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A natural compound found in pomegranates could help alleviate Alzheimer’s symptoms, research suggests. Tanja Ivanova/Getty Images
  • Urolithin A is a natural compound shown to support memory and cognitive function and reduce brain inflammation.
  • A new study in mice suggests that urolithin A may have therapeutic properties in treating Alzheimer’s disease.
  • Consuming certain polyphenols, abundant in pomegranates, can increase gut bacteria’s production of urolithin A.
  • Experts recommend enhancing the body’s production of urolithin A through diet rather than supplementation.

Alzheimer’s disease is a degenerative brain disorder that primarily affects individuals over the age of 65 and is the leading cause of dementia in older adults.

Research indicates that Mediterranean and MIND diets may protect against Alzheimer’s, potentially due to lower intake of inflammatory saturated fats and sugars and higher consumption of vitamins, minerals, omega-3s, and antioxidants.

Since Alzheimer’s is associated with elevated oxidative stress, increased antioxidant intake might be especially beneficial. Antioxidants counteract free radical damage, possibly mitigating disease effects.

A recent study published in Alzheimer’s & Dementia explored urolithin A, a natural compound produced by gut bacteria when they process certain polyphenolic compounds found in pomegranates.

Urolithin A has potent antioxidant and anti-inflammatory effects, along with other potential benefits for brain health.

Researchers treated various Alzheimer’s mouse models with urolithin A for 5 months to assess long-term effects on brain health.

The results showed that urolithin A could enhance learning and memory, reduce neuroinflammation, and improve cellular cleanup processes in Alzheimer’s disease mice.

Although animal studies do not directly translate to humans, experts believe urolithin A may have potential as a future preventive or therapeutic agent for Alzheimer’s disease.

Researchers from the University of Copenhagen in Denmark conducted a study to understand the benefits of long-term urolithin A treatment in Alzheimer’s disease.

Using three mouse models of Alzheimer’s disease, they combined urolithin A treatment with behavioral, electrophysiological, biochemical, and bioinformatic experiments.

After five months of urolithin A treatment, they observed improvements in memory, protein build-up, cell waste processing, and DNA damage in the brains of Alzheimer’s mice.

Additionally, important markers of brain inflammation were reduced, making the treated mice more similar to healthy ones.

The study revealed that urolithin A treatment lowered the excessive activity of microglia, a type of immune cell in the brain.

The researchers also suggest that urolithin A:

  • reduces cathepsin Z, which is elevated in Alzheimer’s and could be a target for Alzheimer’s treatment
  • decreases amyloid beta protein levels and inflammation associated with Alzheimer’s disease development
  • promotes mitophagy, the cleaning out of damaged mitochondria, which is reduced in Alzheimer’s disease

The mitophagy effects from urolithin A may be similar to those seen with nicotinamide adenine dinucleotide (NAD) supplements in Alzheimer’s disease.

Some of the researchers in this study have connections to several companies, including ChromaDex, which is known for its NAD supplement. It’s unclear how these ties might influence the present study’s results.

Medical News Today spoke with Thomas M. Holland, MD, MS, a physician-scientist and assistant professor at the RUSH Institute for Healthy Aging, RUSH University, College of Health Sciences, who was not involved in the study.

He noted that, in the present mouse model study, urolithin A “treatment positively impacted several aspects of brain health, such as improving memory function, reducing harmful protein build-up, decreasing brain inflammation, enhancing cellular waste removal, and preventing DNA damage in key brain regions.”

“Collectively [the results] mean that [urolithin A] can act as a potent anti-inflammatory and antioxidant agent to help clear [amyloid beta, which] prevents the onset of cognitive deficits associated with the pathological [amyloid beta] deposition [and can] regulate cellular energy homeostasis and cell death.”
— Thomas M. Holland, MD, MS

In other words, urolithin A may have multiple mechanisms of action contributing to its positive effects on the brain.

Specifically, Urolithin A may help protect against cognitive decline by reducing inflammation and oxidative stress and promoting the clearance of harmful proteins and damaged mitochondria from the brain.

MNT also spoke with Alyssa Simpson, RDN, CGN, CLT, a registered dietitian, certified gastrointestinal nutritionist, and owner of Nutrition Resolution in Phoenix, Arizona, who was not involved in the study.

She noted the study’s strengths and weaknesses:

“While the study provides important insights into urolithin A’s potential benefits for Alzheimer’s, it is limited by its reliance on animal models and its narrow focus on specific pathways, possibly overlooking broader systemic interactions. However, its strengths lie in the thorough assessment of multiple pathological mechanisms and investigation of long-term treatment effects, which significantly advances our understanding of urolithin A’s therapeutic role in Alzheimer’s.”

“The research indicates that urolithin A treatment shows potential as a new intervention for Alzheimer’s disease by addressing various pathological mechanisms like neuroinflammation, mitochondrial dysfunction, lysosomal dysfunction, and DNA damage, potentially slowing down the progression of the disease,” Simpson added.

However, “[w]hile research on urolithin A offers promise for Alzheimer’s intervention, additional studies, particularly clinical trials, are required to validate its efficacy and safety in humans,” she cautioned.

Holland agreed but highlighted challenges in determining urolithin A’s outcomes and optimal dosage through randomized controlled trials.

He explained that controlling for diet, gut microbiota, and individual health conditions is difficult, and these factors can influence urolithin A absorption and utilization in the body.

Additionally, Holland said that if subjects consume other polyphenol-rich foods, it complicates isolating the effects of the administered urolithin A from that produced naturally through diet.

More research is needed to determine the best urolithin A doses, and the potential risks of long-term supplement use since both of these are unknown.

“There could be risks associated with trying urolithin A pills for Alzheimer’s intervention since there is limited research on their safety and effectiveness,” cautioned Simpson.

Promoting the body’s urolithin A production through diet may be a more natural and safe approach.

Holland explained that urolithin A is a natural compound produced by gut bacteria when exposed to certain polyphenols, like ellagitannins and ellagic acid, which are present in many fruits and nuts.

Holland and Simpson highlighted some of the best food sources of these polyphenols, including:

Both experts stated that pomegranate seeds (arils) and peels are especially abundant in polyphenolic compounds that can be converted to urolithin A.

However, Simpson noted that the bioavailability and effectiveness of urolithin A from pomegranate and other foods might vary due to individual differences in gut microbiota, “influencing the extent of potential benefits.”

Holland supported this, remarking that this study’s “findings reiterate the importance of having a diverse and robust gut microbiota to ensure optimal digestion and absorption of nutrients and polyphenols.”

“Although the work was done in mice and cannot be directly generalized to humans, it builds upon previous research and emphasizes that the foods we consume are crucial for brain health,” he concluded.