By Alma Ross
Pomegranate’s heart benefits have led researchers to investigate in what ways this red fruit can keep us healthy.
In a recent finding, Swiss researchers have identified a new molecule that results from digesting two compounds found in pomegranates: punicalagins and ellagitannins. This unique molecule, known as urolithin A, helps rejuvenate mitochondria, our cellular powerhouses.1
Urolithin A opens the door to potential new therapeutic treatments against age-related disorders, including frailty, which is a risk factor for disability, hospitalizations, and mortality.2
What is Urolithin A?
Urolithin A is produced by the body after ingesting compounds found in pomegranate such as punicalagins and ellagitannins and can help recycle defective mitochondria.
What A New Study Showed
Researchers first studied Urolithin A on a common worm called C. elegans. This worm is often used in anti-aging studies because after just 8-10 days it’s considered elderly. Its short lifespan allows scientists to observe and measure the effects of aging in a little over a week.
The researchers administered urolithin A to a group of these worms and noted that lifespan in the urolithin A group increased by more than 45% compared to the control group.1
Next, the team performed several rodent studies and found that urolithin Aimproved muscle function and removed damaged mitochondria before they accumulate and cause cellular dysfunction throughout the body. Scientists know that with age, mitochondria lose their strength and die off thereby “clogging up” cells with debris that impedes their function.
In the first mouse study, urolithin A administration over the long-term was found to increase muscle function of aging mice. Compared to the control group, the supplemented group showed a 57% increase in the level of spontaneous exercise measured by the running wheel and a 9% increase in grip strength.1
In a second mouse study, this time involving a shorter treatment regimen on aged mice, urolithin A was found to increase running endurance by an average of 42%.1
Following these findings on aging mice, the team performed another study, also evaluating the impact of urolithin A on muscle function in young rats. Muscle function was evaluated by measuring voluntary running in activity wheels. Once again, treatment with urolithin A proved to be effective, this time by increasing the running capacity by 65% compared to controls.1
The administration of urolithin A resulted in an enhanced exercise capacity in young and older rodents. Muscle strength increased and running endurance was robustly augmented. Together, these different studies highlight that the administration of urolithin A, both short- and long-term, improved muscle function throughout different stages of life by improving muscle quality.
Urolithin A is generated in the digestive tract as a natural metabolite of punicalaginsand ellagitannins, polyphenol compounds found in pomegranates.10 Pomegranates have been identified as a potent weapon in the fight against aging due to their high content of ellagitannins. Ellagitannins are a natural substance with anti-inflammatory, anti-cancer effects.11-14
Translating these Findings into Humans
Over time, the constant strain of energy production takes a toll on the mitochondria and energy output declines. At this point, these mitochondria function poorly and are basically useless. In young, healthy cells, the drop in performance of the mitochondria is identified by the body and the mitochondria are swiftly broken down, disassembled, and eliminated in a process called mitophagy. In this way, defective or less-than-optimal mitochondria are eliminated, giving room to new mitochondria and ensuring that optimal cellular function is maintained.
With age, our cells struggle to recycle defective mitochondria, leading to a progressive build-up of malfunctioning mitochondria that take up valuable space in the body’s cellular system. This mitochondrial degradation affects the health of the cells, gradually weakening tissues. This process has been suspected of playing a role in many disorders of aging, such as Parkinson’s disease.3
In humans, the inability to remove these useless mitochondria in skeletal muscle has been linked to reduced mobility in the elderly.1 The progressive decline of muscle function contributes to a progressive state of generalized frailty.
In addition, the frailty associated with old age is an important risk factor for disability, hospitalization and mortality.2 Thus, the muscle weakness seen in the elderly might be due to an increase in the accumulation of useless mitochondria. Results from the rodent studies strongly suggest that improvement of muscle quality may be achieved by enhancing mitochondrial function with urolithin A.
The results from these recent Swiss studies suggest that supplementation with pomegranate extract to boost the body’s content of urolithin A may be an innovative approach to maintaining healthy mitochondrial and muscle function.
