Top 7 Evidence-Based Recommendations
We read 120+ human studies and meta-analyses and prioritized actual outcomes (mortality, function, cardiovascular events) over hype. No affiliate fluff—just what moved the needle in randomized trials, with precise doses you can use today.
Quick Reference Card
Ranked Recommendations
#1Top Choice
The only supplement combo with RCT signals for lower long-term cardiovascular mortality
Dose: Selenium yeast 200 mcg/day + CoQ10 200 mg/day for 48 months; benefits persisted at 10‑year follow‑up
Time to Effect: Months; mortality signal seen across 4 years with durable 10‑year benefit
How It Works
Evidence
In 443 older adults (70–88) with low selenium, 4 years of selenium yeast 200 mcg + CoQ10 200 mg cut cardiovascular mortality vs placebo (HR≈0.51) with benefits persisting to 10 years. Multiple mechanistic sub-studies (thiols, miRNA, metabolomics) align with reduced oxidative stress. Hypothesis-generating but the rare mortality signal in a supplement trial. [2] [3] [21]
Best for:Adults 60+ with low selenium intake (common in parts of Europe; test if unsure), seeking heart-centric longevity support
Caution:Selenium has a U-shaped risk—avoid >400 mcg/day chronically; CoQ10 may interact with warfarin (monitor INR).
Tip:Use selenized yeast (not selenomethionine alone) and a bioavailable CoQ10; ubiquinol can raise blood levels more than ubiquinone, but KiSel-10 used ubiquinone—so match the evidence or switch form if you struggle to raise CoQ10 levels. [3] [18]
#2Strong Alternative
The mitophagy switch for aging muscle (and likely mobility span)
Dose: 500–1,000 mg/day
Time to Effect: 6–16 weeks
How It Works
Evidence
Best for:People 50+ aiming to maintain muscle endurance/mitochondrial health—key to independence and survival
Caution:Generally well-tolerated; mild GI effects possible.
Tip:If you don't naturally convert pomegranate polyphenols to Uro-A, standardized Uro-A (500–1,000 mg) bypasses microbiome "non-producer" status. [19]
#3Worth Considering
The aging muscle and brain helper hiding in plain sight
Dose: 3–5 g/day (no loading needed)
Time to Effect: Days to weeks for strength; weeks to months for function/cognition
How It Works
Creatine buffers cellular ATP in muscle and brain, supporting strength, power, and possibly memory—functions tightly linked to healthy lifespan. [6]
Evidence
Best for:Adults 50+ doing resistance training or with low dietary creatine (plant-forward eaters)
Caution:May raise creatinine (lab artifact); consult if kidney disease.
Tip:Monohydrate is king—cheap, proven, and effective. Take anytime; pairing with training improves outcomes. [8]
#4
Small but real cardiovascular risk reduction—mind the AFib trade-off
Dose: 1–2 g/day combined EPA+DHA with meals; if targeting CV risk, higher EPA‑only doses are Rx territory
Time to Effect: 3–6 months for lipid/inflammation changes; event curves separate over years
How It Works
EPA/DHA modulate membrane signaling, inflammation, and thrombosis; EPA-only appears to drive more of the event reduction in trials. [4]
Evidence
Best for:People with elevated CV risk who accept a small AFib risk for small CV-death risk reduction
Caution:AFib risk rises with dose; discuss with your clinician if you have arrhythmia history.
Tip:Take with the biggest fat-containing meal for absorption. For evidence analogs to trials, choose concentrated EPA if advised by your clinician. [4]
#5
Refuels glutathione and mitochondria; early human RCTs look promising
Dose: Glycine 3–6 g/day + NAC 3–6 g/day in divided doses in studies; practical start: 1.5–3 g of each twice daily with food
Time to Effect: 2–16 weeks
How It Works
Evidence
Placebo-controlled RCT in older adults (n=24) for 16 weeks: GlyNAC improved GSH, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial function, and physical function measures; supportive dose-finding RCTs show improved redox status. Mortality data lacking. [10] [11] [12]
Best for:Adults 60+ with fatigue, metabolic or redox stress markers who tolerate NAC
Caution:NAC can cause nausea/heartburn; may interact with nitroglycerin.
Tip:Titrate up slowly and split doses; pair with protein/resistance training for functional gains.
#6
Arterial-stiffness helper in select groups—not a magic decalcifier
Dose: 180 mcg/day MK‑7 in trials (multi‑year)
Time to Effect: Months to years
How It Works
K2 activates matrix Gla protein, an inhibitor of vascular calcification; may modestly improve arterial stiffness in some populations. [16]
Evidence
Best for:Postmenopausal women with high arterial stiffness; those on long-term K-poor diets
Caution:Interacts with warfarin (contraindicated).
