Longevity Supplements That Actually Have Human Data

No supplement has been proven to extend human lifespan, and that trial would take decades. But a small group of longevity supplements do have randomized human trials showing effects on muscle, cellular markers, biological-age clocks or cognition, while many popular ones still rest mainly on mouse or worm studies. This guide ranks them by the strength of their human evidence, explains what each trial actually found, and is honest about where the evidence runs out.

Key facts

• "Works in mice" and "works in people" are different claims. Many lifespan results in animals have not been tested, or have not held up, in humans.
• The strongest human evidence is for healthspan outcomes such as muscle strength, endurance, cellular markers, biological-age clocks and memory scores, not lifespan itself.
• Creatine, omega-3s, multivitamins and urolithin A have the strongest randomized trial data for aging-related outcomes. Taurine, Ca-AKG, low-dose lithium, spermidine and ergothioneine are still mostly preclinical or observational in people.
• Some heavily marketed compounds, such as resveratrol and high-dose antioxidant vitamins, have been disappointing in human trials.
• We include our own Ares ingredients in this ranking, and not all of them land in the top tier.

How we rank the evidence

We use three tiers based on the best human research available as of October 2026:

• Tier 1: Replicated human trials. Multiple randomized, placebo-controlled trials, or large multi-year randomized trials, showing effects on aging-related outcomes.
• Tier 2: Early human evidence. At least one controlled human trial or strong human data, plus a solid mechanism and animal evidence.
• Tier 3: Mostly preclinical. Promising animal or cell data, but human evidence is limited to associations, uncontrolled studies, small pilots or biomarkers.

We also flag compounds whose human trials have been disappointing. Two rules apply throughout: a biomarker change is not the same as a longer or healthier life, and a trial of one compound tells you little about a combination of several.

The longevity supplement evidence scorecard

Tier 1: longevity supplements with replicated human trials

Creatine. Creatine is not just for athletes. A meta-analysis of 22 randomized trials with 721 older adults found that creatine taken during resistance training produced greater gains in lean tissue mass (about 1.4 kg more than placebo) and in upper- and lower-body strength (Chilibeck et al., 2017). Muscle strength is one of the strongest predictors of healthy aging, which is why this unglamorous compound belongs at the top.

Omega-3s. The DO-HEALTH trial, led by Heike Bischoff-Ferrari, followed older adults in Europe for three years. A 2025 analysis of 777 participants published in Nature Aging reported that 1 gram of omega-3s daily modestly slowed three of four DNA-methylation aging clocks, by roughly three months over the three years, with vitamin D and home exercise adding small benefits on one of the clocks, PhenoAge (Bischoff-Ferrari et al., 2025). It was a post hoc analysis, so it needs confirmation, but it is one of the few randomized trials to test a supplement against biological-age clocks.

Multivitamins. The COSMOS trials, run by Harvard-affiliated researchers, tested a daily multivitamin against placebo in older adults. A pooled analysis of three COSMOS cognitive studies found small but statistically clear benefits for global cognition and episodic memory, which the authors estimated as equivalent to about two years less cognitive aging (Vyas et al., 2024).

Urolithin A. Urolithin A is a postbiotic: a compound gut bacteria make from ellagitannins in pomegranates, walnuts and some berries. Not everyone's microbiome makes it efficiently, which is the case for taking the finished molecule. It first drew attention in a 2016 Nature Medicine paper showing it switched on mitophagy, the recycling of worn-out mitochondria, and extended lifespan in worms (Ryu et al., 2016). The human trials:

• Andreux et al., 2019 (Nature Metabolism). The first-in-human trial in sedentary older adults tested single doses up to 2,000 mg and daily doses of 250 to 1,000 mg for 28 days. It was well tolerated, and the 500 and 1,000 mg daily doses produced a molecular signature of improved mitochondrial and cellular health.
• Singh et al., 2022 (Cell Reports Medicine). In middle-aged adults given 500 or 1,000 mg a day for four months, muscle strength rose about 12% and some endurance measures improved, although the primary endpoint, peak power output, did not change significantly.
• Liu et al., 2022 (JAMA Network Open). In adults aged 65 to 90 given 1,000 mg a day for four months, hand and leg muscle endurance improved versus placebo, but the primary endpoints (six-minute walk distance and maximal ATP production) did not differ significantly.
• Denk et al., 2025 (Nature Aging). Four weeks of 1,000 mg a day shifted immune-cell composition toward a more youthful, less exhausted profile in healthy middle-aged adults.

