Does a healthy ketogenic diet cause irreversible insulin resistance?

#314

I ate the typical standard approved diet for 70+ years before I started eating keto. Fortunately, either due to genetics (thank you, ancestors!) or just dumb luck I did not experience any noticeable metabolic problems. During the decade of my 60s I gained about 25-30 pounds of excess weight and now, with the knowledge I have gained by much learning, I attribute that to insulin resistance. It took me about 6 months on keto to return to approximately the same overall body weight and comp I was at the age of 18. Overall I’m healthy and fit, much more so than others of my age. I am supremely grateful for it.

That said, I don’t measure glucose frequently, but when I do so it’s within the ‘normal’ range. I add the scare quotes because as Bikman has pointed out, ‘normal’ is defined in terms of eating SAD. I no longer eat SAD so what’s normal for the people who do so may or may not be normal for me. Also, as Bikman has again pointed out, ‘normal’ is a moving target and it didn’t necessarily move from ‘150 or below’ to ‘110 or below’ because scientists and doctors discovered something we did not know previously. It may have moved simply to sell more drugs - cynical interp. But whatever it is, I feel healthy and energetic, don’t exhibit any signs of ill health and enjoy eating the foods I eat that keep me consistently in ketosis.

My suspicion is that damage caused by eating SAD for years/decades is not and can not be resolved quickly or easily for many people either because the extent and/or severity of the damage is too great or simply because they drew a short straw from the genetic pool. The problem is not keto. Keto is the solution, but it’s not magic nor a miracle. It’s a biochemical process that given sufficient time will normalize one’s metabolism. Still, if something is broke beyond total repair, it will never get totally repaired.

(Joey) #315

I think this is the crux of the matter.

The “may or may not” part is what troubles some - but not all - of us who are witnessing higher (naturally self-produced) glucose levels.

#316

Hmm, what about auto-immune conditions? (It’s what I’m dealing with, and it feels hopeless at times.) Auto-immunity is so poorly understood. Why on earth would the body continue to attack itself for years and decades after an infection or whatever other (unknown) trigger?

(Joey) #317

That’s a powerful point! I’m much humbled by your reply.

#319

Exactly!

I’m sorry you have to go through it!

My mother and one brother also suffer from autoimmune diseases. My husband, who has no insulin resistance (measured with insulin and plasma glucose tests) and is healthy and does a lot of exercising, also. Was hospitalized for almost 3 weeks, almost died.

What about cancer? Dr Hallberg (Virta) said she did all the right things (interview with Peter Attia). She was diagnosed with stage 4 lung cancer.

All those people with type 1 diabetes…

Etc.

(Bacon is a many-splendoured thing) #320

A very interesting study, thanks for posting the link. My questions about it are that it seems to have been of short duration, since they say it ended on day 3. That is by no means long enough to reach fat-adaptation, and I wonder what the results would have been if the study had run a few months. (Which would have been difficult and very expensive to do.) There also doesn’t seem, at least to my cursory glance, to have been any checking to see how insulin-resistant the subjects were. I’m sure that would have had an effect on the results.

On the other hand, I was surprised to see that fat was 70% and protein 30% of calories in the intervention diet. These are the proportions of a carnivore diet, representing equal amounts of protein and fat by weight. Usually “low-carb” in such studies means nothing of the sort, as we would see it. The complete absence of carbohydrate is probably the reason they called the intervention diet “high-protein,” because otherwise critics might have objected, on the grounds that carbohydrate is an essential nutrient.

One fascinating result was not what I would have expected:

Endogenous glucose production, ie, glucose derived from glycogenolysis and from gluconeogenesis, was lower when subjects were in the H condition [carb-free intervention diet] than when subjects were in the N condition [standard diet].

Very interesting.

(Joey) #321

@PaulL I track with all of your comments and observations about this interesting study, although I didn’t find the results to be quite so surprising. Especially as you properly note that the zero-carb (“H”) subjects were not likely fat-adapted (in ketosis) immediately prior to the experiment.

