- Urolithin A is a natural compound that supports memory and cognitive function and reduces brain inflammation.
- A new study in mice suggests that urolithin A may have therapeutic properties in the treatment of Alzheimer’s disease.
- Consumption of certain polyphenols, abundant in pomegranates, may increase the production of urolithin A by intestinal bacteria.
- Experts recommend increasing the body’s production of urolithin A through diet rather than supplementation.
Alzheimer’s disease is a degenerative brain disease that mainly affects people over the age of 65.
Research indicates that
Since Alzheimer’s disease is associated with elevated oxidative stress, increased antioxidant intake could be particularly beneficial. Antioxidants neutralize the damage caused by free radicals, possibly mitigating the effects of disease.
A recent study published in
Urolithin A has
Researchers treated various mouse models of Alzheimer’s disease with urolithin A for 5 months to assess the long-term effects on brain health.
The results showed that urolithin A could improve learning and memory, reduce neuroinflammation, and improve cellular cleaning processes in mice with Alzheimer’s disease.
Although animal studies are not directly applicable to humans, experts believe that urolithin A may have potential as a future preventative 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 bioinformatics experiments.
After five months of urolithin A treatment, they observed improvements in memory, protein accumulation, cellular waste processing and DNA damage in the brains of mice with Alzheimer’s.
Additionally, important markers of brain inflammation were reduced, making the treated mice more similar to healthy mice.
The study found that urolithin A treatment reduced excessive activity in microglia, a type of immune cell in the brain.
Researchers also suggest that urolithin A:
- reduces cathepsin Z, which is elevated in Alzheimer’s disease and may be a target for Alzheimer’s disease treatment
- decreases levels of beta-amyloid protein and inflammation associated with the development of Alzheimer’s disease
- promotes mitophagy, the cleaning of damaged mitochondria, which is reduced in Alzheimer’s disease
The mitophagic effects of urolithin A may be similar to those seen with nicotinamide adenine dinucleotide (NAD) supplements in
Some of the researchers in this study have ties to several companies, including ChromaDex, known for its NAD supplement. It is unclear how these connections might influence the results of the present study.
Medical news today spoke with Thomas M. Holland, MD, MS, physician-scientist and assistant professor at the RUSH Institute for Healthy Aging, RUSH University, College of Health Sciences, who did not participate in the ‘study.
He noted that, in the current mouse model study, urolithin A treatment “had a positive impact on several aspects of brain health, such as improved memory function, reduced accumulation of harmful proteins, decreasing brain inflammation, improving the elimination of cellular waste, and preventing DNA damage in key regions of the brain.
“Collectively, (the results) mean that (urolithin A) may act as a potent anti-inflammatory and antioxidant agent to help eliminate (beta-amyloid, which) prevents the onset of cognitive deficits associated with pathological deposition ( beta-amyloid) (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 removal of harmful proteins and damaged mitochondria from the brain.
MNT also spoke with Alyssa Simpson, RDN, CGN, CLT, registered dietitian, certified gastrointestinal nutritionist and owner of Nutrition Resolution in Phoenix, Arizona, who was not involved in the study.
She highlighted the strengths and weaknesses of the study:
“While the study provides important information on the potential benefits of urolithin A for Alzheimer’s disease, it is limited by its reliance on animal models and its narrow focus on specific pathways, neglecting perhaps broader systemic interactions. However, its strengths lie in the in-depth evaluation of multiple pathological mechanisms and the study of long-term treatment effects, which significantly advances our understanding of the therapeutic role of urolithin A in Alzheimer’s disease.
“Research indicates that urolithin A treatment has potential as a novel intervention for Alzheimer’s disease by addressing various disease mechanisms such as neuroinflammation, mitochondrial dysfunction, lysosomal dysfunction, and damage to DNA, potentially slowing the progression of the disease,” Simpson added.
However, “although research on urolithin A shows promise for Alzheimer’s disease intervention, additional studies, particularly clinical trials, are needed to validate its effectiveness and safety in humans,” she warned.
Holland agreed but highlighted the challenges of determining optimal outcomes and dosing of urolithin A through randomized controlled trials.
He explained that it is difficult to control diet, gut microbiota and individual health conditions, and that these factors can influence the absorption and use of urolithin A in the body.
Additionally, Holland said that if subjects consume other polyphenol-rich foods, it makes it difficult to isolate the effects of administered urolithin A from that produced naturally through the diet.
Further research is needed to determine the best doses of urolithin A and the potential risks of long-term supplement use, as both of these are unknown.
“There may be risks associated with testing urolithin A pills for Alzheimer’s disease intervention because research into their safety and effectiveness is limited,” Simpson cautioned.
Promoting the body’s production of urolithin A through diet may be a more natural and safer approach.
Holland explained that urolithin A is a natural compound produced by gut bacteria when exposed to certain polyphenols, like ellagitannins and ellagic acid, found in many fruits and nuts.
Holland and Simpson highlighted some of the best food sources of these polyphenols, including:
Both experts said pomegranate seeds (arils) and peels are particularly 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 may vary due to individual differences in the gut microbiota, “influencing the extent of potential benefits.”
Holland supported this, noting that the “results of this study 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 on previous research and highlights that the foods we eat are crucial for brain health,” he said. he concluded.