A 2024 systematic review in Ageing Research Reviews summarizes the human literature (Kuerec et al., 2024). The honest caveats: missed primary endpoints, small samples, and funding by the company that makes the most-studied ingredient. It has fewer trials than NMN or NR, but more consistent data on muscle and mitochondrial outcomes. Read the full urolithin A breakdown.

Tier 2: early but real human evidence

NAC and GlyNAC. N-acetylcysteine (NAC) supplies cysteine, usually the bottleneck building block for glutathione, the body's main internal antioxidant. Most of the aging-specific data comes from GlyNAC, glycine plus NAC, studied by a group at Baylor College of Medicine. A 24-week open-label pilot in eight older adults reported improvements in glutathione, oxidative stress, mitochondrial fuel use, inflammation, insulin resistance, strength and cognition (Kumar et al., 2021). A 16-week randomized, placebo-controlled trial in 24 older adults reported similar improvements in glutathione, oxidative stress, physical function and several hallmark-of-aging markers (Kumar et al., 2023). Two caveats: the signal is for the combination, not NAC alone, and the trials used about 100 mg of glycine and about 130 mg of NAC per kilogram of body weight daily, several grams of each for most adults and far more than typical supplement doses. Read more on NAC and GlyNAC.

Sulforaphane. Sulforaphane forms when glucoraphanin in broccoli sprouts meets the enzyme myrosinase. It activates Nrf2, a switch for the body's own antioxidant and detoxification enzymes. A 12-week randomized trial of 291 adults in Qidong, China, found a broccoli sprout drink increased excretion of the airborne pollutants benzene (by 61%) and acrolein (by 23%) (Egner et al., 2014). A separate 12-week randomized trial of concentrated broccoli sprout extract in 97 people with type 2 diabetes reported lower fasting glucose in obese participants with poor control (Axelsson et al., 2017). Neither tested aging outcomes directly, and bioavailability depends heavily on formulation. Read more on sulforaphane.

NAD+ precursors (NMN and NR). These reliably raise NAD+ levels in people (Martens et al., 2018; Yi et al., 2023). Functional results have been smaller: one trial found 250 mg of NMN daily improved muscle insulin sensitivity in a small group of postmenopausal women with prediabetes (Yoshino et al., 2021), but improvements in muscle performance and metabolism have been inconsistent across trials. For a direct comparison with urolithin A, see Urolithin A vs NMN.

Tier 3: promising, mostly preclinical

Taurine. A 2023 Science paper reported that blood taurine falls with age in mice, monkeys and people, and that taurine supplements extended lifespan in mice and improved health markers in monkeys (Singh et al., 2023). The human side has since been challenged: a 2025 study in Aging Cell of 137 men aged 20 to 93 found no association between circulating taurine and age, muscle mass, strength, physical performance or mitochondrial function (Marcangeli et al., 2025). The animal data is striking, but the human premise is contested and no aging trial has been done in people, which is why taurine sits in Tier 3 here. Read more on taurine.

Calcium AKG. Alpha-ketoglutarate (AKG) is a Krebs-cycle metabolite that also helps regulate DNA and histone methylation, linking metabolism to epigenetics (Gyanwali et al., 2022). The animal data is among the most dramatic on this list: AKG extended lifespan in worms by inhibiting ATP synthase and TOR (Chin et al., 2014), and Ca-AKG started late in life extended lifespan and compressed frailty in mice (Asadi Shahmirzadi et al., 2020). In people, the most-cited report is an uncontrolled, retrospective analysis of 42 adults taking an AKG-plus-vitamins product, which reported an average 8-year drop on a DNA-methylation clock (Demidenko et al., 2021). Without a placebo group that number can't be taken at face value. The placebo-controlled ABLE trial, testing 1 g a day in 120 middle-aged adults (Sandalova et al., 2023), had not published its results as of this update. Read more on Ca-AKG.

Low-dose lithium. Lithium is best known as a prescription mood stabilizer; the longevity interest is in trace amounts far below drug doses. A 2011 study found higher natural lithium in Japanese drinking water correlated with lower all-cause mortality across 18 municipalities, and low-dose lithium extended lifespan in worms (Zarse et al., 2011). That is a population correlation, not proof of cause. A 2025 Nature paper reported that lithium is depleted in the brain early in Alzheimer's pathology and that lithium orotate prevented Alzheimer's-like pathology and memory loss in mouse models and aging mice (Aron et al., 2025). That is compelling preclinical work, not evidence that lithium supplements prevent dementia in people. At prescription doses lithium has a narrow safety margin and is monitored for thyroid and kidney effects, so anyone considering even low-dose lithium should talk to a physician first. Read more on lithium.

