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Fasting,ketosis and cancer

ketosis cancer thomas seyfried fasting

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#31 MrHappy

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Posted 24 March 2013 - 08:25 PM

See, Mr. Happy, I read the links and the key phrase is this: "The stimulation of mitochondrial function, at the expense of glycolysis, reverses the Warburg effect and is thought to block the growth advantage of highly glycolytic tumors." I.e. the tumor relies on glycolysis because that's what allows it to grow. Even though glycolysis produces only 2 ATP molecules as opposed to 30+ ATPs produced in mitochondira via oxidative phosphorylation, the tumor uses the intermediaries of glycolysis to build new cells. That's the main reason. It's like you have some timber and you can use it to build a shack or you can burn it to make a steam engine to do some work. The tumor is driven to build, while mitochondria run their steam engines. Only because the tumor is prevented from building with DCA and other agents does not mean that it will not resume building once the favorable conditions return. Cancer seems more complex than this model.


The point being is that it seems if the mitochondria are stimulated (using DCA), the cancer cells 'wake up' and initiate apoptosis, it's not just starving the energy source.

So, it seems you can slow/halt some forms of cancer progression with ketosis (and possibly allow your immune system time/resources to destroy cancerous cells, according to at least 1 human study so far) and that mitochondria appear to be a valid target in most types of cancers.

#32 Luminosity

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Posted 25 March 2013 - 02:51 AM

Women seem to feel worse on low fat or low carb diets, and binge more, but that doesn't mean those diets are optimal for men.

Mr. Happy, I've never run into a vegetarian on a low carb diet before, but I'm glad you are eating a lot of greens. In the old days, it was the Atkins diet and it was pretty produce free. Not good. The increased need for water to that extent doesn't sound normal. There is a possibility that you may be straining your kidneys, which in Chinese medicine are the seat of the life force.

Consider that you might have had an allergy or sensitivity to gluten or certain foods you are no longer eating. Some people have a hard time digesting all those whole grains and plant proteins. I did when I was a vegetarian. If you have blood type O, this is especially likely. Glad you are feeling better but I would encourage you to look into this more when you can. I've been on many many diets and I've found that Chinese medicine has the most wisdom, and I follow their dietary principles now. They eat a balanced diet and eat moderately, among other things. I also think there is something to the Eat Right For Your Blood Type diet. I don't believe in it 100%, but it has some wisdom.

This is a link to my thread on Chinese medicine:

http://www.longecity...inese-medicine/


I don't think the need for carbs is exclusive to depressed people. Only the Eskimos have not eaten carbs. So that's most people throughout history. That's a lot of depressed people.

Edited by Luminosity, 25 March 2013 - 02:55 AM.

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#33 xEva

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Posted 27 March 2013 - 12:16 AM

A ketogenic diet is very different from a fast. It is meant to mimic certain aspects of a fast but only therapeutic ketogenic diets with very low calories approach the real thing.

And by the way, it is not true that cancer cells feed exclusively on glucose. Even Seyfried says that they feed on glutamate too, A few years back an idea was popular that cancer cells do not have functioning mitochondria, which proved to be wrong.

Not true, ketogenic diets can be just as ketogenic as fasting without calorie restriction though they do need to limit protein as well as carbohydrates. A diet of 85% calories from fat produces very high blood ketones (BHB), the same level as fasting. Example: http://livinlavidalo...y-121-150/16095


Yes but here we discuss ketogenic diets as possible therapies for cancer, and in this case, the number of calories matters. A lot. I don't have the links handy, but even Seyfried stresses this in his interview. The real thing is fasting. Ketogenic diets only mimic certain aspects of its metabolism.

EDIT: I just looked at the ketosis graphs in the link and they are very different from what is seen during a fast. They do not jump like that up and down. The liver produces ketones at a constant rate once the metabolism switches to ketosis. The peripheral muscles adapt to ketosis by refusing both glucose and ketones and feeding on FFAs instead. This allows the level of beta-hydroxybutyrate in the blood to grow steadily until, at day 17 on average, it flattens out and remains the same for the duration of the fast. And yes, the level can reach 5-7 mMol/L, just what Jimmy got on several days. But the dynamics reflected in the graph is vastly different. Again, the main difference is that the fasting graph is smooth, not volatile.


