57 replies to this topic

[ImmInst]

Urolithin A makes worms live longer and mice run further, and may be the first chemical discovered that can improve the quality of ageing muscle

View the full article

[maxwatt]

I am surprised this has not received more attention.  If you dig down to the underlying papers, the work comes out of Auwerx' lab in Europe.  He worked with David Sinclair and Guarante on some of the early Resveratrol papers and has been pursuing other anti-aging molecules since then.

 

What is significant her is that Urolithin A eliminates faulty mitochondria from muscle cells, and is potential a cure for mitochondrial myopathy, a major wasting disease of aging.  It also acted very quickly in aged mice, and had them running on a treadmill with the youngsters in a matter of days.  Human trial are underway.

 

First problem, there is no ready source of Urolithin A.  It is produced in the mammalian gut by metabolizing ellagatonins (e.g., ellagic acid) in pomegranates, walnuts or strawberries, but only if one is lucky to have a microbiome with the right bacteria.  Many people have none at all.  This might account for the inconsistent results in trials of pomegranate.  The bacteria that convert ellagic acid to urolithin A are species of Gordonibacter speciaes, and perhaps others. 

[lemonhead]

Chestnuts?

http://phenol-explor.../polyphenol/417

[aconita]

Ellagic acid comes quite cheap, it would be interesting to know if there is a simple way to check if one's gut is able to convert it into urolithin or not, once you know your gut can is easy to supplement just ellagic acid, if you can't you know is better not to waste money on it.

 

Unfortunately to simply check for the right bacteria presence doesn't seem to be so straightforward, maybe a urolithin blood test after an ellagic acid load?

 

One of the sources of polyphenols is pomegranate extract. During digestion, various constituants of the pomegranate extract are converted by the gut flora into urolithin C, which is then transformed into urolithin D, A, and, finally, into urolithin B.

Consequently, small amounts of urolithin B can be found in the blood of human patients fed with pomegranate extract; urolithin B amount in the blood is much lower than urolithin A amount.

[0005] Beside being of lower abundance in the blood, at least in comparison with urolithin A (Gonzalez-Barrio et al., 2012), the antioxidant and anti-inflammatory properties of urolithin B are much weaker than the other related compounds, such as urolithins A, C and D, as well as a whole polyphenol extract. [0006] Beside the antioxidant action, ellagitannin-derived compounds such as urolithin A or B, have been shown to have direct anti cancer activity, at least on breast and on prostate cancer cell lines, probably due to inhibition of testosterone-induced cell proliferation of MCF-7 cells and/or on inhibition of aromatase activity (Adams et al., 2010).

 

 https://www.google.c...4111580A1?cl=en

[aconita]

Urolithin B seems even better than A or at least worth consideration:

 

PubMed:

  Gastrointestinal stability of urolithins: an in vitro approach. PubMed: Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells. PubMed: Preparative isolation and purification of urolithins from the intestinal metabolites of pomegranate ellagitannins by high-speed counter-current chromatography. PubMed: Pilot walnut intervention study of urolithin bioavailability in human volunteers. PubMed: Pomegranate phenolics inhibit formation of advanced glycation endproducts by scavenging reactive carbonyl species. PubMed: Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells. PubMed: Influence of gut microbiota-derived ellagitannins' metabolites urolithins on pro-inflammatory activities of human neutrophils. PubMed: Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. PubMed: Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials. PubMed: Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species. PubMed: Urolithins display both antioxidant and pro-oxidant activities depending on assay system and conditions. PubMed: Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. PubMed: In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells. PubMed: Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells. PubMed: Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and associated molecular markers in human colon fibroblasts. PubMed: Metabolism of oak leaf ellagitannins and urolithin production in beef cattle. PubMed: Strawberry processing does not affect the production and urinary excretion of urolithins, ellagic acid metabolites, in humans. PubMed: Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy. PubMed: Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro. PubMed: Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cells. PubMed: Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice. PubMed: A concise synthesis of glucuronide metabolites of urolithin-B, resveratrol, and hydroxytyrosol. PubMed: Dissimilar in vitro and in vivo effects of ellagic acid and its microbiota-derived metabolites, urolithins, on the cytochrome P450 1A1. PubMed: Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins. PubMed: Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans. PubMed: Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers. PubMed: Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. PubMed: Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. PubMed: Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability.

