Healthspan Evidence Profiles

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…

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…

Exercise carries a stronger human outcome base than any graded supplement in this registry — decades of randomized trials and large cohorts with hard endpoints including all-cause…

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

The Mediterranean dietary pattern has hard-endpoint randomized evidence (PREDIMED) for cardiovascular event reduction — unusual among dietary interventions, which are dominated by…

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…

Sleep duration and quality are among the most consistently associated exposures in observational aging research, across very large cohorts. The gap is interventional: trials that…

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.…

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.…

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…

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…

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…

Time-restricted eating changes when you eat rather than what. Randomised trials show modest metabolic changes, but most run for weeks rather than years, and several find the benefit tracks…

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

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,…

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…

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…

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…

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…

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…

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…

Trials report modest changes in blood pressure and stress markers over weeks to months. Blinding is impossible and active-control design is inconsistent, so it is frequently unclear whether…

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…

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…

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…

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…

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

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…

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.…

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.…

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…

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…

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…

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…

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…

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…

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…

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…

Human randomised trials exist, which is why this is graded rather than screened out. Reported cortisol reductions are real, but a 2020 replication decoupled the marker from the outcome:…