Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes
 

Highlights

• •Fasting mimicking diet induces prenatal-development gene expression in adult pancreas
• •FMD promotes Ngn3 expression to generate insulin-producing β cells
• •Cycles of FMD reverse β-cell failure and rescue mice from T1D and T2D
• •Inhibition of PKA or mTOR promotes Ngn3-driven β-cell regeneration in human T1D islets

Summary

Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing β cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models. In human type 1 diabetes pancreatic islets, fasting conditions reduce PKA and mTOR activity and induce Sox2 and Ngn3 expression and insulin production. The effects of the FMD are reversed by IGF-1 treatment and recapitulated by PKA and mTOR inhibition. These results indicate that a FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D patients and reverse both T1D and T2D phenotypes in mouse models.

http://www.cell.com/cell/fulltext/S0092-8674(17)30130-7

"oh, would that I were a mouse!"
Thanks for sharing RawNut.

Why "mimick" fasting?!?!?!?

Just Don't Eat.

It's the panic of low blood sugar talking when people act like skipping a meal is some kind of looming doom.

I find this topic interesting. Not sure it's settled science but according to Longo's research, you can't duplicate these same benefits by intermittent fasting 16,18 or even 36 hours but really need the several days. The whole purpose for the fasting mimicking is that most people are unable or unwilling to do a true fast for 4 or 5 days. If you can still get the benefits by eating 500 calories a day for 4 days, it seems like a good option to me. I have tried it, along with the 5:2 approach, and found I did overeat after stopping, but even if that negated any weight loss, it still should provide the regenerative effects.

Why limit options, if there are more than one that works?

Seems as though the mimicking diet is the same as the Newcastle protocol?? 500 cals per day.

I get it, and yes. So there is a "floor" by which the body regards itself to be in the fasting zone.

I am probably speaking from my own experience; where it was always easier to not eat at all than it was to eat in small bits. :lol:

I can identify with the feeling of panic. The more metabolically out of whack that I became the more exaggerated those BG swings would get. Crashing BG after eating a junky carb meal put me in a mode where the only thing that I could think about was to eat something to get my BG back up. Eating more carbs provided quick but temporary relief. Over time I developed a near pathological fear of missing a meal and of not having food handy for a moment of "need". I don't think that I missed a meal for at least two decades and supplemented that with ever increased snacking. Doing my first 18 hour IF 2 years ago was a big deal for me. I skipped breakfast on that one and was amazed that hunger didn't get me. I did my first 24 hour fast a few weeks later with real fear and trepidation. That first longer fast went OK, too. It took several IFs to retrain my brain to lose that fear. It was so wonderful to NOT be either eating or thinking about eating during every waking hour. These days missing a meal is nothing. Most weekdays I eat only 2 meals and don't snack in between. A few years ago I would not have thought that was even possible for me -- not without miserably suffering from hunger, anyway.

So for people who are where I was, the fast mimicking diet probably sounds like a better idea. The problem for me is that underrating is harder to do than not eating. When I had a lot of extra fat on me I could get away with eating less than my BMR required. These days I find eating less than 1500 calories a day tough to do even with healthy LCHF macros. The hunger does get me. If I'm going to fast then I need to do that "Don't Eat" thing.

In the first video, Dr. Valter Longo (one of those listed in the cell.com OP study article) says that he tried getting water only fast research backing and could not due to concerns for safety, so he added / created the fasting-mimicking diet and then got going on human studies. Fascinating interview (first video), and the second is a (shorter) TEDx talk.

Valter Longo, Ph.D. on Fasting-Mimicking Diet & Fasting for Longevity, Cancer & Multiple Sclerosis 10-1-2016
( Dr. Rhonda Patrick is great! )

Fasting: Awakening the Rejuvenation from Within | Valter Longo | TEDxEchoPark 12-5-2016

I find the easiest fasting mimicking diet to do is heavy cream in coffee. None of that 50 calories a day stuff, that just covers one coffee. Like Ken, small amounts of food can be harder for me than outright fasting, cream in coffee doesn't seem to be a problem that way for me. From the purity standpoint--if you find a modified fast easier, I say go for it. Is a pure water fast better? I've never seen Longo's modified fast put up against a pure fast directly, so I don't know. I know there's evidence for benefits from either one. Water fasting is certainly liable to be a stronger dose. Is the strongest dose possible always ideal? If we had no data on a fasting mimicking diet, as a caution we could tell people to only do pure water fasts, we wouldn't know how much food it would take to ruin the therapeutic benefits of fasting. We have a growing body on the benefits of the fmd, I think it makes sense to admit that it exists. :lol:

I first heard of Valter Longo on the Kevin Rose podcast. Subsequently, I have seen a lot of copy cat or home grown Fast Mimicking diets. These often include avocados and protein powder, aiming for that 500 calorie range. I am not sure if it was implied or inferred, but I had the impression from Longo that he developed a specific diet, not just a calorie target, to promote atophagy for those 5 Fast Mimicking days. It may be that he just wanted to sell his product, and I didn't buy it nor am I promoting it, but if you accept his research, and do not want to buy his product, you may be better off just doing a true fast.

I don't think there's a whole lot of mystery that goes into this. Protein not too high, carbs fairly low, what little calories largely from fat. Most of the difference between a fast and feeding metabolically is the difference between metabolizing exogenous vs. endogenous fuels--the more of your fuel is coming from fat, the more you're mimicking fasting. The protocol likely doesn't depend on what's been left in (nuts, green veggies etc.) as it depends on how little has been left in for the period of the "fast."

They are somewhat secretive about the ProLon package, but my understanding is that it is basically fat free with the 500 calories from protein and carbs .

That doesn't fit with what I've heard from anecdotes from people who actually did the protocol. Longo prefers real food, so it's really just a matter of people looking at the stuff when it's sent to them.



https://www.quora.com/What-are-the-...ras-ProLon-diet

I honestly don't see anything special about this formulation.

Maybe I just read something into what he said. Hard to argue with reports from people who have actually purchased the product.