Metabolic Flexibility - Get Real


The study was tightly controlled and thoroughly measured.

They measured insulin sensitivity by analyzing glucose homeostasis and insulin sensitivity decreased on the keto diet.

Also the study’s primary objective was to see what happens on the transition from a baseline diet to the keto diet. So that’s what they did.

Maybe the study would have been more useful if the order was randomized :man_shrugging:


Yeah, unfortunately the Virta Health study has these flaws:

  1. They did not show “reversal”, just remission; your diabetes is not reversed unless you start tolerating carbs again; I was thus expecting them to measure insulin sensitivity via the glucose clamp technique (the gold standard) but they didn’t
  2. The study was in free living subjects and thus not tightly controlled; the effects of any intervention tend to diminish in a tightly controlled clinical environment
  3. Many of the subjects suffered weight loss, which is great, because weight loss was shown to increase insulin sensitivity, possibly the only lifestyle intervention known to reverse early stage diabetes; unfortunately weight loss is a huge confounder and in its presence you can’t say much about the intervention itself – you have to show that the intervention works independently of weight loss otherwise you can attribute it all to weight loss

N.b. this assertion that weight loss improves insulin sensitivity was tested in multiple randomized controlled trials, some of them year long – see this meta review of RCTs and note that a high quality evidence like this can rarely be seen in nutrition science:

I understand that viewpoint and agree somewhat. When you feel great, keep doing whatever it is that you’re doing. I’m only thinking of the people that don’t feel so great.

Also ethanol is toxic for the liver and carbs are not and we’ve got the evidence for it, in spite of Robert Lustig making a compelling case for fructose, plus we’ve got evolutionary evidence that we’ve been eating starchy roots for hundreds of thousands of years.

Here’s what popped in my news feed today :slightly_smiling_face:

Personally I wish Keto would be divorced from the “carbs are poison” myth, as it’s not an evidence based narrative.

(Windmill Tilter) #23

I think this a brilliant point, and one that is very seldom addressed in the keto community. My expectation is that if keto results in significant weight loss e.g. BMI 30 to BMI 25, this will sort itself out, but it’s possible that’s not the case.

It makes me wonder if insulin sensitivity has ever been compared between two cohorts, one of which reduced BMI via “low carb” and one which had reduced BMI via the ubiquitous mediterranean diet (or analog) to compare insulin sensitivity via a glucose clamp test.

It would imagine that the low carb cohort would do reasonably well, but if not, it would be something worth pondering.

(mole person) #24

Dead on and beautifully expressed. 1 and 2 aren’t so bad though.

  1. Drug free remission of T2D is fairly huge in and of itself and any protocol that produces that results is medically valuable.

  2. Different experiments test for different things and the finding that a ketogenic diet results in diabetes remission in free living subjects is interesting on its own but without proper controls it’s impossible to know what the exact cause is or if it could be achieved with another type of intervention.

  3. This one is huge. Weight loss is correlated with soooo much disease remission that as long as you fail to control for it you can have no idea that the ketogenic state matters one whit except as an appetite suppressant, which is something we’ve known for 100+ years already.

(Doug) #25

Yes, “reversal” is a big thing, and I’d say there are gradations of it. Some doctors will say ‘reversed’ after a certain number of low-enough A1C tests over a certain timespan, but the question of glucose tolerance could certainly remain.

Or, let’s say the glucose clamp technique is used, and good insulin sensitivity is there. How long will this remain the case, on a carb-heavy diet afterward?

I’d say we never get all the way back, so to speak, unless a relatively extreme factor is present, like being obese from childhood and then becoming really lean. Otherwise, age and time work against us; normally we become more insulin resistant as we get older. And those beta cells in our pancreas - we may have whacked a bunch of them in our high blood sugar days. How long for them to repopulate, and do they fully do that?

I’m 60. In this respect I don’t think there’s really any returning to age 20.

(charlie3) #26

I eat two meals, one is fish and beef, the other is a large salad with oil and vinegar. The salad is 40 grams net carbs, not 20 grams total, to avoid diet fatigue. I get the “flexibility” to eat this way with activity, 2 x 1 hour sessions on an air bike which burn about 1100 calories on top of about 1600 calories resting.

I think I still don’t understand “insulin resistance”. Isn’t it really the cells resisting more glucose when they are already full to capacity?

