NAD+ going up, a mouse living longer, or a marker improving does not establish longer human life.
Creatine · omega-3 for selected indications · vitamin D deficiency correction · magnesium deficiency correction · protein/fiber adequacy
Quick reference · signature artifact
The Evidence Tier List
Tier names answer “what can we honestly claim in humans?” They do not say a product is safe, necessary, or better than food, exercise, sleep, and indicated medical care.
NMN/NR · GlyNAC · berberine · taurine · glycine · urolithin A · fisetin
Resveratrol · spermidine · CoQ10 for longevity · collagen lifespan claims · most senolytic stacks
High-dose beta-carotene or vitamin E · detoxes · mega-dose stacks · unverified sexual/weight-loss products
Rapamycin · metformin · acarbose: intriguing animal or disease evidence, not self-experiment instructions
How to grade a supplement claim
Human outcome beats biomarker.
Deficiency correction is different.
A nutrient can be essential and valuable when deficient without improving lifespan in well-nourished people who add more.
Brand quality matters.
U.S. supplements are not pre-approved for safety, effectiveness, or label accuracy. USP/NSF certification is a quality signal, not proof of benefit.
Absence has two meanings.
“No data” is not “works”; a convincing null outcome trial is stronger evidence than a mechanism story.
Working knowledge
Compound-by-compound ledger
| Compound / tier | What human evidence supports | Reported study amount / cost order | Risk, interaction, honest verdict |
|---|---|---|---|
| DEMONSTRATED Creatine monohydrate | Strong evidence for strength/lean-mass performance with resistance training; no human lifespan endpoint. | Common trial maintenance: 3–5 g/day; low cost. | Weight gain from water is common. Kidney disease and medication context require clinician input. Verdict: useful performance tool, not an anti-aging drug. |
| DEMONSTRATED Omega-3 EPA/DHA | Specific prescription/high-risk cardiovascular evidence differs from over-the-counter fish oil; general-population lifespan claim is not established. | Trials vary widely; VITAL used 1 g/day marine omega-3. Moderate cost. | Bleeding/atrial-fibrillation context and formulation matter. Verdict: indication-specific, not a universal longevity capsule. |
| DEFICIENCY Vitamin D | Corrects deficiency and supports bone/mineral physiology; broad supplementation has not proven longer life in replete adults. | RDA is 600–800 IU/day by age; studies vary. Low cost. | Excess can cause hypercalcemia; test/risk context matters. Verdict: correct deficiency, do not megadose for longevity. |
| DEFICIENCY Magnesium | Essential nutrient; evidence supports treatment of deficiency, not a generic lifespan benefit. | RDA is 310–420 mg/day from all sources. Low cost. | Diarrhea and kidney impairment risk; it can interact with some antibiotics. Verdict: food/test context first. |
| FOOD FIRST Protein / fiber | Adequate protein supports muscle during training/aging; fiber-rich food patterns support cardiometabolic health. Neither is a magic powder. | Dietary targets are individualized; food cost varies. | Renal disease and GI disorders change advice. Verdict: fix the diet before branded “longevity” blends. |
| EMERGING NMN | Human trials can raise NAD-related metabolites; functional/lifespan outcomes remain early and inconsistent. | Published trials have used 250–1,200 mg/day; high cost. | Long-term safety and meaningful outcome evidence are unsettled. Verdict: interesting mechanism; save money unless uncertainty is the point. |
| EMERGING Nicotinamide riboside (NR) | Raises NAD+ in human studies; no human lifespan outcome. | Common trials: 100–1,000 mg/day; high cost. | “Raises NAD+” is a surrogate, not a benefit. Verdict: no demonstrated longevity reason to buy it. |
| EMERGING GlyNAC | Small trials report changes in glutathione, mitochondrial and functional measures in older adults; replication/outcomes needed. | Study protocols vary by body weight; moderate cost. | Small-study optimism is not a lifespan result. Verdict: early signal only. |
| EMERGING Berberine | Can affect glycemic/lipid markers in studies; product quality and trial heterogeneity are major limitations. | Often studied around 500 mg 2–3×/day; low/moderate cost. | GI effects and interactions with glucose-lowering medicines. Verdict: do not substitute for diagnosis or medication management. |
| EMERGING Taurine | Human evidence is not a lifespan trial; much longevity enthusiasm comes from animal/mechanistic work. | Studies vary; low cost. | More is not automatically better. Verdict: food/nutrition context before a longevity claim. |
| EMERGING Glycine | Some small metabolic/sleep studies, no convincing human lifespan outcome. | Reported studies vary; low cost. | Not a replacement for protein adequacy or sleep treatment. Verdict: low priority. |
