CheatSheet: The "top 12" longevity supplements

A review of NMN, omega-3s, metformin, AKG and 8 other popular anti-aging supplements.

Oct 28, 2025

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In the past year, I’ve been asked many times about anti-aging supplements, during which time the longevity hype machine has revved up considerably. In this post, I provide a fact-based review of the “top 12” longevity supplements — so called not because they each work as some people may claim but, rather, because they tend to be mentioned most often among longevity chiselers.

Caveat 1: By far the most effective human longevity boosters are physical activity, whole-food nutrition, sleep and reliable person-to-person connection. Unless and until you have all those bases covered, supplements aren’t going to help you live substantially longer or better.

Caveat 2: There are no drugs, supplements or clinical interventions that have been been proven to slow or reverse aging in humans. Some compounds may help you sleep better (which is good for longevity); build more lean muscle (which is good for longevity); increase cardiovascular health (good for longevity!); or boost immune function (also good for longevity). But as yet there is no data from randomized controlled trials in humans, which is the scientific gold standard, proving a longevity benefit for almost any drug or supplement.

Certainly not for overhyped products like NAD+.

All that said, here’s what you should know for the “top 12” supplements that longevity influencers tend to talk about.

1 | NMN: The NAD+ precursor hawked by influencers

What it is
Nicotinamide mononucleotide (NMN) is a precursor molecule to NAD+, a coenzyme found in every cell of your body. NAD+ declines by roughly half between youth and middle age. (See the link above for my specific deep dive into NAD+ supplements.)

How it works
NMN converts to NAD+ in cells. NAD+ powers metabolic reactions, DNA repair and mitochondrial energy production. More NMN theoretically equals more NAD+, which equals restored cellular function.

The claimed benefits in humans
Improved physical endurance, better metabolic health, enhanced cognitive function and slowed biological aging. The supplement industry promises rejuvenation at the cellular level.

What the science actually says
A 2022 trial tested 300, 600 and 900 mg daily for 60 days in 80 middle-aged adults. Blood NAD+ levels increased. Walking distance improved slightly. People reported feeling better on health questionnaires.

The catch: Most studies lasted only 60 days. We have almost zero data on what happens when humans take NMN for years. The FDA briefly tried banning NMM supplements in 2022 because a pharmaceutical company filed to develop it as a drug— revealing the Wild West nature of this market. After significant pressure from supplement industry groups, the FDA reversed its decision last month, allowing NMN to be sold (by essentially anyone) as a dietary supplement.

The bottom line
NMN has been shown in some studies to increase blood NAD+ and might improve physical function in the short term. Long-term human data doesn’t exist yet.

2 | Rapamycin: The transplant drug going rogue

What it is
Rapamycin is an FDA-approved immunosuppressant drug, originally isolated from soil bacteria on Easter Island (known as Rapa Nui). In transplant patients, high doses suppress the immune system to prevent organ rejection.

How it works
Rapamycin inhibits mTOR (mechanistic target of rapamycin), a protein that regulates cell growth, metabolism and aging. At low, intermittent doses, it may mimic some benefits of caloric restriction.

The claimed benefits in humans
Extended lifespan, improved muscle mass and bone density, reduced age-related disease and enhanced immune function, despite being an immunosuppressant at higher doses.

What the science actually says
Rapamycin extends lifespan in mice by up to 60%. The first long-term human trial — the PEARL study published in 2024 — gave 185 adults aged 50-85 either 5 or 10 mg weekly for 48 weeks. Women taking 10 mg gained lean muscle mass. Men gained bone mineral content. No serious side effects appeared.

A University of Washington dentist is testing rapamycin for gum disease in adults over 50, based on the theory that if rapamycin targets aging systemically, it should improve oral health.

Tech entrepreneur Bryan Johnson famously tried rapamycin before quitting, citing elevated blood glucose and poor wound healing.

The bottom line
Promising early human data, but you need a doctor willing to prescribe off-label. This is not for amateurs. Side effects remain uncertain for long-term use in healthy people.

3 | AKG: The metabolite with mouse credentials

What it is
Alpha-ketoglutarate, known as AKG, is a metabolite — an intermediate compound in the Krebs cycle, the cellular energy factory in mitochondria.

How it works
AKG participates in energy production and acts as a signaling molecule for cellular processes including epigenetic regulation and protein synthesis. Blood levels of AKG drop tenfold between age 40 and 80 in humans.

The claimed benefits in humans
Reduced biological age by up to 8 years, improved healthspan, better bone and cardiovascular health and enhanced athletic performance.

What the science actually says
A 2020 study found that mice given AKG starting at middle age lived 12% longer and showed 40% improvement in healthspan. A preliminary uncontrolled study claimed an 8-year reduction in biological age with AKG supplementation, though that finding hasn’t been replicated.