 

[aconita]

It seems that after all chances to be able to convert ellagic acid into urolithins are quite good :

 

Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three urolithin-producing groups. "Phenotype A" produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. "Phenotype B" produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10-50%). "Phenotype 0" (5-25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers' health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.

 

http://www.pubfacts....ithin-phenotype

 

Urolithin B seems to go for about 120$/g  but dosage is mysterious...

[alc]

 

What is significant her is that Urolithin A eliminates faulty mitochondria from muscle cells, and is potential a cure for mitochondrial myopathy, a major wasting disease of aging.  It also acted very quickly in aged mice, and had them running on a treadmill with the youngsters in a matter of days.  Human trial are underway.

 

 

This connect the dots to recent work by Dr João Passos at Newcastle University, that was discussed:

 

"Mitochondria shown to trigger cell ageing"

 

http://www.ncl.ac.uk...ggercellageing/

 

So might be an indication that will cast some good results.

 

Prof. Johan Auwerx is also involved in Mitobridge

 

http://www.mitobridge.com/about/us/
 

[maxwatt]

I would not use Urolithin B.  There are three types of human biome: those that produce no urolithin from ellagic acid, those that produce urolithin A and those that produce Urolithin B.  Those whose gut microbes produce Urolithin B tend toward metabolic syndrome and cancer.

 

http://www.pubfacts....ithin-phenotype

 

 

 

 

It seems that after all chances to be able to convert ellagic acid into urolithins are quite good :

 

Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three urolithin-producing groups. "Phenotype A" produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. "Phenotype B" produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10-50%). "Phenotype 0" (5-25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers' health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.

 

http://www.pubfacts....ithin-phenotype

 

Urolithin B seems to go for about 120$/g  but dosage is mysterious...

 

[maxwatt]

 

 

What is significant her is that Urolithin A eliminates faulty mitochondria from muscle cells, and is potential a cure for mitochondrial myopathy, a major wasting disease of aging.  It also acted very quickly in aged mice, and had them running on a treadmill with the youngsters in a matter of days.  Human trial are underway.

 

This connect the dots to recent work by Dr João Passos at Newcastle University, that was discussed:  the usual story told about the development of Eukarotes is that one somehow ingested a bacteria, and instead of eating it, kept it alive as an energy source.  But in light of the papers cited below, maybe it was the other way around: a bacteria parasitized a Eurokyrote, and used it to provide a more stable environment insead of eating and killing it.  And death occurs when the bacteria - now become mitichondria - revert to type and run amok, destroying their host. 

 

"Mitochondria shown to trigger cell ageing"

 

http://www.ncl.ac.uk...ggercellageing/

 

So might be an indication that will cast some good results.

 

Prof. Johan Auwerx is also involved in Mitobridge

 

http://www.mitobridge.com/about/us/
 

 

 

This is signifucant, and I expect rapid progress in this area.  But it got me to thinking:

 

[aconita]

Those whose gut microbes produce Urolithin B tend toward metabolic syndrome and cancer.

 

Interesting...

 

It has to be seen if the responsible is urolithin B or the particular kind of microbioma, I guess, since urolithin B itself seems quite beneficial.

 

Definitely needs more research.

[pone11]

Ellagic acid comes quite cheap, it would be interesting to know if there is a simple way to check if one's gut is able to convert it into urolithin or not, once you know your gut can is easy to supplement just ellagic acid, if you can't you know is better not to waste money on it.

 

Unfortunately to simply check for the right bacteria presence doesn't seem to be so straightforward, maybe a urolithin blood test after an ellagic acid load?

