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Why do people consider ketosis "stressful" to the body?

by 18373 · August 20, 2013 at 12:09 PM

I've been asking people this in comments whenever it comes up, particularly in discussions of adrenal issues, but no one seems to want to answer. The only idea I can think of is that there is an assumption that gluconeogenesis is stressful. But why would that be? The body is breaking down and building up different substances constantly. And it's not like consuming glucose gives it to you for free. It still has to be digested and broken down.

I realize that the zeitgeist has changed recently regarding ketosis. Paul Jaminet considers it a powerful tool, but with costs, such that one should only use it if necessary for its therapeutic value. He has written extensively about his ideas as to why it may be dangerous, but though I deeply respect his experience, knowledge, and contributions, I don't find his arguments compelling. They seem to be based on anecdote, followed by much thoughtful speculation on plausible mechanisms. This is very valuable, but still hypothetical, and it's important to carefully distinguish hypothesis-forming science from evidence.

Kurt Harris has lately roughly quadrupled his own intake of carbs, I infer because he judged it to be affecting his energy levels when highly active, and now states that one shouldn't be in ketosis all the time. Presumably, like Jaminet, he would make an exception for those who are deriving specific important benefits. Of course, he owes no one a justification, but I would like to understand his ideas better. There are plenty of people who report feeling more energized in ketosis, and even some of those who do find they need a carb boost for high intensity exercise (which again, isn't everyone) can often get by with as little as 30 grams targeted at the right time.

Personally, I am one who needs the therapy, so it isn't a question for me of whether stay in ketosis, it's a given. But the more I research it, the more natural and health-promoting it seems to be. I'm not finding evidence of it being stressful to the body. If there really are significant costs, that are shown by actual evidence, I'd like to know about it. I'd also like to hear more about where people are getting the idea, that for instance, if you have cortisol regulation problems, ketosis is too stressful, or other sources for people to hypothesize that it might be a problem, other than the two above.

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18373 · March 07, 2011 at 07:52 PM

(Edit July 2012: Please see Ketogenic Diets, Cortisol, and Stress: Part I — Gluconeogenesis for my updated and referenced explanation of why gluconeogenesis does not raise cortisol.)

I think I have found my answer in comments from Dr. K. and Phoenix.

There is definitely a widespread view that gluconeogenesis necessarily raises cortisol beyond what is needed without gluconeogenesis. I think the evidence is softer than it appears.

It is undisputed that cortisol stimulates gluconeogenesis. See, e.g. The Physiology of Stress: Cortisol and the Hypothalamic-Pituitary-Adrenal Axis. This leads to the claim that continual gluconeogenesis requires continually raised levels of cortisol. That's not logically implied and I'm not sure it's true. For example, Dr. Eades says, in response to a related question:

[M]ost of the time during fasting, the hormone glucagon,which is the counter-regulatory hormone to insulin, drives gluconeogenesis, not the stress hormone cortisol.

This seems consistent with this primer on glucagon physiology, which says:

When hypoglycemia is produced in humans by injection of insulin, release of glucagon is stimulated along with that of other counterregulatory hormones when the plasma glucose decreases below 3.8 mM (~68 mg/dl) (Figure 11). Restoration of euglycemia is due to a compensatory increase in hepatic glucose production. Although secretion of catecholamines, growth hormone, and cortisol are stimulated along with that of glucagon, only the increases in plasma glucagon and catecholamines coincide with or precede the compensatory increase in the glucose production rate (66,67). That glucagon is the major acute glucose counterregulatory hormone is suggested by the fact that inhibition of the plasma glucagon responses by somatostatin markedly attenuates the compensatory increase in the glucose production rate and impairs restoration of euglycemia following insulin administration (Figure 12). Prevention of cortisol secretion (68), adrenergic blockade (66), adrenalectomy (65), or acute growth hormone deficiency (66) does not appreciably affect immediate glucose counterregulation. The effects of glucagon during restoration of euglycemia involves both glycogenolysis and gluconeogenesis, predominantly the former (69).

This does, suggest, however, that whenever blood sugar goes sufficiently low, cortisol rises. Note that this is no more likely to occur in a ketogenic state than a non-ketogenic state. In fact, most people report much more stable blood sugar levels on a ketogenic diet than otherwise. It may be relevant for fasting, though. If there is a regular stream of dietary protein available for conversion to glucose, blood sugar will probably not drop so low as to raise the cortisol alarm. This is consistent with Chris Kresser's post on [i]ntermittent fasting, cortisol and blood sugar, in which he says that some of his patients, already on a low carb, paleo diet, cannot successfully do intermittent fasting because of cortisol dysregulation. In these cases, he has them eat every 2-3 hours, and they improve. He never suggests, though, that they should abandon carbohydrate restriction.

