Urolithin A and NAD+ are two of the most-discussed molecules in the cellular health space, and they are frequently marketed together as a longevity stack. Both have genuine research behind them, and both are connected to mitochondrial function. Understanding how they relate, and where that relationship is well-supported versus speculative, matters if you are trying to make an informed decision about supplementation.
The short version: urolithin A and NAD+ act through distinct but potentially complementary mechanisms that converge on the same target, the health and efficiency of your mitochondria. This article explains those mechanisms, what the current human evidence shows for urolithin A specifically, and why the overlap with NAD+ pathways is biologically plausible even if direct interaction studies in humans are limited.
Key Takeaways
- Urolithin A and NAD+ both target mitochondrial health but through distinct mechanisms: urolithin A primarily activates mitophagy (clearance of damaged mitochondria), while NAD+ is a coenzyme central to energy metabolism and sirtuin activity.
- Human evidence for urolithin A is growing, including a 2025 randomized trial that measured immune-cell markers [1] and a 2024 systematic review [2]but remains limited in scale compared to some established interventions.
- There is no well-established evidence in the reviewed studies that urolithin A directly raises NAD+ levels; the relationship between the two is better described as working on overlapping biological targets.
- Much of the brain-related research on urolithin A is preclinical; translating these findings to human cognitive outcomes requires further trials.
- Gut microbiome composition affects how much urolithin A a person produces from food, which is why absorption and individual response to dietary sources vary significantly.
Why Mitochondria Are Central to Both
Mitochondria are the organelles responsible for producing the majority of cellular energy in the form of ATP, and they are deeply involved in how cells respond to stress, regulate inflammation, and ultimately age. Mitochondrial function declines measurably over a lifetime: the organelles accumulate damage, their membrane potential weakens, and the cellular machinery for removing dysfunctional ones slows down. This deterioration has been linked to many of the hallmark features of aging [3].
NAD+ (nicotinamide adenine dinucleotide) is an essential coenzyme that sits at the center of this process. It shuttles electrons during oxidative phosphorylation inside mitochondria, serves as a substrate for energy-sensing enzymes called sirtuins, and is consumed by DNA repair proteins called PARPs. NAD+ levels fall substantially with age, and this decline appears to impair mitochondrial efficiency. Urolithin A, meanwhile, works through a different entry point: it triggers the selective removal of damaged mitochondria through a process called mitophagy, making way for healthier replacements. Neither molecule is doing the same job, but both are aimed, in different ways, at keeping the mitochondrial pool functional.
How Urolithin A Works: The Mitophagy Mechanism
Urolithin A is a postbiotic compound produced in the gut when certain bacteria metabolize ellagitannins, polyphenols found in foods like pomegranates, walnuts, and some berries. A widely reported action, mainly in worms, cells and mice, is its ability to induce mitophagy [12][13][14][15]a form of selective autophagy that targets and degrades mitochondria that have lost their membrane potential or accumulated damage [4].
Research note: In a short trial of an NMN product in overweight or obese middle-aged and older adults, muscle strength, fatigability, aerobic capacity and stair-climbing power did not differ significantly from placebo, a comparator point for NAD-boosting claims [18].
Mitophagy is a quality-control process. When it operates efficiently, the cell keeps a relatively clean pool of mitochondria and can replace dysfunctional ones with new, better-performing organelles through mitochondrial biogenesis. When mitophagy is impaired, as it tends to be with aging, damaged mitochondria persist, leak reactive oxygen species, and activate inflammatory pathways. In worm and cell studies, urolithin A is reported to restore this recycling process; that has not been shown in people [12][16][14]. A mouse study reported that it can promote estrogen receptor-mediated mitochondrial biogenesis signaling, but a 2024 systematic review of human studies found no effect on mitochondrial biogenesis [2][5].
Importantly, urolithin A is not absorbed the same way in every person. Gut microbiome composition determines whether someone produces urolithin A from dietary precursors at all, which is part of why supplemental forms have become a focus of clinical research [2].
Where the Two Pathways Overlap
Because both NAD+ and urolithin A act on mitochondrial integrity, their effects can converge even when the mechanisms are distinct. Sirtuin enzymes, which depend on NAD+ as a substrate, are involved in regulating mitophagy through pathways that include PINK1 and Parkin, the same proteins urolithin A engages. That is a hypothesis: in cells, the PINK1 protein recruits PARKIN to damaged mitochondria and urolithin A raised PINK1 and Parkin in mouse macrophage cells, but no human study has tested whether NAD+ status changes urolithin A’s effect [14][15].
This overlap is biologically plausible, but it is worth being precise about what the current evidence does and does not support. The studies available on urolithin A, including a 2024 systematic review of human trials [2]do not primarily measure NAD+ levels as an outcome. The research on urolithin A is built around markers of mitophagy activation, mitochondrial gene expression, muscle performance, and immune cell function. The idea that urolithin A directly raises circulating NAD+ is not established by the evidence reviewed here.
