Episode 102
Urolithin A - Mitochondrial Miracle in the Petri Dish
Urolithin A: What It Is, How It Works, and Why Your Gut Decides Everything
By Dr. Terry Simpson
Most people hear the name Urolithin A and think it belongs in a commercial about prostate health. It sounds like something a man named “Gary, 62,” would talk about while fishing. But Urolithin A has nothing to do with plumbing. Instead, it sits at the center of a new wave of longevity science focused on how our cells clean up old, broken parts.
As we age, our mitochondria—the tiny power centers inside our cells—start to slow down. They build up damage and stop working well. Eventually, this pile-up makes us lose strength and energy. That’s where Urolithin A comes in. It helps switch back on a process called mitophagy, which is basically the cell’s recycling program for old mitochondria.
Where Urolithin A Really Comes From
You cannot eat Urolithin A directly. Instead, your body makes it when your gut bacteria break down special plant compounds called ellagitannins. These are found in foods like:
- pomegranates
- walnuts
- berries
- green tea (yes, really)
Green tea is usually known for its catechins, but it also contains ellagitannins like strictinin. After you drink it, your gut bacteria break these tannins apart and create ellagic acid, which can later turn into Urolithin A.
However, this only works if you have the right microbes. And here’s the surprising part:
Most people do not.
Studies show that only 12% to 40% of adults naturally produce Urolithin A from food. Everyone else makes little to none because their gut bacteria simply aren’t built for the job.
How Your Gut Decides Everything
Your microbiome—the community of bacteria living in your digestive system—decides whether you make Urolithin A or not.
People who produce Urolithin A usually have:
- more diverse gut microbes
- special bacteria like Enterocloster and Gordonibacter
- the right genes inside those microbes to do the chemical conversion
People who don’t produce it (called “metabotype zero”) lack those bacteria or the gene pathways needed. Eating more pomegranates or drinking more green tea does not fix this. No diet, including keto or Mediterranean, has been shown to turn a non-producer into a producer.
This is why two people can eat the same food, and only one makes Urolithin A.
What Urolithin A Does in Humans
In older adults, researchers have tested Urolithin A supplements for up to 4 months. These studies show several encouraging results:
- muscle endurance improves
- inflammation markers decrease
- mitochondrial health markers look better
Even so, there are limits. Trials show no meaningful improvement in:
- walking distance
- ATP (cellular energy) production
- overall physical function
So the biology looks better, but major clinical outcomes have not changed.
What Happens in the Lab (But Not Yet in Humans)
Scientists also study Urolithin A in senescent cells—cells that have stopped dividing but still cause inflammation. In the lab, Urolithin A can:
- reduce senescence markers
- calm inflammatory signals
- restore mitophagy
- improve oxidative stress
- even strengthen circadian rhythms inside aging cells
All of this sounds exciting. However, these findings are from cell culture, not humans. They give us clues, not guarantees.
Food vs Supplements
You cannot get Urolithin A directly from food. You only get the precursors, and only people with the right gut bacteria turn those precursors into Urolithin A.
Supplements bypass the microbiome entirely and give everyone measurable Urolithin A, even non-producers.
Foods that contain ellagitannins include:
- pomegranates
- walnuts
- raspberries
- blackberries
- some teas, especially green tea
But none of these will raise Urolithin A levels if your gut bacteria cannot perform the conversion.
Is Urolithin A Safe?
Short-term human studies show that Urolithin A is safe and well-tolerated. Most people experience no side effects. When side effects do show up, they are usually mild digestive symptoms like bloating or softer stools.
What we don’t know:
- long-term safety
- pregnancy or breastfeeding safety
- multi-year use
- effects in chronic disease
In other words, the short-term data look good, but the long-term story hasn’t been written yet.
Should You Take It?
Here is the simple answer:
Urolithin A is biologically promising but clinically modest.
It improves certain cellular markers and may boost muscle endurance in older adults.
It does not reverse aging or change major health outcomes—not yet.
