Rapamycin for APOE4 Carriers: 400 Patients, Zero Dementia (Expert Q&A Recap)
We sat down with a doctor who has 300 person-years of rapamycin data. Some of it surprised me.
Key takeaways · TL;DR
Dr. Alan Green's clinical cohort of 300-400 APOE4 carriers on rapamycin recorded zero dementia diagnoses over an average 5 years. Dr. Grant Fraser warns that compounded capsules deliver only one-third of the dose, personalized blood-level dosing varies 6x between similar patients, and only coated FDA-approved tablets should be used.
Definition
Blocking the mechanistic target of rapamycin pathway, which triggers autophagy and cellular cleanup linked to longevity and neuroprotection.
The mTOR pathway regulates cell growth, protein synthesis, and nutrient sensing. Chronic activation accelerates aging-related damage, while periodic inhibition via rapamycin triggers autophagy (cellular self-cleaning) and clears damaged proteins including amyloid-beta and tau aggregates relevant to Alzheimer's. Pulsed weekly dosing, rather than continuous daily dosing, appears to provide longevity benefits without the chronic immunosuppression seen in transplant patients on daily doses.
Rapamycin Formulation Quality for APOE4 Carriers
| Formulation | Absorption | Cost | Recommendation |
|---|---|---|---|
| Compounded capsules | ~33% of stated dose | Variable | Avoid per Dr. Fraser |
| Coated FDA-approved tablets | Full dose | ~$0.65/mg at CVS with GoodRx | Preferred |
| Liquid/sublingual | Variable | Variable | Not preferred without blood-level validation |
Hi Phoenix friend,
We just hosted one of the most requested expert Q&As in Phoenix history.
Dr. Grant Fraser. Board certified in anti-aging and regenerative medicine. 29 years as an ER physician. And over 300 person-years of clinical experience managing rapamycin in patients. (More details about Dr. Fraser below)
More than 50% of his patients are APOE4 carriers. He's also one himself.
We spent over an hour going deep on rapamycin for APOE4: dosing, side effects, when to start, what most people get wrong, and some data that stopped me mid-sentence.
The full Q&A is on YouTube (link below). But here are 3 things that stood out to me.
1. 400 APOE4 patients. Five years. Zero dementia diagnoses.
Dr. Alan Green (a pioneer in rapamycin prescribing) had roughly 1,500 patients on rapamycin before he passed. 300 to 400 of them were APOE4 carriers, mostly in their 60s through 80s.
Prime time for cognitive decline.
Not a single one received a dementia diagnosis over an average of five years.
Now, there are caveats. These patients were affluent, educated, and health-conscious (just by the nature of seeking out someone like Dr. Green). Those factors alone lower dementia risk. But zero out of 300 to 400? Dr. Fraser put it simply: "Seems very unlikely that rapamycin had nothing to do with that."
2. Your rapamycin capsules might only absorb a third of the dose.
This one shocked a few of our members.
If you're taking compounded rapamycin capsules, Dr. Fraser says you're likely only absorbing about one-third of the dose. The capsule gets destroyed in your stomach before the drug can do its job.
His recommendation: only use coated, FDA-approved tablets. They're cheaper too. About 65 cents per milligram at CVS with a GoodRx coupon.
Several Phoenix members on the call were taking compounded capsules and had no idea.
3. Same weight. Same age. 6x the dose.
This is why "just take 5mg a week" is a bad protocol.
Dr. Fraser shared that he has two patients. Same weight, same gender, similar age. One needs 3mg to hit target blood levels. The other needs 18mg.
That's a 6x difference.
Without measuring blood levels (he targets 3 ng/mL at 50 hours post-dose), you're either underdosed and wasting money, or overdosed and risking metabolic side effects. Personalization isn't optional here. It's the whole game.
There's a lot more in the full conversation.
We covered when to start based on your genotype (4/4 vs 3/4 vs 4/2), how to time rapamycin around workouts to protect muscle growth, why Brian Johnson stopped (and why Dr. Fraser didn't), a sleep medication that actually lowers beta amyloid levels, and a bunch of live member Q&A.
Who is Dr. Grant Fraser:
Board Certified: American Board of Anti-Aging and Regenerative Medicine, with fellowship modules in Cardiology, Endocrine and Gastroenterology.
Board Certified American Board of Family Medicine.
Fellow of the Australian College of Rural and Remote Medicine with Advanced Specialty Training in Emergency Medicine and Generalist Emergency Medicine Post Fellowship Certification.
Fellow of the Australian College of General Practitioners.
29 years of experience in Emergency Medicine and Rural Generalist Medicine.
Dr. Fraser’s Youtube channel
This is the kind of conversation that happens inside The Phoenix every month.
If you're already a Phoenix member: submit your questions for our next Q&A with Dr. Fraser on lipid management for APOE4 carriers inside the community. You can also vote on future topics and guests you'd like us to bring on.
If you're not a member yet (and you read this far), you're probably a good fit.
The Phoenix is where APOE4 carriers stop guessing and start running structured experiments, tracking what actually works, and getting direct access to experts like Dr. Fraser who understand our genetics.
Talk soon,
Kevin
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