Click here to view the embedded video.

As you watch this long video (and you should watch it; it’s extremely entertaining and filled with a ton of good info), there are a few things you should note.

Before we get to that though, let me fill you in on the LEARN diet.

Most of you, I’m sure, are familiar with the ultra-low-fat Ornish diet and the 30-40-30 protein-carb-fat ratio of the Zone diet, but you may not be aware of the LEARN diet.  LEARN stands for Lifestyle, Exercise, Attitudes, Relationships and Nutrition and is the brainchild of Kelly Brownell at Yale.  The LEARN diet is a low-calorie regimen that recommends 55-60 percent of calories as carbohydrate and under 10 percent of calories as saturated fat.  The LEARN program is big with academics (since it was created by one of their own) and is the diet typically used when a diet program is required as part of a study.  In fact, the LEARN manual was developed to bring some consistency to the nutritional regimens followed in research.  As a consequence of its widespread use in academia, it has also become the program that pretty much mirrors the national guidelines.  Or, to put it another way, the nutritional guidelines set by academics pretty much mirror the LEARN program.

If you look at the carb content of the LEARN program and realize that it is the basis for the national nutritional guidelines, you can LEARN why we have an obesity epidemic.  But that’s another subject.

First off, at about 17:10 in the video, Dr. Gardner talks about how Dean Ornish got mad at him for publishing this study.  (So did Barry Sears, author of the Zone, but Dr. Gardner didn’t mention him.)  Both Ornish and Sears got their noses out of joint after this study and sniffed that the study results didn’t really apply to their programs because clearly the data showed that the subjects assigned to their specific diets really weren’t following the diet as designed.  Both missed the point.

As Dr. Gardner plainly says, the study is of specific diet books and how patients lose (or don’t lose) weight following these books.  You can’t recruit a million people for a nutritional study in which you hold their hands throughout.  But you can write a book that a million or more people read and follow.  What Gardner was looking for in this study was how people would do following a diet book advocating a specific program as compared to others on different diet books promoting different diets.

As part of the structure of the study, he randomized subjects to the various diets, then had them come in weekly for eight weeks to visit with a dietitian who went over the book with them.  He relates an interesting story at about 26:10 that I’m sure is absolutely true.  Many of the people who were randomized to their particular diet were demoralized because they had already done that diet in the past and hadn’t done particularly well on it.  After going through the book with the dietitian, these same people realized they hadn’t really read the book very well – if at all – the first time through.  Once they really read and understood it, they were fired up and ready to go.  Based on may questions MD and I have received about our books, I know this only too well.

Earlier in the video, at about the 17:10 point, Dr. Gardner makes an observation that all of us using low-carb diets know well.  He is discussing how reducing carbs makes triglycerides go down and adding fat makes HDL go up.  He then says that all these people have come into the clinic he is involved with after having been on Ornish or McDougall only to find their triglycerides have skyrocketed and their HDLs have dropped off the chart.  He tells them to replace some of the carbohydrate with good quality “unsaturated fats” (sigh), and their labs revert to normal.

At about the 29:00 mark, Dr Gardner points out that as the data came in and was charted, it became apparent that it was difficult for people to stick with the Ornish or Zone diets, and when these subjects fell short of following their specific program, their macronutrient-consumption data ended up falling right smack into the middle of the LEARN data, or the national nutritional guidelines.  Those on the Atkins diet morphed a little (toward a more Protein Power sort of plan, but not quite), but not nearly as much as those on the low-fat diets did.  After a year, the data ended up showing a bunch of subjects essentially following the national nutritional guidelines and another, smaller bunch, following a semi-Atkins diet.

As Dr. Gardner points out, in virtually every parameter measured, those following the Atkins book who ended up following a semi-Atkins diet triumphed over those following the other books, all of whom ended up following the national nutritional guidelines.  Which, of course, is no surprise to most readers of this blog.

But it was a huge surprise to Dr. Gardner, a 25-year-long vegetarian.  He admitted it was a bitter pill to swallow, but the data are what the data are.  And he was man enough to admit it.  I think this study and Dr. Gardner’s engaging presentation style will start getting some notice from mainstreamers.  King Canute couldn’t hold back the tide, and I don’t think the lipophobes will be able to hold back low-carb diets forever.  This is a great video to show Doubting Thomases if they will take the time to watch it.

Aside from the finding that the low-carb diet was vastly superior, a lot of other data came to light as a consequence of this study.  Some people did great on Ornish or the Zone while others did poorly on Atkins.  Why?  You would think that since all the subjects were humans, they would all respond the same way, but they didn’t.

This intrigued Dr. Gardner, so he began slicing and dicing the data to see what he could come up with.  At about the 40:00 point on the video, he discussed a few papers showing that people who are insulin sensitive actually do better on high-carb diets than they do on low-carb diets, whereas those who are insulin resistant do just the opposite.

I pulled all the papers he discussed and plan on reading them over the next ten days while I’m spending (literally) about 24 hours in an airplane seat.  (As part of our Sous Vide Supreme tour, MD and I leave tomorrow for Dallas, then Vancouver, Seattle, San Francisco, Chicago, New York, and Las Vegas, so I’ll have plenty of time to read.) I do find this information fascinating, but I have a few reservations as well.  There are very few moderate to significantly overweight people who aren’t insulin resistant to some degree, so I’ll be curious to see how the authors of these papers define insulin resistance.

