Karl Popper, metabolic advantage and the C57BL/6 mouse


Based on the number of comments I get and the number of questions that come through the email on our website, it seems that there is much confusion about the interplay of calories, the caloric deficit, weight loss, and weight gain. I’ll use this space to expand on my views of these complex and confusing issues.First, let’s look at a concept that will help explain a lot. It’s a concept that Gary Taubes explores in great detail in his book Good Calories, Bad Calories, which, by the way, is available now. (Grab a copy and spend a fascinating couple of days poring over it. The rewards will be immense.) The concept in question is interpretation of the energy balance equation, which looks like this:

ΔWeight = Calories in – Calories out

What this equation basically says is that the change in weight (ΔWeight) equals the number of calories consumed minus the number of calories burned off in the process of daily living.

Most people interpret this equation to mean that it is driven from the right hand side. In other words, if you want to reduce your weight (have the change in weight go in a negative direction) you must either eat fewer calories or exercise more or both. Thus the advice that we have all heard to eat less and exercise more. And, as far as the manipulation of that equation on paper goes, that is a correct way of looking at it. But is that how it works in life?

If we accept as true that this equation is driven from the right side and we couple that acceptance with the certain knowledge that the incidence of obesity is of epidemic proportions, then all we can say is that all these obese people eat too much and don’t exercise enough. In other words, they eat like hogs at the trough and they’re lazy. That is the only conclusion we can draw. And, if that conclusion is true, then the way to treat the obesity epidemic is to make everyone eat less and exercise more.

Problem is, that doesn’t work in the long run. Numerous studies show that people can restrict calories and lose weight…over the short term. They can’t seem to do it over the long haul, however. All the subjects in the Keys study lost a huge amount of weight while on a restricted diet and a lot of exercise, but as soon as the study was over, they gained all their lost weight back plus some, which is what typically happens with overweight people who lose substantial weight dieting. The medical literature is pretty conclusive on the idea that you can’t lose weight by exercise (See Gary Taubes’ article in this week’s New York magazine for a fuller treatment of this subject) because people tend to eat more to compensate for the exercise that they do…and it doesn’t take much overeating to compensate for a fair amount of exercise.

The energy balance equation is much like the Arkansas Razorbacks football team this year: they both look good on paper. But the reality is much different. I don’t know how to explain the Arkansas Razorbacks, but I can make a stab at the seemingly bizarre workings of the energy balance equation.

Instead of looking at the equation as one that can be driven only from the right side, let’s look at it from the position that it may be driven from the left. What if the change in weight drove the amount of calories eaten and the amount of caloric energy dissipated? I can think of one situation where the equation makes perfect sense looked at that way.

Think of teenagers. What do they spend inordinate amounts of time doing? Eating and sleeping, right? Teenagers eat all the time and they’re chronically tired. Given the chance, most of them would sleep until noon or later every day. And just try to get one to help around the house. When you do, what do they say: ‘I’m tired.’ And they are tired. Look at how much they sleep.

If the energy balance equation were driven from the right side, all these teenagers should be fat, fat, fat. And, though childhood and teen obesity is on the rise, most teenagers are still thin and lanky. Why? How can this be with the amount they eat and the amount they lay around the house?

Besides laying around the house, eating everything that’s not nailed down, and being obnoxious, what are teenagers doing? They are growing. The majority of people gain most of their height during their teenage years. To build the bone and muscle required to add several inches of height requires a lot of food. Remember, most of the food we eat goes to maintaining the energy levels we need just to live. We burn up a lot of calories just sitting around staring out the window. Teenagers burn those calories, too, but also have to provide for all the energy needed for growth, and that’s not to mention the raw materials for that growth, which can’t be burned as energy.

In teenagers it’s the change in weight (ΔWeight) on the left side of the equation, i.e., growth, that drives the right side of the equation. They eat more and sleep more because they’re growing. They don’t grow because they eat more and sleep more. Not only do these teenagers grow in height, they grow other ways as well: males have a rapid increase in their muscularity; females put on more fat in all the right places. And it’s not only teenagers. Rats that have been genetically and/or surgically altered gain more weight than those that haven’t. Animals that hibernate increase body fatness around hibernation time even if in captivity and with their food restricted. In none of these situations are the changes driven by the amount eaten.

If the energy balance equation runs that way for teenagers why not for the rest of us as well? What if underlying levels of fatness or genetics or _____ (we’ll fill in the blank later) cause us to eat more and burn less?

If we read interviews with the subjects in the Keys starvation study, we find that although they were worked hard as part of the study protocol, when they didn’t have to work, all they did was lay around and sleep. They were chronically tired. They limited their activity as much as possible to conserve the energy contained in the small amounts they ate. Their tiredness and lassitude was driven by the fact that their Δ Weight had dropped thanks to their semi-starvation diets. Their bodies were trying to compensate for the decreased caloric intake by making them exceptionally tired and decreasing their will to move.  They were driving their energy balance equations from the left side.

Almost no evidence exists in the medical literature showing that manipulation of the right side of the energy balance equation does much of anything over the long run. Studies on long-term calorically restricted dieting show that subjects lose weight early on then tend to stop losing weight and then regain what they lost plus some. No evidence exists to show that exercise accomplishes anything in the long run. Sure, there are studies done with subjects in a hospital where they can be watched closely and don’t have to rely on recall to have their diets determined, the so-called metabolic ward studies But these studies are prone to error as well. (We’ll discuss these errors in a later post in more detail) And even if they are error free, they are meaningless as far as free living people are concerned. These same studies were conducted in concentration camps during WWII. Almost all of the prisoners lost large amounts of weight, but, just as with the Keys study, they were chronically hungry, they obsessed on food, they were depressed, they slept at every opportunity and they limited their volitional activity.

So, there you have it. Just go on a concentration camp diet and you’ll lose a lot of weight quickly and easily. The problem is, however, that no one can really go on a concentration camp diet for any length of time unless in a concentration camp. Hunger is too compelling. If you go on a calorically-restricted diet for any length of time (i.e., you’re trying to manipulate the left side of the equation by changing one of the components on the right side) your body kicks in and makes you hungry and sooner or later you’re going to give in. At the same time your body will make you tired, sleepy and lazy, and you will conserve as many calories as possible. Because the right side is driven by the left, you are doomed to failure.

So does this mean that if we’re fat we’re doomed to a lifetime of fatness? Are we captives to the left side of our energy balance equations with no chance for escape?


Let’s take a look at how we can manipulate the left side of the equation to get us where we want to be.

First, let’s look at what’s driving the left side of the equation. What’s making us eat more? What’s making us want to move less? Well, for starters, hunger is making us eat more. That and the ready availability of food. Even if we were a little hungry we probably wouldn’t eat unless the food was at hand. We would have to let our hunger reach a higher level before we would seek out food that cost us a lot of activity to get. If all we have to do is reach into a bag of chips, we can sate our hunger (at least temporarily) pretty easily. If we have to get up and cook something, that’s another story.

Forgetting about the availability of food, let’s focus on hunger. Hunger is nature’s way of telling us that we need to eat. Why would nature tell us we need to eat, though, when we’re carrying 40 pounds of excess fat? A couple of reasons. First, one of the signals that the fat cells are sending telling the brain that they’re full – leptin – is blunted. Another reason is that elevated insulin levels – and virtually everyone with an excess 40 pounds of fat has too much insulin – help drive the hunger response in a number of ways. Too much insulin can drop blood sugar levels, and as we’ve discussed, a falling blood sugar drives the urge to eat. Too much insulin also traps the fat in the fat cells. As MD and I discussed in Protein Power, insulin not only drives fat into the fat cells, it also keeps fat there once it’s in. The cells of the body need constant nourishment, not just that that they receive during the normal three meals per day. The body takes in the excess energy consumed during those meals, converts it to fat and stores it in the fat cells. If all systems are working properly the stored energy is released as needed during the time between meals and distributed to the cells via the blood. If insulin levels remain high, the fat can’t get out of the fat cells. So, the individual cells are starving despite the fact that there is abundant energy locked away in the fat cells.

But what about blood sugar? If the cells can’t get to the fat, can’t they use blood sugar? Sure they can. But where are they going to get it? If they consume what’s in the blood, then that level drops and stimulates appetite. In the presence of elevated insulin levels gluconeogenesis doesn’t operate very well, so it’s tough to make more blood sugar. The body finds itself between a rock and a hard place and puts in an SOS call to the brain.

When the brain gets this message, it cranks up all its hunger machinery and off you go looking for food. You eat some chips or a bowl of ice cream or whatever you can get your hands on. The levels of sugar and fat go up in the blood, the cells are happy for a while, and insulin is busy trying to shove it all away into the fat cells. Soon everything stabilizes back to where it was before you noshed on whatever it was you noshed on. Then the cycle repeats. This disregulated metabolism and hyperinsulinemia is what we fill in the blank above.

Now, let’s look at what happens when you intervene with a low-carb diet. You eat a steak and a few low-carb veggies. Your body gets a big influx of fat and protein and a little bit of carb. None of these foods serves to raise insulin levels a lot, so insulin goes up only a little. But along with the insulin now comes a squirt of glucagon, insulin’s counter regulatory hormone. Glucagon can drive gluconeogenesis to make blood sugar if needed, and glucagon also stimulates the activity of hormone-sensitive lipase, the enzyme that transports fat out of the fat cells (also discussed in Protein Power) .

