segamartinez

The Bad Cholesterol Myth

2011-05-10T07:37:00.000-07:00

Here is a succinct statement from a researcher about the so-called "good" and "bad" cholesterol (hat tip: Richard Nikoley).

The bottom line: LDL is a delivery mechanism.

"What our study found was that the more LDL-cholesterol, the so-called 'bad cholesterol' you had in your blood, the better you built muscle with resistance training. LDL is not "bad," it is an essential physiological component of our blood that does a job, and, we need to back off calling it 'bad cholesterol.'"

The Robert Lustig Diet?

2011-05-05T04:53:00.000-07:00

I get a number of inquiries, both through the search engines and in person, regarding Dr. Lustig, and what diet he recommends. The following is not the “Lustig Diet” per se, but it is what he and the University of California, San Francisco Center (UCSF) for Obesity Assessment, Study & Treatment (COAST) recommends.

From Sugar: The Bitter Truth:

We write this on the back of a matchbook. It’s just as simple as you can make it. We have four things we teach the kids to do, and the parents.

1. Get rid of every sugared liquid in the house. Bar none. Only water and milk. There is no such thing as a good sugar beverage. Period.

2. Eat your carbohydrate with fiber. Why? Because fiber is good. Fiber is supposed to be an essential nutrient and we can talk later if you want, after the cameras turn off, as to why fiber is not an essential nutrient – because the government doesn’t want it to be. Because then they couldn’t sell food abroad.

3. Wait 20 minutes for second portions, to get that satiety signal.

4. Finally, buy your screen time minute for minute with physical activity. That’s the hardest one to do. If you play for ½ hour, you can watch TV for ½ hour. You want to watch TV for an hour? Play for an hour. That one’s a hard one.

We follow our patients every three months. Here’s my question: does it work? What do you think? Yeah, it works.

In sum:

1. Eliminate sugar-sweetened beverages.
2. Eat carbohydrates with natural sources of fiber
3. Wait 20 minutes for second portions
4. Buy screen time with physical activity, minute for minute.

Are a balanced diet and moderation really the answers?

2011-05-03T16:51:00.000-07:00

I can’t tell you how many times I have heard from one of my colleagues in nutrition tell me “everything in balance and moderation.” Virtually any time we start talking about what constitutes a healthy diet, they invariably tell me it’s all about eating a balanced diet and eating everything in moderation, even if it’s unhealthful.

As someone who cannot eat cookies in moderation, or smoke cigarettes in moderation, this advice drives me up the wall. When we’re talking about smoking, we try to get the smoker to quit, we don’t tell them cigarettes are good in moderation. If it’s the cigarettes that are giving us lung cancer and it’s the sugar, refined, and easily digestible carbohydrates that are making us fat and sick, why is it copacetic to prescribe these foods, not only in moderation, but as part of a presumably “balanced” diet.

There’s also this notion that if we restrict our consumption, and say, try to eliminate a six-soda-a-day habit from our diet, we’re going to be more likely to give in to our cravings, than if we moderated our soda drinking and allowed for one can of soda per day. This study seemed to demonstrate that people who restricted carbs craved them less than people who ate them in “moderation.” This makes intuitive sense, does it not?

I quit smoking about 15 years ago. I used to smoke a pack of cigarettes a day. Now I don’t even give it a thought. Even when all my friends are doing it and everyone around me is smoking. I haven’t had a cigarette in 15 years, but by the logic of dietitians, I should crave cigarettes more than if I practiced balance and moderation and cut down to five cigarettes a day for the last 15 years.

Likewise, I don't eat sugar and sweets, but still attend the office birthday gathering that includes a supermarket sheet cake. I don't have any cake. Does that make me some sort of freak? Sort of. People are somewhat bemused by my abstention and I think it makes them question their own behavior and I'm silently judging them. Well, I'm not.

I have a strange feeling that if I continued to smoke five per day and managed to cap it at five, which I would argue would have been excruciatingly difficult on a daily basis, I would have much greater cravings for a cigarette today. In fact, if I had any inkling at all to light up, it would be a greater craving than what I now experience having eliminated them. Yet this is what we are telling fat people to do. Don’t eat the entire pizza, fatty. But don't deprive yourself, either. Just have one slice and savor those bites. Or, perhaps I should give myself that piece of cake because otherwise I will want that piece of cake so badly that I will give into my cravings, and wind up in a food coma under an overpass on route 128.

It’s actually quite ludicrous. Perhaps the lean dietitian doesn’t have cravings for carbs the same way someone who is morbidly obese does and telling someone to feed their habit, but only in small doses, is torturous for many people. I for one find little more ironic than the “Fun Size” snickers bar.

In other words, I would rather go through the pain for a week or two and kick my habit and not have to give it much thought, if it all, for the rest of my life, rather than walking a tightrope of balance and moderation on a daily basis.

A common response to telling people to eat a more ancestral diet is that they "just can't live without" fill-in-the-blank-sugary-doughy-starchy-goodness (cookies, cake, pie, pasta, bread, candy, soda, bagels, etc). I thought this was the case myself years ago. Giving up "an entire food group" [1] is daunting at first, but after you give it up for a while, amazingly, you don't miss it. To go back to cigarette smoking, during the first few days of quitting, all I could think about was having just one cigarette and that I could never live without nicotine. But, as it turns out, the things we just can't live without, we can live without, so long as we live without them. Keeping them in our lives in moderation is a recipe for disaster for many people.

When I ask dietitians and dietitians-in-training what constitutes a balanced diet, they generally tell me that it’s 60% carbohydrate 25-30% fat and 10-15% protein.

One of these things is not like the others, Can you tell which thing is not like the others...By the time I finish my song?

Let’s go to Walter Cronkite circa 1964: ‘Well folks, there are still a few states that have yet to report the results, but we can safely say that the election is still up for grabs at this point. The American people are “balanced” in their decision for who is going to be inaugurated in January. Lyndon Johnson currently holds 61% of the popular vote while Barry Goldwater sits comfortably at 39%.’

I’m sure if you check the archives, this is not exactly the way it went down in the newsrooms.

This happened to be the largest landslide in American presidential-election history.

If our “balanced” macronutrient diet represented three candidates running for president, carbohydrates would represent the largest landslide in presidential history.

Also, the macronutrient group we eat the most of also happens to be the only non-essential category of the three.

We can live without dietary carbohydrates, yet they dominate the current US recommendations for consumption. What’s wrong with this picture?

Quality of the diet dictates quantity of the diet so the worst thing the government could have said, and the cruelest joke they could have played on the public (it would be funny if it weren’t so tragic) was to encourage a decrease in the quality of the diet while prescribing a conscious reduction in the quantity as well.

Think about an Atkins diet for a moment. An induction diet generally consists of - eating to satiety - meat and vegetables. It encourages adequate protein consumption, high fat consumption, and cholesterol consumption, all of which are essential components of the diet.

The promulgation of a low fat, low cholesterol, low calorie, diet, has undoubtedly done us more harm than good. The subtext has always been about moderation and (energy) balance. Problem is, it doesn't work.

Almost all of the research that has been done in the last fifty years has been conducted in the context of a low fat diet for heart-health and weight-loss so it seems that we have some catching up to do.

Something that Jeff Volek mentioned in an interview with Jimmy Moore is that when we're long gone we will look back at the last 30 years of nutrition as the dark ages because people will realize we missed the boat by putting so much effort into low fat and really ignoring the concept of carbohydrate restriction.

Dr. Eades noted much of this in a blog post entitled Last gasp of the dark ages of nutrition. In it, he cites quotes from the New York Times and Wall Street Journal telling us that it’s all about counting calories, and then goes on to dismantle this notion and how the conventional wisdom views everything with a biased lens.

Eades also points to a an illuminating quote by the physicist Max Plank, who said, “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it.”

The sad reality is we may be reaching a breaking point where our healthcare system can't sustain this level of obesity and diabetes and not only are the opponents dying out, but the population at large seems to be getting sick, fat, and dying as a result of their recommendations.

Well, almost there, guys. We’re getting closer and closer to the breaking point as the obesity epidemic and diabetes epidemic - to name two - increase unabated while you admonish people for their lack of will power.

So let's get some fresh blood in there. Let's put a few new cars on the road and be sure to ‘kick the tires’ of the low carbohydrate hypothesis. But the important thing is to allow the low carbohydrate vehicle out of the garage and put some miles on it so we can properly evaluate it.
____________________

[1] This phrase turns out to be nonsense, but this is how dietitians like to pooh-pooh an Atkins or Paleo diet - grasping for straws at this point - remember when these diets gave us heart disease, cancer, obesity, diabetes? Turns out when we lose this "food group" we lose the diseases as well. But check out this article, Paleo Diet: Caveman diet draws grunts from nutritionists (hat tip to Angelo Coppola at Latest in Paleo #13), subtitled: Avoiding entire food groups is a mistake, critics say. Perhaps, grains shouldn't be considered a food group when they weren't consumed for more than 99% of our existence on earth as a species? Are cookies a food group?

High Fat Diets: The Sweet Deception

2011-04-27T06:34:00.000-07:00

Robert Lustig was recently interviewed by KQED and had this to say:

How do you get diet induced obesity in a rat? People say put them on a high fat diet. Garbage.

You can't get a rat to eat a high fat diet...unless you add 20% sucrose to the diet. Basically you're giving them cookie dough.

But if you give them lard they won't eat it. They actually lose weight on that because that's the Atkins diet for them. It's not palatable. They don't like it and they actually lose weight and their metabolic parameters improve.

The only way to get an animal; a rat, monkey, or any other animal, for that matter, to eat a high fat diet is to lace the fat with sucrose.

So the question is: which is doing the damage, the fat or the sucrose in that case? And the answer is both.

In a recent post entitled Diabetic nephropathy and the lost Swede at Hyperlipid, Peter links to a recent paper in PLoS which demonstrated a partial reversal of diabetic nephropathy in mouse models.

“These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention,” conclude the authors of the paper.

Peter goes on to cite a Swedish paper - that the recent paper above did not cite - which demonstrated a reversal of renal failure by a low-carbohydrate diet.

While the PLoS study neglected to mention the Swedish paper, they referenced a 2007 paper entitled A high-fat, ketogenic diet induces a unique metabolic state in mice.

Bottom line for these researchers? “These data indicate that KD [Ketogenic Diet] induces a unique metabolic state congruous with weight loss.”

The diets were:

1) Control, or, Chow (16.7% fat, 26.8% protein, 56.4% carbohydrate (6.5% sucrose))
2) High Fat (45% fat, 24% protein, 35% carbohydrate (17% sucrose))
3) Ketogenic Diet (95% fat, 5% protein, 0% carbohydrate)

Wait, so which one is the “high-fat” diet, again? “High-fat” is 45% fat, while KD is 95% fat. It has been mentioned before at this blog, and warrants mentioning again: in science, you need well-defined variables.

When researchers compare a low-carbohydrate diet to a low-fat diet, what constitutes “low” depends on which team of researchers you ask. There is no well-defined number or percentage. Also, invariably, when the diets are compared, the low-carbohydrate diet is ad libitum, which is a fancy way of saying “all-you-can-eat.” The low-fat diet is restricted in calories, but more often than not, the researchers do not make this distinction throughout their articles. These are just a couple of examples to the limitations of the current definitions, and there are more, to be sure.

With a “high-fat” diet which happens to contain 162% more sucrose as a percentage of carbohydrates compared to the chow, perhaps the researchers and the people reporting the results should mention something about this? Considering when the researchers remove the sucrose and add fat (i.e., the ketogenic diet), the problems magically disappear, it just might warrant mentioning, and might bring into question the quite liberal use of the term "high-fat" in this context.

While Dr. Lustig and I can agree that we think it’s garbage to claim that we induce obesity by feeding mice, or humans for that matter, a “high-fat diet,” it seems we part ways regarding why the mice eat less on a ketogenic diet (i.e., a high-fat, little-to-no-carbohydrate diet) and also regarding what is doing the damage. Lustig thinks its sucrose and fat? A little bit odd coming from the guy who said “It ain't the fat, people.” Perhaps I'm picking nits, but doesn’t this imply that you need to feed a human both sucrose and fat to induce damage? (I would also like to address the idea that the KD is not “palatable” and the absurd implication that dieters eat less out of boredom that many researchers, academicians, journalists, physicians, and authors alike invoke, but will save it for another post. To keep you “satiated” in the interim, here is a great post by Dr. Eades on the subject.)

In other words, if we had two arms of a randomized controlled trial (RCT):

1. 2500 kcal: 90% Fat; 10% Protein; 0-1% CHO
2. 2500 kcal 0-1% Fat; 10% Protein; 90% Sucrose;

Would both of these groups lose weight and improve their metabolic parameters? Let’s say prior to baseline they have an average BMI of 32, and they have been relatively weight stable in the past 6 months eating:

2500 kcal: 30% Fat; 10% Protein; 60% CHO (about 20% sucrose)

As Lustig has said, a calorie is not a calorie, and calories can be isocaloric, but not isometabolic.

In other words, the second arm of the RCT is taking in 90%, or about 2250 calories of sugar, and 1125 calories of fructose. This amounts to about 281 grams. Lustig has said to shoot for less than 50 gm.

Why would the fructose be particularly damaging? After all we’re talking about “fruit” sugar. How can something in fruit be bad for us? Sugar is natural. Have we just refuted the idea that sugar is toxic, poison, and evil?

As Gary Taubes pointed out in a recent interview on NPR, and Paracelsus (not sure if it was on NPR as well) in the early 16th century, the effective dose makes the poison.

One of the points biochemists will make is you can’t just say that something is natural.

A metaphor is I could lean on you and apply a gentle pressure for 10, 20 minutes, an hour, it’s not going to do you any harm. But if I take that same amount of pressure and condense it into a split-second, then I’m hitting you in the arm pretty hard, and it hurts, and I’m going to cause swelling and pain, etc.

And that’s what we’re doing when we consume these sugars in this quantity and especially in liquid-form, it’s like we’re hitting the liver with them, and the liver responds by going “ouch,” and turns it into fat and becomes a little insulin resistant, and then the rest of the body becomes insulin resistant, and over the course of months or years, you end up quite likely with this problem called metabolic syndrome, and all of these chronic diseases stem from there.

As Dr. Lustig pointed out in an interview with Jimmy Moore:

Basically, if you look at the stereoscopic model of fructose, you can’t even imagine how it can stay together as a ring. It’s going to fly apart almost on contact and that means that that reactive ketone group that’s in the fructose is going to react with just about any protein around and it’s going to contribute reactive oxygen species, which ultimately cause vascular damage. That’s basically you down the road to cardiovascular disease. If you’ve let that fructose get past your liver, you’re screwed.

We shouldn’t let researchers, or journalists, or professors, or anyone for that matter, off the hook when they implicate a “high-fat” diet in causing, or even curing, an ailment, without them making the distinction that a “high-fat” diet is a “high-fat-high-sugar” diet in this context.

It could be likely that the increase in sugar is the driver of disease, while the “high-fat” content is along for the ride. The results of the 90% fat ketogenic diets certainly seem to make a case for it.

The Russian Literature Paradox

2011-04-21T05:02:00.000-07:00

And in knowing, that you know nothing, makes you the smartest of all. - Socrates

When I was attending Gary Taubes’s lecture at Tufts University, there was a fair amount of “audience participation.” I mean this somewhat facetiously because I was practically the only individual taking part.

Taubes would present a slide and a quote by someone in the field of nutrition and he would ask the audience of predominately nutritional science students and professors to raise their hands if anyone had heard of the quoted person.