I also think there is something to the Eat Right For Your Blood Type diet. I don't believe in it 100%, but it has some wisdom.


I too very much admire Chinese culture and medicine. As for the Eat Right For Your Blood Type diet, it's one of the worst flops found on the net. Even the author himself renounced this idea -- years ago! And yet the people who know little of physiology and biology and understand even less keep promoting it tirelessly. Please stop :)

For your information: even pigeons have several blood types and they always have had the same diet and the same culture.

Edited by xEva, 27 March 2013 - 12:31 AM.


#34 alecnevsky

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Posted 27 March 2013 - 01:21 AM

Can someone familiar with ketogenic diet clear this up for me? I've been on high fat, high protein, low carb for about a month now (abs. no gluten or grains.) I feel great, but am concerned about brain function in particular. Suppose my glucose intake is at most 20% of before (predom. in form of carrots and yams,) should I expect my brain to have adapted to some extent to ketogenic metabolism? Or am I still due to supplement glucose? I eat spoons of butter (in various ways) every day btw.

Now, regarding ketostix. If the Inuit, 100% carnivorous, groups do not show any high readings of ketone bodies or acids in urine (which has been documented,) what does a high reading actually suggest? (i.e., do measurements higher than trace suggest starvation or disruption of homeostasis of some form?)

Edited by alecnevsky, 27 March 2013 - 01:23 AM.


#35 xEva

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Posted 27 March 2013 - 01:32 AM

Now, regarding ketostix. If the Inuit, 100% carnivorous, groups do not show any high readings of ketone bodies or acids in urine (which has been documented,) what does a high reading actually suggest? (i.e., do measurements higher than trace suggest starvation or disruption of homeostasis of some form?)


Regarding ketostix, you should get them and they still should show acetoacetate in urine. When fasting, the adaptation to the ketosis of starvation takes place at an average of 17 days, and that's when urine ketones become low or disappear altogether. This adaptation takes longer on a diet, so ketostix should still be useful to you. You can judge when you fully adapt by the disappearance of ketones from urine.

#36 alecnevsky

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Posted 27 March 2013 - 02:05 AM

So even if you're eating 4k calories in fats, meats and vegetables (which I can hardly call malnutrition,) the body, being maladapted to that type of diet, will be overproducing ketones in response to the change for more than 17 days? And for less than 17 in starvation regime?

I wonder whether I can expect to see previous energy levels (earlier glucose-induced feelings of satiety too would be nice.)

Mr. Happy could you elaborate on the length of your adaptation experience and whether ketostix were useful/indicative of anything?

#37 xEva

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Posted 27 March 2013 - 03:24 AM

So even if you're eating 4k calories in fats, meats and vegetables (which I can hardly call malnutrition,) the body, being maladapted to that type of diet, will be overproducing ketones in response to the change for more than 17 days? And for less than 17 in starvation regime?



The way you pose the question shows that you do not understand. Any drastic change in a diet or environment requires time for the body to adapt. It's not like you flip a switch and voila, a new circuitry is running. Depending on the nature of the change, and whether it is the first time or a repeat, will influence how quickly this adaptation will take place.

Your other misconception is: ketones are not overproduced, when they are spilled in the urine. They are rather 'unclaimed'. And finally, in starvation, it takes from 14 to 23 days to get to a new state of homestasis, or 17 days on average. I'm not sure how long it takes on a diet. I believe it's longer than a month though.

#38 alecnevsky

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Posted 27 March 2013 - 04:10 PM

Ah, thank you xEva! So the ketone bodies are unclaimed in the adaptation stage b/c the body is still adapted to glucose metabolism and is not efficiently using them? Does this imply the hunger felt at 4k of fat, meat, veg calories versus, say, 2k of carbs? Or this is a glycemic load issue?

I read a quote from Schwatka expedition, which hinted at hunger in initial stage of high-fat high-protein diet :"When first thrown wholly upon a diet of reindeer meat, it seems inadequate to properly nourish the system, and there is an apparent weakness and inability to perform severe exertive fatiguing journeys. But this soon passes away in the course of two or three weeks."

#39 DR01D

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Posted 27 March 2013 - 04:18 PM

"When first thrown wholly upon a diet of reindeer meat, it seems inadequate to properly nourish the system, and there is an apparent weakness and inability to perform severe exertive fatiguing journeys. But this soon passes away in the course of two or three weeks."


