Urolithin A vs NAD+: A Guide to Mitochondrial Supplements
Urolithin A activates mitochondrial recycling. NAD+ is a coenzyme that fuels energy production. Urolithin A has stronger human clinical evidence.
What to know
Urolithin A and NAD+ both support cellular energy and mitochondrial health, but they work differently.
New research questions the long-held assumption that NAD+ declines with age.
NAD+ precursor supplements show limited human benefits; pooled randomized trials found no clear benefit from NR or NMN for muscle mass, strength, or function in adults over 60.
Urolithin A has a strong human track record with positive placebo-controlled evidence for muscle strength* and mitochondrial health.
Urolithin A and NAD+ are some of the most discussed nutrients in longevity. Both play a role in how your cells make energy, but they work in very different ways, and the research behind them has evolved significantly in the past several years.
If you are curious about the difference between Urolithin A and NAD+, this article is for you.
What is Urolithin A?
Urolithin A is a postbiotic, a beneficial compound made by your gut rather than found directly in food. When you eat certain polyphenols, your gut bacteria convert them into Urolithin A.[1]
The catch: not everyone's microbiome can do this. A clinical study found that only about a third of healthy adults produce meaningful levels of Urolithin A on their own, and most who do still don't make enough to reach a beneficial dose.[2] That's why direct supplementation with a clinically validated form of Urolithin A (i.e., Mitopure®) is the most reliable way to get a consistent, effective dose.[3]
How Does Urolithin A Work?
Urolithin A targets mitochondrial health, a foundational hallmark of aging, and it supports a specific quality-control process known as mitophagy. Mitophagy naturally becomes less efficient as we age, which contributes to the accumulation of dysfunctional mitochondria in our tissues.[4]
When taken in its clinically validated form Mitopure, Urolithin A is safe, bioavailable, and induces a molecular signature of improved mitochondrial and cellular health in older adults.[5]
5 Key Urolithin A Benefits: What The Research Shows
There are 25 human clinical trials evaluating the benefits of Mitopure, and hundreds of preclinical studies exploring promising areas of research on the molecule. The clinical benefits stem from the positive impact Urolithin A has on the mitochondria.
A clinical study with Mitopure demonstrated that mitochondrial renewal increased by approximately 40% over baseline after 16 weeks.[6]
The research on Urolithin A is more compelling than that on mitochondrial biomarkers. Studies show meaningful clinical outcomes that can benefit several areas of health and longevity. Let’s break down what the research says:
1. Urolithin A and muscle health
While Mitopure’s mechanism is cellular, the results are present in noticeable outcomes. Mitopure consistently demonstrates improvements in muscle health across a wide range of populations, from middle-aged adults to older adults to trained athletes. Here's what the trials found:
- Strength: a ~12% improvement in muscle strength after 16 weeks, with no change to diet or exercise.[7]*
- Endurance: up to 17% (leg) and 26% (hand) improvement at a daily dose of 1,000 mg, again with no change to exercise.[8] ‡
- Recovery: 1000 mgs daily supports recovery during periods of intense training.[9]‖
The benefits hold across very different populations, from resistance-trained athletes in their 20s to middle-aged and older sedentary adults.*‡
‡ Our clinical studies showed that sedentary adults aged 65-90 improved muscle endurance, measured as leg and hand repetitions to fatigue, after daily supplementation with 1,000 mg Mitopure.
‖ The clinical study showed that daily supplementation with 1,000 mg Mitopure® for 6 weeks supported recovery during intense preseason training in academy‑level soccer players.
2. Urolithin A and immune health
Mitopure's mitochondrial support may help address age-related immune decline.†
A newer randomized, placebo-controlled trial reported that 1000 mg of Urolithin A supplementation shifted immune cell profiles in healthy middle-aged adults toward a more youthful, less exhausted state.[10] This is an active and fast-developing area of Urolithin A research.†
†Our randomized, placebo-controlled clinical study showed that supplementation with Mitopure® 1,000 mg for 4 weeks was associated with improvements in mitochondrial health of immune cells, favorable shifts in T-cell populations (including naïve cells), and markers of healthy immune function, in healthy, middle-aged adults.
3. Topical Urolithin A and skin health
When applied topically, Mitopure has been studied for skin aging in a randomized clinical trial. Topical Mitopure was found to§:[11]
- Visibly reduce the appearance of wrinkle depth and volume after only 2 weeks.
- Upregulate genes related to collagen organization in just 8 weeks of topical use.
- Reduce redness, including UV-induced visible irritation
- Support a 14% reduction in erythema, indicating protection against UV-induced damage within 24 hours.
