Does a healthy ketogenic diet cause irreversible insulin resistance?

#213

The problem is (or it isn’t, but I’ve found no evidence to reassure me that it is ik): on a normal person glucagon says: liver, do your job and dump glucose! Liver obliges!

That’s wonderful. However, 2 problems: if ketones are so wonderful and I’m in ketosis, why I need so much glucose to get up a flight of stairs?

Second problem: on a normal person, by at least 2 processes, the muscles that needed the glucose use it and your blood level is lower again in no time.

In a few of us posting in this and other threads, it stays up.

Suppose it stays up because my muscles actually prefer ketones. Fine by me to flee the tiger running. However, that glucose that my liver dumped is therefore being kept unattended in my plasma.

I haven’t found evidence it isn’t doing what too much glucose in your blood does: damage!

Besides your wishful thinking (mine too, I want to hope!), do you know for sure from what level high BG is ok? For a woman?

I added “for a woman”, because mean BG increases with age. For women it seems to be linear. By that curve, instead of in my 50s, I’m in my 70s!

#214

“He feels”, “perhaps”…

If I had t2 patients who finally got to control their BG and get it pretty level, I wouldn’t worry as much as I was worrying before.

How much you worry also depends where you start, what are your conditions. Also, if a person is getting depression from trying so hard to control BG, or other things, as a dr I would also try to find a place where there’s a balance, a realistic place where to tell my patients that it is ok. Quality of life passes also by being able to balance these things. So, I totally see where he may be coming from.

I appreciate you trying to help. Thank you very much!

(Bacon is a many-splendoured thing) #215

The interesting point for me is that there isn’t any evidence high BG is bad, either, if one is in ketosis. We need a lot more research before we start jumping to conclusions.

A lot of the damage of the standard American diet comes from the elevated insulin that results from the elevated glucose. So I’m wondering just how damaging elevated glucose might be, if our insulin is still low enough for us to remain in ketosis.

(Bacon is a many-splendoured thing) #216

Glucagon and insulin are not the only things regulating gluconeogenesis. A study on mice of (various types) that lack the ability to produce neither glucagon nor insulin (they start with mice that genetically lack the ability to make one of them, and then knock out their ability to make the other) shows that they never become diabetic, and their blood sugar remains stable.

Apparently, Type I diabetes is a disease of being able to produce glucagon without being able to produce insulin to regulate it (each of them helps regulate how much of the other the pancreas produces, since the α- and β- cells are right next to each other in the Islets of Langerhans). With both hormones out of the picture, other bodily mechanisms take over to regulate blood sugar.

For one thing, being in ketosis means that fatty acid metabolism is powering our endurance performance. But we still need glucose to power our explosive performance.

I should add that these remarks of mine are pretty speculative. But if people can argue that there is no evidence to show that long-term keto eating is safe (despite the experiences of quite a few people and the evolutionary evidence), then it can also be argued that there is no evidence to show that long-term keto eating is unsafe, either. What we need is to gather data. As the Dudes’ dogma goes: “Show us the data!”

#217

From my limited layman understanding, it seems that the reason why your blood glucose was increasing when doing even the least amount of activity and not going down is as follows:

  • The brain can use 15-20% of circulating ketones for its energy needs. The remaining 80-85% must come from glucose and the brain is uncompromising in obtaining this

  • On a low carb/keto diet, it is widely accepted that that the brain will obtain the glucose it needs through gluconeogenesis.

  • If for any reason the brain is unable to get enough glucose via diet and/or gluconeogenesis, it will increase cortisol levels in the body.

  • Increased cortisol levels = increased gluconeogenesis = higher blood sugar (that are not absorbed by the muscle due to the cortisol reducing muscle uptake of glycogen)

  • Medium/High Intensity activity/exercise (perhaps as defined by your heart rate zone when doing it?) also increase cortisol levels. This elevated cortisol even more, stimulating more gluconeogenesis and further increasing blood sugar.

Upping your carbs likely gave your brain a bit more glucose, removing the need for the brain to increase cortisol . You also switched to lower intensity exercises, which stimulate less cortisol. Lower cortisol = reduced gluconeogenesis = lower blood sugar.

Though, I am not sure how the consumption on unsaturated fats factor into the equation

Also, I wonder why the brain wasnt able to get enough glucose via gluconeogenesis in the first place if someone was eating enough protein.

My current theory is that perhaps gluconeogenesis is not as efficient in providing the brain with glucose in some people and perhaps those people will need to eat the upper keto carb limit (30-50g) or possibly even higher to avoid this situation.

That said my question remains as well: If blood sugar remains high, does being in ketosis somehow prevent resultant damage from high blood sugar? There are only assumptions and opinions in response to it. No studies or research we can point to for definitive answers. So for me, as far as I am concerned and until research says otherwise, having high blood sugar while on keto will cause damage, particularly with an equally elevated Hba1c.