Over the course of a couple of years I've made changes to improve my diet. I've noticed two things.

A) When I change my diet I often feel weaker or have less stamina when I lift weights. This lasts for a couple of weeks.
B) I almost always get a few pimples on my face after I change my diet. This happens despite the fact that when I've switched it's always been towards healthier foods.

So I'm pretty sure that any significant change to diet has a wide range of effects on the body. It wouldn't have to be a change from carbs to proteins. Pretty much anything seems to do it.

Edited by DR01D, 27 March 2013 - 04:21 PM.

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#40 xEva

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Posted 27 March 2013 - 05:46 PM

Ah, thank you xEva! So the ketone bodies are unclaimed in the adaptation stage b/c the body is still adapted to glucose metabolism and is not efficiently using them? Does this imply the hunger felt at 4k of fat, meat, veg calories versus, say, 2k of carbs? Or this is a glycemic load issue?

I read a quote from Schwatka expedition, which hinted at hunger in initial stage of high-fat high-protein diet :"When first thrown wholly upon a diet of reindeer meat, it seems inadequate to properly nourish the system, and there is an apparent weakness and inability to perform severe exertive fatiguing journeys. But this soon passes away in the course of two or three weeks."


Yes, you can say that the hunger you felt at 4K of fat and meat was due to most of your cells still expecting glucose instead.

As for the adaptation, it always seems to go in stages. For example, in starvation ketosis, which I am most familiar with, there are at least 3 stages of adaptation before a new equilibrium is reached. That the fatigue passed in 2-3 weeks in the quote you give, does not necessarily imply the full adaptation, but only a stage in adaptation. I'd bet that ketonuria would still be present at that stage. I'd expect that the person would feel even better with a full adaptation, and this can be marked by disappearance of ketonuria or by monitoring other objective metabolic parameters, not just subjective feelings.
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#41 DePaw

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Posted 28 March 2013 - 06:05 PM



#42 xEva

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Posted 29 March 2013 - 03:05 AM



I am at the 6 min mark of Nora Gedgaudas' lecture on a ketogenic diet, and already have an objection. She says that a human baby becomes ketotic upon the first feeding, because of the high content of fat in human milk. This is patently wrong, for 2 reasons.

First, the first 2-day milk, called colostrum, is mostly water +electrolytes, protein and immunoglobulins. It is well known that colostrum is very poor in both sugars and fat. wiki on colostrum: "Colostrum is very rich in proteins, vitamin A, and sodium chloride, but contains lower amounts of carbohydrates, lipids, and potassium than normal milk."

The newborn is ketotic in a few hours after birth, because, having been cut off from the umbilical cord supply and not yet fed, it is actually fasting. And from what I recall reading, the newborn ketosis disappears very quickly once the babe is fed.

Second, it is well-known that human milk (whose final composition establishes in the following days to weeks) is very poor in fat, containing one of the lowest levels of fat among mammals.


Following this, I lost interest hearing what else Nora Gedgaudas has to say. Sorry.

#43 MrHappy

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Posted 29 March 2013 - 10:07 AM



I am at the 6 min mark of Nora Gedgaudas' lecture on a ketogenic diet, and already have an objection. She says that a human baby becomes ketotic upon the first feeding, because of the high content of fat in human milk. This is patently wrong, for 2 reasons.

First, the first 2-day milk, called colostrum, is mostly water +electrolytes, protein and immunoglobulins. It is well known that colostrum is very poor in both sugars and fat. wiki on colostrum: "Colostrum is very rich in proteins, vitamin A, and sodium chloride, but contains lower amounts of carbohydrates, lipids, and potassium than normal milk."

The newborn is ketotic in a few hours after birth, because, having been cut off from the umbilical cord supply and not yet fed, it is actually fasting. And from what I recall reading, the newborn ketosis disappears very quickly once the babe is fed.

Second, it is well-known that human milk (whose final composition establishes in the following days to weeks) is very poor in fat, containing one of the lowest levels of fat among mammals.


Following this, I lost interest hearing what else Nora Gedgaudas has to say. Sorry.


Yup - carb:protein:fat ratio average is like 7:1:2 for the first three weeks and 7:1:4 thereafter.

