Two very different interventions — a gut-microbiome-derived postbiotic and a light-based therapy — offer an interesting look at how mitochondrial function can be supported through different mechanisms: clearing out damaged mitochondria on one hand, and directly powering the electron transport chain on the other.
Urolithin A
Singh et al. (2022) ran a randomized, double-blind, placebo-controlled trial testing whether Urolithin A supplementation could improve markers of mitochondrial dysfunction. Urolithin A is a postbiotic — a compound the gut microbiome produces from polyphenols called ellagitannins, which are found in foods like pomegranates, berries, and walnuts. It had previously been shown to activate mitophagy, the process that clears out dysfunctional mitochondria that tend to accumulate with age.
The results were notable given that participants (overweight adults ages 40–64) weren’t athletes and didn’t add exercise as part of the intervention. Those receiving 500 mg/day of Urolithin A saw a significant 12% increase in muscle strength over four months, without any change in lean body mass or fat mass on DEXA scanning — suggesting the strength gain reflected genuine improvement in muscle function rather than a change in body composition. At 1,000 mg/day, participants showed statistically significant increases in both peak VO2 and VO2 max within just 60 days, along with cycling 15% farther and walking 33 meters farther in a six-minute walk test — all considered clinically meaningful improvements.
The 500 mg group also showed reduced plasma acylcarnitines, suggesting improved beta-oxidation and more effective transport of long-chain fatty acids across the mitochondrial membrane. C-reactive protein dropped in both intervention groups — meaningful given that CRP was elevated at baseline, as expected in an overweight population, indicating the supplementation had an anti-inflammatory effect as well.
Muscle biopsies added mechanistic detail: in the 500 mg group, specific mitochondrial genes were activated and the PINK1/Parkin mitophagy pathway was upregulated, indicating an improved ability to clear out damaged mitochondria. The researchers hypothesize that removing mitochondria that had been generating excess reactive oxygen species may be the mechanism behind the reduced inflammation. At the 1,000 mg dose, mitochondrial proteins involved in the TCA cycle, fatty-acid oxidation, the electron transport chain, and oxidative phosphorylation were all upregulated, with the 500 mg group showing intermediate improvement across several of these markers.
One striking detail: even though Urolithin A is a product of the human microbiome, only 15% of participants had detectable plasma levels at baseline — and this was consistent with other studies. Not everyone’s gut microbiome produces meaningful amounts of this postbiotic. That’s part of why the researchers chose an overweight population for this trial: they anticipated Urolithin A might help reverse some of the muscle impairment that mitochondrial dysfunction tends to cause in this group. The authors raise an interesting possibility: once damaged mitochondria stop contributing as heavily to oxidative stress, the resulting drop in inflammation could remove a negative feedback signal that was suppressing the production of new, healthy mitochondria — potentially creating a virtuous cycle rather than just addressing existing damage. Improved cellular respiration can lead to healthier tissues and a reduction in oxidative stress.
Photobiomodulation
Argenta et al. (2017) took a completely different approach to supporting mitochondrial function, testing photobiomodulation (low-level laser therapy) for chemotherapy-induced peripheral neuropathy — a condition affecting up to half of cancer patients following chemotherapy. Their randomized, sham-controlled trial enrolled 70 female participants previously treated for various cancers, most commonly ovarian, uterine, and breast cancer. Laser therapy was delivered by a trained technician in 30-minute sessions, 18 times over six weeks, while the sham device produced only heat with no light.
The intervention group showed a significant improvement in neuropathy symptoms, and that improvement held up at follow-up ten weeks later. The proposed mechanism ties back to mitochondrial function directly: the authors cite multiple studies showing that proteins in the mitochondrial membrane can use the energy delivered by light to support cellular respiration — essentially giving a struggling electron transport chain an outside energy assist.
The Takeaway
These two studies approach mitochondrial support from opposite directions — one clearing out dysfunction at the cellular level through mitophagy, the other directly assisting respiration with light — but both point to the same underlying principle: mitochondrial health isn’t fixed, and it can be meaningfully influenced through targeted interventions, even in populations (overweight adults, post-chemotherapy patients) where you might expect the damage to be more difficult to reverse.
The content of this blog is for educational purposes and is not intended as medical advice. Please work with a qualified healthcare provider for personalized guidance.
References
Argenta, P. A., Ballman, K. V., Geller, M. A., Carson, L. F., Ghebre, R., Mullany, S. A., Teoh, D. G. K., Winterhoff, B. J. N., Rivard, C. L., & Erickson, B. K. (2017). The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: A randomized, sham-controlled clinical trial. Gynecologic Oncology, 144(1), 159–166.
Singh, A., D, A. D., Andreux, P. A., Fouassier, A. M., Blanco-Bose, W., Evans, M., Aebischer, P., Auwerx, J., & Rinsch, C. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine, 3(5).
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