Can Urolithin A protect against aging?
Research suggests that Urolithin A may promote mitochondrial health
Mimi Lalaa
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What are urolithins?
Unlike their precursor, polyphenols, urolithins are not found in food. Polyphenols are abundant in many fruits and vegetables. After consumption, some of the polyphenols are absorbed directly by the small intestine, while others are broken down by the digestive bacteria into other compounds, some of which are beneficial. For example, certain types of intestinal bacteria break down ellagic acid and ellagitannins to urolithins, which can improve human health [1].
While urolithins are still being investigated as a class, 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 studied urolithin to date.
What is the purpose of Urolithin A?
Since urolithin A is found in various tissues, it is said to have an effect on several organ systems in worms, cells, mice and humans. In particular, there is significant cell, animal, and human data that support the idea that urolithin A promotes mitophagy. Mitophagy is a process by which damaged mitochondria are removed from the cell, which promotes the growth and maintenance of healthy mitochondria.
Mitochondrial dysfunction is one of the hallmarks of aging. Unfortunately, aging causes mitophagy in cells to decrease [2], which in turn causes damaged mitochondria to build up. As a result, reactive oxygen species can build up and promote inflammation. In addition, fewer dietary precursors may be converted into urolithin A with increasing age [3].
Dietary sources of Urolithin A
So far, research has found that pomegranates, strawberries, blackberries, walnuts, chestnuts, pistachios, pecans, brewed tea, and wines and spirits aged in oak barrels contain ellagic acid and/or ellagitannins [4, 5].
The potential of Urolithin A to improve mitophagy
A study from 2016 showed that urolithin A improves muscle function in aged mice and extends the lifespan of worms [6]. These promising results led to the same research group carrying out studies in humans. More studies on supplemental urolithins are needed to determine whether they are beneficial for people who do not consume enough ellagic acid and ellagitannins. There are also concerns about low dietary production of urolithin A, which is dependent on health status, intestinal health, and age [7].
Availability of Urolithin A in foods compared to dietary supplements
Urolithin A, available in pill and powder form, is marketed as a dietary supplement that can reduce age-related cell decline by improving mitochondrial health. The first phase 1 clinical trial using a pure urolithin A supplement in 100 inactive older adults was financed by Amazentis [8]. Work published prior to this study demonstrated the safety and effectiveness of urolithin A and demonstrated 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 asked to refrain from taking supplements that could impair muscle or mitochondrial function [8].
Participants were asked to consume either 100% pomegranate or 500 milligrams of a urolithin A supplement at two separate time intervals. This study examined the extent to which pomegranate juice promotes the formation of urolithin A in the intestine compared to the dietary supplement. A stool sample was collected during the screening phase, and dried blood and plasma samples were collected before participants consumed the pomegranate juice or supplement. Further samples were then taken 6 and 12 hours after ingestion.
At the start of the study, only 12% of participants had detectable urolithin A in their blood. The results showed that 27% of participants were unable to convert pomegranate juice into urolithin A and 33% were unable to convert pomegranate juice into urolithin A. The study also showed that plasma urolithin A levels were six times higher in the supplement group than in the pomegranate group.
The researchers' microbiome results showed that the composition of intestinal bacteria differed between the group that did not produce urolithin A and the group that produced little urolithin A. The authors found that two specific types of bacteria abounded in the group with high urolithin A production. However, no differences were found between the group with low urolithin A production and the group with high urolithin A production. Although other researchers have suggested possible candidates when analyzing human stool samples [9, 10], it is not yet clear which bacteria in the intestine produce urolithin A [7].
Based on the first promising results in the human study, two more clinical trials with urolithin A are currently being carried out: ENDURO and NOURISH.
The differences between the microbiome of people who produce enough urolithin from food and those who do not produce enough urolithin from food need further research.
Human study on the Mediterranean diet
In 2020, an eight-week human study examined the effects of Mediterranean and Western diets on the intestinal microbiome [11]. Eighty-two men and women who were overweight or obese were told to follow a Mediterranean diet or maintain their normal diet. The Mediterranean diet was tailored to the participants' current calorie and macronutrient intake to increase acceptance. The participants documented their daily food consumption and physical activity and were checked for compliance by study staff every two weeks.