#44 DePaw

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Posted 29 March 2013 - 02:53 PM

Yet fat makes up the biggest portion of the calories.
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#45 xEva

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Posted 29 March 2013 - 10:25 PM

Yup - carb:protein:fat ratio average is like 7:1:2 for the first three weeks and 7:1:4 thereafter.


The proportions you give are of 'normal milk', not colostrum, which has no more than traces of fat and little carbs. And yet she claims that newborn is ketotic due to the milk rather than to the fact that it is fasting. She sounds incompetent as far as knowledge of basic physiology is concerned.

I sort of skimmed the middle part (let it run its course on the background) and heard her in the very end vigorously deny that a ketogenic diet induces insulin resistance -- for those who 'fall off the wagon', as she puts it just before that last question. This insulin resistance is part of the adaptation to ketosis and is due to muscles ignoring glucose in presence of high levels of FFAs. She does not seem to realize that going back from ketosis to a carb-based diet also requires adaptation and takes time.

So, I think she is rather incompetent and her nervous giggles confirm it (her mannerisms are of a petty thief who is not sure if he's been caught already or people simply do not care about the stolen trinkets).


DePaw, Breyer's ice cream ratio is approx. 4:1:2 http://www.breyers.c...natural-vanilla (I made protein 3.5g instead of 3g for simplicity). And yet no-one advocates ice cream as a ketogenic food ;)
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#46 DePaw

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Posted 30 March 2013 - 11:00 AM

That's because an adult's brain uses up some much less fuel than an infant's does, it's the same that an adult can eat more carbs and stay in ketosis if they exercise heavily, it uses up the carbs fast enough that the rest of the body has to remain in ketosis.

#47 xEva

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Posted 30 March 2013 - 02:48 PM

That's because an adult's brain uses up some much less fuel than an infant's does, it's the same that an adult can eat more carbs and stay in ketosis if they exercise heavily, it uses up the carbs fast enough that the rest of the body has to remain in ketosis.


Did you hear this from a similarly dubious source like the vimeo you linked above?

You seem to think that a ketogenic diet is any diet high in fat. Unless such a diet is very low on calories, it's actually a 'metabolic syndrome developing diet'. High fat with plenty of calories from carbs is the standard American diet, better known as SAD. I saw plenty of examples on other forums (here people tend to be knowledgeable) where people make a similar mistake: they wanna go ketotic, but they still love their carbs, so they 'compromise' while coming up with all sorts of mistaken rationalizations, like you do. But it is easy to learn by monitoring your progress with ketostix and a blood glucose meter.

Edited by xEva, 30 March 2013 - 03:09 PM.

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#48 DePaw

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Posted 30 March 2013 - 04:39 PM

You can be ketogenic without being low in calories as long as it is indeed high in fat, but also low in carbohydrates. Body builders use cyclic ketogenic diets, normally it take 1-2 weeks for the body to adapt to ketosis, which is why the atkins induction phase is that long, but by timing their carbohydrates with the exercise the body builder uses them all up in the heavy exercise and enters back into ketosis straight away, and they repeat this as a weekly cycle.

Ketostix are not a reliable way of monitoring ketosis, as the long in ketosis you are the more adapted your body becomes to it and you stop excreting urinary ketones, also many other things can skew a reading such as hydration level. The best way to monitor ketosis is with a blood ketone monitor which works just like a glucose monitor except it measures beta-hydroxybutyrate (BHB).

" they 'compromise' while coming up with all sorts of mistaken rationalizations, like you do" I don't, I understand the science and biochemistry behind ketosis VERY well.
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#49 xEva

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Posted 30 March 2013 - 07:04 PM

I understand the science and biochemistry behind ketosis VERY well.


I disagree :) Your mistake is to dismiss the origin of a ketogenic diet in the adaptation to starvation as a curious but largely irrelevant to you fact. From this mistake everything else follows. To learn the stages of the starvation response is not difficult though. It's just a collection of a few facts.

Here is one such fact: to conserve protein during starvation, skeletal muscles ignore glucose. For the same reason, they also ignore ketones and feed exclusively on free fatty acids. The mechanism of this adaptation is simple: high level of FFAs flag to the skeletal muscles 'we must be starving => ignore glucose'.

