Urolithin A

Urolithin A: The Microbiome-Derived Molecule That’s Redefining Health, Aging, and Performance

In recent years, a quiet revolution has been taking place in the world of health sciences—one driven by the unexpected power of our gut microbiome. At the center of this revolution lies a molecule you’ve likely never heard of: Urolithin A. This microbiome-derived metabolite is now at the cutting edge of research into aging, muscle health, metabolic diseases, and even cognitive function.

Spoiler alert, our tried and trusted product is by Codeage, a liposomal version with CoQ10 and resveratrol.

What Is Urolithin A?

Urolithin A (UA) is not something you directly consume. Rather, it is a metabolite produced in the gut when certain bacteria transform polyphenols—specifically ellagitannins and ellagic acid—found in foods like pomegranates, berries, and walnuts. Yet, despite these foods being common, only around 40% of people can efficiently convert these precursors into Urolithin A due to variations in their gut microbiota.

That’s where direct Urolithin A supplementation comes into play—and with it, an explosion of scientific interest.

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The Science of Urolithin A: From Gut to Cellular Renewal

Before exploring the research on urolithin A an interesting study confirmed that “differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation” (source).

Mitophagy: Cleaning House at the Cellular Level

One of Urolithin A’s most well-documented mechanisms is its ability to stimulate mitophagy, the selective recycling of damaged mitochondria—a process that declines with age. Studies across species, from C. elegans (a worm) to humans, have shown that Urolithin A activates the PINK1/Parkin pathway, facilitating mitochondrial quality control and rejuvenation.

Enhanced mitophagy translates into:

• Improved mitochondrial respiratory function

• Higher endurance and energy output

• Protection against age-related muscle decline

In humans, clinical trials show that UA administration increased biomarkers of mitochondrial function and reduced acylcarnitines—byproducts that signal poor mitochondrial fatty acid oxidation.

Anti-inflammatory Power

Chronic inflammation, or “inflamm-aging,” is a hallmark of age-related diseases like Alzheimer’s, diabetes, and cardiovascular disease. Urolithin A exerts strong immunomodulatory effects, attenuating the production of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β across multiple tissue types, including the brain, liver, adipose, and gut.

Mechanistically, UA:

• Inhibits NF-κB signaling

• Reduces reactive oxygen species (ROS)

• Modulates the aryl hydrocarbon receptor (AhR) and Nrf2 antioxidant pathways

It even shows promise in neuroinflammation, improving microglial function and protecting against Alzheimer’s-like pathology in mouse models.

Muscle Health & Physical Performance

As we age, our muscles naturally weaken—partly due to a decline in the body’s ability to recycle damaged mitochondria, the energy powerhouses of our cells. A recent clinical trial (source) explored how Urolithin A (UA) could help counter this decline. A 4-month, in placebo-controlled study in middle-aged adults, participants who took UA showed impressive results: muscle strength increased by around 12%, and there were noticeable improvements in aerobic endurance and physical performance, such as distance walked in six minutes.

While there wasn’t a major change in peak power output, other markers told a compelling story. UA lowered inflammation (measured by C-reactive protein) and improved mitochondrial efficiency, as seen through reduced acylcarnitine levels. Researchers also found a boost in the activity of proteins related to mitophagy and mitochondrial function in muscle tissue. These findings suggest that UA may be a powerful ally in promoting healthier aging and stronger muscles. Similar studies have found similar results (source).

Metabolic and Cardiovascular Effects

Urolithin A also plays a role in metabolic regulation, making it a candidate for treating metabolic syndrome and obesity-related disorders. It activates:

• AMPK, promoting fatty acid oxidation and improving insulin sensitivity.

• PPARγ, a key regulator of glucose and lipid metabolism.

These effects have been linked to:

• Reduced weight gain in high-fat diet models.

• Improved lipid profiles.

• Lowered systemic inflammation and insulin resistance.

Moreover, Urolithin A attenuates atherosclerotic and cardiac inflammation markers, indicating cardiovascular benefits.

Neurodegenerative Conditions

Urolithin A has been studied in both Alzheimer’s and Parkinson’s disease (PD).

PD is a long-term, progressive brain disorder that affects movement and other functions. It becomes more common with age, making older adults particularly vulnerable.

