Thursday, November 24, 2011

Tales of the Metabolically Deranged

Happy Thanksgiving!  I'm probably in too good of a mood to write this post properly, but I have a moment right now and must seize the opportunity, and I'm going to try to make this short but cogent.  A few days ago I noted that I don't agree with Mercola and Rosedale about their characterization (paraphrased, as it wasn't quite as black and white) of glucose as toxic and human beings as on a linear path to diabetes.  Whether or not anyone cares about my opinion as a psychiatrist is another question :-) Commenter js290 wrote the following:

You should read more carefully what Dr. Rosedale wrote in the link you supplied. Your characterization of it is entirely [sic] accurate.

I wrote that I read the articles a couple of times, and found them flabbergasting.  Js290 wrote back:

The way I read it, Dr. Rosedale offered the most generalized solution. The abstraction he makes is we simply define a gradient of metabolic derangement from 0% (healthy) to 100% deranged (diabetic). His argument seems to be simply, the diet that is therapeutic for fully metabolically deranged cannot be unhealthy for the metabolically healthy.
Analogously, it's similar to most of the paleo stance on gluten grains: just because it's tolerable doesn't make it optimal.
Given that you have written about brains function on ketones, that for the same number of carbon atoms, fatty acids produce more ATP than glucose, that the body is capable of producing all the glucose it needs, Dr. Rosedale's view is by far the most generalized and better abstraction from a health perspective. 
Why come up with many different models for different use cases when a single model will work? This is how evolution and natural selection does things: the best abstraction wins.
I think js290 encompasses in a nutshell exactly why I find the theories so puzzling.  I don't see why we should use sick people to tell us what is optimal for all people.  Nor do I know the definition of "metabolically deranged" - do we mean pre-diabetic and type II diabetic?  Obese?  Metabolic syndrome?

I disagree with the characterization that the "derangements" are linear.  My understanding of physiology is that those with healthy beta cell function can do very well with a wide variety of carbohydrate intake and it shouldn't matter that much for optimal health.  We are obligated to use glucose for fuel - we have systems in place to deal with physiologic amounts of glucose.  I also don't think that post-prandial glucose "spikes" are particularly abnormal or dangerous unless they are very high and last a long time.  I don't think glucose or carbohydrates as a macronutrient class per se cause diabetes.  Once you get past a tipping point and start taking out beta cells, hyperglycemia, insulin resistance, and increasing damage occurs, then you have fewer options, dietarily speaking.  Even then, a hard core ketotic zero carber who never cheats may be in good stead, but those who cheat are now (physiologically) even more insulin resistant than they would have been if they ate enough carbs to keep them out of deep ketosis all the time… so glucose "spikes" and area under the curve for glucose and insulin would be even higher than if there were more carbs eaten on a regular basis.

In addition, since the liver will make a bunch of glucose via gluconeogenesis, I don't see much harm in eating moderate amounts of glucose so our liver doesn't need to make it, unless you are needing to stay in deep ketosis for medical reasons. Six of one, half a dozen the other.

And, of course, I think there are certain brain illnesses that could very well benefit from deep ketosis (for some of these conditions it is merely theoretical, for others there are case studies or even pilot data, for epilepsy there is a lot of data) - brain cancers, migraines, epilepsy, bipolar disorder, dementia, autism, and schizophrenia.

In general, I think it is reasonable that fasting and autophagy should be engaged in on an intermittent basis for all individuals, including heathy ones - I know that if on one particular day I personally eat high carb or low carb, I wake up the next morning in ketosis.  That is a sign of metabolic flexibility, which is a positive sign of a healthy metabolism.

Well, that is my opinion.  Starchy root vegetables and fruit are good sources of nutrients and in general less expensive than good quality meat, though perhaps not less expensive or easier to store than than good quality fat, calorie for calorie.  The nutrients in starch tend to be somewhat different than the ones in fat.   I find them pleasurable to eat, personally, and my kids certainly prefer the starch and fruit to just fat, green leafy vegetables, and meat.  Perhaps they would truly want mountains of candy and chocolate and their preferences shouldn't guide our health speculations… well, that's my opinion.  I simply don't think there is enough evidence to suggest that zero carb diets are optimal for everyone for longevity and health, either from an experimental perspective or from a common sense, physiologic perspective.


