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Creatine+ is an advanced creatine system designed for longevity, strength, and cognition. Creatine+ combines ultra-high quality creatine monohydrate with HMB to increase lean muscle and strength and reduce muscle damage associated with exercise, and pomegranate extract standardized to punicalagins—precursors to urolithin A to promote mitochondrial renewal and cellular energy production.
The short answer
Urolithin A (UA) is a naturally occurring compound produced when certain gut microbes transform polyphenols found in foods such as pomegranates into a bioactive metabolite.
Why has it attracted so much scientific attention? Because urolithin A appears to support one of the body's most fundamental cellular maintenance processes: mitophagy, the selective recycling of damaged mitochondria.
Mitochondria are often described as the "powerhouses" of the cell because they generate the energy needed to support virtually every biological process—from muscle contraction to brain function. As we age, mitochondrial quality and efficiency decline. Emerging research suggests that urolithin A may help support mitochondrial renewal, promote muscle function, and enhance cellular resilience.
What is urolithin A?
Urolithin A is a metabolite. That means it isn't the compound you consume directly from food. Rather, it is a product created when your body processes other compounds.
Specifically, urolithin A is formed when gut microbes metabolize a class of polyphenols called ellagitannins—or punicalagins, which are ellagitannins unique to pomegranates.
Ellagitannins are found in foods including:
- • Pomegranates
- • Walnuts
- • Raspberries
- • Strawberries
- • Blackberries
Among these foods, pomegranates are considered one of the richest dietary sources of ellagitannins (or punicalagins). After consumption, ellagitannins are converted into ellagic acid, which certain gut bacteria can then transform into a series of compounds known as urolithins, including urolithin A.
In other words:
Pomegranate → Ellagitannins (Punicalagins) → Ellagic Acid → Urolithin A
Why is urolithin A important?
The excitement surrounding urolithin A centers on mitochondria. Mitochondria generate ATP, the energy currency that powers our cells. However, mitochondria are constantly exposed to stress and damage. Over time, less functional mitochondria can accumulate. Researchers believe this decline in mitochondrial quality contributes to many features of aging, including reductions in:
- • Muscle function
- • Endurance
- • Energy production
- • Cellular resilience
To counter this, cells employ a quality-control process called mitophagy. Mitophagy selectively identifies and removes dysfunctional mitochondria so they can be replaced with healthier ones. You can think of it as routine maintenance for your cellular batteries. Emerging evidence suggests that urolithin A may help support this process.
What is Mitophagy?
Mitophagy is a specialized form of autophagy. Autophagy literally means "self-eating" and refers to the recycling of damaged cellular components. Mitophagy focuses specifically on mitochondria.
Healthy mitochondria are essential because they:
- • Produce ATP
- • Help regulate metabolism
- • Support muscle contraction
- • Influence cellular signaling
- • Help maintain tissue function
As we age, mitophagy appears to become less efficient, resulting in the accumulation of older, less functional mitochondria. Supporting mitochondrial quality control has therefore emerged as a promising strategy for promoting healthy aging.
What does the research say about urolithin A?
Most of the early excitement surrounding urolithin A came from preclinical studies demonstrating activation of mitophagy pathways. More recently, researchers have begun evaluating whether these findings translate to humans.
Urolithin A and muscle endurance
In a randomized, placebo-controlled clinical trial involving older adults, participants received one of the following for four months:
- • 500 mg/day of urolithin A
- • 1,000 mg/day of urolithin A
- • Placebo
Compared with placebo, participants receiving urolithin A demonstrated improvements in measures of muscle endurance and favorable changes in biomarkers related to mitochondrial and cellular health. The investigators concluded that urolithin A supplementation was safe and supported mitochondrial health and muscle function. [1]
Urolithin A and muscle performance
A subsequent trial involving middle-aged adults evaluated 1,000 mg/day of urolithin A over four months. Participants receiving urolithin A demonstrated improvements in leg and hand muscle endurance compared with placebo. [2]
Importantly, these studies did not show dramatic increases in muscle mass. Instead, they suggested that supporting mitochondrial quality may influence how muscles function and resist fatigue.
Not everyone produces urolithin A equally
One of the most fascinating aspects of urolithin A biology is that the ability to produce it varies from person to person because it depends on the gut microbiome.
