Assessing the Ability of Urolithin A Supplementation to Improve Human Health via Increased Mitophagy

Mitophagy is the name given to cellular quality control mechanisms responsible for destroying worn and damaged mitochondria. Existing mitochondrial divide to make up the losses. Mitophagy is critical to mitochondrial function, but it declines in effectiveness with advancing age. A number of dietary supplements are thought to upregulate mitophagy in older individuals, thereby improving mitochondrial function and overall health. Urolithin A is one of them, various vitamin B3 derivatives such as nicotinamide riboside another, as well as mitoQ, SkQ1, and other mitochondrially targeted antioxidants. The mechanisms are varied, as a number of different changes with age are implicated in failing mitophagy. There is some positive evidence for health benefits in humans, but overall the data to date is not good enough for real excitement. That is also the case for the results here. Exercise tends to outperform the supplements where the direct comparison has been made.

Urolithin A is a byproduct of a person's gut bacteria and a diet comprising polyphenols found in pomegranates, berries, and nuts. Supplemental urolithin A has been shown in animal tests and molecular studies of humans to stimulate mitophagy. Researchers studied a small cohort of people over age 65 who were randomized to receive a placebo or a daily supplement of 1,000 mg urolithin A for four months. Each of the 66 subjects was confirmed at the outset to have average or subpar capacity to produce adenosine triphosphate (ATP), which mitochondria produce to help cells perform myriad functions. The investigators hypothesized that, if the urolithin A supplement indeed boosted mitophagy, the test cohort would experience improved muscle function and greater ATP output.

Across both cohorts, two comparisons of muscle function were found to support the thesis, but two others did not. Two measures of muscle endurance were improved in the supplemented group compared to the placebo group. Endurance was measured with exercises involving the hand and leg. Researchers measured the increase in the number of muscle contractions until fatigue between a baseline test and the final test four months later. Measures of distance covered during a six-minute walk improved markedly between tests at baseline and four months in both the supplement and placebo groups. However, researchers saw no significant effect of the supplement compared with the placebo. Measures (via magnetic resonance spectroscopy) of improvement of maximal ATP production did not change significantly between baseline and four months in either group.

Plasma samples also were collected from study participants at the outset, at two months and four months. The purpose was to assess supplement's potential effect on urolithin A bioavailability and on biomarkers of mitochondrial health and inflammation. In the test cohort, Urolithin A was associated with a significant reduction in several acylcarnitines and ceramides implicated for their roles in metabolic disorders involving mitochondria. "These changes suggest that the treatment affects the metabolic condition of people. Even though it didn't affect the maximum ATP production, it improved test subjects' general metabolism."



"Exercise tends to outperform the supplements where the direct comparison has been made"

A relevant question is whether exercise plus supplements is greater or worse than exercise alone.

Posted by: Brad at January 29th, 2022 7:22 PM

Urolithin A, should have effects across the whole body. While exercise might leave some muscle groups out. So for the parts that are exercised, the effect of Ua is folded in, but there might be other tissues where you cannot get direct benefits from the exercise. And if you have partial exercise combined with Urolithin A will be better than partial exercise alone, or Ua alone.

And there are a whole bunch of people which cannot get good exercise due to being functionally disabled to some dergree

Posted by: Cuberat at January 30th, 2022 3:43 PM

Is Urolithin A also recommended for Infants with Mitochondrial Disorder?

Posted by: Marco at January 30th, 2022 10:53 PM

Some additional weapons for mitophagy:
"From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals' memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy."

Posted by: jim at January 31st, 2022 8:38 AM

I find it sadly funny that there's such a thing as "nematode model for AD". Seriously? Nematodes? We are closer to starfish than nematodes.

Posted by: Cuberat at January 31st, 2022 5:38 PM
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