Reduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study.

Although large populations feel fatigue, the standardized medicinal therapy is currently absent. In this study, we determined whether 5-aminolevulinic acid (5-ALA) supplementation alleviates the feeling of fatigue in healthy subjects who feel chronic physical tiredness. Males and females between ages of 20 and 64 who felt physical fatigue on a daily basis, with a visual analogue scale (VAS) for fatigue ≥ 40 mm, a T-score of Fatigue-Inertia in the Profile of Mood States-Second Edition-Adult (POMS2-A) ≥ 50, and a T-score of Vigor-Activity in POMS2-A ≤ 60 were recruited. Seventy eligible participants were randomly assigned to either a 5-ALA or a placebo group. During the 8 weeks of consumption, the subjects completed VAS questionnaires for fatigue and POMS2-A at 4-week intervals. The VAS values for overall feeling of fatigue and feeling of work-related fatigue, and the Anger-Hostility subscale of POMS2-A were decreased by 5-ALA with significant time × group interaction effects (p = 0.040, 0.020, and 0.045, respectively). Besides, the 5-ALA group showed significant differences in Fatigue-Inertia, Depression-Dejection and Total Mood Disturbance scores, when compared between pre- and post-intervention, while the placebo group did not. In conclusion, the oral administration of 5-ALA improves fatigue and negative mood in subjects who constantly feel physical fatigue.This clinical trial was registered with University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000031528 on 2/3/2018.