The study found higher levels of urolithin A glucuronides in the urine of the Mediterranean group compared to the group with a normal diet. It was also found that increased production of urolithin A in urine, including types A, B, C and their glucuronides, was associated with a decrease in highly sensitive C-reactive protein, triglycerides, carnitine in urine, body fat mass, body weight and BMI. The authors attribute the increase in urolithin A in the Mediterranean group to the consumption of walnuts, as the consumption of berries and pomegranates did not increase. In addition, the Mediterranean-diet group had significant decreases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol after four weeks.
The results on the microbiome were also astonishing. When comparing the two groups, the authors used three different meta-romics databases [12] and found that the diversity of the microbiome differed between the two types of diet. These findings should come as no surprise, as other studies have proven that dietary changes can alter microbiome diversity.
Information about the microbiome
The intestinal flora of some people may not break down food sources to urolithin A or only in small amounts. This study suggests that urolithin levels in urine correlate with specific families of intestinal bacteria. Further research is needed to clarify the conversion of ellagic acid and ellagitannins into urolithin A from dietary precursors.
Side Effects of Urolithin A
No side effects have been observed to date, although research suggests that urolithin A may promote mitochondrial health. More human studies are needed to fully explain the role of urolithin A in the characteristics of aging.
Conclusion
The first study concluded that taking a pure urolithin A supplement could increase plasma levels of urolithin A better than pomegranate juice. The second study showed that a specific diet similar to the Mediterranean diet increases urolithin A levels in urine compared to a Western diet.
Given the importance of maintaining mitochondrial health in old age, urolithin A could become increasingly important as a gerontological protector. If you don't frequently consume urolithin A with food, you should pursue this research topic as more data about people is published.
Disclaimer
This article is just a very brief summary. It is not intended as a complete guide and is based on the interpretation of research data, which is naturally speculative. This article is not a substitute for consulting with your doctor about which supplements are or are not right for you.
The original article was published on Lifepan.io and republished here with their consent.
References
- [1] González-Sarrías, A., García-Villalba, R., Núñez-Sánchez, M.A., Tomé-Carneiro, J., Zafrilla, P., Mulero, J.,... Espín, J.C. (2015). Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts. Journal of Functional Foods, 19th https://doi.org/10.1016/j.jff.2015.09.019
- [2] Sakellariou, G.K., Pearson, T., Lightfoot, A.P., Nye, G.A., Wells, N., Giakoumaki, I.I.,... McArdle, A. (2016). Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy. Scientific Reports, 6 (1), 33944. https://doi.org/10.1038/srep33944
- [3] Cortés-Martín, A., Garcia-Villalba, R., González-Sarrías, A., Romo-Vaquero, M., Loria-Kohen, V., Ramírez-De-Molina, A.,... Espín, J.C. (2018). The gut microbiota urolithin metabolitypes revisited: the human metabolism of ellagic acid is mainly determined by aging. Food and Function, 9 (8). https://doi.org/10.1039/c8fo00956b
- [4] Arapitsas, P. (2012). Hydrolyzable tannin analysis in food. Food Chemistry, 135 (3), 1708—1717. https://doi.org/10.1016/j.foodchem.2012.05.096
- [5] Bakkalbasi, E., Mentes, O., & Artik, N. (2008). Food ellagitannins—Occurrence, Effects of Processing and Storage. Critical Reviews in Food Science and Nutrition, 49 (3), 283-298. https://doi.org/10.1080/10408390802064404
- [6] Ryu, D., Mouchiroud, L., Andreux, P.A., Katsyuba, E., Moullan, N., Nicolet-Dit-Felix, A.A.,... Auwerx, J. (2016). Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, 22 (8). https://doi.org/10.1038/nm.4132
- [7] Cortés-Martín, Adrián, Selma, M.V., Tomás-Barberán, F.A., González-Sarrías, A., & Espín, J.C. (2020). Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes. Molecular Nutrition and Food Research, Vol. 64. https://doi.org/10.1002/mnfr.201900952
- [8] Singh, Anurag, D'Amico, D., Andreux, P.A., Dunngalvin, G., Kern, T., Blanco-Bose, W.,... Rinsch, C. (2021). Direct supplementation with urolithin A overcomes limitations of dietary exposure and good microbiome variability in healthy adults to achieve consistent levels across the population. European Journal of Clinical Nutrition. https://doi.org/10.1038/s41430-021-00950-1
- [9] Selma, M.V., Beltrán, D., García-Villalba, R., Espín, J.C., & Tomás-Barberán, F.A. (2014). Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species. Food and Function, 5 (8). https://doi.org/10.1039/c4fo00092g
- [10] Selma, M.V., Tomás-Barberán, F.A., Beltrán, D., García-Villalba, R., & Espín, J.C. (2014). Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut. International Journal of Systematic and Evolutionary Microbiology, 64 (PART 7). https://doi.org/10.1099/ijs.0.055095-0
- [11] Meslier, V., Laiola, M., Roager, H.M., De Filippis, F., Roume, H., Quinquis, B.,... Ercolini, D. (2020). Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Well, 69 (7). https://doi.org/10.1136/gutjnl-2019-320438
- [12] Singh, Amrit, Shannon, C.P., Gautier, B., Rohart, F., Vacher, M., Tebbutt, S.J., & Cao, K.A.L. (2019). DIABLO: An integrative approach for identifying key molecular drivers from multi-omics assays. Bioinformatics, 35 (17). https://doi.org/10.1093/bioinformatics/bty1054
Publiziert
19.3.2024
Kategorie
Lifestyle
Scientific Terms
Polyphenol
Polyphenols are secondary plant substances and are found exclusively in plants. They are found in the outer layers of fruit, vegetables and grains.