 

 

Would it be cheaper to just feed the bacteria pomegranate and red raspberry rather than buying ellagic acid directly?    

 

I worry about supplement manufacturers gaming their supplements by benchmarking to one chemical like ellagic acid, but then leaving out all of the other phytochemicals, or distorting the ratios:

https://www.ncbi.nlm...pubmed/16579739

 

The net effect of that might be that you might not get the same kind of conversion to urolithin A or B from a given supplement that you could from the pure juice.

 

How do you validate the relative composition of other phytochemicals in a given supplement?

[aconita]

Good point!

 

I am not very comfortable too with extracts and isolate substances, it has to be proven that just ellagic acid in isolation leads to the desired outcomes which maybe in this specific case is but can't be given for granted.

 

The posted link states what I can only agree with but the goal has its importance too, if it is a matter of just increasing urolithin or if it is the whole spectrum of health advantages that pomegranate has to offer.

[maxwatt]

Ellqagic acid supplements vary in concentration; the most common on the American market seems to be a 40% extract from pomegranate.  The other sixty percent contains other ellagatanins which can also be converted to urolithins, as well as other substances from whole pomegranate fruit.

As far as supplementing, an unknown percentage of people have the gut biome to that converts elagic acid to urolithing A.  Supplementing with pomegranate extract seems not an unreasonable hail mary pass or shotgun approach.  A recent study   found pterostilbene shifted gut bacteria toward those that produce urolithin A.  I surmise resveratrol has the same effect.  It might not be unreasonable to supplement with ellagic acid and  pterostilbene.                     

[Oakman]

Ellqagic acid supplements vary in concentration; the most common on the American market seems to be a 40% extract from pomegranate.  The other sixty percent contains other ellagatanins which can also be converted to urolithins, as well as other substances from whole pomegranate fruit.

As far as supplementing, an unknown percentage of people have the gut biome to that converts elagic acid to urolithing A.  Supplementing with pomegranate extract seems not an unreasonable hail mary pass or shotgun approach.  A recent study   found pterostilbene shifted gut bacteria toward those that produce urolithin A.  I surmise resveratrol has the same effect.  It might not be unreasonable to supplement with ellagic acid and  pterostilbene.                     

 

I'm conveniently doing that supplementation, in a haphazard fashion. I already takepterostilbene with NR, also Resveratrol, and pomegranate juice... Having just become aware of urolithins' benefits, I've ordered Robuvit > http://www.robuvit.c...ure_161_WEB.pdf  which states, among other things...

 

"Robuvit® metabolites urolithins increase muscle function by rejuvenating mitochondria through accelerated replacement of aged mitochondria by newly synthesised fully operative mitochondria"

 

The supplement is, Robuvit French Oak Wine Extract,  http://www.swansonvi...-mg-30-veg-caps. Given my gut cooperates, I should be producing urolithins A, B, & C shortly.

 

I'm wondering if I should stop NR while these urolithins induce mitophagy, then resume? Chromadex says NR "Promotes mitochondrial function", but whether that includes or precludes mitochondrial mitophagy, I'm not sure.

[maxwatt]

Hmmmm.  "Mitocondrial function" is rather ambiguous.  NR has been shown to increase the NAD+:NAD ration in mitochondria, and things that do that are pro-longevity.  The point of autophagy is to kill off non functioning mitochondria, by killing the cells that carry them, so they may be replaced by healthy, younger-function mitochondria.  IF the mitochondria are working better due to NR, does this spare them destruction by Urolithin A?  I suspect that cells with a marginal load of unhealthy mitochondria might be spared if NR improves their function.  I think your concern is certainly valid.