Compare this with a fact from a ketogenic diet: FFAs are abundant in plasma.

Question to you: will skeletal muscle use glucose while the levels of FFAs are high?

Answer: no. The muscle will automatically ignore glucose, even if its level is roof high (and regardless of the level of insulin). That's because adaptation to starvation rules and the rule is simple: high level of FFAs = ignore glucose. The solution to this problem is not to increase insulin but to lower the level of FFAs.

That's why when BBs cycle ketogenic diets and increase carbs they eschew fats completely (and I also hope that they use tricks like niacin then -- otherwise FFAs level continues to be high simply due to metabolic inertia).

And it is not true that it takes couple of weeks to fully adapt to a ketogenic diet. It takes longer than a month and the exact number of days depends on many variables.

Here is one of your misconceptions:

... by timing their carbohydrates with the exercise the body builder uses them all up in the heavy exercise and enters back into ketosis straight away, and they repeat this as a weekly cycle.


The full adaptation to ketosis implies that the skeletal muscles will ignore glucose as long as the levels of FFAs in plasma remain high no matter how high the level of glucose is. The levels of FFAs do not drop suddenly, and when they do, this simply causes more body fat to be mobilized.

The bottom line is, it is not so simple to switch back and forth in between fats and carbs, especially when calories from both are abundant. Metabolism is not a circuit board where you just flip the switch and go from one mode to another. It's more like a water tank, and you can't just empty it and pour in a different solution. It's the difference in the composition and characteristics of plasma that define and dictate a metabolic mode.

This means that going from fats to carbs, at least for a while, you will have all symptoms of a metabolic syndrome (= adult onset diabetes). The more you're adapted to a ketogenic diet, the longer it will take to switch back to a carb-based diet.


Ketostix are not a reliable way of monitoring ketosis, as the long in ketosis you are the more adapted your body becomes to it and you stop excreting urinary ketones, also many other things can skew a reading such as hydration level. The best way to monitor ketosis is with a blood ketone monitor which works just like a glucose monitor except it measures beta-hydroxybutyrate (BHB).


If you can afford a blood ketone meter, so much better. As for the ketostix, considering that it costs pennies, I believe it's a very good idea to use it until the full adaptation to ketosis takes place, marked by disappearance of ketonuria. The feedback you get while using ketositx --and a blood glucose meter!-- is invaluable.

Edited by xEva, 30 March 2013 - 07:09 PM.

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#50 Chupo

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Posted 30 March 2013 - 08:05 PM

I'm surprised that Nora doesn't seem to know about peripheral insulin resistance. She isn't completely wrong though. If you use HOMA scores to measure insulin resistance, they do fall on low carb or keto diets. This is likely what she's referring to.
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#51 DePaw

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Posted 30 March 2013 - 09:14 PM

Muscle can and do use ketones for fuel, not just FFAs. The heat uses ketones a lot: http://en.wikipedia....heart_and_brain

#52 xEva

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Posted 31 March 2013 - 05:00 AM

Muscle can and do use ketones for fuel, not just FFAs. The heat uses ketones a lot: http://en.wikipedia....heart_and_brain


I did say skeletal muscle above. I did not repeat it the second time around cause it would sound pedantic.

I'm surprised that Nora doesn't seem to know about peripheral insulin resistance. She isn't completely wrong though. If you use HOMA scores to measure insulin resistance, they do fall on low carb or keto diets. This is likely what she's referring to.


HOMA? You do not mean to say that a computer software that solves the equations that estimate insulin levels from fasting glucose is more revealing than the simple blood glucose test in real field conditions, do you? Come on guys. It's a well-known fact that a temporary "insulin resistance" is a normal and expected consequence of a stretch on a ketogenic diet. Or fasting. And I know about it firsthand.

And why do you need to apologize for Nora? If you want a more competent Nora, here is one:




#53 Chupo

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Posted 31 March 2013 - 05:31 AM

HOMA? You do not mean to say that a computer software that solves the equations that estimate insulin levels from fasting glucose is more revealing than the simple blood glucose test in real field conditions, do you? Come on guys. It's a well-known fact that a temporary "insulin resistance" is a normal and expected consequence of a stretch on a ketogenic diet. Or fasting. And I know about it firsthand.