Recent research suggests that polyphenols—natural compounds found in certain foods—may help slow brain degeneration. In particular, urolithin A (UA). Studies highlight UA’s potential to support mitochondrial function (the energy centers of cells), and its anti-inflammatory, antioxidant, and cell-protective effects.

One review (source) summarises current findings on how urolithin A may benefit brain health, especially in conditions like PD. It covers research from both laboratory and animal studies that suggest UA might protect nerve cells.

Recent research (source) has also shed light on the powerful effects of Urolithin A (UA) on Alzheimer’s disease (AD). One of the key issues in AD is impaired cellular cleanup processes, especially mitophagy (the removal of damaged mitochondria) and lysosomal function. In studies using three different mouse models of AD, long-term Urolithin A treatment led to remarkable improvements in memory, learning, and even sense of smell. It also reduced hallmark signs of AD like amyloid-beta and tau buildup and strengthened brain signalling.

What’s particularly exciting is how UA works: it boosts the function of lysosomes, the cell’s waste disposal units, and helps regulate important enzymes like cathepsin Z. These effects suggest that UA not only protects brain cells but also restores the systems that keep them healthy. This study highlights UA’s potential as a powerful, natural compound in the fight against Alzheimer’s, offering hope for future therapies based on enhancing cellular cleanup and brain resilience.

Urolithin A and the Gut Microbiome: The Production Puzzle

Despite the many health benefits of Urolithin A, a significant limitation is that not all individuals produce it naturally. Gut microbiome composition—particularly the presence of Gordonibacter spp. and Akkermansia muciniphila—determines whether someone is a “UA producer” or falls into a non-producer metabotype.

Interestingly UA producers have been distinguished by having a significantly higher gut microbiome diversity, and ratio of Firmicutes to Bacteroides. If you have done a Healthpath gut test then check these key markers!

This finding has sparked growing interest in UA as a direct supplement to bypass microbiome dependency, especially in the elderly.

Urolithin A as a Supplement: What We Know

A few companies now offer UA as a nutraceutical, and clinical data on safety and efficacy are growing:

• Bioavailability: UA is efficiently absorbed in its free form.

• Dosing: In rodent models, effective doses range from 10–50 mg/kg/day, while human trials have used up to 1,000 mg/day without major adverse effects.

• Safety: To date, studies report a good safety profile. However, long-term human trials are still limited.

The Future of UA: From Molecule to Movement

Urolithin A represents a convergence of microbiome science, nutritional therapeutics, and cellular biology. Its ability to address muscle decline, inflammation, and metabolic dysfunction—three central aspects of aging—positions it as a promising intervention in the longevity and wellness space.

But we are still early in the story. Key questions remain:

• Who benefits most from UA: elderly, athletes, or the metabolically compromised?

• What are optimal dosing schedules?

• How can we integrate microbiome profiling to personalise Urolithin A interventions?

Final Thoughts

In an era of hyper-personalised medicine and preventive health, Urolithin A stands out as a naturally-derived yet scientifically robust compound. Whether you’re seeking enhanced energy, better aging, or simply a healthier mitochondria ecosystem, this gut-born molecule might soon become part of your health toolkit.

And perhaps most importantly, Urolithin A research reminds us that the path to vitality might just begin in the gut—and lead all the way to the powerhouse of the cell.

Our recommended product is Urolithin A by Codeage.

References:

1. D’Amico, D., et al. (2021). Impact of the Natural Compound Urolithin A on Health, Disease, and Aging. Trends in Molecular Medicine, 27(7), 687–699. https://doi.org/10.1016/j.molmed.2021.04.009

2. Toney, A.M., et al. (2021). Immunomodulatory Role of Urolithin A on Metabolic Diseases. Biomedicines, 9(2), 192. https://doi.org/10.3390/biomedicines9020192

3. Zhao, H., et al. (2023). Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects. Nutrients, 15(20), 4441. https://doi.org/10.3390/nu15204441

4. Singh et al., (2022) Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults, Cell Rep Med, 17;3(5):100633 https://pubmed.ncbi.nlm.nih.gov/35584623/

5. Singh et al., (2022) Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults, Eur J Clin Nutr;76(2):297-308