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Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

I-Chen Tsai, Chih-Wei Hsu, Chun-Hung Chang, Ping-Tao Tseng, Ke-Vin Chang
Frontiers in Pharmacology 2022 13:883251

Bibliography

PubMed
PMID 36091835
PubMed Central
PMC9449413
DOI
10.3389/fphar.2022.883251
Funding
National Taiwan University Hospital, Bei-Hu Branch; Ministry of Science and Technology, Taiwan (MOST 106-2314-B-002-180-MY3; MOST 109-2314-B-002-114-MY3); Taiwan Society of Ultrasound in Medicine. APC supported by the Ministry of Science and Technology of Taiwan and Taiwan Society of Ultrasound in Medicine.
Competing interests
I-Chen Tsai reported being the founder of InnovaRad Inc.; the remaining authors declared no commercial or financial relationships that could be construed as a potential conflict.

Study snapshot

DesignPRISMA 2020 systematic review and random-effects meta-analysis of RCTs; PubMed, Embase, CENTRAL, Web of Science and ClinicalTrials.gov searched through January 2022; INPLASY202210113; RoB2, sensitivity analysis and meta-regression.
ModelHealthy and clinical populations with fatigue outcomes, including chronic fatigue syndrome, fibromyalgia, heart failure, obesity, breast cancer, ESRD, poliomyelitis, multiple sclerosis and healthy fatigued adults.
Sample13 RCTs; 1,126 participants; mean age 49.3 ± 12.6 years; 25.6% male.
InterventionCoQ10-only or CoQ10-containing supplementation versus placebo; doses and formulations varied.
Duration4 to 24 weeks across included RCTs.
EndpointsPrimary: fatigue score change; Adverse events; Subgroup effects by population and formulation; Dose-response meta-regression; Duration-response meta-regression

What the study showed, in plain terms

Across 13 randomized trials and 1,126 participants, CoQ10 was associated with a modest reduction in fatigue compared with placebo: Hedges’ g −0.398 (95% CI −0.641 to −0.155; p=0.001). The result remained statistically significant in leave-one-study-out sensitivity analyses.

The evidence was heterogeneous (I²=69.5%). Benefit was statistically significant in the subgroup using CoQ10-only formulations but not in studies of CoQ10-containing combination products. Meta-regression found larger fatigue reductions with higher daily dose (coefficient −0.0017 per mg; p<0.001) and longer treatment (−0.0042 per day; p=0.007).

Only one gastrointestinal adverse event was reported among 602 CoQ10-exposed participants. The pooled result supports a fatigue-symptom signal, but because conditions and fatigue scales varied, it should not be converted into a blanket claim of improved energy or objective exercise performance.

Key findings

  • Fatigue: Hedges’ g −0.398 (95% CI −0.641 to −0.155), p=0.001; I²=69.5%.
  • Sensitivity analysis: significance was retained after removal of any single study.
  • CoQ10-only formulations showed a significant subgroup effect; CoQ10 combination products did not.
  • Dose meta-regression: coefficient −0.0017 per mg/day, p<0.001; duration coefficient −0.0042 per treatment day, p=0.007.
  • Safety: one gastrointestinal adverse event among 602 CoQ10-treated participants in the included trials.

What this study can and cannot tell us

  • Moderate-to-high heterogeneity (I²=69.5%) reflects different diseases, doses, durations and fatigue instruments.
  • Fatigue is largely patient-reported; the result does not prove improved VO2max, power output or other objective performance endpoints.
  • Dose- and duration-response findings come from between-trial meta-regression and are not equivalent to a randomized dose-ranging trial.
  • Trials did not generally follow participants after discontinuation, so persistence of benefit is unknown.

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