Testosterone is best known for its role in sexual health, but its effects go far beyond libido. It plays an important role in maintaining muscle mass, bone density, mood, cognitive function and overall metabolic health in men and women. While testosterone is often considered a male hormone, a decline in levels can affect both genders and is more common than many people realize. It is estimated that between 10 and 40% of adults worldwide are affected by testosterone deficiency.
In men, testosterone levels typically begin to decline around age 40, at a rate of about 1% per year. Women also experience an age-related decline in testosterone that persists over the years after menopause and is often given less attention in clinical practice. Symptoms of low testosterone in both sexes can include fatigue, reduced motivation, poor concentration, loss of muscle mass, reduced bone density, low libido, and adverse changes in body composition.
The traditional treatment for low testosterone is testosterone replacement therapy (TRT). Although TRT can be highly effective, it may not be suitable for everyone and has potential disadvantages including fertility suppression, increased hematocrit, prostate problems, skin reactions and the need for ongoing treatment. As a result, there is growing interest in non-hormonal approaches that support the body’s natural testosterone production rather than directly replacing the hormone.
A compound that is gaining increasing interest in this area is geranylgeraniol (GG). GG is a naturally occurring isoprenoid produced via the mevalonate pathway, the same pathway responsible for the synthesis of cholesterol and coenzyme Q10 (CoQ10). GG sits upstream of CoQ10 in this pathway and serves as an obligatory substrate for its synthesis, meaning that without GG the body cannot produce CoQ10. It is also found in foods such as annatto seeds, flax seeds, olive oil and sunflower oil. Beyond its role as a CoQ10 precursor, GG appears to support bone health, glucose regulation and steroid hormone synthesis.
Preclinical studies have shown that GG can stimulate testosterone production through activation of the cAMP/protein kinase A signaling pathway. Further in vitro and animal studies suggest that GG may support the synthesis of testosterone and progesterone. Because cholesterol serves as a precursor to all steroid hormones, GG’s involvement in cholesterol metabolism and other important cellular processes represents a mechanism by which it may influence steroidogenesis. Importantly, GG appears to be well tolerated and toxicological evaluation has supported daily doses of up to 406 mg without any significant safety concerns reported.
A recently published clinical trial examined whether GG supplementation could affect testosterone levels, CoQ10 status, and measures of general and sexual health in healthy middle-aged adults. The study was an 18-week, single-group, placebo-controlled, crossover design. Participants between the ages of 40 and 65 received a placebo for eight weeks, followed by a two-week washout period and another eight weeks of supplementation with 300 mg of annatto-derived GG per day.
Over the course of 18 weeks, 34 participants completed the experiment. The average age was around 51 years, with the number of women being slightly higher than the number of men. Blood samples were collected after an overnight fast at baseline and at weeks 8, 10, and 18. In addition to validated health questionnaires, several metrics were measured, including total testosterone, free testosterone, sex hormone binding globulin (SHBG), and CoQ10 concentrations. Participant compliance was high and no serious adverse events were reported.
After the intervention, results showed that GG supplementation did not significantly change total testosterone, free testosterone or SHBG levels. However, in men with lower baseline testosterone levels (below 600 ng/dL), GG supplementation resulted in a statistically significant increase in total testosterone. Average testosterone levels increased by approximately 28 ng/dL, suggesting a significant response in this particular group. This effect was not observed in women or men with higher baseline testosterone levels. This could suggest that people who already produce sufficient amounts of a hormone may have limited room for improvement, while people who start with lower amounts may experience a stronger response. Similar patterns have been observed with other nutritional, herbal and pharmaceutical interventions aimed at supporting testosterone production.
Interestingly, although GG supplementation did not significantly increase CoQ10 levels, researchers observed a decrease in CoQ10 during the placebo phase, which remained stable during the GG phase. Since healthy adults usually have sufficient CoQ10 status and strictly regulate its production, no significant increase was expected in this study. However, these results suggest that GG may help maintain coenzyme Q10 levels over time, making it particularly relevant for populations at higher risk of fatigue, including older adults and those taking statin medications. Researchers in this clinical trial also assessed changes in physical, mental and sexual health using validated questionnaires, but found no significant differences between the placebo and GG phases. Considering that participants were generally healthy and functioning well at baseline, there may have been little chance for measurable improvement during the relatively short intervention period.
Overall, these results suggest that while GG is unlikely to produce a dramatic increase in testosterone in healthy adults with normal hormone levels, its effects may be more significant in individuals with lower baseline testosterone levels, where there is more room for improvement. Although testosterone replacement therapy remains an important option for some individuals, these results demonstrate the potential role of non-hormonal nutritional approaches as part of a broader strategy to support hormonal health, particularly for those who are unable or unwilling to use TRT.
As with any individual study, these results reflect a limited amount of evidence and should not be generalized to all populations. Larger studies in target populations such as men with late-onset hypogonadism or those taking statins will help clarify the long-term role of GG supplementation in supporting testosterone and maintaining CoQ10 status in aging adults.
Learn more about hormone health and healthy aging:
A case report of trans-geranylgeraniol supplementation in a 27-year-old man with thyroid dysfunction
Integrative management of estrogen dominance, methylation disorder and histamine intolerance in perimenopause: A case report
A case report of nutraceutical support and urine metabolite testing in a 61-year-old woman with menopausal problems
A Case Report of DIM Supplementation in a 78-year-old Man With Elevated Prostate-Specific Antigen (PSA)
By Jesse Martin, MS