Thread by @mkaeberlein

Drugs versus diets: Here’s some data to support my assertion that rapamycin as a pharmacological intervention for healthy aging is likely to have a better side effect profile than dietary interventions /1

Consider a hypothetical clinical trial of caloric restriction or intermittent fasting. Nearly every participant will experience multiple of the following adverse events: dyspepsia (hunger), headache, dizziness, fatigue, insomnia, poor thermoregulation, … /2

… loss of libido , constipation, diarrhea, nausea, dehydration, irritability, hypoglycemia, halitosis, dysmenorrhea … These are all well-known side effects of fasting. It seems very likely the true AE rate will approach 100% in the CR/IF group /3

The most common side effect in the Mannick 2014 study from 5 mg/wk rapalog (everolimus) was diarrhea in 7.5% of participants. The overall AE rate in this group was 37.7% compared to 20% in the placebo group. No severe AEs in the 5mg/wk group

pubmed.ncbi.nlm.nih.gov/25540326/

In the CALERIE study, dysmenorrhea (severe and frequent menstrual cramps) was experienced by >21% of the CR group. The incidence of nervous system, musculoskeletal, and reproductive system disorders was significantly higher than placebo

ncbi.nlm.nih.gov/pmc/articles/P…

/5

From a purely objective standpoint, the adverse event profile of caloric restriction or intermittent fasting seems likely to be worse than the adverse event profile of rapamycin/rapalogs in this dose range /6