By improving mitochondrial function and energizing cells, this compound helps combat intrinsic and extrinsic aging factors impacting the body and skin.[12]
§ Based on an 8-week randomized clinical trial of 48 healthy women aged 50 to 75 years (topical Mitopure®).
4. Urolithin A and brain aging (preclinical data)
Several preclinical studies suggest that Urolithin A may support brain health. The prestigious Buck Institute for Research on Aging has received National Institutes of Health funding to investigate Urolithin A in the context of brain aging.
Another promising area of research comes from Dr. Carmen Sandi and her Laboratory of Behavioral Genetics at the École Polytechnique Fédérale de Lausanne (EPFL). Her team demonstrated that repairing damaged mitochondria with Urolithin A improved anxiety symptoms in rodents.[13]
More research is needed to determine if humans will experience any brain benefits with Mitopure.
5. Urolithin A and cardiovascular health (preclinical data)
The heart is a continuously working, mitochondria-dense muscle, so mitochondrial quality matters for cardiovascular aging. Preclinical studies suggest Urolithin A may support mitochondrial function relevant to heart health. These findings are from animal and cell models and have not been established in humans.[14]
What is NAD+?
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme your body makes from the vitamin B3 family (eg, niacin, nicotinamide, and nicotinamide riboside). It acts as a shuttle that carries electrons during metabolism, helping your mitochondria generate ATP, the cell's energy currency. NAD+ is also a cofactor for enzymes such as sirtuins, which are involved in many cellular and stress-response processes connected to aging.[15]
For years, a simple story dominated the longevity space: NAD+ levels fall as we age, this decline drives age-related dysfunction, so "boosting" NAD+ with precursor supplements (like NR and NMN) or through IV therapy should restore cellular vitality.[16] The newest research suggests that the story is more complicated than it first appeared.[17]
Do NAD+ levels decline with age?
This is now an open scientific question. A 2026 study in Nature Metabolism measured NAD+ levels in blood across seven independent human cohorts (including elite athletes, sedentary older adults, and lifestyle-intervention participants), using a rigorously validated, high-precision method.
It found that whole-blood NAD+ levels remained remarkably stable with age and across lifestyle interventions. The authors concluded that blood NAD+ is not a reliable biomarker of aging.[18]
An important nuance: this study measured NAD+ in blood, the value most consumer tests and many studies rely on. Declines in NAD+ at the tissue level have been observed in association with several age-related conditions.[19] In other words, the new study challenges blood NAD+ as an aging marker; it does not settle the separate question of what happens to NAD+ inside specific tissues. So the jury is still out.[20]
Do NAD+ supplements work? Are they worth it?
The most comprehensive look to date comes from a 2026 PRISMA-guided systematic review in Ageing Research Reviews, which analyzed 113 eligible studies, including 33 human intervention studies (28 of which were randomized controlled trials) alongside rodent data.[21]
Its takeaway: oral NR, NMN, and nicotinamide generally raise NAD+-related biomarkers in humans, but the effects on outcomes people actually care about, such as metabolic, vascular, and performance measures, are mixed. Notably, the review found no eligible outcome trials testing IV or IM NAD+ for anti-aging or wellness, despite widespread marketing of NAD+ drips.[22]
Zooming in on muscle, one of the most healthspan-relevant domains, a 2025 systematic review and meta-analysis of randomized controlled trials concluded that current evidence does not support NMN or NR supplementation for preserving skeletal muscle mass or function in older adults.[23]
NAD+ supplementation may be helpful in certain populations like women undergoing IVF[24] or people newly diagnosed with Parkinson’s disease,[25] but as a general longevity supplement for healthy adults, the evidence is still mixed.
Urolithin A vs NAD+: How They Compare
Urolithin A and NAD+ both play vital roles in the production of cellular energy and the aging process. However, the way they do so is very different. If you are considering a supplement, understanding this key difference can help you decide which one might be better for you.
How do Urolithin A and NAD+ compare on safety?
Urolithin A: The first-in-human trial and subsequent randomized controlled trials found Urolithin A to be safe and well-tolerated.[26] Mitopure®, the only clinically validated Urolithin A supplement, also holds FDA-notified GRAS ("Generally Recognized As Safe") status as an ingredient, and is NSF and Clean Label Certified.
NAD+ precursors: NR and NMN have generally been well tolerated in the human trials run to date.[27]
Takeaway: Both have acceptable human safety records in the trials conducted so far. Mitopure specifically carries third party quality certifications.
How do Urolithin A and NAD+ compare on mitochondria targeting?