So now between meals we’re in a situation where the cells can get the nourishment they need, so they don’t send the SOS to the brain, and the brain has no need to tell you to eat. So, for the most part, you’re not hungry. As time goes on and you remain on the low-carb diet, you may actually eat more calories than you need to meet all your cellular requirements. What happens then? The brain can send a message to the body to dissipate more calories. You become more active. Instead of dreading working out, you want to work out. You want to move. Even better, internally, where you can’t even sense it, your mitochondria are allowing protons to drift back across the inner mitochondrial membrane and dissipating excess energy. You activate many futile cycles within the cells that ditch excess energy as heat. In short, you’re eating more calories and losing weight to a greater extent than you were when you were simply trying to restrict calories.

When two groups of subjects both eat the same number of calories (but provided by diets of different macronutrient compositions) and maintain the same activity level, yet one group loses more weight than the other, the group losing the greater weight is said to have a metabolic advantage. Or, more specifically, the diet driving the weight loss is said to provide a metabolic advantage.

Some misguided ‘experts’ have been known to say that there is no such thing as a metabolic advantage, despite it’s having been demonstrated in many studies of free living people. But before we get into why these ‘experts’ are wrong, let’s change gears for just a bit.

Sir Karl Popper was a Viennese philosopher considered by many to be the foremost philosopher of the 20th century. Popper fled the Nazis in the late 193os and went to New Zealand; he then moved to England in 1946, where he became a professor at the London School of Economics. He 200px-popper.jpgremained in England until his death in 1994 at the age of 92. During his long career Popper wrote many books and influenced countless scholars. One of his most important achievements was his elucidation of his theory of falsification as laid out in his book The Logic of Scientific Discovery. Many scientists consider Popper’s idea of falsification to be the only major improvement to the scientific method since Francis Bacon came up with the idea.

Although more complex mathematically than it appears on the surface what Popper’s falsification theory does is describes a way in which hypotheses can be stated with accuracy. Remember, an hypothesis is merely a guess or an assertion that requires testing before it can be said to be viable. Hypotheses can be stated in ways that, although they seem reasonable, can never really be tested. Popper wrote that the only way an hypothesis can be considered a valid hypothesis is if it can be falsified.

What does this mean exactly?

Let’s say I come up with the hypothesis that all men must ultimately die. That hypothesis seems reasonable on the surface because no one has lived forever. There is no one living right now that anyone knows of who was born before, say, 1850. So it stands to reason that all men must ultimately die. After all, it jibes with what we’ve observed. But, according to Popper, my hypothesis wouldn’t be very good because it can’t be falsified. All we see when we observe someone die – again, according to Popper – is confirmation of the hypothesis, but never proof. For all we know, there is someone living right now who may never die.

If, however, I change my hypothesis to one that says all men live forever, then I have an hypothesis that can be falsified, so it is a good hypothesis. All it takes is for one man to die, and the hypothesis is disproven. So, since that hypothesis is falsifiable, then it is a valid hypothesis. It’s the same if my hypothesis were that all cats are black. All one would have to do to disprove that hypothesis is to find one white cat.

It seem simplistic but it is important. It has changed the way that scientist state their hypotheses so that they can be falsified. That doesn’t mean that the hypotheses will be falsified, but it’s important to state them so that they can be falsified if such data comes forth.

Now let’s back up to our idea about the metabolic advantage.

Some people claim it exists while others claim that it doesn’t. What’s the truth? We know both groups can’t be correct, so one has to be wrong. The metabolic advantage either exists or it doesn’t. Let’s establish our hypothesis so that it fits with Popper’s concept of falsifiability.

If we hypothesize that there is a metabolic advantage we may have some trouble. Why? Because if we search and search and never find any evidence of a metabolic advantage, all we can say is that we haven’t found it yet. If, on the other hand, we state our hypothesis as follows: There is no metabolic advantage, then all we have to do is find one instance where there is one to disprove that hypothesis. Since that hypothesis can be falsified it is a valid hypothesis. And if we can falsify it, then it’s obverse, i.e., there is a metabolic advantage, is true. Sir Karl would approve.

Now that we have our hypothesis, how do we go about falsifying it? Or at least trying to.

By performing very carefully controlled studies.

We’ll leave the discussion as to why and how for another post, but it should go without saying that metabolic ward studies on humans are fraught with inaccuracies. Why? Because people cheat – even in a hospital. The subjects on Keys starvation experiment were under lock and key and they cheated. Keys dropped some from the study because they cheated. And he threatened others. People on ‘metabolic ward’ are simply inpatients in a hospital. They have visitors. They sneak foods. Subjects participating in free-living studies under report their food consumption; those in metabolic ward studies don’t report. As I say, we’ll go into this in a later post, but just because something is a metabolic ward study doesn’t mean it’s infallible.

What is infallible then? Or at least as infallible as a study on living creatures can be?

Animal studies are pretty much the gold standard for this kind of thing. Lab animals can be kept with whatever amount of food the researchers want to give them. They don’t have visitors, they can’t sneak off to the vending machines and they can’t smuggle in food. Most importantly they are usually all genetically the same and should respond to any intervention in the same way, which can’t be said for human subjects (other than identical twins) in almost any study. Lab animals are excellent study material for evaluation of a hypothesis such as the one we developed.

That’s where the C57BL/6 mouse of the title of this post comes in.

Now I’ve written many, many times over the course of this blog that rats and mice are not just furry little humans. Many experimental results from these animals don’t work the same way with humans, so you’ve got to be careful what you accept as valid as far as humans are concerned. But the laws of thermodynamics DO work the same in all living creatures and in all systems for that matter. So rats or monkeys or mice or armadillos are going to obey the laws of thermodynamics in the same way we humans do. And thermodynamic data we gather from well done animal studies applies to humans just as it does to the animals in question.

A couple of months ago a group from Harvard published a study in the prestigious American Journal of Physiology looking at what happens when diet composition is varied in mice, C57BL/6 mice to be exact.

The researchers divided 32 genetically-identical, 8-week old male mice into 4 groups of 8. Each group was put on a different diet. One group got a high-sucrose, high-fat diet (lucky little buggers since they were all going to die anyway), another got a control diet of regular chow, another got a chow diet that was only 66% of the calories of the control chow diet and the last group got a very-low-carbohydrate ketogenic diet. All the mice got the same number of calories that varied with growth. Here’s how that worked out.

The control mice eating the chow set the caloric consumption for the group. Researchers gave the control mice all the chow they wanted and measured the calories consumed. They then gave that same number of calories to the high-sugar, high-fat group and to the ketogenic diet group. They gave 66% of the control diet calories to the calorically-restricted group. They studied the mice for a little over a month, which is a long time in the life of a mouse.

What were the findings?

The researchers discovered that despite eating the same number of calories as the control mice and the high-sugar, high-fat mice, the mice on the ketogenic diet gained weight at the same rate as those on the calorically-restricted diet. (Remember, mice, unlike humans, continue to grow throughout their short lives, and so will continue to gain weight.) Here is the weight change portrayed graphically.


As you can see from A above, the mice on the ketogenic diet ate the same number of calories as all the other mice did except for the calorically-restricted ones. You can see from B that the mice on the ketogenic diet weighed the same as the calorically-restricted mice despite consuming many more mousy calories. And, finally, you can see from C that the laws of thermodynamics weren’t violated because the mice on the ketogenic diet ran at a hotter temperature than did the other mice.

And I find it curiouser and curiouser that the very diet that provided the metabolic advantage to these mice, the ketogenic diet, is the same diet that has been shown to provide a metabolic advantage to humans.

Intelligent people will look at this tightly-controlled study and say, Hmm, mice that ate a ketogenic diet gained less weight than genetically-identical mice eating the same number of calories but of a different composition. There must be something different about the way a ketogenic diet works because it provides a metabolic advantage, i.e., the animals that followed it gained less than those that didn’t and didn’t do anything volitional to keep from gaining the weight.

At least that’s what the authors of the study said. And one assumes that they are reasonably intelligent. Specifically, they concluded that

feeding of a ketogenic diet with a high content of fat and very low carbohydrate leads to distinct changes in metabolism and gene expression that appear consistent with the increased metabolism and lean phenotype seen. Through a specific dietary manipulation, weight loss can occur secondary to distinct metabolic changes and without caloric restriction. [My italics]

It sounds like a metabolic advantage to me. It sure does. It sure does.

These authors have done other studies with this same strain of mice and found the following:

These data indicate that dietary manipulation is capable of altering energy balance and metabolic state. In these experiments a high-fat, ketogenic diet not only failed to cause obesity but was capable of reversing diet-induced obesity in mice. These data suggest a more complex relationship between fat consumption and obesity than previously thought. Further investigation as to the mechanisms of energy balance in these animals may provide new targets in obesity research.

So, we’ve come full circle. Using the data from these mouse studies we have shown that there indeed is a metabolic advantage in living creatures that doesn’t violate the laws of thermodynamics, and by doing so have falsified the hypothesis (vigorously stated by some) that there is no metabolic advantage. Meaning, of course, that there is indeed a metabolic advantage, which anyone with good sense who has fooled around with low-carb diets realizes.

Karl Popper would be proud of us.

Please note: I reserve the right to delete comments that are offensive or off-topic.