[APBT]

The quote below is from the full text (which is too large for me to post - exceeding 2MB):  http://www.nature.co...ll/nm.4132.html

 

 

 

 

 

DISCUSSION
Optimal mitochondrial activity is essential for the production of cellular energy and the metabolic flexibility of an organism. During aging, there is a progressive decline in mitochondrial function that correlates with the load of mtDNA mutations39. Another hallmark of aging is the gradual decay of protein homeostasis, or proteostasis, notably through the decrease in autophagy40. Mitophagy, a specific form of autophagy by which cells eliminate their damaged mitochondria34, is at the crossroad between these two key hallmarks of aging, making it a compelling therapeutic target for managing the specific health complications associated with aging. Present therapeutic approaches targeting improved mitochondrial function have been designed to stimulate either mitochondrial biogenesis or the respiratory chain, whereas no specific and safe inducer of mitophagy has been described to date41. We found that UA potently induced mitophagy in C. elegans, mammalian cells and rodents, resulting in an overall improvement of multiple cellular and organismal phenotypes (Supplementary Fig. 8a).
In young worms and mammalian cells, the short-term administration of UA decreased the mitochondrial content while maintaining the maximal respiratory capacity. This confirmed that, despite the reduction in the mitochondrial pool following UA treatment, the remaining mitochondria are robust and able to sustain energy needs, potentially by shifting respiration from CI to CII as seen in mammalian cells (Supplementary Fig. 8bd). Notably, a similar shift in respiration from CI to CII during the induction of mitophagy has also been observed in the heart during the perinatal period in mice42. Following long-term exposure, worms responded to the UA-mediated mitophagy by inducing mitochondrial biogenesis. In fact, it has been shown that a coordinated regulation of mitophagy and mitochondrial biogenesis in worms occurs through the skn-1 transcription factor25. This induction of mitophagy in worms by UA led to an improvement of respiratory capacity, mobility and pharyngeal pumping. Our data furthermore suggest that the induction of mitophagy early in life may lead to an increase in mitochondrial content later in life.
Long-term oral administration of UA to rodents also induced mitophagy in the muscle of both young and old animals. This resulted in an enhanced exercise capacity in young rats, whereas UA administration in a NCD or HFD in aged mice, by prevention and intervention modalities, both enhanced muscle strength and robustly augmented running endurance without increasing lean muscle mass. This supports the hypothesis that UA improves muscle cell quality rather than quantity. It also indicates that UA�s effect on muscle function is independent of the diet composition. Furthermore, these rodent studies highlight that UA improves muscle function throughout the different stages of life after a relatively short-term intervention. Notably, the in vivo results were obtained after administration of UA at a dose of 50 mg/kg/d in mice, which is equivalent to 4 mg/kg/d in humans43 and is within standard human dosing regimens employed for both nutrition and pharmaceutical active ingredients.
From a mechanistic angle, it is interesting to point out that UA induces mitophagy subsequently to a reduction in membrane potential. Notably, recent studies with mitochondrial uncouplers, such as niclosamide ethanolamine (NEN) and 2,4-dinitrophenol (DNP), demonstrated beneficial effects of uncoupling specifically on systemic metabolism4446. Although those studies were mainly focused on the liver and did not evaluate the potential contributions of autophagy and mitophagy, there may be some similarities between both the subcellular effects and organismal benefits of UA and these mitochondrial uncouplers that merit further study.
In the clinic, decreased mitophagy in skeletal muscle has been linked to reduced mobility in the elderly. This decline in muscle function observed in the elderly is often part of a larger syndrome, termed frailty, which is an important risk factor for disability, hospitalization and mortality47. A decline in mitophagy in the muscle has been proposed to explain muscle weakness in the elderly, and, in fact, a decrease in mitophagy-related gene expression was reported to correlate with slower walking speed in frail elderly48.
Current therapeutic strategies to prevent or treat muscle weakness and loss have mainly focused on improving muscle mass either through dietary intervention via supplements consisting of blends of proteins and amino acids or by pharmaceutical approaches targeting the myostatin pathway49,50. An investigation by meta-analysis of the clinical effectiveness of protein and amino acid supplementation in the elderly revealed that this approach alone is insufficient to increase body lean mass and muscle strength51. Very recently, a promising antibody drug candidate targeting the myostatin pathway failed in late-stage clinical studies in the muscle-wasting disease sporadic inclusion body myositis52. These observations suggest that modulation of muscle mass alone may not be sufficient to provide a clinically relevant effect on mobility. Improvement of muscle quality by enhancing mitochondrial function, as seen here with UA, instead of or together with muscle quantity may be an alternative strategy for treating impaired muscle functionality. Our data advocate that nutritional supplementation with UA to induce mitophagy holds promise for further development in humans as an innovative approach for improving mitochondrial and muscle function.