Supplements make the most sense for:
- adults over 60
- people with early muscle loss
- individuals who are non-producers
- those wanting to support mitochondrial health
But nothing replaces the basics:
- resistance training
- movement
- eating well
- sleep
- stress control
That is still the foundation of a longer, healthier life.
REFERENCES
(For the blog — as provided)
- Kuerec AH, Lim XK, Khoo AL, et al. Targeting Aging With Urolithin A in Humans: A Systematic Review. Ageing Research Reviews. 2024;100:102406.
- Heilman J, Andreux P, Tran N, et al. Safety Assessment of Urolithin A… Food and Chemical Toxicology. 2017;108:289-297.
- Hasheminezhad SH, Boozari M, Iranshahi M, et al. Biological Activities of Urolithins… Phytotherapy Research. 2022;36(1):112-146.
- Singh A, D'Amico D, Andreux PA, et al. Direct Supplementation With Urolithin A… European Journal of Clinical Nutrition. 2022;76(2):297-308.
- Aichinger G, Stevanoska M, Beekmann K, et al. PBPK Modeling of Urolithin A… Molecular Nutrition & Food Research. 2023;67(15).
- D'Amico D, Andreux PA, Valdés P, et al. Impact of Urolithin A on Health, Disease, and Aging. Trends in Molecular Medicine. 2021;27(7):687-699.
- Gandhi GR, Antony PJ, Ceasar SA, et al. Health Functions of Ellagitannin-Derived Urolithins. Critical Reviews in Food Science and Nutrition. 2024;64(2):280-310.
- Zhang M, Cui S, Mao B, et al. Ellagic Acid and Urolithin A: Sources and Metabolism. Critical Reviews in Food Science and Nutrition. 2023;63:6900-6922.
- García-Villalba R, Giménez-Bastida JA, Cortés-Martín A, et al. Urolithins: Metabolism and Microbiota. Molecular Nutrition & Food Research. 2022;66:2101019.
Transcript
>> Dr. Terry Simpson: As we age, our mitochondria get sloppy. They break
Speaker:down, pile up, and gum up the machinery that keeps
Speaker:our cells running smoothly. And for the last few
Speaker:years, one molecule, urolithin A, has been making
Speaker:headlines for its supposed ability to reactivate
Speaker:the cellular cleanup system that slows as we get
Speaker:older. Before we talk hype, let's start with what
Speaker:urolithin A actually is. It's not something you
Speaker:eat. It's something that your gut bacteria make
Speaker:after you consume foods rich in elegant. These are
Speaker:polyphenols found in pomegranates, walnuts,
Speaker:berries, and green tea. Green tea is famous for
Speaker:its catkins, but it's also a real source of
Speaker:elligechanins like strychnine, meaning it provides
Speaker:the raw ingredients your microbes need to make
Speaker:urolithin A. And if you're lucky enough to have
Speaker:the right gut bacteria, you're lucky. When I first
Speaker:heard about urolithin A, I thought it was a
Speaker:commercial for a urology product. Something for
Speaker:benign prostatic hypertrophy. Maybe a middle aged
Speaker:man named Greg talking about improved flow. I'm
Speaker:sorry, urolithin A. You really deserve better
Speaker:marketing. So today we're going to skip the
Speaker:infomercials and look to the real science. Where
Speaker:urolithin A comes from, how it works, and why your
Speaker:microbiome decides whether pomegranates turn into
Speaker:longevity molecule or just a fruit stain on your
Speaker:favorite white shirt.
Speaker:Today we're continuing our longevity series and
Speaker:making sense of the madness of urolithin A. Yes,
Speaker:you've seen the tiktoks for it. I am, um, your
Speaker:Chief Medical Explanationist, Dr. Terry Simpson,
Speaker:and this is for Q Fork University, where we bust a
Speaker:few myths, make sense of the madness, and teach
Speaker:you a little bit about food and medicine.