Tip:Use MK-7 with a meal containing fat. Don't expect reversal of valve calcification. [17]
#7
They raise NAD+; hard clinical endpoints are scarce so far
Timeline Expectations
Combination Strategies
Heartspan stack
Components: Selenium 200 mcg (yeast) + CoQ10 200 mg + EPA‑dominant omega‑3 1 g
Targets oxidative stress/mitochondria (CoQ10/selenium) plus low-grade inflammation/thrombosis (EPA) for complementary cardiovascular risk effects. [2] [3] [4]
Morning with food for CoQ10/selenium; take omega‑3 with your largest fat‑containing meal.
Shopping Guide
Form Matters
- •Selenium: choose selenized yeast used in trials, not just selenomethionine. [3]
- •CoQ10: ubiquinol raises blood levels more than ubiquinone; KiSel-10 used ubiquinone—either is acceptable, but match evidence or use ubiquinol if levels stay low. [18]
- •Omega-3: favor products listing EPA/DHA content per serving; take with fat to boost absorption. [4]
- •Urolithin A: use standardized Uro-A (not generic pomegranate) due to gut-microbiome conversion variability. [19]
- •Creatine: stick to creatine monohydrate (micronized) for best evidence and value. [8]
Quality Indicators
- •Third-party testing (NSF/USP/Informed Choice).
- •Transparent dosing that matches clinical trials.
- •Oxidation-prone oils (omega-3) sold in dark bottles with recent dates.
Avoid
- •Proprietary blends without exact mg per ingredient.
- •Longevity claims like "reverses aging" or "adds 10 years"—noncompliant marketing.
- •NMN labeling without acknowledging US regulatory uncertainty. [24]
Overrated Options
These supplements are often marketed for longevity but have limited evidence:
Resveratrol
Mechanistically interesting but human RCTs haven't shown meaningful longevity endpoints; decades of hype, little clinical payoff.
Spermidine
Pilot trial hinted at memory gains, but a larger 12-month RCT in older adults with subjective cognitive decline showed no cognitive benefit. [20] [26]
Curcumin for lifespan
Great for aches in some people, but no human data for mortality or aging-rate; bioavailability and consistency issues persist.
Important Considerations
Run supplements by your clinician if you take anticoagulants/antiarrhythmics, have kidney/liver disease, or are pregnant. Supplements complement—not replace—training, sleep, diet, and blood-pressure/lipid control.
How we chose these supplements
We ranked human RCTs and meta-analyses highest, emphasizing meaningful endpoints (mortality, cardiovascular events, physical function). Mechanistic data informed plausibility but didn't drive rank without human outcomes. Doses mirror successful trials when available.
Common Questions
What’s the fastest‑acting longevity supplement?
Creatine improves strength within weeks—especially with lifting. Urolithin A needs 6–16 weeks for endurance biomarkers. [6] [1]
Can supplements actually extend lifespan in humans?
We don't have definitive human lifespan trials. The rare mortality signal is selenium+CoQ10 for CV death in older adults; consider it hypothesis-generating but notable. [2]
Is NMN legal to buy in the US?
FDA said NMN doesn't qualify as a dietary supplement; availability is unsettled and varies by retailer. NR remains available. [12] [24]
Do omega‑3s reduce death risk?
Meta-analyses show small CV-death reductions, but AFib risk rises—discuss with your clinician. [4] [5]
Should I take vitamin D for longevity?
Vitamin D has many uses, but RCTs don't show all-cause mortality benefit in generally healthy adults; a small reduction in cancer death is reported. [15]
Sources
- 1.Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial (2022) [link]
- 2.Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years (2015) [link]
- 3.Selenium and Coenzyme Q10 improve systemic redox status while reducing cardiovascular mortality in elderly (2023) [link]
- 4.Effect of omega‑3 fatty acids on cardiovascular outcomes: systematic review and meta‑analysis (2021) [link]
- 5.Omega‑3 PUFA supplements and cardiovascular outcomes: systematic review/meta‑analysis of RCTs (2023) [link]
- 6.Creatine supplementation and memory in healthy individuals: systematic review and meta‑analysis (2022) [link]
- 7.The effects of creatine supplementation on cognitive performance—randomised controlled study (2023) [link]
- 8.GlyNAC in older adults: randomized clinical trial improving GSH deficiency, oxidative stress, mitochondrial dysfunction, inflammation, and physical function (2022) [link]
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- 16.MK‑7 supplementation improves arterial stiffness in healthy postmenopausal women (3‑year RCT) (2015) [link]
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