The Effects of Geranylgeraniol on Blood Safety and Sex Hormone Profiles in Healthy Adults: A Dose-Escalation, Randomized, Placebo-Controlled Trial

Abstract

Geranylgeraniol (GG), an ingredient extracted from the South American annatto plant, has been shown to benefit bone and muscle health, is crucial in the biosynthesis of menaquinone-4 and coenzyme Q10, and has pain and inflammation reduction activities. However, no known studies to date have demonstrated the safety and impact of GG supplementation in humans. This 8-week, randomized, placebo-controlled, dose-escalated trial was conducted to determine the effect of GG on blood safety and hormone markers in healthy adults. Sixty-six males and females between 30 and 49 years of age were supplemented with either GG or a placebo (PLA) for 8 weeks, with dose escalation from 150 mg to 300 mg occurring after 4 weeks in the treatment group. Changes in complete blood count and comprehensive metabolic panels were analyzed for whole study groups (males and females) while changes in sex hormone panels were analyzed for males and females independently. There were no significant changes in complete blood count, comprehensive metabolic panel, progesterone, estradiol, sex–hormone binding globulin, or dihydrotestosterone (p > 0.05). An exploratory analysis of testosterone levels in a subgroup of males with baseline (Pre) total testosterone < 700 ng/dL (GG = 15; PLA = 13) demonstrated a significant increase (p < 0.05) from Pre to Week 8 in total-, free-, and bioavailable testosterone (+7.5%, +15.0%, and +14.8%, respectively). This study demonstrates that GG does not significantly change the composition of blood chemistry, hematology, or sex hormone profiles in adult males or females. Given the effects observed in the exploratory analysis in a subgroup of males, GG supplementation may be beneficial for testosterone enhancement in male populations subject to low testosterone (i.e., aging males and those with late-onset hypogonadism), but further research is needed.