Evaluation of off-label rapamycin use to promote healthspan in 333 adults, 2023, Kaeberlein et al

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Evaluation of off-label rapamycin use to promote healthspan in 333 adults

Tammi L Kaeberlein, Alan S Green, George Haddad, Johnny Hudson, Anar Isman, Andy Nyquist, Bradley S Rosen, Yousin Suh, Sajad Zalzala, Xingyu Zhang, Mikhail V Blagosklonny, Jonathan Y An, Matt Kaeberlein

Abstract
Rapamycin (sirolimus) is an FDA-approved drug with immune-modulating and growth-inhibitory properties. Preclinical studies have shown that rapamycin extends lifespan and healthspan metrics in yeast, invertebrates, and rodents. Several physicians are now prescribing rapamycin off-label as a preventative therapy to maintain healthspan. Thus far, however, there is limited data available on side effects or efficacy associated with use of rapamycin in this context. To begin to address this gap in knowledge, we collected data from 333 adults with a history of off-label use of rapamycin by survey. Similar data were also collected from 172 adults who had never used rapamycin. Here, we describe the general characteristics of a patient cohort using off-label rapamycin and present initial evidence that rapamycin can be used safely in adults of normal health status.

Link | PDF (GeroScience) [Open Access]
 
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Severity of COVID-19 outcomes among survey participants reporting an infection. Survey participants self-reported SARS-CoV-2 infection as mild (less than 1 week of symptoms, no hospitalization), moderate (more than 1 week of symptoms, no hospitalization), or severe (trip to hospital). Participants also noted whether they suffered from prolonged symptoms consistent with long-COVID. A All participants. A total of 54 individuals who have never take rapamycin are included in the “Non-users” group. Rapamycin users are split into three groups to reflect their use of rapamycin relative to the timing of SARS-CoV-2 infection. Rapamycin users who did not begin rapamycin use until after their SARS-CoV-2 infection (n = 41) are included in the “After infection only” group. Rapamycin users who stopped taking rapamycin during their SARS-CoV-2 infection (n = 17) are included in the “Prior but not during” group. Rapamycin users who took rapamycin continuously throughout their SARS-CoV-2 infection (n = 37) are shown in the “Continuous” group. B Men only. C Women only. Percentages and number of participants in each group are provided in Supplemental Tables 68
 
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Interestingly, only one condition was significantly more common in off-label rapamycin users than non-users: canker sores.

It says things like depression and anxiety were less common, but I don't think any causality can be inferred.

A total of 7 conditions were significantly different between non-users and rapamycin users. The only condition that was significantly more common in rapamycin users was presence of mouth ulceration, a known common side effect of rapamycin usage [53, 54]. Several conditions were significantly less frequent in rapamycin users compared to non-users: abdominal cramps, depression, abdominal pain, muscle tightness, anxiety, and eye pain. A trend toward a higher frequency of infections (respiratory tract, skin, fungal, and urinary tract) among rapamycin users was noted, but did not reach statistical significance.
 
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