HOMA doesn't estimate insulin levels at all. Both Insulin and glucose levels are a part of the equations. It's good for estimating pathological insulin resistance but not physiological IR. I don't deny that ketosis results in physiological IR. It most certainly does. If I hadn't known it, I wouldn't have been surprised that Nora didn't know it.

Edited by Chupo, 31 March 2013 - 05:48 AM.

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#54 alecnevsky

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Posted 31 March 2013 - 07:20 PM

I understand the science and biochemistry behind ketosis VERY well.


I disagree :) Your mistake is to dismiss the origin of a ketogenic diet in the adaptation to starvation as a curious but largely irrelevant to you fact. From this mistake everything else follows. To learn the stages of the starvation response is not difficult though. It's just a collection of a few facts.

Here is one such fact: to conserve protein during starvation, skeletal muscles ignore glucose. For the same reason, they also ignore ketones and feed exclusively on free fatty acids. The mechanism of this adaptation is simple: high level of FFAs flag to the skeletal muscles 'we must be starving => ignore glucose'.

Compare this with a fact from a ketogenic diet: FFAs are abundant in plasma.

Question to you: will skeletal muscle use glucose while the levels of FFAs are high?

Answer: no. The muscle will automatically ignore glucose, even if its level is roof high (and regardless of the level of insulin). That's because adaptation to starvation rules and the rule is simple: high level of FFAs = ignore glucose. The solution to this problem is not to increase insulin but to lower the level of FFAs.

That's why when BBs cycle ketogenic diets and increase carbs they eschew fats completely (and I also hope that they use tricks like niacin then -- otherwise FFAs level continues to be high simply due to metabolic inertia).

And it is not true that it takes couple of weeks to fully adapt to a ketogenic diet. It takes longer than a month and the exact number of days depends on many variables.

Here is one of your misconceptions:

... by timing their carbohydrates with the exercise the body builder uses them all up in the heavy exercise and enters back into ketosis straight away, and they repeat this as a weekly cycle.


The full adaptation to ketosis implies that the skeletal muscles will ignore glucose as long as the levels of FFAs in plasma remain high no matter how high the level of glucose is. The levels of FFAs do not drop suddenly, and when they do, this simply causes more body fat to be mobilized.

The bottom line is, it is not so simple to switch back and forth in between fats and carbs, especially when calories from both are abundant. Metabolism is not a circuit board where you just flip the switch and go from one mode to another. It's more like a water tank, and you can't just empty it and pour in a different solution. It's the difference in the composition and characteristics of plasma that define and dictate a metabolic mode.

This means that going from fats to carbs, at least for a while, you will have all symptoms of a metabolic syndrome (= adult onset diabetes). The more you're adapted to a ketogenic diet, the longer it will take to switch back to a carb-based diet.


Ketostix are not a reliable way of monitoring ketosis, as the long in ketosis you are the more adapted your body becomes to it and you stop excreting urinary ketones, also many other things can skew a reading such as hydration level. The best way to monitor ketosis is with a blood ketone monitor which works just like a glucose monitor except it measures beta-hydroxybutyrate (BHB).


If you can afford a blood ketone meter, so much better. As for the ketostix, considering that it costs pennies, I believe it's a very good idea to use it until the full adaptation to ketosis takes place, marked by disappearance of ketonuria. The feedback you get while using ketositx --and a blood glucose meter!-- is invaluable.



This is very valuable information. Thank you xEva. I think it's very interesting that you say that skeletal muscles in ketogenic body will ignore glucose regardless of its plasma concentration as long as the fatty acid concentration is constant or same as during ketogenic adaptation. Am I understanding this correctly?

Being a student, I am concerned more immediately about brain function than muscle nutrition. Does what you're saying extend analogously to brain metabolism? For example, I read somewhere that fats/ketones can at most account for 75% of brain energy requirements once adapted to ketogenic diet. Does this imply that once adapted to ketogenic diet, it would be futile to use glucose for skeletal muscles but it could still be useful to use glucose for brain energy demands?
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#55 Godot

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Posted 31 March 2013 - 09:33 PM

xEva - You make some very strong statements about ketosis that seem to be quite unique to you, such as the body taking a month to adapt to using ketones efficiently, and peripheral insulin resistance being induced by plasma FFAs irrespective of blood glucose. Could you please provide some sources for these claims?
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#56 xEva

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Posted 31 March 2013 - 10:14 PM

Godot, I just saw your post. I will address it later :)


alecnevsky, you understand it right. High levels of FFAs prevent skeletal muscles from utilizing glucose. This is not something new. Thus the recommendation for people with metabolic syndrome is to loose weight and go on a low fat diet. Both of these measures will lower FFAs concentrations and improve glucose metabolism.