“Who here has heard of Louis Newburgh?” Crickets. I would sheepishly raise my hand.

A few slides would go by. “Anyone familiar with Carl von Noorden?” Hay bale drifts through the room. My hand goes up. "You don't count; you read my book," quipped Taubes. Fair enough.

But I think there’s an important lesson in this.

I have been taking a distance (read: online) clinical nutrition course in which there is a great deal of discussion on the message boards. Each week, a group of two or three students post a question related to the week’s course topic. Gestational diabetes, carbohydrates and diabetes, metabolic syndrome, childhood obesity, bariatric surgery, saturated fats, and so on. And virtually every week, my opinion runs counter to at least 90% of the students.

Seemingly, it should be relatively easy to dismiss the lunatic with the tinfoil hat (it's comfortable, okay?) as a charlatan, but something odd happens en route. I’m the one presenting the science, the history of nutrition, and the observations that refute the claims of the vast majority. This goes off like a fart in church. Everything popular is wrong? Maybe.

Some people in the class are somewhat supportive, but most, at best, are condescendingly back-patting and thanking me, in their best Dr. Oz impression, for “kicking the tires.” This is what Oz said to Taubes during his appearance. In hindsight, Taubes said that he should have responded: ‘well, Dr. Oz, I'm not sure kicking the tires makes a damn bit of difference after you've totaled the car,’ (his other shelved rebuttal allegedly was ‘the jerk store called, and they’re running out of you’) though he also conceded that this would have been edited out, along with his explanation of the complications of cholesterol, and why he declined having a cholesterol test if they weren’t going to do a comprehensive panel, like the one he ended up getting.)

Others in the class claim that I’m introducing “a totally new science” to health and nutrition and that I should start my own special field. Go home and get your shinebox, Bob.

But here’s the rub: I am introducing science - not a ‘totally new science’ - science, into a field that seems to be actively avoiding it. I'm also just bringing up historical information regarding nutrition and it feels like many people think I'm coming out of left field.

I'm seen as a crackpot by the class when I bring up names like Louis Newburgh, Carl Von Noorden, Hugo Rony, Jean Mayer, Julius Bauer, Ancel Keys, John Yudkin, George Mann, George Bray, George Cahill, Eugene Du Bois, Francis Benedict, et al.

If this were a graduate level physics course (and this is something Taubes illuminated in his lecture), if I brought up names like Plank, Einstein, Tesla, Faraday, Heisenberg, Bohr, Curie, Feynman, Volta, Hubble, Fermi, et al., everyone would know who I was talking about, what they accomplished, and their contributions to the field.

In physics, if you didn't recognize these names, you would be laughed out of the field. In public health, you're mocked if you do.

If I polled the class on the recognition of the twelve names in nutrition and weight regulation I mentioned, how many of these people would they recognize? These people are pioneers in the field, yet we’re not taught very much, if at all, about them. I think it would be helpful.

I happen to know the names of guys like Rony and Bauer and their contributions to the field. For the most part, I know them because Taubes knows the names, too, and included them in articles like The Soft Science of Dietary Fat, What if It’s All Been a Big Fat Lie, The (Political) Science of Salt, and wrote books such as Good Calories, Bad Calories and Why We Get Fat.

It doesn’t make me smarter than anyone that I’m the only one in the lecture hall of 200 people to pass the Taubes test, but I would argue it makes me more informed. And one of the limitations to nutrition as I see it, is that if you really want to have a full understanding of obesity, for example, you need to be familiar with endocrinology, metabolism, weight regulation in animals, anatomy, clinical treatment and trials of obesity in humans, anthropology, exercise physiology, reproduction, cell biology, and have a familiarity with the relevant research, epidemiology, and clinical trials, and the list goes on. It might take a few lifetimes to achieve this.

But it doesn’t absolve the field from trying to learn the basic sciences and have at the very least a cursory understanding of the aforementioned topics. Instead, when I invoke biochemistry and endocrinology in the regulation of adipose tissue in my class, or when I tell them that the brain can run predominately on ketone bodies, they respond that I have “interesting opinions.” It’s the science! I’m not making it up!

This brings me to the latest podcast (episode 76) by Robb Wolf and Greg Everett at The Paleo Solution.

Robb was wonderfully agitated by the following question:

6. Brain Function without Dietary Carbohydrate

Craig Says: My girlfriend is a very recent graduate of nursing school and has been very helpful in my transition from a fellow vegetarian to a “things-with-a-face eater.” But she is very hesitant about my adoption of the Paleo diet mostly based on her contention that the brain cannot function properly without complex carbohydrates such as pastas and rice. I’ve been 98% paleo for the last two months with a few slips into ice cream hell. Can you give me a medical explanation that will help me in this battle? She will not join the meat-eating bandwagon but has definitely reaped the benefits of switching our diet to entirely whole foods. She is complete agreement with this aspect of Paleo nutrition but can’t understand the low-carb effect on the brain and other important bodily function. Thanks for being such an accessible and reliable scientific resource.

So Robb dusts off his 4th edition of Stryer’s Biochemistry (I happen to have a copy myself so I think that makes us beaker-brothers or something nerdy - or perhaps we’re just both interested in science - which seems to be such a rarity in the field of nutrition, that it appears peculiar that we would have science textbooks?) and goes to town: the human brain can run predominately on ketone bodies during relative caloric, or carbohydrate, unavailability.

But it, too, brought up a larger point, which is very much related to the previous one about nutritionists having no understanding of the history of the field; they have virtually no understanding of the science behind nutrition as well.

It is valid to point out that physicians receive little to no nutrition training. Chris Kresser was just pointing this out in a podcast with Jimmy Moore. Why listen to your doctor when they have so little training in nutrition? Good question.

But what of the registered dietitians? What are they learning? I happen to be completing my didactic program requirement in dietetics, and feel free to have a look for yourself of the course requirements. There are science courses, to be sure, but it doesn’t seem to explain my experience with dietitians and dietetic students. It is safe to say that most of them don’t understand the biochemistry, endocrinology, biology, physiology, and organic chemistry, for example, at a level where they can explain relatively pedestrian mechanisms of action. To be fair, I was recently trying to work out a problem related to organic chemistry, and turned to an expert in the field, who subsequently asked if I had indeed passed organic chemistry in college. Passed? Yes. Grasped? No. But I’m trying and will continue to do so until I can at least speak the language.

I try to make it a point to surround myself with people who are smarter than me; people who often will tell me that I’m wrong more often than I’m right. Criticism is far more useful than praise. This is how you grow. To remain stagnant is to ignore the voices questioning your methods and results and never seeking alternative explanations or questioning your own ideas. The public health authorities are phenomenal at this.

I don’t think most dietetics students make this kind of effort. What Richard Feynman called “a specific, extra type of integrity that is not lying, but bending over backwards to show how you are maybe wrong, that you ought to have when acting as a scientist.” And “this is the responsibility of scientists,” (perhaps dietitians and public health authorities are immune), “certainly to other scientists, and I think to laymen.”

In fact, most people I know don’t seem to be making the effort, or claim that they just don’t have the time. That’s why I think people like Lalonde, Kresser, Taubes, Lustig, Wolf, et al. are so invaluable, and unfortunately, so rare.

Wolf, later in his diatribe, posited a couple of questions: Why aren’t the nursing and medical students reading the textbooks and scientific literature and questioning the conventional wisdom? And why is the convention wisdom what it is when it seems to run counter to science?

I think it’s because the foundation and core principles of public health operate as a political institution. It may be fair to say that the opposite of science is politics, i.e., politics is anti-science. And this is coming from a blogger who studied political science (an oxymoron, perhaps?) as an undergrad.

Robb also mentioned that he was “mean” to his conference attendees - at a hospital, addressing the medical staff - during a recent presentation and asked them basic biochemistry and metabolism questions; and they could not answer them correctly. And maybe half the people were present to tell Robb what he was saying is wrong.

Sounds a lot like Taubes, his lectures, and his point about the dearth of understanding of one’s own field. Yet these same people in the audience of a Taubes or Wolf lecture are the ones discrediting the lecturer and dispensing the dietary advice; while Gary and Robb are relegated to “kicking the tires.”

Another point that Robb illuminated was The Russian Literature Paradox.

If you run into a PhD in Russian Literature and tell them you read Crime and Punishment, and get into a discussion about Russian lit, and the PhD rattles off names like Alexander Blok, Sergei Yesenin, Anna Achmatova, Marina Tsvetaeva, Osip Mandelstam, Boris Pasternak, Joseph Brodsky, Vladimir Mayakovsky, Ivan Bunin, Vladimir Nabokov, Mikhail Sholokhov, Mikhail Bulgakov, Andrey Platonov, Vassily Grossman and Aleksandr Solzhenitsyn, (I had to look up just a few of these names!) perhaps you should defer to this man’s opinion. It doesn’t mean that his convictions are necessarily true, but it most likely means that he is more informed and has a better grasp on the subject. And perhaps you should educate yourself on the subject before you join the discussion.

With nutrition, everyone eats, therefore everyone is apparently an expert in nutrition. Everyone has an opinion, and anyone who has lost more than three pounds in their life (about 99% of the population), feels that they can instill their wisdom upon the masses to great fanfare.

Problem is, even the supposed experts in nutrition can't tell you who the nutritional European and American equivalents to Nabokov, Dostoyevsky, Gogol, and Chekhov are, but boy are they are willing to commentate and pontificate with great resolve.

With Russian Literature, most people are wise enough to heed the advice of Mark Twain: “It is better to keep your mouth closed and let people think you are a fool than to open it and remove all doubt.”

With nutrition, every Tom, Dick, and Harry - and seemingly every public health authority - has no problem opening their mouths and removing all doubt.

In other words, the "experts" in the field of nutrition do not understand nutrition. Therefore, anyone who can rub two brain cells together can contribute to the field.

Meanwhile guys like Gary Taubes, Robb Wolf, Chris Kresser, Chris Masterjohn, Kurt Harris, Stephan Guyenet, Petro Dobromylskyj, Michael Eades, Robert Lustig, Eugene Fine, Eric Westman, Steve Phinney, Jeff Volek, et al., are having collective aneurysms on a daily basis and at some point, I believe, we are all going to realize that engaging the "experts" in a dialogue is like playing handball against the drapes.

I feel like I speak for the bloggers, physicians, and researchers above in a collective message to the public health authorities, channeling my inner-Will-Hunting: “I’m sorry you can’t do this, I really am, because I wouldn’t have to fuckin’ sit here and watch you fumble around and fuck it up.”

I try - and I think this is a common thread among the aforementioned bloggers, writers, researchers, and physicians above - to treat the field of nutrition like a science, because that’s what it presumably is. And I think a significant part of the reason for the massive health problem we have is that it’s not treated as such.

Low-Carbohydrate Diets and LOSING Weight while Pregnant

2011-04-20T09:46:00.000-07:00

Since my wife is pregnant, I have been thinking more about maternal and fetal issues and how they relate to nutrition, fuel partitioning, and weight management. She is thrilled for me.

One question I had while going for a walk was: Is it dangerous for a woman to lose weight during pregnancy? Dr. James Carlson has reported that he probably worked with thousands of mothers who lost weight during pregnancy on a low-carbohydrate diet and developed healthy babies while dropping as much as 50-60 pounds in the process.

The conventional wisdom holds that a mom shouldn't be losing weight while pregnant because there is an implicit assumption that the mother would be restricting calories; she would be semi-starving herself, therefore she would be starving the fetus, which would obviously be a problem, for both mother and fetus.

However, when you view it from the carbohydrate-hypothesis paradigm, low carbohydrate diets do not restrict calories, they do not restrict essential nutrients, and they generally improve the relative health of the mother, and therefore the baby as well.

When a mother is losing weight on a low-carbohydrate diet, while pregnant or not, she is not losing weight because she is eating less, she is eating less because she is losing weight.

For a non-pregnant woman, more fatty acids are liberated from adipose tissue and she literally has more energy circulating to provide endogenous fuel to her cells and, if she 'overeats,' for increased expenditure through both exercise (“activity thermogenesis”) and non-exercise activity thermogenesis (NEAT). She doesn't eat as much energy because her body is now providing more energy from her fat stores.

If higher levels of insulin drive more fat accumulation, lower levels of insulin help drive fat utilization. (It is worth noting that there is physiological insulin resistance that occurs during pregnancy. This will be covered in a subsequent post.)

For a pregnant woman losing weight on a low-carbohydrate diet, the same holds true as above, but in addition, she is also supplying energy to the baby. She eats less because she is losing weight through lipolysis, and now some of that fuel gets partitioned to the fetus as well. So long as she has ample fat tissue and is providing adequate energy and nutrients for her own needs, as well as her fetus, who cares how many calories she is eating?

A low-calorie, low-fat, low-cholesterol diet flies in the face of reason while pregnant. Keep in mind that this very same argument for pregnant women holds true for the population at large.

The fetus needs adequate energy, fat, and cholesterol for proper and healthy development.

All human beings require the same. To restrict calories, fat, or cholesterol is to restrict the organism from its physiologic needs. If one of these essential nutrients is being restricted, why wouldn’t we feel less than adequate?

For a woman with adequate adipose tissue, losing weight while pregnant is not dangerous, so long as the "weight", i.e., the energy, is being supplied to the fetus.

We're not violating the laws if thermodynamics here, we're transferring our energy to the fetus, and the result is that one system gets relatively smaller (the mother's fat tissue) and another system gets bigger (the fetus).

And for a non-pregnant woman on a low-carbohydrate diet, one fuel supply gets smaller (exogenous calories, i.e., food, i.e., "calories-in") while another fuel supply gets larger (endogenous calories, i.e., body fat, i.e, "calories-out").

We lose weight on a low-carbohydrate diet while we are in "energy balance" as the conventional wisdom portrays it. The conventional wisdom doesn't account for "calories-out" provided by our own energy stores in this context. But this is the fundamental driver of obesity and leanness. Expenditure is exceeding intake at the level of the fat tissue. Isn't that what we care about if we don’t want to be obese?

And for the fetus, does it grow because it takes in more energy or does it take in more energy because it’s growing? So long as we are supplying a metabolically healthy fetus with adequate nutrients, it will take what it needs for normal development. The fetus "eats more" because the fetus is developing and requires more energy.

We haven’t even begun to discuss the importance of breast milk, which also requires fuel to produce (breast milk is fuel, after all); and the rationale is for pregnant women to gain 10 pounds to provide a reserve to be utilized for breast milk. But if the pregnant mother is obese, for example, doesn’t she already have the maternal reserve?

And what does "calories-in/calories-out" have to do with this fuel partitioning as well? Are we that naive to think there has to be a conscious, or behavioral, manipulation of caloric intake in order for us to gain the appropriate weight for breastfeeding as well as embryological and fetal development?

Why are we this naive when it comes to obesity and leanness?

Sugar --> Diabetes, Cancer, Obesity, Metabolic Syndrome?

2011-04-13T08:51:00.000-07:00

In this Sunday's New York Times Magazine, Gary Taubes writes about Sugar and whether it has unique metabolic effects apart from "empty calories" (as we're often told by public health authorities).

The article is now available online. Must read.