Based on my own experience with a whole lot of patients, there are a few, but not many, overweight people–usually women, but occasionally men–whose lab reports show normal insulin sensitivity. I treated them with a low-carb diet, and they did well.  But I didn’t randomize these apparently insulin-sensitive overweight patients into two groups and put one group on a low-carb diet and the other on a low-fat, high-carb diet, so I can’t really say the ones I treated did better than they would have on a low-fat diet.

What I do know, however, is that those who have been overweight and insulin resistant, and who lose their weight and restore their insulin sensitivity with a low-carb diet, will regain in a heartbeat if they go on a high-carb diet for maintenance.  So, it’s hard to reconcile this fact that I know from hands-on experience with the data Dr. Gardner presented.

It could have something to do with the genetics that prevent the development of insulin resistance in the first place.  I’ll post on my thought about this paradox after I’ve read the relevant papers and reflected on them.

I had only one real objection to this presentation.  At the end, during the Q & A, someone asked a question about ketosis, and Dr. Gardner was clearly in above his head.  He did make the distinction between the ketosis one experiences on a low-carb diet and the dangerous ketoacidosis that those with uncontrolled type I diabetes are subject to, but he seemed to be uncertain as to whether low-carb ketosis was harmful over the long run.  He did remark that everyone is in ketosis part of the day, but then he kind of tossed it off by saying that the people on the Atkins diet weren’t really following it that closely and so weren’t really in ketosis for that long.  I wish had addressed the ketosis situation head on.  There is no danger in being in ketosis for extended periods of time.  Ketones are normal fuels of respiration and don’t pose any problems over the long haul.  In fact, some research has shown that ketones are a preferred fuel of many organs including the heart. (Veech et al)

As I’ll be traveling a lot the next 10 days, and since I don’t know my exact schedule even yet, I can’t promise a lot of regular posting.  But I will check the blog often and put up the comments as they come in.  If any of you have experience with trying a low-fat diet after losing on a low-carb diet, I would love to hear about it.

Think again.

A story appeared in the online version of Time Magazine last year that I read when it came out, put aside to blog about later, then got sidetracked.  A reader sent me a link to it a few days ago, which brought it back to the front of my mind.

The article discusses a study being done in Germany using a carb-restricted diet to fight cancer.  In pre-WWII days, a German scientist, Otto Warburg, received a Nobel Prize for his work in sussing out the fact that cancer cells don’t generate energy the same way that normal cells do.  Cancer cells get their energy, not like normal cells, from the mitochondrial oxidation of fat, but from glycolysis, the breakdown of glucose withing the cytoplasm (the liquid part of the cell).  This different metabolism of cancer cells that sets them apart from normal cells is called the Warburg effect.  Warburg thought until his dying day that this difference is what causes cancer, and although it is true that people with elevated levels of insulin and glucose do develop more cancers, most scientists in the field don’t believe that the Warburg effect is the driving force behind the development of cancer.

But it stands to reason that it can be used to treat cancer that is already growing.  Since cancers can’t really get nourishment from anything but glucose, it stands to reason that cutting off this supply would, at the very least, slow down tumor growth, especially in aggressive, fast-growing cancers requiring a lot of glucose to fuel their rapid growth.

Thomas Seyfried (the same Thomas Seyfried mentioned in the article) has shown that ketogenic diets in animals and humans can stop malignant brain tumors.  There is no reason to believe they wouldn’t work in humans as well.

A group in Germany is looking at such diets in a small pilot study.  Patients are only admitted to the study when all standard therapies – chemotherapy, radiation, surgery, etc. – have failed and they have basically been sent home to die.  In fact, a few were so far gone that they died within the first week of starting the study. You couldn’t ask for a study group more destined for failure, but, according to the Times article

The good news is that for five patients who were able to endure three months of carb-free eating, the results were positive: the patients stayed alive, their physical condition stabilized or improved and their tumors slowed or stopped growing, or shrunk.

If you understand the Warburg effect and the metabolism of cancer cells, it’s easy to see why this therapy works, even in patients who at at death’s door.  Since the cancers can use only glucose, and since glucose is made in the cancer cells slowly and inefficiently, the cancer cells have to rely on outside glucose to provide nourishment for their rapid growth and replication.  People on very-low-carb diets produce ketones, which take the place of glucose in other cells that can use these ketones for fuel.  But cancer cells can’t use the ketones since ketones have to be burned in the mitochondria, which are dysfunctional in cancer cells.  If you can keep blood sugar low, then growth of the cancer cells may be held in check long enough for the body’s own previously overwhelmed immune system to rally and beat the vulnerable cancer back.

Now, given all this, if you had a big cancer eating you alive and you were offered a chance for salvation by doing nothing more than following a low-carb diet, would you take it?  I certainly would.  But, not everyone does. I was stunned to read the comments of Dr. Melanie Schmidt, one of the researchers, about people dropping out of the study.

[Some] dropped out because they found it hard to stick to the no-sweets diet: “We didn’t expect this to be such a big problem, but a considerable number of patients left the study because they were unable or unwilling to renounce soft drinks, chocolate and so on.”

Let me see if I’ve got this right.  A lifesaving therapy is offered to patients who have undergone the misery of radiation therapy, chemotherapy, and surgery, and who are beyond hope, and this therapy requires nothing more than eating a lot of butter, meat, cream, cheese, etc. while avoiding most carbohydrates.  And a considerable number” drop out because they can’t give up carbs?

I say it again.  And you don’t think carbs are addictive?

