Rapamycin (Sirolimus) Appetite & Cravings Changes: What the Evidence Actually Shows

What the Rapamune label says about eating-related side effects

Rapamune (sirolimus) is an mTOR inhibitor immunosuppressant approved for prophylaxis of organ rejection in renal transplant patients aged 13 years and older, and for lymphangioleiomyomatosis (LAM) [1]. It has no FDA-approved indication for aging, longevity or healthspan [1].

The label's most common adverse reactions (30% or more) in renal transplant prophylaxis include nausea, constipation, abdominal pain and diarrhea [1]. In the 12-month transplant study table, nausea occurred in 25% of patients taking 2 mg/day, 31% taking 5 mg/day and 29% taking placebo [1]. In the LAM study, the most common reactions (20% or more) include stomatitis, diarrhea, abdominal pain and nausea [1]. These rates come from transplant and LAM dosing, not from low intermittent dosing [1].

What the low-dose trials measured

PEARL was a 48-week decentralized, double-blind, placebo-controlled randomized trial in healthy, normative-aging adults [2]. Participants received placebo, 5 mg or 10 mg of compounded rapamycin once weekly [2]. Its primary outcome, visceral adiposity measured by DXA, showed no statistically significant change (p=0.942) [2]. Adverse and serious adverse events were similar across groups, and blood biomarkers stayed within normal ranges [2]. Lean tissue mass and self-reported pain improved in women taking 10 mg; emotional well-being and general health improved in those taking 5 mg [2]. The authors concluded that low-dose intermittent rapamycin was relatively safe over 48 weeks and that efficacy was not established [2]. There was no lifespan outcome [2].

The older Kraig pilot randomized 25 generally healthy adults aged 70 to 95 to 1 mg rapamycin daily or placebo; 11 rapamycin and 14 placebo participants completed at least 8 weeks [3]. Reported side effects in the rapamycin group were facial rash in 1 participant, stomatitis in 1, and gastrointestinal issues in 2 [3]. The trial reported significant decreases in hemoglobin, hematocrit, red cell count, RDW, MCV and MCH in the rapamycin group [3].

Weight and body composition

PEARL's body-composition result for visceral fat was not statistically significant: p=0.942 [2]. Lean tissue mass improved in women taking 10 mg weekly [2]. The abstract does not report body weight or weight loss [2].