In a related topic, which I think ties in nicely with the article above: I had a message board assignment this week on carbohydrates and diabetes. I thought I would share the commentary, questions, and my responses, below:

From the Moderator:

Carbohydrates sure do get a bad rap. We hear it all the time, “don’t eat “carbs” because you will gain weight.” The Atkins diet is a famous low carb diet that has gained attention from mass amounts of people. Often times, when one food group is severely limited, people consume other food groups in excess. For example, cutting out carbs may cause a person to consume more fat which can be just as harmful. Many people talk about the wonders of low carb diets and how they trick your body into extreme weight loss. While cutting out carbs will likely result in weight loss, it can send the body into a state of ketosis. People are confused when it comes to the topic of carbohydrates, and the truth is, they are an important part of a balanced diet--especially for diabetics. Carbohydrates are the body’s primary source of energy, and as health professionals, it is crucial to emphasize the healthy sources of carbohydrates. Diabetes is growing in epidemic proportions, and patients should be educated to distinguish between a “good” carb and a “bad” carb. According to the article we need to get away from the terms of what is “good” and “bad” and educate people on what is healthy. It is important that diabetic patients understand the glycemic index and how foods affect the body’s glucose levels.

Click on the following link to read the article:
http://www.buffalonews.com/life/health-parenting/health/article384918.ece

1. What is the effect of a low carbohydrate diet on the body, and why do people rely on it for weight loss? Is this a harmful approach for diabetics, Why or Why not?

2. Distinguish the difference between a complex carb and a simple carb.

3. Are potatoes that bad for us? The article insinuates that baked potatoes are not the best choice, would you agree with this statement?

4. Define the terms: glycemic index and glycemic load and explain how we can use these terms to help diabetic patients improve their diets.

5. Evaluate this statement to be true or false and justify your answer: Eating too much sugar causes diabetes.

My Response:

First, I want to address the commentary that preceded the article link and questions.

“Often times, when one food group is severely limited, people consume other food groups in excess.”

Agree. Dietary trade-offs are an inescapable reality.

“For example, cutting out carbs may cause a person to consume more fat which can be just as harmful.”

I feel like this needs to be substantiated with evidence. For example, much of the research conducted in the last ten years in randomized-controlled trials of low-carbohydrate (ad libitum) diets compared to low-fat (calorie-restricted) diets have observed beneficial effects in terms of both weight loss, lipids, and other risk factors for the subjects adhering to the low-carbohydrate diet. Further, most studies show that when people replace saturated fats with carbohydrates, their health prospects worsen.

“Many people talk about the wonders of low carb diets and how they trick your body into extreme weight loss.”

I guess this is true, but for the people that claim that a low-carbohydrate diet “tricks” your body into weight loss, they’re missing the point. For many people going on a low-carbohydrate diet, they shift toward oxidizing relatively more fat for fuel than they have been accustomed to on a high-carbohydrate diet (which can elevate insulin, which promotes fat storage and inhibits fat mobilization). I would argue that when these people lose weight, they’re shedding the excess fat accumulation that has occurred in large part to the quality of their diet. They’re not losing fat because they’re losing weight; they’re losing weight because they’re losing fat.

“While cutting out carbs will likely result in weight loss, it can send the body into a state of ketosis.”

Ketosis is a natural physiological state in the body. In fact, most of us are technically in ketosis overnight (when we sleep) and our brains are primarily using ketones for fuel. The ketone level in our bodies upon waking will be around 5 mg/dl - and on an severely restricted carbohydrate diet (i.e., Atkins induction) the level is around 5 to 20 mg/dl. While you are reading this, it is likely you are in ‘ketosis,’ which is another way of saying you’re burning fat for fuel.

The ketone level in diabetic ketoacidosis typically exceeds 200 mg/dl.

Many diets that are low-carbohydrate are going to be more ketogenic in nature which is not a bad thing and is quite normal from an evolutionary standpoint. It's basically being more 'fat adapted' and using more of your body fat for fuel rather than glucose derived from dietary carbohydrates, which is "the body's preferred fuel" because it wants to get rid of it, i.e, bring blood glucose back to stable levels.

“Carbohydrates are the body’s primary source of energy, and as health professionals, it is crucial to emphasize the healthy sources of carbohydrates.”

This is false. The primary source of energy in the body is derived from fatty acids. You could argue that the body needs glucose to survive, and is vitally important, however there is no dietary need for carbohydrates. They are a nonessential exogenous nutrient.

As health professionals, we should emphasize healthy sources of carbohydrates, over what? Unhealthy sources of carbohydrates? Or emphasize them over all other foods in general? How would you define healthy sources of carbohydrates?

“Diabetes is growing in epidemic proportions, and patients should be educated to distinguish between a “good” carb and a “bad” carb.”

Agree, and at its core, I would say that diabetes is a disorder of carbohydrate metabolism. Even if you’re trapped in the diet-heart paradigm, restricting or virtually eliminating carbohydrates in a diabetic patient has a greater benefit-to-risk ratio.

Again, I would appreciate a definition of what a good carb is and a bad carb is going forward.

1. What is the effect of a low carbohydrate diet on the body, and why do people rely on it for weight loss? Is this a harmful approach for diabetics, Why or Why not?

I would say that most people rely on a low-carbohydrate diet for weight loss because it gets them the results they want. When they stay on a low-carbohydrate diet, they maintain their weight loss from the low-carbohydrate diet, and when they stray from it, i.e., increase their carbohydrate consumption, they gain the weight they lost back, so in that sense, they rely on a low-carbohydrate diet because it’s what makes them lose weight and what keeps it off.

The effect of a low-carbohydrate diet on the body, while this depends on the level of carbohydrate restriction, especially on people who are overweight and obese, generally speaking, is that insulin levels are lowered. Elevated insulin, when working properly, is a signal that there are elevated levels of glucose in the body. Insulin drives nutrients into their tissues, including adipocytes. Insulin also inhibits lipolysis, or the breakdown of triglycerides to be used for fuel. Carbohydrates, especially the most refined and easily digestible, drive insulin secretion. When carbohydrates are removed, insulin levels are lowered and the opposite effect occurs; less nutrients are being partitioned to the fat cells and we observe an increase in lipolysis.

A low-carbohydrate diet is generally not harmful for diabetics, however, since low-carbohydrate diets actually correct some of the abnormalities in diabetic patients (i.e., a low-carbohydrate diet is healthful for diabetics), one of the problems is a reason for contraindicating medications such as insulin and high blood pressure medications because a low-carbohydrate diet has an anti-hypertensive effect and creates a reduced requirement for insulin.

Also, I wanted to add here a quote from the article and my response:

“Everyone agrees that replacing saturated fats with unsaturated fats is good, but citing numerous studies that show an elevated risk of heart disease when carbohydrates replace saturated fats, scientists have been rethinking the role of carbs in cardiovascular disease.”

Everyone does not agree. There are people who believe that saturated fats from animal sources are just as good, if not more beneficial, than unsaturated fats.

Also, it’s not as clear-cut as replacing one type of fat for another. For example, lard, yes, lard, is mostly monounsaturated fat. And the saturated fat in lard has qualities that raise HDL and have no effect on LDL.

Gary Taubes wrote about this in Good Calories, Bad Calories:

"Consider a porterhouse steak with a quarter-inch layer of fat. After broiling, this steak will reduce to almost equal parts fat and protein. Fifty-one percent of the fat is monounsaturated, of which 90 percent is oleic acid. Saturated fat constitutes 45 percent of the total fat, but a third of that is stearic acid, which will increase HDL cholesterol while having no effect on LDL. (Stearic acid is metabolized in the body to oleic acid, according to Grundy’s research.) The remaining 4 percent of the fat is polyunsaturated, which lowers LDL cholesterol but has no meaningful effect on HDL. In sum, perhaps as much as 70 percent of the fat content of a porterhouse steak will improve the relative levels of LDL and HDL cholesterol, compared with what they would be if carbohydrates such as bread, potatoes, or pasta were consumed. The remaining 30 percent will raise LDL cholesterol but will also raise HDL cholesterol and will have an insignificant effect, if any, on the ratio of total cholesterol to HDL. All of this suggests that eating a porterhouse steak in lieu of bread or potatoes would actually reduce heart-disease risk, although virtually no nutritional authority will say so publicly. The same is true for lard and bacon."

And how about human fat? What are we made of?

Ren et al. (2008): Human adipose tissue is composed largely of triglycerides. Seven fatty acids predominate as follows (number of carbons:number of double bonds, typical abundance): myristic (14:0, 3%), palmitic (16:0, 19–24%), palmitoleic (16:1, 6–7%), stearic (18:0, 3–6%), oleic (18:1, 45–50%), linoleic (18:2, 13–15%), and linolenic (18:3, 1–2%) ( 22, 23). These fatty acids account for well over 90% of the fatty acids in human adipose tissue. Odd-carbon fatty acids, longer chain fatty acids, and shorter chain fatty acids account for the remainder. Each of these less-abundant fats individually contributes much less than 1% ( 22).

So our adipose tissue is comprised of the same composition of the foods the public health authorities tell us to avoid. Interesting?

2. Distinguish the difference between a complex carb and a simple carb.

Complex carbohydrates are generally a polymer, containing multiple mono-saccharides linked together. Simple sugars generally refer to the mono-saccharides occurring in foods individually, i.e., no polymer.

Generally, simple and complex carbohydrates refer to sugars and starches, respectively.

Complex carbohydrates, in and of themselves, do not significantly affect the absorption rate of carbohydrates in the body.

3. Are potatoes that bad for us? The article insinuates that baked potatoes are not the best choice, would you agree with this statement?

I feel a little like Bill Clinton here, but, define “us”?

For a metabolically sound, lean individual, a potato may not be particularly deleterious.

If you were to tell the Kitavans that eating tubers were going to compromise their metabolic systems, they would probably argue otherwise and have reportedly lived on a diet high in tubers and starches:

From WholeHealthSource.com:

There's a lot to be learned from the Kitava study. Kitavans eat a diet of root vegetables, coconut, fruit, vegetables and fish and have undetectable levels of cardiovascular disease (CVD), stroke and overweight. Despite smoking like chimneys. 69% of their calories come from carbohydrate, 21% from fat and 10% from protein. This is essentially a carbohydrate-heavy version of what our paleolithic ancestors ate. They also get lots of sunshine and have a moderately high activity level.

Eating potatoes is eating akin to eating glucose. Yams and sweet potatoes, for instance, contain very little amounts of fructose, which may be the necessary agent - in excessive amounts - in causing metabolic disease in otherwise healthy individuals and further exacerbating it in the rest of the population.

For a diabetic, who by definition, has a disorder of carbohydrate metabolism, a potato may not be a good choice at all. Diabetics have a hard time clearing glucose, so it would probably be wise not to challenge the system with a bolus of carbohydrate in any form.

For a diabetic, I would agree that a baked potato is a bad choice of food to eat. For otherwise healthy, lean individuals, I would certainly still argue that potatoes are not “the best choice,” but I also believe that these people can consume this food without inducing damage (but would have to be taken in the context of the exclusion of excess fructose; sugar and HFCS among the major culprits).

4. Define the terms: glycemic index and glycemic load and explain how we can use these terms to help diabetic patients improve their diets.

From The Glycemic Index website (www.glycemicindex.com):

The glycemic index or GI describes this difference by ranking carbohydrates according to their effect on our blood glucose levels... The glycemic index (GI) is a ranking of carbohydrates on a scale from 0 to 100 according to the extent to which they raise blood sugar levels after eating. Foods with a high GI are those which are rapidly digested and absorbed and result in marked fluctuations in blood sugar levels. Low-GI foods, by virtue of their slow digestion and absorption, produce gradual rises in blood sugar and insulin levels, and have proven benefits for health.

Measuring the GI:

To determine a food's GI rating, measured portions of the food containing 10 - 50 grams of carbohydrate are fed to 10 healthy people after an overnight fast. (From wikipedia: The glycemic index of a food is defined as the area under the two hour blood glucose response curve (AUC) following the ingestion of a fixed portion of carbohydrate (usually 50 g).) Finger-prick blood samples are taken at 15-30 minute intervals over the next two hours. These blood samples are used to construct a blood sugar response curve for the two hour period. The area under the curve (AUC) is calculated to reflect the total rise in blood glucose levels after eating the test food. The GI rating (%) is calculated by dividing the AUC for the test food by the AUC for the reference food (same amount of glucose) and multiplying by 100 (see Figure 1). The use of a standard food is essential for reducing the confounding influence of differences in the physical characteristics of the subjects. The average of the GI ratings from all ten subjects is published as the GI of that food.

According to Wikipedia:

The glycemic load (GL) is a ranking system for carbohydrate content in food portions based on their glycemic index (GI) and the portion size. Glycemic load or GL combines both the quality and quantity of carbohydrate in one ‘number’. It’s the best way to predict blood glucose values of different types and amounts of food. The formula is: GL = (GI x the amount of available carbohydrate) divided by 100.

In theory, glycemic index and glycemic load can help diabetics because they help determine what the impact of a particular food will be in the body, and for diabetics especially, they should want to avoid any food that is going to significantly elevate their blood glucose.

One of the severe limitations of glycemic index and glycemic load is that it doesn’t properly account for the amount of fructose consumed in the diet. For example, sucrose (glucose-fructose) has a lower GI than a potato, but I would rather have people eating potatoes than sucrose, if I had to make the choice.

From the subject article: “By contrast, fruit sugars are simple carbs, but they minimally impact blood sugar levels and insulin production.”

Again, we’re talking about fructose here, which many argue is a dose-dependent hepatotoxin. It minimally impacts blood sugar levels because fructose travels straight to the liver, and when consumed in excess, it can create the metabolic damage that is found in metabolic syndrome, insulin resistance, and diabetes.

5. Evaluate this statement to be true or false and justify your answer: Eating too much sugar causes diabetes.

I would say that eating too much sugar [sucrose/HFCS] is a cause of type 2 diabetes. Type 1 diabetes is less clear, but it is possible that excess sucrose can create, promote, or exacerbate an autoimmune disorder in the body.

To say that excess sugar is a cause of diabetes because anything in excess leads to weight gain, which leads to diabetes, wildly misses the point.

There are unique effects of fructose on human metabolism that implicate its consumption in the development of metabolic syndrome, which is virtually synonymous with insulin resistance, which is virtually synonymous with type 2 diabetes. The mechanisms of action are observable and have been shown to uniquely contribute to hepatic insulin resistance, leading to type 2 diabetes, among other issues.

And to come full-circle, this final question is comprehensively addressed in Gary Taubes's New York Times Magazine article (set to print: April 17, 2011) and Robert Lustig's Sugar: The Bitter Truth lecture.

Gary Taubes: The Complications of Cholesterol

2011-04-11T16:55:00.000-07:00

In 2005, my wife and I interviewed Gary Taubes at his apartment in New York City. We were planning on doing a documentary on diet and health, and during this time (January 2005-May 2005) I went on a fast food diet. I was basically doing Fat Head before (I think) Fat Head. (Tom Naughton did an incredible job.)

Whether the documentary will eventually see the light of day is unclear, but I wanted to share some clips on the blog that we produced along the way.

"In the case of diet and heart disease, Ancel Keys's hypothesis that cholesterol is the agent of atherosclerosis was considered the simplest possible hypothesis, because cholesterol is found in atherosclerotic plaques and because cholesterol was relatively easy to measure," writes Gary Taubes in Good Calories, Bad Calories (GCBC). "But as the measurement technology became increasingly more sophisticated, every one of the complications that arose has implicated carbohydrates rather than fat as the dietary agent of heart disease." In this 2005 interview, before the publication of GCBC, Taubes discusses the cholesterol story. A more comprehensive account can be found in Chapter 9 of GCBC: Triglycerides and the Complications of Cholesterol

Below is a transcription:

[00:02:30.06] It's so bizarre, that when you realize what's happening -- I'm going to try and tell it. See if I can get this straight. They come up, they have this guy John Gofman, Berkeley, has this device that can fractionate lipoproteins. Basically, it can take the lipoproteins, which are the carriers of the cholesterol, from your blood. Say you've got so much LDL, so much VLDL, very low density, so much IDL.

