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Scientists Discovered a Supplement That Repairs Aging Mitochondria (500–1,000 mg) – Transcript

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  • Urolithin A is a naturally occurring molecule that cannot be obtained directly from food, requiring gut bacteria to convert food polyphenols called ellagitannins into the active compound.
  • Human clinical trials suggest that urolithin A supplementation between 500 and 1,000 mg can act as a mitophagy activator and improve mitochondrial function and muscle performance.
  • Studies evaluating urolithin A supplementation have observed associated reductions in circulating lipid biomarkers, oxidative stress, and inflammation.
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This next deep dive question is interesting um because I recently started adding it back to my supplement routine. And this is urolithin A. I know we've talked about this before. So Jen submitted a question about urolithin A gaining attention for its anti-aging, mitochondrial support, anti-inflammatory properties, also its benefits for, you know, cancer and just

overall health benefits. Can you please do a deep dive into urolithin A, natural sources, supplementations, and all those things? So as Jen mentioned in her question, urolithin A is something that's a naturally occurring molecule. It has been getting a lot of attention um particularly for its effects on mitochondrial health.

And then that sort of spilling over into longevity cuz mitochondria are very important for longevity. But the first thing that you should know about urolithin A is that you actually can't get it directly from food. It's kind of like the sulforaphane. You get the precursor of it from food, right?

So and then you have to rely on your gut microbiome to convert it into the active compound. So what happens is there are polyphenols called ellagitannins. Those are polyphenols that are found in foods like pomegranates, they're found in raspberries, walnuts, pecans.

And we have gut bacteria that then convert these ellagitannins into urolithin A. However, it all depends again, you know, there's such huge individual variation in terms of gut microbiome composition.

And so some people have a lot of these bacteria that are converting ellagic acid into urolithin A and some people don't have hardly any. >> [snorts] >> And so there's a lot of variation in terms of if you're taking pomegranate or eating raspberries, what what how much urolithin A you're actually making. In fact, there There actually a study published in 2022, it was a crossover study.

So, 100 people found um found that only 12% of these participants, so only 12% of these 100 people actually had detectable levels of urolithin A at baseline, so before any dietary intervention was intervention was done.

And only 2% of those people were actually classified as high producers of urolithin A. Um but even after drinking about 240 ml of pomegranate juice, over 30% of them still showed no detectable levels.

Only 40% actually had high levels. So, 70% of people were making were actually producing urolithin A from drinking this pomegranate juice. Of those 70%, 40% of those people actually made really high levels of the urolithin A, whereas the the other, you know, 30% were just making moderate amounts. And then And then 30% of people made nothing, no

detectable amounts. So, again, it just comes down to having a more diverse gut microbiome, specifically if you have a higher Firmicutes to Bacteroidetes ratio, then it seems that you have better odds of actually producing higher levels of urolithin A in your gut.

So, um that's that kind of comes down to, well, do I have those levels? Have I had a uh you know, microbiome test? And what kind of foods can kind of give me that sort of ratio, right?

Um if you don't want to go there, then we can kind of talk about the supplementation studies. So, there have been a variety of studies looking at actually just supplementing urolithin A. So, there've been some human trials, potential benefits are usually seen between a dose range of 500 to 1,000 mg um with respect to again, 500 being the the minimum effective dose, 1,000 mg being probably where you're going to get the biggest bang for

your buck. Um, but to get 500 mg of urolithin A alone, you'd probably have to drink 1.5 L of pomegranate juice every day, even if you're a urolithin A producer at all.

So, um, if you're one of the low producers, then, you know, you're not going to get anything from the 1.5 L of pomegranate juice a day and with respect to urolithin A. So, I I do think that supplementation becomes a more predictable way of getting a therapeutic dose of urolithin A.

So, um, let's talk a little bit about that. Why why are we even interested in urolithin A? And I know we've talked about this in the past, but urolithin A does affect a process inside of our cells, and it's this process called mitophagy.

So, this is where mitochondria, you know, as you guys all know, mitochondria are very important for producing energy. Mitochondrial health is very, very tightly correlated with neurological health, with muscular health, with longevity, delaying age-related neurodegenerative disease, for example.