Therefore, the result that the zero-carb subjects’ bodies were producing lower overall levels of (endogenous) glucose during this experiment seems like a reasonable observation.

Not being fat-adapted, they were experiencing what any carb-rich eater would likely suffer from - perhaps even early signs of a modest “keto-flu” as their mitochondria were being deprived of their customary energy source.

But looking at the entire summary statement taken together, I found it encouraging to see what was observed during the span of just a few days:

“Endogenous glucose production, ie, glucose derived from glycogenolysis and from gluconeogenesis, was lower when subjects were in the H condition than when subjects were in the N condition … whereas fractional gluconeogenesis was higher. …As a result, absolute gluconeogenesis tended to be higher when subjects were in the H condition than when subjects were in the N condition.”

[For background: gluconeogenesis is the derivation of glucose from non-carbohydrate sources whereas glycogenolysis is the breaking down of stored glycogen into available glucose.]

To me, this demonstrates that the body’s liver will produce a higher level of glucose on demand from non-carbohydrate sources very quickly when subjects are placed on a carb-free diet. As glycogenolysis (glucose produced from carb-based stores) was lowered, the overwhelming proportion of their own glucose production came from gluconeogenesis (non-carb dietary sources) when exertion demanded it.

This simply underscores that (1) the body does not need dietary carbohydrates to power itself and (2) absent carbs, gluconeogenesis kicks into gear upon demand in short order … even if one is not (fully) fat-adapted.

Separately, I found it interesting that the zero-carb subjects were measured as having a markedly higher metabolic rate while sleeping and while resting. Yet these subjects produced less heat while exercising.

One point of curiosity: Since all of the subjects were exercised to the point of exhaustion, I wish there were some discussion of whether there was a meaningful difference between the two subject groups in reaching their respective points of exhaustion (a variation on the Phinney/Volek findings?). If it was covered, I missed it.

Anyhow, this was a fascinating study indeed. It’s great to see that a carb-free eating study of this kind was conducted - back in 2009.

(Bacon is a many-splendoured thing) #322

Well, going on what Bikman says about how glucagon increases in the absence of carbohydrate, thereby stimulating gluconeogenesis, I found it surprising. One would naturally expect a decline in serum glucose when dietary intake drops, but a drop in endogenous production? And I took Phinney’s warnings about salt to heart, so I never experienced any symptoms of hyponatraemia, which is what he says the “keto flu” really is. Nor did I actually experience any symptoms of what might be called carb withdrawal. And not being an endurance athlete, I never noticed a hit to my muscle power, either. I just felt really good, even better than when I had cut out sugar and sweets.

(Bacon is a many-splendoured thing) #323

This would have been my expectation, except that the study seems to be claiming the opposite, that gluconeogenesis was less on the carb-free diet.

If the liver has glucose stored in the form of glycogen, sharing it is not gluconeogenesis, since the latter is a specific process of converting amino acids (and sometimes fatty acids) into glucose, not releasing existing glucose from storage.

Though come to think of it, it is possible that the subjects had enough stored glycogen in their livers to render gluconeogenesis less important for the first few days of a ketogenic diet. That could well explain their findings.

Also, since gluconeogenesis and ketogenesis are both stimulated in the liver by glucagon, it would have been nice if they could somehow have measured the production of ketone bodies independently of the production of glucose.

(Joey) #324

Am I reading this incorrectly?

"… As a result, absolute gluconeogenesis tended to be higher when subjects were in the H condition than when subjects were in the N condition."

(Bacon is a many-splendoured thing) #326

Interesting. I read this in the abstract: “Results: EGP [endogenous glucose production] was lower in the H [intervention] condition than in the N [control] condition.” And the same remark is repeated later. I obviously missed the part you quote. Will have to go back and re-read more carefully later. Though it is surprising that the abstract would contradict the body of the paper. Perhaps they are defining their terms in a non-obvious manner?

