+100%-

Check out Geoff’s Narrations

The GIST

The Blog

THE GIST

  • Another day, another potential mitochondrial enhancer! We just came across LOLA and now we have urolithin A – a most intriguing compound. Urolithin A (UA) is produced by the gut bacteria when they break down the substances found in foods like pomegranates, walnuts, strawberries and raspberries.
  • it’s not new to science; it was discovered about 40 years ago, but more recent interest in its health-enhancing properties has resulted in hundreds of mostly lab and animal studies. UA’s great gift appears to be its ability to enhance mitochondrial production and muscle functioning across a wide range of species (worms, mice, and humans). Interestingly, it does this cleaning up of defective mitochondria (mitophagy, autophagy), a process studies suggest may be impaired in ME/CFS.
  • UA supplementation has been shown to improve both muscle strength, improve mitochondrial efficiency, and reduce inflammation in middle-aged and older adults. Animal studies suggest it can increase lifespan as well.
  • UA research appears to be booming. Just in the past 5 months, UA improved memory and learning in Alzheimer’s mice, suppressed colorectal cancer in the lab, reduced the toxicity of amyloid plaques in mice, reduced cognitive impairment in aging mice by increasing mitochondrial activity, reduced microglial activation in mice, and so on.
  • It’s not all about mice and labs, though. Clinical trials are currently underway to assess UA’s ability to affect the immune system, enhance endothelial functioning, increase glucose metabolism, insulin availability, and energy production, alter the gut flora and boost mitochondrial production, assess skeletal muscle function and iron metabolism, and more.
  • Studies suggest that only about 30-40% of people have the gut flora that produce enough urolithin A (UA) to make a difference.  One review stated that only “a small percentage” of people get enough UA from food to get health benefits from it.
  • Urolithin A supplements are readily available but, as with any supplement, it’s probably best to go with a reputable brand as one study found that some brands may not contain all the urolithin A they purport to.  Mitopure by Timeline has been used in clinical studies and is surely safe, but at $2.08 pill on Amazon in the U.S., it’s also easily the most expensive source. Otherwise, UA is available from $0.33 to $1.28 per pill, and comes in powder form as well.
  • Applying the Arsenau test regarding which treatments to try finds the source of the information regarding UA highly credible, the evidence of its effectiveness fair (a few good human studies have had positive results, the benefit appears to be moderate (but could hit a core problem in ME/CFS/FM), the cost runs from fairly low to fairly high depending on which brand you try, and the risk appears to be low. In other words, if you’re supplement inclined and you can afford it, urolithin A might be something to try.
  • We, of course, don’t have a clue how well it would do in diseases like ME/CFS, FM and long COVID, but if mitophagy is a problem, and people with these diseases are aging more quickly, as some researchers recently suggested, UA’s mitochondrial and lifespan-enhancing possibilities might be helpful.
  • No one supplement is going to do the trick with ME/CFS. With mitochondrial supplements popping up so much we’re going to try to use study results to dream up a possible mitochondrial supplement package for these diseases. If you have ideas please provide them!
  • Thanks to the over 200 people who have contributed to Health Rising’s drive thus far!
Another day, another potential mitochondrial enhancer. We just came across LOLA and now we have urolithin A – a most intriguing compound. Urolithin A (UA) is produced by the gut bacteria – a potential red flag in diseases like chronic fatigue syndrome (ME/CFS), fibromyalgia and long COVID, which feature a less diverse and a dysregulated gut flora. It’s one of several compounds (urolithin A B, C, and D) that gut microbes produce when they break down the ellagitannins found in foods like pomegranates, walnuts, strawberries and raspberries.

Possibility light bulb

Another possible mitochondrial enhancer shows up.

it’s not new to science; it was discovered about 40 years ago, but more recent interest in its health-enhancing properties has resulted in hundreds of mostly lab and animal studies. 

Mitochondrial and Lifespan Enhancer

UA’s great gift appears to be its ability to enhance mitochondrial production and muscle functioning across a wide range of species (worms, mice, and humans). Interestingly, it does this cleaning up of defective mitochondria (mitophagy, autophagy), a process studies suggest may be impaired in ME/CFS. UA is so effective at this process that it’s been called a “first-in-class mitophagy enhancer“.

Reduced mitochondrial cleanup in the muscles (mitophagy) plays a role in the muscle weakening that occurs as we age. UA has been shown to improve both muscle strength and muscle endurance in both younger and older mice, improve mitochondrial efficiency, reduce inflammation, and improve muscle endurance in humans. It also appears to enhance cardiovascular health, improve T-cell functioning (reducing T-cell exhaustion – a problem in both ME/CFS and long COVID), and has neuroprotective and mitochondrial enhancing effects in the brain.

A 2022 study found that middle-aged adults taking two doses/day of Mitopure for four months showed significant improvements in muscle strength (∼12%) and “clinically meaningful” improvements in aerobic endurance (peak oxygen consumption [VO2]) and physical performance (6 min walk test) but no significant improvements on peak power output. Increased mitochondrial gene expression and reduced levels of acylcarnitines and C-reactive proteins suggested Mitopure had improved mitochondrial efficiency and reduced inflammation. The gene expression and proteomic analysis of muscle tissue confirmed that UA’s biggest effect was improved mitochondrial functioning.

muscle endurance woman

Urolithin improved muscle endurance and mitochondrial functioning in middle-age and senior adults.

