From Gut to Mitochondria: Understanding Urolithin A


In my new book, Smarter Not Harder, I talk about how to maximize your health and performance with as little effort as possible. One of the ways I do this is by carefully incorporating powerful supplements into my daily routine. 

One supplement that I use daily, and even mention in my book, is Urolithin A.

What is Urolithin A?

Urolithin A is a postbiotic compound that has been clinically shown to trigger a cellular recycling process called mitophagy.  By stimulating mitophagy, our mitochondria work better, providing much needed energy to our cells to perform at their best.

We don’t get Urolithin A directly from our food. Instead, we rely on our gut microbiome to make it. Unfortunately, studies have shown that less than 40% of the population can make it. And even for those of us who can make it, diet alone would not be enough to see substantial benefits.1 

Over the last 15 years, 300 trials examining the health benefits of Urolithin A have been published, 11 of which were conducted in humans. This makes Urolithin one of the most researched longevity supplements on the market. 

2022 marked a record year in terms of new research surrounding Urolithin A. Across the globe, top-level research institutions conducted numerous pre-clinical and clinical trials examining the diverse potential applications of Urolithin A, improvements in muscle strength and performance, brain and neuroprotective benefits, the immune system, joints, and reproductive health. 

Muscle Health 

Timeline Nutrition, the makers of Mitopure®, has devoted the past decade to studying Urolilthin A’s role in improving mitochondrial function. Last year they published two incredible clinical trials in top-level scientific journals demonstrating improvements in cellular energy and muscle health.

Mitochondrial function and muscle endurance in older adults

This study examined the effects of 1000 mg of Urolithin A in older adults aged 65 and older. This randomized placebo-controlled trial showed significant improvements in endurance in hand and leg muscles after taking Mitopure daily for two months. 

Key takeaways from the trial:*

  • The Urolithin A group saw a 17 % improvement in muscle endurance. This was a significant improvement compared to the placebo group. 
  • Clinically relevant improvements in a 6-minute walk test were seen in the treatment group.
  • The group receiving Urolithin A demonstrated significant reductions in inflammatory markers, including CRP.

The results of this study are important as people over the age of 65 show high rates of muscle decline. Due to health limitations, exercise may be difficult to do regularly and Mitopure may offer a unique way to maintain muscle health in this population. 

Muscle Health in Middle-Aged Adults

This trial evaluated the health benefits of 500 mg and 1000 mg doses of Urolithin A in healthy, overweight individuals aged 40-64 over the course of four months. Eighty-eight sedentary adults were randomized to receive either a 500 mg, or 1000 mg of Mitopure or a placebo. 

Key takeaways from the trial:

  • Both 500 and 1000 mg doses of Urolithin A significantly increased muscle strength in the leg. 
  • 1000 mg of Urolithin A improved exercise-performance measures including V02 max and a six-minute walk test.
  • Muscle biopsies demonstrated activation of mitophagy, and plasma markers showed improvements in mitochondrial health and inflammation in both treatment groups. 
  • Long-term (four months) daily use of Mitopure is safe and well tolerated. 

Age-related muscle decline starts as early as our 30s, yet most people lack a physical activity program that sustains muscle health. These results suggest that having an intervention like Mitopure could be an option to help inactive adults maintain muscle health. 

Rejuvenating the Immune System

Urolithin A has anti-inflammatory properties,2 however, its ability to promote mitophagy may provide additional benefits to the cells of the immune system. This connection may play a role in cancer progression. A pre-clinical trial established a strong connection between Urolithin A, immune health, and cancer. I talk to one of the world’s leading researchers on the topic in podcast episode 999: How Urolithin A Helps Create Super T-Cells & Boosts Immunity.

Urolithin A, immune health, and cancer

T cells are a type of immune cell, an exhaustion of T cells can cause them to become ineffective at fighting viruses and cancer. This prompted researchers to look into Urolithin A’s potential role in supporting immune health. This pre-clinical trial showed that Mitopure was able to improve T memory stem cell function in colorectal cancer models. Key takeaways from the trial:

  • Urolithin A increased the amount of T memory stem cells and suppressed intestinal tumor growth in cancer models.
  • Adoptive cell transfer is a type of immunotherapy used to treat cancer. In this experimental model, Urolithin A augmented the response to this type of therapy
  • Urolithin A triggered mitophagy in T cells. This was linked to the expansion of T memory cell formation.

