>> Dr. Terry Simpson: As we age, our mitochondria get sloppy. They break

down, pile up, and gum up the machinery that keeps

our cells running smoothly. And for the last few

years, one molecule, urolithin A, has been making

headlines for its supposed ability to reactivate

the cellular cleanup system that slows as we get

older. Before we talk hype, let's start with what

urolithin A actually is. It's not something you

eat. It's something that your gut bacteria make

after you consume foods rich in elegant. These are

polyphenols found in pomegranates, walnuts,

berries, and green tea. Green tea is famous for

its catkins, but it's also a real source of

elligechanins like strychnine, meaning it provides

the raw ingredients your microbes need to make

urolithin A. And if you're lucky enough to have

the right gut bacteria, you're lucky. When I first

heard about urolithin A, I thought it was a

commercial for a urology product. Something for

benign prostatic hypertrophy. Maybe a middle aged

man named Greg talking about improved flow. I'm

sorry, urolithin A. You really deserve better

marketing. So today we're going to skip the

infomercials and look to the real science. Where

urolithin A comes from, how it works, and why your

microbiome decides whether pomegranates turn into

longevity molecule or just a fruit stain on your

favorite white shirt.

Today we're continuing our longevity series and

making sense of the madness of urolithin A. Yes,

you've seen the tiktoks for it. I am, um, your

Chief Medical Explanationist, Dr. Terry Simpson,

and this is for Q Fork University, where we bust a

few myths, make sense of the madness, and teach

you a little bit about food and medicine.

Urolithin A is created when your gut bacteria take

alga channins and break them down into various

forms that convert to urolithin A. You're not

absorbing them directly. Your microbiomes are

doing the chemistry for you like it does for a lot

of things. It activates this pathway that does

cellular housekeeping, that tags and recycles old

broken mitochondria. So mitochondria, uh, are the

powerhouse of the cell. I want you to imagine a

cell. So the cell has, if you may recall from

biology, a surrounding membrane, a, uh, nucleus

and mitochondria. And it's the mitochondria that

provide the energy and do the, a lot of the repair

and that your cell needs. When you're young. This

system works beautifully. After age 40, well, it

kind of works like the TSA line during the

government shutdown. Slow backed up and full of

complaints. And urolithin A doesn't create new

mitochondria. It helps your body clean out the bad

ones so the good ones can perform better. Here's,

uh, where urolithin A becomes a tale of two guts.

Your microbiome decides your urolithin a destiny.

It turns out only 12 to 40% of adults naturally

produce urolithin A after eating foods that are

rich in that substance. The urolithin A producers

have gut microbiomes that look like a botanical

garden. Rich diversity. They have a number of key

bacteria that seem to carry the exact genes that

are needed to make urolithin A. But most people

are non producers. They don't have the microbiomes

or the microbiomes with the functional genes. And

no matter how many pomegranates they eat, how much

green tea they drink, they make zero urolithin A.

Do diets fix this? No. No diet. Keto, low carb,

etc. No biohacker, no ancestral diet has been

shown to turn a non producer of urolithin A into a

producer. Now, the Mediterranean diet might give

you more elegant, but it cannot install the

bacteria required to convert them into ua and keto

bacon. It does not care about your mitochondria.

Here's the important part. If you happen to be a

urolithin A producer, diet matters because you

have the right microbiomes. If you're a non

producer, food will never get you there. Hence

supplement, bypass the entire microbiome

bottleneck. Let's look at some actual trials and

the human data. There have been tons of

randomization trials in older adults. Typically 4

months of urolithin A supplementation led to

improved muscle endurance, improved mitochondrial

biomarkers, reduced C reactive protein and

inflammation marker by but importantly, there was

not an improvement in 6 minute walk distance,

there was not an improvement in ATP production,

and there were no changes in major mobility

outcomes. So your mitochondria looked happier. But

in the big clinical outcomes, things didn't

change. Another systemic review where they looked

at five randomized controlled trials involving

about 250 people, had the same story. Better

autophagy markers, modest endurance improvements,

lower inflammatory markers, but no effect on

cardiovascular outcomes, weight or physical

function. Urolithin A is biologically promising,

but it's clinically modest.

Now let's talk about the Hayflick senescent Cells.

As you may recall, our cells are programmed to

die. They will divide 50 plus or minus 10 times.

They go into senescence and retire. Cells stop

dividing and they just sort of hang out. But they

don't hang out in a positive way like grandpa at

the nursing home. They spend their time spewing

inflammatory molecules which really make your

whole body sick. Now, in vitro, meaning in the

laboratory, you, Urolithin A does some kind of

impressive things. It decreases some of the

senescent cells, it suppresses some of the

inflammatory markers, it restores mitophagy, it

improves oxidative stress markers, and it boosts

circadian rhythm amplitude in senescent

fibroblasts. So urolithin A behaves kind of like

a. It tames senescent cells rather than killing

them. But none of this has been shown in human

dishes. It's petri dishes, not clinical outcomes.

In some cancer cell models, urolithin A actually

induces senescence. And that's kind of promising

also. But context matters. This is why we don't

turn lab data into longevity promises. Well, we at

4Q don't. Now let's be clear. You cannot get

urolithin A directly from food. You can only get

it from the precursors. And, and people who have

the right microbiome can convert them. But if you

don't have the right microbiome, you can't. And we

don't seem to be able to give you probiotics to do

this. So what we actually know from safety data in

urolithin A is from studies that last about four

months of daily use. Four months, that's not four

years. In that window when we give patients 250 to

1,000 milligrams a day, there was no significant

severe adverse outcome. There was no dose limiting

toxicity. The side effects were similar to

placebos. There were no liver changes, no kidney

changes, no blood abnormalities, some mild GI

symptoms. Bloating, loose stools is the most

common things. What about long term data? We don't

have it. What about pregnancy data? We don't know

and clearly don't recommend it for people who are

pregnant. There's no multi year use data, there's

no chronic disease safety data. So if someone says

that urolithin A is proven safe long term, they're

selling confidence, they're not selling evidence.

So should you take it? Well, here's a verdict from

us. At 4q, Urolithin A does something real. At the

mitochondrial level. It improves biomarkers, helps

endurance in older adults, it's safe short term.

It bypasses that microbiome bottleneck, but it

does not change major clinical outcomes, it does

not reverse aging, and it doesn't replace the

basics. The basics of lifting weight, moving your

body, eating a Mediterranean style diet, getting

better sleep, managing stress by taking more

walks, and avoiding quacks. Urolithin A is

scientifically interesting, but it is not

scientifically transformative. Save the money for

the supplement. Come on our Mediterranean cruise

this summer and learn about the real science of

longevity and things that will really work. I'm

Dr. Terry Simpson and this has been Fork you where

we break down the science, bust the myths, and

keep you out of quack traps. References for this

will appear on Forku.com and YourDoctorsOrders.com

Go ahead and follow me on TikTok where I'm RTARY

Simpson and Instagram where I'm Rterry Simpsonmd

for real medical science minus the nonsense. And

remember, I'm a physician who's researched and

written this, but I am not your board certified

physician. Before you take any supplements, please

talk to a board certified physician. Before

changing diets, please talk to a registered

dietitian, not a chiropractor, not an Eastern

health medicine type. Nothing like that. Until

then, have a Good week. I'm Dr. Simpson. This is

Forq. Good day. Hey Evo, you're old with an A. It

still sounds like something for your prostate.

>> Speaker B: Yeah, but you medical people have weird names for

most things like that. Still, I'm sure someone

will try to use it for that. Man, we still got

work to do.