The National University of Singapore is currently running a proper trial: 120 middle-aged adults taking 1 gram daily for six months. Investigators are measuring DNA methylation age and multiple biomarkers. Results aren’t published yet.

The bottom line
AKG has spectacular mouse data. Human trials are in progress. It’s too early to make a judgment.

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4 | Omega-3s: The one that actually works

What it is
Omega-3 fatty acids are polyunsaturated fats, specifically EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), found primarily in fatty fish and algae.

How it works
Omega-3s integrate into cell membranes, affecting cellular signaling and inflammation. They influence DNA methylation patterns and may slow epigenetic aging. They also modulate inflammatory responses throughout the body.

The claimed benefits in humans
Slowed biological aging, reduced inflammation, improved cardiovascular health, better cognitive function, decreased cancer risk and protection from falls and infections.

What the science actually says
A 2025 Nature Aging study examined 777 adults aged 70 and older who took 1 gram of omega-3 daily for three years. Biological aging slowed by roughly three months based on DNA methylation clocks.

When combined with vitamin D and exercise, the effects were additive. Previous findings from the same trial showed omega-3 alone reduced infections by 13% and falls by 10%. The combination of all three interventions cut pre-frailty risk by 39% and invasive cancer risk by 61%.

The standard recommendation is 1 to 1.6 grams daily, achievable through two servings of fatty fish per week. Supplements work for people who don’t eat fish.

One caveat, however: A rigorous mouse study found fish oil supplementation did not extend maximum lifespan in genetically diverse mice, suggesting omega-3s improve healthspan without necessarily extending lifespan itself.

Who is/are recommending it
Nearly every credible longevity researcher, cardiovascular specialists, the American Heart Association and, in all likelihood, your primary care physician.

The bottom line
Omega-3 fatty acids have the strongest evidence for slowing biological aging among all supplements reviewed here. One gram daily appears safe and effective. This is the closest thing to a no-brainer on this list.

5 | Metformin: A diabetes drug that may/not help with aging

What it is

Metformin is one of the world’s most widely prescribed drugs for type 2 diabetes, taken by tens of millions to help lower blood sugar, improve insulin sensitivity, and reduce cardiovascular risk. It is under active research for its effects on aging. For a more in-depth dive, read my April post on metformin, GLP-1s and rapamycin.

How it works

Metformin lowers glucose production in the liver and enhances cellular sensitivity to insulin. It activates AMPK, a key energy sensor, and reduces inflammation and oxidative stress. These mechanisms are thought to help counteract biological aging in cells.

The claimed benefits in humans

Enthusiasts claim metformin can delay age-related diseases like heart disease, dementia, and cancer, and may extend lifespan even in healthy people. It is promoted as a tool to slow the biological aging process and improve healthspan.

What the science actually says

Large observational studies consistently show reduced mortality and lower rates of cardiovascular events in diabetics taking metformin versus other diabetes drugs; for example, a UK study with over 180,000 people found reduced all-cause mortality in metformin users. Trials in non-diabetics are limited: The TAME (Targeting Aging with Metformin) trial aims to test metformin’s effect on healthy aging, but is still ongoing. Meanwhile, recent randomized trials and research reviews highlight potential drawbacks. Notably, several studies—including a well-cited 2019 JAMA study of older adults—found that metformin might blunt the benefits of resistance training and contribute to modest muscle mass loss in older adults, raising concerns about its use in healthy aging populations.

The bottom line

Metformin is strongly evidence-based for diabetes and may reduce age-related disease risk, but its anti-aging benefit for healthy people remains unproven, and possible risks—like effects on muscle—should be weighed until results from major clinical trials like TAME are published.

6 | Creatine: Not just for gym bros anymore

What it is
Creatine monohydrate is an organic compound made from three amino acids: glycine, arginine and methionine. Your body produces it naturally, and it’s found in meat and fish.

How it works
Creatine increases phosphocreatine stores in muscles, providing rapid energy during high-intensity activity. It also supports cellular energy metabolism, may enhance mitochondrial function and helps maintain muscle mass.

The claimed benefits in humans
Increased muscle mass and strength, improved bone density, enhanced cognitive function, better exercise performance and protection against age-related muscle loss.

What the science actually says
Creatine has 40 years of safety data in athletes. A 2024 systematic review found creatine combined with resistance training significantly improved muscle mass and upper body strength in older adults compared to training alone.

An eight-week pilot study in Alzheimer’s patients found creatine improved handgrip strength and muscle size—modest but clinically relevant in a population losing muscle rapidly.

A standard dose is 3-5 grams daily.

Who is/are recommending it
Exercise physiologists, sports medicine doctors, geriatric specialists. Increasingly recommended for aging adults, not just athletes. 5 g/day seems to fall under the “can’t hurt” category.