Leave a Reply

Your email address will not be published. Required fields are marked *

73 thoughts on “Karl Popper, metabolic advantage and the C57BL/6 mouse

  1. Interesting that they were C57 mice. In DesMaisons’ book “Potatoes not Prozac,” it was looking at C57 mice that led her to the “aha” hypothesis that there is a subgroup of people who, like C57s, share familial metabolisms that make them predisposed to obesity, alcoholism, and depression. (C57 mice are often the “ones with the disease” in controlled animal studies) .

    Just for fun: The C57 Story by DesMaisons

    Taubes also talks about Hoebel and the rat studies with sugar addiction. There’s a story that when Hoebel was wondering with DesMaisons about how to reliably and quickly induce carb addiction in the rats, she said something like, oh just do what people do. Don’t eat enough all day and binge on whites at night. It would be amusing except it’s not

    Nope, not amusing at all.



  2. Thanks, Dr.Mike, that was a great read. I have a friend who has finally given LC a try and is worried something is wrong – she isn’t hungry anymore and yet she doesn’t feel deprived. Sometimes you have to “do” before you believe. I’m going to print this off and send it to her.


  3. “Glucagon … also stimulates the activity of hormone-sensitive lipase, the enzyme that transports fat out of the fat cells (also discussed in Protein Power) .”

    Wow! As soon as I read that, I had to wonder… if lipase transports fat out of fat cells, then wouldn’t eating dairy products containing lipase (goat milk cheese, for example) help people lose weight???

    I raise dairy goats and a Jersey cow for organic, untreated (ie, raw) pasture-fed milk for milk-share production. I know that, generally speaking, low-carb proponents do not approve of dairy, but I believe there is a HUGE, real, health difference between untreated, organic whole milk and commercial pasteurized milk products that have been fractionated and then reassembled into “whole” milk. I have more than a few customers, babies and adults, whose intestines tie up in painful knots with commercial milk, yet will drive up to 50 miles, one way, to get my raw pasture-fed goats milk which not only doesn’t cause them pain but actually gives them back health.

    Anyway, I often have excess unsold milk which I make into cheese, mostly chevre and goat milk feta, as well as mozzarella and semi-aged cheeses like Monterrey Jack and Queso Fresco.

    Compared to cows milk, goat milk is naturally high in lipase, one reason why it’s more delicate than cows milk. This lipase has a tendency to cause the milk taste “goaty” when handled roughly (as in transport), processed (eg, pasteurization), or when stored too long in the fridge or aged as in cheese… and is the main reason why goat milk for drinking has a bad reputation. In fact, Toggenburg goats were developed especially for cheesemaking, with an especially high lipase milk that tastes goaty even when just drawn. Most other breeds’ milk does not taste goaty when just milked.

    Back to my first comment about lipase, when I make feta cheese, I usually add extra lipase for an extra strong, sharp feta which many customers prefer; I also add it to some chevre, mozzarella and other semi-aged cheeses. In fact, I go through so much lipase I now buy it by the pound.

    Would not eating cheese with extra lipase help digest internal fat?

    Thanks for so many thought-provoking articles.

    Hi Jenny–

    Lipases are enzymes that basically break down a bond in a fat. Hormone sensitive lipase, the one that glucagon influences, helps take the fat from within the fat cell and move it into the blood where it can be transported to the cells to use for fuel. All enzymes are proteins and have a specific structure that allows them to perform the specific tasks the are designed to perform. If this structure is altered, then the enzyme doesn’t work properly. Acid alters the structure of enzymes, so any time you take an enzyme by mouth and it passes through the stomach it is altered and becomes unable to do its job. Insulin is a protein as is any enzyme you want to name, and because it’s a protein, insulin can’t be taken by mouth because it would be destroyed in the stomach acid and become nonfunctional. For this same reason and enzymes that might be in goat’s milk would never make it through the stomach acid with their structures intact. Plus, the lipases in goat’s milk aren’t the very specific lipase required for moving the fat out of the fat cells, so even if they made it through the stomach, they wouldn’t work.



    • Not all digestive enzymes are denatured by stomach acid, because parts of the intestine also digest at acid pH, so enzymes intended for these processes will survive the stomach better. And observation, available to anyone, shows that protease digestive enzymes such as papain or bromelain work even in chewable tablets.
      I believe the difference is that insulin and cell-specific lipase were evolved to work at blood pH so have none of the resistance to stomach acid that digestive enzymes do.
      Also, digestive enzymes may be denatured by extremes of pH, but they can often revert to the active form again once the pH is right for them; this is one mechanism for controlling digestion so that enzymes work in the right order, and nutrients appear in the right sites for absorption.

  4. whammo slammo! great stuff!

    however, in my case, if there is a metabolic advantage, it seems too small to even worry about. When I eat all I want low carb style, I end up about 20 pounds overweight. That’s better than being the 50 pounds plus and climbing that I was before Taube’s’ original NY Times article five years ago, but not quite good enough for me. (It could be the booze throwing things out of whack, I suppose-I have a few drinks 3 or four days a week, normally).

    I’m now using a daily IF routine as a trick to limit calories, and so far it’s working. For the past two months, I’ve maintained my weight comfortably at about 10 pounds lower than I had when eating 3 low carb meals a day (which looked a lot like your food porn pics, btw!).

    So, in your terms, I am successfully and comfortably working the right side of the equation. I don’t see any problem with doing this the rest of my life, actually.

    (btw, I’ve been to that squeeze inn place, had a burger one afternoon there. I was in vacation/cheat mode, haha!. Don’t know about mimosas in the morning tho, certainly not on a skiing day!)

    Hey mrfreddy–

    I’m not saying that calories don’t ever count, because they do. (As Gary Taubes describes it, calories are not an independent variable as many people would like to think.) I’m simply saying that a metabolic advantage can be shown in living creatures that is consistent with the laws of thermodynamics, which disproves the hypothesis that a metabolic advantage doesn’t exist.

    There is much biological variability out there, i.e., we’re not all lab mice with identical genes, so there will be a variation in how people respond to low-carb diets. What I’ve found in many years of practice taking care of thousands of patients is that most – not all, but most – can pretty much maintain their weight eating whatever they want as long as it’s low-carb. The satiating effect of the fat and protein apparently limits their consumption to an amount that maintains their weight. And I’ve discovered that most people who simply cut the carbs can lose weight pretty easily. Once, however, they get to a smaller size, it becomes more difficult to lose as easily for many people. When these folks want to trim off the last few pounds they do need to watch calories a little more closely. When they get to their goal weight (a realistic goal weight based on body fat percentage, not BMI) most are pretty much able to maintain that weight eating what they want – as long as they limit carbs.

    It will be interesting in your case to see what happens if you get down to your goal weight – will you be able to maintain on what you call the “food porn” diet?

    The Squeeze In is famous for breakfast, so you missed out by not having an omelet.



  5. Great post, Mike, as always. Sure bears out what I’ve experienced personally.

    And by the way, from his first ventures into the TV interview circuit, Gary Taubes
    is alternated being flayed alive and praised for his work. Fascinating to see
    the same old same old low-fat misconceptions being slung at him. By people
    who haven’t read the book. The guy has stones, I’ll give him that.

    Hey Walt–

    Gary does indeed have stones. And brains. And it doesn’t matter what these dolts come at him with, the truth is the truth.

    It always amazes me that people can attack a book without reading it. Having said that, I’ve attacked a few without reading them myself, but never without at least having a sense of what the book is about. For example, I’ve attacked Ornish and have never read any of his books from beginning to end. But I have read much of his writing and seen him speak, so I figure I pretty much know what his books are about.



  6. Hi Mike,

    A lot to cover but as I’m still waiting for Gary Taubes long awaited book, I did read his article on exercise and I must admit I was somewhat disappointed. His argument (and yours I think) is that people who exercise to lose weight over eat afterwards. Ah ha – this must mean that exercising causes them to overeat. Now despite there being possible mechanisms why there might be a connection (amongst many other reasons) all that has been established is an association, not causation – and this seems to be the sort of elementary mistake that I’m sure he finds with the ‘science’ of nutrition generally. Surely ‘we’ need to aspire to loftier standards if we are to be taken seriously when disputing the low fat high carb orthodoxy generally?

    He cites as evidence for his claim that lumberjacks eat about twice the calories as tailors(?) if I remember right – what he didn’t show (again as I recall) is the relative percentage of obese lumberjacks and tailors – I don’t have any reliable data either, but I must say, I’ve never met an obese lumberjack!

    The studies he refers to I’m sure refer to subjects trying to lose weight through exercise, right? I’m sure we’d like to know how they became overweight in the first place as habitual overeating (whether driven by unstable insulin/blood sugars or emotional eating behaviours) could easily be the factor which defeats the beneficial effects of exercise as could the common overestimation of the calories burnt we discussed earlier. Were any of these factors discussed or are we just going to leap to the conclusion that any failure to limit intake was solely as a result of the exercise itself?

    Whether you subscribe to Popper’s take on the scientific method or not, one study on rats can only show that metabolic advantage is a possibility – and I’ve never suggested it wasn’t (Feinman and Fine said it was quite a while back). What is of interest is whether it amounts to something significant and therefore easily measurable in human subjects in as close to real life situations as possible whilst retaining accuracy of measurement. It is possible after all that as rats, unlike us, evolved to eat a high carb diet – their response to a ketogenic diet might differ considerably from humans (just as their response to cholesterol does). BTW – I’ve only read the abstract and looked at your graphs but as I see it the calorie restricted and ketogenic groups lost weight (to 85% of their starting point) – not gained (less) as you stated above. Anyway – from a Popper perspective, you and others are now claiming significant metabolic advantage exists (just see this study on rats) – therefore your hypothesis can be falsified if just one tightly controlled study shows no such advantage for humans.