| EMERGING Urolithin A | Human trials report mitochondrial/functional biomarkers; lifespan outcomes are absent. | Studies commonly use 500–1,000 mg/day; high cost. | Short studies cannot settle aging claims. Verdict: interesting but expensive uncertainty. |
| EMERGING Fisetin | Senolytic framing is largely preclinical; small human trials are not lifespan proof. | Intermittent study protocols vary; moderate cost. | Do not copy online “senolytic protocols.” Verdict: not ready for routine self-experimentation. |
| UNPROVEN Resveratrol | SIRT1/longevity narrative outpaced reliable translational evidence; no human lifespan benefit. | Products range widely; moderate cost. | Drug interactions possible. Verdict: a classic mechanism-to-marketing gap. |
| UNPROVEN Spermidine | Observational associations and early studies do not establish longer human life. | Food/supplement amounts vary; moderate cost. | Do not treat a food compound as a validated anti-aging drug. Verdict: wait for outcomes. |
| UNPROVEN CoQ10 | May have selected clinical uses; no general longevity proof outside indication-specific contexts. | Trials often use 100–300 mg/day; moderate cost. | Discuss if on warfarin or with heart failure care. Verdict: not a generic longevity staple. |
| UNPROVEN Collagen | Skin/joint marketing is not lifespan evidence. | Studies commonly use 2.5–15 g/day; moderate cost. | It is protein, not a longevity signal. Verdict: choose for a specific goal, not anti-aging. |
| UNPROVEN Multivitamin | May fill dietary gaps; generally does not turn a well-nourished adult into a longer-lived one. | Label-dependent; low cost. | Can duplicate nutrients and mask deficiency workups. Verdict: insurance is not evidence of upside. |
| CAUTION High-dose beta-carotene | No longevity benefit; harm signal in certain populations, notably smokers in major trials. | Do not use as a longevity intervention. | Verdict: avoid high-dose supplementation unless specifically prescribed. |
| CAUTION High-dose vitamin E | Lower-bias antioxidant meta-analysis found increased mortality signal; other harms depend on dose/context. | Do not use as a longevity intervention. | Verdict: no anti-aging rationale for megadosing. |
| AVOID “Detox” / proprietary stack | Usually lacks a clear molecule, outcome, dose, or independently verifiable evidence. | Often high cost. | Adulteration and interaction risk rises with opacity. Verdict: do not buy a claim you cannot audit. |
| PRESCRIPTION Rapamycin | Robust animal lifespan data; human longevity trial evidence is not established. | Not a supplement; supervised trials use specific schedules. | Immunologic, metabolic and drug-interaction issues. Verdict: do not self-dose; clinical research is not a retail protocol. |
| PRESCRIPTION Metformin | Valuable diabetes drug; proposed aging trials do not make it a proven treatment for healthy people. | Prescription only. | GI effects, B12 considerations and possible exercise-adaptation questions. Verdict: indication-specific. |
| PRESCRIPTION Acarbose | Animal and diabetes evidence does not establish a healthy-person longevity protocol. | Prescription only. | GI effects and glucose context. Verdict: not a supplement stack component. |
Stacking, purity, and the expensive mistakes
The stack problem
Ten compounds create interactions, adherence noise, cost, and no way to know what helped or harmed. Add nothing to solve a vague “aging” feeling.
Third-party testing
USP Verified and NSF certification assess specific quality practices/products. They do not validate a claimed lifespan effect. Avoid products with hidden proprietary amounts.
Test before correction
Vitamin D, B12, iron and some electrolyte questions need clinical context. A supplement can normalize a number while hiding why it was abnormal.
Common mistakes
Buying Tier 2 while skipping Tier 0.
No NAD booster outranks tobacco cessation, activity, sleep, food, and indicated treatment.
“Clinically studied” = proven.
It may mean a short, manufacturer-funded biomarker study—read the endpoint and population.
Ignoring interactions.
Especially risky with anticoagulants, diabetes medicines, kidney disease, surgery, pregnancy, and polypharmacy.
Assuming natural means pure.
The quality and adulteration problem is part of the decision, not a footnote.
Sources and next pages
Sources accessed 2026-08-23: Bjelakovic et al., Cochrane antioxidant review; NIH Office of Dietary Supplements fact sheets; ClinicalTrials.gov (trial-status source); USP Verified; NSF dietary supplement guidance. Trial amounts are cited as examples of research exposure, not recommendations; conclusions are deliberately conservative where outcome evidence is absent.