Dr. Mark Hyman’s Longevity Protocol — Functional Medicine (2025-2026)

Why Longevity takes it: Insurance policy to fill micronutrient gaps from depleted soils/diet — Young Forever / O.N.E. (his brand)

What the evidence says: Large RCTs and the COSMOS program show at most a small cognitive signal and no reduction in all-cause mortality, CVD or cancer in well-nourished adults. A daily multivitamin is a low-risk gap-filler, not a proven longevity intervention.

Why Longevity takes it: Anti-inflammatory; cardiovascular and brain support — Omega-3 Rejuvenate (his brand)

What the evidence says: The 2020 Cochrane review (>160,000 participants) found omega-3 supplements have little or no effect on all-cause mortality or cardiovascular death, with only a small dose-dependent signal for some cardiac events. Reliable for lowering triglycerides, but general longevity benefit in supplement form is unproven.

Why Longevity takes it: Immune, bone and healthy-aging support; most people deficient — Vitamin D Supreme (his brand)

What the evidence says: The large VITAL RCT (n=25,871) was essentially null for its primary endpoints — no reduction in cancer incidence or major CV events in replete adults — though later analyses suggest reduced cancer mortality with latency and lower autoimmune-disease incidence. Correcting genuine deficiency is worthwhile; routine high-dose use in replete people is not shown to extend life.

Why Longevity takes it: Directs calcium to bone and away from arteries — Vitamin D Supreme (his brand)

What the evidence says: The strongest hard-endpoint RCT (AVADEC, Circulation 2022) found K2+D did not slow aortic valve or coronary calcification versus placebo. Mechanistically plausible and observationally linked to less calcification, but interventional evidence for cardiovascular or longevity benefit is weak.

Why Longevity takes it: Cofactor for 300+ enzymes; sleep, stress, blood pressure, insulin — Young Forever / foundational protocol

What the evidence says: Meta-analyses of double-blind RCTs show modest but consistent blood-pressure reduction, and deficiency is genuinely common. The benefit is on validated surrogate endpoints (BP, glucose) rather than a direct longevity outcome, but among the stack this is one of the better-supported items.

Why Longevity takes it: Lowers homocysteine; supports methylation/detox — Homocysteine Supreme (his brand)

What the evidence says: Folic acid/B-vitamins reliably lower homocysteine and modestly reduce stroke risk in some populations (notably low-folate, no-fortification settings), but trials show no all-cause mortality benefit and largely null effects on cognition or cardiac events. Useful for documented elevated homocysteine, not as a blanket longevity measure.

Why Longevity takes it: Gut-microbiome health underpins immunity and inflammation — Seed DS-01 (partner brand)

What the evidence says: RCT benefit is real but indication- and strain-specific (e.g., reduced necrotizing enterocolitis in preterm infants; some infection settings), with no evidence probiotics extend healthspan in healthy adults. Effects do not generalize across products, so a specific SKU claim is not supported for longevity.

Why Longevity takes it: Raises NAD+ to reverse cellular aging — Wonderfeel Youngr NMN (co-branded)

What the evidence says: Human RCTs are small and short: NMN raised NAD+ and improved muscle insulin sensitivity in 25 prediabetic women and moved some fitness measures in dose-ranging trials, several industry-funded. No trial has shown any effect on aging, healthspan or mortality, so the anti-aging claim is mechanistic marketing ahead of the data.

Why Longevity takes it: Sirtuin (SIRT1) activator mimicking caloric restriction — Wonderfeel / Renual (his brand)

What the evidence says: The sirtuin/caloric-restriction-mimetic story derives from yeast and mouse work that failed to replicate cleanly, and resveratrol has poor oral bioavailability. Small human RCTs show inconsistent effects on endothelial or metabolic surrogates and none on aging outcomes; longevity benefit in humans is unproven.

Why Longevity takes it: Mitochondrial energy; replaces statin-depleted CoQ10 — CoQnol 200 (his brand)

What the evidence says: The Q-SYMBIO RCT showed a genuine reduction in major adverse events and mortality — but specifically in chronic heart-failure patients, a disease population. There is no evidence CoQ10 extends healthspan or lifespan in healthy people, so the general longevity claim is not supported.

Why Longevity takes it: Anti-inflammatory; targets inflammaging — Turiva (his brand)

What the evidence says: Meta-analyses support modest symptom relief in osteoarthritis and other inflammatory conditions, roughly comparable to NSAIDs in some trials, but studies are heterogeneous and bioavailability is poor without enhancers. No human data link curcumin to slowed aging or longer life.

Why Longevity takes it: Adaptogen; lowers cortisol and stress load — HPA Adapt / adaptogen line (his brand)

What the evidence says: Multiple RCTs and meta-analyses show it reduces perceived stress, anxiety and cortisol versus placebo, with some sleep benefit. Trials are small, mostly short and frequently manufacturer-funded, and the outcome is stress relief — not a demonstrated longevity effect.

Why Longevity takes it: Antioxidant; mitochondrial and blood-sugar support — Foundational / mitochondrial protocol

What the evidence says: ALA has legitimate evidence for symptom relief in diabetic peripheral neuropathy, but that is a disease indication, not longevity. For healthspan/anti-aging in healthy adults the rationale is purely antioxidant/mechanistic with no outcome data.

Why Longevity takes it: Stimulates mitochondrial biogenesis and cognition — MITO-PQQ (his brand)

What the evidence says: Human evidence is limited to small RCTs on cognitive/mitochondrial surrogates, including one n=34 trial that confounded PQQ with molecular hydrogen and was industry-linked. The mitochondrial-biogenesis mechanism is animal-derived; no human aging or healthspan outcomes exist.

Why Longevity takes it: Immune function and enzymatic support — O.N.E. Multivitamin / foundational

What the evidence says: Zinc (as lozenges started early) modestly shortens common-cold duration and correcting deficiency matters for immunity, but there is no evidence it extends healthspan or lifespan. Chronic supplemental doses above needs can induce copper deficiency, so more is not better.

Why Longevity takes it: Induces mitophagy to renew aging mitochondria and muscle — Renual / Mitopure (his brand/partner)

What the evidence says: Two placebo-controlled RCTs show urolithin A improves muscle mitochondrial biomarkers and some strength/endurance measures in middle-aged and athletic adults, a more credible mechanism (mitophagy) than most stack items. Trials remain small and short with surrogate endpoints and manufacturer involvement, and no longevity outcome has been demonstrated.