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A
Deeper = more human clinical evidence. The line drops from the surface; where it stops is the depth reached.
D+
Dashed bronze line: trials were run and missed their primary endpoint — a finding, not a gap.
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Empagliflozin (SGLT2i)

A+
Cardiology Rx (Repurposed) RenalCardiovascularHepatic

SGLT2 inhibitors (empagliflozin, dapagliflozin) are the highest-evidence longevity compound class in the registry, with A+ grades for both CKD and heart failure indications. The…

Reviewed 2026-03-15

Semaglutide

A+
Metabolic Rx (Repurposed) CardiovascularRenalNeurological

Semaglutide carries some of the strongest human outcome evidence in the ClinEvident registry. Originally approved for type 2 diabetes (Ozempic) and obesity (Wegovy), it has demonstrated…

Reviewed 2026-03-15

Metformin

B-
Metabolic Rx (Repurposed) CardiovascularNeurologicalHepatic

Metformin has extensive observational evidence suggesting longevity benefits, including the landmark UKPDS study showing reduced all-cause mortality in diabetic patients. A 2024 Nature…

Reviewed 2026-03-15

Omega-3 (high-dose EPA / icosapent ethyl, prescription)

B-
Cardiology Rx (Repurposed)

Prescription high-dose purified EPA. One large trial (REDUCE-IT) showed a 25% reduction in cardiovascular events, and it is FDA-approved (2019). BUT the size of that benefit is contested…

Grade and summary pending review
Reviewed 2026-10-22

Urolithin A (Mitopure)

C+
Musculoskeletal Supplement MusculoskeletalCardiovascularImmune

Urolithin A is the cleanest evidence story in the supplement space. Timeline/Amazentis has published six human clinical trials showing improved mitochondrial function and muscle endurance.…

Reviewed 2026-03-15

Colchicine

C+
Cardiology Rx (Repurposed)

An anti-inflammatory drug with two large trials showing it lowers the risk of heart attacks and strokes in people who already have cardiovascular disease. FDA-approved in 2023 for that use.…

Grade and summary pending review
Reviewed 2026-10-22

Acarbose

C+
Metabolic Rx (Repurposed)

A diabetes drug with a large, high-quality trial. It did NOT reduce heart attacks or deaths, but it did reduce progression to diabetes by about 18% in people with prediabetes. Its longevity…

Grade and summary pending review
Reviewed 2026-10-22

Testosterone replacement therapy (TRT)

C+
Cardiology Rx (Repurposed)

For men with DIAGNOSED hypogonadism (clinically low testosterone), a large safety trial (TRAVERSE) found it does not raise major cardiac events, though it carries some real risks. There is…

Grade and summary pending review
Reviewed 2026-10-22

CoQ10 (Ubiquinol)

C+
Cardiology Supplement CardiovascularMusculoskeletal

CoQ10 has the longest clinical evidence history of any longevity supplement. A 2024 meta-analysis found CoQ10 supplementation significantly reduced major adverse cardiovascular events. The…

Reviewed 2026-03-15

Rapamycin (Sirolimus)

C
Longevity Rx (Repurposed) ImmuneCardiovascularNeurological

Rapamycin has the strongest preclinical lifespan extension data of any compound — consistent results across yeast, worms, flies, and mice, including the ITP (Interventions Testing…

Reviewed 2026-03-15

Vitamin D

C
Multi-system Supplement

One of the most rigorously tested supplements in existence. For people who already have adequate levels, the large trials (VITAL, ViDA, D-Health) show it does NOT prevent cancer,…

Grade and summary pending review
Reviewed 2026-10-22

Nattokinase

C
form-specific
Cardiology Supplement

A fibrinolytic enzyme from fermented soy, studied in human trials for effects on clotting markers, with one study using an imaging endpoint. There is a dose gap worth knowing about: trials…

Grade and summary pending review
Reviewed 2026-10-22

Omega-3 (standard EPA+DHA fish oil supplement)

C
Cardiology Supplement

Standard over-the-counter fish oil. Large trials (STRENGTH, VITAL) found NO significant cardiovascular benefit at typical supplement doses. This is a different product and a different…

Grade and summary pending review
Reviewed 2026-10-22

Iron Reduction (ferritin lowering)

C
sex-stratified
Longevity Therapeutic

This entry grades the intervention, lowering body iron through phlebotomy or blood donation, rather than ferritin as a test. Three lines of evidence disagree: observational data is heavily…

Grade and summary pending review
Reviewed 2026-10-22

Spermidine

C-
Longevity Supplement CardiovascularNeurologicalImmune

Spermidine is an autophagy inducer with an interesting epidemiological signal — the Bruneck Study (n=829, 20-year follow-up) found that higher dietary spermidine intake was associated…

Reviewed 2026-03-15

Sulforaphane (preformed)

C-
one sponsorform-specific
Multi-system Supplement

Preformed sulforaphane requires no conversion step, so the dose reaching the bloodstream is more predictable than with precursor forms. Human trials report changes in detoxification and…