And so, um, our mitochondria have to repair themselves. They have they accumulate damage. They're the source of energy, so they're very prone to to taking hits of reactive oxygen species because that's where, you know, the reactive oxygen species are being produced by the mitochondria. So, they, you know, the mitochondria are taking a hit. And so, they do accumulate a lot of damage over their lifespan. And one of the ways that mitochondria get rid of that damage is

by clearing away parts of the mitochondria or even, in fact, the whole mitochondria if the whole mitochondria is damaged through this process of mitophagy. And, um, in fact, there are genetic pathways that are important for mitophagy and some humans have snips in genes that are important for regulating this process of mitophagy that that make them not work very good.

And those people end up with early-onset Parkinson's disease because mitochondrial health is so so important for for um Park for prevent Parkinson's disease and preventing Parkinson's disease. So, it's kind of was I It's been identified as this sort of um quote-unquote first-class mitophagy activator. There are some studies that we talk a little bit about some preclinical studies in aging mice.

Urolithin A has been shown to improve muscular muscle function. It's been shown to increase running capacity. Essentially rejuvenated, you know, older muscles. And um there's some early human studies that are kind of partially supporting this as well. So, in a randomized controlled trial of middle-aged adults that had low cardiorespiratory fitness, they took 500 mg of urolithin A or a placebo daily for 4 months. Then there

was but muscle biopsies that were done. And there was a variety of, you know, genes and proteins that are involved in mitophagy that are involved in mitochondrial energy productions that were shown to increase in in the in the muscle of the people that were actually given urolithin A.

Um urolithin A also reduced several circulating what are called acyl carnitines. So, these are some of lipid biomarkers um that the basically when you reduce them, that has been correlated with improved mitochondrial function.

So, that's something else to consider as well. Um and then another study that was actually published last year gave athletes, again, 1,000 mg of urolithin A and found that they could push harder in static strength test and keep going more reps before tiring um during other tests compared to placebo, but it did not seem to increase the maximum weight they could lift, which is not that surprising because strength um you know, the

most important thing there would be obviously doing you know, doing more doing doing more strength training. Um so it didn't seem to affect the strength, but it did affect you know, pushing harder and doing more reps as well. And then it was associated with some reductions in oxidative stress and inflammation.

Okay, so let's talk a little bit about metabolism. So if you do remember from my recent interview with Dr. Ben Bickman, we talked about ceramides playing a role in driving insulin resistance. When they build up inside the cells of muscle or liver or fat tissue, they can then disrupt insulin signaling.

So blood ceramide levels um in the study that we just talked about actually can reflect somewhat of a insulin resistant state. And so anything that's lowering blood ceramide levels is actually really good for metabolic health. Um so it'd be interesting to see some more studies into this area. Most studies looking at urolithin A are looking at exercise performance or mitochondrial markers, but um I think this is a new area because it it it has

been shown that urolithin A in a couple of studies can reduce ceramides and I do think that um is significant for metabolic health. So hopefully we'll see some more studies on that. There's there's right now just you know, preclinical studies looking at urolithin A and more I think more looking at the polyphenols and ellagic acid and cancer prevention, but there's a lot of things going on with polyphenols as well. And

so that's not an area I'm really going to talk about cuz I don't think there's enough evidence to make any claims about urolithin A and cancer. But I do think for generally just healthy people experimenting with 500 to 1,000 mg of urolithin a day, urolithin A urolithin A a day, um might be something worth trying. I am, like I said, I am adding that back to my supplement routine um as well. The [snorts]

brand that I'm going with is MitoPure. It's kind of expensive. So, um keep that in mind. You know, if anyone finds a cheaper brand that's quality, uh please let me know. But But that's the brand that I've uh decided to go with.

Frequently asked questions

No, urolithin A cannot be obtained directly from food, but instead relies on gut bacteria to convert dietary polyphenols called ellagitannins into the active compound.

Potential benefits are typically seen between a dose range of 500 to 1,000 mg, with 500 mg serving as the minimum effective dose and 1,000 mg providing the largest effect.

Urolithin A affects mitophagy, a cellular process where mitochondria clear away damaged parts or entire damaged mitochondria.