#After effects trial registration#

3, 4 Evidence has shown that mitochondrial dysfunction plays an important role in age-related diseases.

1, 2 Aging is associated with a progressive loss of muscle mass and strength that manifests as reduced physical performance and endurance capacity, imposing a burden on both the individual and society. Older adults (aged ≥60 years) are the fastest growing age group in the world and projected to represent 1 in every 4 adults by 2050.

#After effects trial registration#

Trial Registration Identifier: NCT03283462 Although the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not significant in the urolithin A group vs the placebo group, long-term urolithin A supplementation was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin A may counteract age-associated muscle decline however, future work is needed to confirm this finding. No statistical differences in adverse events were observed between the 2 groups.Ĭonclusions and Relevance This randomized clinical trial found that urolithin A supplementation was safe and well tolerated in the assessed population. These results showed no significant improvement with urolithin A supplementation compared with placebo.

The mean (SD) change from baseline to 4 months in maximal ATP production in the FDI was 0.07 (0.23) mM/s in the urolithin A group and 0.06 (0.20) mM/s in the placebo group for the TA, it was −0.03 (0.10) mM/s in the urolithin A group and 0.03 (0.10) mM/s in the placebo group. The mean (SD) increase from baseline in the 6-minute walk distance was 60.8 (67.2) m in the urolithin A group and 42.5 (73.3) m in the placebo group. Plasma levels of several acylcarnitines, ceramides, and C-reactive protein were decreased by urolithin A, compared with placebo, at 4 months (baseline vs 4 mo: urolithin A, 2.14 vs 2.07 placebo, 2.17 vs 2.65 ). Urolithin A, compared with placebo, significantly improved muscle endurance (ie, increase in the number of muscle contractions until fatigue from baseline) in the FDI and TA at 2 months (urolithin A: FDI, 95.3 and TA, 41.4 placebo: FDI, 11.6 and TA, 5.7 ). These participants had a mean (SD) age of 71.7 (4.94) years, were predominantly women (50 ), and were all White individuals.

Results A total of 66 participants were randomized to either the urolithin A (n = 33) or the placebo (n = 33) intervention group. Adverse events were recorded and compared between the 2 groups during the intervention period. Cellular health biomarkers were investigated via plasma metabolomics. The secondary end points were change in muscle endurance of 2 skeletal muscles (tibialis anterior in the leg and first dorsal interosseus in the hand). Main Outcomes and Measures The primary end point was change from baseline in the 6-minute walk distance and change from baseline to 4 months in maximal ATP production in the hand skeletal muscle. Interventions Participants were randomized to receive daily oral supplementation with either 1000 mg urolithin A or placebo for 4 months. The analysis used an intention-to-treat approach. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Objective To investigate whether oral administration of urolithin A improved the 6-minute walk distance, muscle endurance in hand and leg muscles, and biomarkers associated with mitochondrial and cellular health.ĭesign, Setting, and Participants This double-blind, placebo-controlled randomized clinical trial in adults aged 65 to 90 years was conducted at a medical center and a cancer research center in Seattle, Washington, from March 1, 2018, to July 30, 2020. Urolithin A is a natural gut microbiome–derived food metabolite that has been shown to stimulate mitophagy and improve muscle function in older animals and to induce mitochondrial gene expression in older humans. Importance Aging is associated with a decline in mitochondrial function and reduced exercise capacity.

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