Eight compounds, graded by the quality of the human clinical research available. We do not sell supplements. We cite the studies, describe the trial doses, and are honest about where the evidence runs out.
Evidence-graded compounds
mTORC1 inhibition · PEARL trial 2026
The most evidence-backed longevity compound in human trials. The PEARL trial — the first powered RCT of low-dose rapamycin in healthy adults — reported 2026 data on biological ageing markers, immune function, and healthspan endpoints. mTOR inhibition extends lifespan across every model organism tested.
Read evidence profileGLP-1 receptor agonism · Semaglutide + Liraglutide
Semaglutide (Ozempic/Wegovy) and liraglutide (Victoza/Saxenda) have the most robust human evidence base for weight loss and metabolic benefit of any licensed compound in this class. SURMOUNT and SCALE trial data underpin current prescribing. Cardiovascular outcome trials (LEADER, SELECT) show significant mortality benefit.
Read evidence profileAMPK activation · mitochondrial complex I inhibition
The most widely prescribed diabetes drug, now the subject of the largest longevity trial ever conducted: TAME (Targeting Aging with Metformin). Epidemiological data consistently shows diabetic patients on metformin outlive non-diabetic age-matched controls not taking it. TAME results expected 2026–2027.
NAD+ precursor · sirtuin activation
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are the most commercially marketed longevity supplements. Oral bioavailability is confirmed — both reliably raise blood NAD+. Long-duration human RCTs testing clinical outcomes are still accumulating. The mechanism is solid; the clinical evidence does not yet match the marketing.
Read evidence profileAMPK activation · gut microbiome modulation
An alkaloid extracted from several plants, berberine activates AMPK — the same pathway as metformin — and modulates the gut microbiome. Multiple small RCTs show comparable effects to metformin on fasting glucose and HbA1c. The "nature's metformin" framing has some mechanistic basis; the RCT evidence base is smaller and lower-quality than metformin's.
HPA axis modulation · cortisol reduction · KSM-66
The most evidence-backed adaptogen for stress and cortisol. KSM-66, the standardised root extract, has been assessed in multiple double-blind RCTs showing significant reductions in serum cortisol, stress questionnaire scores, and sleep quality measures. Effect sizes are modest but consistent. The mechanism is plausible; the evidence is stronger than most botanicals but weaker than pharmaceutical-grade compounds.
Androgen receptor agonism · NHANES + Traverse trial
The Traverse trial — the landmark cardiovascular safety RCT of testosterone replacement — found no significant increase in major adverse cardiovascular events in symptomatic hypogonadal men over 33 months. NHANES epidemiological data consistently associates low testosterone with all-cause mortality. TRT in properly diagnosed hypogonadism has the strongest evidence of any hormonal intervention in men.
Read evidence profileNMDA receptor antagonism · FDA-approved esketamine (Spravato)
Esketamine nasal spray (Spravato) received FDA approval for treatment-resistant depression in 2019 — the first new antidepressant mechanism approved in decades. The TRANSFORM-2 trial established efficacy against standard-of-care antidepressants. Racemic IV ketamine has a substantial clinical evidence base in off-label use. Both have rapid onset compared to conventional antidepressants.
Read evidence profileNMDA antagonism · kappa-opioid agonism · dopamine transporter modulation
A psychoactive alkaloid from the Tabernanthe iboga shrub with compelling evidence for opioid withdrawal interruption and addiction treatment. The 2024 Stanford Nature Medicine study (n=30 veterans with TBI) reported extraordinary reductions in PTSD, depression, and disability. Class A controlled drug in the UK — legal treatment is in Mexico under COFEPRIS oversight. Cardiac safety screening is non-negotiable.
Read evidence profileGH secretagogues · tissue repair · metabolic signalling
A broad category spanning licensed medicines (semaglutide — Tier 1 evidence) to research chemicals (BPC-157, TB-500 — Tier 3 only). Mechanistic rationale is strong across the class; human clinical evidence varies dramatically by compound. UK regulatory status ranges from MHRA-licensed prescription medicines to completely unregulated research chemicals with no approved human use indication.
Read evidence profileTier 1 · RCT / Meta-analysis
Direct experimental evidence in humans. At least one randomised controlled trial with a control group, or a systematic review pooling multiple RCTs. The highest evidentiary standard we apply.
Tier 2 · Mechanistic / Observational
Strong mechanistic rationale confirmed in human biology, plus observational, cohort, or small RCT data. Clinical outcome evidence in large controlled trials is not yet established.
Tier 3 · Emerging / Case series
Early-stage human evidence only: pilot studies, open-label trials, or case reports. Mechanistically plausible but insufficiently studied in controlled human settings to draw clinical conclusions.
This is educational information only. Evidence profiles describe what the published research shows — they are not personal medical advice and do not constitute a recommendation to start, stop, or modify any treatment or supplement protocol. Always consult a qualified healthcare practitioner before making changes to your health regimen. ProvenLongevity does not sell supplements and receives no commercial payment for compound coverage.