As a coda to this post, I’ve got to tell you that MD at this very moment is rolling out a fondant that she made a couple of days ago.  She was dragooned into making the birthday cake for our granddaughter whose party is tomorrow.  The kid doesn’t want a store-bought birthday cake, she wants a custom-made cake by her Nanny, which has become a tradition.  She wants a Razor (a Swat Kat) cake, so MD is having to free-hand it.  Although she’s never made a fondant before, she figured that would be the easiest way to frost and decorate the cake she has in mind.  I wandered over to get a cup of coffee and pulled off a tiny piece of the stuff and popped in my mouth just to see what it tasted like.  Her fondant is made with powdered sugar, corn syrup, and lard (not the vegetable shortening called for in the recipe), and it is good beyond belief.  I’m sitting here writing this post, and after a tiny, tiny piece (maybe 3/4 inch by 1/2 inch by 1/8 inch) of fondant, I am obsessing over how easy it would be to walk the 10 feet to where it is and start throwing it down by the handfuls.  So, yes, carbs are addictive.  Especially the carb-fat combo.

Lest you get the wrong idea, our granddaughter’s parents keep her on a kid’s version of the low-carb diet most of the time.  The cake is a once a year deal.  Thank God.

I had a question from a friend today about migraine headaches. I remembered reading about them in Dr. Larry McCleary’s new book The Brain Trust Program, so I thumbed through the book to see what he had to say. (I had read the book in manuscript form, but couldn’t remember the specific recommendation for migraine headaches.) I became engrossed in the material all over again, and after a couple of hours of reading it dawned on me that I hadn’t reviewed the book for this blog.

First, a bit of disclosure. Dr. McCleary is a good friend of mine as well as a business partner for a number of years. And MD and I wrote the Introduction to his book. But we didn’t write it because he was a friend and partner, but because the book is so good.

Before we delve into the book let me tell you a little about Dr. McCleary. He is one of the smartest people I’ve ever met, and I’ve met a lot of smart people in the medical and nutritional business. He graduated at the top of his class from an Ivy League university, got accepted into a big name physics Ph.D program where he stayed for three years and ended up with Roger Penrose (the guy who co-writes the books with Stephen Hawking) as his mentor. When Penrose decided to go back to the UK he wanted to take Larry with him, but Larry had decided that he wanted to bolt from physics and go into medicine instead, so the timing worked out nicely. He graduated first in his class in medical school, then ended up doing a neurosurgery residency and a pediatric neurosurgery fellowship. He had a huge practice in Denver, Colorado where – along with carrying a heavy neurosurgical load – he was the Director of the Neuroscience Research Program at the prestigious Children’s Hospital. And he is the only person I know who reads more medical papers on a daily basis than I do.

MD and I had been encouraging him to write a book for years, and he finally took the plunge. And what a book it is. Most books on the brain written by medical professionals present programs to forestall the inevitable mental decline that comes with aging. These books typically recommend low-fat diets along with a few supplements and some brain exercises to help you keep your mental abilities from drifting away as you reach your golden years. Dr. McCleary’s book is the only one I’ve really seen that tells you not only how to keep your brain from deteriorating with age but shows you how to actually improve cognitive function. And guess what? You don’t improve cognitive function with a low-fat diet. But the book is much more than simply a book on improving your thinking. Among other things it shows how to reduce migraine headaches, improve your ability to study (Dr. McCleary goes into the techniques he used to study so that he could graduate first in his class in every school he attended), protect your brain from excitotoxins and even how to markedly reduce symptoms of menopause.

I’m going to excerpt a little from his section on supplemental nutrition for the brain. Many readers of this blog appear to be interested in krill oil, so we’ll see what Dr. McCleary has to say about it.

Krill, tiny shrimp-like creatures, inhabit the lowest rung of the food ladder, dining mainly on plankton, which are the actual omega-3 factories. As a result, krill enjoy a low risk of being contaminated by the mercury or other toxins present in their larger fishy cousins. Their oil, in my opinion, is the best source of essential brain fats available. Not only does krill oil provide substantial amounts of EPA and DHA but it also contains a rich supply of another group of critical fatty substances necessary for brain and nerve cell membranes to function properly: the phospholipids, which play important roles in signal transmission, in energy generation, and in the construction of the insulation coating myelin (which helps speed conduction along the brain’s communication pathways). The omega-3 fatty acids in krill oil are bound to these phospholipids. This unique relationship greatly facilitates the passage of the fatty acid molecules through your intestinal wall making them much more bioavailable (easily incorporated by the body). The predominant phospholipid in krill oil is phosphatidylcholine, making it a rich source of choline, which many studies have demonstrated as being important in brain development, learning, and memory. It is also the precursor for the vital memory neurotransmitter acetylcholine.

Krill oil also naturally contains high concentrations of a number of healthy antioxidant compounds that not only protect the krill oil but also protect your brain… These include vitamin A, vitamin E, astaxanthin, and canthaxanthin. Astaxanthin forms a special linkage with EPA and DHA, thus making it more readily available to the body than other antioxidants on the market. For this reason, while consumption of fish oil breaks down and therefore decreases your body’s antioxidant concentrations, krill oil actually increases levels of antioxidants in the body.

The parts of the book I found most intriguing are in Part III: Novel Applications of the Brain Trust Program.

One of the incredible interesting applications of the nutritional advice provided in this book is in the reduction of the symptoms of menopause. I’m all for anything that reduces the symptoms of menopause because a certain person I know well who shall remain nameless from time to time experiences these symptoms. And when she experiences them, so do I in a second-hand sort of way. So since I’m impacted, I’m interested.

