| Sumario: | Background: Geranylgeraniol (GG) is a naturally occurring isoprenoid that is involved in steroid hormone synthesis, the endogenous production of coenzyme Q10 (CoQ10), healthy muscle function, bone metabolism, and cellular energy production. Although preclinical research and a recent human study have indicated a potential role for GG in modulating testosterone levels, its effects in middle-aged adults remain unclear. Aim: This study aimed to assess the effects of GG supplementation on testosterone status, coenzyme Q10 concentrations, and validated questionnaires of overall and sexual health in middle-aged healthy adults. Method: This 18-week, single-group, crossover, placebo-controlled trial involved participants aged 40 to 65 years. The intervention consisted of 8 weeks of placebo followed by a 2-week washout and 8 weeks of GG supplementation (300 mg/day). Outcomes were assessed at baseline, Week 8 (after blinded placebo), Week 10 (post-washout), and Week 18 (after blinded intervention). Results: Thirty-four participants completed the study. No significant changes were observed in total testosterone, free testosterone, or sex hormone binding globulin (all P > .05) in the full study sample or within the female subgroup. In the subgroup of men with lower baseline testosterone (<600 ng/dL, n = 8), total testosterone increased significantly following GG supplementation (mean difference = 28.44 ng/dL, 95% CI: 7.45--49.43, P = .015), with a large effect size (Cohen's d = 1.13), indicating a meaningful physiological response. Serum CoQ10 declined significantly during placebo (mean difference = -0.10 µg/mL, P = .03) but remained stable during GG supplementation (P = .9), suggesting a potential maintenance effect. Conclusion: These results highlight GG as a promising natural strategy to support endogenous testosterone production and CoQ10 homeostasis in age-related declines. Further investigation in larger, targeted populations such as men with late-onset hypogonadism or individuals on statin therapy is warranted.
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