Speaker:Urolithin A is created when your gut bacteria take
Speaker:alga channins and break them down into various
Speaker:forms that convert to urolithin A. You're not
Speaker:absorbing them directly. Your microbiomes are
Speaker:doing the chemistry for you like it does for a lot
Speaker:of things. It activates this pathway that does
Speaker:cellular housekeeping, that tags and recycles old
Speaker:broken mitochondria. So mitochondria, uh, are the
Speaker:powerhouse of the cell. I want you to imagine a
Speaker:cell. So the cell has, if you may recall from
Speaker:biology, a surrounding membrane, a, uh, nucleus
Speaker:and mitochondria. And it's the mitochondria that
Speaker:provide the energy and do the, a lot of the repair
Speaker:and that your cell needs. When you're young. This
Speaker:system works beautifully. After age 40, well, it
Speaker:kind of works like the TSA line during the
Speaker:government shutdown. Slow backed up and full of
Speaker:complaints. And urolithin A doesn't create new
Speaker:mitochondria. It helps your body clean out the bad
Speaker:ones so the good ones can perform better. Here's,
Speaker:uh, where urolithin A becomes a tale of two guts.
Speaker:Your microbiome decides your urolithin a destiny.
Speaker:It turns out only 12 to 40% of adults naturally
Speaker:produce urolithin A after eating foods that are
Speaker:rich in that substance. The urolithin A producers
Speaker:have gut microbiomes that look like a botanical
Speaker:garden. Rich diversity. They have a number of key
Speaker:bacteria that seem to carry the exact genes that
Speaker:are needed to make urolithin A. But most people
Speaker:are non producers. They don't have the microbiomes
Speaker:or the microbiomes with the functional genes. And
Speaker:no matter how many pomegranates they eat, how much
Speaker:green tea they drink, they make zero urolithin A.
Speaker:Do diets fix this? No. No diet. Keto, low carb,
Speaker:etc. No biohacker, no ancestral diet has been
Speaker:shown to turn a non producer of urolithin A into a
Speaker:producer. Now, the Mediterranean diet might give
Speaker:you more elegant, but it cannot install the
Speaker:bacteria required to convert them into ua and keto
Speaker:bacon. It does not care about your mitochondria.
Speaker:Here's the important part. If you happen to be a
Speaker:urolithin A producer, diet matters because you
Speaker:have the right microbiomes. If you're a non
Speaker:producer, food will never get you there. Hence
Speaker:supplement, bypass the entire microbiome
Speaker:bottleneck. Let's look at some actual trials and
Speaker:the human data. There have been tons of
Speaker:randomization trials in older adults. Typically 4
Speaker:months of urolithin A supplementation led to
Speaker:improved muscle endurance, improved mitochondrial
Speaker:biomarkers, reduced C reactive protein and
Speaker:inflammation marker by but importantly, there was
Speaker:not an improvement in 6 minute walk distance,
Speaker:there was not an improvement in ATP production,
Speaker:and there were no changes in major mobility
Speaker:outcomes. So your mitochondria looked happier. But
Speaker:in the big clinical outcomes, things didn't
Speaker:change. Another systemic review where they looked
Speaker:at five randomized controlled trials involving
Speaker:about 250 people, had the same story. Better
Speaker:autophagy markers, modest endurance improvements,
Speaker:lower inflammatory markers, but no effect on
Speaker:cardiovascular outcomes, weight or physical
Speaker:function. Urolithin A is biologically promising,
Speaker:but it's clinically modest.
Speaker:Now let's talk about the Hayflick senescent Cells.
Speaker:As you may recall, our cells are programmed to
Speaker:die. They will divide 50 plus or minus 10 times.