The bottom line
Creatine is inexpensive, extensively studied and safe. Helps maintain muscle and possibly bone. Best combined with resistance training. One of the most evidence-based supplements on this list.

What “longevity supplement” do you want reviewed?
Leave a comment and let me know.

7 | Vitamin D: The telomere guardian

What it is
Vitamin D3 is a fat-soluble vitamin produced in skin when exposed to sunlight. It functions more like a hormone than a traditional vitamin.

How it works
Vitamin D receptors exist throughout the body. The vitamin regulates calcium absorption, immune function, and gene expression. It may protect telomeres — the DNA caps at chromosome ends that naturally fray and shorten with age.

The claimed benefits in humans
Slowed cellular aging, reduced risk of age-related diseases, improved bone health, enhanced immune function and better mood and cognitive function.

What the science actually says
A 2025 analysis of the VITAL trial — 25,000 adults over five years — found that 2,000 IU of vitamin D3 daily slowed telomere shortening by about 140 base pairs over four years. Researchers estimate this equals roughly three years of cellular aging prevented.

However, an Australian trial of 1,519 participants found no difference in telomere length with monthly vitamin D supplementation. Some scientists question whether the measurement method (qPCR) used in the positive study is reliable enough.

Most Americans get insufficient vitamin D, particularly those over 70 or with limited sun exposure.

The bottom line
Large-scale trial evidence suggests vitamin D may slow cellular aging. Contradictory results and measurement concerns mean the jury’s still out. Get adequate vitamin D through sun exposure and diet first.

8 | Spermidine: The oddly-named autophagy activator

What it is
Spermidine is a polyamine — a small organic molecule with multiple amino groups. Your body synthesizes it from the amino acids arginine, ornithine and methionine. It’s also found in foods like wheat germ, aged cheese, mushrooms and soy products.

How it works
Spermidine induces autophagy — cellular self-cleaning where cells break down and recycle damaged components. It mimics some effects of caloric restriction and fasting. Spermidine levels naturally decline with age.

The claimed benefits in humans
Extended lifespan, improved cardiovascular health, better cognitive function, reduced inflammation and protection against neurodegenerative diseases.

What the science actually says
A landmark 20-year epidemiological study tracked 829 participants aged 45 to 84. All-cause mortality decreased across thirds of increasing spermidine intake from 40.5 deaths per 1,000 person-years to 15.1. Higher dietary spermidine intake was associated with lower mortality, lower cognitive impairment and lower dementia risk.

A 2024 Nature Cell Biology study showed spermidine levels increased during fasting in yeast, flies, mice and human volunteers, and that fasting’s longevity benefits depend on spermidine synthesis.

But human supplementation trials show mixed results. A 2024 study tested 40 mg/day of high-purity spermidine in healthy older men for 28 days and found it safe but with surprisingly little effect on circulating polyamine levels.

Cognitive studies show variable results: some participants improve, others don’t respond, some decline. Dosing remains uncertain — epidemiological benefits come from dietary intake around 12-15 mg daily, but supplements often use higher doses.

The bottom line
There’s strong epidemiological data linking dietary spermidine to longevity. Early mechanistic science looks promising. But supplementation trials haven’t consistently reproduced benefits. Food sources may work better than pills. Standard doses of 1-3 mg daily appear safe but may not reach tissue levels that trigger autophagy.

9 | Berberine: The bioavailability problem

What it is
Berberine is a yellow alkaloid extracted from several plants including goldenseal, barberry and Oregon grape. It’s been used in traditional Chinese medicine for thousands of years.

How it works
Berberine activates AMPK (AMP-activated protein kinase), the same pathway triggered by exercise and fasting. This affects glucose and lipid metabolism, potentially mimicking some benefits of caloric restriction and metformin.

The claimed benefits in humans
Extended lifespan, improved blood sugar control, better cholesterol levels, weight loss, anti-inflammatory effects and similar benefits to metformin without a prescription.

What the science actually says
Multiple meta-analyses show berberine effectively lowers blood sugar and improves insulin resistance — sometimes matching or exceeding metformin’s effects. One meta-analysis found berberine superior to metformin for improving insulin resistance.

The problem is that less than 1% of berberine is absorbed orally and about 80% of what is absorbed is metabolized in the liver before reaching systemic circulation.

There are essentially zero longevity studies in humans. Berberine increased lifespan in fruit flies, but that’s where the longevity data ends. Safety data is thin—1,600 completed clinical trials for metformin versus only 34 for berberine.

Berberine also inhibits enzymes involved in metabolizing many prescription drugs, creating potential interaction problems.

The bottom line
Good metabolic effects, terrible bioavailability, essentially zero human longevity data. If you need blood sugar control and can’t or won’t take metformin (which has its own problematic side effects, such as muscle loss) berberine might help. But calling it a longevity supplement is wishful thinking.

