The ranked stack · 63 entries
Everything,
in honest order.
The ordering is not up for debate on a whim. Tier decides first — a foundation always sits above a supplement, which always sits above the frontier. Within a tier, a legible score blends impact, evidence, reach, effort, and risk. That's why a grade-A frontier molecule still ranks below a good night's sleep. See the method →
01 Aerobic base: the single best predictor you can change Build cardiorespiratory fitness — mostly easy Zone 2 volume, topped with a little hard work. Few things predict a long, capable life as strongly. Impact Evid. A Effort Risk Worth it 93 02 Sleep: the bottleneck hiding in plain sight Enough sleep, on a regular schedule, with breathing that works — the nightly maintenance window everything else depends on. Impact Evid. A Effort Risk Worth it 93 03 Nutrition: the pattern, not the hack A mostly-whole-food dietary pattern with enough protein and fiber, at an energy intake that matches your goal — the base every stack is built on. Impact Evid. B Effort Risk Worth it 87 04 Resistance training: buying back the decades Lift things a couple of times a week. It defends muscle, bone, glucose control, and independence as you age. Impact Evid. A Effort Risk Worth it 82 05 Alcohol: the health case for the 'good for you' glass has collapsed There is no amount that improves health — the old 'a glass of red is good for you' J-curve was largely a study artifact. Impact Evid. B Effort Risk Worth it 63 06 Protein: enough, spread out, not a religion Get adequate daily protein — more than the bare-minimum RDA if you train or you're older — to support muscle you're trying to keep or build. Impact Evid. B Effort Risk Worth it 63
07 ApoB and LDL: the number that writes your risk over decades Know your ApoB (or LDL-C), because the atherogenic particles it counts are causal in heart disease — and the exposure is cumulative over a lifetime. Impact Evid. A Effort Risk Worth it 88 08 Blood pressure: the silent, fixable multiplier Know your blood pressure and keep it in range — it's one of the most treatable inputs to heart attack, stroke, and kidney disease. Impact Evid. A Effort Risk Worth it 88 09 A1c & glucose: the early-warning numbers that lifestyle moves first The numbers that catch metabolic drift years before diabetes — cheap to measure, and lifestyle moves them first. Impact Evid. A Effort Risk Worth it 77
10 Cancer screening: the tests that actually save lives Age- and risk-based screening for a handful of cancers — colorectal, breast, cervical, lung — where catching it early genuinely changes the outcome. Impact Evid. B Effort Risk Worth it 70 11 The labs that change a decision A small panel that actually moves your hand — lipids/ApoB, blood pressure, A1c, and a few targeted tests — instead of an expensive dashboard you'll never act on. Impact Evid. B Effort Risk Maybe 67 12 hs-CRP: the inflammation number, in context A cheap marker of low-grade inflammation that adds a little to cardiovascular risk prediction — useful at the margins, not a diagnosis. Impact Evid. C Effort Risk Maybe 44
13 Caffeine: the world's most-used drug, treated honestly The best-evidenced legal ergogenic and alertness aid there is — powerful, cheap, and safe within limits, with a real cost to your sleep if you mistime it. Impact Evid. A Effort Risk Maybe 73 14 Creatine: the one supplement that earns its shelf space Creatine monohydrate — the most evidence-backed, cheapest, best-studied performance supplement there is. Boring, and it works. Impact Evid. A Effort Risk Worth it 73 15 Psyllium: the boring soluble fiber that quietly outperforms most supplements A cheap soluble fiber that lowers LDL, steadies blood glucose, and fixes bowel regularity — one of the better-evidenced supplements most people ignore. Impact Evid. B Effort Risk Worth it 63 16 Iron: the right fix when you're low, a real hazard when you're not The definitive treatment for iron-deficiency anemia — powerful when you're genuinely low, and genuinely risky to take when you're not. Impact Evid. B Effort Risk Maybe 58 17 Melatonin: a timing signal, not a sedative A hormone that shifts your body clock — genuinely useful for jet lag and delayed sleep timing, and often mistaken for a knockout pill it isn't. Impact Evid. B Effort Risk Maybe 51 18 Vitamin B12: a real fix for a real deficiency, and nothing more Essential to correct if you're actually deficient — vegans, older adults, long-term metformin or PPI users — and inert if you're already replete. Impact Evid. B Effort Risk Maybe 51 19 Omega-3: where the marketing outran the trials Fish-oil capsules do far less for the average healthy person than the bottle implies — the real cardiovascular signal lives in specific high-risk contexts. Impact Evid. C Effort Risk Maybe 44 20 Vitamin D: correct a deficiency, don't chase a supplement Worth taking if you're actually low; largely inert for hard outcomes if you're already replete. A fix for a deficiency, not a longevity lever. Impact Evid. C Effort Risk Maybe 44 21 Ashwagandha: a real signal for stress, and a real liver caveat An adaptogenic herb with small-but-consistent trials for stress and anxiety — and rare, genuine reports of liver injury that make the risk more than theoretical. Impact Evid. C Effort Risk Maybe 40 22 Magnesium: useful, not magic A reasonable low-stakes add-on when intake is low or sleep quality is mildly off — wildly over-marketed, and not a substitute for fixing the basics. Impact Evid. C Effort Risk Maybe 40 23 Zinc: right tool for two narrow jobs, wrong idea as a daily habit Genuinely useful for shortening a cold if started early and for correcting real deficiency — but chronic high-dose supplementation quietly depletes copper, so more is not better. Impact Evid. C Effort Risk Maybe 40 24 Berberine: real modest effects, and a mountain of hype it doesn't earn A plant alkaloid with genuine but modest effects on glucose and lipids — and a 'nature's Ozempic' reputation it comes nowhere near deserving. Impact Evid. C Effort Risk Maybe 37 25 Curcumin: a modest joint signal wrapped around a bioavailability problem Turmeric's active compound, with a modest anti-inflammatory and joint-pain signal — and a serious absorption problem that most products don't solve. Impact Evid. C Effort Risk Maybe 29 26 Glycine: a small, quiet nudge for sleep quality An inexpensive amino acid with a thin but real signal for better subjective sleep quality when taken before bed — nothing dramatic, and studied only in small trials. Impact Evid. C Effort Risk Maybe 29 27 L-theanine: calm alertness, at a modest scale An amino acid from tea associated with a calm, focused state — mildly promising for acute stress and, paired with caffeine, for attention. Effects are small and the stakes are low. Impact Evid. C Effort Risk Maybe 29
28 Statins: the workhorse of cardiovascular prevention The most-studied cardiovascular drug there is — strong, cheap, and considerably better tolerated than its reputation suggests. Impact Evid. A Effort Risk Know the context 83 29 GLP-1 agonists: a real tool, and a clinician's call A genuinely powerful class of medication for obesity and cardiometabolic risk — with strong trial evidence, real side effects, and a cost profile that belongs in a medical decision. Impact Evid. A Effort Risk Know the context 76 30 SGLT2 inhibitors: diabetes drugs that turned into organ protectors Diabetes drugs that turned out to protect the heart and kidneys, now used well beyond glucose control. Impact Evid. A Effort Risk Know the context 68 31 PCSK9 inhibitors: very low LDL, proven benefit, at a price Injectable antibodies that drive LDL to strikingly low levels, with proven cardiovascular event reduction for high-risk patients — held back mainly by cost and access. Impact Evid. A Effort Risk Know the context 63 32 Ezetimibe: the quiet add-on when a statin isn't enough A well-tolerated pill that lowers LDL by blocking its absorption in the gut, with proven incremental event reduction when added on top of a statin. Impact Evid. A Effort Risk Know the context 60 33 Metformin: a proven diabetes drug with a longevity story that outruns its evidence The first-line