 

[Oakman]

Interesting and encouraging results...hopefully inviting further research.

 

Here's a FREE .pdf full text download page (rather than $$)  > https://www.research...tion_in_rodents

[Richard McGee]

First problem, there is no ready source of Urolithin A.  It is produced in the mammalian gut by metabolizing ellagatonins (e.g., ellagic acid) in pomegranates, walnuts or strawberries, but only if one is lucky to have a microbiome with the right bacteria.  Many people have none at all.  This might account for the inconsistent results in trials of pomegranate.  The bacteria that convert ellagic acid to urolithin A are species of Gordonibacter speciaes, and perhaps others. 

 

Is there any available research indicating what specific bacterial strains convert ellagatonins to urolithin A, and whether these strains could be implanted via some kind of probiotic culture?

 

EDIT:

 

I did find this:

 

"...we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins..."

 

Also: 

 

"...The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378^T, was also demonstrated to produce urolithins..."

 

 

Edited by Richard McGee, 20 November 2016 - 08:29 PM.

[albedo]

Ellqagic acid supplements vary in concentration; the most common on the American market seems to be a 40% extract from pomegranate.  The other sixty percent contains other ellagatanins which can also be converted to urolithins, as well as other substances from whole pomegranate fruit.

As far as supplementing, an unknown percentage of people have the gut biome to that converts elagic acid to urolithing A.  Supplementing with pomegranate extract seems not an unreasonable hail mary pass or shotgun approach.  A recent study   found pterostilbene shifted gut bacteria toward those that produce urolithin A.  I surmise resveratrol has the same effect.  It might not be unreasonable to supplement with ellagic acid and  pterostilbene.                     

 

Thank you for your informative post. Linking also with some other threads, check out also the sarcopenia one, e.g. here. A spin off company of EPFL (Amazentis) is pursuing a clinical trial and might put on the market a supplement based on Urolithin A. I understand all this is based on the work of Prof. J. Auwerx's team at EPFL pursuing also actively the nicotinamide riboside and mitochondrial research, see also here.

[timar]

It is worth noting that compared to the seeds and their juice, the concentration of ellagitannins and thus ellagic acid is several orders of magnitude higher in the bitter white pith (actually the mesocarp) of the pomegranate. Hence the pith, once a waste product from juice processing, is now increasingly sought after as raw material for the production of pomegranate ellagitannin supplements (you can actually see how EPFL researchers prepare the pith for extraction in this video).

 

The ellagitannins were found to be the predominant phenolics in all samples investigated, among them punicalagin ranging from 11 to 20g per kilogram dry matter of mesocarp and peel as well as 4-565mg/L in the juices

https://www.ncbi.nlm...pubmed/23140740

 

This certainly explains the mixed results from trials with pomegranate juice, the ellagitannin content of which is quite low and variable, depending mostly on how long the juice remains in contact with the mesocarp during processing and thus extracting some of its polyphenols.

 

It's pomegranate season right now. I'm having half a pomegranate a day and I always eat the pith together with the seeds. I haven't yet calculated the amount of ellagitannins I'll get from that, but I'm sure it is more than what supplements generally provide - and much more delicious!

 

Just a cautionary note: always wear black clothes when you eat pomegranates this way

Edited by timar, 21 November 2016 - 09:35 AM.

