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

I think the research is totally on the right track though I suspect it doesn't need to be as restrictive re saturated fats to restore pancreatic function

I have been pretty much doing this over the last few months with the exception that I did not particularly restrict saturated fats, so whilst I have definitely eaten more nuts and seeds than I did before , I happily embrace saturated fats too. I simply eat whichever protein source I fancy, where my real restriction comes from trying to keep my proteins at under 70g and my carbs to under 30g. That naturally reduces the amount of for example meats to low portion sizes, I generally eat 80-100g maximum of my main protein in a meal, and considerably less if its cheese or nuts.

I do a few days of very restricted calories - under about 800 and then a few days of rather more - say 1600 average - that's not particularly conscious " strategy" just seems to be what happens after I've tried to go very low calorie for a few days, including fasting.

This week I have recorded a 7 day average of 91% (normal target 91% ) of all blood sugars under 6.7 mmol and 100% of blood sugars under 7.8 mmol (target 99%) despite a couple of meals that included mashed potatoes.

Overall therefore I think I might be on the same track they have just outlined but without the vegan restriction.
 
I have been eating lowish carb/protein and high unsaturated fat for a year now and my numbers have never been better. Perhaps something is going on that I don't know about as I can definitely handle carbs better these days and can't even remember the last time I spiked as high as 7. Hmmm. I am stricter during the week and relax a bit over the weekends so not eating the same ratios/volume every day.

I wonder though, if this way of eating is normal for me, what I would have to do for the "eat normally" weeks? Maybe if I just reined it in for the fasting week then ate more on the normal weeks that would work? Just thinking out loud here as I wouldn't know how a person checks beta cells anyway to tell if anything was improving.
 
If you link through to the actual paper as given earlier.

- fasting phase cleans out non- functioning cells
- feeding phase stimulates the regeneration
- the T1 mice had there Beta cells killed with a drug so obviously not a situation that emulates a hostile immune system
- there is mention of limited clinical trialling but not much detail other than their suggestion that is looks worthwhile to try wider trials.

I'm prepared to be open minded given the evidence from the reported successes with T2s on Intermittent Fasting and also Bernstein and the fact that newly diagnosed T1s can preserve Beta cell function fot extended periods. I doubt T1s could reach full beta cell function but is there a sustainable point where the level of regeneration counters the immune system kill rate?
 
Full text is open access at http://www.cell.com/cell/fulltext/S0092-8674(17)30130-7 . Images and methods are linked via tabs near the top of the article.

Main points:
  • This research involves mice, not humans in any meaningful capacity
  • It uses a "diabetes model", which is not going to be the same as diabetes
  • Fasting consisted of 50% of standard calories on Day 1 & 10% Days 2-4
  • Fasting was followed by up to 10 days of unlimited normal rat chow
  • Fasting cycles apparently continued for a bit over 10 weeks (6 cycles)
The first fatal flaw with this research is in the Methods section, which they've hidden on a separate page from the main body of their paper. They claim to have induced Type 1 diabetes with a single injection of streptozotocin, whereas it actually requires multiple doses. They didn't give the mice Type 1 - they gave the mice hyperglycemia Accordingly, the Type 1 results are already completely meaningless, and there's probably no need to look for further flaws regarding the Type 1 model.

"Type 2" mice were diabetic due to a genetic mutation which impacts leptin, and results in the mice grossly over-feeding themselves. Again, it doesn't sound horribly similar to how Type 2 typically occurs. These mice have elevated insulin at 2 weeks of age, obesity at 3-4 weeks, followed by severe depletion of beta cells (age?), and death by 10 months of age. The mice in the study were aged 10-12 weeks in the pre-treatment monitoring period, then assigned to the fasting or control group.

One potential problem with the Type 2 mice is that they were only 12 weeks old when the fasting and refeeding started, hence their beta cells were still in pretty good shape. Beta cell function was not directly assessed, but calculated based on fasting glucose and insulin levels. The mice were killed, presumably at 150 days after baseline at an age of 7.5 months. Accordingly, it was not shown if the diet resulted in longer life span than expected for that type of mouse, though one graph suggests that 45% of non-fasting mice died prematurely, aged 4.5-6.5 months. There's no mention of the deaths or the actual rates and ages in the text, which is rather suspicious.

The numbers they show for supposed proliferation of new beta cells is a bit dodgy, since the standard deviation is quite large - meaning the values for at least some mice were likely much, much lower.