Regarding the brain function, in the period during the adaptation, while glucose is still low and ketones are not quite high, it's normal to feel brainfogged, irritable and weak.

And I don't think that a ketogenic diet will lead to the brain getting 75% of its energy from ketones. This happens during a fast, after ~3+ weeks of starvation, when the sustained level of beta-hydroxybutyrate reaches 5-7 mMol/L. Maybe a therapeutic ketogenic diet will give you a sustained level of ketones this high -? The numbers I saw were in 3-4 mMol/L range and the Atkins diet types stay at around 2.

The other thing, discussed in this thread above (Jimmy Moore's graphs), is that on a diet, the level of ketones goes up and down, reflecting the fat content of the last meal, while on a fast the levels rise steadily. When they reach their max, that's when the brain switches to getting 75% of its energy demands from ketones.

If you look at the graph (Cahill http://www.med.upenn...08-9Lazar-1.pdf page 8), note how the level of beta-OHB rises steeply until day 10 (that's when, on average, the beginners' brains switch to ~30% of ketones). Then from day 10 to day 17 the level of beta-OHB rises slower. Why? The liver keeps producing ketones at the same rate and their concentration builds up steadily. The slower rising rate after day 10 reflects the fact that the brain began using beta-OHB. If it did not, the graph would keep on rising at the same rate.

Note that the adaptation to ketosis, as far as utilization of beta-OHB by the brain is concerned, occurs in stages: the concentration of beta-OHB must reach a certain level and be sustained for a while, which triggers a qualitative change in brain metabolism. Subjectively, this is perceived as malaise (brainfog + weakness) which appears from nowhere and grows -- and then clears quite suddenly.

Note that eventually the graph of beta-OHB flattens out (here it happens past day 30, but this is a compound graph with data collected from mostly obese people fasting for the first time in their lives, which means that the stages of adaptation are delayed). The flattening of the graph reflects the fact that eventually the utilization of ketones by the brain matches their production rate by the liver. I believe that's when the 75% number is reached.


I hope that now you understand why the adaptation to starvation requires that skeletal muscles ignore both ketones and glucose. This is what allows the level of ketones to rise. As for glucose, this graph does not show it, but in my own experience, which is in line with the studies which I would have to find, each time the brain steps up its beta-OHB consumption, the blood level of glucose rises somewhat. Again, this is easy to understand: the levels of fuels in the blood, ruffly = their production - utilization.

This is what goes on during starvation the metabolism of which a ketogenic diet tries to emulate. How exactly it works out on a diet, I'm not sure, except that all the stages are significantly delayed and certain levels are never reached.


Re carbs on a diet, the main purpose is to provide glucose so that endogenous protein would not be catabolized for its production. The excess triggers a rise in insulin and lowers the level of ketosis. As long as the level of FFAs is high, the skeletal muscle will not utilize it, and it will take a while for it to go to baseline. But you can check it for yourself with a blood glucose meter.

Edited by xEva, 31 March 2013 - 10:18 PM.

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#57 DePaw

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Posted 01 April 2013 - 07:51 PM

" the main purpose is to provide glucose so that endogenous protein would not be catabolized for its production" Gluconeogenesis happens at a constant rate, diet doesn't effect it. http://www.ketotic.o...es-it-turn.html
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#58 xEva

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Posted 02 April 2013 - 06:54 AM

xEva - You make some very strong statements about ketosis that seem to be quite unique to you, such as the body taking a month to adapt to using ketones efficiently, and peripheral insulin resistance being induced by plasma FFAs irrespective of blood glucose. Could you please provide some sources for these claims?


I am surprised that you apparently are not concerned about presenting yourself in such an unfavorable light ..by making a demand like this. It shows how little you know about the subject. And yet your tone is of someone entitled -?? Next time please use Google.

