New study shows urolithin A can improve treatment of Alzheimer’s

Promising postbiotic: Research shows urolithin A can alleviate memory problems and other consequences of dementia.

Alzheimer’s disease, characterized by symptoms such as forgetfulness, difficulty finding words, and confusion, remains one of the most challenging neurodegenerative disorders to treat. With a growing global burden, innovative and proactive strategies are urgently needed, and recent research from the University of Copenhagen has shed light on a natural compound urolithin A, which may offer new hope for cognitive health and Alzheimer’s treatment [1].

Longevity.Technology: Urolithin A is a postbiotic produced by gut bacteria when they metabolize ellagitannins and ellagic acid, polyphenols found in foods such as pomegranates, strawberries and walnuts, a natural process that underscores the importance of a healthy gut microbiome for the production of beneficial compounds. While putative treatments for Alzheimer’s often grab headlines, it is worth noting that research indicates that only a minority of individuals possess the right gut bacteria to efficiently produce urolithin A; in fact, a recent study revealed that after consuming pomegranate juice, a rich source of urolithin A precursors, only 40% of participants converted a significant amount of these polyphenols into detectable levels of urolithin A [2].

The scarcity of urolithin A production in most people highlights the potential benefits of longevity supplements such as Mitopure; these supplements can provide a direct source of urolithin A, bypassing the need for specific gut bacteria. Such interventions are particularly relevant given the promising findings from the University of Copenhagen.

Researchers at the University of Copenhagen discovered that urolithin A stimulates mitophagy, effectively removing damaged mitochondria from the brain. Mitophagy,  a type of autophagy that selectively eliminates mitochondria, is a process crucial for maintaining cellular health and function, and is vital for the survival and health of neurons. Damaged mitochondria, if not adequately cleared, can contribute to the progression of neurodegenerative diseases like Alzheimer’s, and the researchers had previously discovered that nicotinamide riboside was a natural mitophagy inducer. Now their attention turned to urolithin A.

“Many patients with neurodegenerative diseases experience mitochondrial dysfunction,” says Vilhelm Bohr, who is Affiliate Professor at the Department of Cellular and Molecular Medicine at the University of Copenhagen and previously Department Chair at the US National Institute on Aging. “This means that the brain has difficulties removing weak mitochondria, which thus accumulate and affect brain function. If you are able to stimulate the mitophagy process, removing weak mitochondria, you will see some very positive results [3].” 

The team had previously investigated the benefits of urolithin A treatment of an Alzheimer’s disease model (the triple-transgenic AD mouse, 3xTg-AD, which expresses pathogenic forms of amyloid precursor protein, presenillin and tau and demonstrates histological and behavioral signs of Alzheimer’s disease). However, this was over a period of two months, and given that most Alzheimer’s patients are likely to receive treatment and care for an extended period, the team used multiple AD mouse models, treating them with urolithin A for 5 months in order to study the effects of long term treatment [1].

The research team found that long-term urolithin A treatment in mice significantly improved their learning, memory and olfactory function. The treatment also reduced amyloid beta (Aβ) and tau pathologies and improved cellular lysosomal function [1].

The researchers’ findings also suggest that urolithin A is as effective as NAD in promoting mitophagy, positioning it as a potential therapeutic agent for Alzheimer’s disease.

“Our study on mouse models with AD shows that urolithin A, which is a naturally occurring substance in pomegranates, can alleviate memory problems and other consequences of dementia,” says Bohr. “Even though the study was conducted on mouse models, the prospects are positive. So far, research has shown promising results for the substance in the muscles, and clinical trials on humans are being planned [3].”

While the precise dosage and long-term effects of urolithin A are still under investigation, its safety profile appears favorable for preventive use – this is particularly significant as Alzheimer’s disease remains an area with limited effective treatments and a growing need for prevention strategies.

“We still cannot say anything conclusive about the dosage. But I imagine that it is more than a pomegranate a day,” said Bohr. “However, the substance is already available in pill form, and we are currently trying to find the right dosage [3].”

The potential of urolithin A to enhance memory and mitigate Alzheimer’s symptoms without significant side effects makes it a compelling candidate for further research and clinical trials, especially given its natural origin.

“The advantage of working with a natural substance is the reduced risk of side effects. Several studies so far show that there are no serious side effects of NAD supplementation. Our knowledge of urolithin A is more limited, but as I mentioned, clinical trials with urolithin A have been effective in muscular disease, and now we need to look at Alzheimer’s disease.

“If we are going to eat something in the future to reduce the risk of Alzheimer’s, which we talk a lot about, we have to make sure there are no significant side effects [3].”

The implications of these findings extend beyond individual health, touching on the global challenge posed by dementia and Alzheimer’s. According to the World Health Organization, approximately 50 million people worldwide suffer from dementia, with nearly 10 million new cases emerging each year [4]. Alzheimer’s disease accounts for 60-70% of these cases, underscoring the critical need for innovative approaches to prevention and treatment.

[1] https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13847
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821002/
[3] https://news.ku.dk/all_news/2024/05/naturally-occurring-substance-in-pomegranates-can-improve-treatment-of-alzheimers-disease/
[4] https://www.who.int/news-room/fact-sheets/detail/dementia