I want to understand the biological pathways how things work. I’m starting to think that maybe it’s not directly the mTOR inhibition that cause the immunosuppressive, antifungal and anti-inflammatory effect when it comes to rapamycin. I wonder if it’s not more linked to the AMPK activation when mTOR is inhibited. mTOR and AMPK have a strong relation so if you inhibit mTOR than it creates better conditions for AMPK to increase and vice versa.
Very simplistic view of the pathway
Rapamycin > mTOR ↓ > AMPK ↑ = Immunosuppressive ↑ + Antifungal ↑ + Anti-inflammatory ↑
The pathway is important to understand because then we better understand how other interventions also work. For example, today it’s not only rapamycin that has immunosuppressive, antifungal and/or anti-inflammatory effect.
Two other intervention is for example extended fasting or calorie restriction. This two has been connected to immunosuppressive and anti-inflammatory effect. I have never read anything about that these two interventions should have antifungal. Do someone know if they have this effect?
The pathway for these interventions can be simplistic illustrated like this. The mTOR inhibition is usually not as big as when compared to rapamycin.
Fasting or calorie restriction > mTOR ↓ > AMPK ↑ = Immunosuppressive ↑ + antifungal ↑ + anti-inflammatory ↑
Now to the interesting part. If we look at coconut oil or MCT oil then these are usually said to have antifungal and anti-inflammatory effect. Here the pathway would look more like the above. Of course the mTOR pathway will also be lowered because of the AMPK increases.
Coconut oil or MCT oil > AMPK ↑ = Antifungal ↑ + Anti-inflammatory ↑
Can it be that both coconut oil and MCT oil has some immunosuppressive effect? My quess it most likely is so. If someone finds any study or something that supports or not support this post a comment in this thread.
I found this very old study saying that diets high in polyunsaturated fat have higher immunosuppressive effect than diets high in saturated fat.
“diets high in polyunsaturated fat, relative to diets high in saturated fat, are more immunosuppressive and are better promotors of tumorigenesis.”
Source: Lipids and immune function - PubMed
So when it comes to coconut oil and MCT oil then these contains primarily of saturated fat. So it probably looks like there is some kind of similiar pathway and my quess is that everything regarding the immunosuppressive, antifungal and anti-inflammatory effects are more connected to the AMPK activation.
Lets look at something else for example garlic. I seems like it has both antifungal and anti-inflammatory effects but does it have immunosuppressive effect? I quickly looked around and found this study.
“Under certain conditions garlic extract may act as immunosuppressive for downregulation of pro-inflammatory responses.”
Source: Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic): A Review - PubMed
So here the pathway looks like this.
Garlic > AMPK ↑ = Immunosuppressive ↑ + antifungal ↑ + anti-inflammatory ↑
When people say that rapamycin is dangerous because it has immunosuppressive effects then also garlic, cocunut oil and other AMPK activators are also dangerous because they use the same pathway.
Now to the verry interesting question. Now that we digged little bit in to the pathways can it be that you could get similiar lifespan benefits as rapamycin with other AMPK activators. For example if we just find the right dose when it comes to garlic extracts we most likely could mimic the effects of rapamycin.
This goes also back little bit into one of my earlier threads here in the forum were I pointed out that it’s more important to look at the overall dose of mTOR inhibition than just the dose of rapamycin (The total dose (regime) of mTOR inhibition vs Rapamycin dose regime). Because one person can for example practice fasting, calorie restriction and take rapamycin and one other person is just taking rapamycin. Very simplistic conclusion is that the first person probably will generally need to take little bit less rapamycin than the second for the similiar effect on lifespan.
This thread has opened my eyes to also take in consideration the overall AMPK actication dosage.
PS. Sorry about the long thread but I felt it is a important topic to raise.