PracticeFebruary 22, 202612 min read
The Dosing Question Nobody Wants to Answer Cleanly
Weekly, biweekly, cycled, pulsed — a field guide to what the human data supports, what it doesn't, and what remains educated guesswork.
If you talk to ten longevity-curious clinicians, you will hear ten dosing protocols. That is not because the field is chaotic. It is because the field is young, and thoughtful people are reasoning from mechanism because the outcome data hasn't arrived yet.
The core intuition is straightforward: continuous mTORC1 inhibition produces the side effect profile familiar from transplant medicine — mouth sores, lipid changes, glucose disturbances. Intermittent inhibition, in mice, appears to preserve the healthspan benefit while attenuating the side effects. So the human protocols cluster around 'pulse it and let mTOR come back up between doses.'
What that pulse should look like in a 55-year-old human, at what weekly dose, for how many years — those are open questions. The Mannick trials on immune function used low weekly dosing over six weeks. Off-label practice has largely followed that shape, with a lot of local variation.
I am not going to tell you what to do. I am going to tell you what the evidence supports, what it suggests, and where the reasoning becomes speculative — so that you and your clinician can have the conversation with your eyes open.
By the author
Written with curiosity, humility, and evidence. Corrections and counter-arguments are welcome — this journal treats reader pushback as a feature, not a bug.
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