Based on this information, I believe the notion that ketosis is stressful is simply a pervasive myth. Gluconeogenesis is mediated by glucagon, not cortisol. Cortisol will only be raised if there is hypoglycemia from fasting or from excess insulin. In fact, since the best way to control insulin is to lower carbs, ketogenic diets probably reduce the need for cortisol by providing better blood sugar control.

(Edited to fix a link typo.)

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39204 · March 03, 2011 at 07:50 PM

I've remained thoroughly unconvinced with regard to the merits of ketosis all throughout my research into various aspects of paleo. If we are to point to a specific extant HG society as a model for what we should personally eat, it seems logical that we would choose one that occupies the same location and eats the same food that we as hominins did for the bulk of our evolution. As such, our last possible choice would be an outlier such as the Inuit, unless we ourselves are descended from them. It's clear that because hominins evolved for 6-7 million years in E. Africa and because the flora and fauna present there are fairly consistent over time, we would do well (if our goal is to model our diet after that of a HG society) to use data from study of the Hadza over most any other.

Though we likely added various abilities digestion-wise over time as we moved out of Africa such as lactase persisting into adulthood etc., I find it hard to believe that along the way we lost the ability to safely digest the tubers and berries that the Hadza consistently seek out in large amounts (and sometimes eat almost exclusively for days) and in the 60K or so years that we've been out of Africa have rapidly evolved into carnivores.

That all being said, there are those I'm sure who acknowledge that we likely continue to be omnivorous but can lose body fat more effectively on a carnivorous diet + coconut or whatever the dominant protocol is currently. Similarly, I remain unconvinced that the efficacy of such an approach is markedly greater than that of an individual who simply restricts fructose as much as possible and restricts starch to whatever level stays below their glycogen storage capacity threshold. Insulin preferentially stores excess blood glucose as glycogen, likely for the simple reason that the ATP cost as a % of the energy being processed is roughly 7% to convert glucose to glycogen and 25% to convert it to fat. There's simply no way that we would have evolved to preferentially store glucose as fat when there is glycogen storage capacity free. My personal experience confirms this, as I can eat significant quantities of mashed potato before, during and after my resistance workouts without any sort of increase in adiposity, provided that I am not consuming these amounts on low-draw days. In fact, on Tues & Thurs I skip starch intake altogether and just run on glycogen stores since I don't do anything beyond walking for 4-5 miles.

As for the stress issue, I think it could be argued that at the very least, a rapid transition down to non-significant quantities of glucose could temporarily starve the brain of energy or cause rapid catabolism of muscle tissue for energy. In fact, isn't gluconeogenesis with a protein substrate either from dietary protein or muscle constantly occurring during ketosis? As such, wouldn't the toxic ammonia produced during deamination result in a greater level of stress on the body?

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1945 · March 01, 2011 at 03:24 PM

But is there any compelling reason/evidence that one should avoid it, especially if trying to lose bodyfat?

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1329 · August 20, 2013 at 11:03 AM

I understand you want evidence, and I'm not sure I can provide any of that, but I have some thoughts on the subject.

I've delved into Peat, and Danny Roddy et al, and although I think some of it is misled, there are some important bits I've taken from it, which the evidence does appear to support. Stuff that the paleo community is down with anyway... let me run with this and I will gratefully receive any criticism on it...

The saturated fat / metabolism thing seems to me to be very important. Simply, if you are eating mostly saturated fat, this is being turned into metabolic hormones and making you lean and energetic.

It seems that when people gain a lot of weight in the first place, the primary common denomenator is high PUFA intake, particularly the n-6 fats.

So I have to ask - is there an evolutionary reason for why metabolism slows down under these conditions? Is the organism attempting to protect itself from the damaging or carcinogenic effects of attempting to metabolise these unstable fats?

What I am guessing is that "ketosis" of coconut oil, butter etc is perfectly healthy and in many circumstances preferable (there appear to be some functions that require ketones rather than glucose, right?). However, ketosis of stored PUFA, which will happen when you put yourself into a fasting state after having gotten overweight from PUFA is probably "stressful" (the end-result of which dependent on many other factors).

What I am ultimately interested in is how to fast oneself out of a PUFA-ridden obesity (not for me, I'm pretty lean now, but just for understanding), whilst mitigating the stress of metabolising all that PUFA.

As vitamin E saturates unsaturated fats, I imagine a complex of E with other transport etc antioxidants is perhaps the required food.

And the way to find this in a wholefoods context would be through green smoothies, quite possibly.

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30 · July 30, 2012 at 01:48 PM

Ketosis SUCKS!

Training day without carbs = WASTE OF YOUR TIME

Consecutive deficit days = RECIPE FOR FAILURE due to fatigue, hunger and stress which cause eating spree sooner or later

The formula to leaning out quickly, successfuly and stress free is: Eat -30% maintanance on REST DAYS

Eat +10 maintanance on TRAINING DAY (Which for me is 270g carbs of GLORY) you add zero fat just some muscle - So its a win win of eating some food, and not gaining fat.

You cycle and repeat until your six pack visible in RELAXED state, then you can switch things up and eat +30%, -10% (rest day)... Until reach desired muscle size. Or just maintain lean body by eating at 0%.

1g carb = 4 cals, 1g protein = 4 cals, 1g fat = 9 cals. Average sedentary maintanance is 2100. For muscle building its 2.5g per kg body weight recommended, but if you're not into muscle you can eat more carbs instead :)

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762 · March 01, 2011 at 02:04 PM

Hi Ambimorph,

One may consider ketosis 'stressful' in two ways depending on whether the stress response derives from the excretion or synthesis of proteins.

We commonly equate stress with hypercortisolism or HPA (hypothalamic-pituitary axis) dysfunction. However, biology also recognizes another type of stress- an increase in defective (e.g. misfolded or mutated) proteins or the proteins needed to deal with those defective proteins.

Ketosis is stressful in that it alters protein synthesis.

Hope this helps, Mike

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6629 · August 20, 2013 at 04:33 AM

What about the drastic alterations of hormones in men eatin VLC. Like low free T, TC, weird Estrogen levels and Progesterone issues, lethargy, TSH and T3/4 change, and total lack of sex drive.

Wait? What!? What am I talking about. Simple. google "low carb low sex drive" or "low carb no sex drive" or "zero carb no sex drive, cold all the time" look at the thousands of unfortunate souls.

And lets see, then theres the fact that not a single elite athlete, not a single one, stays zc, vlc, or lc much of the time or at all.

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905 · January 17, 2013 at 10:44 AM

Does anyone have any research/anecdotal evidence/opinion on how the amount of daily protein intake 'stresses' the body? I've noticed lately that my urine smells quite distinct and I suspect that is the ammonia from deamination but I can't figure out if that is because I'm eating too much protein and therefore 'burning it for fuel' or it's the other way around, that I'm eating too little protein (and not enough fat to fuel my body) and my body is breaking down muscle to get the extra energy.

I bike 10k at least five days per week, at least one sprint session (running) and one to two weight training sessions per week (the latter is more focused on a high number of reps and keeping a somewhat high intensity). I weigh 50-52kg @ 178cm so I'm quite low in bodyfat. I eat around 1.75-1.9g protein/kg per day. Which corresponds to 18-22% of my energy intake.

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324 · March 01, 2011 at 02:21 PM

I believe when speaking of stress he not only means the HTPA, but the organs as well, one of the main concerns with this diet from a "dieticians" stand point is the stress on the kidneys, and their filtering efficacy. A lot of people are also worried about "high protein" damage on kidneys. It's all a crock of shit if you'll excuse my french. Look up the studies and you'll see they were all done on patients with kidney failure on dialysis. At that point almost anything would cause the kidney function of those patients to come spiraling down. If kidneys can filter acetaminophen, other pharma poison meds, and whatever else the typical american would ingest on a daily basis, it can sure as hell handle by products of the body AS IT WAS CREATED TO DO. and yes this is only speculation, but our ancestors did this for THOUSANDS of years, without body issues. CASE & POINT. On top of that there are dozens of studies out there that say the BRAIN functions MORE efficiently on KETONES, than ANY OTHER source of energy. so there's your food for though. I drink a min of a gallon of water a day, with hydration I believe comes effective and easy kidney function. So pound down that Hydrogen Di-Oxide! Do the research and piece it together for yourself.

The whole point of this paragraph was to review some positive effects and dis-spell some myth, and basically to throw my opinion in there that you're doing it right.

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680 · August 25, 2012 at 08:00 AM

Let me put it this way: If Dr. Kurt Harris says ketosis is neither beneficial (over the long-term) nor necessary, and Jimmy Moore says the opposite, well, that about settles it, wouldn't you say?

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