    I look forward to your analysis of the metabolic ward studies (which purport to demonstrate this) – but as I understand it, you are suggesting that either only the low carb group cheated, or that they cheated more than the other groups. If this is the case, should we then conclude (too be fair) that in real life the low carb group are about as likely to continue with the program as Keys’ conscripts?

    Again as I understand it, your view on metabolic advantage is that a low carb diet not only is inefficient in terms of supplying our energy needs (futile cycling etc) but it also stimulates our metabolism to something akin to the teenager example you posted (strangely I seem to recall being able to stay up till all hours (when I could get away with it) and being almost constantly physically active – I certainly ate a lot, but don’t remember the sleeping till noon bit at all!). In the first case – what do you suggest was the evolutionary advantage in this wasting of energy? Wouldn’t there be an advantage when the (low carb) food was scarce of selection for the efficient use of whatever was available? In the second instance is this metabolic boost easily measurable? Do low carbers have a measurable increase in body temperature as the rats did? Are there any simple tests to demonstrate how we are processing food for fuel differently?

    Its late … I’ll think of more questions tomorrow! (I’m sure you can’t wait)



    Hey Malcolm–

    To answer all these questions I would need to write two more long posts, and I have neither the time nor the energy to do so. You may have to do some independent research on your own.



  7. “You can see from B that the mice on the ketogenic diet weighed the same as the calorically-restricted mice despite consuming many more mousy calories.”

    Considering they were eating different food, you could also suppose that the method for calculating a calorie in each type of food is in error.

    I have always found the calories in = calories out idea stupid. We are not perfect burning machines. At the most simplistic level, we have varying amounts of waste depending on what we eat. If you can consume fat to lube things up and fix constipation, obviously all that fat is not being absorbed.

    Hi George–

    I suppose the method for calculating the calories in the different types of food is in error, but I doubt it. That would be an error that trained researchers would be unlikely to make.

    As to the idea that eating more fat results in more fat through the colon…the papers I’ve seen show that normal humans get rid of about 6 grams of fat in their stool irrespective of how much fat they eat. The job of the small intestine is to absorb fat, and it does that job remarkably well.



  8. The Taubes book is definitely a rewarding read, and probably needs at least a couple of re-reads. Lots of info in there.

    While reading the bits about metabolism that you discuss here, I had a “lightbulb moment” about intermittent fasting (and maybe this is all known, but I thought it was interesting). One of the things that seemd magic about IF was that you could eat the same total calories, but by redistributing it you could lose weight, “turn on” the sirtuin genes which are apparently related to longevity, and so forth.

    It all makes perfect sense now. You burn off extra calories you eat (as long as you don’t spike your insulin), and once they’re gone, you’re cells are in “semi-starvation mode”. Hence burning of fat stores begins, sirtuin genes activated, and so forth.

    I wish medical and nutritional research would put more emphasis on this kind of thing: figuring out the natural mechanisms of the body and how to use them to our advantage, rather than “bending metal” with drug interventions. Sadly, as you can only patent drugs, I suspect this will largely remain wishful thinking.


    Hey Dave–

    Sadly, all the money is in patented drugs, so that’s where a lot of research dollars go.



  9. Thank you so much for this post! This helped me to understand why, since I’ve been IFing (fast-5) and LCing together, I have more energy than I know what to do with. I seriously have been trying to find ways to exhaust myself so I am not bouncing off the walls. Excellent post!

    Glad you enjoyed it.

  10. ((It will be interesting in your case to see what happens if you get down to your goal weight – will you be able to maintain on what you call the “food porn” diet?))

    I ‘ve been thinking about starting a blog soon just to track my progress, stay tuned…

    I’m waiting with worms on my tongue.



  11. Excellent post! I’m looking forward to receiving Gary Taubes’ book that i preordered 2 months ago. It was only mailed wednesday but last night i dreamt that my doorbell rang and the postman gave me the book. I started reading it and then woke up. LOL That’s how much I’m looking forward to this book.


    I hope it lives up to your expectations. I think it will.

  12. Awesome post Dr. Mike; a veritable tour de force. Maybe you should submit it to one of the scientific or medical journals for publication. :-)

    Of course the folks at some of the “main stream” medical pubs would probably want to reject it because it is truly reasoned and evidence-based and perhaps dangerous to whatever their pre-conceived notions may be (or maybe the interests of some of their corporate sponsors?). I will concede that maybe I”m over the top on this. But if I’m incorrect about the cavalierly dismissive attitude of many of these publishers (and so much of mainstream medicine too) about this kind of information, I have to wonder what are the reasons they aren’t getting the information out there to practitioners and the public? As the father said to the teenage son who came home with the bad report card, “….son, is it ignorance or apathy?” …….Or something much worse?


    Hi Will–

    Thanks for the kind words. If and when you read Taubes’ book you’ll understand why these kinds of information don’t get out. Just look at the hatchet job they’re doing on his book already. Look at the links some of the other commenters have included. It boggles the mind.



  13. “… since I’ve been IFing (fast-5) and LCing together, I have more energy than I know what to do with. I seriously have been trying to find ways to exhaust myself so I am not bouncing off the walls.” — kar kar

    I know what its like, I just went out on the BMX bike to run the dog off-road and the heat index is above 90F and Fridays are usually my rest day. I haven’t changed my weight routine in years; the difference now, after almost 2 mo on IF, is now am building muscle and burning fat.

    It must be an anabolic hormone and gene expression thing going on because I am almost 60!

    Hey, Mike–

    Good for you. I love to hear about one of us old guys doing so well.

    Keep after it.



  14. “In case you didn’t know, Gary Taubes was on “Nightline” last night … and the low-fat sheep on the ABC board are baa-ing in complete dismay. You’ll also notice the judicious cuts ABC did on Taubes’ remarks.

    A link to the segment:


    “The problem now is that carbohydrates are full of sugar.”

    OMG I never thought I’d hear such a blatantly stupid “nutrition expert” . Can you believe this?

    Oh, I believe you. I’ve been in this business for a long time, and I know the depth of the dumbth of some of these ‘experts’ they trot out.



  15. Wow. That Nightline video really made me mad. What a hack job. Let’s hope that not all the press he gets is that poorly done.

    Don’t hold your breath. This is the press we’re talking about, after all.

  16. Hi Doc–any ideas on how to get to a really low bodyfat %? I’ve gotten mine to the 7-8% range in the past with a moderate carb diet (about 120 g of carbs per day) and a lot of work in the gym. Right now I’m in the 10-12 % range which is still pretty lean but at my age (41) I want to see how ripped I can get. I know I’ll have to watch the carbs more closely and probably pay more attention to calories too.


    Hi Paul–

    To get to your desired body fat percentage you will definitely need to watch both carbs and calories.

    Keep me posted.



  17. Dr. Mike: My question/comment is really about Taubes’s exercise article. Couldn’t exercise aid weight loss by improving insulin sensitivity and therby lowering circulating insulin? The increased sensitivity could result from a) the exercise itself aiding in the transport of glucose during the exercise; b) increased muscle mass to fat ratio; c) some sort of conditioning of the muscle to absorb glucose with less insulin. Thanks, and I really enjoy your posts!

    Hi Sam–

    Everything you wrote is true, but the long term studies don’t seem to support the idea that people can lose much weight by simply exercising.



  18. ugh, the abc news link ends with “everything in moderation.” i hate that line! its the automatic defense mechanism for people who havent done the reading… another example of “balanced” journalism, i suppose.

    thank god we have your blog to set us straight. great post!

    You are correct. Every moron who thinks he/she knows anything about nutrition always utters the everything-in-moderation line. It drives me nuts. I can’t even begin to tell you how many times I’ve run into people who, when I tell them what I do, say: Well, I believe in everything in moderation. And some of them are grossly overweight. Moderation, indeed! It is truly an expression for the simple minded.



  19. The fact that people tend to gain weight back after they lose it is more of a behavioral and environmental issue rather than a biological one IMO. Biologically, humans are programmed to eat when food is available. Food is always available in abundance and of the low-quality, obesity-promoting variety, and people simply lack the behavioral discipline to continue restricting their calories and staying active enough to stave off weight gain.

    The fact that there are even a few determined, disciplined individuals who are able to lose weight and keep it off would support this.

    But how do we know those determined, disciplined individuals don’t have their determination and discipline driven from the left side of the equation?



  20. Thank you, thank you, thank you … I’m more hungry for all your information than a table full of carbs! Picked up Taubes’ book on Monday – can’t read it fast enough.
    One question – I subscribed to having your postings delivered to my email and that happened for a while, then it stopped. I tried signing up again but it confirms that I am already a subscriber … yet no more emails. Is there something more I should do?


    I wish I could tell you what to do, Donna, but I’m clueless. I’ll ask my web guy to see if he can fix it.



  21. Thank you so much for this post and for the recommendation of the Taubes book. I have almost finished it and have found it both fascinating and horrifying at the same time. Is there anything we low carbers can do to influence the NIH or the FDA to fund studies comparing the low carb diet to the low fat diet? Are there any influential senators/congressmen we can contact to demand they spend money on this issue? Taubes has clearly dileneated that the FDA food pyramid is based upon assumption rather than research evidence and that there are still no funded studies to look at fat metabolism, weight loss diets, insulin etc in spite of all the research evidence that says the low carb diet works and the low fat diet does not. I would think that if a lot of us low carbers/voters could make a lot of noise during this campaign year, we might have some influence. I am all fired up to try to do something to influence our legislators and have no idea how to go about it. Please advise.