[00:03:02.17] And look, VLDL seems to be as much of a risk factor if not more. If you believe his equations, it's a greater risk of heart disease than LDL. And VLDL carries the triglycerides. Then another group of scientists, Pete Ahrens and some other people, Margaret, whose name I'm going to forget at the moment, who really did great work and I shouldn't forget her name, and it's embarrassing.

[00:03:30.20] Margaret [Albrink] got marginalized. She was at Yale and she took a job at West Virginia and it was like 'poof' -- West Virginia, who cares? Her husband got a job there, we don't care what you have to say. Anyway, they pushed. They said triglycerides, they're as great a risk factor as cholesterol. The studies show it. So in '67, this guy Donald Fredrickson and Robert Levy and a guy named Lees, they're at NIH and they put this five part series in the New England Journal of Medicine on -- it's called lipoprotein disorders, basically, and they classify them as five different lipoprotein disorders.

[00:04:04.02] Some of them are low LDL and some of them are low VLDL or high VLDL or high triglycerides. And they want to know how these things, the portion in the population at large, because they've just been studying patients who were referred to them at NIH. Frederickson and Levy are big deals at NIH. Back then it was the National Heart Institute instead of NHLBI.

[00:04:26.08] So they get funding to give money to Framingham and five other big population studies, to see how much LDL -- how these lipoprotein disorders appear in the population. For the first time ever, these studies are going to measure LDL and VLDL cholesterol, total cholesterol. Nobody's ever measured VLDL or triglycerides in large populations. It's never been done. Now for the first time ever these big studies like Framingham have the money to do it.

[00:05:01.23] Frederickson, Levy and Lees also give them a ... they come up with a technology that makes it relatively inexpensive to measure these things. You don't need this huge equipment that Gofman had at Berkeley. So they go off to do this study and the problem is you can't measure LDL directly. Don't know the details why, but it can't be done. What you have to do is measure total cholesterol, triglycerides, and HDL and you do this equation and you calculate LDL.

[00:05:31.28] So they have to measure HDL also. Now, since 1950 or '51, I forget which, people have been saying HDL is the single most important risk factor for heart disease, and it's been ignored because if HDL is high, that means it's good for you. It's part of total cholesterol and Ancel Keys has been saying that total cholesterol is bad for you and that has to be low. And how do you make sense of part of total cholesterol being good, when total cholesterol is bad. And this is very confusing.

[00:06:01.05] So HDL has been ignored. Now they have to measure HDL in order to come up with the number for LDL. The head of -- the guy who does the biostatistics for Framingham and NIH and all these studies [Tavia Gordon] decides he's got the HDL data, this is now mid-70s, let's look at it. So he looks to see what kind of risk factor HDL is and lo and behold, HDL is four times a better predictor of heart disease than LDL. Total cholesterol, he finds out, is meaningless.

[00:06:30.23] Total cholesterol doesn't predict heart disease. This is what's being measured. It's meaningless. LDL is a "marginal predictor." This is the phrase they use. And HDL, four times better. Four times more accurate at predicting heart disease. If HDL is low, that's a powerful indicator that you're going to get heart disease. And on top of it, for women, HDL is the only number that matters. So in 1976 they publish these articles. Two articles in particular.

[00:07:01.23] One from Framingham alone. And one from Framingham and the other five groups together. Two different types of studies. Both of them say the same thing. Total cholesterol is meaningless. LDL is a marginal predictor of heart disease risk. HDL is the single best predictor. And triglycerides are also a good predictor. Now the problem is, you have a half billion dollars of studies dedicated to lowering total cholesterol, the LRC, Lipid Research Clinics trial, and MRFIT trial, are both aimed at lowering total cholesterol.

[00:07:36.22] So what they say, and you see this in the papers. They say total cholesterol is meaningless but LDL makes up the biggest part of total cholesterol and we know that LDL is a marginal predictor. So we're going to play up how good LDL is. And as you watch the papers the adjectives used to describe it as a risk factor get more and more ... zealous, as the time ... it goes from being marginal to robust, without the data ever changing.

[00:08:08.12] And we're going to say everything we had said about total cholesterol, all the studies from the 1950s and 1960s, the famous seven countries studies, had all measured total cholesterol. They say "everything we say about total cholesterol is now going to apply to LDL cholesterol. And the MRFIT?? study and the Lipid Research Clinic study we're going to say are aimed at lowering LDL cholesterol.

[00:08:29.23] That's what we're trying to do because LDL is a predictor." Now the problem is, that in the clinic, where doctors all around the world are measuring total cholesterol, they're measuring something that's meaningless. But you can't measure LDL cholesterol. They don't have a test for it. You've got to measure all these other things and calculate LDL cholesterol which is too difficult to do.

[00:08:56.20] And it's not the kind of thing that they can tell doctors to do, because they're going to have all kinds of problems with mistakes and errors, and all these things that have to be worked out that they can't do. Meanwhile they have the doctors measuring total cholesterol. They're doing it all over the world. They say, in the clinic -- and you read this in the articles, I'm not making this up -- in the clinic, total cholesterol is a good enough substitute for LDL cholesterol that people can keep measuring total cholesterol and use that as their guide. So the study says that total cholesterol is meaningless.

[00:09:29.27] In the scientific discussion we're going to replace LDL ... total cholesterol with LDL cholesterol, because that's a marginal predictor, and then in the clinic we're going to re-replace LDL cholesterol with total cholesterol going back to the meaningless predictor on the basis that it's a close enough substitute for LDL that it'll suffice. So within three years, they can say that doctors should continue measuring total cholesterol, even though they now know that total cholesterol is meaningless. Meanwhile HDL and triglycerides just still continue to get left out totally because what do you do about that?

[00:10:00.15] And it's four times the predictor. [interviewer] And the problem ... the interesting thing is ...

Robert Lustig: Do Low Insulin Levels Cause Low-Carbohydrate Diets?

2011-04-04T06:07:00.000-07:00

In a January episode of The Livin’ La Vida Low Carb (LLVLC) Show (Episode 429) with Jimmy Moore, Robert Lustig was the featured guest on the pocast, and what transpired was particularly illuminating for several reasons. I want to share one of them below.

(Dr. Lustig’s Sugar: The Bitter Truth lecture is approaching 1,000,000 views on youtube, and justifiably so.)

During the podcast, Jimmy asked Dr. Lustig about a study he had mentioned on a prior podcast of LLVLC (Episode 378):

Lustig: That was a pilot study. Everyone got drugged. It was not controlled it was not blinded and we went on a fishing expedition in which we gave people a drug that blocked insulin release called Octreotide. Octreotide is usually used to treat acromegaly, which treats growth hormone (GH) excess because it blocks growth hormone release as well as insulin release and so people who have pituitary tumors and oversecrete GH are on this drug. We used [Octreotide] instead to block insulin release and what we found was there was a group, out of the 44 we treated, 8 of them responded amazingly well.

Lustig: Their appetites went away, they stopped snacking between meals, their carbohydrate intake went down like a stone from 900 calories a day from carbohydrate to 350. They felt better and they lost a lot of weight. 12.6 kg in 24 weeks. And we didn't tell them to change the composition of their diet or to lose weight, they just did it, all by themselves.

Lustig: This was kind of amazing. But it only happened in eight out of the 44 study participants. It was cause-and-effect in the eight, or 18% of the subjects, because we could look before and after the treatment, and it turned out that the 18% who responded, all had one thing in common: all hypersecreted insulin. Their insulin response to glucose were all the same as each other and very different from the 36 who did not.

Lustig: So what we end up doing in this study was finding a subset of people who hypersecrete insulin, who oversecrete insulin for the same amount of glucose. Now, those people are walking the streets, they don’t know who they are, they don’t know what they look like. The doctors taking care of them don’t know who they are either. But we’ve shown in a clinic, where we do OGTT, as routine in our clinic, because that’s how we sort patients.

Lustig: This is going back to the first point; not everybody’s the same. We are not the same. Obesity is not a disease, it is a phenotype of many different pathologies. What we did in the study was we found one pathology. We found one reason for obesity. And we found one treatment that worked for obesity.

Lustig: You might say that you found the data post hoc, it wasn’t randomized, it wasn’t controlled, it wasn’t blinded. To which I would say: We did it again. We did it again in a randomized, double-blind, placebo-controlled fashion in a clinical trial. … The same group of people responded; the same group of people who hypersecreted insulin to start with.

I think this is fascinating for many reasons, but something that should not be overlooked is the pattern, or arrow of causation, that appears to be occurring in the subjects who are responding to the Octreotide.

Normally, we, the proponents of the carbohydrate/insulin hypothesis, would say that a low-carbohydrate diet causes lower levels of insulin. However, what Lustig has really shown in the studies above is that the causality can be flipped: lower levels of insulin can cause a low-carbohydrate diet.

As Dr. Lustig said, “They had a change in macronutrient preference. They were carboholics. We blocked their insulin, and now, they couldn’t care less about carbohydrate. By getting their insulin down, we changed what foods they ate.”

Acutely, when we eat a meal rich in carbohydrates, our insulin goes up in response. For the uninitiated, elevated levels of insulin in the body used to be a strong clue that there are an abundance of carbohydrates in the bloodstream. Insulin tells the muscles to burn carbohydrate for fuel and for the adipocytes to store nutrients as fat and inhibit the release of fat into the bloodstream. Why waste any stored fat when we have an abundant supply of energy in the bloodstream? Also, we know that elevated blood sugar is not a state we want to be in for several acute and chronic reasons, so the priority becomes clearing carbohydrates.

I say “used to be a strong clue,” because more and more people are becoming chronically hyperinsulinemic, insulin resistant, and type-2 diabetic.

Acute 'hyperinsulinism' may be seen as something physiological and not necessarily pathological: we eat like the Kitavans for a meal, lots of carbohydrates from glucose sources, and our insulin goes up, we burn carbohydrates for fuel, we temporarily inhibit lipolysis and store fat, but over time (perhaps overnight) we are ultimately homeostatic: our weight may fluctuate, but not by much, and we remain relatively weight stable and relatively lean.

Chronic hyperinsulinemia is another, and pathological, story. If you have elevated insulin levels most of the time, our bodies don’t know the difference between our acute response to a carbohydrate-rich meal and the chronic condition of hyperinsulinemia, so the response in the body is relatively the same. Fuel is partitioning in the same manner where insulin is telling muscles to burn carbohydrate; and fat tissues to store fat and protein, and to hang on to it.

Carbohydrates become the body’s food of choice. A hyperinsulinemic state can sap glucose from the energy supply because it ‘thinks’ glucose is in high supply. But it’s not. You should be burning free fatty acids (FFAs) for fuel while glucose is in relatively short supply. Not so for people who are chronically hyperinsulinemic. They crave carbohydrates because that’s what they can utilize for fuel and it is also what happens to be in short supply because of the way their fuel is partitioned.

The obese, hyperinsulinemic, will eat; store a little more of it as fat, and their insulin remains relatively elevated for longer periods of time; and they eat a little more, and they store a little more and burn a little less than a healthy, lean individual who is relatively insulin sensitive, a ‘hypo-secreter’ of insulin, if you will. And so the fat begins to accumulate progressively on the fat person, while the lean person remains in "energy balance."

The fat person isn’t fat, and isn’t getting fatter because he’s eating more; the fat person was, and is, eating more because he’s fat, and getting fatter. (Thank you, Gary Taubes, who would like to thank George Wade, who should probably thank Hugo Rony back to 1940. This isn't a new observation, but most people, i.e. the conventional wisdom interpret it from the wrong side of the 'arrow' of causality, at least when it comes to us weak-willed humans.)

The healthy, lean individual isn’t lean because he’s eating less; he’s eating less because he’s lean. The healthy person will eat; store fat, and then burn fat, so that he is in “caloric balance,” but calories really don’t have anything to do with it.

As Lustig noted, essentially the fundamental way an obese, hyperinsulinemic individual gets fat out of the fat tissue is to lower insulin levels. Octreotide did the trick in his patients.

Low-carbohydrate, slow-carbohydrate, and safe-carbohydrate (Lustig: “I'm for safe carb, rather than low-carb, as a generalization”) diets, for example, can do the trick as well.

And, just as Lustig pointed out that when he blocked insulin secretion in subjects who otherwise secreted too much insulin and they went from “carboholics” to ostensible Atkins-dieters; the logic would hold that if you took a healthy individual and gave them a drug (insulin is on the nose) that kept insulin elevated, we would see the opposite: we would induce “carboholism.”

We're not just playing with words when we observe that, people who go on low-carbohydrate diets have lower levels of insulin, and people on high-carbohydrate diets have higher levels of insulin, and we conclude:

Lower levels of insulin cause low-carbohydrate diets...

...and...

...Higher levels of insulin cause high-carbohydrate diets.

And both may be a "vicious" cycle where lower levels of insulin leads to a lower-carbohydrate diet, which lowers insulin levels, which leads to a lower-carbohydrate diet.

The same holds true inversely: higher levels of insulin leads to a higher-carbohydrate diet, which raises insulin levels, which leads to a higher-carbohydrate diet.

HIT, IF, HIIT and body fat

2011-03-24T11:05:00.000-07:00

I have been a proponent of High Intensity Interval Training (HIIT), Intermittent Fasting (IF), and High Intensity Training (HIT) as methods to improve my body composition.

I’m seemingly reading an article every week about the benefits of Tabata training, or HIIT, especially when checking out the tweets of @HealthHabits. Here are a few links that I have ran across:

You Don’t Know HIIT

HIIT is your best choice for burning off Belly Fat

10 more reasons to love High Intensity Interval Training

HIIT v.s. Type 2 Diabetes

Take a look at the laundry list of benefits from the 10 reasons post by Health Habits:

HIIT was better than the standard multidisciplinary approach (exercise, diet and psychological support) at helping overweight kids reduce their cardiovascular risk factors. Here’s the study
HIIT can prevent cardiac death in type 2 diabetic individuals. Here’s the study
HIIT should be a required treatment for all Metabolic Syndrome patients. 16 weeks of HIIT training significantly reduced their risk of cardiovascular disease, in terms of improved VO2max, endothelial function, blood pressure, insulin signaling, and plasma lipid composition. Here’s the study
HIIT substantially improves insulin action. Say bye-bye to type 2 diabetes & metabolic syndrome. Here’s the study
HIIT increases levels of HDL cholesterol – that’s the good cholesterol. Here’s the study
HIIT improves the HRR (Heart Rate Recovery – a measure of how quickly your heart returns to normal post-exercise)) in already well-trained cyclists. Here’s the study
HIIT drastically improves cardiovascular function (V02max) in patients with COPD (Chronic Obstructive Pulmonary Disease) Here’s the study
Interval training produced a 302% greater increase inV02max when compared to a long, slow distance training protocol. Here’s the study
HIIT significantly improved the aerobic fitness of a group of prepubescent children (aerobic fitness measured by peak oxygen consumption Here’s the study
HIIT improves the erectile function of hypertension patients Here’s the study fellas

What’s not to like?

Moving on to Intermittent Fasting (IF), Martin Berkhan has an informative site, Leangains, where much of the success of his program he attributes to IF.

Here are a few of his posts on IF:

Intermittent Fasting For Weight Loss Preserves Muscle Mass?