drug for type 2 diabetes with a strong, decades-deep safety record — and an anti-aging reputation that has gotten well ahead of what's actually been shown in humans. Impact Evid. A Effort Risk Know the context 57 34 Tadalafil: the daily pill with a surprisingly friendly profile A long-acting PDE5 inhibitor taken as a low daily dose — FDA-approved for both erectile dysfunction and benign prostatic hyperplasia, cheap as a generic, and generally well tolerated. Impact Evid. A Effort Risk Maybe 49 35 Testosterone (TRT): a treatment for a diagnosis, not an upgrade Appropriate treatment for diagnosed hypogonadism — not an anti-aging shortcut for normal men. Impact Evid. B Effort Risk Know the context 47 36 Low-dose aspirin: right after a heart attack, wrong for most healthy people Valuable after a cardiovascular event, but for primary prevention the bleeding risk usually outweighs the benefit. Impact Evid. A Effort Risk Know the context 46 37 PT-141 (Vyleesi): an FDA-approved libido drug with a gray-market shadow Bremelanotide, a melanocortin agonist FDA-approved as Vyleesi for low sexual desire in premenopausal women — genuinely approved for that use, and unapproved (off-label) for everyone else who buys it as a peptide. Impact Evid. B Effort Risk Maybe 39 38 Enclomiphene: raising your own testosterone, with a catch A SERM that raises the body's own testosterone by nudging LH and FSH — preserving fertility unlike TRT — but not FDA-approved and available only through compounding. Impact Evid. B Effort Risk Know the context 34 39 Low-dose naltrexone: cheap, intriguing, and under-studied Naltrexone at a fraction of its usual dose (1.5–4.5 mg), used off-label for chronic pain, fibromyalgia, and some autoimmune conditions on genuinely thin but interesting evidence. Impact Evid. C Effort Risk Know the context 28
40 Urolithin A: a mitochondrial supplement with actual human trials — and modest results A gut-microbiome metabolite that improves mitochondrial quality — with a few real human RCTs showing modest muscle and endurance effects. Impact Evid. C Effort Risk Know the context 40 41 GHK-Cu: a copper peptide where the cream is the evidence A copper-binding tripeptide used topically for skin, hair, and wound repair — with modest but real human skin data for the cream, and unproven claims for the injectable systemic version. Impact Evid. C Effort Risk Know the context 37 42 NMN & NR: the biomarker moves, the outcome is missing NAD+ precursors that reliably raise a biomarker — with almost no evidence yet that the biomarker translates to living longer or better. Impact Evid. C Effort Risk Know the context 32 43 Rapamycin: the most interesting molecule we can't yet recommend The strongest animal-longevity signal in the field — and almost no human outcome data. A fascinating hypothesis, not a protocol. Impact Evid. D Effort Risk Know the context 29 44 Spermidine: the autophagy molecule with a promising epidemiological shadow A dietary polyamine tied to autophagy and, in observational data, to longer life — with human trials still small and early. Impact Evid. C Effort Risk Know the context 29 45 Methylene Blue: a real drug with real risks, and a biohacker halo it hasn't earned A century-old redox dye and approved emergency antidote, repurposed by biohackers for low-dose cognitive and mood claims that rest on a few small human studies. Impact Evid. C Effort Risk Know the context 28 46 Thymosin alpha-1: the peptide with real trials — and real caveats An immune-modulating peptide with a genuine clinical footprint abroad (hepatitis B, sepsis, cancer adjunct, studied in COVID) — but not FDA-approved in the US for general use. Impact Evid. C Effort Risk Know the context 28 47 Cerebrolysin: real trials, genuinely uncertain answers A porcine-brain-derived peptide mixture used clinically abroad for stroke and dementia, with actual RCTs and Cochrane reviews that land on 'probably no benefit.' Impact Evid. C Effort Risk Know the context 24 48 SS-31 (elamipretide): the mitochondrial peptide that actually went to trial — and mostly missed A mitochondrial-targeted