New Dr. Fung blog post on Fasting and Autophagy

(Doug) #1

https://idmprogram.com/fasting-and-autophagy-mtor-autophagy-1/

“This new section covers mTOR, autophagy and mitochondrial disease, which you’ll see later, ties in very closely with the origins of cancer.”

(Mel Soule) #2

Doug,

Thank you for posting this. Very glad to see Dr. Fung celebrate Yoshinori Ohsumi, the 2016 Nobel prize winner for Medicine for his work on autophagy. Very thrilled to see Dr. F bring mTor to the forefront of discussion here. Prior it was Ron Rosedale who carried that banner and woke me up to the need to monitor protein if you want to spend more time in maintanence and repair and less in growth. More time in maintanence and repair equals a longer healthspan for us all.

(Doug) #3

Mel, it does seem to be a “big deal” in the grand scheme of things. I wonder where we will be in 20 years.

(Mel Soule) #4

Yes it does my friend. Oodles and oodles of bucks going into research in this field right now. Pharma can smell an opportunity especially one so plainly obvious as a drug target. I’ve heard Ron Rosedale mention at an Ancestral Health talk he gave in the Q&A that he was taking himself low dose rapamycin to down regulate this age promoting pathway. Been doing a deep dive into the literature on this myself lately because after getting control of insulin resistance with the LCHF strategy, I’m now trying to sort out the “how much protein” wars. Rosedale suggests low, so does Phinney et al. Fasting blood sugar should be the guide according to Phinney. If carbs are low, and FBS is high back off on the protein until the sugar comes down. Then thats the right amount of protein for maintenance. Rosedale suggest 0.5 gms/kg lbm. My FBS is 74 and protein is at 0.5 gms/kg lbm. I might be at the right bus stop here. KCKO

(Doug) #5

Mel, that reasoning seems sound to me. Not a weightlifter myself, but have known many from being on internet gaming teams with them - and at times the weightlifting/bodybuilding community has just gone crazy with protein, eating large amounts while also taking protein supplements - much of this coming from a “more is better” mindset.

Meanwhile, in the U.S., for example, how often do we see protein deficiency? Aside from rare, extreme cases and eating disorders, almost never, I think.

#6

One thing the blog does not address is the duration of fast required to trigger autophagy. Does anyone have the study background for duration?

#7

Google is my friend…

https://besynchro.com/blogs/blog/the-profound-benefits-of-fasting-and-autophagy

The study looking at liver cells found that the number of autophagosomes increased 300% after 24 hours of fasting, and a further 30% after 48 hours of fasting. Studies looking at autophagosomes in brain cells had a similar findings. [8]

[8] http://www.tandfonline.com/doi/full/10.4161/auto.6.6.12376

(Doug) #8

Information on humans is woefully small and incomplete. Mice really ramp up autophagy by 24 hours and increase it further by 48. It also operates on difference schedules per body part, i.e. the liver will be different from the brain, etc.

From what I’ve read, autophagy goes hand-in-hand with the activation of AMPK (adenosine monophosphate-activated protein kinase) and the suppression of the mTOR pathway (mechanistic target of rapamycin or ‘mammalian target…’).

Between 24 and 36 hours after eating, our bodies have pretty well taken all the energy from that food, and we’ve burned well into or through the stored glycogen. Autophagy really gets going during this time frame, again - from what I’ve read. Some people say it peaks at 3 days; I don’t know. Some people say autophagy is always going on, a little bit, and that it increases after fasting for 18 hours.

Seems to me that once the process is occurring bigtime, then we ought to give it some time to do its work, so I’m in favor of fasting for 3 to 5 days, if not longer. It’s hugely an individual thing - how well we respond to longer fasts.

https://www.myhealthwire.com/news/herbs-supplements/963

(Mel Soule) #9

Keigan thank you for posting this. The liver and brain mouse studies is new to me and intriging. Duplicating this work in humans would be a rough go trying to get a protocol like this through an IRB. However, believing as I do that there is a Grand Homology driving evolution some systems working in less evolved species have been shown to be conserved in higher order ones.

Doug, that is my understanding as well. I thank you as well for posting the link to the AMPk post. Clearly the best expose I’ve seen to date on how this pathway and mTOR relate. Outstanding resource.

(Doug) #10

Mel, all this stuff is new to me this year; very glad that I’m learning about it “better late than never.” With the potential that autophagy may have for cancer treatment and preventation, and the same for some neurodegenerative diseases, Alzheimer’s for one, I think we’ll see more and better information in the future. Trials are going on right now for some drugs that kickstart autophagy, so their definitely is interest.

My gut feeling, which may be worthless, is that a mouse is going to be no slower than a human, and probably faster in some or all respects of autophagy. To have a mouse go 48 hours without eating is pushing it close to the edge - many will be dead in another day. If I had to pick an equivalent date for fasting humans, I’d say months, anyway.