    Hi Pam–

    It is my view that politicians of every stripe regard worry the most about unemployment – primarily their own. If enough people write and/or call their congressional reps and senators, these people will take action. But only if they view the numbers involved in any movement to be large enough to cause them election problems will they make any move to help.

    I wish you luck.



  22. I notice in the charts you posted the high fat and high carbohydrate diet is just listed as the high fat diet. I guess old habits die hard.
    It’s too bad all the mice were harvested like that. I’d like to have seen how the lifespans of the keto mice compared to the lifespans of the calorie restricted mice. I’ve been searching the net, and I’ve found lots of studies where carbohydrate or protein restriction increased the lives of flies or mice or rats, but have yet to find one where fat restriction did. I can’t believe that this is because no one has tried to prove that fat restriction will increase lifespan, given the current environment.

    Hi drosart–

    You are correct about the longevity studies. And you are also correct in pointing out that people tend to call a high-fat, high-carb diet a high-fat diet. Old habits do indeed die hard. Plus, I heard from someone who knows the people involved in this mouse study, and they are die hard low-fat diet believers.



  23. It seems many “know-it-alls” now admit that low-carbing can work both for weight-loss and for a better health. But as soon as you go into “cholesterol/saturated-fat has never been proven bad for HUMANS” most intelligent people go berserk! What is it about the word Cholesterol that triggers such a response! My father in law cautions me to not eat so much shrimp while on low-carb because of the cholesterol (duh?!) I got myself food poisoned the other day on shrimps, so I think twice because of that. But the cholesterol?

    Didn’t all this start from feeding rabbits (herbivores) cholesterol in some experiment?

    I cite Chris Cornell:
    “The biggest lies are more likely to be believed…”

    Hi Theresa–

    If you can get Gary Taubes’ book in Sweden, you will learn how cholesterol got such a bad name. All undeserved, of course. And some of it did come from feeding rabbits cholesterol.



  24. (Sorry for all the typos. English is not my native tongue 😉

    Hi Theresa–

    I fixed all your typos. Don’t worry about it. You did a much, much better job than I would have done trying to make a comment in Swedish.



  25. Okay, while I’m thinking about longevity–
    Most of the worlds longest living populations seem to live either on or near mountains, or in valleys. There would probably be a higher ratio of anaerobic to aerobic activity for these peoples, even when just going about their everyday activities. The vegan set try to show that low meat consumption makes these people live longer, but make a very weak case.
    You really should write another book. Not that I don’t enjoy reading your stuff for free.

    Hi drosart–

    I don’t know where the worlds longest living populations live, so I can’t really comment.

    But I am glad you enjoy reading the stuff for free. If you ever get tired of reading it for free, let me know, and I’ll give you an address where you can send a check.



  26. I love reading for hard facts as much as my concentration despises wading through literary mediocrities. So, to you, Doc (and those who threw comments before mine), I say many thanks for reviving my interest in just READING. You Guys are the true saints of the world wide web! And if responsible for making me express myself the way I do here is the left or the “traditional” right mode of my calorific ingestion, I certainly intend to read more!

    Hi Manyanya–

    Thanks for the kind words. I’m glad you enjoy the posts and comments.



  27. ugh, the abc news link ends with “everything in moderation.” i hate that line! its the automatic defense mechanism for people who havent done the reading… another example of “balanced” journalism, i suppose.

    That article reads like it was written by a computer and not a human being.

    Maybe it was. Or maybe by an unthinking robotic-like human.



  28. Interesting post! What i’m concerned about however is the fact that just because there is a metabolic advantage to a particular diet- doesn’t mean that it is healthier (it seems to be implied by your tone in the post). There is also a metabolic advantage to a super high carb and ultra low fat diet – but that is certainly not healthy. With all the benefits coming out about IF and other protocols – nutrient timing might be the holy grail of human wellness (before breakthroughs in cellular genetics). It seems that the only true fact we can count on in nutrition is to eat the most nutrient dense foods possible.

    Hi Aaron–

    As far as I know, there has never been a metabolic advantage attributed to “super high carb” or “ultra low fat” diets. Even with low-carb diets the metabolic advantage isn’t much of a deal. If you look at the studies showing the greatest metabolic advantage it’s about 300 Calories, which isn’t a whole lot.



  29. If I read your blog correctly, what you are saying is not that low carb diets have metabolic advantage or disadvantage, but rather that they have a differential metabolism. If you eat a diet high in fat and low in carbs, the body will produce more heat with less fat storage. If you eat a high carb diet your body will create more fat and produce less heat.
    This makes sense from the paleolithic point of view. Summer would be the period where more carbs would be available to ancient man in the form of plant foods. While in winter, his primary, and in many cases, his only food source would be the fat and protein of animals. In summer man would tend to store fat. In winter (he) would tend to burn it when it was needed to keep warm.
    This theory could be fairly easily tested using a crossover design. Take a group of people or (animals). Put them in a calorimeter so you can measure body heat. First you feed them a high fat diet and measure total energy given off, then you put them on a high carb diet and do the same thing. If done with people, it might be done after an overnight fast.
    The only problem is that according to Malcom Kendrick, author of The Great Cholesterol Con, it has already been done. From his Red Flags Daily column of Jan. 25, 2003 ATKINS AND THE FIRST LAW OF THERMODYNAMICS (http://www.thincs.org/Malcolm.htm#atkins)

    “I watched a programme on the Atkins diet a couple of nights ago. On this programme they got identical twins and put one on the Akins diet, and the other a low fat diet. They then stuck them both in sealed rooms where all energy expenditure could be monitored. Oxygen use, loss of ketones in urine and breath. They collected everything, which sounds a bit yucky, but there you go. The findings were that over a two week period the twin on the Atkins diet lost approximately one extra calorie in ketone bodies. Equivalent to about one grain of sugar. Which is exactly what I expected.”

    In Horizon’s investigation identical twins were put on different diets, one on the Atkins diet and one on a conventional low fat diet. Each was fed identical amounts of calories for two weeks.The twins were then locked inside a sealed chamber so that Professor Joseph Donnelly could calculate how quickly their bodies were burning calories. Over 24 hours the twin on the Atkins diet did lose more calories than the twin on low fat, but only 22. Professor Donnelly even checked the twins’ urine for calories and found that the Atkins dieter had lost less than a single calorie more than his brother on low fat.
    Donnelly concluded that: “the differences were too small to suggest there’s anything significant going on”.

    So late last year (BBC) Horizon commissioned a scientific investigation in to whether Dr Atkins’s theories of how calories are lost on his diet were real or just wishful thinking. The study took place at Kansas University. Somewhere on this sprawling campus a man was locked inside a tiny room. He was there for a whole day and night. His identical twin was subjected to the same treatment. They had both donated their bodies to one of the first attempts to find evidence that you really do lose more calories than normal on the Atkins diet. The team behind this unique study was headed by Joe Donnelly.

    Prof JOSEPH DONNELLY: The concept is very interesting, it’s very controversial, in science it’s very nice to be there. It’s nice to do something that isn’t boring, there are millions of people interested in Atkins, really right, wrong or indifferent. So we’re very interested and eager to see the results.

    NARRATOR: For two weeks one of the twins was put on the high fat, high protein Atkins diet. While the other was put on the conventional low fat diet. They were then locked inside this sealed chamber. By measuring how much oxygen they breathed in and out the computers could calculate how quickly their bodies were burning fuel. The hope was that this would begin to answer whether more calories are worked off on the Atkins diet by breaking down fats and proteins. Donnelly also tested Dr Atkins’s theory of calories lost as ketones down the toilet. The twins had to donate their bodily fluids for the duration of their internment.

    Prof JOSEPH DONNELLY: We’ve collected a litre and a half of urine at each collection period. They’ll be analysed for urinary ketones and then we will know how many calories are lost in the urine. NARRATOR: If Dr Atkins’s theories were right the twin on the Atkins diet should be losing significantly more calories than the twin on low fat. In the morning the twins were released and the results were in. To prove you burn off significantly more calories breaking down the Atkins diet researchers expected the twin on Atkins to have lost at least a hundred calories more than the twin on low fat. And the Atkins dieter did lose some more calories this way, but a total of just twenty two.

    Prof JOSEPH DONNELLY: Twenty two calories is too small to suggest that there really is anything going on.

    NARRATOR: In other words burning fats and proteins appeared to take up hardly any more energy than burning carbohydrates. It seemed Dr Atkins’s theory that you lose calories when breaking down his diet might be wrong. Next the researchers looked to see whether any calories were lost as ketones in the urine. The twin on the Atkins diet had lost less than a single calorie more than his brother on low fat.

    Prof JOSEPH DONNELLY: This is not enough to suggest that this particular demonstration showed a difference.

    NARRATOR: It seemed being in ketosis made barely any difference at all. Again Dr Atkins’s theory appeared to be wrong. This came as little surprise to Donnelly.

    Prof JOSEPH DONNELLY: I think the results are what we expected. There’s no difference between the two diets.

    I have searched in vain for an actual scientific journal reference to the above quotes. It is also unclear how the Atkins twin first lost 22 more calories, but then analyzing the urine loses only 1 calorie. The first measurement was apparently heat loss as measured by oxidation. The second was apparently for urinary ketones. It does not appear to be evidence for metabolic advantage or as I prefer to call it differential. Thanks for the time and space to comment.