On the stack question, one mouse study of a multi-ingredient product that included urolithin A and nicotinamide riboside reported a 33% longer median remaining lifespan, but urolithin A alone was not tested and the study was industry-funded. In the same study, NMN and nicotinamide riboside alone did not significantly change median lifespan [17].
What Human Evidence Exists for Urolithin A
A 2025 randomized, placebo-controlled trial examined the effect of urolithin A supplementation on age-related immune decline. The primary outcome was a very small shift (0.50 percentage points) in the share of naive-like CD8+ T cells at 1,000 mg a day for 4 weeks, a cell-marker result that did not measure mitophagy itself; the trial was funded by Amazentis [1].
Maximal muscle ATP production did not improve on urolithin A versus placebo
Urolithin A has not been shown to raise muscle energy output in people.
Mean change in maximal ATP production from baseline to 4 months in 66 adults aged 65 to 90. Source: Liu et al., JAMA Network Open 2022; Kuerec et al., Ageing Research Reviews 2024.
Data table
| Item | Value |
|---|---|
| Hand muscle (FDI), urolithin A | 0.07 mM/s |
| Hand muscle (FDI), placebo | 0.06 mM/s |
Chart: urolithinhub.com: Maximal muscle ATP production did not improve on urolithin A versus placebo
Embed this chart
Free to reuse on your site. Copy the code below; please keep the credit link.
A 2024 systematic review covering human studies on urolithin A found a dose-dependent anti-inflammatory effect, some upregulated mitochondrial genes and increased muscle strength and endurance, but no effect on maximal mitochondrial ATP production, biogenesis or physical function [2], though the authors noted that study sizes were generally small and longer-term trials are still needed [2]. For muscle specifically, mitochondrial health is a key determinant of muscle quality across aging: a relationship that is well-established in the literature and makes mitophagy-enhancing compounds a logical area of investigation [6].
Urolithin A in Brain and Nerve Cell Research
Much of the preclinical interest in urolithin A alongside NAD+-related research involves the brain, where mitochondrial dysfunction plays a prominent role in neurodegenerative conditions. In animal models, restoring mitophagy has been shown to reduce amyloid-beta and tau pathology and reverse cognitive deficits [7]. Urolithin A and related compounds have been investigated in this context, with preclinical findings suggesting benefits in models of cognitive impairment, including through inhibition of the NLRP3 inflammasome and mitochondrial protection [8].
There is also preclinical evidence that urolithin A can protect retinal neurons from acute degeneration, at least partly through selective autophagy pathways [9], and that enhancing mitophagy more broadly may be relevant to slowing neurodegeneration [10]. These findings are in animal or cell models; human neurological trials specifically for urolithin A are not yet available among the reviewed evidence.
Muscle Aging, Sarcopenia, and the Mitochondrial Connection
Age-related muscle loss, or sarcopenia, involves a progressive decline in both muscle mass and function that begins in middle age and accelerates later in life [11]. Mitochondrial dysfunction is considered one of several contributing factors: as mitochondrial quality falls in muscle cells, energy production becomes less efficient, and the cells become more susceptible to atrophy signals.
This is an area where urolithin A research has produced some of the more concrete human data. The systematic review [2] found that urolithin A supplementation was associated with improvements in mitochondrial gene expression in skeletal muscle. Reviews examining nutritional strategies for maintaining muscle health in aging have pointed to mitochondria as a tractable target [6], which situates urolithin A as one of several candidate approaches alongside better-established interventions like resistance exercise and adequate protein intake.
🛒 Where to Buy Urolithin A
- Timeline Mitopure SoftgelsClinically studied
softgels, 500 mg/day: The clinically studied form (Amazentis); used in the human trials. - Pure Encapsulations Renual
caplique capsules, 250 mg Mitopure Urolithin A/serving (with resveratrol + CoQ10): adds resveratrol and CoQ10, a combination the published urolithin A trials did not test. - ProHealth Longevity Urolithin A
capsules, 500 mg: Longevity-focused brand, often higher dose. - Double Wood Urolithin A
capsules, 250-500 mg: Budget-friendly, widely available, COA on request.
As an Amazon Associate we earn from qualifying purchases. Prices and availability vary; verify dose and third-party testing before buying.
A Note on the Evidence
The evidence reviewed here includes mostly small trials and preclinical studies; urolithin A is not approved to treat, prevent, or cure any disease, and individual responses to supplementation will vary. People who are pregnant, immunocompromised, or taking medications, particularly immunosuppressants, should consult a qualified healthcare provider before adding urolithin A or NAD+ precursor supplements to their routine.
Frequently Asked Questions
Does urolithin A raise NAD+ levels?