  1. Well said Emily! Happy Thanksgiving!

  2. Not only is insulin sensitivity a big deal, but the other argument seems to be that glucose is more reactive than fat and glycates proteins/causes oxidative stress. Well don't we have anti-glycation enzymes and antioxidants? And aren't these things determined by the quality of our diets? The defense against the reactivity of glucose is pretty impressive, almost like we evolved to be able to use it for energy!

    Nobody says that fat is bad because when it isn't metabolized quickly enough it accumulates in the cell and causes insulin resistance. Okay well raw vegans say that, but they say a lot of questionable things.

  3. Dr. Deans,

    I'm in no position to formulate the degree in which people can tolerate different forms of fuel. But, I agree with you it's probably not linear, and I don't think Dr. Rosedale's statements is making that argument. From his perspective, he seems to be looking for a more optimal and generalized diet that promotes health that can be backed up by scientific research. I think his basic point really is a diet that is therapeutic for obese and diabetic cannot (should not and will not) harm those who are not obese and diabetic. That's what it means to have the most generalized solution.

    Very simply, if healthy person A has no side effects from both diet Y and diet Z. But, metabolically broken person B suffers side effects from Y but therapeutic effects from diet Z, why would a health care professional waste time with diet Y when diet Z works in both cases? Another way to think about it is the number needed to treat (NNT) favors diet Z: NNT-B(dietZ) < NNT-B(dietY) and NNT-H(dietZ) >> NNT-H(dietY). No discussion of causality needed yet. We're just measuring the outputs of the metabolic black box.

    I want to avoid presenting a false dilemma here, but it's legitimate to ask in which direction a more "optimal" diet for "health" points. Your major contribution to this discussion on the blogosphere, I think, is Your Brain on Ketones. I'm just trying to put this in the context of an optimal and most generalized solution because that's how I was trained to solve problems. I agree with you that we should have better metrics of metabolic broken-ness so that it's lees of a black box. A solution with too many "if-then statements" is not a very good solution. :-)

    Anyway, thanks for the response and Happy Thanksgiving! :-)

  4. “Once you get past a tipping point and start taking out beta cells, hyperglycemia, insulin resistance, and increasing damage occurs, then you have fewer options, dietarily speaking. Even then, a hard core ketotic zero carber who never cheats may be in good stead, but those who cheat are now (physiologically) even more insulin resistant than they would have been if they ate enough carbs to keep them out of deep ketosis all the time… so glucose "spikes" and area under the curve for glucose and insulin would be even higher than if there were more carbs eaten on a regular basis.”

    I don’t understand how “hard core ketotic zero carbers” could become more insulin resistant than those maintaining a low but regular (100 gms/day?) carb intake. It is my understanding that once carbs are low enough for the body to switch to ketones, receptors become more abundant, i.e. normal, and insulin sensitivity returns to normal. If my understanding is correct then, the body then once again becomes able to deal with a cheat amount of carb, much like a pre-metabolic syndrome healthy person. A low but moderate carber’s body may not return to a normal receptor density to the same degree and would therefore continue to face glucose & insulin swings.

    On a different topic – magnesium – I understand that organic forms (citrate, etc) have a bio-availability around 30% whereas magnesium oxide has very poor (0%? 5%? 10%?) availability. Any idea what the bio-availability of the magnesium in Epsom Salts is? It’s a highly water soluble form.

  5. A very thoughtful post. I lost a good deal of weight, and had big improvements in my blood lipids, on a low-carb diet with very little starch or fruit, but I would not go out on a limb and say you are wrong to include some starches or fruit. A friend of mine had similar results with Weight Watchers, which is a low-fat approach.