(Michael - When reality fails to meet expectations, the problem is not reality.) #218

A layman’s understandable explanation:

Being Patient: Ketones are an alternative source of fuel for our brain. Are they as efficient of a fuel as glucose?

Benjamin Bikman: The best available evidence suggests they’re more efficient. You literally create more chemical energy when the brain is burning a ketone than it does burning glucose. We say that ketones are an alternate fuel, but the reality might be that it’s the primary fuel.

Case in point: If we start to increase ketones in the blood of a person, even though ketone [levels] are much lower than glucose, maybe it’s only a quarter as much in the blood, even still, the brain immediately starts relying on ketones. As ketone [levels] go higher and higher and higher, the brain continues to rely on the ketones more and more as its fuel.

My lab [was] able to get tissue from donors and study the difference in gene expression between those genes that are involved in glucose-burning versus ketone-burning in people who had died with Alzheimer’s disease and with no Alzheimer’s disease. It was the glucose-burning genes that were compromised, not the ketone-burning genes. That is so powerful because if a person has an energetic gap, well then let the brain eat ketones and ketones can more than fill that energetic gap and improve cognitive performance.

Low blood keton levels
#219

Certainly one possibility based on limited evidence.

(Joey) #220

This thread got me wandering down the rabbit hole some more…

I appreciate the understandable concerns expressed in this thread can’t be addressed absent specific on-point scientific evidence. It would need to show that slightly elevated - but highly stable - glucose levels [arising from carb-restricted gluconeogenesis (“physiologic IR”)] do NOT lead to the kind of tissue damage wrought by markedly wider swings in glucose - but with lower lows and higher highs - from the more prevalent carb-infused diet [associated with “pathologic IR”].

I’m a science fan, too, and would love to take comfort in such a study.

But lacking evidence hasn’t stopped me from continuing to read what is available on the topic. Most of it seems aimed at lowering concerns over keto’s long-term effects on diurnal glucose levels. Although such claims are made without being able to cite hard evidence since apparently it doesn’t exist.

This situation hasn’t stopped me from sticking my finger with a needle from time to time :wink: And I seem to get the same results over and over again, quite reliably.

Never having been diabetic, I am now 2+ years into a diligent low-carb WOE (leafy green veggies with dinner meat/fats are my primary source of minimal carbs), my fasting serum glucose - including dawn effect - routinely hovers around 100 mg/dL.

The “big” intra-day swings take me from the mid-90s to the mid 100-teens, i.e., +/- about 20 mg/dL throughout the day.

For example, today I measured glucose every 1/2 hour following lunch…

97 mg/dL - 16 hr fasted state, after a cardio workout just before lunch
111 mg/dL - 30 min post-prandial
115 mg/dL - 60 min post-prandial
118 mg/dL - 90 min post-prandial
118 mg/dL - 120 min post-prandial
114 mg/dL - 150 min post-prandial
(got bored and pin-cushioned, gave up testing)

FWIW, lunch consisted of a hard-boiled egg, salami, beef stick, guacamole, chunk of extra sharp cheddar, a Brazil nut - not atypical.

None of this proves anything.

Perhaps I am doing grave damage to my organs, brain and toes by spending most of my afternoon with glucose above 100 mg/dL?

Perhaps I need to consider taking medication to better manage what keto has done to my glucose level?

My hunch is that there is nothing the medical community could offer this “carb-starved” body (insulin? a return to eating pizza crust, pasta, and rice?) to change this glucose profile for the better. It appears the patient is in stable condition.

Given my other biomarkers (minimal Trigs, super high HDL, declining CAC score, minimal inflammation markers, norm/low blood pressure), it’s my stronger hunch that a stable - albeit higher - glucose level that is being naturally-produced by my body is quite healthy.

As we often say, we’re all different n=1 individuals with unique needs that change over time. I can’t give anyone else advice on what’s right for them at this moment in their own lives. Please do what you believe you need to do to take the best care of yourself!

Sharing is caring. Just my $0.02 :vulcan_salute:

(Michael - When reality fails to meet expectations, the problem is not reality.) #221

According to the current paradigm ketones can be utilized for up 2/3 - 3/4 the brain’s energy requirement, but some glucose is always required. Ben Bikman, who has specialized in the study of ketones and the brain, says he sees no evidence the brain requires any glucose. That’s why I quoted Bikman in my previous post:

Also, I will point out that during fetal development the gestating baby is in ketosis and its brain continues to use ketones preferentially after birth. It’s only with the transition to a high carb diet that glucose becomes the predominant brain fuel.

(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.

(Bacon is a many-splendoured thing) #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.

(Bacon is a many-splendoured thing) #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.