That FFAs induce insulin resistance in skeletal muscle is an old, widely known fact. The relevant developments in this area started in 1963, when Randle proposed a hypothesis about the responsible mechanism. However, the methods that could effectively test his hypothesis were not developed until 1990s and that's when most of the relevant research took place. The original Randle idea was not confirmed, but the dust in this area of research has not yet settled and the debate about the exact metabolic pathways involved still goes on. Here is what I bumped into tonight:

How Free Fatty Acids Inhibit Glucose Utilization in Human Skeletal Muscle 2004
...plasma FFA elevation decreases whole body glucose disposal by 46% and muscular glycogen synthesis by 50%. These results are in agreement with previous findings that a twofold elevation of plasma FFA decreases nonoxidative glucose metabolism and glycogen synthase activity in skeletal muscle biopsies (2).

the decrease of both intracellular free glucose and G6P along with reduced rates of glycogen synthesis indicates that FFA primarily inhibit glucose transport in human skeletal muscle.

Recently, evidence was provided for the link between FFA and insulin signaling in human skeletal muscle. After 6 h of lipid infusion, reduction in whole body glucose disposal by 43% was accompanied by...

Conclusions
Studies in humans clearly demonstrated that FFA directly inhibit glucose transport and phosphorylation in skeletal muscle, which is mainly responsible for glucose disposal under insulin-stimulated conditions and for impaired glucose uptake in insulin-resistant states such as obesity and type 2 diabetes mellitus. These findings also indicate an important role of nutrition, particularly increased consumption of lipids and FFA, for the pathogenesis of insulin resistance.
The original Randle paper: Effects of low-carbohydrate diet and diabetes mellitus on plasma concentrations of glucose, non-esterified fatty acid, and insulin during oral glucose-tolerance tests. 1963

Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. 1997
physiological elevations in plasma FFA concentrations inhibit insulin stimulated peripheral glucose uptake in a dose-dependent manner in normal controls and in patients with NIDDM.
Physiological levels of plasma non-esterified fatty acids impair forearm glucose uptake in normal man 1990
We conclude that the maintenance of physiological plasma non-esterified fatty acids levels is associated with a decrease in forearm and the whole body insulin-stimulated glucose uptake.
Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation 1999

In summary,1) acute and chronic FFA elevation induces insulin resistance;
Effects of Oral Fat Load on Insulin Output and Glucose Tolerance in Healthy Control Subjects and Obese Patients Without Diabetes 2005
Elevated levels of plasma nonesterified fatty acid (NEFA) cause peripheral insulin resistance by inhibiting insulin-stimulated glucose transport, phosphorylation, and glycogen synthesis (1–5). They further cause hepatic insulin resistance resulting in increased endogenous glucose production in relation to the degree of hyperinsulinemia (6–9).
Effect of a Sustained Reduction in Plasma Free Fatty Acid Concentration on Intramuscular Long-Chain Fatty Acyl-CoAs and Insulin Action in Type 2 Diabetic Patients

Elevated plasma FFA concentrations impair glucose metabolism by inhibiting the more proximal steps of insulin action in muscle (5–11) as well by augmenting basal hepatic gluconeogenesis and impairing the suppression of hepatic glucose production by insulin (7,12,13).

In summary, the results of the present study demonstrate that a sustained reduction in plasma FFA concentrations after 7 days of acipimox therapy in type 2 diabetic patients 1) enhances insulin-mediated whole-body glucose disposal, ... 3) reduces fasting and postprandial plasma glucose concentrations, 4) improves the basal hepatic insulin resistance index,

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Regarding your second request, about the adaptation time.. When it comes to ketogenic diet, Chupo is your man.

Chupo, I meant to ask you on the other thread. Do you remember, how long it took for ketonuria to disappear?

#59 Godot

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Posted 02 April 2013 - 11:44 AM

xEva - I'm not sure what about my request read as a demand to you. It was not intended that way. Thanks for the references.
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#60 Chupo

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Posted 03 April 2013 - 07:42 AM

Regarding your second request, about the adaptation time.. When it comes to ketogenic diet, Chupo is your man.

Chupo, I meant to ask you on the other thread. Do you remember, how long it took for ketonuria to disappear?


I don't remember exactly so don't quote me on this but I'd guess between one and two months. The morning readings stayed the highest the longest, probably due to concentrated urine, but they eventually fell as well.
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