Shop
-1.png)
eStoreRx™
Online Supplement Dispensary
eStoreRx™ is an easy direct-to-patient ordering & fulfilment program for lifelong wellness.
Results from a 2023 randomized, double-blind, placebo-controlled study revealed compelling findings on the impact of pomegranate (Punica granatum) extract on skin health, particularly through the gut-skin axis. Twenty-eight healthy adults aged 25–55 were administered either 75 mg of punicalagin, a potent polyphenol found in pomegranate (PE), or a placebo for four weeks. One of the most remarkable outcomes of PE supplementation was a significant increase in circulating levels of urolithin A (UA)—a powerful, gut-derived metabolite associated with a range of systemic and skin health benefits.
Upon ingestion, ellagitannins—polyphenolic compounds found in pomegranate—are hydrolyzed into ellagic acid in the gastrointestinal (GI) tract. Gut microbiota then metabolize ellagic acid into bioactive urolithins, with urolithin A being the most prominent. Following its synthesis and intestinal absorption, UA enters systemic circulation and is further processed in the liver before being distributed to various tissues, including the skin.
UA has been shown to exert broad systemic effects that translate into improved skin health. These include antioxidant action, support for a healthy inflammatory response, gastrointestinal support, and cellular benefits—such as the activation of mitophagy—the process responsible for the removal of damaged mitochondria. Notably, PE supplementation also led to alterations in the gut microbiome, as highlighted in the same 2023 study. Increases in beneficial microbial species—including Coprococcus eutectus, Roseburia faecis, Roseburia inulinivorans, Ruminococcus bicirculans, Ruminococcus calidus, and Faecalibacterium prausnitzii—were observed.
Individual variability in circulating UA levels is largely attributed to differences in gut microbiota composition, underscoring the significant role of the microbiome in mediating health outcomes. The study also noted increased circulating levels of short-chain fatty acids (SCFAs), including propionate and acetate—metabolites known to modulate systemic inflammation and support metabolic health. These measurements were made via stool sample collection and venipuncture.
A 2025 study published in Molecules further supported the metabolic benefits of pomegranate, demonstrating its ability to improve metabolic profiles in humans. Additionally, another study in mice found that punicalagin helped reduce obesity-induced inflammatory and oxidative stress responses through activation of the Nrf2/Keap1 signaling pathway.
Beyond its metabolic effects, pomegranate and its urolithin A metabolites have shown neuroprotective and anti-neuroinflammatory properties. They have also been linked to the mitigation of inflammatory intestinal barrier dysfunction, which may further promote systemic skin health.
Psychoneuroimmunology (PNI)—the study of interactions between the nervous, endocrine, and immune systems—emphasizes their collective influence on skin. During stress, activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system increases the release of cortisol and catecholamines, which modulate immune responses. In the skin, this neuroimmune dysregulation can result in elevated pro-inflammatory cytokines, which can exacerbate skin conditions. Metabolism plays a central role in this process, linking stress responses to immune activation. Stress can disrupt glucose and lipid metabolism, impede mitochondrial function, and increase oxidative stress—all of which compromise skin barrier function and immune response.
In fact, a previous 2022 study by the same authors found that oral pomegranate extract improved skin appearance and altered biophysical measures of the skin. These benefits were attributed to its antimicrobial properties and rich polyphenol content. Other studies have demonstrated that pomegranate protects against UVA and UVB-induced damage in human skin fibroblasts, reduces oxidative stress, exhibits anti-glycation properties, and prevents alcohol-induced intestinal permeability and hepatic inflammation—highlighting its systemic protective effects that benefit the skin.
Microbial genera implicated in urolithin biosynthesis include Lactobacillus, Roseburia, Fusobacterium, Streptococcus, Slackia, and Bacillus. The increased abundance of Roseburia following PE supplementation suggests a microbial mechanism underlying the elevated plasma levels of urolithin A. UA mediates its benefits through several biological mechanisms, most notably through mitophagy via the PINK1/Parkin signaling pathway. This process maintains mitochondrial quality, supports cellular energy production, and contributes to skin vitality and healthy aging.
The enhancement of UA production appears to depend on both the availability of ellagitannin-rich substrates, such as punicalagin and gut microbiota composition that favors urolithin-producing taxa. Additionally, UA enhances the body’s antioxidant defenses by upregulating enzymes such as superoxide dismutase, which neutralizes reactive oxygen species. It also promotes angiogenesis—critical for wound healing and tissue regeneration—and reduces inflamm-aging– the chronic, low-grade inflammation that accelerates skin aging.
PE not only shifts microbial composition but also boosts microbial function. The expression of genes responsible for SCFA synthesis—particularly for acetate and propionate—increased significantly. These SCFAs are known for their effects on the body’s inflammatory response and their role in maintaining the integrity of the gut-skin axis.
By supporting mitochondrial function and promoting cellular turnover, UA contributes to overall metabolic and neurological health, which further supports skin health via the principles of PNI. The main study also found that PE led to favorable changes in both the gut and skin microbiota. In the gut, PE increased SCFA-producing bacteria such as Roseburia faecis, Coprococcus eutectus, and Faecalibacterium prausnitzii. These microbes produce acetate, butyrate, and propionate, all of which help modulate immune responses and reduce systemic inflammation—indirectly supporting skin health.
On the skin, PE supplementation resulted in a notable rise in Staphylococcus epidermidis and Bacillus species. S. epidermidis, in particular, enhances the skin’s innate immunity by producing antimicrobial peptides that help defend against pathogenic bacteria, strengthening the skin barrier.
Intriguingly, individuals with a higher abundance of Eggerthellaceae in their gut experienced a greater reduction in transepidermal water loss (TEWL) and wrinkle severity. PE also stimulated microbial pathways involved in the biosynthesis of branched-chain amino acids, such as L-isoleucine, which is linked to improved collagen production and skin structural integrity. Additionally, there was increased microbial gene expression related to the production of B vitamins and folate, essential for DNA repair, cellular regeneration, and overall skin vitality.
Collectively, these findings suggest that pomegranate extract (PE) modulates the gut microbiome to enhance the production of bioactive metabolites—such as short-chain fatty acids and urolithin A—that influence systemic inflammation, mitochondrial function, and cellular homeostasis, all pivotal to skin health. Microbial shifts and upregulation of genes related to vitamin and amino acid metabolism further support a systemic role. The integration of these effects via the gut-skin axis and psychoneuroimmunological pathways highlights the potential of PE as a multifactorial modulator of skin function.
Submit your comment