And I’m not the only one who is interested. I saw a recent blurb showing the results of an Archer Daniels Midland survey showing that a majority of women want their doctors to inform them about non-medical options for relieving the symptoms of menopause.

As part of the ADM-sponsored survey, “Women & menopause: a look at supplement use,” 1,258 women between the ages of 40 and 55 were polled.

A third of these women indicated they do try natural supplements for the relief of menopausal symptoms, and a quarter said natural supplements are their “treatment of choice.”

Also, according to ADM, nearly all the respondents who are using dietary supplements for hot flashes say these are their “favorite method of treatment”.

Of course, this survey is totally self-serving because what ADM is really interested in is selling women on the idea of using soy products, produced naturally by ADM, to relieve these symptoms. But given the recent controversy over hormone replacement therapy, I’m sure many women are indeed looking for a natural way to reduce the often completely miserable symptoms of menopause.

(By the way, I would encourage anyone thinking of taking soy to reduce the symptoms of menopause or for anything else to spend the time going through the soy section of the Weston Price Foundation site.)

Dr. McCleary’s method of treating menopausal symptoms doesn’t use soy, but uses another natural substance instead: ketone bodies.

How do ketones treat these symptoms? They do so by replacing glucose that’s lacking from the estrogen-deprived brain.

Dr. McCleary provides a fascinating discussion of what happens in the brain that results in hot flashes when estrogen is withdrawn after many years of constant exposure. During these years of exposure estrogen becomes intimately involved in the development of the shuttles that transport sugar into the brain cells. With estrogen present – as it is in the premenopause years – these shuttles transport about 40 percent more sugar into the brain cells than would be transported without the estrogen. When the estrogen goes away at menopause, the shuttling of sugar into the brain cells decreases, and the brain cells become a little starved for energy. Dr. McCleary explains how the hypothalamus responds to this starvation by

stepping up the release of norepinephrine [adrenaline], which acts to raise the level of sugar in the blood, to raise the heart rate, and to raise the body temperature. The hot flash, then, is a specific outward sign of the brain’s trying to protect itself from blood sugar starvation.

Long time readers of this blog will know that ketone bodies are water-soluble fat breakdown products that can pinch hit for glucose in the brain and other tissues. Dr. McCleary shows how ketones do this to prevent hot flashes, and he even gives a recipe for a ketone cocktail to provide even more ketones to feed the hungry brain that isn’t getting enough sugar.

No other brain book written discusses this kind of information, I can assure you. And the bits I’ve discussed here just scratch the surface. I encourage you to order a copy of The Brain Trust Program and add it to the core of your low-carb library. You can get additional information and updates about his research from Dr. McCleary’s blog.

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?

Hardly.

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 remained 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.

]]> http://www.proteinpower.com/drmike/ketones-and-ketosis/karl-popper-metabolic-advantage-and-the-c57bl6-mouse/feed/ 66 http://www.proteinpower.com/drmike/ketones-and-ketosis/metabolism-and-ketosis/ http://www.proteinpower.com/drmike/ketones-and-ketosis/metabolism-and-ketosis/#comments Wed, 23 May 2007 03:50:03 +0000 mreades http://www.proteinpower.com/drmike/?p=719

Since posting the piece on ketone bodies and their causing breathalyzer problems I’ve had enough comments and emails to make me realize that there are probably many people unsure of what ketones really are, where they come from and why. Let’s take a look at the goals and priorities of our metabolic system to see what happens. I’m going to try to keep the biochemistry to a minimum, so fear not.

The primary goal of our metabolic system is to provide fuels in the amounts needed at the times needed to keep us alive and functioning. As long as we’ve got plenty of food, the metabolic systems busies itself with allocating it to the right places and storing what’s left over. In a society such as ours, there is usually too much food so the metabolic system has to deal with it in amounts and configurations that it wasn’t really designed to handle, leading to all kinds of problems. But that’s a story for another day.

If you read any medical school biochemistry textbook, you’ll find a section devoted to what happens metabolically during starvation. If you read these sections with a knowing eye, you’ll realize that everything discussed as happening during starvation happens during carbohydrate restriction as well. There have been a few papers published recently showing the same thing: the metabolism of carb restriction = the metabolism of starvation. I would maintain, however, based on my study of the Paleolithic diet that starvation and carb restriction are simply the polar ends of a continuum, and that carb restriction was the norm for most of our existence as upright walking beings on this planet, making the metabolism of what biochemistry textbook authors call starvation the ‘normal’ metabolism.

So, bearing in mind that carb restriction and starvation are opposite ends of the same stick and that what applies to one applies to the other, let’s look at how it all works. I’ll explain it from a starvation perspective, but all the mechanisms work the same for a carb-restricted diet.

During starvation the primary goal of the metabolic system is to provide enough glucose to the brain and other tissues (the red blood cells, certain kidney cells, and others) that absolutely require glucose to function. Which makes sense if you think about it. You’re a Paleolithic man or woman, you’re starving, you’ve got to find food, you need a brain, red blood cells, etc. to do it. You’ve got to be alert, quick on your feet, and not focused on how hungry you are.

If you’re not eating or if you’re on a low-carbohydrate diet, where does this glucose come from?