(Bacon is a many-splendoured thing) #327

I think it was you who posted a link to a paper by Cahill stating almost that, but interestingly, Cahill is also the source of the estimate that the brain needs a minimum of 130 grams of glucose a day. Cahill’s experiment on fasting subjects using a euglycaemic hyperinsulinaemic clamp would tend to support the notion that the brain doesn’t actually need glucose at all, if ketones are providing sufficient energy.

(Joey) #328

The part I quoted above is just the rest of the same sentence after a semicolon. FWIW, I didn’t find it to be contradictory but I did have to read it a few times to digest the nuance being drawn between fractional and absolute. (And “endogenous” includes two sources of non-dietary glucose production, further complicating interpretation.)

(Michael) #329

Just read the linked paper by @Belisarius, and it is interesting. I really wish they had measured glucagon and not JUST insulin, that may have given a different story. Of course, without being fat adapted, that also kind of throws a wrench in the numbers, with ketone production not being efficiently used with (some?) of those involved and energy being wasted as ketones in the urine.
Another thing that might have helped was measuring (at least in the liver), the glycogen stores at the end of the 3 days. Since the carb eaters would have re-filled their glycogen reservoirs easily and thereby reduced their need for GNG over continued dips into their glycogen stores, this result is not too surprising really - but might have been more valuable with fat adapted participants.
Here is a summary for those who are confused by the statements
H (no carbs) - glucose produced = 181 g/day (of which 172 from GNG and 9 from glycogen)
E (carbs) - glucose produced = 226g g/day (145 from GNG and 81 from glycogen).
Carb eaters re-fill their glycogen stores faster and higher and are able to use their quick-access sugars more easily, while the H group would not have the stores and decide to use GNG to stop from completely depleting the glycogen stores. This should not surprise anyone on these forums and is completely logical.

Separately, not ONE response to the paper/article noting that eating Fat produces GNG based solely on fat intake. A steady increase (straight line) based on food intake. This is a pure study with type I diabetics and (to my mind putting protein aside) makes it pretty clear that GNG is not purely demand driven. Obviously demand does influence production, but not solely.

@SomeGuy But I can change my average glucose level from (approximately) 5.6 mmol/L average for one day, eat twice as much protein the next day and have an average that day of 6.2 and then eat less the next day and have my average (with a continuous glucose monitor) fall back to 5.6. All from diet, eating the same foods but a different volume. Does my bodies demand for blood glucose rise by 0.6 mmol/L just because I ate more that day? How would this work and make sense to you?

(Joey) #330

Makes perfect sense to me. I don’t recall disputing the notion that serum glucose is both demand-driven and supply-driven, along with other hormonal factors.

The amount & source of dietary energy and to extent to which you expend that energy are relevant variables - along with how insulin is released and how responsive one’s tissues are to that insulin - in determining serum glucose levels at any particular moment.

Sorry if I’ve posted anything confused on such matters 'tho I don’t recall doing so. :man_shrugging:

(Bacon is a many-splendoured thing) #331

This appears to be an artefact of not being fat-adapted. Volek’s team showed that fat-adapted athletes who’d been on a ketogenic diet for two years or more had glycogen stores indistinguishable from those of carb-burning athletes.

(Bacon is a many-splendoured thing) #332

It would be interesting to know if this fluctuation represents a real change, or is simply an artefact of the margin of error. Most home devices are not all that precise. On the other hand, if this is repeatedly reproducible, then it probably is real, even though the results fit within an accuracy of ±0.2.

(Michael) #333

It is reproducible (I have repeated multiple times) both within the same week (back and forth) using the same CGM and then again on a different weeks using a second CGM to reproduce. Again, I can raise and then lower and then raise again based on food intake (carnivore so all fat and protein, with the linked paper on fat showing the results could not be caused by just fat in a person who can produce insulin).

(Michael) #334

Here is Ben Bikman repeating it all in one video as I had described above. I do not have time now, but I am going to start a separate thread since I have found the original papers demonstrating most of what Ben describes. https://www.youtube.com/watch?v=MEzAvos1jak

#337

I think this relevant here: