Effects of intravenous injection of high-dose ascorbic acid on mitochondrial DNA copy number in chronic fatigue patients : a randomized-controlled study

Abstract

Fatigue is related with mitochondrial energy systems. Mitochondrial components can be impaired by reactive oxygen species. Vitamin C has been used as a therapeutic agent for fatigue recovery. However, the effect of that is still vague. To explore changes in fatigue scores and mtDNA copy numbers after high-dose vitamin C injection in chronic fatigue patients, double-blind randomized trial was performed. Sixty participants with moderate-severe fatigue for more than 6 months were enrolled. Each participant received a single treatment of either vitamin C 10g or same volume of normal saline. Primary outcomes are fatigue scores by brief fatigue inventory-Korean version and mitochondrial DNA (mtDNA) copy number in whole blood and buccal epithelial cell, 2 weeks later.Mean fatigue scores were improved in both vitamin C group (n=30, 6.3±1.1 to 5.1±2.1, p=0.006) and placebo group (n=30, 6.6±0.9 to 5.6±1.6, p=0.001) (p=0.582, intergroup). In vitamin C group, mtDNA copy number was slightly increased (blood: 71.89±35.14 to 72.08±34.33, p=0.688; saliva: 398.25±326.65 to 415.56±347.49, p=0.915), while that of placebo group was decreased (blood: 74.18±29.12 to 66.47±31.74, p=0.283, saliva: 349.02±305.60 to 317.23±270.19, p=0.631). In subgroup analysis, divided into four groups according to fatigue recovery and intervention, More subjects in vitamin C group (15/15, 50%) experienced fatigue recovery than placebo group (8/22, 27%), (p=0.055).In vitamin C and fatigue recovery group, mtDNA copy number was higher. However, the other subgroups showed lower changes. In vitamin C group, participants with lower initial mtDNA copy numbers had higher mtDNA copy number (p=0.001) and lower fatigue scores (p=0.026) than participants with higher initial copy number in peripheral blood. However, the placebo group did not show significances (p>0.05, both). In saliva sample, the change of mtDNA copy number was same (p=0.031), but we did not confirm the fatigue recovery (p=0.740). There was no important adverse event.We cannot confirm fatigue recovery and mtDNA copy number increase by high-dose vitamin C injection in all participants. However, this treatment can reduce chronic fatigue and increase the mtDNA copy number on chronic fatigue patient with low mtDNA copy number. Clinically, fatigue patient with low mtDNA copy numbers may receive more benefit from this treatment.