Does a healthy ketogenic diet cause irreversible insulin resistance?

(Michael - When reality fails to meet expectations, the problem is not reality.) #222

Pertaining to the OP question. I’ve commented several times above so I will only add a couple of points here. If there were something per se about ketosis or eating to sustain ketosis that leads to steadily rising BG levels, systemic insulin resistance and an unhealthy outcome all of us would experience it. Many folks on this forum, myself included, have been in continuous ketosis for years and maintain normal glucose control which suggests normal insulin sensitivity. As I’ve mentioned multiple times, keto is a process of metabolic normalization that takes time to fix whatever has been broke from previous years/decades eating otherwise. That might be longer than you thought.

Finally, if there were something intrinsic to ketosis or eating to sustain ketosis that resulted in an unhealthy outcome, I think we would not be here discussing it. The die was cast 4 1/2 million years ago when a group of primates - who would eventually become us - abandoned the ability to metabolize cellulose.

(Michael - When reality fails to meet expectations, the problem is not reality.) #223

Michael Eades - ‘A New Hypothesis of Obesity’

The cool biochem starts about 1/3 of the way in.

19%20PM

#224

Perhaps. However the point I was trying to make is that there is some obligate need for the brain to get some of its energy from glucose - be that 20%/40% etc and this remains the case no matter how high ketone levels are.

Therefore, individuals whose brain struggle to get this 20/40/Other% of energy from glucose will perhaps see the brain induce a release of cortisol after which their blood sugar will be observed as rising.

The question is…why are those affected not able to obtain the glucose required for their brain from gluconeogenesis - they are certainly consuming enough protein to provide the raw material for it. The answer to that question is subject to various theories and assumptions based on very limited evidence - many of such which you have posted. Perhaps it is glucose/insulin sensitivity, perhaps it’s something else.

In the meantime however, I guess the needful must be done by those affected with high blood sugar & rising Hba1c. Be that by increasing carb intake to increase glucose available to the brain and/or taking steps to amend excercise routines to those that stimulate less cortisol.

The answer to each and every problem while in keto is perhaps not necessarily always “eat less carbs” and each case must be considered based on its circumstances. It may well be “eat slightly more carbs” for these individuals.

(Michael - When reality fails to meet expectations, the problem is not reality.) #225

As Bikman points out, the brain will use as much ketones for its energy as it can get. If it can get 100% it will use 100% - no glucose required. If you think about it this makes perfect sense. The brain requires ‘energy’ - a lot of it, all the time - and the more efficient the energy source the more efficient the brain functions. Ketones yield multiple times the energy of glucose per unit and less ‘exhaust’ to get rid of. Bikman has demonstrated this with elderly Alzheimer patients. Their brain function improves when given exogenous ketones. The ketones go right to their brains. Their brains utilize the ketones in preference to any available glucose. Bikman additionally points out his examination of brain tissue from deceased Alzheimer patients - it’s their glucose processing that was damaged whereas their ketone processing remained normal.

Thus, I see no reason to suspect that lower glucose to the brain causes folks who are in continuous ketosis to boost gluconeogenesis - and elevates BG and insulin - to make up the shortfall. This is probably exactly what happens to folks who are not in ketosis and cortisol may be the mechanism. I think if this happens when someone is in continuous ketosis then something is haywire either in the brain or glucose metabolism (by which I mean all the hormones and processes involved in managing glucose production and utilization). Of course, ketogenesis and/or lipolysis might be impaired and/or damaged and so can not supply the brain with adequate ketones. But either way, it’s still not ketosis per se causing the problem - not all of us in long term ketosis experience this. I think the problem is residual dysfunction from pre-keto high carb eating. I don’t think eating carbs is a way to help alleviate it, just prolong or make it worse.

(You've tried everything else; why not try bacon?) #226

Is this really true? On what data are you basing this?

I know that George Cahill estimated the brain needed 130 g of glucose a day, but Benjamin Bikman has challenged that notion, saying that so far as he can tell, the brain needs no glucose at all, given abundant ketones. His standing challenge, which I understand has not yet been met, is for someone to produce data showing just how much glucose the brain actually needs.

