A new study published in GeroScience addresses the efficacy and side effects of off-label rapamycin as a preventive therapy to maintain health [1].
From a small island to a life-extending drug
When 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 problems such as kidney transplant rejection, heart stents, and rare, progressive lung disease.
However, research has shown that it can extend lifespan and health in animals [3]. Clinical trials are underway to evaluate whether it has the same effect in humans. The first 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 health span.
Survey Results: Informative, but with limitations
The authors of this paper created an online survey and received responses from 333 people taking rapamycin off-label, which is usually done in an effort to extend life span. 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 were not taking rapamycin.
While informative, this analysis should be interpreted with caution. This off-label user group is small and, as a self-reported survey, may be biased towards people with a positive experience. The authors sought to recruit a diverse group of participants. However, they could not rule out the possibility that people taking rapamycin and experiencing an adverse reaction were not adequately represented.
Additionally, the authors noted that the study group might also be biased in overall health, as study participants had healthier lifestyles than the general population. This was true for both the control group and the rapamycin group. Therefore, the findings of this study may not apply to less healthy people.
The dosing strategy of rapamycin varies
Participants in this survey took rapamycin with different dosing strategies and for different lengths of time. Approximately 90% of off-label rapamycin users reported taking rapamycin once a week. Others took it every two weeks, every day, or every few days.
The doses of rapamycin were also very different. Six milligrams was the most common dose among those taking rapamycin weekly. For others, doses ranged from 2 milligrams to 20 milligrams for men and 14 milligrams for women.
Some of the survey 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 data interpretation more difficult. By comparison, a clinical trial would have larger groups of people taking the same dose for the same time to make comparisons more reliable.
The reported benefits and side effects of rapamycin
An essential part of the project was the evaluation of the side effects of rapamycin. Mouth ulceration was the only condition that users reported more frequently than the control group. This was not surprising, as mouth ulceration is a commonly known side effect of rapamycin.
The researchers also observed a trend indicating higher rates of reported infections among rapamycin users. However, it did not reach statistical significance.
Off-label rapamycin users have reported numerous benefits, including decreased abdominal cramps, depression, abdominal pain, muscle stiffness, anxiety, and eye pain.
Rapamycin and COVID-19
This study was conducted in 2022, so survey participants were asked to report their experiences with COVID-19 infection. For this disease, infection rates were similar between off-label rapamycin users and nonusers. However, there were differences regarding the course of the infection.
The authors found 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 users of rapamycin reported fewer harmful, long-term, and post-viral (“long COVID”) effects than non-users. This finding, coupled with rapamycin’s anti-inflammatory properties, could make it a good candidate for intervention as a treatment for long-term COVID. The authors suggest the need for clinical trials to determine if this is the case.
Despite the limitations, the 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 youth, confidence, calmness, anxiety, and generalized aches and pains.
These 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, TL, Green, AS, Haddad, G., Hudson, J., Isman, A., Nyquist, A., Rosen, BS, Suh, Y., Zalzala, S., Zhang, X., Blagosklonny, MV , An, JY and Kaeberlein, M. (2023). Evaluation of the off-label use of rapamycin to promote health span in 333 adults. GeroScience, 112. Advance publication online.
[2] Vzina, C., Kudelski, A., & Sehgal, SN (1975). Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of producing streptomycete and isolation of the active principle. The Journal of antibiotics, 28(10), 721726.
[3] Saxton, RA and Sabatini, DM (2017). mTOR signaling in growth, metabolism and disease. Mobile, 168(6), 960976.
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