    P.S. I’d like to see an entry devoted to Vitamin D, an item that you have modified your opinion about since Protein Power where you specifically recommended against supplements, but now if I remember correctly take 5000 IU / day of Vitamin D. It appears to be one the most exciting items in its role in cancer prevention, heart disease, flu, etc.

    Hi Mark–

    Your first paragraph pretty much sums up my thinking on the issue. The study involved in the BBC show you mentioned as – as far as I know – never been published. Even if it had been published, the time span is pretty short to draw any conclusions. This is the first I’ve ever heard of it, however. I would be nice to see more data.

    Thanks for the links.

    And I have changed my thinking about vitamin D. I’m working sporadically on a post on the subject.



  30. Hi Doc,

    Maybe it’s just me but I don’t really care what the government does about weight loss studies and the like. I’ve been seriously LC’ing for about a year and it has done wonders for my weight, bodyfat % and triglyceride levels. There is no other diet or exercise that could come close to what my LC diet is doing. On that note, I’ve told many people how I’ve lost weight and they all say the same things; moderation, eat less fat, and “how boring LC is”. If everyone else wants to be ignorant and wants to parrot what they hear and read in the mainstream press then let them be obese. I’m living proof this type of lifestyle works. It could also be a case of schadenfreude because it seems to me most people don’t want to give up something to get something they want.

    The other factor in this for me is the near conspiracy between big pharma and our government. How many times have we been led to believe there is going to be a magic pill we can take and it will make us skinny? Wasn’t it the FDA (Fraudulous Dietary Administration) that approved Phen-Fen? The “magic pill” for me STAY AWAY FROM CARBS IN ALL FORMS. How much easier can it be?

    Hi Ed–

    Thanks for the testimonial. There’s nothing like personal experience to make a believer out of someone.



  31. HA HA HA. HA HA HA.


    “Many parts of the world, including Mexico and Europe, have rising rates of obesity and diabetes, despite having little or no high fructose corn syrup in their foods and drinks.” So this makes it OK to saturate our food supply with this franken-food?

    Amazing, ain’t it?



  32. My response to the “everything in moderation” cop-out is “the typical modern industrial diet doesn’t provide carbohydrates in moderation”.

    Precisely. A very good response. I’m going to steal it.



  33. Another quote from the Nightline video:

    “Carbs spike insulin, and insulin creates sugar”

    Just shoot me.

    Anyway, loved the blog. I must run hotter than I used to, because I’m still fairly sedentary (nothings changed there), yet I consume almost double the calories that I used to on high carb. My weight stays the same =/- .5 lb. The thought of the left side of the equation driving all this is intriguing.

    Hi Karen J–

    That someone could actually say the quote you posted out loud and on air defies belief. These dolts will stop at nothing.



  34. Does saying that “the left hand of the equation drives the right hand” imply that there is a ‘set point’ that the body is working towards? I’m having a hard time connecting the dots between a ketogenic diet (or any diet for that matter) and it’s impact on the left hand side of the equation. Given the way the experiment was constructed, I’m not sure if we can derive any conclusions. If the rats on the ketogenic diet were allowed to consume freely, perhaps they would have eaten more and the path of weight gain would have tracked the others. The only way to really know which diet has the most impact on the left side of the equation would be to give each group a tailored diet and then let them eat to their hearts’ content. The body’s tendency to take less calories from the diet is interesting but we are left with the question as to whether and compensating forces (in the form of hunger) would have had a further impact on the weight of the mice.

    Hi Robin–

    You’re confusing the two things. In the mouse study the researchers took the left side of the equation away in terms of driving anything. They gave the mice a specific number of calories and showed that the mice on the ketogenic diet gained the least weight on an identical number of calories, which means that the ketogenic diet provides a metabolic advantage. You’re correct in saying that the only way to check this in humans is to give different groups different diets and let them eat all they want and see what happens. When this has been done with low-carb diets as one of the test diets, those on the low-carb diets spontaneously reduced their caloric intake, i.e., the left sides of their equation drove the right sides.



  35. Wot about Vit D from a full spectrum light source like Solux…any good Sir ?

    The full-spectrum lights do okay (supposedly) to relieve the symptoms of SAD, but I don’t hink they do much to stimulate the production of vitamin D. Since you’re in the far north where it’s difficult to get enough strong direct sunlight even in the summer, I would recommend a bunch of vitamin D3 for you and yours.



  36. Great post. This one goes into my Best of Eades file. I’ve got Gary Taubes book now too so I am loaded for bear. I think I will teach an LC cooking class at the local community college next semester so I can disseminate this information.

    Go for it!

  37. We can get Taubes’ book here in Sweden. I have pre-ordered it so it will arrive in a couple of days. It will be a very interesting read. I read some other book on obesity a couple of years ago and he was featured in it alot. Seems to be on top of things, that guy.

    Regarding Taubes’, I found a PDF on the internet somewhere regarding his article about it all being a big fat lie in the New York Times(?) where most of the “big guys” he quoted in that article really washed their hands about many things he had quoted from them. I haven’t found any document with Taubes’ comments on that, though. But it would be very informative to know his responses. Do you know what I’m referring to?


    (Swedish isn’t a first choice language if one wants to get around, if you know what I mean. And please, correct my typos in this post, too, it makes me feel better about posting.)

    Hi Theresa–

    Taubes’ article in the New York Times several years back that you refer to is what put him on the map with the general population. Until then he had spent most of his career researching and writing about complex scientific issues, especially those involving physics. He took on the field of diet and nutrition because because during the writing of a long article for the journal Science (the most prestigious scientific journal in the United States) he discovered the cluelessness of the nutritional establishment and wanted to explore the situation. He interviewed many ‘scientists’ for his NY Times article who gave him the results of their data and their interpretations. When these scientists appeared in the Times article along with their opinions, they caught a lot of heat from their colleagues, so they backtracked and denied that they had said what they really said.



  38. (Epiphany alert) I think I’ve finally got it! Now, I have been one of the folks that don’t believe in any metabolic advantage (MA) of eating LC because the controlled metabolic studies don’t support this hypothesis; however, after reading this post, as well as devouring Taubes’s book, I think I finally have it. I think that many people don’t agree there is a metabolic advantage because it appears to violate the law of thermodynamics, and this is what I use to argue. OK, in light of another interpretation of the law which does not invalidate it, which you’ve discussed in your post, maybe the problem in the two camps (pro-MA & anti-MA) is a matter of semantics. If we accept that eating LC returns us to the diet that we evolved on as a species, then the healthful side effects of the diet (e.g., weight loss, more energy, etc.) happens not so much as a result of a metabolic advantage as it is a metabolic “restoration”. I hope I’m making sense since this is coming off the top of my head . . .

    Great post.

    Hi Muata–

    I do think you’re making sense. But the laws of thermodynamics (the second law) imply that there should be an additional metabolic advantage of the kind I’ve been talking about.



  39. I believe that it’s not an advantage, but normal physiology for those with certain genetic traits.

    If C57 mouse develops carb sensitivity (thus associated diseases of metabolism: obesity, depression, and alcoholism)… then isn’t it more appropriate to say carbs cause a metabolic DISadvantage, whereas low carb allows for normal energy use/balance thus health?
    Considering how highly carb sensitive the C57 mouse is, the increased energy production on the same number of calories when eating a very high fat diet might only reflect normal metabolism… the higher carb diets would reflect some shade of metabolic abnormality.

    I’m very much like C57 mouse, depression, obesity, and alcoholism are all diseases in my primary relatives. I personally have had obesity and depression. I know first hand how it feels to go from a high carb diet to a ketogenic diet. Overnight, my depression was reduced tremendously. I could eat and feel a “stop” feeling. I lost weight rapidly. I have a BMI of 20 from 46, and I haven’t been anywhere near overweight in years. I eat at least 1650 cals to maintain. If I eat more (but lower carbs), I do not gain. If I increase carbs, but not calories, I gain body fat. If I eat both more carbs and calories I gain body fat incredibly quickly.

    Because of how awful I feel on carbs, and how remarkably it messes up anything relating to energy regulation/balance/use, to eat low carb doesn’t feel like an “advantage”. I consider high carb a “disadvantage”, as much as casein might be a “disadvantage” for some types of autism. The health problems I have to deal with are a direct result of carbohydrate; abstaining is as logical as not drinking poison. Not because this is an advantage…but because, the mental and physical freeze of a plate of pasta is so totally and unambiguously a negative.

    Sometimes, I think people who don’t have the same kind or degree of carb sensitivity people like I do, find it hard to comprehend how a calorie can’t be a calorie. I believe I have an extreme reaction to carbs; most people are some degree carb sensitive, but I am significantly so.
    Because, for some people — most people — a calorie IS a calorie, more or less. If they eat pasta, if they eat crackers, if they eat bread… nothing happens. They don’t get the coldness of thought, they don’t lose the ability to regulate weight (hunger makes sense, fat burning is preserved), there is no chronic hypoglycemia, etc. At worst, they might gain 20 lbs and feel a bit more tired. Few people get as fouled up as me (severe depression, hypoglycemia, PCOS, morbid obesity — while being relatively YOUNG mind you, less than 20 years old) or the C57 mouse.