Grade and summary pending review
Reviewed 2026-10-22

NR (Nicotinamide Riboside / Tru Niagen)

C-
Longevity Supplement CardiovascularNeurologicalHepatic

NR (Tru Niagen by ChromaDex) shares the NAD+ precursor mechanism with NMN but has a slightly stronger evidence base. ChromaDex has published more clinical trials and holds actual patents…

Reviewed 2026-03-15

Berberine

C-
Metabolic Supplement

A supplement with a large base of trials showing it improves blood sugar and lipids — but most of those trials are low quality, and all measure surrogate markers, not hard outcomes like…

Grade and summary pending review
Reviewed 2026-10-22

Akkermansia muciniphila

C-
form-specific
Metabolic Supplement

A gut commensal studied as a pasteurised preparation rather than a live culture, and the pasteurised form performed better in the randomised trial. Endpoints were metabolic markers measured…

Grade and summary pending review
Reviewed 2026-10-22

NMN (Nicotinamide Mononucleotide)

C-
Longevity Supplement CardiovascularNeurologicalMusculoskeletal

NMN is among the most popular longevity supplements, but there is a significant gap between consumer enthusiasm and published clinical evidence. Human trials to date are small (typically…

Reviewed 2026-10-22

C15:0 (pentadecanoic acid)

C-
form-specific
Metabolic Supplement

C15:0 is an odd-chain saturated fatty acid found mainly in dairy fat. Human evidence is thin: one small trial reporting a change in a liver enzyme, alongside observational work that cannot…

Grade and summary pending review
Reviewed 2026-10-22

Sulforaphane (glucoraphanin + active myrosinase)

C-
form-specific
Multi-system Supplement

Glucoraphanin delivered together with active myrosinase converts to sulforaphane during digestion. Conversion is more reliable than precursor alone but still less predictable than taking…

Grade and summary pending review
Reviewed 2026-10-22

Astaxanthin

C-
one sponsor
Longevity Supplement

A carotenoid with human trials reporting changes in skin and eye surrogate markers. The trials are small and short, and none measure clinical outcomes. A large share of the published work…

Grade and summary pending review
Reviewed 2026-10-22

D+Q (Dasatinib + Quercetin) Senolytic

D+
Longevity Rx (Repurposed) ImmunePulmonaryRenal

D+Q is the original senolytic combination, pioneered by James Kirkland at Mayo Clinic. The concept — selectively killing senescent cells — is compelling, and preclinical data is strong.…

Reviewed 2026-03-15

Ergothioneine

D+
one sponsor
Longevity Supplement

An amino acid derivative notable for having a dedicated transporter in human tissue, which is unusual and has driven scientific interest. Human trials are few and use biomarker endpoints.…

Grade and summary pending review
Reviewed 2026-10-22

Molecular hydrogen (H₂)

D+
form-specific
Inflammation Supplement

Hydrogen-rich water and inhaled hydrogen gas have been studied in small trials using biomarker endpoints. Delivery route changes the dose substantially, so dissolved and inhaled hydrogen…

Grade and summary pending review
Reviewed 2026-10-22

Taurine

D+
Longevity Supplement

A supplement popular after a 2023 animal study, but the human evidence is limited to short trials on surrogate markers (blood pressure, lipids) — no human longevity outcomes. The idea…

Grade and summary pending review
Reviewed 2026-10-22

Fisetin

D+
Longevity Supplement ImmuneNeurologicalMusculoskeletal

Fisetin exemplifies the senolytic evidence gap. A 2018 preclinical study identified it as the most potent senolytic flavonoid, extending healthspan in aged mice. This generated enormous…

Reviewed 2026-03-15

Quercetin (standalone)

D+
Inflammation Supplement ImmuneCardiovascular

Quercetin as a standalone supplement has weak evidence for longevity. Its primary interest is as the 'Q' in D+Q senolytic therapy, but without dasatinib, quercetin alone has not…

Reviewed 2026-03-15

Sulforaphane (glucoraphanin alone)

D+
form-specific
Multi-system Supplement

Glucoraphanin without added myrosinase relies on gut bacteria to convert it, and that conversion varies widely between individuals. The practical consequence is that the same capsule can…

Grade and summary pending review
Reviewed 2026-10-22

GlyNAC (glycine + N-acetylcysteine)

D+
Longevity Supplement

The dramatic 'reverses aging hallmarks' headlines come from one very small trial at a single lab. A larger independent trial did NOT confirm the main result (it missed its primary…

Grade and summary pending review
Reviewed 2026-10-22

Low-dose lithium

D+
Neuro Rx (Repurposed)

One of the most scientifically intriguing dementia-prevention candidates — a 2025 mechanism plus three small trials all point the same direction. But the human evidence is still small and…

Grade and summary pending review
Reviewed 2026-10-22

R-1,3-butanediol

D
form-specific
Metabolic Supplement

A ketone precursor that raises circulating beta-hydroxybutyrate. Human evidence is limited and short-term, covering metabolic and performance markers. An identity caveat matters here: most…

Grade and summary pending review
Reviewed 2026-10-22