Today we’re talking about a compound that promotes mitochondrial health & ATP production,
yet it declines with age, you can’t get it from any food, and most of us can’t make it.
So, what is it?
We’re talking about Urolithin A.
Stay tuned to learn how to boost your levels of Urolithin A.
Today, we’re going to be talking about another compound that is naturally produced inside of the human body,
that can potentially have a big impact on healthy aging and longevity.
And that’s Urolithin A.
This molecule show a lot of promise, but not everyone can produce it.
We’ll be taking a look at what Urolithin A is, how it works,
how it’s produced in the body…or not, and it’s impact on aging.
We’ll also be examining some studies that seem to back all of this up.
Alright, let’s start off by talking about what is Urolithin A.
Urolithin A is a gut microbiome-derived metabolite.
That means that bacteria that live in the gut convert precursors into Urolithin A.
You can’t obtain Urolithin A from any foods that I know of, although you can obtain the precursors from food.
Urolithin A is a peptide, which means that it’s a protein that’s made up of short chains of amino acids.
And it’s something that occurs naturally in the human body.
But it’s what it does in the body, and the benefits that it bestows, that are the subject of today’s video.
So, it seems that the primary path that Urolithin A uses is through mitophagy,
which is a form of autophagy that recycles the mitochondria, which in turn are the powerhouses of the cells.
They produce ATP, or adenosine triphosphate, the universal power source of all cells, whether plant or animal.
The mitochondrial create ATP through a process called "cellular respiration"
where they metabolize the food we eat and the air we breathe into ATP.
But the mitochondria tend to disfunction more and more the older that we get.
This is because the individual mitochondria don’t produce as much ATP as they once did,
and because there are fewer and fewer functional mitochondria as we age,
and more and more dysfunctional mitochondria.
A study by Frank Schallenberg estimates the everyone over the age of 40 has some level of mitochondrial dysfunction.
Mitophagy is a form of autophagy that recycles these dysfunctional mitochondria
and use the recycled components to build new mitochondria.
So, mitophagy is one way to improve mitochondrial dysfunction, which is reversible, by the way.
And improved mitochondrial function means improved ATP production,
making more energy available to run all the processes of life.
So, Urolithin A works by boosting mitophagy and mitochondrial function in cells.
Taking supplemental Urolithin A increased biomarkers for mitochondrial function in elderly people.
It also blunts inflammatory responses.
As I mentioned earlier, Urolithin A is a gut microbiome-derived metabolite,
converting it’s precursors into Urolithin A.
Those precursors are a class of polyphenols called ellagitannis and ellagic acid.
Urolithin A is not found in any foods that I know of, but ellagitannis and ellagic acids are.
These polyphenols are found in pomegranates, raspberries, strawberries and walnuts, to name a few.
But here’s the thing.
Only about 40% of all human beings are capable of converting ellagitannins and ellagic acid into Urolithin A.
Everybody’s microbiome is different, because of diet, genetics, race, culture, sex…
a whole slew of different things can impact our microbiome.
And of those 40% that CAN convert polyphenols into Urolithin A, almost none of them can convert enough.
So…I need to talk about the whole concept of getting the micronutrients that we need from food,
versus getting Urolithin A directly through supplementation.
Now, I’ll freely admit, getting your micronutrients through the food you eat is the best way to get them, and the most bioavailable.
But here’s the problem, you have to consume so much food to obtain the micros in the quantity desired.
And those foods often contain other things that you really don’t need or even want in those quantities.
I personally feel that it’s the macronutrients in food that should be driving the decision about how much to eat, not the micronutrients.
Case in point.
Pomegranates have long been known to have excellent healthy benefits.
They contain some great compounds, things like ellagitannis, particularly a form called punicalagin.
These are hydrolyzable tannins and they hydrolize in the stomach, releasing ellagic acid.
But the great benefits of pomegranates aren’t because of ellagitannis or ellagic acid.
Eating a pomegranate doesn’t boost levels of either in the bloodstream.
That’s because they undergo a biotransformation in the gut, specifically in the colon.
They get converted into a class of phenolics called urolithins.
But, you’d have to drink 5 glasses of pomegranate juice to generate the equivalent of 500 mg of urolithin A…
if you can even convert it at all.
And pomegranate juice has a very high amount of dietary sugars and carbs.
5 glasses has a lot more sugar and carbs than you want, or need.
So, to create Urolithin A in the body, you need a good source of ellagitannins, like pomegranates.
But you also need to be one of those people who can convert ellagitannins into Urolithin A.
So, Urolithin A can come from pomegranates, if you consume enough of them AND if you’re a converter.