Cahill himself did an experiment on his fasting subjects, using a hyperinsulinaemic euglycaemic clamp to drive their glucose down to levels that would normally cause coma or death. But the subjects were fine, being in fasting ketosis (i.e., with serum β-hydroxybutyrate between 3.5 and 6.0). The researchers were scared to go further, and they realised afterward that what they had done was highly unethical (certainly no IRB would tolerate such an experiment these days), so they downplayed the incident and buried it in the back of their writeup, according to Dr. Phinney.

#227

I have read this quite a few times over the years. The source that immediately comes to mind is Dr Nadir Ali. I’ll link to one of his videos below but feel free to go through his videos for references etc

From around 5:50 in the video below.

Also, the same question you posit could equally apply to your statements. You have cited Bikman’s theories , one n=1 experiment and a research that seem to have been stopped halfway ableit for seemingly ethical reasons. Does that then make it universally true & certain that NO glucose is required for the brain?

Therefore while this uncertainty exists, let each person assess their results on a ketogenic diet (in light of their rising blood sugar) on their individual circumstances and do the needful to correct this… including the possibility of increasing dietary carbohydrates.

(bulkbiker) #228

If glucose is “required” for the brain then gluconeogenesis will provide it.
No dietary glucose whatsever would be required though.

(Michael - When reality fails to meet expectations, the problem is not reality.) #229

Maybe you missed it, but @PaulL noted that Bikman issued a challenge to the scientists who study this stuff to show any data that indicates the minimum glucose requirement of the human brain. I don’t know specifically how long this challenge has been outstanding, but it’s at least a few years already. No one has offered any data yet. It’s not like this is some scientific backwater - it’s a major field of scientific endeavor, especially as it relates to declining brain function with age. Still, no data has yet been proffered. My guess: ketones are the primary, preferred and most efficient fuel - glucose the emergency backup. Human beings evolved for several million years primarily in a state of continuous ketosis. The brains of our ancestors were not running on glucose.

#230

Yes, that is what is expected. That is the theory.

However see my earlier statement and question on this in post 223 on if/why there could be situations where gluconeogenesis is not effectively providing the required glucose needed for the brain.

#231

Again - perhaps.

That is the point I keep repeating. A Bikman quote here, a Phinney theory there, a scientific challenge so steadfastly issued - does not a conclusive evidence provide. Perhaps the brains of your ancestors were running on glucose.

Perhaps will continue to be my position until more research emerges beyond what the limited evidence, opinions and theories currently available.

(You've tried everything else; why not try bacon?) #232

I looked at that video, and while Ali asserts that the brain needs 30% of its energy in the form of glucose, he does not cite any studies to support that assertion. So I’m still looking to know what data that assertion is based on. As we periodically discover, a lot of the conventional wisdom is not actually anchored in any science. I suspect that it may start out as some expert’s best guess, but in the transmission from person to person, it eventually becomes accepted as Gospel.

I’m not saying that Bikman is right to assert that the brain needs no glucose, either, but the fact that a researcher with his credentials can’t find any evidence in the literature to support the notion of the brain’s need for glucose is telling. It seems that we often have to go back and question what we think we know, every so often.

For example, a hundred thirty years ago, when all scientists could measure was the caloric content of food, the idea that restricting calories might lead to weight loss made a great deal of sense. But with the discovery of the hormones glucagon and insulin, the discovery of ATP, Krebs’s work to elucidate fatty-acid metabolism (the Krebs cycle is named in his honour), and the discovery of the radioimmunoassay that lets us measure hormone levels (for which Yalow won the Nobel prize; her partner Berson would have shared it, had he still been alive), and much other research that has taken place, we now have a much more nuanced understanding of how the body operates, and we can see that the body’s hormonal response to the foods we eat is much more important than our level of caloric intake.

(You've tried everything else; why not try bacon?) #233

But what we are all trying to say is that there is no evidence on either side of the issue, so trying to assert that the brain does need glucose is just as unfounded an assertion as saying that the brain does not need glucose.

So show us the data on which your opinion is based. And before you raise the issue, remember that Bikman’s challenge is not proof that the brain needs no glucose, merely an attempt to elucidate where the idea that the brain must have glucose came from. If you knew where to find the data, you could settle this issue right away, by producing a study or two for us to look at.

