CheatSheet: The "top 12" longevity supplements

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

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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. In order of analysis, they are:

1. NMN

2. Rapamycin

3. AKG

4. Omega-3

5. Metformin

6. Creatine

7. Vitamin D

8. Spermidine

9. Berberine

10. COQ10

11. Glycine

12. Magnesium

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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.

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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