Urolithin A: Benefits and Side Effects
Let's take a look at urolithin A, a natural metabolite produced by gut bacteria breaking down polyphenols in food.
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[What is urolithin A?]
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Urolithin A is not found in food; however, their precursors are polyphenols. Polyphenols are abundant in many fruits and vegetables. When consumed, some polyphenols are absorbed directly by the small intestine, while others are degraded by digestive bacteria into other compounds, some of which are beneficial. For example, certain species of gut bacteria break down ellagic acid and ellagitannins into urolithins, which may improve human health. Although urolithin A as a class is still under investigation, urolithin A and urolithin B are well known in humans. Here, we focus on two human studies that measured plasma or urine levels of urolithin A, the most widely studied urolithin to date.
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[What is the use of urolithin A?]
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A variety of tissues contain urolithin A, so it has been suggested that it affects multiple organ systems in worms, cells, mice and humans. In particular, there is significant cellular, animal and human data to support the idea that urolithin A increases mitochondrial autophagy. Mitochondrial autophagy is the process by which damaged mitochondria are removed from cells, thereby promoting the growth and maintenance of healthy mitochondria. Mitochondrial dysfunction is one of the hallmarks of aging. Unfortunately, aging leads to a decrease in the cell's mitochondrial autophagy capacity, which in turn leads to the accumulation of damaged mitochondria. As a result, reactive oxygen species can accumulate and promote inflammation. Additionally, they may convert fewer dietary precursors to urolithin A as they age.
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[Dietary sources of urolithin A].
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So far, studies have found pomegranates, strawberries, blackberries, camu camu, walnuts, chestnuts, pistachios, pecans, brewed teas, and oak-aged wines and spirits to contain ellagic acid and/or ellagitannins.
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[The potential of urolithin A to improve mitochondrial autophagy].
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A 2016 study showed that urolithin A improved muscle function in aged mice and extended the lifespan of worms. These promising results prompted the same research team to conduct human studies. More research on urolithin supplementation is needed to determine if they are beneficial for those who do not consume enough ellagic acid and ellagitannins. There are also concerns about the low dietary yield of urolithin A, depending on health status, gut health, and age.
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[Availability of Urolithin A in food compared to supplements].
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Urolithin A is available in pill and powder form and is marketed as a supplement that may reduce age-related cellular decline by improving mitochondrial health.Amazentis funded the first Phase 1 clinical trial of a pure urolithin A supplement in 100 sedentary older adults. Papers published prior to the trial demonstrated the safety and efficacy of urolithin A and showed benefits for mitochondrial health. Participants in this recently published clinical trial were divided into three groups based on their circulating urolithin A glucuronide levels and were asked to avoid dietary supplements that could affect muscle or mitochondrial function. Participants were asked to take either 8 ounces of 100% pomegranate or 500 mg of urolithin A supplements in two divided doses. The study examined differences in pomegranate juice compared to supplements that produce urolithin A in the gut. A stool sample was taken during screening, and dried blood and plasma samples were taken before participants consumed either pomegranate juice or the supplement. Additional samples were then collected at 6 hours and again at 12 hours after ingestion.
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At the start of the study, only 12 per cent of participants had detectable urolithin A in their blood.The results showed that 27 per cent of participants had poor conversion of pomegranate juice to urolithin A. The results showed that 27 per cent of the participants had poor conversion of pomegranate juice to urolithin A. In addition, 33 per cent of participants were unable to convert pomegranate juice into urolithin A. The study also showed that the plasma urolithin A level in the supplement group was six times higher than that of the pomegranate group. The researchers' microbiome results showed that the composition of gut bacteria differed between the non-urilithin A-producing and low urilithin A-producing groups. The authors did note that there were two specific bacterial types in the high-producing urolithin A group. However, no differences were observed between the low-producing urolithin A and high-producing urolithin A groups. Although other researchers have suggested possible candidates for analysing human faecal samples, it is not yet clear which bacteria in the gut produce urolithin A. Because of the promising initial results of the human studies, two additional clinical trials of urolithin A are underway: ENDURO and NOURISH. more research is needed to understand the difference between people who produce enough urolithin from food and those who do not. microbiome differences between people who produce enough urolithin from food and those who do not.
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[Human Study of the Mediterranean Diet]
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In 2020, an eight-week human study examined the effects of Mediterranean and Western diets on the gut microbiome.82 overweight or obese men and women were asked to eat a Mediterranean diet or maintain a normal diet. The Mediterranean diet was matched to the participants' current calorie and bulk nutrient intake to improve compliance. Participants recorded their daily diet and physical activity, and researchers assessed their adherence every fortnight. The study showed that the Mediterranean group had higher urinary levels of urolithin A glucuronide compared to the normal diet group. They also showed that increased production of urolithin A, including types A, B, and C, and its glucuronides, was associated with lower high-sensitivity C-reactive protein, triglycerides, urinary carnitine, body fat mass, body weight, and BMI. The authors attributed the increase in urocalcitonin A in the Mediterranean group to walnut intake, as there was no increase in berry or pomegranate intake. In addition, the Mediterranean diet group had significantly lower LDL and HDL cholesterol at 4 weeks. The results for the microbiology group were also interesting. The authors integrated three different metagenomics databases when comparing the two groups, and they noted different microbiome diversity between the two diets. These results are not surprising, as other studies have demonstrated that dietary changes can alter microbiome diversity.
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[Microbiome]
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Some people's gut flora may not break down food sources into urolithin A, or may only do so at low levels. This study suggests that urinary levels of urolithin are associated with specific families of gut bacteria. More research is needed to elucidate the conversion of ellagic acid and ellagitannins from dietary precursors into urolithin A.
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[Urolithin A Side Effects]
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To date, no side effects have been observed, although studies suggest that urolithin A may promote mitochondrial health. More human studies are needed to fully explain its role in aging characteristics.
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[Conclusion]
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The first study concluded that taking pure urolithin A supplements improved plasma urolithin levels better than pomegranate juice. The second study suggests that specific dietary patterns, such as a Mediterranean-like diet compared to a Western diet, increase urolithin A. Considering the importance of maintaining mitochondrial health as we age, urolithin A may continue to garner more evidence as gero-protective. If you don't regularly consume urolithin A in your food, you may want to consider focusing on this research topic as more human data is published.
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