Similar findings occurred in the double-blinded, placebo-controlled, randomized ENERGIZE clinical trial taking place at the University of Washington Medical Center and the Fred Hutchison Cancer Research Center in Seattle, Washington. Older adults (65-94) taking 1,000 mg in the morning on an empty stomach with a glass of water had a significant improvement in muscle endurance, reduced plasma levels of several acylcarnitines, ceramides (biomarkers of mitochondrial health), and C-reactive protein (inflammation).

UA research appears to be booming. Just in the past 5 months, UA improved memory and learning in Alzheimer’s mice, suppressed colorectal cancer in the lab, reduced the toxicity of amyloid plaques in mice, reduced cognitive impairment in aging mice by increasing mitochondrial activity, reduced microglial activation in mice, and so on.

It’s not all about mice and labs, though. Clinical trials are currently underway to assess UA’s ability to affect the immune system, enhance endothelial functioning, increase glucose metabolism, insulin availability, and energy production, alter the gut flora and boost mitochondrial production, compare Mitopure’s bioavailability with pomegranate juice, assess skeletal muscle function and iron metabolism, and more.

Dietary Urolithin A vs Supplements

Studies suggest that only about 30-40% of people sufficiently break down ellagitannins enough to produce urolithin A (UA) in their gut. One review stated that only “a small percentage” of people get enough UA from food to get health benefits from it.  Attempts to identify the gut bacteria responsible for producing have failed thus far.

Buying Urolithin A

Urolithin A supplements are readily available but, as with any supplement, it’s probably best to go with a reputable brand. The news from a recent study that assessed UA levels in supplements was mostly good: of the 4 brands tested, two were very close to the manufacturer’s claims, while one exceeded it by almost 30%, and one was 16% lower. The names of the brands were not given. (The news regarding nicotinamide was worse with 8/16 brands containing less than 20% of the claimed levels and three containing none.)

Mitopure by Timeline has been used in clinical studies and is surely safe, but at $2.08 pill on Amazon in the U.S., it’s also easily the most expensive source. Otherwise, UA is available from $0.33 to $1.28 per pill, and comes in powder form.

Test

Applying the Arseneau test suggested that if you’re into supplements and can afford it, urolithin A might be worth a try.

Applying The Arseneau Test

The Arseneau test assesses the factors below to help decide whether or not to try a new treatment. It comes from a presentation given by Dr. Ric Arsenau, a Canadian ME/CFS/FM doctor.

  • The credibility of the source – with many studies and even a few human ones, the credibility of the source is good.
  • The quality of the evidence – Pretty good – few human trials have been done, but a couple of high-quality trials have had good results in healthy humans.
  • The benefit, cost, and the risk-benefit analysis – the benefit appears to be moderate (but could hit a core problem in ME/CFS/FM), the cost runs from fairly low to fairly high depending on which brand you try, and the risk appears to be low.

If you’re supplement inclined and you can afford it, urolithin A might be something to try.

How to Decide Which Treatments To Try for ME/CFS and Fibromyalgia: The Ric Arseneau Talk

Conclusion

UA might be the rare real deal. It’s been extensively studied – mostly in animal models and the lab for sure – but the few healthy human trials have gone well, and more are underway.

We, of course, don’t have a clue how well it would do in diseases like ME/CFS, FM and long COVID, but if mitophagy is a problem, and people with these diseases are aging more quickly, as some researchers recently suggested, UA’s mitochondrial and lifespan-enhancing possibilities might be helpful.

Longevity Research: Could it Turn Back the Clock in long COVID and ME/CFS?

That said, UA does not appear to be a super supplement (is there one?). The increases in muscle endurance are generally around 15-20% – a nice increase but not staggering. It does appear, though, to be having a positive effect biologically.

Question mark balls

Could urolithin A help with ME/CFS, FM and long COVID?

Thus far, though, we have one study that’s assessed autophagy in ME/CFS, three fibromyalgia mouse studies suggesting mitophagy / autophagy is a problem, and a couple of studies suggesting that impaired autophagy is in long COVID, as the virus appears to reduce autophagy. In other words, we have arrows pointing to autophagy/mitophagy being a problem but not a lot of solid evidence.

I never think that any one supplement is probably going to do it, and honestly, mitochondrial supplements have never done much for me. (Then again, I’m horrible at maintaining my supplement regimens).

With UA and LOLA popping up recently, though, I’m wondering what the studies suggest the best mitochondrial supplement package for these diseases might be. That will be coming up in a future blog but first, please offer your ideas. (Thanks to Neilly for the urolithin A tip.)

Health Rising’s Quickie Summer Donation Drive

Curious piggy

We are on the lookout for new treatment possibilities for these disease.

Thanks to the 235 people who have helped bring Health Rising get to about 75% of the way to its goal of $20,000. Because Health Rising is almost entirely (as in like 97%) community supported thanks to everyone who helping keep us online and spreading the news.

Urolithin A, LOLA, methylene blue, oxaloacetate, a new anaerobic exercise program, rapamycin, Putrino’s autonomic rehabilitation program, Tomnya, Copaxone, Baritcinib, monoclonal antibodies… it goes on and on. We are committed to keeping up with new treatment possibilities that have been showing up for these diseases.

If learning about new treatment possibilities floats your boat please support us in a manner that works for you.

GIVE A ONE-TIME DONATION


GIVE MONTHLY



HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT
A BIG thanks to the 320 people who helped make Health Rising's fundraising drive a success!

Stay Up to Date with ME/CFS, Long COVID and Fibromyalgia News

Get Health Rising's free blogs featuring the latest findings and treatment options for the ME/CFS, long COVID, fibromyalgia and complex chronic disease communities. 

Thanks for subscribing! :)

Pin It on Pinterest

Share This