Fasted Training Boosts Muscle Growth?

Brief Summary of Popular Approaches to Intermittent Fasting

Dr. Eades also wrote a two part post on Tim Ferriss’ blog:

Real Life Extension: Caloric Restriction or Intermittent Fasting (Part 1)

Real Life Extension: Caloric Restriction or Intermittent Fasting (Part 2)

From Eades in Part 1:

Intermittent fasting (IF) reduced oxidative stress, made the animals more resistant to acute stress in general, reduced blood pressure, reduced blood sugar, improved insulin sensitivity, reduced the incidence of cancer, diabetes, and heart disease, and improved cognitive ability. But IF did even more. Animals that were intermittently fasted greatly increased the amount of brain-derived neurotrophic factor (BDNF) relative to CR animals. CR animals don’t produce much more BDNF than do ad libitum fed animals.

Eades concludes in Part 2:

It’s looking like the intermittent fast is another of those ideas in science that looks good in animal studies then not so good in human studies, proving once again that rats and mice aren’t simply furry little humans. And it appears – for humans, at least – that the intermittent fast is indeed beginning to look like the reality of a late-night gimmicky infomercial: long on promises, short on delivery. I suspect that it is also a cautionary tale about the applicability of caloric restriction studies to humans.

Sorry to be the bearer of bad news, but that’s the way science sometimes works. Lab results and reality are often two different animals.

Then there is Body by Science (by Doug McGuff), Slow Burn Training (by Fred Hahn), and High Intensity Training (The HIT FAQ has been around for quite a while) and you could argue that HIT can trace its origins back to the 6th century BC and Milo of Croton:

Legends say he carried his own bronze statue to its place at Olympia, and once carried a four-year-old bull on his shoulders before slaughtering, roasting, and devouring it in one day. He was said to have achieved the feat of lifting the bull by starting in childhood, lifting and carrying a newborn calf and repeating the feat daily as it grew to maturity. (Wikipedia)

Milo was using the principles of progressive overload training, which is essentially the foundation of any HIT program. You need to put the muscle under enough load that it induces a compensatory response that ultimately builds more muscle.

If you read Body by Science, the author claims that you can achieve the following in 12 minutes a week:

Build muscle size and strength
Optimize cardiovascular health
Ramp up your metabolism
Lower cholesterol
Increase insulin sensitivity
Improve flexibility
Manage arthritis and chronic back pain
Build bone density
Reduce your risk for diabetes, cancer, heart attack, and more

I don’t think it would be a misrepresentation to say Slow Burn Training with Fred Hahn seems to incorporate many of the same principles as Body by Science with Doug McGuff. Mr. Hahn included Body By Science and a book by Matt Bryzcki - who had a big hand in the HIT FAQ - in his top ten strength training books.

Admittedly, I tend to gravitate toward these things because of the purported changes they can induce in the interior milieu.

You are not what you eat, you are what you do with what you eat.

With exercise, it’s not so much about what we do or how much we do it, it’s about how our body responds to the stimulus it is given that we should care about.

So I was listening to a podcast by Jimmy Moore called Low Carb Conversations (you down with LCC?) with Tom Naughton as a guest, who started talking about advice given to people who are going through a weight loss stall while dieting or on a low-carb diet.

Tom had some great points to make (paraphrasing a bit):

Naughton: You become fat for a biochemical reason. And right now, you are as fat as you biologically need to be.

Because of the hormone balance [or imbalance, short-term leading to long-term], you are as fat as you need to be to allow the body to supply itself with fatty acids.

You can continue doing things with your diet, maybe with some HIIT, [or HIT] maybe with IF, but all those things are going to accomplish is to change your biochemistry in such a way that your body is willing to live with less body fat.

When I thought about what Tom was saying, I thought about it in this context: even engaging in HIT, HIIT, and IF is trying to consciously manage our weight, so long as we essentially have to keep these things up in perpetuity in order for them to have lasting effect.

They induce internal changes, but they are fleeting if we don’t continue to get to the weight room and overload our muscles, or sprint in between telephone poles for the rest of our lives. Perhaps our ancestors didn’t have “conscious control” over these behaviors; maybe they had to run from a predator or two, or chase down their dinner, and they had to ‘lift things up and put them down’ out of necessity, but having to rely less on these forms of movement and eating patterns most likely has next to nothing to do with why we get fat as a species.

The key is almost assuredly diet - and you could argue that we need to consciously control what we put into our shopping carts in modern times - however, after this decision is made and we choose to eat only protein and fat from unadulterated, naturally-occurring animals for example, our weight should settle to a relatively healthy level (if we have no underlying metabolic, hormonal, enzymatic, etc. damage) unconsciously.

We don't need to consciously eat more or less. We don't need to consciously move more or less. The quality of the food will dictate our normality. Not quantity. Quantity is a side-effect of quality. We eat less and move more because we're getting leaner, not the other way around.

As you move farther back in time, it becomes progressively more difficult to make the argument that we had conscious control over what we ate. We ate what was available, and while this doesn't imply that whatever was available was necessarily good for us, it does suggest that if the overwhelming majority of the population did not get fat and sick, the quality of the diet probably played the starring role in the health of most societies.

Animals in the wild don't seem to become chronically fat until they eat food they are not accustomed to and almost assuredly not well-adapted to eat. There was a recent article discussing captive gorillas succumbing to human diseases of civilization, notably obesity and heart disease. What happened when the gorillas were taken off of their captive diet of “high vitamin, high sugar, and high starch foods to make sure they got all their nutrients.” Can you say iatrogenic? What happens when you provide an environment for gorillas in which they can only access the foods they presumably could in the wild?

Going back to this natural diet has changed gorilla behavior. Before, gorillas only ate during a quarter of their day because the food was so packed with nutrients. Now at Cleveland, they spend 50-60 percent of their day eating which is the same amount as in the wild. With all this extra eating, the gorillas have doubled their caloric intake, yet at the same time have dropped 65 pounds each. This brings their weight more in line with their wild relatives.

Getting back to HIIT, HIT, and IF, it's not likely that these were the determining factors for preventing or acquiring obesity and western disease if they needed to be under our conscious control. They still may be useful, where you could make the argument that sprinting every once in a while, walking often, missing a few meals here and there are a big part of our history and part of what makes us human. This is Sissonian philosophy at its finest and it’s probably not a bad idea to emulate this.

Now back to Mr. Naughton:

Naughton: All of us are going to hit a certain level of body fat that our bodies do not want to drop below. If that happens to be 20% body fat and you just can't get below it, then focus on the improvements that you've already made, focus on how much better you feel, but understand that depending upon how much metabolic damage you've already done, you may never get to the level of leanness that you had when you were 20. It just might not happen.

As I’ve heard Gary Taubes say: a restricted-carbohydrate diet will help you get to
the leanest you can naturally be, but the leanest you can be may not necessarily be lean.

I want to point out that it's not necessarily phrased in the right context that your body doesn't want you to be leaner than 20%, where the implication is that we seem to be fighting our bodies (and when people invoke 'set point,' the implication is that we're fighting our brain), rather this is where our body fat "settles" at when we have our ducks in a row to the best of our ability, i.e., a good diet, HIIT, HIT, and IF and it settles where it settles. We most likely have a settling point, not a set point.

The way our settling point would lower is to help remove whatever is damming up the system. Might be that insulin is overly secreted and we can't get it in check with
conventional means, or that we’re resistant to insulin, or it could be another factor or force within that is contributing to the lake overflowing, or in the case of humans, over-sized and/or over-numbered, fat cells.

This is what many people in the CrossFit community, and the bodybuilding community come to grips with when they may settle at 14% body fat, and then they train regularly and settle around 10% (so long as they continue their regimen) and then they come to guys like me, but more often and recognizably to someone like Robb Wolf and say "how
do I lean-out?" and the morbidly obese person might overhear the conversation and will think this person must be on drugs or has an eating disorder. They might be right.

Now the 10% dude starts focusing on getting more sleep, getting more sunshine, doing heavier lifting and lower intensity workouts and restricting calories and their body fat may settle around 6%.

So they remain at 6%, and their body fat settles at this level, which means the competition of forces leads to a fat mass that comprises 6% of this person's total body weight. They are dispensing every conscious and unconscious weapon they can think of to try and keep their fat mass down.

It’s as if he’s bailing out a leak in a boat and he has found a strategy where he can stay afloat (in this case 6% body fat is his buoyancy) as long as he keeps churning.

But once some of the forces are removed, for example, no more weight lifting sessions, the fat may settle at a different level. And say he decides to start drinking 3 Big Gulps a day along with a cavalcade of sugar and refined-carbohydrate-laden foods, and he becomes hyperinsulinemic. This is an added force on the system and is likely to change where his fat mass settles.

With IF as a strategy for weight loss, it may not be a stretch that it is similar to caloric restriction (CR) in that both will have to be theoretically implemented for life in order to maintain the change induced by the strategy.

But the same can be said of a low-carb or Paleo diet; these things need to be maintained in order to maintain the effects they are having on (and in) the body. In the modern world, we need to consciously avoid carbohydrates at every turn if we're on a low-carbohydrate diet and we have to avoid about 85% of the offerings in a typical grocery store if we're eating Paleo (or low-carb). The percentage of food that we shouldn't be eating in a grocery store might be the same number as the prevalence of obesity (last time I checked it was hovering around 70%). But if we can navigate past the soda, sweets, and snacks aisle, and fuel our bodies with the appropriate foods, consciousness has nothing to do with why we get fat.

This also makes any recommendation to go on a low-carb diet for weight loss, and then once you reach a desirable weight, go ahead and revert back to the Standard American Diet (SAD) - but be sure to practice calorie balance! - patently absurd.

Every Tom, Dick, and Harry can tell his office colleagues or park bench neighbors the latest on reducing diets. More than in any other illness, the physician is called upon only to do a special trick, to make the patient do something—stop eating—after it has already been proved that he cannot do it. -Hilde Bruch, The Importance of Overweight

And one distinction that should be made between IF and CR is that many of the purported benefits of IF are not from a reduction in calories, whereas CR implies that you are going to have to go starving on some level for the rest of your life to maintain the benefits of CR.

Even those people who are properly informed and anxious to exercise voluntary control, frequently fail in the prevention of overweight. Evidently, it is not an easy matter continuously to overrule persistent impulses. Unfortunately we cannot in most cases correct these impulses by attacking their source, namely, the anomaly of the regulatory mechanism; and so long as man has to rely on his will power to suppress persistent impulses, prevention of obesity will remain a relatively rare accomplishment. -Hugo Rony, Obesity and Leanness

Saturated and Fat and Heart Disease

2011-03-17T04:08:00.000-07:00

Most people think that it’s saturated fat that can lead to elevated levels of cholesterol (specifically, LDL), and because our cholesterol goes up, we will be at an increased risk of heart disease and death.

Here is a 40-second advertisement from the UK Government regarding saturated fat:

Interesting to note (and Tom Naughton did as well in Big Fat Fiasco) that apparently saturated fat is a liquid in the refrigerator and solid at room temperature. And if you follow the logic that anything that clogs your drain-pipe will clog your arteries, probably leaves you with just H2O to consume.

The incidence of heart disease is not decreasing, yet we’re eating less saturated fat.

Also, invoking the logic that saturated fat raises cholesterol; and high cholesterol clogs your arteries; and clogged arteries cause heart disease; therefore a diet high in saturated fat causes heart disease is a logical fallacy (and one could argue that each link in this chain is unsubstantiated as well).

Drinking excess water leads to frequent urination. Frequent urination is linked to diabetes. Therefore, drinking too much water will give you diabetes.

There is an increase in sales of ice cream in the summer. There is a higher incidence of drowning in the summer. Ice cream leads to drowning.

There is an increase in the number of observed umbrellas outside when it’s raining. Umbrellas cause rain? No. They’re at the scene of the crime, but not necessarily the culprit.

A clinical trial in the 1970s tested the effects of a cholesterol-lowering drug called clofibrate, which lowered cholesterol in subjects. The trial had to be stopped because the men taking the pill had a 47% higher death rate than the placebo group. [1]

By the same logic invoked above, I can say that a low-fat diet reduces cholesterol, and lower cholesterol (via clofibrate) led to more deaths, therefore low-fat diets kill you.

Virtually every trial that tried to support the fat/heart disease connection has failed. What do good scientists do when faced with overwhelming contradictory evidence? They admit their hypothesis failed and they explore other questions.

If you replace saturated fat in your diet with cereal, skim milk, a banana and an orange, your LDL may go down, but your triglycerides will go up. Your HDL will go down. And now you’re at a higher risk of heart disease. These are better predictors than LDL, but they, too, have their limitations.

Also, More saturated fat does not mean less HDL, as many people seem to believe. In a meta-analysis of 27 studies on serum lipids (Mensink and Katan, 1992), the study noted: “All fatty acids elevated HDL cholesterol when substituted for carbohydrates, but the effect diminished with increasing unsaturation of the fatty acids.”

In other words, if the diet was rich in saturated fats, it would increased HDL, and if you replace the saturated fats with unsaturated fats (or synthetic trans fats), your HDL is likely to decrease.

In a 2010 meta-analysis of prospective cohort studies evaluating the association between saturated fat with cardiovascular disease, the authors, Siri-Tarino, Sun, Hu, and Ronald Krauss stated: “there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD.”

In another article by the same authors: “An independent association of saturated fat intake with CVD risk has not been consistently shown in prospective epidemiologic studies, although some have provided evidence of an increased risk in young individuals and in women. Replacement of saturated fat by polyunsaturated or monounsaturated fat lowers both LDL and HDL cholesterol.”

Another study from 2010 (Yamagishi et al.) entitled “Dietary intake of saturated fatty acids and mortality from cardiovascular disease in Japanese,“ found that people who ate the most sturated fat had a lower risk of cardiovascular disease and the authors stated, keeping in mind that stroke is a bigger public health threat than heart disease in Japan: “SFA intake was inversely associated with mortality from total stroke, including intraparenchymal hemorrhage and ischemic stroke subtypes, in this Japanese cohort.”

But can the associative studies be reconciled with experimentation and mechanisms of action? [2]

The Siri-Tarino (2010) article continued: “replacement of saturated fat by polyunsaturated or monounsaturated fat lowers both LDL and HDL cholesterol. However, replacement with a higher carbohydrate intake, particularly refined carbohydrate, can exacerbate the atherogenic dyslipidemia associated with insulin resistance and obesity that includes increased triglycerides, small LDL particles, and reduced HDL cholesterol. In summary, although substitution of dietary polyunsaturated fat for saturated fat has been shown to lower CVD risk, there are few epidemiologic or clinical trial data to support a benefit of replacing saturated fat with carbohydrate. Furthermore, particularly given the differential effects of dietary saturated fats and carbohydrates on concentrations of larger and smaller LDL particles, respectively, dietary efforts to improve the increasing burden of CVD risk associated with atherogenic dyslipidemia should primarily emphasize the limitation of refined carbohydrate intakes and a reduction in excess adiposity.”

In other words, it’s the carbohydrates, not the dietary fats that are contributing to CVD risk associated with atherogenic lipid dysreguation.

After we eat a meal with a lot of sugar and/or carbohydrates, the bloodstream gets flooded with glucose, and the liver takes some of the glucose and converts it into triglycerides for storage. The triglycerides are fused to the apo B protein and to the cholesterol that forms.

