Ursolic acid

Ursolic acid is a triterpenoid found in apple peel, rosemary and holy basil, and it is sold almost entirely on the strength of one line of mouse work from a single laboratory reporting that it induced muscle hypertrophy and reduced muscle atrophy.

The Interventions Testing Program tested it in the cohort built around the acarbose dose-response study. Acarbose at three doses raised median male longevity by 16 or 17 percent at the two higher doses and 4 to 5 percent in females, and raised the 90th percentile age in males at every dose. Three other interventions were run in parallel: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole, and INT-767. None of these affected lifespan at the doses tested.

The human record is one small study. Sixteen healthy men, mean age 29, were randomised to eight weeks of resistance training with or without ursolic acid, taken as one capsule three times daily. Body fat percentage fell significantly in the supplemented group. Body weight, body mass index, lean body mass, glucose and insulin were unchanged. IGF-1 and irisin rose from baseline within the supplemented group, and several strength measures rose from baseline in that group, though with seven and nine participants per arm the study cannot support much weight.

That is the whole human literature on a compound sold widely as a muscle-building supplement.

A lifespan null from this programme is a real, expensive, well-powered finding, and it is narrower than it sounds. What was tested was one concentration in the diet, started at one age, in one mouse strain, with death as the endpoint. A null tells you that this dose, in these animals, did not move that endpoint. It does not tell you the compound is inert, that a different dose would also fail, that the mechanism is wrong, or that the reason people actually take it has been refuted. Those are separate questions and most of them were never asked. The failure mode this site is trying to avoid runs in both directions: treating a mouse lifespan positive as proof that a supplement works, and treating a mouse lifespan null as proof that it does nothing.

Ursolic acid is the entry in this batch where the honest answer is that very little is known, and where both the enthusiastic and the dismissive readings overreach.

The mouse lifespan null is real: fed at the dose the ITP selected, ursolic acid did not change survival, in a cohort where acarbose in the next cage produced one of the programme's largest male effects. That rules out one specific claim.

It does not address the claim the product is actually sold on, which is muscle. The preclinical muscle work is largely from one research group, the human work is 16 people, and the compound's low oral bioavailability means the relationship between a capsule and tissue exposure is unknown. The right description is that a widely sold muscle supplement has been tested in fewer people than would fill a small classroom, and separately has been shown not to extend mouse lifespan.

The Interventions Testing Program is funded by the National Institute on Aging and run in parallel at three independent laboratories, in Bar Harbor, Ann Arbor and San Antonio. It uses UM-HET3 mice, a four-way genetic cross, so no result can be an artefact of a single inbred background. Both sexes are studied, cohorts are sized to detect roughly a 10 percent shift in lifespan, compounds are fed in the diet from a stated starting age, and the programme commits in advance to publishing negative results alongside positive ones. That last commitment is why this batch can exist at all: almost no other part of ageing research reliably tells you what did not work.