If you’re starving glucose can really come from only one place and that is from the protein reservoir: muscle. A little can come from stored fat, but not from the fatty acids themselves. Although glucose can be converted to fat, the reaction can’t go the other way. Fat is stored as a triglyceride, which is three fatty acids hooked on to a glycerol molecule. The glycerol molecule is a three-carbon structure that, when freed from the attached fatty acids, can combine with another glycerol molecule to make glucose. Thus a starving person can get a little glucose from the fat that is released from the fat cells, but not nearly enough. The lion’s share has to come from muscle that breaks down into amino acids, several of which can be converted by the liver into glucose. (There are a few other minor sources of glucose conversion: the Cori cycle, for example, but there are not major sources, so we’ll leave them for another, more technical, discussion.)

But the breakdown of muscle creates another problem, namely, that (in Paleolithic times and before) survival was dependent upon our being able to hunt down other animals and/or forage for plant foods. It makes it tough to do this if a lot of muscle is being converted into glucose and your muscle mass is dwindling.

The metabolic system is then presented with two problems: 1) getting glucose for the glucose-dependent tissues; and 2) maintaining as much muscle mass as possible to allow hunting and foraging to continue.

Early on, the metabolic system doesn’t know that the starvation is going to go on for a day or for a week or two weeks. At first it plunders the muscle to get its sugar. And remember from a past post that a normal blood sugar represents only about a teaspoon of sugar dissolved in the entire blood volume, so keeping the blood sugar normal for a day or so doesn’t require a whole lot of muscular sacrifice. If we figure that an average person requires about 200 grams of sugar per day to meet all the needs of the glucose-dependent tissues, we’re looking at about maybe a third of a pound of muscle per day, which isn’t all that big a deal over the first day. But we wouldn’t want it to continue. If we could reduce that amount and allow our muscle mass to last as long as possible it would be a help.

The metabolic system could solve its problem by a coming up with a way to reduce the glucose-dependent tissues’ need for glucose so that the protein could be spared as long as possible.

Ketones to the rescue.

The liver requires energy to convert the protein to glucose. The energy comes from fat. As the liver breaks down the fat to release its energy to power gluconeogenesis, the conversion of protein to sugar, it produces ketones as a byproduct. And what a byproduct they are. Ketones are basically water soluble (meaning they dissolve in blood) fats that are a source of energy for many tissues including the muscles, brain and heart. In fact, ketones act as a stand in for sugar in the brain. Although ketones can’t totally replace all the sugar required by the brain, they can replace a pretty good chunk of it. By reducing the body’s need for sugar, less protein is required, allowing the muscle mass (the protein reservoir) to last a lot longer before it is depleted. And ketones are THE preferred fuel for the heart, making that organ operate at about 28 percent greater efficiency.

Fat is the perfect fuel. Part of it provides energy to the liver so that the liver can convert protein to glucose. The unusable part of the fat then converts to ketones, which reduce the need for glucose and spare the muscle in the process.

If, instead of starving, you’re following a low-carb diet, it gets even better. The protein you eat is converted to glucose instead of the protein in your muscles. If you keep the carbs low enough so that the liver still has to make some sugar, then you will be in fat-burning mode while maintaining your muscle mass, the best of all worlds. How low is low enough? Well, when the ketosis process is humming along nicely and the brain and other tissues have converted to ketones for fuel, the requirement for glucose drops to about 120-130 gm per day. If you keep your carbs below that at, say, 60 grams per day, you’re liver will have to produce at least 60-70 grams of glucose to make up the deficit, so you will generate ketones that entire time.

So, on a low-carb diet you can feast and starve all at the same time. Is it any wonder it’s so effective for weight loss?

There’s a hold up in the Bronx,
Brooklyn’s broken out in fights.
There’s a traffic jam in Harlem
that’s backed up to Jackson Heights.
There’s a scout troop short a child,
Kruschev’s due at Idlewild!
Car 54 where are you?

Anyone who watched TV in the early sixties no doubt remembers the hilarious show Car 54 Where Are You? starring Fred Gwynne and Joe E. Ross as New York uniformed police officers Francis Muldoon and Gunther Toody. Muldoon and Toody were well meaning but hopelessly inept, always screwing things up in outrageous fashion, causing no end of grief and embarrassment to their precinct commander Captain Block, who had to sort out the idiocy and try to make things right.

Now comes the medical equivalent of Muldoon and Toody in the persons of in-training physicians Tsuh-Yin Chen, M.D. and William T. Smith, M.D. The role of precinct commander in this production is played by one Klaus-Dieter Lessnau, M.D., who, unlike Captain Block, only adds to the problem with another layer of ignorance and stupidity. And whereas Car 54 Where Are You? left its viewers with their sides hurting from laughter, the repercussions of our medical drama will be felt painfully in the world of nutrition for years to come. A well-respected medical journal will have a blot on its record in much the same way CBS did after rushing to air the discredited George Bush Air National Guard story before it was authenticated, and, lastly, the whole episode will serve as a cautionary tale to anyone considering going to the emergency room of a teaching hospital.

Our drama unfolds not on the TV screen but in the emergency room of Lenox Hill Hospital in New York. The script for this show is contained in an article in the current issue of The Lancet entitled “A life threatening complication of Atkins diet.” Let’s tune in.

First, a brief synopsis of what happened–a treatment as they say in Hollywood–then we’ll review the case in more detail to see what really happened.

An obese woman who had been on the Atkins diet for the previous month came to the emergency room complaining of shortness of breath. The resident physicians who saw her found evidence of elevated ketone bodies in her blood, diagnosed her with ketoacidosis, admitted her to the intensive care unit, gave her IV fluids, tested and x-rayed everything, and discharged her four days later after a complete recovery. The resident physicians along with their attending physicians wrote this case up as an example of what could happen to someone following a low-carb diet and got it published in a prestigious British medical journal, accompanied with an editorial issuing a further warning as to the risks of low-carb dieting. The press was all over the story and one of the attending physicians issued statements to anyone who called.

