A Randomized, Double-Blind, Placebo-Controlled Trial Comparing the Effects of Commercially Available Ubiquinone, Ubiquinol, and Geranylgeraniol Dietary Supplements on Plasma CoQ10 Concentrations.

Abstract

Background: Coenzyme Q10 (CoQ10) plays a fundamental role in energy production and antioxidant activity in humans. Direct supplementation with both the ubiquinol and ubiquinone forms of CoQ10 increases circulating concentrations, although comparative efficacy remains uncertain. Furthermore, nutrients supporting endogenous CoQ10 production, such as geranylgeraniol (GG), suggest that supplementation may indirectly increase CoQ10 concentrations.

Methods: A randomized, double-blind, parallel-arm, placebo-controlled trial was conducted comparing 8 weeks of label-dose supplementation with commercially available formulations of (1) ubiquinone; (2) ubiquinol; (3) GG; (4) ubiquinol + GG; and (5) placebo among healthy adults. The primary outcome was plasma CoQ10 concentrations. Secondary outcomes included lipid concentrations, markers of kidney and liver function, and validated questionnaires (PROMIS-Global Health, Profile of Mood States-Vigor subscale, and SF-36 Vitality subscale) assessing physical and mental health. Mean changes were compared across study arms using analysis of covariance (ANCOVA). Bonferroni correction for multiple comparisons was applied to the comparisons to placebo, and statistical significance was set at p < 0.0125. Tukey's multiple comparison procedure was applied to comparisons between each of the active study products, and statistical significance was set at p < 0.05.

Results: A total of 150 participants were randomized. The mean age was 52.1 years, and the sample was diverse with respect to sex and race/ethnicity. Changes in CoQ10 with ubiquinone (+ 1.46), ubiquinol (+ 2.29), and ubiquinol + GG (+ 2.45) were greater than placebo (p < 0.0001). There were no differences between GG and placebo, ubiquinone and ubiquinol, or ubiquinol and ubiquinol + GG (p ≥ 0.15). Ubiquinol + GG (+ 0.99 mg/L) outperformed ubiquinone (p = 0.045). There were no differences versus placebo in questionnaires (p > 0.16). Adverse events were rare across all study arms.

Conclusions: Supplementation with ubiquinone, ubiquinol, and ubiquinol + GG was well-tolerated and increased CoQ10 concentrations among healthy adults. While GG had no independent effects on CoQ10 concentrations, an interaction effect cannot be excluded, and this should be evaluated in a future factorial trial specifically designed for this purpose. Future studies evaluating the impact of ubiquinone + GG may also be warranted. Trail Registration: ClinicalTrials.gov: NCT06640465.