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Best Evidence-Based Supplements for Longevity 2026

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Creatine Monohydrate

Creatine is the most research-backed supplement in existence and the biggest surprise in longevity research: over 700 peer-reviewed studies, originally studied for athletic performance, now showing compelling evidence for cognitive aging protection and muscle preservation in older adults. The mechanism is straightforward — creatine replenishes ATP faster, improving cellular energy availability. For adults over 50, muscle preservation (sarcopenia prevention) is one of the strongest predictors of lifespan. The Examine.com grade: A for cognitive function in sleep-deprived adults, A for lean mass in resistance-training adults. Dose: 3-5g daily. Cost: approximately $0.10 per day. No loading phase required. No credible evidence of kidney damage in healthy adults despite the persistent myth.

Vitamin D3 + K2

Approximately 42% of American adults are vitamin D deficient (serum 25-OH-D below 20 ng/mL), and deficiency correlates with 35+ disease states including cardiovascular disease, autoimmune conditions, and all-cause mortality. The evidence for supplementation in deficient individuals is strong: a 2022 VITAL trial of 25,000 participants found 2,000 IU/day D3 reduced cancer mortality by 25%. The K2 pairing matters: D3 increases calcium absorption, but without K2 (specifically MK-7 form), that calcium may deposit in arteries rather than bones. The combined D3+K2 approach is now standard in longevity medicine. Dose: 2,000-5,000 IU D3 + 100-200 mcg MK-7 K2 daily. Get baseline bloodwork first — optimal level is 40-60 ng/mL, not just above deficiency threshold.

Magnesium Glycinate

Magnesium is involved in over 300 enzymatic reactions in the body, yet 68% of Americans do not meet the RDA. The specific form matters: magnesium oxide (the cheapest form) has approximately 4% bioavailability; glycinate and malate forms reach 50-80%. Research links adequate magnesium to better sleep quality (RCT evidence), reduced blood pressure, improved insulin sensitivity, and lower all-cause mortality. The 2025 meta-analysis of 13 prospective studies found each 100mg/day increase in dietary magnesium associated with a 7% reduction in cardiovascular mortality. Dose: 200-400mg elemental magnesium as glycinate or malate, taken at night. The most common side effect of the oxide form (loose stools) is absent with glycinate.