Let’s look a little deeper. This is the patient’s history:

In February, 2004, we saw a 40-year-old obese white woman who complained of dyspnoea (shortness of breath). 5 days earlier, her appetite had decreased, and she had felt nauseous and had since vomited four to six times daily. She became increasingly short of breath, and presented to us as an emergency.

She had strictly followed the low-carbohydrate high-protein Atkins diet, eating meat, cheese, and salads for the previous month.

This lady was truly on the Atkins Diet:

She took vitamins recommended by the diet: chromium picolinate, Atkins Basic3 (multivitamins; Atkins Nutritionals, Inc, USA), Atkins Essential Oils (omega fatty acids), Atkins Dieters’ Advantage (electrolytes and extracts), and Atkins Accel (a “thermogenic” formula). As instructed by the original Atkins diet book, she monitored her urine twice daily, with dipsticks strongly positive for ketones. She reported a weight loss of about 9 kg over this 1-month period.

Here is her presentation and the doctors’ physical findings along with my commentary:

On presentation to the emergency department, our patient was in moderate distress, with a respiratory rate of 20-30 breaths per min.

‘Moderate distress’ breathing at a rate of 20-30 breaths per minute? I don’t think so. A normal respiratory rate is between 12-20 breaths per minute, but obese people tend to breath a bit faster since they have a lot going on metabolically and need a little more oxygen. I wouldn’t say that an obese person breathing 20-30 times per minute was in distress, especially in view of the rest of the physical exam, which we’ll see in a moment. The resident physicians are trying to make a case for severe metabolic acidosis with this patient. If the patient truly was in severe metabolic acidosis (as type I diabetics can be if they go into ketoacidosis) she would have been demonstrating a type of breathing called Kussmaul breathing, which is characterized by rapid, deep, labored, sighing breaths familiar to anyone who has ever seen a bad case of ketoacidosis. We’re this patient exhibiting Kussmaul breathing, I’m sure it would have been identified as such in the published case report.

On examination, her bowel sounds were hyperactive and she had mild epigastric tenderness. Otherwise, clinical examination was unremarkable with normal vital signs.

Okay, when the resident physicians listened to this patient’s abdomen they heard more active, louder bowel sounds than normal and when they pushed on her abdomen she told them it was mildly tender. And her clinical examination was ‘unremarkable’ and her vital signs (blood pressure, heart rate, etc.) were normal. It doesn’t sound like someone in distress to me. When patients are in distress, their heart rates and/or blood pressure readings are usually elevated.

Her body-mass index was 41.6 kg/m2.

Interestingly, the case report doesn’t tell us this patient’s height or weight, only her body mass index (BMI). I assumed a height of 5′ 5″, which, when run through the BMI calculator, gives a weight of 250 pounds.

So, let’s see what we’ve got so far. An obese, 40 year old lady who has been nauseated and vomiting (4-6 times per day) for the past five days shows up in the emergency room. She is breathing a little faster than normal, but, given her weight, probably not by much. She doesn’t appear to be in any distress and all her vital signs are normal. Her abdomen is a little tender (whose wouldn’t be after vomiting for five days?) and her bowel sounds are hyperactive (think of the last time you got some kind of abdominal flu; I would be willing to bet that you could hear your own bowels gurgling without the aid of a stethoscope). Every doctor who has taken care of patients for any length of time has seen this same picture countless times. It’s a diagnosis that can be practically made from across the room.

The patient has gastroenteritis, an infection (probably viral) of the gastrointestinal tract. She may be a little dehydrated if she hasn’t been able to keep any fluids down, but she has probably been able to hold some fluids on her stomach or her blood pressure would be low and her heart rate rapid from the dehydration. If you’re the physician taking care of this patient you might want to run a couple of other tests just to make sure, which you do and find out that her blood sugar is normal (so you know she isn’t a diabetic in ketoacidosis) and her amylase is okay (so she doesn’t have acute pancreatitis) and her liver enzymes are normal (so she probably isn’t afflicted with hepatitis) and her white blood cell count is elevated, which goes along with an infection. You then might drip a liter of fluid into her intravenously to rehydrate her and make her feel better, give her a shot to reduce the nausea and vomiting or maybe a prescription for a suppository for the same thing, tell her to drink only clear fluids, and come back if she doesn’t get any better. In virtually all cases the patient will get well.

Then as you’re discussing all this with the patient, you find out that OH MY GOD, SHE’S BEEN ON THE ATKINS DIET! Now, if you’re an experienced physician, you tell her to not worry about her diet for a while until she gets over her nausea and vomiting, but that once she’s recovered she can return to her low-carbohydrate weight-loss efforts..

If you’re Muldoon and Toody, however, you panic. Low-carb diets cause ketosis, you think. Maybe she’s in ketoacidosis, which can be fatal. Since you’re an idiot, you ignore her normal blood sugar level, which should tell you that she’s making plenty of her own insulin. As the level of ketone bodies rises in the blood, it stimulates the release of insulin from the pancreas. The spurt of insulin then shuts down the process that makes ketones. Ketones only rise to dangerous levels in people who have type I diabetes and can’t make their own insulin. If the system didn’t work this way, people who starved would die from ketoacidosis relatively quickly, but they don’t; they live for weeks without food before they succumb to protein malnutrition, not ketoacidosis. The idea that this patient, who had a normal (or probably an elevated) insulin level was in dangerous ketoacidosis is absurd, but Muldoon and Toody don’t realize this because the patient HAS BEEN ON THE ATKINS DIET, FOR GOD’S SAKE.

