The Longevity Foundational Stack: Omega-3, Vitamin D, Magnesium, and Creatine

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The longevity supplement category is dominated by NMN, NR, resveratrol, and rapamycin analogues — none of which have human all-cause-mortality data. The boring supplements that DO have outcome trial evidence are far less marketed. The four with the strongest healthspan signal in large RCTs: EPA-dominant omega-3 (REDUCE-IT, OmegAD), vitamin D in deficiency (multiple cohort + RCT), magnesium for cardiometabolic correlates, and creatine for muscle/cognitive aging.

Layer 1: EPA-Dominant Omega-3, 1.5–2 g EPA + DHA Daily

Multiple meta-analyses show omega-3 reduces cardiovascular mortality in adults with established CVD or elevated triglycerides. REDUCE-IT showed 25% CV-event reduction at 4 g icosapent ethyl. The lower-dose 1.5–2 g range has smaller but consistent signals for inflammatory and mood endpoints. See omega-3 form piece.

Layer 2: Vitamin D — Repletion to 30–50 ng/mL

Vitamin D deficiency (≤20 ng/mL) is associated with all-cause mortality in large cohorts. Repletion in deficient adults reduces fall risk in elderly and respiratory infections in adolescents and adults. VITAL was null in already-replete adults — the benefit is specifically deficiency correction. Test and treat. See vitamin D piece.

Layer 3: Magnesium, 300–400 mg Elemental Daily

Magnesium intake is inversely associated with cardiovascular, metabolic, and all-cause mortality in cohort studies. About 50% of US adults consume below the EAR. Supplementation reduces BP modestly, improves insulin sensitivity in deficient adults, and may reduce migraine frequency. Glycinate form preferred for tolerability. See magnesium piece.

Layer 4: Creatine Monohydrate, 5 g Daily

Creatine has emerged as a healthspan rather than just a sports supplement. Trial evidence supports preserved lean mass in older adults, reduced fall risk, modest bone density support, and cognitive benefits in sleep-deprived/elderly populations. See creatine and aging piece and cognitive piece.

What NOT to Take

NMN raises blood NAD+ but has zero human longevity outcome data — see NMN piece. NR (nicotinamide riboside) same issue. Resveratrol's longevity hypothesis collapsed in human trials — see resveratrol piece. Avoid multivitamin megadoses — USPSTF found no CV or cancer benefit. Skip "longevity peptides" without prescription. Skip rapamycin protocols without longevity-clinic medical supervision.

How to Run the Stack

Get baseline 25-OH-D, omega-3 index if available, and metabolic panel. Layer omega-3 1.5–2 g + magnesium glycinate 300 mg + creatine 5 g daily. Vitamin D to repletion. Sleep, exercise, plant-rich diet, social engagement, and not smoking outperform every supplement combination by orders of magnitude. The "boring" lifestyle stack is where the actual healthspan gains live. See related heart health stack.