[timar]

OK, I have done the math. The most reliable literature I have found shows a content of about 40% total ellagitannins in the dry mass of mesocarp. Assuming a moisture content of 90% and an amount of 50 g edible mesocarp per medium-sized pomegranate (which I have just measured myself weighting only the soft parts on which the seeds sit, not the leathery peel), you end up with about 2 grams of ellagitannins per pomegranate, ~50% of which is in the form of punicalagin (HHDP-gallagyl-hex).

 

To put this into perspective, walnuts, one of the richest known dietary dietary sources of ellagitannins, contain about 1.6 g per 100 g, the often cited strawberries only 100 mg (source). Of course, ellagitannins are not entirely hydrolized to ellagic acid, but that is not even neccessary in order to supply your gut bacteria with a substrate for producing urolithins.

Edited by timar, 21 November 2016 - 01:44 PM.

[APBT]

It seems that after all chances to be able to convert ellagic acid into urolithins are quite good :

 

Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three urolithin-producing groups. "Phenotype A" produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. "Phenotype B" produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10-50%). "Phenotype 0" (5-25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers' health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.

 

 

 

 

FULL TEXT:  

Attached Files

•  Ellagic Acid Metabolism by Human Gut Microbiota - Consistent Observation of Three Urolithin Phenotypes in Intervention Trials, Independent of Food Source, Age, and Health Statu.pdf   478.12KB   797 downloads

[albedo]

 

It seems that after all chances to be able to convert ellagic acid into urolithins are quite good :

 

Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three urolithin-producing groups. "Phenotype A" produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. "Phenotype B" produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10-50%). "Phenotype 0" (5-25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers' health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.

 

 

 

 

FULL TEXT:  

 

 

Interesting. So barring conditions such as dysbiosis and looking at healthy subjects it looks like we have a reasonable chance of producing urolithin A which the work at EPFL shows has the max potential for mithophagy and muscle benefits. Also prior stratification for phenotype A-B-0 looks important to study target interventions with pomegranate extract or equivalent.

 

 

Previous studies from other groups also showed the presence of these three phenotypes, which were within the ranges shown here. For example, a previous study of the urinary urolithins
produced after the intake of raspberries by healthy volunteers (n= 10) showed that 70% were only urolithin A excreters (phenotype A), 20% excreted in addition isourolithin A and urolithin B (phenotype B), and 10% were nonexcreters (phenotype 0).10

 

 

 

[Izan]

bump.

[albedo]

There are preliminary results of the first human controlled trial presented at a frailty dedicated conference ICFSR 2017 in Barcelona this week. See my post in LC here:

http://www.longecity...ndpost&p=813945

 

[albedo]

http://pdf.amazentis...27April2017.pdf

[Oakman]

http://sciencebusine...it.com/?p=30766

[albedo]

Update news: AMAZENTIS got additional funding (~8m$) for two clinical trials on their pomegranate supplement. The first (Kevin Conley, UoW) will look at healthy people 65 yo and older with initiating muscular fraily and the second (Canada) will look at endurance increase by Urolithin A of people 45-65 yo with obesity.

 

Bioenergetics and Muscle Function Improvement With AMAZ-02 in Elderly Skeletal Muscle (ENERGIZE Trial)

https://clinicaltria...how/NCT03283462

 

AMAZ-02 Effect on Exercise ToLerance in Healthy, Overweight Middle Aged Subjects (ATLAS Trial) (ATLAS)

https://clinicaltria...how/NCT03464500

[maxwatt]

You can get your microbiome sequenced here www.ubiome.com with a "smartgut" test.  Don't know if they test for the Gordonibacter that converts elligatanins to urolithin.  Awaiting my kit results.

[Daniel Cooper]

It's been a couple of years since this information was released.  I'm somewhat surprised that no one is marketing a gordonibacter urolithinfaciens probiotic at this point.  Seems like a market opportunity is going unmet.