A new study published in GeroScience addresses the efficacy and side effects of off-label rapamycin as a preventive therapy to maintain healthspan [1].
From a small island to a reportedly life-extending drug
When it was discovered in 1972 on the island of Rapa Nui, rapamycin was described as an antifungal substance [2]. Fifty years later, its many properties are better known, and the FDA has approved it for such issues as kidney transplant rejection, cardiac stents, and a rare and progressive lung disease.
However, research has demonstrated that it can extend lifespan and healthspan in animals [3]. Clinical trials are underway to assess whether it has the same effect in humans. Early results show relatively modest side effects.
But, some people don’t want to wait for the lengthy clinical trial and FDA approval process. They started using rapamycin off-label in hopes of extending their healthspan.
Survey results: informative, but with limitations
The authors of this paper created an online survey and received replies from 333 people who take rapamycin off-label, which is usually done in an effort to extend healthspan. The participants were encouraged to report how much rapamycin they use, their experiences with taking it, and any side effects. There was also a control group of 172 people who do not take rapamycin.
While informative, such analysis needs to be interpreted cautiously. This group of off-label users is small and, as a self-reported survey, may be biased toward people with a positive experience. The authors tried to recruit a diverse group of participants. However, they could not rule out the possibility that people who took rapamycin and had an adverse reaction were not adequately represented.
Additionally, the authors noted that the study group may also be biased in overall health status, as the study’s participants had healthier lifestyles than the general population. This was true for both the control group and the rapamycin group. Therefore, the results of this study may not apply to less healthy people.
Rapamycin dosing strategy varies
This survey’s participants have been taking rapamycin with different dosing strategies and over different lengths of time. Around 90% of off-label rapamycin users reported taking rapamycin once a week. Others took it every two weeks, daily, or every few days.
Doses of rapamycin were also very different. Six milligrams was the most common dose among those who took rapamycin weekly. For others, doses ranged from 2 milligrams to 20 milligrams for men and 14 milligrams for women.
Some of the survey’s participants were people who had just started using the compound, and some participants had been taking it for over 10 years. The median time was 218 days.
These differences make interpreting the data more difficult. In comparison, a clinical study would have larger groups of people taking the same dose for the same time in order to make the comparisons more reliable.
Rapamycin’s reported benefits and side effects
One essential part of the project was assessing rapamycin’s side effects. Mouth ulceration was the only condition that the users reported more frequenly than the control group. This was not surprising, as mouth ulceration is a commonly known side effect of rapamycin.
Researchers also observed a trend pointing to the higher frequency of reported infections among rapamycin users. However, it didn’t reach statistical significance.
Off-label rapamycin users reported several benefits, including decreases in abdominal cramps, depression, abdominal pain, muscle tightness, anxiety, and eye pain.
Rapamycin and COVID-19
This study was conducted in 2022, so the survey’s participants were directed to report their experiences with COVID-19 infection. For this disease, infection rates were similar between off-label rapamycin users and non-users. However, there were differences regarding the course of infection.
The authors discovered that people who took rapamycin regularly reported a lower incidence of developing moderate or severe COVID-19, whether they took it before, during, or after infection.
Similarly, continuous rapamycin users reported fewer detrimental, long-term, post-viral effects (“long COVID”) than non-users. This result, along with rapamycin’s anti-inflammatory properties, may make it a good candidate for intervention as a treatment for long COVID. The authors suggest the need for clinical trials to determine if this is the case.
Despite limitations, results are encouraging
Survey participants reported improved quality of life after using off-label rapamycin. They reported improvements in their “health, happiness, brain function, feelings of youthfulness, confidence, calmness, anxiety, and generalized aches and pains.”
Those results are encouraging, but it is essential to note that they originated from a self-reported online survey with many inherent limitations. A double-blind, randomized clinical trial is essential to confirm these results.
Literature
[1] Kaeberlein, T. L., Green, A. S., Haddad, G., Hudson, J., Isman, A., Nyquist, A., Rosen, B. S., Suh, Y., Zalzala, S., Zhang, X., Blagosklonny, M. V., An, J. Y., & Kaeberlein, M. (2023). Evaluation of off-label rapamycin use to promote healthspan in 333 adults. GeroScience, 1–12. Advance online publication.
[2] Vézina, C., Kudelski, A., & Sehgal, S. N. (1975). Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. The Journal of antibiotics, 28(10), 721–726.
[3] Saxton, R. A., & Sabatini, D. M. (2017). mTOR Signaling in Growth, Metabolism, and Disease. Cell, 168(6), 960–976.
