What Research Suggests About Urolithin A and Cellular Energy

• Thymic output declines, reducing newly formed T cells — One of the core shifts involves the thymus, the organ that produces naïve T cells. With age, thymic activity declines, leading to fewer newly formed T cells entering circulation. Because naïve T cells are your front-line responders to unfamiliar pathogens, this reduction makes it harder for your immune system to mount strong first-time responses.

• Memory T cells accumulate, limiting adaptability — As naïve T cells drop, memory T cells become a larger share of your immune system. Memory cells help with threats you have already encountered but bring little support when something new appears. This shift explains why older adults respond less robustly to vaccines and face more risk from novel infections.

• Inflammaging becomes a defining feature of later life — As immune cell patterns shift with age, the body enters a state of persistent, low-grade inflammation. This phenomenon, known as inflammaging, reflects higher levels of inflammatory mediators circulating at rest and is considered one of the central characteristics of an aging immune system. Learn more about this in “‘Inflammaging’ Is a Lifestyle Phenomenon, Not a Universal Aging Trait.”

• Urolithin A increased naïve CD8 T cells — Participants who received urolithin A showed a significant increase in naïve CD8 T cells, which behave more like younger, freshly formed immune cells. These cells respond more reliably to threats and carry fewer markers of exhaustion. Alongside this shift, CD8 T cells also showed about a 15% increase in their ability to use fatty acids for energy, suggesting better metabolic flexibility.

• Innate immune cells showed stronger surveillance profiles — Urolithin A supplementation increased a subtype of natural killer (NK) cells known for being the most active in identifying and eliminating infected or abnormal cells. These NK cells deliver the strongest cytotoxic activity, so having more of them strengthens rapid-response immunity.

• Signs of increased mitochondrial biogenesis appeared within CD8 T cells — Participants who took urolithin A showed higher expression of markers associated with PGC-1α, the protein that guides mitochondrial growth and renewal.

This points to a process where immune cells were not only clearing out older, less efficient mitochondria but also strengthening their overall energy system, giving them a more reliable foundation when they activate or stay engaged for longer periods.

• Functional tests showed stronger immune responses — When researchers activated T cells in the lab, those from the urolithin A group produced more tumor necrosis factor (TNF), a cytokine that signals rapid immune engagement. Monocytes also demonstrated better uptake of E. coli particles, indicating improved ability to recognize and engulf microbial targets.

• Molecular programming shifts within immune cells — Single-cell analysis showed that urolithin A reshaped inflammatory and metabolic pathways across multiple immune cell types, pointing toward coordinated changes that support stronger, more balanced immunity as you age. As the researchers explained:

“Exploratory single-cell RNA sequencing demonstrated urolithin A (UA)-driven transcriptional shifts across immune populations, modulating pathways linked to inflammation and metabolism.

These findings indicate that short-term UA supplementation modulates human immune cell composition and function, supporting its potential to counteract age-related immune decline and inflammaging.”⁵

• Cancer — Urolithin A shows anticancer activity mainly in preclinical work. Laboratory and animal studies report that it slows the growth of several tumor types, promotes cancer cell death (apoptosis), and interferes with pathways that support proliferation and invasion.

Reviews describe these effects in models of breast, pancreatic, oral, and other cancers, and highlight actions such as inhibiting NF-κB signaling, activating FOXO1 (a transcription factor that supports cellular stress responses and regulates genes involved in survival and repair), and triggering autophagy-related cell death in tumor cells.⁷

• Muscle strength — In a randomized clinical trial published in JAMA Network Open, older adults aged 65 to 90 were given 1,000 mg of urolithin A per day for four months. Results showed significantly improved muscle endurance, measured as the number of contractions until fatigue in both hand and leg muscles, compared with placebo.⁸

A separate trial in middle-aged adults, published in Cell Reports Medicine, found that daily urolithin A supplementation led to improvements in quadriceps strength, enhanced exercise performance, and favorable shifts in several biomarkers associated with mitochondrial health within a similar timeframe.⁹

• Fatty liver — In a mouse model of fructose-induced fatty liver disease, urolithin A supplementation reduced hepatic steatosis and improved the balance between fat creation and fat breakdown in the liver by impairing lipogenesis and enhancing β-oxidation.¹⁰ In parallel, a Biomedicines review notes that urolithin A attenuates inflammation in liver tissue in metabolic models, helping to stabilize the hepatic environment under stress.¹¹

• Metabolic disorders — Urolithin A has been studied extensively in models of obesity, Type 2 diabetes, and metabolic syndrome. In laboratory and animal models, urolithin A reduced triglyceride accumulation in fat cells and liver cells by lowering genes that drive fat creation and activating AMPK, an energy-sensing pathway that shifts cells toward burning stored fat instead of stockpiling it.¹²