    This certainly might explain the failure of low carb diets to demonstrate a “metabolic advantage” in the twin study mentioned above by Mark. Unless the twins were specifically like me, or C57 mouse, then there will BE NO significant difference if eating whole grain bread or if eating nuts. The differences noted between cal in/out observed is not evidence of an “advantage”… it’s a study in the difference between pretty significant hypometabolism, and metabolic imbalances (resulting from an intolerance to a dietary factor), VS normal physiology (when that factor is removed).

    This thing, it’s more like an idiosyncratic reaction to a protein. Twins with a peanut allergy, will demonstrate marked differences when diets do and don’t contain peanut protein. Twins without an allergy won’t.

    Yea, I think, it makes all the difference when we frame things a bit differently: maybe the “default” for some people isn’t “baseline wellness” but rather significant disease process attributed to an intolerance for our cultural nutrition (very high in carb). When these people switch to high fat, what we observe isn’t “an advantage”, but rather how things should have been working all along. Improvement (including changes in energy production) will be only as proportional as the degree of prior unwellness.

    Either way, this entry makes clear that a calorie is not always a calorie (that restricting them will produce predictable results on body fat level no matter what kind are consumed). Thanks.

    I guess we’ve got a problem of semantics here. I see exactly what you mean, and I agree that the carb effect in terms of poor health should be a DISadvantage. But what I’m talking about is the ‘wasted’ calories in one diet as compared to another containing the same number of calories. If you are trying to lose weight, then this wasting of calories is a real advantage.



  40. I’m very interested in the obesity-alcoholism-depression combination as they seem to be related–at least, I can provide a ton of anecdotal evidence to support this idea.

    This combination of propensities are all mutually reinforcing. I used to work around recovering addicts and there was a joke in the group that Reese’s peanut butter cups were the best solution to an overwhelming urge to binge on the drug of choice.

    Also, there has been an interesting development amongst weight-loss surgery candidates–I’m sure you’ve seen this–there is an extremely high counter-addiction behavior strategy among those who have lost a lot of weight in this way and physically can no longer tolerate their former food addiction, alcohol being the drug of preference. Carnie Wilson has been very public about her experience with this.

    I think there is at least a small subgroup of people that do need IFing or additional caloric restriction in order to arrive at a healthy weight. This may be because they LACK a certain INBORN metabolic advantage (the so-called “survivor type” conservation gene that has been hypothesized) OR a lacking a particular psycho-spiritual metabolic advantage, if you’ll allow the term.

    It may be that this depression-addiction type cannot survive without the mood altering effects of food. Saturated fat and salts provide a substantial mood altering effect, so these people may, in fact, be prone to increased caloric intake no matter WHAT they do.

    Cream in the coffee, certain salty seasonings, intensely flavorful saturated fats, and perhaps artificial sweeteners, in this case, would all cause a potential increase in calories.

    I have observed this in myself–I have to carefully control certain low-carb foods (like high fat cheeses, high saturated fat meats, artificial sweeteners, and yes, even some low-carb vegetables) because they will induce calorie binges which completely stalls out my weight-loss. So far, I have successfully lost up to 40 lbs (in the past, only to regain) using an LC lifestyle, but I have yet to achieve a healthy weight and maintain it because I think I am prone to high(er) calorie eating no matter what I do. I say high(er) because I think that there are other people that CAN sustain a healthy weight at that calorie level or much higher (my husband being one of them, or many folks on his side of the family).

    So I have to eat a very low calorie, restrictive, AND ketogenic diet to succeed. (At least, this is my current hypothesis.)

    I’ll let you know if has been “Popperized”–but I’m hoping this is one hypothesis that will NOT be falsified.

    Asta la pasta, Dr. Mike.


    Hi Jennifer–

    Your description of your condition is precisely the reason that I say that the energy balance equation is driven from the left side. Or, as Gary Taubes puts it, the calories in/calories out components on the right side of the equation are not independent variables. In other words calories in is a function of the biologic system on the left side. People can withstand hunger for only so long, then they give in to it and consume more calories, which means that ‘calories in’ are a function of hunger and are not an independent variable in free living people.



  41. I found this paragraph in another commenter’s link about fatty livers in mice:

    Although the rodents’ livers weighed the same whether they ate fast- or slow-digested starch, fat made up 12 percent of the liver in mice fed the amylopectin-rich diet. That’s double the fat content of livers in animals that had eaten the slow-digested starch. For perspective, Ludwig notes, people whose livers contain 10 percent fat are considered to be suffering from “advanced” nonalcoholic fatty-liver disease.

    I’m assuming this is yet another reason that eating the livers of pastured (grass-fed, not grain fed) beef and other animals is fairly healthy, besides the toxicity of factory farmed animal’s livers.

    Hi Anna–

    I guess that would be another reason to eat the livers from pastured or grass-fed animals, but really the fat in their livers (other than any toxic accumulation it might contain) shouldn’t affect our own because it’s just like any other fat we eat.



  42. Dr. Mike,

    Please devote some of your attention to the most important thing mentioned the article…please, please, please find some macronutrient that will fix the Razorbacks!

    (trying to muster sincere enthusiasm) Go Hogs!

    Hey Justin–

    I’m good but I’m no magician.



  43. So what about the comment in this article about acidic urine and that it leaches calcium out of bone? Is this something to be concerned about?





  44. Hi Dr. Eades:

    Do you have any insight on the Pauling and Rath theory of the role of Lipoprotein a, lycine, and vit C on heart health? I just finished reading Malcolm Kendrick’s book “The Great Cholesterol Con” where I came across this theory, and I have seen other references to it since. When I conducted literature searches, I found that most of the research in this area was done in the early 1990’s and then not since. I guess my big question is why was it not pursued? Thanks for the interesting information. Always very entertaining and informative.


    Hi Olga–

    Thanks for the kind words about the blog.

    I’m somewhat familiar with the Pauling/Rath theories, but I don’t totally buy into them for reasons that are beyond the scope of the comment section to deal with. It would require almost a book-length post to explore these issues at length.



  45. being a bit retro and stuck in the eart of darkness for 3 years means i only just saw this!

    Hilarity of course is when Ornish is asked what he had for breccy he says an egg white omelette and blueberries


    Dr come on let’s hear you take the shitty stick.And on a very personal and juvenile note…he’s a very strange looking fella is Ornish

    Hey Simon–

    I’m not going to rise to the bait.



  46. Hey Doc,

    Good post. Reading Taubes. It’s a bit of a slog (I need a scorecard to keep the fat zealots apart from the fiber people and the carb people, and I’m only 125 pages in), but a good slog. Dunno that the book is gonna change anything. Borders had it stashed in with Diet books, not out front, on an end cap, or any place they put new books they intend to sell. They did have a few copies.

    Any rate, that’s not what I’m on about. It’s about government and nutrition. As an insider, I’m pretty sure that it’s about the money. Money is what gets people elected (so they think, and mostly they’re right), so they go where the money is. As Chris Rock noted, there’s money in the medicine, no money in the cure. They’re still kicking themselves about the lost revenue from curing polio. The drug companies that is. But if you think on this, the folks that have money tend to be “medicine” people rather than “cure” people. Drug companies. Package Goods companies like General Mills and Unilever. They make their money selling you a solution that you take the rest of your life. It’s good business. I wouldn’t be in the cure business either, not if I had to worry about revenue. Have come to the conclusion that campaign finance, hard core, top to bottom, hard, soft, and invisible money, needs an overhaul in the interest of the non-political donors. When we’re back to democracy, instead of the dollarocracy we currently have, we might be able to expect worthwhile solutions from government.

    Thanks for the post.

    And thank you for the commentary. You’re right. All the money is in the cure; almost none is in prevention. That’s how come there are countless weight-loss diet books but no books – as far as I know – on how to diet to keep from becoming fat in the first place.



  47. Hi there!

    I read Taubes’ book. I have one question that I thought of while I was reading the aging chapter. Let’s say one was female, 40 pounds overweight, insulin resistant, and destined to be diabetic at age 45. At the age of 30 they go on a low carb diet lose the weight (gets down to 20% fat) and stays there for good, will any of the aging process be reverse (i.e. will the atheromas disappear)?


    Hi Mmmm–

    That specific question has never been studied so I can’t answer it accurately. But, my best guess is that it probably would.



  48. Long ago I have decided to eat for clarity and energy, instead of joy. While I enjoy pleasingly tasting food, I choose foods that make me feel good. I want to be as active and creative as I can be. Over the years, I have eliminated cigarettes, coffee, thee, chocolate and alcohol, resulting in better sleep, more energy in the morning, a stronger body and more clarity of mind. Not that I don’t like all those ‘vices’, but there is a choice to make: do I want my excitement during the day come from what I eat; or from dancing, paragliding, writing. I want to be hungry for life rather than for choice foods.

    My diet has slowly evolved into a low fat, high protein diet with lots of salad and lightly baked veggies, with the carbs coming from sweet fruits, like mango and banana.
    In the past weeks, I have been further eliminating carbohydrates. My friends are telling me that my face is sometimes very white. Is this a temporary thing, because my body is switching from a carbohydrate into a ketogenic metabolism?

    In the last week I have been eating nuts and banana’s when I danced a lot – for example during a tango marathon, when I dance up to 14 hrs in a 24 time span. After reading your blog, I am going to experiment with eating more fat during my meals to keep my energy coming. I guess that on a low fat and low carb diet you are starving yourself a bit. In fact I have been losing weight. My weight is now about right so I will eat more fat and oil to stabilize it.