(Mike Glasbrener) #27

A well controlled study does not make Interpretation of it’s results accurate. A two day study on weight lifting would conclude that weight lifting destroys muscle tissue and is terrible for improving muscle mass. Long term adaption to diet takes time. It takes many, many weeks to become truly fat adapted. Most people who commit to keto plateau after a few weeks. This is because the inflammation has been addressed. However, their body is still transitioning to being efficient at burning fat, fat adapted. Thus a study of 4 weeks in length doesn’t really address how effective a diet is. Secondly, the cholesterol results are fairly useless. Total cholesterol isn’t terribly useful unless one is eating a carby diet, in which case it’ll be mostly hdl which is the body’s attempt to store fat in cells which are rejecting it due to insulin resistance.

(Mike Glasbrener) #28

Indeed! Insulin resistance is when cells don’t “want” to store more fat. The pancreases then ramps up more insulin production to force the cells to uptake the poisonous high levels of blood sugar. The damaging cycle continues until the pancreas can not keep up and one is now T2 “diabetic”. To make matters worse the chronic high levels of insulin have made the regrow the of beta cells in the pancreas impossible. Calling morning effect insulin resistance is just confusing things for most people. It’s good to understand it as one meters blood sugar though.

(Justin Jordan) #29

I am 100% in for metabolic flexibility to eat carbs. Keto is a tool, not a religion.

Or rather, it should be.

(Todd Allen) #30

Dose makes the poison. In rats the LD50 for water is 90 g/kg and for glucose is less than 26 g/kg. Chronic poisoning symptoms typically develop at lower doses than those needed to produce acute toxicity.

(mole person) #31

There are two separate things happening. Most people aren’t getting new intolerances. Rather, they are discovering, once they begin restricting what they eat, that illnesses and conditions that they have suffered from for years or even decades just go away.

I went keto for weight loss, but serious medical conditions that had been quality of life destroying for the previous decade subsided significantly when I was ketogenic. When I went fully carnivore my conditions went into such a deep remission that I am now off all three medications that I was taking for the pain control and I’m back to having the life I lost. I again am able to take multi-week deep bush camping trips. Something I gave up a decade ago because everything always hurt. I thought that I was just past it age-wise. But I feel again as good as I ever did.

Anyhow, a lot of people here have similar stories. They aren’t getting new intolerances, they are figuring out really old ones that they had no idea were related to diet. My pain was all neurological, ffs. Nobody thought diet could be a factor. Nevermind plants in general.

I think that this is also a thing. But not as big a deal. When I hang with family I often end up eating wrong things as my pain conditions will not flair immediately. However some things that I eat will give me bad stomach aches that I wouldn’t have gotten from eating those things before keto. However, it’s pretty dose dependant and it’s self correcting. If I pig out on a bag of nuts after 3 months of eating nothing but steak, liver, and fat I will feel horrible in a way that would not have been prior to going keto/carnivore. But if I eat a 1/4 cup a day to start and increase slowly I’m fine. Same with everything. My gut flora does need some time to adjust but there are no new permanent intolerances.


The first problem is thinking that eating some carbs when wanted needs to be “justified”. We’re not vegans, this isn’t religion, it’s our WOE. When a HCLF eater wants to eat some fatty delicious dinner they just eat it, and make it a once in a while thing, no different for us. When we are full blown carbivore’s if we were to eat the amount of fat we eat normally (typically) we’d feel like crap, possibly sick, and most likely have some nice time looking at the inside of our bathrooms. When people who eat strict keto for a prolonged time eat even ignoreable amounts of carbs, we’ll say the “good” ones. It typically ends with them feeling like crap, waking up the next day feeling like they got backed over by a truck. To pretend that eating something possibly as simply as a slice of pizza or maybe a “normal” desert doing that causing that effect being ok is nuts. Being so inflexible that simply eating something different than normal making you feel sick is crazy. I can eat keto for as long as I want and be fine, if I want to eat 1, 2, 3, 4, 5 “normal” meals in a row… nothing happens. I’ll burn off the carbs and go back into ketosis. Compared to me of a couple years ago that would have carb hangover for 2-3 days, feel like crap, sleep like crap, have brain fog, spend the better part of the week and sometimes longer getting back into ketosis. That’s not the case anymore. I can’t think of an argument of NOT wanting to have that flexibility. I feel better, my A1C averages 4.8-5.2, and no more crazy blood sugar spikes from eating things that used to do just that. It’ll rise, but since I’m not hyper sensitive anymore I go up, and come back down, not a spike and crash.

(Michael - When reality fails to meet expectations, the problem is not reality.) #33

@lfod14 Here’s what I think currently. And as I pointed out in the OP, I am open to changing my mind if presented with convincing evidence to the contrary. I think folks have got ‘metabolic flexibility’ backwards. I posted a link in my OP that I think correctly defines metabolic flexibility.

Unless one is diabetic and/or severely insulin resistant or otherwise metabolically deranged, we already have the capability to metabolize carbohydrates and utilize glucose. We don’t need to practice. Gluconeogenesis (unless deranged) synthesizes all the glucose we need for the cells and organs that require it and it gets used fairly efficiently. Therefore, we have zero need to eat carbohydrates, since they are simply exogenous sugar of various molecular structures. Eating carbohydrates just forces our metabolism to deal with excessive amounts of sugar. Some of us manage to do so successfully some not so much. And the ability to deal with the excessive sugar load successfully declines with age for most of us.

Metabolic flexibility is actually the ability to metabolize fatty acids and ketones efficiently. People who fuel their metabolism primarily by eating carbohydrates and burning glucose, can not do so. These are the people who are not ‘metabolically flexible’. Upthread, @fabia mentions that virtually everyone goes into ketosis overnight, which might or might not be the case. Depends on how much, what kinds and what time the last high carb meal was consumed before going to sleep for the night. The sugar-burner may or may not be in ketosis by morning. But even if a sugar-burner is in ketosis by morning, he/she is not utilizing ketones and fatty acids efficiently. Quite the contrary. The cells and organs of a sugar-burner are habituated to burn glucose not fatty acids and ketones. Everyone of us who has been eating ketogenically for more than a few months knows that fat adaptation - the efficient utilization of fatty acids and ketones - takes time. Dipping in and out of ketosis in the morning won’t cut it.

Metabolic flexibility is not the ability to eat a high carb meal and not want to puke afterwards. That’s total nonsense. Yet that’s what I see being advocated. Or such stuff as “I can eat 100+ grams of carbs per day and stay in ketosis because of metabolic flexibility”.

It’s not religion to accept the scientific fact that we have zero need to consume carbohydrates and eat accordingly. Nor to say so.

Mike's Excellent Glucose Monitor Adventure
(Windmill Tilter) #34

I think much of this is a misunderstanding over terms. What you have defined above is fat adaptation.

As previously noted, metabolic flexibilty is defined in medical literature as the capacity for an organism to adapt fuel oxidation to fuel availability. Whether or not carbs are biologically necessary is interesting but not particularly relevant to the discussion.

Using the actual definition of the term “metabollically flexible”, if one person is capable of eating every possible food known to existence in a state of perfect health, they are metabolically flexible. If another is only capable of eating the thigh meat of a single species of artic mole or face fatal consequences, they are not metabolically flexible.

Provided you accept the medical definition of the term under discussion, do think it more rational to aspire to be the perfect omnivore, or the mole person? Provided you had the godlike metabolism of the perfect omnivore, are there particular foods that you would exclude given that all foods leave you in the same state of perfect health? If so, why?

(charlie3) #35

What most diet research rarely accounts for is activity, how many more calories are burned above RMR. Perhaps the majority of Dr. Westman’s patients are sedentary so 20 grams of total carbs max is a must. If you are burning double the RMR and consuming it with activity perhaps double or triple 20 total grams doesn’t have a significant effect because it’s all burned for fuel.

(Michael - When reality fails to meet expectations, the problem is not reality.) #36

@Don_Q Maybe I’m not being clear, but isn’t that what I just said? Edible food for humans consists of carbohydrates, proteins and fats, along with assorted micronutrients. All humans who are not metabolically compromised in one way or another have the capability to metabolize carbohydrates efficiently. Those who become fat adapted by keeping glucose and insulin at or near baseline concentrations by avoiding unnecessary carbohydrate consumption are also capable of utilizing fatty acids and ketones efficiently. That makes them more metabolically flexible. People whose primary metabolic fuel is carbs/glucose can not and consequently are less so. I’m not saying people whose primary fuel is carbs/glucose don’t burn fatty acids, they don’t do it efficiently simply because they’re in a perpetual state of ‘sugar saturation’ and glucose habituation.

Contrarilly, I think whether or not carbs are biologically necessary is very relevant. I doubt that you would claim that having the ability to down a fifth of bourbon every day demonstrates ‘metabolic flexibility’. For a very large number of people, downing 300+ grams of carbs per day is no different except the specific damage inflicted. If someone wants to die with a healthy liver I don’t think them irrational to minimize liquor consumption. And if someone wants to die in a state of metabolic good health I don’t think them irrational to minimize carb consumption.

Unless someone finally proves beyond all doubt that Ancel Keys was right after all and the last 40+ years and the world-wide epidemic of obesity, T2D and CVD didn’t happen. We just imagined it.

(Windmill Tilter) #37

That’s much clearer to me, and I think we agree. If a person is incapable of metabolizing carbohydrates efficiently, they are metabolically deranged.

My point is that strict adherence to sub 20 carbs per day for years at a time leaves people unable to metabolize carbohydrates efficiently. I actually did a bit of a self-experiment on this last night. I added half a can of kidney beans to my nightly supper of hamburger, which is about 33 grams of net carbs. I’m a former vegan who lived on the stuff prior to reading Dr. Fung and starting keto so I figured that was a safe bet.

Guess what happened? I wound up on the can for a good portion of the evening. I can’t digest them anymore apparently. I hadn’t eaten them for a long time. I’m metabolically deranged! Ironically that was the same reaction my body had to meat back when I was a metabollically deranged vegan.

Put in the terms of the present discussion, I’m as metabolically inflexible now, as I was when I was a carb burning, sugar eating vegan. You may judge that as progress, but you’ll forgive me if I attribute that to an article of faith rather than reason.

On the bright side, this whole discussion has got me thinking more seriously about the importance of metabollic flexibity. I just made a 5lb batch of hamburger and this time I added in 15g of beans and 15g of rice to each 1lb portion. I plan on adding in other foods that I’ve not eaten in a while so that I can start to repopulate my digestive track with all the wee beasties whose populations I’ve allowed to decline.

Heresy or not, it’s better than being stuck in the john… :yum:

(Windmill Tilter) #38

As I mentioned in my post above, having been convinced by my newfound inability to digest kidney beans that metabolic flexibility is a more pressing issue than I had realized, I’ve started adding in small quantities of basic carb foods that I want to retain the ability to digest in the future.

I typically have 1lb of hamburger for dinner on days that I’m not doing extended fasting, so that seemed like an easy medium. It’s 73/27 hamburger, so the massive fat load should insulate me a bit from the carbs I hope. This is what it looks like. It’s actually still pretty close to the keto guidelines. Maintaining metabolic flexibility needn’t be drastic I don’t think.

I’m trying to think of other foods to start adding in. I guess 10g of wheat flour is a natural choice, but ironically, for all my prattling about metabolic flexibility, I’m loath to do it. I think I’ll leave that one for last. :smile:

Does anyone else do this sort of thing? I’m curious what other folks have done to keep the pumps primed for eating non-keto fare every now and then.

(Michael - When reality fails to meet expectations, the problem is not reality.) #39

I’m all in favour of self-experimentation. I don’t interpret your beans experiment an indication that you are metabolically inflexible. As you say, this is semantics. Sure, it might mean you’ve lost the ability to digest kidney beans, or not. Further experiments required. But my response is “if so, then so what?” You have not lost anything because the kidney beans have nothing you need. As I said to @lfod14 I don’t think metabolic flexibility means you can eat a high carb meal and not puke afterwards.

This is why I keep coming back to the biological irrelevance of consuming carbs. If you adhere to the official medical definition, then consuming bourbon also indicates metabolic flexibility. If you counter by saying ethanol is toxic, I counter by saying so is glucose. In sufficient quantity over sufficient time they are equally toxic. Glucose maybe moreso.

As long as gluconeogenesis functions normally, there is neither need nor benefit to consuming exogenous sugar in the form of carbs. Whether or not you can do so or bother to do so is irrelevant. What is not irrelevant is that the exogenous sugar causes a cascade of events that blocks your ability to metabolize fats efficiently, thus making you less metabolically flexible.

(squirrel-kissing paper tamer) #40

Yes, each week I usually buy something I rarely get and habituate my body to it. Sometimes there’s more bathroom time afterward, sometimes not. Some examples are peanuts, edamame, onions, chocolate, olive oil instead of butter, salad, fried chicken, yogurt. Some days I have mostly meat but I like the flexibility and variety doing this. Plus, I feel I’m casting a wide nutrient net because I don’t supplement.