Current evidence suggests that approximately 70–90% of healthy adults can produce at least some urolithin A after consuming ellagitannin-rich foods such as pomegranate, although only about 40–50% are considered highly efficient urolithin A producers. In other words, most people appear capable of generating urolithin A—but the amount can vary considerably. [3]
Encouragingly, these metabolic responses may not be entirely fixed. Emerging research suggests that consistent exposure to ellagitannin-rich foods, such as pomegranate extract, may enhance urolithin production in some individuals over time, potentially by encouraging the growth and activity of microbes involved in this conversion. The science is still evolving.
So why use pomegranate extract?
If urolithin A is the active metabolite, why not simply consume urolithin A directly? Both approaches exist.
Direct urolithin A supplementation bypasses the microbiome conversion step. Pomegranate-derived ellagitannins, however, offer a different approach: providing the natural precursors that the body can convert into urolithins.
Pomegranate has been consumed for centuries and delivers a rich source of bioactive polyphenols beyond urolithin precursors. Pomegranate extract has also been shown in clinical studies to increase beneficial short-chain fatty acids (acetates and propionates) that are important for protecting the gut barrier, supporting healthy inflammation, and gut-body communication. [4] It’s also been shown to modulate the skin microbiome and improve wrinkle severity as well as supporting performance outcomes (at 750 mg daily doses). [5,6]
Importantly, pharmacokinetic studies using standardized pomegranate extracts have shown that urolithin A metabolites become detectable in circulation approximately 8 hours after ingestion, consistent with gut microbiota-mediated conversion. [7]
This makes pomegranate extract an attractive way to harness the gut microbiome's metabolic potential.
Why we included pomegranate extract in Creatine+
At first glance, creatine and pomegranate might seem like an unexpected pairing. But they support energy from complementary perspectives.
Creatine helps replenish ATP rapidly during high-intensity effort. It provides the immediate energy reserve needed to support strength and performance.
Pomegranate-derived urolithin A precursors, on the other hand, may help support the long-term health and renewal of the mitochondria responsible for sustained energy production.
You can think of it this way:
- • Creatine helps support immediate energy availability.
- • Pomegranate-derived urolithin precursors help support the quality of the cellular machinery that produces energy over time.
Together, they represent two distinct but complementary aspects of muscle energetics.
The bottom line
Aging affects more than how much energy we have. It also influences how efficiently our cells produce and maintain that energy. Urolithin A has emerged as an intriguing compound in longevity science because it appears to support mitophagy—the process by which cells recycle and renew their mitochondria.
What makes its story particularly compelling is that it sits at the intersection of nutrition, the microbiome, and healthy aging.
Pomegranates don't contain urolithin A itself. Instead, they provide the raw materials that gut microbes transform into this bioactive metabolite and current evidence suggests that most healthy adults can generate urolithin A to varying degrees.
Supporting healthy aging isn't only about producing energy. It's also about maintaining the cellular systems—and microbial partners—that help generate it in the first place.
References
1. Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism. 2019;1:595–603.
2. Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in middle-aged adults: a randomized clinical trial. Cell Reports Medicine. 2022;3(5):100633.
3. Tomás-Barberán FA, García-Villalba R, González-Sarrías A, et al. Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. J Agric Food Chem. 2014;62(28):6535–6538.
4. Sivamani RK, Chakkalakal M, Pan A, et al. Prospective Randomized, Double-Blind, Placebo-Controlled Study of a Standardized Oral Pomegranate Extract on the Gut Microbiome and Short-Chain Fatty Acids. Foods. 2023 Dec 19;13(1):15.
5. Chakkalakal M, Nadora D, Gahoonia N, et al. Prospective Randomized Double-Blind Placebo-Controlled Study of Oral Pomegranate Extract on Skin Wrinkles, Biophysical Features, and the Gut-Skin Axis. J Clin Med. 2022 Nov 14;11(22):6724.
6. Torregrosa-García A, Ávila-Gandía V, Luque-Rubia AJ, et al. Pomegranate Extract Improves Maximal Performance of Trained Cyclists after an Exhausting Endurance Trial: A Randomised Controlled Trial. Nutrients. 2019 Mar 28;11(4):721.
7. Wang YH, Mondal G, Khan W, et al. Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for characterizing pomegranate extract pharmacokinetics in humans. J Pharm Biomed Anal. 2023;233:115477.
