Urolithin A, a metabolite of ellagitannins in pomegranates, boosts immune cells’ ability to combat tumors by inducing a process known as mitophagy.
STORY AT-A-GLANCE
- Urolithin A (UA) has emerged as a powerhouse player in the fight against cancer, as it may naturally boost tumor-fighting immune cells.
- UA is a metabolite of ellagitannins in pomegranates that has anti-inflammatory and anticancer effects.
- UA “recycles and renews mitochondria” by inducing a biological pathway known as mitophagy—the process of cleaning out your mitochondria, allowing them to function at their best. This changes T cells’ genetic program, making them more able to fight tumors.
- In an upcoming clinical trial, UA will be used in people with colorectal cancer to determine its effectiveness.
Pomegranate Compound Improves Immune Cells’ Cancer-Fighting
Urolithin A is a metabolite of ellagitannins in pomegranates. (3) Researchers from the Georg Speyer Haus in Frankfurt am Main, Germany, revealed that UA “recycles and renews mitochondria” by inducing a certain biological pathway.Your mitochondria are often called the powerhouse of cells due to their role in energy production. UA induces a process known as mitophagy, by which old, damaged mitochondria in T cells are replaced with new ones. Mitophagy refers to “a cytoprotective process that limits both the production of [reactive oxygen species] ROS and the release of toxic intramitochondrial proteins.” (4)
“The researchers demonstrated the therapeutic potential of urolithin A in two ways: On the one hand, urolithin A can be used as a food in the preclinical model, which limits tumor growth and even acts synergistically with existing immunotherapy.
Is UA Pomegranate’s Anti-aging Secret?
Urolithin A not only may play a role in [healing] cancer but also other age-related diseases, which are often the result of a buildup of dysfunctional mitochondria. “It’s the only known molecule that can relaunch the mitochondrial clean-up process, otherwise known as mitophagy,” Patrick Aebischer, who co-authored a 2016 study on UA’s ability to induce mitophagy, (8) explained. “It’s a completely natural substance, and its effect is powerful and measurable.” (9)In a study involving nematode C. elegans (roundworms), lifespan increased by more than 45 percent when the worms were exposed to UA. In rodent studies, older mice also experienced anti-aging benefits from UA, including 42 percent better endurance than control mice of the same age. (10)
One caveat: Gut microbes are required to metabolize ellagitannins, which are found in pomegranate, into UA. But with age, alterations in the microbiome lead to reduced production of UA. According to a study in Immunity, older adults produce less than half the UA as younger people. (11)
Studies involving concentrated forms of UA have shown that dietary supplementation may also be capable of inducing mitophagy and slowing the progression of aging-related diseases. (12) Human clinical trials have also been promising. When healthy but sedentary older adults were given UA over a four-week period, it induced a molecular signature that suggested improved mitochondrial and cellular health. (13)
Pomegranate, Urolithin A for Cancer Treatment and Prevention
UA has anti-inflammatory and anticancer effects, making it a promising compound for cancer treatment and prevention. The substance has proven beneficial in models of pancreatic cancer, and it’s suggested that it may be useful for preventing immune suppression that’s associated with chronic inflammation in cancer. (15) Further, as noted in a study published in OncoTargets and Therapy: (16)“Growing studies have found that urolithin A downregulates multiple tumor pathways in colon, prostate, and bladder cancer through downregulating several oncogenes such as mTOR and K-Ras, upregulating tumor suppressor genes such as p53 and EGFR.”That study referred to UA as a “natural anticancer drug” that “can be used as a first-line chemotherapeutic drug combination candidate to prevent drug resistance.” (17) The researchers found UA inhibited the epithelial-to-mesenchymal transition, which plays a fundamental role in tumor progression. (18)
“The results of apoptotic analyses implicated that fruit juice might trigger the apoptosis in DU145 cells via death receptor signaling and mitochondrial damage pathway ... 11 proteins were deregulated in affected DU145 cells with three upregulated and eight downregulated proteins.
“These dys-regulated proteins participated in cytoskeletal functions, antiapoptosis, proteasome activity, NF-κB signaling, cancer cell proliferation, invasion, and angiogenesis ...
“Among urolithins, UA shows anticancer, anti-inflammation, and antiaging effects and has demonstrated compelling biological activities. The direct effects of UA have been studied in different types of cells in vitro, including human prostate and colorectal cancer cells and B16 melanoma cells. In these experiments, UA consistently prevented cancer cell proliferation and metastasis, arguing for a potential anticancer effect of UA.”
More UA Benefits: Muscle Endurance, Anti-obesity
UA has benefits beyond cancer control, including improving skeletal muscle performance and mitochondrial health in older adults. In a trial of 66 people who received either 1,000 milligrams of UA or a placebo daily for four months, the UA group had a significant improvement in muscle endurance, based on the number of muscle contractions to fatigue—in both hand and leg skeletal muscles. (24)C-reactive protein, a measure of inflammation, also decreased after UA supplementation. Researchers concluded, “Long-term urolithin A supplementation was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin A may counteract age-associated muscle decline.” (25)
UA’s anti-obesity effects are also worth noting. The compound prevents diet-induced obesity and metabolic dysfunctions in rodent models, without causing any adverse effects. It also enhances thermogenesis in brown adipose tissue, increasing energy expenditure, and induces browning of white adipose tissue. (26)
This is a good thing, as brown fat is a beneficial form of fat that may generate heat and burn glucose and fats through a mitochondrial reaction mediated by mitochondrial uncoupling protein 1. (27)
“Besides the antiobesity effect, UA causes a series of beneficial metabolic effects, including improved insulin sensitivity and reduced systemic inflammation and fatty liver, which are at least partially due to weight loss ... UA enhances adipose tissue production of T3, which subsequently activates transcription and translation of the thermogenic genes PGC1a and UCP-1, leading to higher EE [energy expenditure] and lower body weight.”Beyond UA, the antioxidants in pomegranates also help quench inflammation that contributes to the destruction of cartilage in your joints, a key reason for the pain and stiffness felt by many osteoarthritis sufferers. One study even found that pomegranate juice blocked the production of a cartilage-destroying enzyme. (29)
How to Eat Pomegranate
Many of pomegranate’s—known as “the jewel of autumn”—beneficial polyphenols are stored in the peel, which is why pomegranate peel powder is one of my favorite supplements.Research shows pomegranate peel contains more than twice the amounts of antioxidants—specifically phenolics, flavonoids, and proanthocyanidins—than the pulp, for instance, and has been shown to protect low-density lipoprotein against oxidation to a far greater degree than pulp. (30, 31)
Pomegranate peel powder, pomegranate peel extract, and UA supplements are different ways to get more concentrated effects of this superfood. However, many people enjoy eating pomegranates as a snack.
- Cut off the crown, then cut the pomegranate into sections.
- Place the section in a bowl of water, then roll out the arils with your fingers (discard everything else).
- Strain out the water and enjoy the arils whole, seeds and all.
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