#1

i am 73 and have been taking 6mg rapamycin/weekly for three years. Rapamycin has restored my teeth strength and cardiac function. I tried to use 3mg with GFJ, but it gave me unbearable itching and hives. so i asked AI and and it said rapamycin is influencing mast cell activation. The following is what chatGPT replied:

Rapamycin (Sirolimus) is an mTOR inhibitor that primarily affects cell growth, immune function, and inflammation. Its impact on mast cells is complex and context-dependent. Here’s what we know:

Potential Adverse Effects of Rapamycin on Mast Cells

  1. May Increase Mast Cell Activation in Some Cases
  • Rapamycin inhibits mTOR, which is crucial for cell metabolism and immune regulation.
  • Some studies suggest that mTOR inhibition can lead to mast cell hyperactivity, potentially increasing histamine release in certain conditions.
  1. Can Impair Gut Barrier Function, Leading to Histamine Issues
  • Long-term rapamycin use alters gut microbiota, which may disrupt histamine metabolism and increase gut-derived histamine.
  • Some users report digestive issues and increased food sensitivities, possibly linked to mast cell overactivation.
  1. May Suppress Regulatory T Cells (Tregs), Affecting Mast Cell Control
  • Tregs help regulate immune tolerance, and their suppression could indirectly lead to higher mast cell activation in allergic individuals.

Since you’re considering rapamycin for longevity, it’s important to monitor how it affects your histamine levels and mast cell activity. If you notice symptoms like flushing, itching, digestive issues, or increased allergies, it could indicate that rapamycin is influencing mast cell activation.

Ways to Mitigate Potential Mast Cell Issues While Taking Rapamycin:

  1. Support Gut Health – Take low-histamine probiotics (Bifidobacterium strains) and avoid high-histamine foods.
  2. Increase DAO Activity – Consider DAO enzyme supplements if histamine intolerance symptoms arise.
  3. Stabilize Mast Cells – Supplements like quercetin, magnesium, and vitamin C may help counteract any potential mast cell overactivity.
  4. Monitor Dosing Frequency – Some people find intermittent dosing (e.g., once weekly) better tolerated than daily use.
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#2

We need the actual papers that this type of summary references to be able to evaluate the data. What dose, what animal models, N=?, etc…

You could probably generate any headline about “potential” adverse events on any given biological process, given high enough, or frequent enough, dosing.

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