Rapamycin (Sirolimus) Month-by-Month: What Actually Happens in the First 3 Months

What the 48-week PEARL trial found

PEARL (NCT04488601) was a double-blind, placebo-controlled trial in healthy, normative-aging adults who took placebo, 5 mg or 10 mg of compounded rapamycin once weekly for 48 weeks [1]. The primary outcome, visceral adiposity measured by DXA, did not change (p=0.942), and changes in blood biomarkers stayed within normal ranges [1]. Lean tissue mass (p=0.013) and self-reported pain (p=0.015) improved in women taking 10 mg, and emotional well-being (p=0.023) and general health (p=0.004) improved on 5 mg, with no other significant effects [1]. The authors called 48 weeks of intermittent low-dose rapamycin relatively safe and said efficacy was not established; there was no lifespan outcome [1]. The trial used compounded rapamycin, and compounded drugs are not FDA-approved [4][1].

What the smaller pilot found

Twenty-five generally healthy adults aged 70 to 95 were randomized to 1 mg rapamycin daily or placebo; 11 in the rapamycin group and 14 in the placebo group completed at least 8 weeks [2]. Facial rash occurred in one person, stomatitis in one and gastrointestinal issues in two [2]. In the pilot's rapamycin group, hemoglobin, hematocrit, red blood cell count, RDW, MCV and MCH decreased significantly [2].

A vaccine result that belongs to a different drug

The finding that an mTOR inhibitor improved influenza vaccine response by about 20% in older volunteers came from RAD001 (everolimus), not sirolimus, and measured antibody response rather than lifespan [5].

What the Rapamune label says

• Boxed warning: increased susceptibility to infection and possible lymphoma and other malignancies from immunosuppression; use is not recommended in liver or lung transplant patients [3].
• Hypertriglyceridemia occurred in 45% of renal transplant patients on 2 mg/day and 57% on 5 mg/day, against 23% on placebo; the label states that any patient given Rapamune should be monitored for hyperlipidemia [3].
• Because sirolimus can cause fetal harm, the label recommends highly effective contraception during treatment and for 12 weeks after the last dose [3].
• The label says grapefruit juice must not be taken with Rapamune or used to dilute it, and advises avoiding strong CYP3A4 or P-gp inhibitors and inducers such as ketoconazole, itraconazole, clarithromycin, rifampin or rifabutin [3].

Longevity use is off-label; the label's approved uses are renal transplant rejection prophylaxis in patients 13 and older and lymphangioleiomyomatosis [3]. HealthRX.com offers rapamycin by prescription.