StackGuide

The ranked stack · 46 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 →

I

Foundations

Sleep, training, nutrition. The unglamorous base that does most of the work. If these are shaky, everything above is noise.

II

Heart & Metabolic

The risk numbers that predict how the decades go: blood pressure, ApoB, glucose. Measured, then managed.

III

Tests & Labs

Tests that change a decision, and the expensive noise that doesn't. Information is only useful if it moves your hand.

IV

Supplements

A short list earns its shelf space. Most don't. Graded honestly, dosed specifically, never as a substitute for the base.

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
V

Medications

Real tools with real mechanisms and real trade-offs. Adult context, not fear or hype — and a conversation with a clinician, not the internet.

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 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 38 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
VI

Frontier

Peptides, rapamycin curiosity, the experiments. Plausible mechanisms, thin human evidence. Interesting is not the same as proven.

39 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 40 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 41 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 42 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 43 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 44 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 45 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 46 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