo-controlled trial Albina Nowak, MD ∗ , Lukas Boesch, MD, Erik Andres, MD, Edouard Battegay, PhD, Thorsten Hornemann, PhD, Christoph Schmid, PhD, Heike A. Bischoff-Ferrari, PhD, Paolo M. Suter, PhD, Pierre-Alexandre Krayenbuehl, MD Abstract Background: Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials.Background: Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. Methods:This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29±6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D<20mg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. Result:Themean age of the participants was 29±6 years, 53%were women. Mean FAS decreased significantly more in the vitamin D group ( 3.3±5.3; 95% confidence interval [CI] for change 14.1 to 4.1) compared with placebo ( 0.8±5.3; 95% CI for change 9.0 to 8.7); (P=0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P=0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23–5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R= 0.22, P=0.02). Conclusion: Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency. This study was registered at the www.ClinicalTrials. gov Protocol ID NCT02022475. Abbreviations: 25(OH)D = 25-hydroxyvitamin D, BDI = beck depression inventory, BMI = body mass index, BQF = basic questionnaire for fatigue, CFS = chronic fatigue syndrome, FAS = fatigue assessment scale, FCA = fatigue course assessment, IQR = interquartile range, ISI= insomnia severity index, IU= international unit, M.I. N.I=mini international neuropsychiatric interview, MD= medical doctor, OR = odds ratio, PTH = parathyroid hormone, RCT = randomized clinical trial, TSH = thyroid stimulating hormone.