Mitophagy
From ancient Greek μmítos, German 'thread' and ancient Greek φαγεν phagein, German 'eat'
Mitophagy is a process by which damaged mitochondria are removed from the cell, which promotes the growth and maintenance of healthy mitochondria.
Mitochondrion
Mitochondria are often referred to as the cell's powerhouse and break down nutrients to generate energy in a process called cellular respiration. They contain their own circular genome.
Microbiome
Greek micrós mikrós “small”, Greek βoos bios “life”
All microorganisms and their collective genetic material found in or on the human body or in any other environment.
C-reactive protein (CRP)
“C-reactive protein” (CRP) is the most important blood laboratory value for identifying and monitoring inflammation in the body. CRP is a protein that is produced in the liver. (https://www.gesundheit.gv.at/labor/laborwerte/infektionen-bakterien/crp.html)
Gerontology
from ancient Greek γων Géron, German “old man”, as well as lógos, German “teaching”
Gerontology, also known as aging science, is the science of the process of aging and old age as a phase of life. It investigates aging processes from biological, medical, psychological and social aspects, and looks at the phenomena, problems and resources associated with aging.
What are urolithins?
Unlike their precursor, polyphenols, urolithins are not found in food. Polyphenols are abundant in many fruits and vegetables. After consumption, some of the polyphenols are absorbed directly by the small intestine, while others are broken down by the digestive bacteria into other compounds, some of which are beneficial. For example, certain types of intestinal bacteria break down ellagic acid and ellagitannins to urolithins, which can improve human health [1].
While urolithins are still being investigated as a class, 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 studied urolithin to date.
What is the purpose of Urolithin A?
Since urolithin A is found in various tissues, it is said to have an effect on several organ systems in worms, cells, mice and humans. In particular, there is significant cell, animal, and human data that support the idea that urolithin A promotes mitophagy. Mitophagy is a process by which damaged mitochondria are removed from the cell, which promotes the growth and maintenance of healthy mitochondria.
Mitochondrial dysfunction is one of the hallmarks of aging. Unfortunately, aging causes mitophagy in cells to decrease [2], which in turn causes damaged mitochondria to build up. As a result, reactive oxygen species can build up and promote inflammation. In addition, fewer dietary precursors may be converted into urolithin A with increasing age [3].
Dietary sources of Urolithin A
So far, research has found that pomegranates, strawberries, blackberries, walnuts, chestnuts, pistachios, pecans, brewed tea, and wines and spirits aged in oak barrels contain ellagic acid and/or ellagitannins [4, 5].
The potential of Urolithin A to improve mitophagy
A study from 2016 showed that urolithin A improves muscle function in aged mice and extends the lifespan of worms [6]. These promising results led to the same research group carrying out studies in humans. More studies on supplemental urolithins are needed to determine whether they are beneficial for people who do not consume enough ellagic acid and ellagitannins. There are also concerns about low dietary production of urolithin A, which is dependent on health status, intestinal health, and age [7].
Availability of Urolithin A in foods compared to dietary supplements
Urolithin A, available in pill and powder form, is marketed as a dietary supplement that can reduce age-related cell decline by improving mitochondrial health. The first phase 1 clinical trial using a pure urolithin A supplement in 100 inactive older adults was financed by Amazentis [8]. Work published prior to this study demonstrated the safety and effectiveness of urolithin A and demonstrated 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 asked to refrain from taking supplements that could impair muscle or mitochondrial function [8].