More detailed experiments in preadipocytes (the precursor cells that eventually mature into fat cells) found that urolithin A lowered triglyceride content and suppressed the expression of several key genes that help regulate fat storage, glucose transport, and fatty acid binding, so reducing their activity helps keep fat accumulation under control while still allowing fat cells to form normally.¹³

Several studies also showed that urolithin A protected mice and rats from high-fat diet-induced obesity and insulin resistance by supporting thermogenesis, increasing browning responses (a shift toward a more metabolically active type of fat cell), reducing oxidative stress, and lowering inflammatory activity within adipose tissue.¹⁴

• Urolithin A is naturally produced in your body — When you eat foods rich in ellagitannins, a class of polyphenols found in pomegranates and some berries, these plant compounds are first converted into ellagic acid and then transformed into different urolithins depending on which microbial species live in your gut.¹⁵

• Not everyone forms urolithin A efficiently — The ability to generate urolithin A depends entirely on your gut microbiota composition. Factors such as age, diet, medication use, and overall microbial diversity influence whether the conversion occurs.

Only about 40% of adults produce detectable levels after consuming ellagitannin-rich foods like pomegranate juice. Even among individuals who do produce it, output varies widely, which is why supplementation has become the most reliable way to achieve consistent levels.¹⁶

• How it’s delivered matters — Because urolithin A exerts its mitophagy action inside the mitochondria, it’s important to deliver it directly into the mitochondria. This is essential because mitochondria are constantly being damaged.

They contain the furnace of energy production, and because most people consume excess linoleic acid (LA) from seed oils, their mitochondria get destroyed prematurely. These damaged mitochondria need to be recycled; if they just accumulate, your cellular energy production collapses.

• Newer systems are being developed to improve this targeted delivery — Without mitochondrial targeting, much higher doses of urolithin A are required to reach the same intracellular effect (about 1,000-fold higher). Most formulations currently available do not include this targeting technology, but next-generation approaches are being designed to deliver urolithin A directly to the mitochondria so effective levels can be achieved with lower amounts.

• Urolithin A is also part of a paired approach — Urolithin A must be used in conjunction with PQQ (pyrroloquinoline quinone), which activates PGC-1α to stimulate mitochondrial biogenesis. This combination is important, as urolithin A clears out the damaged mitochondria while PQQ generates fresh replacements.

1. Remove processed foods and vegetable oils from your diet — Processed products are typically made with seed oils that contain large amounts of LA, which interferes with mitochondrial function and reduces your ability to generate energy efficiently. Nuts, seeds, and most restaurant meals contribute additional LA, since commercial kitchens rely heavily on these oils.

Chicken and pork often contain higher levels of LA as well, due to the way they are commonly raised and fed. Center your diet around whole foods and choose low-LA fats such as grass fed butter, tallow, and ghee. Aim to keep your daily LA intake under 5 grams, ideally aiming for less than 2 grams. Use an online nutrition tracker like the upcoming Mercola Health Coach App to monitor your intake.

2. Optimize your carbohydrate intake for cellular fuel — A balanced diet rich in the right carbs and free of ultraprocessed foods feeds your mitochondria with the glucose they’re designed to burn. Focus on whole fruits and white rice first, then gradually bring in root vegetables, legumes, and well-tolerated grains as your gut improves. Aim for 250 grams of healthy carbs daily to keep your thyroid working at full capacity.

3. Reduce exposure to environmental toxins — Your cells are exposed to synthetic chemicals every day. Substances such as endocrine-disrupting chemicals (EDCs) from plastics, estrogen-mimicking compounds like xenoestrogens, and widespread electromagnetic fields (EMFs) interfere with how efficiently your mitochondria produce energy. When these exposures accumulate, mitochondrial function declines.

Taking steps to limit this burden can make a meaningful difference. Choose household items made from natural materials whenever possible, and store food in glass instead of plastic. Creating a low-EMF sleeping environment is also helpful, as it allows your cells to recover overnight with less external stress. Collectively, these changes reduce the strain placed on your body.

4. Get proper sun exposure — Regular sun exposure supports cellular energy by stimulating the production of mitochondrial melatonin, which provides strong antioxidant protection inside your cells. However, it’s best to avoid direct sun during peak hours (typically 10 a.m. to 4 p.m. in most parts of the U.S.) until you have minimized seed oils in your diet for at least six months, as the buildup of LA in your tissues makes your skin more prone to sunburn.

5. Boost NAD⁺ Levels — Taking niacinamide at a dose of 50 mg three times a day helps raise your NAD⁺ levels, which supports mitochondrial energy production. Adequate NAD⁺ is essential for proper cell-death signaling and strengthens your immune system’s ability to recognize and clear damaged cells.