Highlights
- Urolithin A (UA) is a molecule derived from pomegranates, berries etc., and promotes mitophagy (elimination of defective mitochondria)
- A clinical trial tested 50 healthy middle-aged subjects, half of whom received 1000mg/day of UA for 4 weeks to test its effect on immune aging
- At the end of the study, the treatment group had newer, healthier T-lymphocytes and other immune cells such as NK cells and monocytes
- The treatment was well tolerated
Urolithin A (UA) for mitochondrial health
Urolithin A (UA) is derived from compounds called ellagitannins found in pomegranates, berries and tree nuts.Our gut microbiome converts these into UA which is then absorbed by the body. UA has recently generated a lot of interest for its ability to remove and recycle damaged mitochondria, a process called mitophagy. The newer and healthier mitochondria that take their place are energetically more active and provide protection against diseases and aging. Previous clinical trials have shown the beneficial effects of UA in muscle and heart function.
Clinical trial shows promising results
In a randomized, double-blind, placebo-controlled clinical trial, 50 healthy adults between 45–70 years were recruited, 25 of the subjects were given 1,000 mg oral UA daily for four weeks while the rest received placebo. Primary endpoints of the study were to observe changes in T-cell and immune metabolism. Secondary endpoints evaluated the health of other immune cells.
The study found that after 4 weeks, the treatment group had:
- More youthful CD8 T-cells with fewer signs of T-cell exhaustion. CD8 or cytotoxic T-cells directly attack and kill infected and cancer cells.
- The CD8 T-cells were more metabolically fit: they consumed fatty acids and amino acids more efficiently.
- NK (natural killer) cells and non-classical monocytes numbers increased. These are two immune cell types of the innate immune system that are tuned to find and destroy cancer cells and virus-infected cells. The classical monocytes which are typically more pro-inflammatory had a less-inflammatory phenotype.
- The CD-8 T-cells had more mitochondrial biogenesis but the overall mitochondrial amount remained unchanged
- Level of inflammation in plasma was either stable or decreased, which is a positive sign of reduced inflammaging
Safety and efficacy of UA in immune health
While long term effectiveness and safety of UA supplementation is not known, this study demonstrated that daily supplementation with 1000mg UA for 4 weeks is safe and well tolerated.The data shows improvements in immune health in that there is evidence of a slowdown in immune aging and reduced overall inflammation. The longest clinical trial with UA has been for 4 months at 1000mg/day and was well tolerated.
Denk, D. et.al. Effect of the mitophagy inducer Urolithin A on age-related immune decline: a randomized, placebo-controlled trial. https://doi.org/10.1038/s43587-025-00996-x
Singh, A. et. al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. https://doi.org/10.1016/j.xcrm.2022.100633