Participants were asked to consume either 100% pomegranate or 500 milligrams of a urolithin A supplement at two separate time intervals. This study examined the extent to which pomegranate juice promotes the formation of urolithin A in the intestine compared to the dietary supplement. A stool sample was collected during the screening phase, and dried blood and plasma samples were collected before participants consumed the pomegranate juice or supplement. Further samples were then taken 6 and 12 hours after ingestion.
At the start of the study, only 12% of participants had detectable urolithin A in their blood. The results showed that 27% of participants were unable to convert pomegranate juice into urolithin A and 33% were unable to convert pomegranate juice into urolithin A. The study also showed that plasma urolithin A levels were six times higher in the supplement group than in the pomegranate group.
The researchers' microbiome results showed that the composition of intestinal bacteria differed between the group that did not produce urolithin A and the group that produced little urolithin A. The authors found that two specific types of bacteria abounded in the group with high urolithin A production. However, no differences were found between the group with low urolithin A production and the group with high urolithin A production. Although other researchers have suggested possible candidates when analyzing human stool samples [9, 10], it is not yet clear which bacteria in the intestine produce urolithin A [7].
Based on the first promising results in the human study, two more clinical trials with urolithin A are currently being carried out: ENDURO and NOURISH.
The differences between the microbiome of people who produce enough urolithin from food and those who do not produce enough urolithin from food need further research.
Human study on the Mediterranean diet
In 2020, an eight-week human study examined the effects of Mediterranean and Western diets on the intestinal microbiome [11]. Eighty-two men and women who were overweight or obese were told to follow a Mediterranean diet or maintain their normal diet. The Mediterranean diet was tailored to the participants' current calorie and macronutrient intake to increase acceptance. The participants documented their daily food consumption and physical activity and were checked for compliance by study staff every two weeks.
The study found higher levels of urolithin A glucuronides in the urine of the Mediterranean group compared to the group with a normal diet. It was also found that increased production of urolithin A in urine, including types A, B, C and their glucuronides, was associated with a decrease in highly sensitive C-reactive protein, triglycerides, carnitine in urine, body fat mass, body weight and BMI. The authors attribute the increase in urolithin A in the Mediterranean group to the consumption of walnuts, as the consumption of berries and pomegranates did not increase. In addition, the Mediterranean-diet group had significant decreases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol after four weeks.
The results on the microbiome were also astonishing. When comparing the two groups, the authors used three different meta-romics databases [12] and found that the diversity of the microbiome differed between the two types of diet. These findings should come as no surprise, as other studies have proven that dietary changes can alter microbiome diversity.
Information about the microbiome
The intestinal flora of some people may not break down food sources to urolithin A or only in small amounts. This study suggests that urolithin levels in urine correlate with specific families of intestinal bacteria. Further research is needed to clarify the conversion of ellagic acid and ellagitannins into urolithin A from dietary precursors.
Side Effects of Urolithin A
No side effects have been observed to date, although research suggests that urolithin A may promote mitochondrial health. More human studies are needed to fully explain the role of urolithin A in the characteristics of aging.
Conclusion
The first study concluded that taking a pure urolithin A supplement could increase plasma levels of urolithin A better than pomegranate juice. The second study showed that a specific diet similar to the Mediterranean diet increases urolithin A levels in urine compared to a Western diet.
Given the importance of maintaining mitochondrial health in old age, urolithin A could become increasingly important as a gerontological protector. If you don't frequently consume urolithin A with food, you should pursue this research topic as more data about people is published.
Disclaimer
This article is just a very brief summary. It is not intended as a complete guide and is based on the interpretation of research data, which is naturally speculative. This article is not a substitute for consulting with your doctor about which supplements are or are not right for you.
The original article was published on Lifepan.io and republished here with their consent.