Gary Taubes wrote in Good Calories, Bad Calories (2007):

The triglycerides constitute the cargo that the lipo-proteins drop off at tissues throughout the body. The combination of cholesterol and apo B is the delivery vehicle. The resulting lipoprotein has a very low density, and so is a VLDL particle, because the triglycerides are lighter than either the cholesterol or the apo B. (In the same way, the more air in the hold of a ship, the less dense the ship and the higher it floats in the water.) For this reason, the larger the initial oil droplet, the more triglycerides packaged in the lipoprotein, the lower its density.

The liver then secretes this triglyceride-rich VLDL into the blood, and the VLDL sets about delivering its cargo of triglycerides around the body. Throughout the process, known poetically as the delipidation cascade, the lipoprotein gets progressively smaller and denser until it ends its life as a low-density lipoprotein—LDL. One result is that any factor that enhances the synthesis of VLDL will subsequently increase the number of LDL particles as well. As long as sufficient triglycerides remain in the lipoprotein to be deposited in the tissues, this evolution to progressively smaller and denser LDL continues. It’s this journey from VLDL to LDL that explains why most men who have high LDL cholesterol will also have elevated VLDL triglycerides. “It’s the overproduction of VLDL and apo B that is the most common cause of high LDL in our society,” says Ernst Schaefer, director of the lipid-metabolism laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. None of this, so far, is controversial; the details are described in recent editions of biochemistry textbooks.

How this process is regulated is less well established. In Krauss’s model, based on his own research and that of the Scottish lipid-metabolism researcher Chris Packard and others, the rate at which triglycerides accumulate in the liver controls the size of the oil droplet loaded onto the lipoprotein, and which of two pathways the lipoprotein then follows. If triglycerides are hard to come by, as would be the case with diets low in either calories or carbohydrates, then the oil droplets packaged with apo B and cholesterol will be small ones. The ensuing lipoproteins secreted by the liver will be of a subspecies known as intermediate-density lipoproteins—which are less dense than LDL but denser than VLDL—and these will end their lives as relatively large, fluffy LDL. The resulting risk of heart disease will be relatively low, because the liver had few triglycerides to dispose of initially.

If the liver has to dispose of copious triglycerides, then the oil droplets are large, and the resulting lipoproteins put into the circulation will be triglyceride-rich and very low-density. These then progressively give up their triglycerides, eventually ending up, after a particularly extended life in the circulation, as the atherogenic small, dense LDL. This triglyceride-rich scenario would take place whenever carbohydrates are consumed in abundance. “I am now convinced it is the carbohydrate inducing this atherogenic [profile] in a reasonable percentage of the population,” says Krauss. “. . . we see a quite striking benefit of carbohydrate restriction.”

Low-Carbohydrate Studies: Part IV

2011-03-14T17:24:00.000-07:00

Previous related posts:

Part I | Part II | Part III

“It would not perhaps be too fanciful to say that a new idea is the most quickly acting antigen known to science. If we watch ourselves honestly we shall often find that we have begun to argue against a new idea even before it has been completely stated.” –Wilfred Trotter, cited in W.I.B. Beveridge, The Art of Scientific Investigation, 1950.

Weight Loss and Macronutrient Composition

The carbohydrate hypothesis is not a new idea - it has been invoked in one way or another for at least 185 years (23), but it is perceived as a new phenomenon, or "fad," by the researchers conducting diet studies as well as the public health authorities, and they have argued against the hypothesis before it has been completely stated and properly explained.

The unrelenting argument made by proponents of the positive-calorie hypothesis is that the only thing that matters in terms of weight loss, weight gain, or weight maintenance is balancing calorie intake with calorie expenditure. There is nothing special about different proportions of carbohydrates, fats, and protein when it comes to weight control, it’s all about energy in versus energy out, 'a calorie is a calorie is a calorie,' say the researchers in diet studies. (They might, on the other hand, tell you that too much dietary fat will cause heart disease, so eat a low-fat diet, but that’s another story.)

When weight loss turns out to be greater on a low-carbohydrate diet compared to a low-fat diet, which is often the case, the authors will make note that the reason why the low-carb dieters lost more weight was because they consumed less calories.

What escapes the researchers, who are supposedly testing the carbohydrate hypothesis – that it’s the carbohydrates that make us fat, not the fat and protein – is the question as to why the low-carb group which is unrestricted in calories would consume less than a low-fat group of dieters who are restricted in calories?

Also, if the researchers could suspend their calories-in/calories-out hypothesis belief for just a few more moments, and apply the carbohydrate hypothesis, perhaps the weight loss observed on the low-fat, calorie-restricted diets, too, stem from the reduction in carbohydrates from baseline. That is, when subjects go on a clinical low-fat diet, they are not only eating less fat, they’re eating less of everything, because they are also restricted in calories. These people are not only eating less dietary fat than before their diet began, but they’re also eating less carbohydrates.

In a 2010 study by Foster et al. in the Annals of Internal Medicine (1), the authors also noted that the similar weight losses observed with low-carbohydrate and low-fat diets in their study demonstrated that the comprehensive lifestyle intervention produced the same energy deficit in both groups, despite marked differences in their behavioral targets.

However, there are a number of possibilities as to why weight loss was the same in both groups. As previously discussed, the low-carbohydrate group were increasing their carbohydrate consumption until a “stable and desired weight was achieved.” It’s possible that by the end of the study, both groups were eating a similar diet in terms of nutrient composition.

Also, as noted above, the authors added another variable to the study: "Both diets were combined with behavioral treatment." This is an admitted limitation of the study by the researchers, and makes it impossible to discern whether the behavioral modification alone was responsible for the weight loss in both groups, whether the low-carbohydrate diet and low-fat, low-calorie diets played the predominant role in weight loss, or whether it was a combination of behavioral modification and the diets (or increased expenditure, as the subjects were instructed to participate in 200 minutes of aerobic exercise per week). The inclusion of a behavioral treatment in a diet study testing the effectiveness of two different diets invalidates the proposed hypothesis. This should be covered in greater detail in a separate blog post.

The authors (1) concluded that the long-term findings in an outpatient setting in which there were not significant differences in weight was consistent with data from short-term metabolic ward studies (2-4) showing that macronutrient composition did not influence weight loss when energy content was fixed.

Trials from short-term metabolic wards are particularly illuminating since these types of studies usually have the ability to control a number of variables that under non-metabolic ward conditions are otherwise uncontrolled. Investigators can carefully measure the food to be administered to the subjects and monitor the amount and type of food eaten. To be sure, metabolic ward studies are not without limitation, but they can generally close a number of the loopholes that arise in outpatient settings.

Self-reporting nutrient intake is one of the biggest limitations to most diet studies, and this was the supposed reason why Foster et al. (1) did not collect any nutrient intake data from their subjects.

In other words, with inpatient metabolic wards studies, as compared to the Foster et al. (1) study, the researchers fed the subjects the food they were supposed to eat; the researchers monitored how much food the subjects ate, the researchers collected the data on food intake; the researchers analyzed the data on how much food the subjects were eating; and the researchers reported how much food their subjects actually ate rather than: not feeding, monitoring, collecting, analyzing, nor reporting the amount and type of food their subjects were eating, and estimating how much food the subjects that dropped out of the study ate and how much weight they might have lost had they stuck around (this is called ‘Intention to Treat Analysis, or ITT, and should be discussed in detail in a later post), which is what the researchers did in Foster et al. (1) as well as many other randomized trials of low-carbohydrate diets compared to low-fat, calorie-restricted diets (5-10).

Whether a diet study with no recording or reporting of intake is more limited than a study with self-reporting may be open for debate, however, a study comparing two different diets with no data on what their subjects actually ate is invalid in terms of making conclusions about the effects of such diets in the trial.

The metabolic ward studies cited in the Foster et al. (1) paper were:

Yang and Van Itallie, 1976 (2): 800 kcal diets (isocaloric)

Golay et al, 1996 (3): 1000 kcal diets (isocaloric)

Boden et al, 2005 (4): (“usual diet,” followed by a low-carbohydrate diet)

In Yang and Van Itallie (2), intake for the "mixed" diet contained 90 g/d of carbohydrates, where the typical recommendations of 55-65% carbohydrates based on a 2000-calorie diet amounts to as much as 325 g/d of dietary carbohydrates. This is a potential 72% reduction in the carbohydrate content of the diet of a diet that is supposedly liberal in carbohydrates, if we presume subjects were eating something close to a mixed diet prior to the study. If we had an idea what the low-carbohydrate diet subjects in Foster et al. (1) were consuming at 24 months, it may have been instructive. It would be likely that the low-carbohydrate group were consuming more than 90 g/d of carbohydrates by the end of the study, which means that they would have been eating more carbohydrates on a “low-carbohydrate” diet than a “mixed diet.”

To wit, in Gardner et al. (6), a one-year randomized trial among 311 overweight/obese (body mass index, 27-40), nondiabetic premenopausal women, "Participants were randomly assigned to follow the Atkins, Zone, LEARN, or Ornish diets and received weekly instruction for 2 months, then an additional 10-month follow-up."

In the Atkins group, after 2 months, subjects reported an average intake of 1381 calories, with 17.7% derived from carbohydrates, which amounts to approximately 61 g/d.

After 6 months, subjects reported an average intake of 1538 calories, with 29.5% derived from carbohydrates, which amounts to approximately 113 g/d.

After 12 months, subjects reported an average intake of 1599 calories, with 34.5% derived from carbohydrates, which amounts to approximately 138 g/d.

It’s important to note that the nutrient intake data was collected via self-reporting, which can be unreliable, however it does provide trends in dietary patterns in which we can glean some potentially useful information. The Gardner et al. (6) study helps illustrate the point that for most of the trial, subjects were reportedly eating more carbohydrates than the low-fat, isocaloric (or "mixed") diets from the metabolic ward studies (2, 3).

A significant limitation in regard to the nutrient composition of the diet with the Yang and Van Itallie (2) study is the low caloric content of the diet for both groups, which makes the "mixed" diet a "low-carbohydrate diet," or at least lower than subjects trying to adhere to a low-carbohydrate diet.

Golay et al. (3) had the same limitation. Subjects were assigned to either a 15% carbohydrate diet or a 45% carbohydrate diet. The 45% carbohydrate diet consisted of an average of 115 g/d carbohydrates, an amount below the Atkins subjects from Gardner et al. (6) after 12 months (138 g/d).

For the sake of argument, take an example of a metabolic ward study conducted on two individuals, both eating 10 calories per day for two weeks.

One individual is assigned to a low-fat diet. The subject is fed a diet that is 60% of calories from carbohydrate, 25% fat, and 15% protein.

The other individual is assigned to a low-carbohydrate diet: 20% of calories from carbohydrate, 65% fat, and 15% protein.

If there was no difference in weight loss between the two subjects (i.e., both individuals lost 5 kg), would the authors conclude that the results were consistent with metabolic ward studies showing that macronutrient composition did not influence weight loss when energy content was fixed?

Would they comment on whether in fact these individuals may have been starving on both diets and that individuals severely restricting their intake of nutrients may be fundamentally different from patients who are allowed diets unrestricted in calories?

Also, if the researchers are testing the carbohydrate hypothesis, this type of study would not refute it because in both groups, carbohydrate consumption would be considered very low (1.5 g/d of carbohydrates in the low-fat group and 0.5 g/d of carbohydrates in the low-carbohydrate group per day) and both were effective for weight loss.

In the third metabolic ward study referenced by Foster et al. (1), Boden et al. (4) was an inpatient comparison of two diets on the same 10 individuals (obese patients with type 2 diabetes), beginning with the "usual diet," which consisted of continuing their usual diet for 7 days, followed by a 14-day ad libitum, low-carbohydrate diet. From the abstract:

“On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days).”

Doesn’t this beg the question: why would the subjects voluntarily reduce their intake from their “usual diets” by over 1000 calories when they went on a “low-carbohydrate diet” for two weeks?

Also, note the Atkins diet was ad libitum in the Gardner et al. (6) study and subjects reportedly consumed just 1381 calories, well below their baseline of 1888 calories. The relevant question is whether there is a relationship between the carbohydrate content of the diet and caloric consumption, and claiming that ‘macronutrient composition did not influence weight loss when energy content was fixed’ does not answer it.

The authors in Boden et al. (4) stated:

"In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain."

It should be highlighted that the authors concluded that the low-carbohydrate diet resulted in “spontaneous reduction in energy intake to a level appropriate to their height” and that “weight loss was completely accounted for by reduced caloric intake.”

Again, the authors need to address the phenomenon of subjects voluntarily reducing their caloric intake when “patients could eat protein and fat as much and as often as they wanted,” including “beef patties, ground turkey patties, chicken breasts, turkey slices, fresh ham slices, raw or steamed vegetables, butter, and diet gelatin,” and “as with their usual diets, participants could request allowable items that were not available from the hospital kitchen, such as fresh fish, eggs, various cuts of beef, cream, and additional vegetables,” as well as “limited amounts of cheese and cream cheese,” in addition to “specific brands of salad dressings and snack foods suggested by Dr. Atkins, including Atkins-brand foods (4).”

During the first week of the study, on the usual diet, patients maintained their usual eating and activity patterns, and the authors concluded “mean caloric intakes and total energy expenditures were in balance (approximately 3100 kcal/d) and body weights remained stable."

The authors stated that because all weight loss was due to loss of fat, and they estimated that the caloric deficit plus changes in body water accounted for all weight loss, they concluded that their data did not support the concept that the weight loss induced by the low-carbohydrate diet was due to different metabolic utilization of macronutrients (12, 13).

The researchers admittedly had no explanation for why the subjects spontaneously reduced their appetite (4). The authors in Boden et al. (4) noted that lack of variety and palatability have been incriminated, but were not supported by their reports from subjects via visual analogue scale questionnaires.

It’s also not supported by observational accounts. Journey over to Dr. Michael Eades’s blog for a tale of two diet studies, which illuminates some of these accounts and compares the Minnesota starvation study by Ancel Keys to a low-carbohydrate study by John Yudkin (14). This blog post further discusses the fact that low-carbohydrate dieters voluntarily reduce their caloric consumption to levels that Keys subjected his subjects to in order to induce starvation in a relatively high-carbohydrate diet.

The authors in Boden et al. (4) postulated that decreased serum insulin levels observed in their subjects on a low-carbohydrate diet may have reduced appetite because studies in humans have found that insulin increased food intake (15-17).

Also, the authors found mean plasma leptin levels were lower, and thought this may have to do with caloric restriction (18, 19) and decreased insulin levels (20) or because leptin sensitivity had increased. They concluded that in view of the appetite-suppressing effect of leptin (21), lower leptin levels may have stimulated appetite and limited diet-induced weight loss.

It seems odd to state that there is no metabolic advantage to a low-carbohydrate diet and that macronutrient composition makes no difference in terms of weight regulation, when, if their hypotheses above are true, wouldn’t it be an advantage that when insulin levels are low, more stored fat is mobilized? However, according to the logic of Boden et al. (4), if the low-carbohydrate dieters are mobilizing more stored fat, and thus they require less calories than someone on a low-fat diet who is mobilizing less, it's somehow irrelevant to the conversation of weight gain and it’s still the calories that matter.

Note that the authors in Boden et al. (4) are addressing the question of why their subjects reduced their caloric intake volitionally on a low-carbohydrate diet unrestricted in calories, which is a discussion that most of the journal articles comparing low-carbohydrate, ad libitum and low-fat, calorie-restricted diets omit. So kudos.

The statement regarding decreased insulin levels reducing appetite and lower leptin levels stimulating appetite is contradictory. On one hand, the investigators are trying to make the case for why the patients reduced their caloric intake by a reduction in appetite (3111 kcal/d to 2164 kcal/d, a 30% voluntary reduction in energy intake), yet conversely argue that the lower leptin levels may have increased their appetite.