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10 | CoQ10: The mitochondrial support

What it is
Coenzyme Q10 (ubiquinone) is a fat-soluble compound your body produces naturally. It exists in every cell, primarily in mitochondria.

How it works
CoQ10 transfers electrons in the mitochondrial respiratory chain, helping produce ATP (cellular energy). It also functions as an antioxidant, protecting cell membranes and DNA from oxidative damage.

The claimed benefits in humans
Extended lifespan, improved energy levels, better cardiovascular health, enhanced mitochondrial function and protection against neurodegenerative diseases.

What the science actually says
CoQ10 levels decline with age in some but not all tissue. Animal studies show mixed results: one study found mice supplemented with CoQ10 had an 11.7% increase in mean lifespan and 24% increase in maximum lifespan. But other studies found no lifespan extension.

In humans, the evidence focuses on specific conditions rather than longevity. A Swedish study found selenium and CoQ10 supplementation improved vitality and reduced cardiovascular mortality in older adults over a 12-year span.

But a large phase III Parkinson’s trial using up to 2,400 mg/day found no convincing evidence CoQ10 helped. Alzheimer’s studies remain inconclusive.

CoQ10 levels fall with statin use, which inhibits its synthesis. Some benefits may come from correcting medication-induced deficiency rather than anti-aging effects.

The bottom line
The evidence for CoQ10 is speculative.

11 | Glycine: The simple amino acid with complex effects

What it is
Glycine is the simplest amino acid—just two carbons, one nitrogen, and a few hydrogens. Your body makes it, and it’s abundant in collagen-rich foods like bone broth, meat and gelatin.

How it works
Glycine serves as a building block for proteins, especially collagen. It’s a precursor to glutathione (the master antioxidant) and creatine. But the longevity angle involves glycine N-methyltransferase (GNMT), which clears excess methionine by converting glycine to sarcosine. This mimics methionine restriction, which extends lifespan in animals.

The claimed benefits in humans
Extended lifespan, improved sleep quality, better metabolic health, enhanced autophagy, reduced inflammation and protection against age-related diseases.

What the science actually says
A 2019 study from the NIA Interventions Testing Program found that 8% glycine in the diet led to a 4-6% increase in median lifespan in genetically diverse mice — significant and reproducible across three test sites.

In humans, studies are limited. A 2023 systematic review found the nervous system showed the most positive effects, including improved psychiatric symptoms and better sleep in small studies. But these had high risk of bias.

The real excitement comes from a 2024 Science Advances study showing GlyNAC (glycine + N-acetylcysteine) reversed multiple aging hallmarks in older adults, improving mitochondrial function, oxidative stress and molecular age scores.

Standard doses in human studies range from 3-5 grams daily.

The bottom line
Solid animal data for glycine’s ability to extend lifespan. Plausible mechanism through methionine metabolism and autophagy. Cheap, safe and widely available. Human longevity trials don’t exist yet, but the mechanistic story is certainly interesting.

12 | Magnesium: The unglamorous essential

What it is
Magnesium is a mineral — element 12 on the periodic table. (I’ve written a previous post about my adventures in magnesium supplement hell.) It’s the fourth most abundant mineral in your body, required as a cofactor for over 600 enzymatic reactions.

Not everyone needs or should want to take supplemental magnesium.

How it works
Magnesium is involved in DNA synthesis and repair, protein synthesis, energy production (ATP synthesis), calcium signaling and maintaining cell membrane integrity. It affects virtually every biological process that declines with age.

The claimed benefits in humans
Protection against age-related diseases, better cardiovascular health, improved bone density, enhanced cognitive function, reduced inflammation and regulation of all 12 hallmarks of aging.

What the science actually says
A comprehensive 2024 review in Nutrients examined magnesium’s relationship to all hallmarks of aging. The authors found evidence linking magnesium to genomic stability, telomere maintenance, epigenetic regulation, mitochondrial function, nutrient sensing, cellular senescence and inflammation.

Magnesium deficiency is extremely common in older adults. Western diets are notoriously low in magnesium. Deficiency is linked to increased inflammatory markers, cardiovascular disease, diabetes, osteoporosis and cognitive decline.

The recommended daily allowance is 310-320 mg for women and 400-420 mg for men. Typical Western diets provide only 50-80% of this.

Unlike other, higher profile supplements, magnesium addresses an actual widespread deficiency rather than trying to pharmacologically extend lifespan.

The bottom line
Not glamorous, but magnesium deficiency is real and common in older adults. It affects every aging pathway. Getting adequate magnesium through diet (leafy greens, nuts, whole grains, fish) or supplementation (magnesium glycinate or threonate for better absorption) is basic maintenance, not moonshot longevity.

What “longevity supplement” do you want reviewed next?

Taurine is on my list. Leave a comment and let me know.