This is not clearly established by the current evidence. Urolithin A has been shown to activate mitophagy and improve markers of mitochondrial health [4], but human studies on urolithin A have not primarily measured NAD+ as an outcome [2]. The two molecules work on overlapping pathways without one necessarily increasing the other.
What is mitophagy and why does it matter?
Mitophagy is the selective recycling of damaged or dysfunctional mitochondria. When this process works well, cells maintain a healthier population of mitochondria. When it becomes impaired with aging, damaged mitochondria accumulate and drive chronic inflammation and energy deficits. Urolithin A has been identified as a compound that can stimulate mitophagy in human cells [4].
Is there human evidence for urolithin A supplementation?
Yes, though the evidence base is still developing. A 2025 randomized, placebo-controlled trial funded by Amazentis found a very small shift (0.50 percentage points) in naive-like CD8+ T cells; it did not measure clinical outcomes [1]. A 2024 systematic review found effects on mitochondrial gene expression in skeletal muscle and some exercise performance markers, but noted that larger and longer trials are needed [2].
Can urolithin A help with muscle aging?
Some evidence suggests it may support mitochondrial quality in skeletal muscle, which declines as part of the aging process that contributes to sarcopenia [11]. Nutritional strategies targeting mitochondria are an active area of research for preserving muscle function in older adults [6], and urolithin A has been studied in this context with encouraging early results [2]. It is not a substitute for resistance exercise, which remains the most robust intervention for muscle health.
What does the research say about urolithin A and the brain?
Preclinical research suggests that restoring mitophagy, the mechanism urolithin A engages, can reduce markers of neurodegeneration in animal models [7], and urolithin A-related compounds have shown protective effects on mitochondrial function in models of cognitive impairment [8]. However, human clinical trials specifically examining urolithin A for cognitive outcomes are not yet available in the reviewed evidence, so this remains an area of ongoing investigation.
Should everyone produce the same amount of urolithin A from food?
No. Urolithin A is produced by specific gut bacteria from ellagitannin precursors in foods like pomegranates and walnuts. Because gut microbiome composition varies considerably between individuals, some people produce substantial urolithin A from dietary sources and others produce very little or none at all. This variability is one reason supplemental urolithin A is being evaluated in clinical trials [2].
References
- Denk D et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nature aging (2025). PMID 41174221
- Kuerec AH et al. Targeting aging with urolithin A in humans: A systematic review. Ageing research reviews (2024). PMID 39002645
- Marei HE et al. Mitochondria at the heart of aging: structure, function, and failure. Journal of translational medicine (2026). PMID 42032617
- Borsky P et al. Distinct roles of urolithin A and spermidine in mitophagy and autophagy: implications for dietary supplementation. Nutrition research reviews (2025). PMID 41404767
- Chen P et al. Urolithin A protects against domoic acid-induced cognitive deficits via promoting estrogen receptor-α-mediated mitochondrial biogenesis signaling in mice. Free radical biology & medicine (2025). PMID 40818743
- Broome SC et al. Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing. Sports medicine (Auckland, N.Z.) (2024). PMID 39060742
- Fang EF et al. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nature neuroscience (2019). PMID 30742114
- Chen P et al. Methylated urolithin A, mitigates cognitive impairment by inhibiting NLRP3 inflammasome and ameliorating mitochondrial dysfunction in aging mice. Neuropharmacology (2024). PMID 38636727
- Jiménez-Loygorri JI et al. Urolithin A promotes p62-dependent lysophagy to prevent acute retinal neurodegeneration. Molecular neurodegeneration (2024). PMID 38890703
- Pradeepkiran JA et al. Are mitophagy enhancers therapeutic targets for Alzheimer's disease?. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2022). PMID 35585708
- Dao T et al. Sarcopenia and Muscle Aging: A Brief Overview. Endocrinology and metabolism (Seoul, Korea) (2020). PMID 33397034
- Ryu D et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature medicine (2016). PMID 27400265
- Gao Z et al. Urolithin A protects against acetaminophen-induced liver injury in mice via sustained activation of Nrf2. International journal of biological sciences (2022). PMID 35342347
- Mohsin M et al. Urolithin-A supplementation alleviates sepsis-induced acute lung injury by reducing mitochondrial dysfunction and modulating macrophage polarization. Mitochondrion (2025). PMID 40328344
- Peter M. J. Quinn et al. PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. Acta Neuropathologica Communications (2020). PMID 33168089
- Chen X et al. Impaired mitophagosome-lysosome fusion mediates olanzapine-induced aging. Aging cell (2023). PMID 37828862
- Weiss B et al. SRN-901, a Novel Longevity Drug, Extends Lifespan and Healthspan by Targeting Multiple Aging Pathways. Drug design, development and therapy (2026). PMID 42011226
- Karol Mateusz Pencina et al. Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. The Journal of Clinical Endocrinology & Metabolism (2023). PMID 36740954
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.