Now, to make things worse, if you are a converter, as you age,
your ability to convert ellagitannins and ellagic acid into Urolithin A goes into decline, becoming less and less.
As a result, across the board, for all aging adults, Urolithin A levels drop, and so does mitophagy.
And so does mitochondrial function.
In fact, mitochondrial dysfunction is one of the Hallmarks of Aging.
Now, there’s been several studies on the effects of supplemental Urolithin A on the aging process,
but they’ve all been conducted by a company called Amazentis, which makes a Urolithin A supplement.
So, you need to take this information with a grain of salt.
That said, let’s take a look at some of these studies.
This study was looking at the effect of Urolithin A on the mitochondria, particularly in muscle tissue.
When they fed Urolithin A to c. elegans worms, they found that the worms increase their lifespans by about 50%.
When they fed it to mice, they found that the Urolithin A increased muscle endurance by about 40%, allowing them to run longer.
They also experienced a 10% increase in muscle strength.
Now, these were normally aged mice that were “metabolically challenged”, meaning that they were fat, over-fed mice.
They then treated older mice to supplemental Urolithin A for a few months and found that same 40% increase in muscle endurance.
Finally, they tested the supplements on humans, and found that they seemed to provide similar benefits.
These were human aged 45-65, who received a daily dose of 500 mg and were tested for 4 months.
And the researchers found an increase in muscle strength in the leg muscles of the participants.
They also compared drinking 1 glass of pomegranate juice against supplementing with 500 gm of Urolithin A,
by measuring the levels of Urolithin A in the blood after 24 hours.
And what they found was a 6-fold increase in Urolithin A levels in the supplements, compared to the pomegranate juice.
Now, they only saw an increase in Urolithin A with the pomegranate juice in 40% of the users, because the rest weren’t converting.
However, among those supplementing with Urolithin A, they saw in increase in Urolithin A in the blood in 100% of those participants.
Another study found that the pathways in which Urolithin A stimulates mitophagy are the same for c. elegant, mice and for humans.
This same pathway is conserved across all species.
They tested healthy, elderly males and females aged 61-85,
and they gave them a single dose of Urolithin A up to 2000 mg per day, for 28 days.
The participants showed increase biomarkers of mitochondrial health,
and they determined that Urolithin A is safe, bioavailable and that it positively impacts mitophagy.
The final study was looking at the effect of age-related loss of muscle mass and strength
that shows up as a reduction in physical performance and endurance capacity. You know…sarcopenia.
The decline in mitochondrial efficiency and the resulting loss of ATP production in skeletal muscle
is associated with a decline in performance and an increase in fatigue.
So, they conducted a 4-month trial with 66 older adults, aged 60-90,
and what they were looking for were any changes in a 6-minute walking distance and maximal ATP production in the hand.
They tested at 2 months and then again at 4 months.
Half the group were on a placebo and the other half were supplementing with Urolithin A.
Both groups saw an increase in the 6-minute walk with the Urolithin A group improving by 14.9%
and the placebo group improving by 10.1%.
This was probably because both groups were exercising during the trial, although this wasn’t controlled by the researchers.
This wasn’t enough of an improvement to conclude that there was a significant effect,
although there was definitely a trend that looked promising.
For the improvement in ATP production, again, there wasn’t enough of an improvement to conclude a significant effect.
There were some secondary outcomes that were interesting, though.
They measured the number of muscle contractions for both the leg muscles and the muscles of the hand, to determine endurance.
At the 2-month mark, there was a significant improvement in the Urolithin A group over the placebo group, \
but at 4 months it turned out the the placebo group had a parallel improvement…
so again, no significant effect of treatment, although there was an interesting trend.
Now, this was a small trial, and it showed some interesting trends,
even if it didn’t result in any definitive improvements, suggesting the need for a larger trial, and one that included controlled exercise.
The researchers concluded that Urolithin A may be a promising approach
to counteract age-related loss of muscle mass and strength.
Like I said earlier, all three trials were conducted by Amazentis, who make a Urolithin A supplement.
As most studies into longevity seem to turn out,
the trials in worm and mice produced more promising results than the ones in humans,
but the human trial did look promising.
So, in terms of recommendations, I would probably try the Urolithin A supplement for myself,
track my results and determine for myself if supplementing with Urolithin A had any beneficial effect on me, personally.
Thing is, it’s kinda spendy and I can’t really afford it right now.
But, if I ever do try it, I’ll put up a video with my results and conclusions.
And that’s it for this video.
If you’d like to learn more about the various longevity molecules and compounds that you can take as supplements,
check out this playlist.
I’m outta here, thanks for watching. Catch ya next time.