Encouraged by their initial findings, the study authors are currently conducting clinical trials testing a special delivery method of finely calibrated doses of urolithin A in humans. These trials are currently taking place in a number of hospitals across Europe.4
Urolithin A Helps Fight Cancer
Despite aggressive surgical care and chemotherapy, nearly 50% of people with colorectal cancers develop recurrent tumors.5 This may be due in part to the survival of dangerous colon-cancer stem cells that resist conventional chemotherapy and act as “seeds” for subsequent cancers.6
In an interesting finding, researchers exposed colon-cancer stem cells from a patient with colorectal cancer to either a mixture containing 85% urolithin A or 30% urolithin A. The results were impressive. The higher urolithin A concentration mixture was most effective at inhibiting the number and size of colon-cancer stem cells and inhibiting the activity of aldehyde dehydrogenase, a marker of chemoresistance.7
This therapeutic approach is exciting because traditional therapies against cancer lack the ability to kill or stop the proliferation of cancerous stem cells. These new findings support the notion that a nutrient approach may prove valuable as an alternative treatment or preventive intervention for targeting these harmful cells.
The connection between pomegranate and its neuroprotective effects against Alzheimer’s disease has been well established in animal studies.8 However, the bioactive constituents for this action were unknown until now.
Alzheimer’s disease is expected to affect over 115 million people worldwide by the year 2050.9 A group of researchers looked at a previous animal study that reported on the anti-Alzheimer’s effects of pomegranate extract constituents.8
The team evaluated the ability of these components to cross the blood-brain barrier and found that a methylated form of urolithin A (mUA), derived from pomegranate, along with other urolithins were capable of doing so.
And, although more research is needed, the authors concluded that urolithins are the possible compounds responsible for the anti-Alzheimer’s effects that include protection against neurotoxicity and b-amyloid fibrillation. These results are promising, and suggest the need for exploring other naturally-based dietary intervention strategies for preventing or slowing down the progression of Alzheimer’s.
The results and data from these various studies further support the importance of polyphenol metabolite compounds like urolithin A from pomegranate and their role in the fight against colon cancer and neurodegenerative diseases.
The discovery of urolithin A, that results from the punicalagins and ellagitannins compounds found in pomegranates, provides new opportunities to fight age-related decline of mitochondrial function and the resulting frailty and loss of muscle.
By helping cells renew themselves and optimizing muscle performance, pomegranate extract and its newly identified metabolite, urolithin A—could prove successful.
Along with these findings, there is supportive evidence of the powerful effects that urolithin A has against Alzheimer’s disease and cancer, offering yet another tool to fight against these devastating conditions that affect many aging individuals.
This nutritional approach opens up possibilities that traditional pharmaceutical approaches have never explored.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med. 2016;22(8):879-88.
- Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-56.
- Perier C, Vila M. Mitochondrial biology and Parkinson’s disease. Cold Spring Harb Perspect Med.2012;2(2):a009332.
- Available at: http://labiotech.eu/switzerland-unlocks-the-secret-to-pomegranates/. Accessed June 5, 2017.
- Patel BB, Majumdar AP. Synergistic role of curcumin with current therapeutics in colorectal cancer: minireview. Nutr Cancer. 2009;61(6):842-6.
- Subramaniam D, Ramalingam S, Houchen CW, et al. Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem. 2010;10(5):359-71.
- Nunez-Sanchez MA, Karmokar A, Gonzalez-Sarrias A, et al. In vivo relevant mixed urolithins and ellagic acid inhibit phenotypic and molecular colon cancer stem cell features: A new potentiality for ellagitannin metabolites against cancer. Food Chem Toxicol. 2016; 92:8-16.
- Yuan T, Ma H, Liu W, et al. Pomegranate’s Neuroprotective Effects against Alzheimer’s Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites. ACS Chem Neurosci.2016;7(1):26-33.
- Available at: https://www.nia.nih.gov/research/publication/longer-lives-and-disability/burden-dementia. Accessed June 5, 2017.
- Seeram NP, Henning SM, Zhang Y, et al. Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J Nutr. 2006;136(10):2481-5.
- Mele L, Mena P, Piemontese A, et al. Antiatherogenic effects of ellagic acid and urolithins in vitro. Arch Biochem Biophys. 2016;599:42-50.
- Hollebeeck S, Winand J, Herent MF, et al. Anti-inflammatory effects of pomegranate (Punica granatum L.) husk ellagitannins in Caco-2 cells, an in vitro model of human intestine. Food Funct. 2012;3(8):875-85.
- Ismail T, Calcabrini C, Diaz AR, et al. Ellagitannins in Cancer Chemoprevention and Therapy. Toxins.2016;8(5):151.
- Adams LS, Zhang Y, Seeram NP, et al. Pomegranate Ellagitannin-Derived Compounds Exhibit Anti-proliferative and Anti-aromatase Activity in Breast Cancer Cells In Vitro. Cancer prevention research (Philadelphia, Pa.). 2010;3(1):108-13.