Caffeic acid phenethyl ester dosage and evidence

Nobody has published a study of CAPE itself in people. In mice, it did not extend lifespan at either dose by the NIA program's standard test. A 2024 second look, using a test that counts early deaths more, found a 5 percent gain in typical female lifespan at 300 ppm.

CAPE (caffeic acid phenethyl ester) is one of the active parts of propolis, the sticky resin honeybees use to seal their hives. In a dish, it is studied as a blocker of NF-kappa B, a master switch for inflammation. In rats and mice, it is studied for calming inflammation and cell damage in models of blocked blood flow, arthritis and chemical injury. It is sold as a pure lab chemical, and it turns up in varying amounts in propolis supplements.

Nobody has run a study of CAPE in people. A PubMed search for human trials of CAPE finds nothing. Propolis extracts have been tested in people for various conditions. But how much CAPE they hold depends on which plants the bees visited, and it is rarely measured. So those studies cannot be read as studies of CAPE. Nobody has measured how the pure compound is absorbed or cleared in a person.

In mice, the NIA lifespan program fed CAPE at 30 and 300 ppm from 4 months of age and reported it as a no. Neither dose made either sex live longer by the standard test. The 2024 second look with the Gehan test found that at 300 ppm, typical (median) female lifespan was 5 percent higher than untreated mice. That was 147 treated females against 289 untreated. By the standard test it just missed. By the Gehan test it just passed. Males showed nothing at either dose. The survival curves fit the standard test's assumptions, so the standard test was a fair test here. It simply came up short.

CAPE is not an approved drug anywhere. It is sold as a supplement ingredient, most often inside propolis products.

The National Institute on Aging runs a mouse lifespan program called the Interventions Testing Program. It tests each compound at three labs at the same time: The Jackson Laboratory, the University of Michigan and UT Health San Antonio. The mice are a mixed breed, so a result is less likely to be a quirk of one strain. Males and females are both tested and judged separately. The three labs' results are then pooled. Every result gets published, whether or not the compound worked. It runs on public money from the National Institute on Aging, with no drug company money. CAPE was tested at 30 and 300 ppm from 4 months and reported as a no in both sexes.

Some results on these pages are called "Gehan-only". That is a weaker claim than "made mice live longer", so it needs explaining. The program's standard test counts every death the same. In 2024 a group at UT Health San Antonio went back over all the program's survival data from 2004 to 2022. That covered 132 compound and sex pairs. They used a second test, called the Gehan test. It gives more weight to deaths that happen young and in midlife. Five compounds that failed the standard test passed this one: metformin, enalapril and 17-DMAG in males, and CAPE and green tea extract in females. The authors say this is the pattern you would expect from something that stops mice dying young and then stops helping. In their words, the effects are "limited to midlife and may not be effective at older ages". They did not report any adjustment for running so many tests at once. So a Gehan-only result means fewer mice died young. By old age the groups caught up, and the oldest mice lived no longer.

For CAPE the story is thinner than for the other Gehan-only wins. Its survival curves fit the standard test's assumptions, so that test was the right one, and it just missed. The Gehan test just passed. Those two results sit either side of the usual cut-off. Read them as one finding, a borderline 5 percent gain in typical female lifespan, not as one no and one yes. There is no human research because CAPE is a natural product nobody can patent. The propolis industry sells the whole resin, not the pure molecule. No sponsor, no trial, no answer either way.