Peter Attia Supplement Protocol — Complete Guide with Evidence Ratings
Overall evidence: Grade CEvery item independently graded A–D on human evidence — dose, timing, the rationale, and where the science actually lands.
Peter Attia's stack is unusually disciplined and biomarker-driven: rather than chasing anti-aging pills he doses to specific labs (omega-3 index ~12%, 25-OH-vitamin-D 40-60 ng/mL, homocysteine <9) and has publicly abandoned hyped compounds like resveratrol (which he calls nonsense) and cooled on metformin for healthy, fit people. The best-supported pieces are narrow: creatine for muscle/strength, vitamin D for correcting deficiency, and magnesium/glycine/ashwagandha for sleep. His most speculative move is weekly rapamycin, which he openly frames as a personal bet grounded in mouse data, not human longevity evidence. As a whole the protocol optimizes healthspan proxies and risk factors more than it proves lifespan extension.
Omega-3 (EPA/DHA fish oil)
MixedWhy Attia takes it: Raise omega-3 index toward ~12% for cardiovascular and brain health — The Drive podcast; AMA #69
What the evidence says: In general populations the two big RCTs were null for primary prevention: VITAL (Manson 2019) found no reduction in major CV events or cancer, and ASCEND was null in diabetics. Benefit is confined to high-triglyceride statin patients using 4 g/day prescription icosapent ethyl in REDUCE-IT, not OTC fish oil. Reasonable for correcting a low omega-3 index but not proven to extend lifespan.
Where to buy Omega-3 on iHerb →Vitamin D3
MixedWhy Attia takes it: Maintain serum 25-OH-D in a 40-60 ng/mL target range — The Drive podcast; AMA #69
What the evidence says: VITAL (Manson 2019) found no reduction in cancer or CVD in a largely replete population, and the D-Health trial (Neale 2022) showed no all-cause mortality benefit. Value is mainly in correcting genuine deficiency. Attia's target-to-a-lab approach is defensible, but the longevity claim for replete adults is not supported.
Magnesium (multiple forms incl. L-threonate)
MixedWhy Attia takes it: Repletion of a commonly low mineral; sleep and neuromuscular support — The Drive podcast; AMA #69
What the evidence says: A small RCT in elderly insomnia (Abbasi 2012) showed modest sleep improvement, and a 2021 meta-analysis (Mah) found sleep-onset latency ~17 min shorter than placebo but rated the evidence low quality. Cheap and reasonable for repletion, but the sleep signal rests on small, biased trials.
Methylated B-vitamins / folate + B12
MixedWhy Attia takes it: Keep homocysteine below ~9 for vascular and brain health — The Drive podcast; AMA #69
What the evidence says: The Cochrane meta-analysis (Marti-Carvajal 2017, 71,422 patients) found homocysteine-lowering did NOT reduce MI or all-cause mortality, only a small stroke reduction. Benefit concentrates in deficient subgroups (CSPPT; VITACOG). Homocysteine is a biomarker whose broad lowering has not moved hard endpoints.
Creatine monohydrate
SupportsWhy Attia takes it: Support muscle mass/strength and brain bioenergetics with aging — The Drive podcast; AMA #69
What the evidence says: The strongest item in the stack: meta-analysis in older adults (Forbes 2021) shows creatine plus resistance training reliably increases lean mass and strength (muscle evidence approaches A). Cognitive benefits are real but modest (Prokopidis 2023). Excellent safety record.
Glycine
MixedWhy Attia takes it: Shorten sleep latency and improve sleep quality — The Drive podcast (sleep protocol)
What the evidence says: Small crossover RCTs (Bannai 2012) report improved subjective sleep and reduced daytime fatigue under partial sleep restriction. Evidence is limited to small trials with no hard or longevity outcomes. Low-risk and plausibly useful for sleep, but weakly evidenced.
Ashwagandha (Withania somnifera)
MixedWhy Attia takes it: Reduce stress/cortisol and improve sleep quality — The Drive podcast (sleep protocol)
What the evidence says: A 2021 meta-analysis (Cheah) found a small significant sleep improvement, and an RCT (Chandrasekhar 2012) reported reduced perceived stress and cortisol. Trials are small, short and often industry-linked, with no longevity data and rare hepatotoxicity reports. Reasonable short-term for stress/sleep, unproven for lifespan.
Curcumin (bioavailable / Theracurmin)
MixedWhy Attia takes it: Anti-inflammatory; possible cognitive benefit — The Drive podcast
What the evidence says: A single small 18-month RCT (Small 2018, n=40) using a bioavailable curcumin improved memory and lowered amyloid/tau PET signal in non-demented adults, an encouraging but isolated result. Broader curcumin research is hampered by poor bioavailability and no longevity endpoints.
AG1 / greens powder
UnprovenWhy Attia takes it: Micronutrient insurance to cover dietary gaps — The Drive podcast (has voiced skepticism)
What the evidence says: AG1 has essentially no independent longevity RCTs. The closest signal is COSMOS-Mind (Baker 2022), where a standard multivitamin modestly improved cognition, but multivitamins are null for mortality and AG1 is not the tested product. Attia has himself questioned greens powders.
Rapamycin (sirolimus)
Unproven (human)Why Attia takes it: mTOR inhibition; robust lifespan extension in animals — AMA #35; The Drive; 60 Minutes
What the evidence says: Rapamycin extends lifespan in mice even when started late (Harrison 2009, NIA ITP). But the first RCT in healthy humans, PEARL (Moel 2025), found it safe over 48 weeks while missing its primary endpoints, with only modest secondary signals. No human evidence it extends lifespan; Attia is explicit it is a personal bet.
