Rapamycin & Low Dose Naltrexone
- a potentially powerful combination!
Rapamycin + Low Dose Naltrexone (LDN) is a fascinating and potentially synergistic combo—especially for APOE4 carriers, where immune modulation is key to slowing neurodegeneration.
Why This May Be Powerful in APOE4
APOE4 brains live in a state of chronic immune priming, with:
Overactive microglia
Poor autophagy
Pro-inflammatory cytokine bias (IL-1β, TNF-α)
Higher baseline mTOR signaling
Rapamycin helps recalibrate mTOR and microglial behavior, while LDN can enhance endorphin tone and Treg balance, adding a gentler, compensatory immunoregulation. Together, they may:
Reduce inflammatory burden
Support immune resilience rather than full suppression
Help balance the immune–neuroendocrine axis (especially relevant in stress-sensitive APOE4s)
Avoid over-inhibition that might occur with higher-dose rapa alone
Any Risks or Conflicts?
Generally, no direct interaction is known between LDN and rapamycin, but consider:
Both modulate the immune system—though via different axes (rapa = innate, LDN = regulatory/autoimmune).
If you're also taking vaccines or biologics, the additive immunomodulation should be monitored.
Both are low-dose and well-tolerated when timed appropriately.
What I’m doing
Since 2021, I take 6mg rapamycin once weekly. Dr. Alan Green (pioneer in off-label rapamycin use for APOE4 AD prevention), increased my dose to 8mg due to my age and two copies of this deleterious gene about a year later. Since I regularly monitor labs, and saw my lymphocytes were staying below range on 8mg, I have gone back to 6mg weekly and remain at that dose. In early 2025 I added LDN to my stack. It is generally taken at night to align with our body’s natural endorphin rhythm. I quickly noticed how it “tanks” my deep sleep (as measured by my Oura ring) so I moved to a morning dosing and am currently taking 3mg daily.
👥 Anecdotal and Clinical Reports
LDN + Rapamycin is already being used off-label by some functional medicine and biohacking clinicians in autoimmune disorders, CFS, and neurodegeneration.
Some Alzheimer's prevention protocols are exploring this combo, especially when there's evidence of brain fog, poor sleep, or mood instability (LDN helps here).
Summary
Rapamycin + LDN is a rational, immune-calibrating duo, especially for:
APOE4 carriers
Those with elevated inflammatory markers
People experiencing neuro-inflammatory symptoms (brain fog, poor sleep, fatigue)
Anyone aiming to preserve cognition with mild immune suppression