The fasting mice, while doing better than the unlimited over-eaters, still weren't looking too good by the end. Day 90 shows control mice with no insulin, but the fasting mice are barely doing any better. Plus standard deviation isn't shown at that one time point, which is interesting to say the least, and measurements from day 120 and 150 are omitted, even though those days are included in other results. Fasting blood glucose is around 300 (16.7) around day 135, which is pretty dismal, and appears to be trending upward - no data for day 150. In general, glucose and insulin values are not shown at consistent intervals, meaning the researchers may have selected the days which made the fasting group look best. Values are also not clearly matched up with dietary periods (fasting or refeeding), despite the description claiming they are - there don't appear to be clear refeeding periods which should be twice as long as the fasting period, and all of the intervals look about the same.

Glucose tolerance showed the same rise and decline for the fasting mice as for the control mice, just with a lower starting point. Fasting mice showed a better reaction to insulin, but that doesn't support the suggestion that this diet potentially results in no need for insulin.

There's also no mention of correcting the threshold for statistical significance, to take into account the likelihood of false positives when making numerous comparisons.

At best, this is an extremely preliminary study. There is absolutely no way that anyone can speculate that it would be applicable to humans with Type 2, and it doesn't involve Type 1 at all, despite claims to the contrary. I rate this study a big fat "MEH"
 
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Hi,
Just read a BBC news item about reversing diabetes including Type 1 amazingly !!! (OK it's only in mice) if put on an extreme LCHF "fasting" diet for 5 days in every 30. What I understand is the starvation bit sends the old beta cells into a panic and triggers the pancreas to create islet (insulin producing cells) - don't get the science to be honest. As I'm on insulin I'm not stupid enough to try this at the moment without talking to my consultant but all the same quite excited that it maybe possible to reverse Type 1. Is this old news for you guys ? Is this something my DSN would laugh at and tell me to "Get Real". I am also very sceptical about medical advances based on news stories as they seem to change daily. Should I mention this the next time I meet my Consultant....Or have a reality check... on the positive...reading the article has made me happy for the first time in months....so that can't be bad....

Best regards....and hope you are all well,

Mark
 
Thanks @ME_Valentijn, I'm late to the party it seems....I thought there would be some scepticism ....rightly so it appears...But LCHF keeps raising its head as good for Type 1's....Dietician appointment in a few weeks, will discuss as my BG is becoming a bit erratic...not sure why as I'm eating the same sort of food and qty...Mark
 
It sounds very similar to the Newcastle and Glasgow University experiment with Roy Taylor.
http://www.ncl.ac.uk/magres/research/diabetes/low-calorie-diets/
Very low calorie (800) and liquid diet. Has been proven in humans to reverse the symptoms of diabetes in Type 2 diabetics. It was inspired by the diet programme for people who have undergone bariatric surgery. It was found that these patients often had improved pancreatic function after surgery but in the end it was put down to their diet.
It's a very interesting theory. Let's hope it works.
 
Yes, good points.
I am waiting for Zoe Harcombe to take this apart, not that you haven't done a great job.
I have some reservations
1. I am sure I have read that mice have been induced to grow beta cells before, but, although mice and humans are very similar, the results couldn't be replicated in human cells.
2. I am very uncertain about the efficacy for Type 1. For Type 2, is there any need to regrow beta cells in most cases? Is there any research to show that beta cells don't recover all by themselves if keto or LCHF diets are applied?
3. I don't understand why researchers don't look at all the current diets and how well they do, rather than set up new models. I wish someone would look at the statistical evidence available on this forum for how actual diets affect actual humans.
 
BrianTheElder said:
1. I am sure I have read that mice have been induced to grow beta cells before, but, although mice and humans are very similar, the results couldn't be replicated in human cells.
Click to expand...
Mice and humans aren't that similar ... the one exception is the immune system.
 
Here is the article: link

And here is the peer-reviewed journal: link

To summarize it:

- FMD (fasting mimicking diet) first reduces β-cell number, but then it returns to normal levels after re-feeding, "suggesting an in vivo lineage reprogramming."

- FMD as a low protein, low sugar cyclic diet used in the study.

- FMD cycle suppressed cytokine production associated with β-cell damage, and increased the number of cytokines associated with β-cell regeneration.
"...FMD cycles reduce inflammation and promote changes in the levels of cytokines and other proteins, which may be beneficial for the restoration of insulin secretion and the reversal of hyperglycemia."

- (after comparing healthy human vs T1D cultured pancreatic islets) "...These results raise the possibility that the effect of the FMD on pancreatic regeneration in T1D subjects could be mimicked or enhanced by pharmacological inhibition of these pathways."

So this isn't a magic bullet for type 1-s, but with applied diet AND/OR shutting down the mTOR and PKA pathway (with medication), this could be successful. Now the good news is that we have inhibitor drugs for them.

Thoughts?
 
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Apparently Metformin is an mTor inhibitor in itself.

AFAIK, PAK inhibtors are in clinical trials and mainly intended to be anti-cancer drugs.
 
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