Speaker:They go into senescence and retire. Cells stop
Speaker:dividing and they just sort of hang out. But they
Speaker:don't hang out in a positive way like grandpa at
Speaker:the nursing home. They spend their time spewing
Speaker:inflammatory molecules which really make your
Speaker:whole body sick. Now, in vitro, meaning in the
Speaker:laboratory, you, Urolithin A does some kind of
Speaker:impressive things. It decreases some of the
Speaker:senescent cells, it suppresses some of the
Speaker:inflammatory markers, it restores mitophagy, it
Speaker:improves oxidative stress markers, and it boosts
Speaker:circadian rhythm amplitude in senescent
Speaker:fibroblasts. So urolithin A behaves kind of like
Speaker:a. It tames senescent cells rather than killing
Speaker:them. But none of this has been shown in human
Speaker:dishes. It's petri dishes, not clinical outcomes.
Speaker:In some cancer cell models, urolithin A actually
Speaker:induces senescence. And that's kind of promising
Speaker:also. But context matters. This is why we don't
Speaker:turn lab data into longevity promises. Well, we at
Speaker:4Q don't. Now let's be clear. You cannot get
Speaker:urolithin A directly from food. You can only get
Speaker:it from the precursors. And, and people who have
Speaker:the right microbiome can convert them. But if you
Speaker:don't have the right microbiome, you can't. And we
Speaker:don't seem to be able to give you probiotics to do
Speaker:this. So what we actually know from safety data in
Speaker:urolithin A is from studies that last about four
Speaker:months of daily use. Four months, that's not four
Speaker:years. In that window when we give patients 250 to
Speaker:1,000 milligrams a day, there was no significant
Speaker:severe adverse outcome. There was no dose limiting
Speaker:toxicity. The side effects were similar to
Speaker:placebos. There were no liver changes, no kidney
Speaker:changes, no blood abnormalities, some mild GI
Speaker:symptoms. Bloating, loose stools is the most
Speaker:common things. What about long term data? We don't
Speaker:have it. What about pregnancy data? We don't know
Speaker:and clearly don't recommend it for people who are
Speaker:pregnant. There's no multi year use data, there's
Speaker:no chronic disease safety data. So if someone says
Speaker:that urolithin A is proven safe long term, they're
Speaker:selling confidence, they're not selling evidence.
Speaker:So should you take it? Well, here's a verdict from
Speaker:us. At 4q, Urolithin A does something real. At the
Speaker:mitochondrial level. It improves biomarkers, helps
Speaker:endurance in older adults, it's safe short term.
Speaker:It bypasses that microbiome bottleneck, but it
Speaker:does not change major clinical outcomes, it does
Speaker:not reverse aging, and it doesn't replace the
Speaker:basics. The basics of lifting weight, moving your
Speaker:body, eating a Mediterranean style diet, getting
Speaker:better sleep, managing stress by taking more
Speaker:walks, and avoiding quacks. Urolithin A is
Speaker:scientifically interesting, but it is not
Speaker:scientifically transformative. Save the money for
Speaker:the supplement. Come on our Mediterranean cruise
Speaker:this summer and learn about the real science of
Speaker:longevity and things that will really work. I'm
Speaker:Dr. Terry Simpson and this has been Fork you where
Speaker:we break down the science, bust the myths, and
Speaker:keep you out of quack traps. References for this
Speaker:will appear on Forku.com and YourDoctorsOrders.com
Speaker:Go ahead and follow me on TikTok where I'm RTARY
Speaker:Simpson and Instagram where I'm Rterry Simpsonmd
Speaker:for real medical science minus the nonsense. And
Speaker:remember, I'm a physician who's researched and
Speaker:written this, but I am not your board certified
Speaker:physician. Before you take any supplements, please
Speaker:talk to a board certified physician. Before
Speaker:changing diets, please talk to a registered
Speaker:dietitian, not a chiropractor, not an Eastern
Speaker:health medicine type. Nothing like that. Until
Speaker:then, have a Good week. I'm Dr. Simpson. This is
Speaker:Forq. Good day. Hey Evo, you're old with an A. It
Speaker:still sounds like something for your prostate.
Speaker:>> Speaker B: Yeah, but you medical people have weird names for
Speaker:most things like that. Still, I'm sure someone
Speaker:will try to use it for that. Man, we still got
Speaker:work to do.