    It is now easy for me to control my weight, of which I had lost control in the last 5 yrs. The more I eliminate carbs, the fewer times I binge eat – in the past a huge problem for me. Thanks for your work, it helps me choose good foods for my body and mind.

    Hi Robin–

    I’m glad to hear you’re doing so well. I have no idea why your face is sometimes white – this isn’t something I’ve seen in my long experience.



  49. “That’s how come there are countless weight-loss diet books but no books – as far as I know – on how to diet to keep from becoming fat in the first place.”

    This attitude is unfortunately true. When I wrote a book about how to prevent diabetes, it didn’t sell. When we simply changed the title to Prediabetes, it sold much better.

    I have a relative who says constantly, “Why should I worry about a disease I might never get?” even though the disease in question has a strong genetic component. I think people who aren’t yet fat feel the same way.

    And I confess I wouldn’t rush out and buy “How not to get cancer,” “How not to get Alzheimer’s,” “How not to get Parkinson’s,” etc. There would just be too many disease I didn’t want to get.

    Hi Gretchen–

    It’s sad but true. People are eternally optimistic in the sense that they don’t believe any disease will befall them, including obesity. It’s the same reason no one goes to the doctor to keep healthy – they all go when they’re sick. No one is going to go out and buy a book on how to prevent a specific disease if they think they’re never going to get it. But once they do, they buy everything they can find on the subject.

    This rationale is why the cholesterol lowering drugs make so much money. Elevated cholesterol isn’t a disease – it’s a lab finding. And the evidence indicates that it isn’t even really a risk. But the drug companies have managed to get it stuck in the minds of most everyone as a disease, so everyone who has a little bit of an elevated cholesterol is interested in finding out how to treat it.



    P.S. Your test comment came through. I deleted it.

  50. Hi Dr Eades,

    Thanks for explaining metabolic advantage and the mouse study in easy to understand English. I liked this post a lot!

    Can I get your advice on a matter? I’ve been trying to eat Paleo with low carbs to remain in a ketogenic state. The problem is that I suffer from insomnia and have very poor sleep when I am carb-depleted. I have tried fruit before bed – apples, oranges, melons, bananas. They help only if I eat an enormous quantity before bed, but the deepest sleep still comes only when I eat starchy carbs like bread, pasta and biscuits. I had some pasta and biscuits last night and haven’t had such restful sleep in a week. The sun here rises at 6am and on Paleo the brightness wakes me up at 6am. With the starchy carbs I am in perhaps deeper sleep and don’t get woken up till it’s really bright.

    I am torn between Paleo-keto and deep sleep. What would you suggest?


    Hi Insomniac–

    You might want to try some melatonin. Maybe a mg or so of the sublingual variety, taken just as you’ve turned off the lights. And you might consider a little 5-hydroxy tryptophan. Maybe 100 mg or so taken around dinner time. The 5-hydroxytryptophan is the immediate precursor to serotonin. When you eat carbs before bedtime, you are bringing on an increase in serotonin, which makes you sleepy. You can do the same thing with the 5-hydroxytryptophan. The other thing you could consider is keeping on a low-carb diet, but not going into such deep ketosis. Try increasing your carbs a little at the evening meal – just enough to prevent ketosis – but not a huge amount. One or all of these three things have worked for most of my patients who have problems sleeping on a ketogenic diet.

    Good luck.


  51. Sorry, I forgot to add that I already practice good sleep hygiene, have the room as dark as possible etc. Every night I take valerian and ZMA but they help only a little. I used to take benzodiazepines because that’s what the doctors gave me for the insomnia, but they had terrible effects and I went off them myself.

    I took note of all this before answering the other comment.


  52. As a teenager I weighed less about 8stone 10 lbs (122 lbs). I stayed at that weight for many years. Even during my military service when there was planty of food I stayed at this constant weight. Perhaps this low weight for height, I’m 5ft 9In, might have been occasioned by the very low carbohydrate diets (& very low everything else) that we in the UK existed on during the 1939-45 war.
    However when I was 28 in the 1960s my living & working situation changed & I gained weight very quickly going to 13 stones (182lbs) in about six months. During this period my diet included much more carbs especially potatos. (My landlady thought I needed ‘feeding up’).
    Since those days my weight has stabilised to a comfortable 11stone 10lbs(164lbs).
    My point is that reducing carbs may not reduce weight by very much as you state but increasing carbs very definitely will increase weight.

  53. Hello Dr. Mike,

    It seems to me that one factor contributing to the metabolic advantage of your low carb diet recommendation is increased testosterone levels brought about by increased saturated/monosaturated fat, cholesterol, and protein consumption. There have been studies correlating this to increased testosterone and resulting in significant muscle and strength gains. Increased lean body mass raises the base metabolism which helps to burn off fat.

    I recently (this week) read a very good article which cited such a study in a men’s fitness magazine at my local grocery store. Next time I’m there I’ll try to find it and let you know what magazine it is and what study they cited. It was a very good article for supporting that the current recommendations for low fat and avoided saturated fat especially are utter “bullshit” and “lies”.

  54. Hello,

    I stumbled upon Taubes’ book recently and it was quite the eye opener, even though I was already convinced that low carb is the best way to go in life. I love this post about calories, and the law of thermodynamics or counting calories has never particularly concerned me, however I have recently started eating restrictively low carb to ketogenic levels after a few years of sadly succumbing again to the carb addiction, and I’m wondering if there is a cause for concern in not eating enough calories while low carbing, as opposed to concerns of eating too much. In other words, if eating low carb and eating a lot of calories will not cause harm/weight gain, simply drive us to expend more energy, I assume that eating too few calories will have the opposite effect and slow weight loss over the long term… but in your experience have you found that that is indeed the case when very low carb is involved?

    It’s been my experience that people both reduce calories and increase activity spontaneously on low-carb diets. It doesn’t take as many good-quality calories (the kind one gets on a whole-food low-carb diet) as it does low-quality calories to provide all the energy needs plus allow the body to access the fat stores for more. As energy becomes freely available to the body, it responds by increasing activity to burn off any extra. It’s a double whammy for the good, which is why people generally lose more on low-carb diets as compared to low-fat diets of an equivalent number of calories.

  55. Hello,
    I’m a research assistant of neurology department of 19 Mayıs University Medical Faculty in Samsun-TURKEY.
    I need a number of C57BL6 mouse/mice for my dissertation. Because, I will use this animals to create a Multipl Sclerosis model and I will investigate the protective and improvement effect of a certain substance on this models. But I can’t find this kind of animal (C57BL6 mice/mouse) in Turkey. İf I can find, I will apply for financial support to my Universty Project Support Committee and I hope will pay for them.
    Can you help me about how can I find this mouse/mice or you can instruct for me?
    I appreciate you for it. Thank you

    I have no idea how to obtain these mice. Perhaps through a laboratory supply house. Good luck.

  56. So in simplest terms – well the simplest I can come up with 😉 you lose more weight on a ketogenic diet than a high carb diet, NOT because you wildly violate the laws of thermodynamics… but because you run hotter.

  57. I found your article really interesting and intelligent. However, I disagree on a few things.

    I’m not so sure that Popper would be so happy.

    There is a section of your post, “But the laws of thermodynamics DO work the same in all living creatures and in all systems for that matter. So rats or monkeys or mice or armadillos are going to obey the laws of thermodynamics in the same way we humans do. And thermodynamic data we gather from well done animal studies applies to humans just as it does to the animals in question.”, the conclusion of which (the last sentence) does not logically follow from the previous two sentences, has not been independently tested and does not appear testable. Even if it resulted to happened in some case (and I underline “if”), you can’t possibly say that it would be true in all cases: you can only reword it to refer just to that well specified case.

    Of course the laws of physics will be the same for all animal species, but different species may apply them differently and make different use of them. That is why the third sentence does not derive logically from the two preceding it.

    Think of the law of gravity. It’s the same for all animals, but some animals jump higher or even fly: that shows that, even if a law of physics works entirely in the same way for all species and all animals have to obey it, the way they do it may produce completely different results.

    The fact that mice, unlike humans, continue to grow throughout their lives seems to me a good candidate to indicate a difference in that sense.

    In this case in particular, I’m not clear what this study is showing that we didn’t know already from human research.

    We knew already, from case studies, randomizes studies and more recently even longitudinal long-term studies of humans, that ketogenic diets produce short-term weight loss, but that the weight is regained after a year or less. Exactly as with all other diets.

    Could it be because, at the end of the day, humans can’t keep on ketogenic (as well as other) diets, although the mice did not have a choice?

    Or could it ALSO be due to other differences between humans and mice, of which we know nothing yet?

    Finally, Popper does not phrase his theory in terms of “valid”, “good” or “bad” hypotheses and theories, but “scientific” or “metaphysic (pseudo-scientific)”. It’s an important difference, because you can have a false (so, not valid) scientific hypothesis.

  58. The thing I want to know from a study like this is not just the weights of the mice in question but body composition of the mice as well. It would be interesting to compare the % body fat and the % muscle weight of the mice being studied. I suspect the calorie restricted mice have less muscle tone and perhaps a higher body fat percentage than the low carb / high fat mice. Being that I’ve tried over 15 years a bunch of variations on the calorie restriction diets, I was often dissatisfied that I would lose muscle as a result of extreme calorie restriction. Sure I’d lose the weight, but my fat percentage wouldn’t change that much or would actually go up. :-(