Ergothioneine. Ergothioneine is a diet-derived antioxidant, found mainly in mushrooms, that the body actively transports into cells. Biochemist Bruce Ames proposed it as a candidate "longevity vitamin" (Ames, 2018). In a Swedish cohort of 3,236 adults followed for about 21 years, higher blood ergothioneine was associated with lower overall mortality (Smith et al., 2020), but that is an association, not a trial. The only controlled trial we found is a one-year pilot in 19 older adults with mild cognitive impairment, which reported better learning-test scores and stable markers of nerve damage compared with placebo (Yau et al., 2024). Larger trials are needed before it can move up a tier.

Spermidine. Higher dietary spermidine intake was linked to lower mortality in a 20-year population study of 829 adults (Kiechl et al., 2018), but a 12-month randomized trial of 100 older adults with subjective memory complaints found no significant effect on memory or biomarkers (Schwarz et al., 2022).

The disappointments

Resveratrol became famous for activating sirtuins, but reviews of human trials describe mixed, mostly modest results, limited by poor bioavailability (Berman et al., 2017).

High-dose antioxidant vitamins are the cautionary tale. In a large Finnish trial of male smokers, beta-carotene supplements increased lung cancer incidence (ATBC Study Group, 1994), and a Cochrane review of randomized trials found beta-carotene, vitamin E and higher-dose vitamin A did not lower mortality and may raise it (Bjelakovic et al., 2012). More antioxidant is not automatically better.

Why these compounds target different hallmarks of aging

Aging researchers describe aging as a set of interacting "hallmarks", categories of cellular damage and dysregulation that build up over time (López-Otín et al., 2023; Kroemer et al., 2025). Several are directly relevant here:

• Mitochondrial dysfunction. Mitochondria turn nutrients into ATP, the cell's fuel, and accumulate damage with age. They are a recognized nutritional target for preserving muscle and physical function (Broome et al., 2024). Urolithin A, Ca-AKG and NAD+ precursors act here.
• Redox imbalance. Glutathione, built from cysteine, glycine and glutamate, tends to fall with age. NAC, glycine and sulforaphane support the body's own antioxidant defenses rather than acting as antioxidants themselves.
• Declining autophagy and mitophagy. The cell's recycling systems slow with age. Urolithin A targets mitophagy; low-dose lithium is studied for autophagy and neuronal resilience.
• Cellular senescence and inflammaging. Senescent cells pile up and drive low-grade inflammation. Taurine reduced senescence markers in mice.
• Epigenetic drift. AKG is a cofactor for enzymes that maintain DNA and histone methylation patterns, which is why biological-age clocks are a natural endpoint for Ca-AKG trials.

What the research does not say

• No human lifespan extension. Lifespan data for every compound here comes from worms, flies or mice.
• Biomarkers are not outcomes. A change in glutathione, NAD+, a methylation clock or blood glucose is encouraging but does not guarantee a longer or healthier life.
• GlyNAC is not NAC alone. The strongest NAC aging data is for the glycine-plus-NAC combination at high doses.
• The taurine premise is contested in humans. Whether blood taurine actually declines with human age is now disputed.
• Supplements are not disease treatments. Research on lithium in Alzheimer's or sulforaphane in diabetes does not show that supplements prevent or treat those conditions.
• Animal effect sizes don't transfer cleanly. Mice are short-lived, genetically uniform and kept in controlled conditions, and their metabolism differs from ours.

How to think about combining them

Single-compound trials don't predict combinations. Nearly every trial cited here tested one compound alone, with GlyNAC the deliberate exception. How several compounds behave together, at human doses, over years, is essentially unstudied.

Different mechanisms are the case for combining. Because these compounds act on different hallmarks, they are not redundant in principle. That is a rationale, not evidence of extra benefit.

More antioxidant activity is not always better. NAC and sulforaphane both act on redox biology, and over-suppressing reactive-oxygen signaling may blunt some useful adaptations, such as responses to exercise. The aim is to support the body's own defense capacity.