T memory stem cells are one of the most potent types of immune cells, and they play a role in anti-tumor immunity and the results of this study are an important step forward in learning how Urolithin A may help in human cancer progression. Surely, new clinical trials investigating Urolithin A’s role in human immune function and cancer treatment will be published in the upcoming years.

Joint Health

Mitochondrial dysfunction has been linked to the development of different types of arthritis.3,4 It makes sense that researchers would want to investigate how improving mitochondrial health could impact arthritis disease progression. 

Urolithin A Improves Mitochondrial Health in Osteoarthritis Models

Mitochondrial decline and reduced levels of mitophagy are commonly seen in cartilage cells contributing to the progression of osteoarthritis. This pre-clinical trial showed that  Urolithin A could improve mitochondrial health in these cells.  Additionally it protected against cartilage degradation and reduced arthritic pain and inflammation in disease models.

Key takeaways from the trial:

  • Urolithin A supplementation increased mitophagy of the knee cells from both healthy donors and donors with osteoarthritis.
  • Urolithin A supplementation protected against cartilage damage, improved joint inflammation, and reduced pain levels in mouse models of arthritis. 

Osteoarthritis is the most common age-related joint disorder. It causes debilitating pain and immobility for millions of people worldwide. Finding new strategies to help minimize pain and improve mobility are critical for people living with arthritis.  The results of this trial establish a strong connection between mitochondrial health and osteoarthritis and make a case for human studies to investigate the role Urolithin A may play in osteoarthritis. 

Reproductive longevity

Egg cells (oocytes) contain the largest amount of mitochondrial DNA than any other cell in the human body. Not surprisingly, mitochondrial dysfunction has been associated with reproductive aging and egg quality.

Mitophagy supports egg quality and reproductive longevity

The study looked at the relationship between mitochondrial health, oocyte quality, reproductive longevity, and Urolithin A’s role in promoting mitophagy in worm models of reproductive cells. 

Key takeaways from the trial:

  • Mitochondrial health is a key determinant of oocyte quality and the longevity of our reproductive capabilities.
  • Mitophagy plays an important role in the health of oocyte mitochondria.
  • In worms, Urolithin A was able to improve mitochondrial health and reproductive span.

In the US, birth rates for women over 30 continue to increase, yet at this same age, female reproductive decline starts. As more people are starting families later in life, it is important to find ways to extend reproductive health. Based on the results of this study, Urolithin A could be a way to support egg quality and reproductive health. 

Neurodegenerative disease

It has been well established that mitochondrial decline plays a role in neurodegenerative diseases, including Parkinson’s and Alzheimer’s.5 This fact is prompting researchers to examine Urolithin A and it’s impact on mitophagy in these types of chronic conditions.

Urolithin A and Alzheimer’s disease

This pre-print explores the neuroprotective effect of Urolithin A-induced autophagy in mouse models of Alzheimer’s disease.

Key takeaways from the trial:

  • Urolithin A induced autophagy and increased the clearance of plaques found in the brain in these mouse models.
  • Urolithin A was able to prevent behavioral deficits.
  • Interestingly, Urolithin A supplementation was found to extend the lifespan of mice

The results of this study suggest that autophagy induced by Urolithin A may offer some hope in the battle against Alzheimer’s and demonstrate the need for further research into this novel compound. Additionally, this study continues to build on previous works looking at Urolithin A as a longevity-promoting molecule. 

Based on all of this incredible research, you can see why I use Mitopure as part of my longevity strategy.

Head on over to Timeline Nutrition and use code Dave10 to get 10% off your next order.



  1. Singh A, D’Amico D, Andreux PA, et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2022;76(2):297-308. doi:10.1038/s41430-021-00950-1
  2. Toney AM, Fox D, Chaidez V, Ramer-Tait AE, Chung S. Immunomodulatory Role of Urolithin A on Metabolic Diseases. Biomedicines. 2021;9(2):192. doi:10.3390/biomedicines9020192
  3. Clayton SA, MacDonald L, Kurowska-Stolarska M, Clark AR. Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis. Front Immunol. 2021;12. Accessed December 18, 2022.
  4. Mao X, Fu P, Wang L, Xiang C. Mitochondria: Potential Targets for Osteoarthritis. Front Med. 2020;7. Accessed December 18, 2022.

5. Wang Y, Xu E, Musich PR, Lin F. Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure. CNS Neurosci Ther. 2019;25(7):816-824. doi:10.1111/cns.13116




Not Harder

Smarter Not Harder: The Biohacker’s Guide to Getting the Body and Mind You Want is about helping you to become the best version of yourself by embracing laziness while increasing your energy and optimizing your biology.

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