If their appetite was increased, why were they eating 1000 fewer calories than their usual diet? Are the authors arguing that if leptin levels remained the same, they would have further reduced their caloric intake? It’s entirely possible, but the authors are probably closer to the truth by reasoning that perhaps leptin sensitivity had increased. More leptin may be detected because more fat is mobilized (via lower levels of insulin) with a restricted-carbohydrate diet.

Also, insulin is the primary regulator of fat storage and is the “gatekeeper” for fat mobilization and storage. This is isn't controversial from a biochemical standpoint. When insulin levels are elevated, fat storage is promoted and fat mobilization inhibited. Conversely, when insulin levels are low, fat mobilization is promoted and fat storage inhibited. That carbohydrates drive insulin secretion, and insulin promotes fat deposition is central to the carbohydrate hypothesis. In this scenario, an increase in caloric intake and/or a decrease in energy expenditure are side effects of eating a diet high in sugar and easily digestible carbohydrates.

In Boden et al. (4), the low insulin levels of the subjects meant that they had relatively more access to their stored adipose tissue relative to when they were on their “usual” diet. If more free fatty acids are available for use, it is conceivable that they would need less exogenous fuel and their energy intake requirements would decrease (to the possible tune of a 30% reduction, as witnessed in the study). The “dieters” are eating their own adipose tissue. In this context, the voluntary decrease of 1000 kcals makes more sense: there’s no caloric deficit per se, rather the Atkins subjects are supplementing their exogenous fuel with endogenous sources (liberated fatty acids from adipose tissue).

Ultimately, while the authors address the question of why their patients reduced caloric intake, they didn’t have any answer, as was noted in the paper.

Likewise, it is not a sufficient explanation by Foster et al. (1) to conclude that macronutrient composition does not affect weight loss by citing three metabolic ward studies; two in which the researchers were ostensibly comparing low-carbohydrate diets to very low-carbohydrate diets (2, 3), and a third study that observed a voluntary reduction in 1000 calories from their usual diet (4).

Even if you are a proponent of the calories-in/calories-out hypothesis, if lowering carbohydrates seems to induce lower caloric consumption, while lowering fat doesn’t have the same effect, wouldn’t you entertain the notion that macronutrient composition does in fact influence weight loss, and the decreased caloric consumption seen on a low-carbohydrate diet may be a consequence of the restricted-carbohydrates in the diet? And the caveat that macronutrient composition does not influence weight loss when energy content is fixed only seems to be applicable if we are starving our subjects.

In light of this, a good test of the competing calories-in/calories-out and carbohydrate hypotheses would be an isocaloric metabolic ward study in which the groups were not starved, or semi-starved, rather the two groups are fed high-calorie diets with different macronutrient composition. This would eliminate the fact that when subjects are treated to semi-starvation diets of different macronutrient compositions, they’re invariably eating fewer carbohydrates than they were before the intervention, even if they're placed in the low-fat-diet group.

In a study by Shai et al. (24) for example, the low-fat dieters reduced their carbohydrate consumption by 83 g/d from baseline after 24-months on the diet in a 24-month study. The low-fat diet group in Gardner et al. (6) (LEARN) reportedly reduced their carbohydrate consumption by 37 g/d after 12-months in a 12-month study. Perhaps the reported weight loss on these diets is also due to the restricted nature of the carbohydrates, and perhaps the improvement of the quality of the carbohydrates on such diets (which will be discussed in more detail later)?

A good place to start (and for me to end this post) in the search for a true test of the carbohydrate hypothesis is the type of trial that Gary Taubes proposed in the afterword of Good Calories, Bad Calories (22):

[T]here are indeed relatively simple experiments that could establish whether it’s excess calories that make us fat (the conventional wisdom) or purely the effect of carbohydrates on insulin and insulin on fat accumulation (the carbohydrate hypothesis).

Such experiments could be done with a dozen subjects in to two to three months and so would be inexpensive, at least by the standards of modern medical research. One caveat is that they would require that their human subjects be treated to some extent like laboratory animals. They would be housed in a metabolic ward and fed three or more meals a day. In the ideal situation, the subjects would never leave the ward and be under constant observation—as was the case with Vilhjalmur Stefansson and his colleague Karsten Anderson in the first weeks of their 1928 meat diet experiment—so that the opportunity to cheat on their diets would be minimized. In one variation of the experiment, the subjects would be randomized into two groups. One group, the controls, would be fed a balanced diet, relatively rich in carbohydrates, constituting 3,000 or even 4,000 calories a day. The other would be fed a diet of equal caloric content, but severely carbohydrate restricted—preferably less than sixty grams of carbohydrates a day.

The carbohydrate-restricted diet would lower insulin levels significantly. According to the carbohydrate hypothesis, this would reduce fat accumulation independent of the calories consumed. The fatty acids liberated from the fat tissue would be burned as fuel and energy expenditure would increase in these subjects. The balanced diet would have no effect on insulin levels and those subjects would not be expected to lose weight or increase energy expenditure. (Because even the balanced diet might represent an improvement in the quality of the carbohydrates in the subjects’ diet—calories from sugar, white bread, white rice, and beer, for instance, might be replaced by calories from whole grains and green vegetables—there is always the possibility that even the control group in such a study will lose some weight, even if the amount of calories consumed has no effect.)

The study would have to run for at least two months, long enough to establish a significant amount of fat loss if the carbohydrate hypothesis is correct. The researchers would measure energy expenditure before the experiment began and then at regular intervals throughout the experiment. (A technology known as doubly-labeled water would allow this to be done within 10 percent accuracy.) Insulin levels would also be measured regularly, as would any other blood biomarkers or risk factors for heart disease that the researchers might choose (and be able to afford). Body composition, before and after the experiment, should be analyzed as well to establish the proportion of lean and fat tissue lost (if any).

Such an experiment would go a long way toward determining the validity of the two competing hypotheses: is it the quantity of calories that determines our weight and fat accumulation or the quality? I would argue, as I’ve been doing widely since this book came out, that such an experiment is absolutely fundamental to understanding the cause not only of obesity, but of heart disease, cancer, and diabetes, as well.

____________________

1. Foster GD, Wyatt RW, Hill JO, Makris AP, Rosenbaum DL, Brill C, Stein RI, Mohammed BS, Miller B, Rader DJ, Zemel B, Wadden TA, Tenhave T, Newcomb CW, Klein S. Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet. Ann Intern Med. 2010;153:147-157.

2. Yang MU, Van Itallie TB. Composition of weight lost during short-term weight reduction. Metabolic responses of obese subjects to starvation and lowcalorie ketogenic and nonketogenic diets. J Clin Invest. 1976;58:722-30. [PMID: 956398]

3. Golay A, Allaz AF, Morel Y, de Tonnac N, Tankova S, Reaven G. Similar weight loss with low- or high-carbohydrate diets. Am J Clin Nutr. 1996;63:174-8. [PMID: 8561057]

4. Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP. Effect of a lowcarbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med. 2005;142:403-11. [PMID: 15767618]

5. Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003;348:2082-90. [PMID: 12761365]

6. Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003;348:2074-81. [PMID: 12761364]

7. Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003;88:1617-23. [PMID: 12679447]

8. Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A lowcarbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004;140:769-77. [PMID: 15148063]

9. Stern L, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004;140: 778-85. [PMID: 15148064]

10. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005;293:43-53. [PMID: 15632335]

11. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007;297:969-77. [PMID: 17341711]

12. Atkins RC. Dr. Atkins’ New Diet Revolution. New York: Avon Books: 1992.

13. Greene P, Willett W, Devecis J, Skaf A. Pilot 12-week feeding, weight-loss comparison: low-fat vs. low-carbohydrate (ketogenic) diets (Abstract). Obes Res. 2003;11:A23.

14. Eades MR. Is a calorie always a calorie? The Blog of Michael R. Eades, M.D. September 11, 2007

15. Rodin J, Wack J, Ferrannini E, DeFronzo RA. Effect of insulin and glucose on feeding behavior. Metabolism. 1985;34:826-31. [PMID: 3897769]

16. Holt SH, Miller JB. Increased insulin responses to ingested foods are associated with lessened satiety. Appetite. 1995;24:43-54. [PMID: 7741535]

17. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med.1993;329:977-86. [PMID: 8366922]

18. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW,
Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292-5. [PMID: 8532024]

19. Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab. 1996;81:3419-23. [PMID: 8784108]

20. Boden G, Chen X, Kolaczynski JW, Polansky M. Effects of prolonged
hyperinsulinemia on serum leptin in normal human subjects. J Clin Invest. 1997;100:1107-13. [PMID: 9276727]

21. Campfield LA, Smith JF. Central integration of peripheral signals in the regulation of food intake and energy balance: role of leptin and insulin. In: Bray GA, Bouchard C, eds. Handbook of Obesity. 2nd ed. New York: Marcel Dekker;2003:461-79.

22. Taubes G. Good Calories, Bad Calories. Knopf. 2007.

23. Brillat-Savarin JA. The Physiology of Taste. 1825.

24. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, et al; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359:229-41. [PMID: 18635428]

Low-Carbohydrate Studies: Part III

2011-03-13T06:29:00.001-07:00

(Originally posted September 1, 2010)

“You don’t see something until you have the right metaphor to let you perceive it." –Robert Stetson Shaw, physicist

Imagine a clinical trial of two drugs to see if they were effective at lowering triglycerides. Subjects are randomized into one of two groups. One group starts on 100 mg of “Triglycerpro” and the other takes 100 mg of “Lipidgone." The Triglycerpro group swallows 100 mg of Triglycerpro once a day for 30 weeks. The Lipidgone group ingests 100 mg of Lipidgone once a day for 10 weeks. After 10 weeks, the dosage begins to drop by 5 mg/d per week, so by week 20 they're taking 50 mg a day of Lipidgone - by week 29 they're taking 5 mg a day of Lipidgone - and in the last week the pill is ostensibly a placebo at 0 mg.

Here is what the table might look like (change in triglycerides in mg/dL):

If the Lipidgone group showed superior results in lowering triglycerides after 10 weeks - and then between weeks 10-20 the results were still in favor of Lipidgone, but the effectiveness seemed to decrease - finally, between weeks 20-30 the Triglycerpro group showed more favorable results, how would researchers interpret the results? They would probably include the possibility that Lipidgone is more effective at lowering triglycerides than Triglycerpro and that the decreased effectiveness of Lipidgone over time was due to the lowering of the dosage.

Why don’t the researchers discuss the same possibility when evaluating a low-carbohydrate diet in which the effective dosage is being decreased by increasing the level of carbohydrate in the diet over time?

In Part I (1) of this series, I discussed the recent low-carbohydrate vs. low-fat, restricted-calorie study by Foster et al. (2) that appeared in the pages of the Annals of Internal Medicine last month, and the premise behind low-carbohydrate diets and low-fat, low-calorie diets. In Part II (3) the issue of triglycerides in relation to low-carbohydrates was covered. In Part III, the gradual increase of dietary carbohydrates on low-carbohydrates will be the topic of discussion.

In the design of the Foster et al. (2) study for the low-carbohydrate diet, patients were instructed to limit consumption of carbohydrates to 20 g/d during the first 12 weeks of treatment. After the first 12 weeks, patients were then instructed to gradually increase carbohydrate intake (5 g/d per week).

Quite often, part of the protocol of low-carbohydrate groups is to “severely” restrict carbohydrates for the first two weeks, and then gradually add carbohydrates (2, 4-8) and in the case of the Foster studies, add them “until a stable and desired weight [is] achieved, (2, 5)." The Atkins diet prescribes this type of feeding pattern (9).

One possibility of the observed outcomes in studies conducted on low-carbohydrate diets is: if the theory holds true that the carbohydrates determine weight gain, the more carbohydrates added in the diet, the lesser the weight loss (or greater the weight gain). Invariably, the subjects on the low-carbohydrate diet increase their carbohydrate intake over time, either by prescription and/or long-term noncompliance.

For the first six months, when “several randomized trials over the past 6 years have demonstrated that low-carbohydrates produced greater short-term (6 months) weight loss than low fat, calorie-restricted diets (2),” this is when carbohydrate consumption is at its lowest, i.e., it’s truly a low-carbohydrate diet.

In a systematic review of low-carbohydrate diets in 2003, Bravata et al. (10) categorized the various low-carbohydrate diets being tested into three groups: 1) lowest-carbohydrate diets (≤ 20 g/d of carbohydrates), 2) lower-carbohydrate diets (≤ 60 g/d of carbohydrates), and 3) higher-carbohydrate diets (> 60 g/d of carbohydrates).

Studies of the lower-carbohydrate diets tended to have a shorter duration than studies of higher-carbohydrate diets. Studies of the lowest-carbohydrate diets had shorter duration averages than the lower- and higher-carbohydrate diets. Only five studies evaluated lower-carbohydrate diets for more than 90 days, and these studies were nonrandomized and noncontrolled designs (11-15). The Bravata et al. (10) review included 107 articles describing 94 dietary interventions reporting data for 3268 participants; 663 patients received diets of 60 g/d or less of carbohydrates—of whom only 71 received 20 g/d or less of carbohydrates (16-26).

So the observed short-term success of a low-carbohydrate diet might be due to the fact that this is the period when carbohydrate intake is lowest.

“Of the 34 of 38 lower-carbohydrate diets for which weight change after diet was calculated, these lower-carbohydrate were found to produce greater weight loss than higher carbohydrate diets (10)”—“an average of 37 pounds when carbohydrates were restricted to less than sixty grams a day, compared to 4 pounds when they were not,” noted Gary Taubes in Good Calories, Bad Calories (27).

With most of these trials, the carbohydrate content gradually increases, which essentially makes it less and less of what the researchers are testing for. If researchers prescribed a low-fat diet, for example, with instructions to gradually increase dietary fat 3g/d per week “until a stable and desired weight was achieved,” wouldn’t the authors point out that one of the major limitations to the study was that they were progressively adding fat to a low-fat diet, and the progressive decline in weight loss may be attributable to a progressive increase in the consumption of fat? And since the Atkins approach is arguing that the carbohydrates make us fat, it would predict, as well as any researcher who read the book or understands the principles, that the more carbohydrates added back to the diet, the lower the weight loss - to the point of weight gain if continually increased?

Again, because the subjects are supposedly gradually increasing their carbohydrate intake over the course of the study, or at least until a desired weight was achieved, the dosage of the treatment is effectively being reduced. “It's akin to comparing the effects of two anti-depressants and the advice on one of them was to lower the dosage in small increments after three months until a “stable” mental state was achieved (i.e., depression returned),” noted Gary Taubes.

Likewise, if the low-fat, low-calorie group was instructed to gradually increase their fat and caloric intake over time, it should be pointed out that this could in fact lower the effect of what the authors are testing. If the authors recorded energy intake, for example, and it was found that the low-calorie female subjects were supposed to be eating an average of 1350 calories, but were reporting an intake of 2300 after 12 months, it would probably be noted in the discussion that if the subjects didn't lose weight or perhaps gained weight, this would provide them some useful arithmetic.

It should have been discussed that it was possible the initial significant decrease in weight in the low-carbohydrate group in Foster et al. (2) was in fact, due to the restricted nature of the carbohydrates, and that when carbohydrates were increased over time, weight loss stalled, and eventually reversed between 12 and 24 months.

