by Nicolas Hulscher, MPH

The Great Testosterone Decline

A 2025 systematic review/meta-regression by Santi et al covering 1,064,891 healthy men (1,256 papers; 1,504 study groups; 1971–2024) found a significant negative trend in serum testosterone across the last five decades in all age groups.

The decline remains after adjusting for age, BMI, assay type, and even environmental/demographic moderators. Importantly, luteinizing hormone (LH) declines in parallel, suggesting a central (hypothalamic–pituitary) component rather than a purely testicular failure; FSH showed no clear trend.

Testosterone underpins energy, mood, body composition, libido/sexual function, erythropoiesis, bone density, and cardiometabolic health. A multi-decade population drift downward has obvious implications for fertility and men’s health.

As a result, there is growing interest in so-called “testosterone boosters”— compounds marketed to ameliorate or reverse this hormonal decline.

What “Testosterone Boosters” Actually Raise Serum Total Testosterone?

Morgado et al (2023) systematically reviewed all data published in the last two decades on testosterone boosters and determined their efficacy. They found 52 clinical trials spanning 28 proposed testosterone boosters (TBs) and judged efficacy strictly on serum total testosterone (sTT) vs placebo in four groups: healthy men, male athletes, men with late-onset hypogonadism (LOH), and infertile men.

Their “effective” label required ≥2 independent positive studies in a given population; “possibly effective” meant a single positive randomized trial:

Effective

• β-Hydroxy β-methylbutyrate (HMB) — naturally occurring metabolite of the amino acid leucine

  • Effective for male athletes (≥2 positive RCTs).

  • ~11–22% serum total testosterone (sTT) increase after 10–12 weeks (3 g/day; p < 0.05), depending on sport and training status.

• Betaine (trimethylglycine) — naturally occurring derivative of the amino acid glycine

  • Effective for male athletes (≥2 positive RCTs).

  • ~64–94% sTT increase after 2–14 weeks (2–2.5 g/day; p < 0.05).

Possibly Effective (single positive RCTs; needs replication)

• Tongkat Ali (Eurycoma longifolia) — root extract

  • Possibly effective for healthy men and those with late-onset hypogonadism (LOH).

  • ~10–15% sTT increase after 2 weeks (600 mg/day; p < 0.05).

• Ashwagandha (Withania somnifera) — root extract

  • Possibly effective for healthy men.

  • ~14–17% sTT increase after 8 weeks (300 mg twice daily; p < 0.05).

• Shilajit (purified Himalayan mineral resin)

  • Possibly effective in healthy middle-aged men.

  • ~20% sTT increase after 90 days (250 mg twice daily; p < 0.05 vs placebo).

• Pomegranate and cacao mix (Punica granatum rind + Theobroma cacao seed)

  • Possibly effective in men with LOH.

  • ~21–25% sTT increase after 56 days (200–400 mg/day; p < 0.05; clear dose response).

• Aromatase inhibitor (non-hormonal)

  • Possibly effective in resistance-trained men.

  • +283% sTT increase after 8 weeks (unspecified dose; p < 0.01).

No Reliable Effect

• Vitamin D (cholecalciferol) — 10 RCTs; null overall unless correcting frank deficiency; no effect in replete athletes (p > 0.05).

• Zinc and/or Magnesium (ZMA) — 5 RCTs; largely null for sTT (one zinc-only arm showed free T ↑ but no total change).

• Tribulus terrestris — mixed/mostly null across healthy, athletes, infertile, and LOH groups.

• Creatine — no consistent effect on sTT despite ergogenic benefits.

• β-Alanine — no sTT change.

• D-Aspartic Acid (DAA) — transient rise week 1 lost by week 4 (p > 0.05).

• Lepidium meyenii (Maca) — no sTT effect (p > 0.05).

• Isoflavones — null or slightly negative trend (p > 0.05).

• Trigonella foenum-graecum (Fenugreek) — small free T changes only; no sTT difference.

• Arginine — no effect on sTT (p > 0.05).

• L-Carnitine — no effect on sTT; some sperm-motility improvement only.

• Dehydroepiandrosterone (DHEA) — variable free T ↑ but no consistent sTT gain.

• Coenzyme Q10 — no change in sTT (p > 0.05).

• Lipoic acid — no effect on sTT (p > 0.05).

• Virgin argan oil / extra-virgin olive oil — methodological issues; no significant increase.

• Jingui Shenqi pill — single-arm; no placebo; unclear effect.

• Calcium gluconate + exercise — authors claimed positive but no additive sTT effect vs exercise alone (p > 0.05).

Conclusion

Out of 28 total compounds, only two (HMB and Betaine) consistently increased serum total testosterone in placebo-controlled human trials.

Five others—Tongkat Ali (Eurycoma longifolia root), Ashwagandha (Withania somnifera root), Shilajit (purified Himalayan mineral resin), pomegranate and cacao mix (Punica granatum rind + Theobroma cacao seed), and a non-hormonal aromatase inhibitor—showed possible short-term efficacy in single or context-specific studies.

The remaining 21 “boosters”—including Vitamin D, Tribulus, ZMA, Creatine, Fenugreek, Maca, and DAA—failed to reliably raise testosterone in nutrient-sufficient adults, but may benefit those who are deficient.

While supplements may offer marginal or context-specific benefits, the most powerful drivers of testosterone remain foundational lifestyle factors — consistent resistance training, adequate sunlight exposure and sleep, nutrient-dense whole foods, and maintaining healthy body composition.

As Wrzosek et al indicated:

• Most factors influencing testosterone levels in men are modifiable, such as diet, amount of sleep or stress levels.

• Zinc is a cofactor of LH and FSH enzymes catalyzing the synthesis of trophic hormones of the pituitary. Zinc deficiency correlates with lower testosterone levels.

• The reduction of sleeping time to 5 hours per day during a single examination contributed to reducing testosterone levels by 10–15%.

• In the case of people with healthy weight, too low calorific value of diet may result in the reduction of testosterone levels in men.

• Excessive body mass may lead to higher levels of cortisol and affect androgens levels. Hair analysis of people of different body mass showed higher cortisol levels and lower testosterone levels in obese people.

Nicolas Hulscher, MPH

Epidemiologist and Foundation Administrator, McCullough Foundation

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