Rankings / Longevity
Longevity — Supplements
NAD+ precursors, alpha-ketoglutarate, astaxanthin, sulforaphane, GHK-Cu, tretinoin — the over-the-counter longevity supplement aisle.
| # | Compound | Ev | Bn | Sf | Grade · Score |
|---|---|---|---|---|---|
| 1 | Lutein + Zeaxanthin Macular xanthophyll carotenoid | 8 | 6.5 | 9 | A+ 8.2 |
| 2 | Tretinoin (all-trans retinoic acid) Retinoid — RAR agonist | 10 | 10 | 5 | A 8 |
| 3 | Alpha-ketoglutarate (Ca-AKG) TCA cycle intermediate | 6 | 5 | 9 | B+ 7.1 |
| 4 | Astaxanthin Carotenoid antioxidant | 6 | 5 | 9 | B+ 7.1 |
| 5 | Glycine (longevity / metabolic) Amino acid / methionine restriction mimetic | 6 | 5 | 9 | B+ 7.1 |
| 6 | Glycine + NAC (GlyNAC) Amino acid combo | 6 | 5 | 9 | B+ 7.1 |
| 7 | NAD+ / NMN / NR NAD+ precursor | 6 | 5 | 9 | B+ 7.1 |
| 8 | Sulforaphane Nrf2 activator | 6 | 5 | 9 | B+ 7.1 |
| 9 | ACE inhibitors / ARBs (telmisartan / losartan / enalapril) RAAS inhibitor / repurposed cardiometabolic | 6 | 5 | 7 | B- 6.3 |
| 10 | SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) SGLT2 inhibitor / glucoretic | 6 | 5 | 5 | C+ 5.5 |
| 11 | 17-alpha estradiol Non-feminizing estrogen | 2 | 5 | 7 | C- 4.5 |
| 12 | Censavudine / TPN-101 (LINE-1 suppression) Reverse transcriptase inhibitor (NRTTI) | 2 | 5 | 5 | D+ 3.7 |
| 13 | GDF11 Circulating factor | 2 | 5 | 5 | D+ 3.7 |
| 14 | Klotho Anti-aging protein | 2 | 5 | 5 | D+ 3.7 |
| 15 | C60 (carbon 60 / buckminsterfullerene) Fullerene / antioxidant | 3 | 2 | 4 | D 3.3 |
| 16 | NDGA (nordihydroguaiaretic acid) Plant lignan / ITP geroprotector | 3 | 3.5 | 3.5 | D 3.3 |
| 17 | Plasma exchange / young plasma Dilutional therapeutic | 3 | 3.5 | 3.5 | D 3.3 |
| 18 | Yamanaka factors / partial reprogramming Epigenetic reprogramming | 2 | 5 | 3.5 | D 3.1 |
| 19 | ER-100 (partial epigenetic reprogramming) Partial epigenetic reprogramming | 2 | 8 | 2 | D 2.9 |
This is the over-the-counter longevity aisle — NAD+ precursors, polyphenols, polyamines, senolytics in supplement form. It is also the category where marketing outruns human evidence by the widest margin. Mouse data is everywhere; randomised human outcome data is rare. The rankings here are deliberately conservative: a compound that reliably moves a biomarker still scores as moderate until it shows it changes something you would actually feel or live longer for.
What the human data supports
NAD+ precursors (NMN, NR) reliably raise NAD+ levels in people — that part is real and well-replicated in RCTs. What no human trial has yet shown is that raising NAD+ extends healthspan or lifespan; the dramatic mouse results have not translated, so these sit at moderate evidence. Urolithin A (Mitopure) has the cleanest supplement data here: randomised trials (2019, 2022) show measurable improvements in mitochondrial and muscle-endurance markers, though the effect is modest. Spermidine has intriguing observational links to longevity and small trials on memory in older adults, but nothing definitive.
The cautionary tale
Resveratrol is the category’s lesson in hype. It launched a thousand red-wine headlines, then ran into poor oral bioavailability and a string of unimpressive or null human trials — it ranks low here for a reason. Fisetin, the senolytic everyone is excited about, is still almost entirely preclinical; the Mayo Clinic human trials are what would move its tier. Calcium alpha-ketoglutarate (Ca-AKG) rests on mouse lifespan data plus small, uncontrolled human reports.
The high scorer, with fine print
Tretinoin earns an A in this category, but read the label: its strong evidence is topical, for photoaged skin, not systemic longevity. It is the most evidence-backed "anti-aging" compound most people can access — for skin. Treat the category’s top score as a reminder that an "anti-aging" claim is only as good as the endpoint it was actually tested against.
Frequently asked
Do NMN and NR actually extend lifespan?
They reliably raise NAD+ levels in humans, which is well established. But no human trial has shown they extend lifespan or healthspan — the striking results are from mice and have not translated yet. That gap is why they sit at moderate, not strong, evidence here.
Why does resveratrol rank so low?
Despite the early hype, resveratrol has poor oral bioavailability and a track record of unimpressive or null human trials. The rankings reflect the published human evidence rather than the marketing, so it lands near the bottom of the longevity supplements.
Which longevity supplement has the best human evidence?
Among supplements, urolithin A has the cleanest randomised human data, showing modest improvements in mitochondrial and muscle-endurance markers. For accessible compounds overall, topical tretinoin has the strongest evidence — but for skin aging specifically, not whole-body longevity.
Is fisetin a proven senolytic?
Not yet in humans. The senolytic excitement around fisetin rests largely on preclinical work; Mayo Clinic human trials are ongoing, and a positive peer-reviewed readout is what would raise its tier.
Scores reflect the published evidence, not a recommendation to use any compound or protocol. Nothing here is medical advice. How we score →