    After talking about our experiences, we wondered if the big win is simply a low-*junk* diet. My working definition of that would be no sweets, no sugary drinks, and no manufactured foods that did not exist in, say, 1940. Cream, butter, fatty meats, potatoes (prepared at home), white bread, fruit, vegetables; no candy, no soda, no fruit juice, no pastries, no cake, no pie. Low-carbers, low-fatters, vegans, and paleos would all find some things to object to, but surely there would be some benefit. A pity that an investigation into this approach would be unlikely to obtain funding.

  6. Well said.

    Also, one thing thing that doesn't come up very often talking about low-carb or paleo, is that many people just don't feel very well psychologically eating that way; anxiety, feeling blue etc are common complaints of very low-carb diets.

    This is something that I think the paleo movement are ridiculously bad at adressing. They wipe it under the rug with "it passes in a couple of weeks", which is obviously wrong since low-carb studies commonly have trouble keeping participants eating low-carb.

  7. A lot of diets can reverse diabetes and treat obesity. I've seen a lot of people have great success with a vegan diet, is a vegan diet healthy long term?? Not in my experience. I think the same can be said for VLC diets, although they'd probably fare better than vegan diets if they eat the whole animal(glands, organs etc.)

  8. Heretic!!! LOL

    No, I totally agree with you. I think Rosedale has gone off the deep end with his extreme recommendations. Glucose toxicity begins at 0mg/dl?? I can't believe that guy is a real doctor.

  9. Not to mention the fact that we now know that diabetes is not always progressive. Some people with pre-diabetes will NEVER develop full-fledged insulin-dependent T2DM, no matter how crappy their diet is.

    People without a gallbladder may not digest fat well. Does that mean healthy people with intact gallbladders shouldn't eat fat?

    People with hereditary hemochromatosis should avoid iron-rich foods like organ meat and oysters. Does that mean all people should avoid those foods?

    Even if glucose is toxic for diabetics, it doesn't follow that it's a problem for the metabolically healthy. Nor does it follow that excess glucose caused diabetes in the first place (I'm not saying it isn't a factor, but I am saying you can't logically draw that conclusion without supporting evidence demonstrating it to be true.)

  10. What about the fact that LC diet is a great tool for normalizing such wide spread condition as a hypertension? My mom is off her BP medicine after switching on LC. May be there too many sick people in the population who should watch their carbs? They are not necessary the ones with well-defined mental issues or diabetes, but also people with less-optimal health.

  11. "Whether or not anyone cares about my opinion as a psychiatrist is another question"

    Pfft. Most only care about the opinions of doctors of organs that they actually use ^_~

    "Why come up with many different models for different use cases when a single model will work? This is how evolution and natural selection does things: the best abstraction wins." (js920)

    False. If this were true, we wouldn't even make ketones; we (life) have burnt glucose for much longer than fat. Nature selects for fitness, not abstraction.
    (Disclaimer: I am neither a biologist nor a medical doctor.)

    "I'm just trying to put this in the context of an optimal and most generalized solution because that's how I was trained to solve problems."

    That is a noble goal. Generalization, though, must be done with care; medicine isn't mathematics (not for a very long way down, at least). To paraphrase Albert Einstein: "as simple as possible, but no simpler." (Also, E=m (in natural units, of course) but that's neither here and now nor there and then ^_^)

  12. Excellent post! Happy Thanksgiving, Emily. It just occurred to me while reading your post, that morning breath may be stronger in an individual who is not keto adapted (i.e., does not have a flexible multi-fuel metabolism). When they wake up in the morning following an all-night fast, their body is not able to effectively utilize the ketones, and thus it is excreted in the breath. I'm sure others have had this insight, too, but I don't remember coming across this yet in the blogosphere.

  13. @Aaron Blaisdell: Dr. Rosedale actually mentions this fact about ketosis, "It isn’t necessarily ketosis that we want…it is the burning of those ketones that is beneficial, and the two are often opposite. Ketosis is what is left over from not having burned them. Eating carbs can inhibit the burning of ketones that the MCTs may be making, thus resulting in ketosis, but not necessarily ketone utilization."

    @Chris Kresser: It's not just a matter of whether glucose is toxic, the knowledge of which could help determine how much extra glucose each person can tolerate. The more fundamental question is whether dietary glucose is necessary if the liver can meter the production of glucose needed by the body. What health benefits would one gain by ingesting an unnecessary nutrient?