peptide (elamipretide) with real Phase 2/3 human trials in mitochondrial disease, heart failure, and dry AMD — most of which failed their primary endpoints. Impact Evid. C Effort Risk Know the context 24 49 Resveratrol: the longevity molecule that didn't survive contact with humans The red-wine 'longevity molecule' that launched a thousand supplements and then failed to deliver in humans. Impact Evid. D Effort Risk Skip it 22 50 BPC-157: fascinating in rodents, unknown in humans A 'healing peptide' with genuinely interesting animal data and essentially no human trials, sold gray-market with unknown safety. Impact Evid. D Effort Risk Know the context 21 51 Selank: a Russian anxiolytic peptide the West has never verified A synthetic tuftsin-analog peptide used in Russia for anxiety, with small domestic trials and essentially no independent evidence. Impact Evid. D Effort Risk Know the context 21 52 Semax: a Russian nootropic with a thin evidence trail A synthetic ACTH(4-10) fragment used in Russia for stroke and cognition, with almost no independent Western evidence. Impact Evid. D Effort Risk Know the context 21 53 GH secretagogues: raising a hormone isn't the same as slowing aging Sermorelin, ipamorelin and similar peptides that nudge growth-hormone release — marketed for anti-aging on evidence that doesn't exist. Impact Evid. D Effort Risk Know the context 18 54 MOTS-c: a real exercise signal, an unproven exercise-in-a-vial A mitochondrial-derived peptide that your own muscle releases during exercise — with striking mouse metabolic data and no human trials of the injected version. Impact Evid. D Effort Risk Know the context 18 55 Senolytics: one of the best longevity ideas, and not yet a protocol Drugs that try to clear 'zombie' senescent cells — one of the most promising longevity ideas, and nowhere near ready to self-administer. Impact Evid. D Effort Risk Know the context 18 56 5-Amino-1MQ: a mouse fat-loss molecule sold as if the trial already happened An oral NNMT-inhibitor 'research compound' marketed for fat loss on the strength of a single mouse study, with zero human trials. Impact Evid. D Effort Risk Skip it 10 57 Dihexa: a spectacular animal claim with no human data An angiotensin-derived 'nootropic' peptide reported to be extraordinarily potent for synaptogenesis in animals — with zero human trials and gray-market supply. Impact Evid. D Effort Risk Skip it 10 58 DSIP: an old sleep peptide that never resolved Delta Sleep-Inducing Peptide — a decades-old sleep peptide with sparse, inconsistent human data and no modern trials. Impact Evid. D Effort Risk Skip it 10 59 Pinealon: a nootropic peptide known almost entirely to one lab's cell cultures A synthetic tripeptide (Glu-Asp-Arg) marketed as a neuroprotective nootropic, with evidence that is almost exclusively animal and in-vitro from a single research group. Impact Evid. D Effort Risk Know the context 10 60 TB-500: the recovery peptide that healed rats and skipped humans A synthetic fragment of thymosin beta-4 sold as a 'healing/recovery' peptide — with real animal tendon and wound data, no human trials, WADA-banned status, and a gray-market supply. Impact Evid. D Effort Risk Know the context 10 61 Thymalin: immune 'rejuvenation' resting on one lab's open-label trials A thymic peptide bioregulator claimed to restore immune function and extend life in the elderly, backed almost entirely by single-group, open-label Russian studies. Impact Evid. D Effort Risk Know the context 10 62 Epitalon: a telomere fantasy built almost entirely on one Russian lab A synthetic pineal tetrapeptide claimed to lengthen telomeres and extend lifespan, resting on decades of single-group data and zero independent human RCTs. Impact Evid. D Effort Risk Know the context 7 63 Khavinson peptide bioregulators: a whole class built on one lab's word The Russian 'peptide bioregulator' family (epitalon, thymalin, cortexin, cerluten, ventfort and more) — tissue-specific peptides claimed to reverse aging, resting on decades of single-group, hard-to-verify evidence. Impact Evid. D Effort Risk Skip it 7