Referenzen
- [1] González-Sarrías, A., García-Villalba, R., Núñez-Sánchez, M.A., Tomé-Carneiro, J., Zafrilla, P., Mulero, J.,... Espín, J.C. (2015). Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts. Journal of Functional Foods, 19th https://doi.org/10.1016/j.jff.2015.09.019
- [2] Sakellariou, G.K., Pearson, T., Lightfoot, A.P., Nye, G.A., Wells, N., Giakoumaki, I.I.,... McArdle, A. (2016). Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy. Scientific Reports, 6 (1), 33944. https://doi.org/10.1038/srep33944
- [3] Cortés-Martín, A., Garcia-Villalba, R., González-Sarrías, A., Romo-Vaquero, M., Loria-Kohen, V., Ramírez-De-Molina, A.,... Espín, J.C. (2018). The gut microbiota urolithin metabolitypes revisited: the human metabolism of ellagic acid is mainly determined by aging. Food and Function, 9 (8). https://doi.org/10.1039/c8fo00956b
- [4] Arapitsas, P. (2012). Hydrolyzable tannin analysis in food. Food Chemistry, 135 (3), 1708—1717. https://doi.org/10.1016/j.foodchem.2012.05.096
- [5] Bakkalbasi, E., Mentes, O., & Artik, N. (2008). Food ellagitannins—Occurrence, Effects of Processing and Storage. Critical Reviews in Food Science and Nutrition, 49 (3), 283-298. https://doi.org/10.1080/10408390802064404
- [6] Ryu, D., Mouchiroud, L., Andreux, P.A., Katsyuba, E., Moullan, N., Nicolet-Dit-Felix, A.A.,... Auwerx, J. (2016). Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, 22 (8). https://doi.org/10.1038/nm.4132
- [7] Cortés-Martín, Adrián, Selma, M.V., Tomás-Barberán, F.A., González-Sarrías, A., & Espín, J.C. (2020). Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes. Molecular Nutrition and Food Research, Vol. 64. https://doi.org/10.1002/mnfr.201900952
- [8] Singh, Anurag, D'Amico, D., Andreux, P.A., Dunngalvin, G., Kern, T., Blanco-Bose, W.,... Rinsch, C. (2021). Direct supplementation with urolithin A overcomes limitations of dietary exposure and good microbiome variability in healthy adults to achieve consistent levels across the population. European Journal of Clinical Nutrition. https://doi.org/10.1038/s41430-021-00950-1
- [9] Selma, M.V., Beltrán, D., García-Villalba, R., Espín, J.C., & Tomás-Barberán, F.A. (2014). Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species. Food and Function, 5 (8). https://doi.org/10.1039/c4fo00092g
- [10] Selma, M.V., Tomás-Barberán, F.A., Beltrán, D., García-Villalba, R., & Espín, J.C. (2014). Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut. International Journal of Systematic and Evolutionary Microbiology, 64 (PART 7). https://doi.org/10.1099/ijs.0.055095-0
- [11] Meslier, V., Laiola, M., Roager, H.M., De Filippis, F., Roume, H., Quinquis, B.,... Ercolini, D. (2020). Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Well, 69 (7). https://doi.org/10.1136/gutjnl-2019-320438
- [12] Singh, Amrit, Shannon, C.P., Gautier, B., Rohart, F., Vacher, M., Tebbutt, S.J., & Cao, K.A.L. (2019). DIABLO: An integrative approach for identifying key molecular drivers from multi-omics assays. Bioinformatics, 35 (17). https://doi.org/10.1093/bioinformatics/bty1054
Publiziert
19.3.2024
Kategorie
Lifestyle
Wissenschaftliche Begriffe
Polyphenol
Polyphenols are secondary plant substances and are found exclusively in plants. They are found in the outer layers of fruit, vegetables and grains.
Mitophagy
From ancient Greek μmítos, German 'thread' and ancient Greek φαγεν phagein, German 'eat'
Mitophagy is a process by which damaged mitochondria are removed from the cell, which promotes the growth and maintenance of healthy mitochondria.
Mitochondrion
Mitochondria are often referred to as the cell's powerhouse and break down nutrients to generate energy in a process called cellular respiration. They contain their own circular genome.
Microbiome
Greek micrós mikrós “small”, Greek βoos bios “life”
All microorganisms and their collective genetic material found in or on the human body or in any other environment.
C-reactive protein (CRP)
“C-reactive protein” (CRP) is the most important blood laboratory value for identifying and monitoring inflammation in the body. CRP is a protein that is produced in the liver. (https://www.gesundheit.gv.at/labor/laborwerte/infektionen-bakterien/crp.html)
Gerontology
from ancient Greek γων Géron, German “old man”, as well as lógos, German “teaching”
Gerontology, also known as aging science, is the science of the process of aging and old age as a phase of life. It investigates aging processes from biological, medical, psychological and social aspects, and looks at the phenomena, problems and resources associated with aging.
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