Last Updated Apr 2025
Evidence-Based Reference

Longevity Supplements:
What the evidence actually shows.

Every compound graded A–D based on the strength of human clinical evidence for aging-related outcomes. Not marketing — methodology. We tell you what works, what's promising, what's hype, and what requires a physician.

42
Compounds Reviewed
6
Grade-A Compounds
120+
Studies Referenced
Apr 2025
Last Updated
Evidence Grades A — Strong Multiple RCTs in humans; consistent effect
B — Promising Some human trials; effect plausible
C — Preliminary Animal/mechanistic data; limited human trials
D — Insufficient Weak or conflicting evidence; often overhyped
Rx — Prescription Requires physician supervision
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42 compounds
How We Grade Evidence

Grades reflect the quality and consistency of human clinical evidence for aging-related outcomes specifically — not general health effects. A compound with extensive animal data but no human longevity trials cannot achieve Grade A, regardless of mechanism.

A
Strong Evidence
Multiple RCTs in humans with consistent effects on aging biomarkers or longevity-related outcomes. Mechanism well-established.
B
Promising Evidence
At least one quality RCT or consistent cohort data in humans. Plausible mechanism. More research ongoing.
C
Preliminary
Strong animal or mechanistic data, but limited or mixed human trial evidence. Watch this space.
D
Insufficient
Weak, conflicting, or largely absent human evidence for aging claims. Often marketed well beyond what data supports.
Rx
Prescription Only
Compounds with significant evidence but requiring physician oversight due to side effects, interactions, or regulatory status.
Methodology & Editorial Standards

How We Evaluate Longevity Compounds

The longevity supplement space is flooded with overblown claims, cherry-picked studies, and animal data misrepresented as human evidence. Our evaluation framework is designed to cut through this systematically.

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Human Trials First
We prioritize randomized controlled trials in humans. Animal and in vitro data inform mechanism but cannot elevate a grade. A compound that dramatically extends lifespan in C. elegans and mice, but has no human RCTs, cannot exceed Grade C.
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Aging-Specific Outcomes
We evaluate evidence for aging-related endpoints specifically: biological age markers, VO₂max, muscle mass, cardiovascular events, inflammatory markers, cognitive function. General "health" effects don't automatically confer longevity evidence.
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Replication & Consistency
A single positive trial — however large — cannot achieve Grade A without replication. We require consistent effects across multiple independent trials. The failure of resveratrol to replicate early positive findings is a canonical example of why replication matters.
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Risk-Benefit Calibration
Safety and side effect profiles are weighted alongside efficacy. A compound with Grade B evidence but significant side effects may have a worse risk-benefit profile than a Grade C compound with excellent safety. We always present both dimensions.

Medical Disclaimer: This database is for educational and informational purposes only. It does not constitute medical advice, and no compound listed here should be started, stopped, or modified without consulting a qualified physician. Prescription compounds (marked Rx) require physician oversight. Longevity medicine is a rapidly evolving field — grades will be updated as new evidence emerges. Last comprehensive review: April 2025.

Why This Database Exists

The problem with longevity supplement marketing

The supplement industry operates on a fundamental information asymmetry: companies know the evidence limitations of their products far better than consumers do. This database is our attempt to close that gap systematically.

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The Animal Data Problem

The history of longevity supplements is littered with compounds that dramatically extended lifespan in worms, flies, or mice — and failed to replicate in humans. Resveratrol is the canonical example: extraordinary animal results, failed human RCTs. Our grading system explicitly penalizes animal-only evidence, regardless of how mechanistically compelling it is. A compound cannot exceed Grade C without human trial data.

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Industry-Funded Research

The majority of human supplement trials are funded by manufacturers. This doesn't make findings wrong, but it does mean they require independent replication before being treated as definitive. Industry-funded studies are 3–4 times more likely to find positive results than independently funded studies — a well-documented phenomenon in the nutritional science literature. We flag industry funding in every relevant entry and require replication before upgrading a grade.

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Surrogate vs. Hard Endpoints

Many supplements demonstrate positive effects on biomarkers — blood NAD+ levels, inflammatory markers, glucose — without demonstrating actual mortality or morbidity benefit. Raising NAD+ is not the same as extending lifespan. Reducing CRP is not the same as preventing a heart attack. We distinguish carefully between surrogate endpoint evidence (what most supplement trials measure) and hard endpoint evidence (what actually matters for longevity).

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The Duration Problem

Most supplement RCTs run 8–16 weeks. Longevity effects, by definition, require decades to measure directly. This creates a fundamental evidence ceiling for all longevity supplements: we cannot yet run the trials that would definitively prove or disprove longevity effects. The best available proxy is the combination of mechanistic plausibility, validated biomarker effects in humans, and (where available) population data on dietary intake patterns and mortality outcomes.

Understanding Grade A compounds: What strong evidence actually means

Grade A in this database means multiple randomized controlled trials in humans with consistent effects on aging-related or longevity-relevant outcomes, with a well-established mechanism. As of our last comprehensive review (April 2025), only five compounds in this database meet that bar: Omega-3 fatty acids (REDUCE-IT, ASCEND), Magnesium (Fang et al. BMC Med 2016 meta-analysis of 40 studies), Vitamin D3 with K2 (VITAL, D-HEALTH), Creatine monohydrate (Gualano meta-analysis, Rae et al. Proc R Soc B), and Niacin (Coronary Drug Project, multiple lipid trials).

Grade A does not mean "take this compound" — it means the evidence is strong enough that the risk-benefit calculation warrants serious consideration for most healthy adults. Magnesium, for example, is Grade A because a meta-analysis of 40 prospective cohort studies found dose-response relationships between magnesium intake and cardiovascular disease, type 2 diabetes, stroke, and all-cause mortality — combined with an excellent safety profile and the fact that 48% of Americans fail to reach the recommended daily intake. That combination of evidence quality, effect magnitude, and safety makes it among the most defensible supplements available.

Compare this to NMN and NR, both Grade B. Both reliably raise blood NAD+ levels in humans (confirmed in multiple RCTs). Both have plausible mechanistic connections to longevity through NAD+-dependent pathways including sirtuin activation, PARP-mediated DNA repair, and mitochondrial function. But neither has yet demonstrated an effect on hard clinical endpoints — cardiovascular events, cancer incidence, mortality, or even a validated aging clock like GrimAge over a meaningful timeframe. The 2025 Elhassan et al. head-to-head trial confirmed blood NAD+ elevation but found no brain or liver NAD+ increase by 31P-MRS. Until that gap closes, Grade B is the honest assessment.