So let’s all chill and agree to disagree. You have your trusted sources to rely on for your belief, and we have our trusted sources who have called that belief into question. Until there are some actual data to examine, we won’t be able to determine who is correct.

(Michael - When reality fails to meet expectations, the problem is not reality.) #234

I like Dr Ali a lot and in fact I have posted some of his talks on this forum. He adheres to the current paradigm that the brain requires some glucose. But like all others who do so he does not cite any data in support. Bikman has said essentially ‘I can’t find any evidence that the brain requires glucose - does anyone else have something?’ So far apparently no one does. The brain has mitochondria and that indicates it is not dependent on glucose. The blood/brain barrier keeps out the large fatty acid molecules but ketones pass through freely. My opinion is that’s the way it is because for at least 2-3 million years of living primarily in ketosis that was the most efficient way to keep the brain functioning efficiently at the level of energy requirement it has. All those who tried something different left the pool long ago.

#235

Exactly. As I have stated from my very first post: “Perhaps”.

Let each person carry out their own adjustments to their own diet as there is no evidence either way.

(Robin) #236

The End.

(Michael - When reality fails to meet expectations, the problem is not reality.) #237

This discussion reminds me of the related contention that carbs are essential. Even though that claim has been proven wrong there are still many proponents. As Max Planck famously commented (paraphrased): new ideas don’t win over their opponents; the opponents eventually die and younger scientists who are not committed to the old paradigm accept the new one. I think that’s going to happen here. Some older and influential scientists are going to have to die first, but eventually the paradigm will change to accept the new idea that the brain has zero need for glucose when it has access to sufficient ketones.

(GINA ) #238

I have no dog in the ‘the brain needs glucose’ fight, but it did lead me to wonder something.

It is not strictly universal, but most people have more energy and a better attention span in the morning. As a school administrator I can tell you it is true for children and teachers. We usually put the afternoon slump down to getting tired as the day goes on, or sleepy after lunch, but what if it is the effect of the brain having access to what few ketones people on a ‘normal’ diet have… those from their overnight fast? Overnight ketones are gone in a few hours, and as people eat their SAD diet junk no more are created. Their brain stops working as well and they get foggy and tired.

(Michael - When reality fails to meet expectations, the problem is not reality.) #239

You could say the same is a direct consequence of the morning glucose ‘dawn effect’. As the morning wears on that early ‘hit’ of glucose gets burned out, the brain returns to its normal daily drudge of extracting energy from an inferior source. Finally, the bolus of lunch diverts most of the available glucose to the stomach and gut so the brain decides it’s time for a nap.

I find it highly unlikely that folks eating SAD produce any ketones overnight. This could be measured, of course, if anyone wanted to do the experiment. During both of my CGM experiments I had normal glucose through the night with a slight bump up just before getting up in the morning. And I’ve been in continuous ketosis for years. The times when my glucose was lowest were always just before the ‘dawn affect’. I doubt that anyone eating SAD would get their glucose that low unless they’re suffering some metabolic disorder. Or were on a very strict calorie and carb restricted weight-loss diet.

(You've tried everything else; why not try bacon?) #240

I thought the data showed otherwise, though I may well be wrong. It’s not much, but it’s a small amount. I am in the middle of watching a Phinney video where he mentions ketones after the overnight fast. I’ll go back and see if he refers to a paper with data. In any case, I’ll be posting the video as a reference, because it has a lot of good stuff about glucose levels and insulin resistance/sensitivity and mentions several relevant studies.

(Michael - When reality fails to meet expectations, the problem is not reality.) #241

I don’t have any data either. What I’m thinking is: if someone eats 2000+ calories of glucose during the day (500+/- grams of carbs, which is typical SAD) and elevates his/her insulin sufficient to deal with it, I doubt that person is actually in a ‘fasted state’ overnight, which means no lipolysis and no ketogenesis. In my pre-keto life, I seldom went to bed hungry and almost never awakened hungry the following morning. So I presume my metabolism had plenty of glucose to work with overnight. Not even to mention GNC. When I started keto with a 4-day water fast, I did not experience hunger until the second day of the fast. That means for the first 24+ hours my metabolism still had lots of glucose to burn.

That’s why I think a person on a typical SAD regimen would have to do something unusual - like fast for a day first - to produce ketones overnight.