It should also be noted that a common response to the question of gradually increasing carbohydrates is that this is typical on an Atkins diet. This may be true, but then the authors are testing the effect of an "Atkins Diet," not necessarily a low-carbohydrate diet, and it should be noted throughout the paper.

Just as referring to a low-fat, restricted-calorie diet simply as a “low-fat diet” can be misleading - and the authors in Foster et al. (2) do this repeatedly in the article in addition to the title, not to mention a number of other articles with the same omission - referring to a low-carbohydrate diet that progressively increases dietary carbohydrates can be misleading as well.

To wit, in the case of Foster et al. (2), patients were allowed to increase their carbohydrate consumption from 20 g/d at 12 weeks, to 480 g/d at 104 weeks, which would be an intake significantly greater than the amount of carbohydrates that the low-fat dieters were theoretically consuming; approximately 186 g/d for women and 227 g/d for men.

In Gardner et al. (28), Atkins diet subjects were reporting (albeit, self-reporting can be unreliable and invalid) an intake of 138g/d of carbohydrates, on average. This may be considered a low-carbohydrate diet by many, including the USDA, however it should be noted that the carbohydrate intake of the subjects on an Atkins diet are consumed on a sliding (progressively increasing) scale, which makes the data difficult, if not impossible to interpret.

In a clinical research setting, a fixed number of carbohydrates should be implemented (unless testing the "Atkins Diet" specifically), otherwise investigators will be trying to pin down a moving target.

Another example: if investigators were testing the calories-in/calories-out hypothesis on a low-calorie diet - 1100 calories during week 1 – and the subjects progressively increased their daily caloric intake each week, for example 1200 kcals in week 2, 1300 kcals in week 3. . . . progressively increasing in 100 kcal/d weekly increments to 3600 kcals/day in week 26 in a 6-month study, and the subjects went from weight loss in the first six weeks, then gradually regained it from weeks 7-14, then gained weight over baseline from weeks 15-26, would the authors conclude that the increase in calorie consumption accounted for the weight change?

(Here is what the table might look like; change in weight in kg from baseline:)

You bet they would.

Likewise, if investigators are testing the carbohydrate hypothesis – that carbohydrates make us fat – on a low-carbohydrate diet – 10 g/d carbohydrates during week 1 – and the subjects progressively increased their daily carbohydrate intake each week, for example 20 g/d carbohydrates in week 2, 30 g/d in week 3. . . . progressively increasing to 260g carbohydrates in week 26 in a 6-month study, and the subjects went from weight loss in the first six weeks, then gradually regressed toward baseline from weeks 7-26, would the authors conclude that the increase in carbohydrate consumption accounted for the weight change?

(Here is what the table might look like; change in weight in kg from baseline:)

Not likely.

Because of the calories-in/calories-out bias, investigators attribute increased energy intake as the cause of fat loss or fat gain, when it may be a side-effect of the nutrient composition of the diet.

If researchers want to test the carbohydrate hypothesis, they need subjects to follow a low-carbohydrate diet in which carbohydrate levels are low (of the < 30 g/d variety) and constant. (Or, perhaps more appropriately, carbohydrates should be assigned per body weight, for example, 0.5 gm carbohydrate per kg of body weight.) Also, in order to test the carbohydrate hypothesis, the calories-in/calories-out hypothesis needs to be shelved and not wedged into the picture. (One way of doing this is through isocaloric diets). Or at least have a discussion about the hypothesis you're testing and why you thought "the low-carbohydrate [ad libitum] diet would produce greater weight loss at 2 years than a low-fat, restricted calorie diet (2)."

____________________

1. Kaplan B. Part I.

2. Foster GD, Wyatt RW, Hill JO, Makris AP, Rosenbaum DL, Brill C, Stein RI, Mohammed BS, Miller B, Rader DJ, Zemel B, Wadden TA, Tenhave T, Newcomb CW, Klein S. Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet. Ann Intern Med. 2010;153:147-157.

3. Kaplan B. Part II.

4. Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003;88:1617-23. [PMID: 12679447]

5. Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003;348:2082-90. [PMID: 12761365]

6. Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A lowcarbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004;140:769-77. [PMID: 15148063]

7. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005;293:43-53. [PMID: 15632335]

8. Sondike SB, Copperman N, Jacobson M. Effects of a Low-Carbohydrate Diet on Weight Loss and Cardiovascular Risk Factors in Overweight Adolescents. J Pediatr 2003;142:253-8.

9. Atkins RC. Dr. Atkins’ New Diet Revolution. New York: Avon Books: 1992.

10. Bravata DM, Sanders L, Huang J, et al. Efficacy and Safety of Low-Carbohydrate Diets: A Systematic Review. JAMA. 2003;289(14):1837-1850.

11. Fleming RM. The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors. Prev Cardiol. 2002;5:110-118.

12. Nobels F, van Gaal L, de Leeuw I. Weight reduction with a high protein, low carbohydrate, calorierestricted diet: effects on blood pressure, glucose and insulin levels. Neth J Med. 1989;35:295-302.

13. Rabast U, Kustner H, Zang E, Ehl M, Kasper H. Outpatient treatment of obesity using a lowcarbohydrate diet. Med Klin. 1978;73:55-59.

14. Kirby RW, Willmann HK. Carle Morbid Obesity Clinic: an outpatient semistarvation ketogenic program. Carle Selected Papers. 1985;37:14-16.

15. Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE. Effect of 6-month adherence to a very low carbohydrate diet program. Am J Med. 2002;113:30-36.

16. Rosen JC, Gross J, Loew D, Sims EA. Mood and appetite during minimal-carbohydrate and carbohydrate- supplemented hypocaloric diets.AmJ Clin Nutr. 1985;42:371-379.

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Heart Disease, Genes, and Apolipoproteins

2011-03-13T06:07:00.000-07:00

We were recently discussing an article entitled Attacking Heart Disease at its Genetic Base in a Nutrition course.

The article noted that children could be genetically tested early in life so that “diet and other lifestyle changes would be started before damage begins.”

The questions posed to the class included whether we thought that this is the direction we should be taking as far as prevention is concerned, and was it wise to wait for our children to be tested before beginning to introduce them to a healthy lifestyle.

I think a big part of life and raising children is working off of the best information we have available to make choices about how we should live our lives and prevent disease. So, before any genetic test have been conducted, I don’t think most parents are going to be actively drowning their kids in a pool or allowing their children to live what they perceive to be an unhealthy lifestyle before they can be tested for genetic markers.

“Someday, health professionals will have a fairly complete profile of the human genes involved in raising or lowering risk, says Ordovas. Children could be tested early in life so that diet and other lifestyle changes would be started before damage begins.”

The implicit assumption in the statement above is that our genes may determine a relatively different lifestyle in order to express or not express certain traits. In this regard, dietary advice may be different than what we’re accustomed to.

For example, a high-fat diet may increase pattern B LDL in a genetically susceptible subset of the population, so they may need to avoid a high-fat diet, whereas there is another subset that would thrive on a high-fat diet, and would increase pattern A LDL, which would be a healthy lifestyle choice for them.

So, in a sense, I do think it’s a direction we should take as far as prevention is concerned. We should use the information gleaned from genetic testing in conjunction with what is considered a healthy lifestyle. In that respect, no, we should not ignore a healthy lifestyle before we are tested for genetic markers.

*****

Much of the article in question revolved around the “Apo” genes and the role they play in the development and protection of heart disease. The apo genes serve as blueprints for apolipoproteins. And what do genomics, genotypting, and phenotyping have to do with the discussion?

Apolipoproteins are proteins that carry lipids in the blood and control the metabolism of lipoprotein molecules. The apolipoproteins bind to lipids to form lipoproteins, which transport the lipids through the lymphatic and circulatory systems (wikipedia).

As the name implies, lipoproteins are complexes of phospholipids and apoproteins.

The lipid components of lipoproteins are not soluble in water (“oil and water don’t mix”), however because they amphiphatic molecules, they can surround the lipids, creating a lipoprotein particle that can be carried through the circulation. Dietary lipids also travel through the circulation via chylomicrons, that enable fat to move through the bloodstream.

Lipoproteins are the vehicles that shuttle non-water soluble triglycerides, cholesterol, and cholesteryl esters through the water-based based circulation, or bloodstream. [1]

Lipoproteins are classified by their density, which is determined by the ratio of phospholipid-to-apoprotein they contain (lipid being less dense than protein. Out of this we get the familiar terminology of VLDL, LDL, IDL, and HDL, and their subclasses.

Despite these terms often referred to in the pejorative (or complimentary in the case of HDL), they are essentially just transport molecules. VLDL is a lipoprotein synthesized by the liver and its purpose is to deliver cholesterol, cholestryl esters, and triglycerides to peripheral tissue. IDL is a VLDL that has been depleted of most of its triglyceride content and that is returned to the liver for recycling. HDL is involved in the removal of excess cholesterol from cells, returning it to the liver where it’s metabolized to bile acids and salts. LDL, derived from VLDL and ID, delivers the large amount of cholesterol and cholestryl esters it contains to peripheral tissues. Together, HDL and LDL essentially maintain the cholesterol balance of the body.

Nutritional genomics is defined as “the study of consequences of the influence of nutrients and other bioactive food components on the expression of the genetic material (Krause’s Food & Nutrition Therapy).”

Also germane to the discussion is phenotype. Phenotype is an organism’s actual observed properties (morphology, development, behavior) that result from the expression of specific genes of the genotype.

An organism’s genotype is a major, but not exclusive, influencing factor in the development of its phenotype. Phenotype is plastic; it can be influenced by environmental factors. In the context of human nutrition, we’re talking about nutrition, exercise, stress, sleep, disease, and pollution, all of which can have a substantial influence on phenotype (i.e., gene expression).

The genetic makeup generally is not the be-all and end-all for health and longevity, rather, it’s the phenotype, which is the expression of your genes, that is more important. In other words, if you have a genetic makeup which makes you more susceptible to heart disease, but those genes are not being expressed, then who cares, right?

The effect that the environment can have on gene expression is profound, and in this regard,
we probably have more control over our genetic expression than we think.

Ordovas explains that four main components under genetic control contribute to coronary artery disease risk, known as "syndrome x":

high blood lipids—total and LDL cholesterol, triglycerides;
impaired glucose tolerance and diabetes;
high blood pressure;
obesity (in the abdomen).

These components are more related to disorders of carbohydrate metabolism than anything else and studies show that when we lower the carbohydrate-content of the diet, these factors improve and the inverse is true as well. Most notably, perhaps, is the independent role sugar, and maybe even more specifically, fructose, play in the development of metabolic syndrome.

“The trouble is, people respond differently to lifestyle changes or to medications, Ordovas says. For instance, reducing total fat and saturated fat in the diet doesn't necessarily improve people's blood lipids equally—if at all. That's due to small differences in their genes.”

The trouble is, reducing total fat and saturated fat in the diet is misguided. It physiologically SHOULD NOT improve blood lipids, so the results are going to be poor from the outset, and the problem, or limitation to the studies on humans reducing fat intake, is that they also restrict the number of calories on their diet, and since most diets in the US are high in carbohydrates (and sugar and easily digestible “grain-based desserts” for example), the intervention diets necessarily reduce the carbohydrate content of the diet, and this could also explain any benefit seen with a ‘fat-reducing’ diet, where the subjects actually lower carbohydrates more than any other macronutrient.

“For example, "people with the APOE4 genotype are prime candidates for diet therapy. If they follow the standard cholesterol-lowering diet, they can expect about a 30-percent decrease in LDL cholesterol—which is what one can achieve with cholesterol-lowering drugs. But the APOE4 genotype is a poor responder to the best of these drugs."

Another confounder is LDL cholesterol sub-particles. We now know that the size and density of the LDL itself is a risk factor for heart disease. So a decrease in LDL cholesterol may not be as important as its density. For instance, if the total LDL cholesterol decreases, but the LDL itself becomes smaller and denser, we may have increased our risk for heart disease. Or, conversely, we can eat a diet higher in fat, which may raise LDL cholesterol or keep levels relatively the same, but shift the particles to a larger and fluffier profile, and making them less atherogenic.

For example, Siri and Krauss (2005) looked at the influence of dietary carbohydrate and fat on LDL and HDL particle size [2]:

Abstract: “Variations in the size and density distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles have been related to risk for cardiovascular disease. In particular, increased levels of small, dense LDL particles, together with reduced levels of large HDL and increases in small HDL, are integral features of the atherogenic dyslipidemia found in patients with insulin resistance, obesity, and metabolic syndrome. Increased dietary carbohydrates, particularly simple sugars and starches with high glycemic index, can increase levels of small, dense LDL and HDL, primarily by mechanisms that involve increasing plasma triglyceride concentrations. Low-carbohydrate diets may have the opposite effects. Diets with differing fatty acid composition can also influence LDL and HDL particle distributions.”

*****

Ordovas believes this research on genetic factors influencing cardiovascular health will become more critical as people in developing countries adopt the higher fat diets and sedentary ways of the West. For many generations, there has been little selection against genes that predispose to coronary artery disease in these populations, so high-risk mutations have built up. These genes didn't express because the people were physically active and ate very low-fat diets.

Going back to phenotype, you can make an argument that certain genes weren’t expressed because the environmental factors didn’t cause us to express them. The fact that Ordovas has implicated high-fat diets and physical activity reveals his bias toward these two factors.

The lipid hypothesis of heart disease is so incomplete that it’s hard to take anything Ordovas says seriously after reading how he zeroes in on a high-fat diet and how it will presumably negatively affect coronary disease rates. Although, I wouldn’t rule out the idea that when Ordovas was quoted as saying - “[developing countries] are adopting a Western lifestyle, and we are seeing a huge increase in heart disease," - the author of the article inferred the Western lifestyle to be encapsulated by high-fat diets and inactivity.

Go back to the types of foods, rather than too much food, as the underlying issue of the growth of obesity, heart disease, and the many other associated diseases witnessed in more and more populations. I would hypothesize that the introduction to a significant amount of sugar and refined flour added to a population precedes the introduction of the aforementioned diseases. The fact that populations eat too much is a symptom of an underlying abnormality caused by the type of food in the diet. I would also imagine that the expression of genes that have deleterious effects would not be caused by foods we have been eating for millions of years, such as animals and their accompanying nutrient profile in terms of both quantity and quality, rather it would be the introduction and over-abundance of foods that are excessively high in substances that we are not well-adapted to eat.

It’s our actions that determine our fate, for the most part. Genes are involved, but they are in a sense downstream from the environment, which influences the expression of our genes, our phenotype.

It’s not a weak will or a behavioral aberration that’s pandemic: it’s not that we’re too damn lazy and we eat too much, it’s that we are choosing, and being told to, eat the wrong foods, which is driving our actions, i.e., eating too much and moving too little, which can be observed as the cause of the problem, when it is more likely to be an effect.

*****

So what can we do to prevent heart disease and other maladies of modern civilization (and increasingly, developing countries)?

Eat food we are genetically well-adapted to eat (meat & vegetables, some fruit, seeds, nuts and tubers).

Work and play the way were are genetically adapted to (frequent low-level aerobic activity such as walking; infrequent high-intensity exercise such as interval training and resistance training).

Get adequate amounts of sleep, sunshine, and social interaction.

Engage your brain, i.e., do things that stimulate thought.

____________________

1. Anybody who says that saturated fat is “artery-clogging,” you can use this information as an indicator that they have no idea what they’re talking about.

2. Siri PW, Krauss RM. Influence of dietary carbohydrate and fat on LDL and HDL particle distributions. Curr. Atheroscler. Rep. 2005;7(6):455-9.