Metformin
MixedWhy Attia takes it: AMPK activation / geroprotection (his earlier rationale) — AMA #35; blog
What the evidence says: No completed longevity RCT exists (TAME unfunded), so human geroprotection is unproven. Attia cooled on it partly because Konopka 2019 showed metformin blunted the mitochondrial and cardiorespiratory adaptations to exercise in older adults. Defensible in type 2 diabetes; unproven and possibly counterproductive for healthy non-diabetics.
Akkermansia muciniphila probiotic (Pendulum)
MixedWhy Attia takes it: Support metabolic/glucose control and gut barrier — The Drive podcast
What the evidence says: A single small proof-of-concept RCT (Depommier 2019, Nature Medicine) found pasteurized A. muciniphila improved insulin sensitivity and some metabolic markers in overweight volunteers. One small, short exploratory trial with no clinical or longevity endpoints.
How this stack works
Attia optimises risk factors and repletion more than novel geroprotection: the targets are omega-3 index, 25-OH vitamin D, homocysteine, and lean muscle mass, with weekly rapamycin as his one mechanistic mTOR bet. Notably he has dropped resveratrol and cooled on metformin for healthy, fit people.
Evidence summary
About 4 items reach B for narrow endpoints (creatine for muscle, vitamin D for deficiency, magnesium and ashwagandha for sleep), ~6 are C (omega-3, folate/B-vitamins, glycine, curcumin, metformin, Akkermansia), and 2 are D (rapamycin, AG1). No component has RCT evidence of extending human lifespan, so the stack grades C overall.
Risks & interactions
Rapamycin (weekly, off-label) is an immunosuppressant and needs medical supervision; his lipid drugs are prescription. High-dose vitamin D should be titrated to blood levels, not mega-dosed. Most supplements here are low-risk, but none substitutes for the proven levers Attia himself ranks first: exercise, sleep, and aggressive lipid management.
Who this is for
A disciplined, biomarker-driven template for people who already have training, sleep and lipids handled and want to correct measured deficiencies. The rapamycin element is an experimental personal bet, not a recommendation. Little here is worth copying without the lab testing that guides it.
Sources
- Manson JE (2019). Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer (VITAL). N Engl J Med. doi:10.1056/NEJMoa1811403 · PMID 30415637
- ASCEND Study Collaborative Group (2018). Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus (ASCEND). N Engl J Med. doi:10.1056/NEJMoa1804989 · PMID 30146932
- Bhatt DL (2019). Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (REDUCE-IT). N Engl J Med. doi:10.1056/NEJMoa1812792 · PMID 30415628
- Manson JE (2019). Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease (VITAL). N Engl J Med. doi:10.1056/NEJMoa1809944 · PMID 30415629
- Neale RE (2022). The D-Health Trial: vitamin D and mortality. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(21)00345-4 · PMID 35026158
- Abbasi B (2012). The effect of magnesium supplementation on primary insomnia in elderly: a double-blind placebo-controlled trial. J Res Med Sci. doi:10.4103/1735-1995.129163 · PMID 23853635
- Mah J (2021). Oral magnesium supplementation for insomnia in older adults: a systematic review and meta-analysis. BMC Complement Med Ther. doi:10.1186/s12906-021-03297-z · PMID 33865376
- Marti-Carvajal AJ (2017). Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. doi:10.1002/14651858.CD006612.pub5 · PMID 28816346
- Huo Y (2015). Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China (CSPPT). JAMA. doi:10.1001/jama.2015.2274 · PMID 25771069
- Smith AD (2010). Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment (VITACOG). PLoS One. doi:10.1371/journal.pone.0012244 · PMID 20838622
- Forbes SC (2021). Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults. Nutrients. doi:10.3390/nu13061912 · PMID 34199420
- Prokopidis K (2023). Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of RCTs. Nutr Rev. doi:10.1093/nutrit/nuac064 · PMID 35984306
- Bannai M (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. doi:10.3389/fneur.2012.00061 · PMID 22529837
- Bannai M (2012). New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. doi:10.1254/jphs.11r04fm · PMID 22293292
- Cheah KL (2021). Effect of Ashwagandha (Withania somnifera) extract on sleep: a systematic review and meta-analysis. PLoS One. doi:10.1371/journal.pone.0257843 · PMID 34559859
- Chandrasekhar K (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety. Indian J Psychol Med. doi:10.4103/0253-7176.106022 · PMID 23439798
- Small GW (2018). Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. Am J Geriatr Psychiatry. doi:10.1016/j.jagp.2017.10.010 · PMID 29246725
- Baker LD (2022). Effects of cocoa extract and a multivitamin on cognitive function: a randomized clinical trial (COSMOS-Mind). Alzheimers Dement. doi:10.1002/alz.12767 · PMID 36102337
- Harrison DE (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. doi:10.1038/nature08221 · PMID 19587680
- Moel M (2025). Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY). doi:10.18632/aging.206235 · PMID 40188830
- Konopka AR (2019). Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. doi:10.1111/acel.12880 · PMID 30548390
- Depommier C (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. doi:10.1038/s41591-019-0495-2 · PMID 31263284
Some “where to buy” links are affiliate links (iHerb). We may earn a small commission at no extra cost to you. Affiliate relationships never influence our evidence grades, which are based only on published research.
Compare the experts: see how this stacks up against every protocol we grade in the Longevity Protocol Comparison →