Urolithin A: Across multiple human RCTs, Urolithin A produces a molecular signature of improved mitochondrial and cellular health and improved mitochondrial biomarkers. Critically, it works by directly stimulating mitophagy.[28]
NAD+ precursors: NR reliably raises NAD+ levels, and some studies show a mitochondrial signal; for example, a twin study found NR improved muscle mitochondrial biogenesis.[29] But across human trials, whether raising NAD+ translates into a consistent mitochondrial or clinical benefit has been inconsistent.
Takeaway: Urolithin A shows a consistent signature of improved mitochondrial health across human trials and is the only one of the two that targets mitochondrial recycling and renewal. NAD+ precursors raise the NAD+ substrate, but the human evidence that this translates into mitochondrial benefit is mixed.
How do Urolithin A and NAD+ compare on building strength?
Urolithin A: In a randomized, placebo-controlled trial, middle-aged adults taking Urolithin A for 16 weeks, with no change to diet or exercise, saw a ~12% improvement in muscle strength.[30]*
NAD+ precursors: A 2025 systematic review and meta-analysis of randomized controlled trials concluded that current evidence does not support NR or NMN supplementation for muscle mass, strength, or gait speed in adults over 60.[31]
Takeaway: On muscle strength, the human evidence favors Urolithin A; it has positive RCT data, while pooled RCTs of NR/NMN show little to no muscle benefit in older adults.
In Summary: Is Urolithin A Better Than NAD+?
There are no head-to-head studies comparing the effectiveness of Urolithin A vs. NAD+. However, when you line up the existing human research side by side, the contrast is evident:
- Safety: both are well-tolerated in trials;[32] Urolithin A additionally holds FDA-notified GRAS status as an ingredient.
- Mitochondrial health: Urolithin A shows a consistent molecular signature of improvement and uniquely drives mitochondrial renewal;[33] NAD+ precursor results in humans are inconsistent.[34]
- Muscle strength: Urolithin A has positive RCT data;[35]* pooled NR/NMN RCTs show little benefit.[36]
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References
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D'Amico, D., Andreux, P. A., Valdés, P., Singh, A., Rinsch, C., & Auwerx, J. (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
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Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature metabolism, 1(6), 595–603. https://doi.org/10.1038/s42255-019-0073-4
- ↑
Vinten, K. T., Trętowicz, M. M., Coskun, E., van Weeghel, M., Cantó, C., Zapata-Pérez, R., Janssens, G. E., & Houtkooper, R. H. (2025). NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Nature metabolism, 7(10), 1974–1990. https://doi.org/10.1038/s42255-025-01387-7
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Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature metabolism, 1(6), 595–603. https://doi.org/10.1038/s42255-019-0073-4
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Singh, A., D'Amico, D., Andreux, P. A., Fouassier, A. M., Blanco-Bose, W., Evans, M., Aebischer, P., Auwerx, J., & Rinsch, C. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell reports. Medicine, 3(5), 100633. https://doi.org/10.1016/j.xcrm.2022.100633
- ↑
Prokopidis, K., Moriarty, F., Bahat, G., McLean, J., Church, D. D., & Patel, H. P. (2025). The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. Journal of cachexia, sarcopenia and muscle, 16(3), e13799. https://doi.org/10.1002/jcsm.13799
- ↑
Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature metabolism, 1(6), 595–603. https://doi.org/10.1038/s42255-019-0073-4
Vinten, K. T., Trętowicz, M. M., Coskun, E., van Weeghel, M., Cantó, C., Zapata-Pérez, R., Janssens, G. E., & Houtkooper, R. H. (2025). NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Nature metabolism, 7(10), 1974–1990. https://doi.org/10.1038/s42255-025-01387-7 - ↑
Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature metabolism, 1(6), 595–603. https://doi.org/10.1038/s42255-019-0073-4
- ↑
Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature metabolism, 1(6), 595–603. htt
Vinten, K. T., Trętowicz, M. M., Coskun, E., van Weeghel, M., Cantó, C., Zapata-Pérez, R., Janssens, G. E., & Houtkooper, R. H. (2025). NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Nature metabolism, 7(10), 1974–1990. https://doi.org/10.1038/s42255-025-01387-7 - ↑
Singh, A., D'Amico, D., Andreux, P. A., Fouassier, A. M., Blanco-Bose, W., Evans, M., Aebischer, P., Auwerx, J., & Rinsch, C. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell reports. Medicine, 3(5), 100633. https://doi.org/10.1016/j.xcrm.2022.100633
- ↑
Prokopidis, K., Moriarty, F., Bahat, G., McLean, J., Church, D. D., & Patel, H. P. (2025). The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. Journal of cachexia, sarcopenia and muscle, 16(3), e13799. https://doi.org/10.1002/jcsm.13799