r/Rapamycin

There are now 2 studies that have been published about the use of weekly Rapamycin (LDR) for MECFS, with encouraging yet small results.
But:
- Other studies about the use of LDR for dementia show there is an increase of neurofilaments (Nfl), a biomarker of neurons destruction, associated with a lower decrease in brain volume (which is very different from neurons quantity).

- They claim it *might* be the result of autophagy, i.e. your neurons clean the Nfl, instead of the classical conclusion of neurons destruction. Which means le Nfl level should eventually settle back to normal... which has never been observed with LDR.

- High-dose rapamycin used for immuno-suppression has proven to not be toxic to neurons over years, nor to elevate the Nfl levels either. And contrary to higher doses, LDR stimulates your neurons and may activate something fishy that could mean the elevated Nfl are indeed the result of brain damage.

The ongoing trials about LDR never measure the Nfl, which is bad as this might be the indication of a ticking bomb for the millions who may want to try it.

We conducted a single arm trial of low dose rapamycin (1 mg/day for 4 weeks) in cognitively normal adults aged 45 to 65 years, prior to detectable AD pathology, stratified by APOE genotype. The primary outcome was cerebral blood flow (CBF), while secondary outcomes included plasma metabolomics, inflammatory cytokines, AD biomarkers, and gut microbiome composition.

Twenty-three participants completed the study, including nine APOE4 carriers and fourteen non-carriers. Rapamycin significantly increased CBF in APOE4 carriers, with increases exceeding 15% across multiple brain regions, and improved metabolic and inflammatory profiles with minimal adverse effects. In contrast, non-carriers showed no significant change in CBF and exhibited distinct physiological responses, highlighting genotype dependent effects.

These findings suggest that rapamycin may mitigate early cerebrovascular and systemic dysfunction in APOE4 carriers and support a precision medicine approach in which therapeutic response is influenced by genotype.