Lithium is the cautious one. Even at low doses it interacts with several drug classes and calls for individual medical guidance in a way the others generally do not.

The foundations come first. No supplement substitutes for sleep, resistance training, whole-food nutrition, alcohol moderation and stress management. The supplement evidence is best treated as a layer on top of those.

Where Ares fits

Ares, our human formula, contains urolithin A (500 mg), calcium AKG (1,000 mg), NAC (600 mg), taurine (1,000 mg), broccoli sprout extract (250 mg, a source of sulforaphane) and low-dose lithium orotate (120 mg). On this scorecard that is one Tier 1 ingredient (urolithin A), one Tier 2 ingredient (sulforaphane) and three Tier 3 ingredients (taurine, Ca-AKG and lithium), plus NAC, which is ranked here only as part of GlyNAC (Tier 2); those trials paired it with glycine at much higher doses, so that rating does not carry over to NAC alone. Ares does not contain added glycine or ergothioneine; both are covered above for completeness.

We're also transparent about doses. Ares' 500 mg of urolithin A sits at the low end of the doses that showed functional effects in human trials (500 to 1,000 mg a day). Its 1,000 mg of Ca-AKG is in line with the roughly 1 g a day used in human Ca-AKG studies such as ABLE. Its 600 mg of NAC is a common supplemental dose but far below the weight-based GlyNAC doses, and Ares does not add glycine. Its 1,000 mg of taurine is above typical dietary intake and within the 1 to 3 g a day used in many human studies, but below the human equivalent of the mouse lifespan doses. Its 250 mg of broccoli sprout extract is the weight of the extract, not of sulforaphane; clinical studies have typically delivered tens of milligrams of sulforaphane or glucoraphanin equivalents. Its 120 mg of lithium orotate supplies roughly 4 to 5 mg of elemental lithium, a trace amount far below prescription doses. We chose the ingredients because they address different aging pathways, mitochondria, cellular energy, antioxidant defense and cellular maintenance, not because any single trial tested this combination. If you're curious how we put them together, see Ares, and read the full reasoning in My Longevity Stack.

Deep dives and head-to-head comparisons

Each Ares ingredient has its own evidence review, and two comparisons cover the questions we get most:

• Urolithin A vs Calcium AKG: two mitochondrial approaches with very different levels of human evidence.
• Urolithin A vs NMN: mitophagy versus NAD+ restoration.
• Single-ingredient reviews: urolithin A, Ca-AKG, NAC and GlyNAC, taurine, sulforaphane and low-dose lithium.
• The bigger picture: Human longevity science in 2026 and what centenarians eat, take and avoid.

Frequently asked questions

Has any supplement been proven to extend human lifespan? No. A human lifespan trial would take decades. The best evidence is for healthspan measures such as strength, endurance, cellular markers, cognition and biological-age clocks.

What is the most evidence-based longevity supplement? Creatine, omega-3s and multivitamins have the most replicated randomized trial data for aging-related outcomes. Among newer longevity compounds, urolithin A has fewer trials than NMN or NR but more consistent human data on muscle and mitochondrial outcomes.

What dose of urolithin A has been studied? Human studies have used daily doses from 10 mg up to 1,000 mg (Kuerec et al., 2024). The longer muscle trials used 500 and 1,000 mg a day, and the first human trial reported its molecular effects at 500 and 1,000 mg.

Are NMN and NR worth it? They raise NAD+ reliably, but human trials have shown only modest or inconsistent functional benefits so far.

Does Ca-AKG have human trials? Only early ones. The best-known human report was uncontrolled, and the placebo-controlled ABLE trial had not published results as of October 2026. The strong lifespan data is in mice.

Is low-dose lithium safe to take? Supplemental lithium orotate supplies far less lithium than prescription doses, but human aging evidence is preliminary, and lithium interacts with several medications. Talk to a physician first, especially if you are pregnant, nursing, or take prescription medication.

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Published by the SciRouter Editorial Team for general educational purposes. Last updated October 2026.

Educational disclaimer. This article is for educational and informational purposes only and is not medical advice. It summarizes published scientific research and does not endorse any specific product, supplement, drug, or treatment. These statements have not been evaluated by the Food and Drug Administration, and any products mentioned are not intended to diagnose, treat, cure, or prevent any disease. Always consult a licensed physician before starting, stopping, or changing any supplement or medication, especially if you are pregnant, nursing, have a medical condition, or take prescription medication.