A Step-Change in Our Approach to Mitochondrial Care with Urolithin A

This blog was co-authored by Dr. Fitzgerald and Jennifer Scheinman MS, RDN, CDN.

Over the last decade, there has been an explosion of research looking at bioenergetics (energy metabolism) and the role our energy generators – the mitochondria – play in human health and longevity. 

 

From Dr. Fitzgerald:

In functional medicine, we’ve long been aware of bioenergetics – the need to “tend to our patient’s mitochondrial health,” and as such, we readily employ a litany of nutrients –  from CoQ10 to carnitine and lipoic acid and others – whenever we deem them indicated. 

There have not been, however, many nutrients to blast onto the bioenergetics center stage with quite the impressive force as the postbiotic rock star Urolithin A. With studies published in top-tier journals such as Nature and Cell – and with 11 (yes, eleven) compelling human clinical trials – if this compound hasn’t made it to the top of what you’re using for patients (and taking yourself), read on. 

What’s a postbiotic? Postbiotics are non-viable beneficial microorganisms and/or the beneficial metabolites that they produce. In the case of Urolithin A, it’s a compound produced by certain helpful microbes that offers beneficial effects for their host humans. 

 

My journey to Urolithin A came through my research and interest in epinutrients.

Epinutrients are nutrients that have some demonstrated ability to be able to favorably alter how genes are expressed. Very simply put, we think epinutrients support turning on genes associated with health and longevity and inhibiting genes that promote inflammation, disease, and accelerated aging. If you are familiar with my work, you know that I hypothesize that a root mechanism of action for many of those gorgeous polyphenols we include in the Younger You program (think EGCG, curcumin, quercetin, fisetin, resveratrol)  may be their extraordinary ability to sweet talk gene expression via favorable alteration of DNA methylation and other epigenetic marks. And I believe the polyphenol content of our program – a whopping 3000+ milligrams per day (akin to a Mediterranean diet on steroids) – played a key role in the 3+ years bio age reversing benefit we noted in both of our publications. Early research suggests that Urolithin A may be favorably impacting biological aging, and I’ll be paying close attention as that research evolves. 

 

Urolithin A is special – both in its studied actions and how it’s produced.

It’s different than the aforementioned polyphenols. Urolithin A is a postbiotic nutrient, so it’s a product of microbial action on the foods that contain the UA precursor compounds, ellagitannins, and ellagic acid (found in pomegranates, berries, and some nuts). However, only 1 in 3 people house the correct microbiome to make Urolithin A.

 

Are you a Urolithin A producer? Take the test

I was pretty excited to learn that I make a smidge of Urolithin A. But only a smidge. So this means I have some of those favorable gut bugs that can make it- but not enough to pump out the levels needed to exert the benefits noted in those 11 clinical trials I mentioned above.

Circling back to epinutrients. Thus far, to my knowledge, we don’t have any good data on Urolithin A’scapacity to influence the epigenome. However, we know its polyphenolic precursor compounds, ellagic acid and ellagitannins, have been identified to be epinutrients. My suspicion is that we’ll learn soon enough that Urolithin A can indeed sweet talk the epigenome, and perhaps some of the mechanisms teased out by the extensive research are mediated by this effect. I look forward to this research moving forward, and perhaps participating in some of it. 

 

Let’s chat for a minute on one of my favorite Urolithin A studies

The ATLAS trial was a double-blind, randomized, placebo-controlled study aiming to investigate if supplementation with Urolithin A would improve muscle function and physical performance in healthy middle-aged adults. 

In this study, 88 participants (40-64 years old), predominantly overweight with low physical endurance, were followed over four months. They were randomized into three groups: a control given a placebo, a second group administered 500mg of Urolithin A (Mitopure) daily, and a third with a 1000mg daily dose. 

The results were incredible. Both Urolithin A groups displayed improvements in muscle strength and performance.

• The 500 mg group showed a significant 12 percent increase in hamstring muscle strength
• The 1000 mg group demonstrated clinically meaningful improvements in V02 max and a 6-minute walk test. 
• Inflammatory biomarkers were also measured throughout the study, and at the end of the trial, C-reactive protein – a measure of inflammation – was reduced. 

All of this with no change in diet or exercise as part of the study design!

We know that muscle decline starts in our 30s and with a rate of loss at  3-8 percent every decade, so finding ways to slow or even reverse this decline is vital. While exercise and nutrition will always be the foundation to support and manage muscular health as we age, adherence can be a challenge for many of our patients. Having other agents in our bag of interventions, like Urolithin A, can be a game changer.

 

Here’s more from Jennifer Scheinman, MS, RDN, CDN and the team at Timeline about how this all comes together:

How does Urolithin A work?

At the heart of Urolithin A’s power is a process known as mitophagy, the cellular recycling process where old damaged mitochondria are degraded and replaced with newer, more efficient ones. 

Why is this so crucial? Mitochondrial health is intrinsically tied to the vitality of our cells and, by extension, our overall health. As we age, our mitochondria begin to deteriorate, leading to decreased energy production, reduced cellular function, and an accumulation of dysfunctional mitochondria. This decline is not just about feeling fatigued; it’s a hallmark of aging and is linked to several age-related diseases.

Urolithin A’s ability to trigger mitophagy is akin to a cellular spring cleaning. By promoting the removal of damaged mitochondria, Urolithin A ensures that our cells remain vibrant, energetic, and function at their optimal levels. This cellular rejuvenation, as seen in clinical trials, translates to tangible health benefits, like improved muscle function.

 

Can’t I just consume the precursors to Urolithin A to achieve the same effect?

While foods like pomegranates contain ellagitannins and ellagic acid, precursors to Urolithin A, the body’s conversion to this beneficial compound isn’t guaranteed. In fact, as noted above, most of us don’t naturally produce Urolithin A due to variations in our gut microbiota. And even for those who can make it, they would have to drink 6 glasses of pomegranate juice to get the same dose as seen in the clinical trials. (If you wear a continuous glucose monitor, as I do sometimes, you’ll quickly realize that consumption of this much pomegranate juice – or ANY pomegranate juice for some of us – results in a steep, unacceptable blood sugar spike)

 

In summary

In an age where the science of health and longevity is growing, understanding and harnessing the potential of groundbreaking compounds like Urolithin A to target the hallmarks of aging is essential. As we continue to bridge the gap between nature, nutrition, and science, the promise of a healthier, more vibrant future becomes increasingly attainable. 

For those keen on delving deeper into mitophagy, and this fascinating nutrient, your journey need not end here: 

Mitopure® is the first and only clinically-validated Urolithin A supplement. Timeline, the company behind Mitopure, was founded by doctors and scientists dedicated to using a biotech approach to nutritional compounds. They put Urolithin A on the map with their rigorous research published in medical journals like JAMA Open Network and Nature Metabolism. You can learn more about Mitopure, the science, and review their published papers at TimelineNutrition.com. 

Now, researchers around the world are studying it for a wide range of benefits, from cognitive decline to exercise performance and immune health. 

About Timeline: Timeline is a Swiss longevity brand created by the MDs and PhDs who have pioneered the research on Mitopure (Urolithin A) for over a decade. As scientists, we know that physical decline from aging can’t be stopped. However, through its groundbreaking science, Timeline is committed to developing products designed to help reduce the impact of time on health. For more information, please visit timelinenutrition.com.