In their frenzy of misdiagnosis, the panic-stricken Muldoon and Toody check the patient’s blood levels of beta-hydroxybutyrate, a specific ketone body, and find it to be high. They, of course, don’t bother to realize that, the Atkins diet notwithstanding, elevated levels of ketones would be expected since the patient hadn’t been able to hold anything on her stomach for five days, and when people don’t consume food they break down body fat for energy and produce ketones in the process. Nope, that would be way too rational. These doctors-in-training have the diagnosis of ketoadidocis burned into their brains thanks to the red herring of the Atkins diet, and they’re looking for anything to confirm it. They check a bunch of other labs that don’t really show anything all that earth shattering (and, in fact, don’t even really compute–but that’s a technical issue beyond the scope of this post) and admit the patient to the intensive care unit. Car 54 Where Are You?

In a typical teaching setting, the next morning the resident physicians would present their patient who is now resting comfortably in the intensive care unit at about $5,000 per day, and whom, in their own minds at least, they had just snatched from the jaws of impending death from ketoacidosis, to their attending physician. In a typical teaching hospital, the attending physician, who would have had a number of years of patient experience, would gently (or maybe not so gently) tell the residents that they had overreacted a little and would walk them back through the situation with a Socratic-type dialogue that would probably go something like this:

‘You checked this patient’s blood sugar and it was normal, right? Okay, now, what does that blood sugar tell you about the condition of the patient’s pancreas? Uh huh, that’s right, it’s making plenty of insulin. Okay, now, if the patient is making plenty of insulin, is it really possible that she could be in life-threatening ketoacidosis? Okay, guys, let’s review how ketones are made…’ You get the picture. I know how these little dialogues go because I was a resident at one time and I was on the other end of a number of them. In fact, I had an attending physician in surgery, famous for his sarcasm, who, had I done something like these two had done here, would have led me through the whole Socratic-dialogue process so that I could see every misstep I made along the way, then would have shaken his head and said, “Well, Doc, which is it? Are you stupid or do you just not care?”

But that wasn’t how this one must have gone there at the Lenox Hill Hospital. Instead of Captain Block gently reading Muldoon and Toody the riot act, our leader, Dr. Klaus-Dieter Lessnau, must have fallen into the OH MY GOD SHE’S BEEN ON THE ATKINS DIET trap. Instead of showing his underlings the folly of their ways, he jumped right in there with them, wallowed in their stupidity, kept this poor patient in the intensive care unit for four days, and may have even said, ‘let’s write a paper on it.’ After the paper was published and made the news, our attending was ever so eager to bask in his 15 minutes of fame and talk to any reporter that called and further memorialized his own boneheadedness. See here, here, and here. Had members of the press possessed even a smidgen of medical knowledge or had they checked with anyone other than Dr. Lessnau himself, the many pieces appearing about this fiasco might have been entitled something along the lines of:

Buffoons misdiagnose mild gastroenteritis, cost patient thousands.

Unfortunately, however, the press, afflicted with its own pro-low-fat bias, has been more than happy to take this opportunity to lambaste low-carb diets. Car 54 Where Are You?

In a perfect world, after this idiocy had consumed both the residents and their attending physician, and was then written up and sent out to journals for publication, someone, somewhere, with good sense, doing peer review would see it, realize it for what it was, and reject it. I have no way of knowing, but I suspect from the dates involved that that is exactly what happened. These events took place over two years ago in February of 2004, and were, I’m sure, written up shortly thereafter, and shipped off to some medical journal. I seriously doubt that The Lancet was the first choice. I would imagine that these authors received a number of rejections, but kept sending the paper out. It finally fell on fertile soil with The Lancet where not only did the editors fall for this ignorance hook, line, and sinker, they saw fit to publish a supporting editorial written by a dietitian turned PhD at the University of Minnesota. Car 54 Where Are You?

The editorial goes through the following argument. Although a number of studies have shown the low-carbohydrate to be superior to the low-fat diet in oh so many ways, we’ve got to be concerned about dieter safety. The report by Muldoon and Toody shows what can happen to a dieter on a low-carbohydrate diet. This patient could have died. The Atkins diet (and by extension all low-carbohydrate diets) are unbalanced. If you don’t believe it, compare the Atkins diet to the 2005 US Dietary Guidelines (and we all know how perfect those are). We’ll even provide the table. There, you see:

Clearly, the Atkins diet is not nutritionally balanced.

And they finish off with:

Special care needs to be taken when formulating the best prescription for weight loss, because people choosing to lose weight range from being marginally to significantly overweight, and might have a wide range of disease risk factors with varying levels of severity. As researchers and clinicians, our most important criterion should be indisputable safety, and low-carbohydrate diets currently fall short of this benchmark.

So, with this paper and accompanying editorial all the low-fat zealots have gotten what they’ve been waiting for. For years when MD and I and Robert Atkins and Ron Rosedale and Robert Crayhon and Jonny Bowden and a host of others have extolled the virtues of the low-carbohydrate diet, all the naysayers said: Where are the studies? All your clinical experience is simply anecdotal; we want to see the science. Show us the studies.

Well, over the last three or four years these pinheads have been deluged with studies showing the superiority of the low-carb diet over the low-fat diet for not just weight-loss, but for lipid lowering, blood sugar control, and blood pressure reduction as well. In any head to head challenge, the low-fat diet hasn’t been able to lay a glove on the low-carb diet.