  14. The linear way of thinking is so much a hallmark of scientific reductionism and its problems. Anyone ever heard of a vicious cycle? A virtuous cycle? Isn't that possible here? There are other elements involved that propagate the good/bad effects of glucose? Moreover, what about a systems based approach? Looking at only glucose as the enemy makes for a good arguing point, but isn't it possible that a normal person can eat a wide range of foods--even wheat, milk, and what your mother fed you growing up? Has anyone met anyone over 100 years old? Did they get their with a ketogenic diet? Did they never eat starches or desserts occassionally? Are their 100 year old eskimos?Though I am a low-carb advocate, I am not a total no-carb advocate across the board! Isn't that the same logic that brought us to this point? Demonization and beatification of nutrients is silly. It's not either-or, folks. It's not: your either with the food terrorists or not when it comes to food.

  15. @js290. thanks for the quotes. I know that a diet too high in carbs can kick a person out of burning the ketone bodies they produce, but my understanding (Emily herself has said this many times) that with a moderately low (compared to SAD) level of carb consumption, one can maintain metabolic flexibility and switch easily and efficiently between burning glucose as a fuel and burning free fatty acids and ketones as a fuel. My comment, however, specifically raised the idea (new to me, but perhaps not to others), that it is the inefficiency in burning ketones, in particular by most people on an agricultural and especially industrial, high-carb diet, that is responsible for bad, smelly, morning breath. My experience is that ketone breath (which I had when I first went Paleo very-low-carb) resembled morning breath in a striking way. I don't get it any more, now that I can burn ketones as a fuel. I still get morning breath, but I have the sense that it is not as powerful as it was in my SAD days. (I'll have to ask the wife for confirmation on this point.)

  16. I find the analysis to be of the either or variety, and many of us with normal weight have issues such as CAD from eating for decades the recommended SAD diet. In my case as a 60 year old with CAD and a family heart disease history, i find it interesting that when I look at NMR results the percentage of small LDL to total LDL is about 45-50% with the inclusion of "safe starches" and with little to zero "safe starch" see the small LDL at close to zero. Oh, no diabetes, normal weight, thyroid,D, blood glucose levels and whatever else may be out there. I would suggest that for people such as myself if one believes small LDL is a risk factor for CAD, and can only be affected by carbs that limited to no carbs is the way to go.
    We older folks may not have a system due to aging that can accomodate diets for the 20-30 yr old Paleo types. Dr. Rosedale treats diseased people; he directionally may be more right than wrong

  17. I've been pouring over your blog and many other sources on the gluten issue. It's sooo interesting and I definitely think we have a gluten epidemic in this country. NYT's magazine came out with an article last week, which wasn't too helpful except for the 2nd page where they talk about the 1998 and 2033 studies...I know you mentioned that the blood tests aren't definitive, but these high numbers of positive blood tests are amazing.

  18. Too low of glucose can also cause other problems, such as high cortisol. Cortisol is involved in gluconeogenesis (producing glucose from fats and proteins), so when you're not ingesting glucose in food then your body is producing a lot of cortisol to generate it from fats and proteins. That's why I like to follow Mark Sisson's carbohydrate curve. He says that staying between 50 - 100g is good for weight loss while you can easily maintain weight between 100-150, and you start gaining weight at much higher levels. But again, this also depends on each person.

    Regarding bad breath, I'm pretty sure that bad breath on a SAD diet is from overproduction of bacteria in the mouth. Every time I eat something sugary, I can feel my breath change. I like to think that I also gave them something tasty to eat. Bacteria love sugar just like we do!

  19. A TED talk about insulin, FOXO, and longevity:

  20. Interesting point on the cost of calories. Here's some numbers I recently calculated for the cost of 1000 calories from different food:
    canola oil @225/L: 25c
    medium ground beef @200/lb: 145
    butter @300/lb: 95c
    Sugar @100/kg: 25c
    Potato @25c/lb: 55c
    quick oats @175/kg: 45c


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