Is Urolothin A the Ultimate Longevity Supplement?

The claims are it will renew your mitochondria, boost your strength, bolster your VO2max, and act like exercise in a pill. Is this fact or fiction? Here's what you need to know.

Urolithin A is claimed to be exercise in a pill, a potent weapon against aging that will rejuvenate your mitochondria and make you stronger and younger even without exercising, eating well, or fasting.

Dr. Mark Hyman lists it as the best way to clean up old mitochondria and create new ones, central to fixing the feeling of having no energy. Hyman has endorsed Mitopure, the major brand behind the product, as “a real scientific breakthrough. It’s the first product to unlock a precise dose of purified urolithin A.”

Dr. Rhonda Patrick lists it as a central way to address age-related mitochondrial decline.

The Swiss company Amazentis makes Mitopure. They developed it in conjunction with the Swiss Federal Institute of Technology de Lausanne, protected it with 56 patents, and launched a long-term research program on it. “At our core,” they write, describing the purpose of their research program, “we stand against pseudoscience.”

A 2016 paper in Nature Medicine by Amazentis authors launched the mechanistic claims that urolithin A lengthens lifespan in worms and leads to increased endurance and strength in rodents by stimulating mitophagy. Mitophagy is the clearance of bad mitochondria to make way for new, freshly made mitochondria.

Ever since this paper was published, nearly every other paper and review that studies urolithin A cites it as foundational evidence that stimulating mitophagy is its central mechanism of action.

Amazentis-affiliated papers love to call urolithin A a “first.” It is a “first in class” natural plant-based stimulator of mitophagy. In 2019, they published the “first-in-human” randomized, double-blind, placebo-controlled trial with urolithin A.

According to Amazentis-affiliated randomized controlled trials, four weeks of 500-1000 milligrams per day of urolithin A has a similar impact on mitochondrial health as ten weeks of aerobic exercise or twelve weeks of high-intensity interval training.

Better yet, these trials show that 1000 milligrams per day of urolithin A for four months will make you 12% stronger and increase your VO2 max by 14% without even exercising!

Most urolithin A papers take the mitophagy claims at face value without probing deeper into what urolithin A is doing at a mechanistic level. Close examination of the foundational 2016 paper suggests it is stimulating more fundamental pathways shared by other polyphenols, and these include inhibition of complex I of the mitochondrial respiratory chain.

That puts urolithin A into the class of “Good-For-You Toxins” that I described in my Hormesis Lesson, where a little bit of something bad for our cells can provide the stimulus we need to improve our cellular defenses.

It also raises important questions about how much is too much over what period of time, whether it needs to be cycled, and whether it is equally good for everyone or could be hurting some people who are bad candidates for it.

There are some indications from the trials that headaches and gastrointestinal problems are fairly common side effects, indicating not everyone’s metabolism is being optimized.

Further, Mitopure costs $100-125 per month. Is this doing something special over and above what a good diet does for you that is worth that kind of money?

Finally, while Amazentis stands against pseudoscience at its core, the claim that you can increase strength and VO2 max without exercising deserves some closer scrutiny before we throw $125 per month at it.

In this article, we examine the findings of the randomized controlled trials, put urolithin A into its appropriate context as a plant polyphenol, and form a working model of its mechanism of action that can help us properly interpret the trials. From this, we form conclusions about who should be taking urolithin A and why, and how to know if it might be right for you.

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