Now that the low-fatters have been bloodied with all these studies they have been demanding for years, they haven’t given up, they’ve only changed their strategy. Since they can’t successfully argue on the merits, they’re resorting to scare tactics. Sure, they’ll say, you’ll lose weight alright, solve your lipid problems, and all the rest, but look at that poor lady who almost died. It was written up. That could happen to you, you know.

And to think that The Lancet has been a party to this travesty is almost beyond belief until it is recalled that it was The Lancet that published the Dean Ornish I’ve-proved-that-my-diet-has-reversed-heart-disease paper back in 1990. Like the current paper, the 1990 Ornish paper, in my opinion, was not worthy of publication without some serious rewriting. But, it is obvious that the powers that be at The Lancet have a bias in favor of low-fat dieting. And, based on the publication of these two papers, not just a mild bias, but a totally slanted perspective. In fact, I think that the name of the journal should be changed the The Slantcet.

Car 54 Where Are You?

Anti-aging scientists are now pretty sure that one of the forces behind the aging and senescence process is the junk protein matter that accumulates in the cells, hampering cellular function. If the junk builds up enough, it basically crowds out the working part of the cell, killing the cell off in the process. As this inexorable process proceeds, more and more cells function less and less well until we, as a being, cease to function. There are other processes driving the aging function besides this accumulation of cellular debris, but if we can make some headway with cleaning out the junk, then we should be able to make the cells, and by extension us, function better for longer.

We have little chemically-operated waste disposal systems in our cells called lysosomes. Cellular debris that gets hauled to the lysosomes and dumped in gets degraded into individual amino acids, which are released into the circulation and used to re-synthesize other, functional, proteins. The process of transporting the junk proteins to the lysosomes is handled by enzymes designed for that purpose found within the cells. As long as the enzymes are working up to snuff, the junk doesn’t accumulate. But as the Nature paper shows, the aging process takes its toll. Random errors in protein synthesis of these enzymes due to the aging process means that some end up being functional while others aren’t. The non-functional enzymes then not only don’t help haul the junk to the lysosomes, they themselves become junk. It’s easy to see what’s going to happen as time marches on.

But how can we slow this process and de-junk our cells?

Stay in ketoses a lot of the time. How do we stay in ketosis? By following a low-carbohydrate diet.

How does ketosis help us de-junk our cells?

A paper was published in the Journal of Biological Chemistry last year that tells the story. Ketones stimulate the process of chaperone-mediated autophagy (CMA). What is CMA? It is

a cellular process that allows cells to remove proteins, organelles, and foreign bodies from the cytosol [the watery interior of the cell] and deliver them to the lysosomes for degradation.

Why would the body be designed for ketones to stimulate CMA? Simple. Ketosis is one of the signs of long term starvation. Ketones are produced throughout the day and are perfectly normal, but sustained ketosis takes place during starvation and sends a message that the body needs to conserve both glucose and protein. The body begins to conserve glucose by signaling to many of the organs and tissues to start using ketones for energy instead of glucose. The body conserves protein by decreasing its use of glucose because in the absence of dietary carbohydrate (as in starvation) the body makes glucose out of protein. Conserving glucose by switching to ketones allows the body can preserve its protein stores. The other thing the body can do is to make sure that the protein it does break down to use for glucose formation comes from non-essential sources. What more non-essential source can we have than useless junk proteins floating around in the cells?

The ketones themselves stimulate the process of CMA to salvage all the junk protein to be used for glucose conversion. Ain’t nature great?

Now, all we have to do to slow the aging process is to stay in some degree of ketosis most of the time and let nature take her course and clean all the junk out of our cellular attics. How do we do that? Easy. Keep our carbohydrate intake at (or preferably below) 100 grams or so per day. Why that particular number? Let’s figure.

It takes about 200 grams of carbohydrate per day to provide glucose for all the structures in the body that require it. After a period of low-carbohydrate intake or starvation that amount required drops to about 130 grams per day because about 70 grams are replaced by ketones. We never really get below that because certain cells can’t convert totally to ketone use and continue to require some glucose. For instance, the red blood cells must use glucose for energy as do some cells in the kidneys and the brain and central nervous system. But not to worry, the liver can easily make 200 plus grams of sugar per day to ensure that these tissues get all they need. But the liver makes most of this glucose via a process called gluconeogenesis (the generation of ‘new’ glucose) out of protein.

So, if we decrease our carbohydrate intake to below, say, 50 grams per day, the amount advised in Protein Power and other enlightened books on carb restriction, we’re in a deficit to the tune of about 150 grams per day. No problema. The liver makes up the deficit out of protein. As we start making ketones to replace the glucose, the deficit drops to about 80 grams per day, which the liver can easily provide. But here is the neat part. Most of the glucose the liver makes won’t really come from protein from our tissues; it will come from the protein we eat. We’re not starving; we’re eating a high-protein diet. So we have plenty of protein to make glucose as we need it without robbing our muscles and other protein tissues that would get pillaged were we really starving.

But, deep in the bowels of our cells this fact is unknown. All the cells know is that ketones are all over the place, which is the signal to start the CMA process to break up junk protein.

We end up losing body fat, which is both burned for energy and converted to ketones to replace glucose, while at the same time we maintain our needed protein structures because we’re eating protein, and we de-gunk our cells. All while eating steak and eggs and lambchops and ham and…

It just one more reason the low-carb diet rules.