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Nutrition Past and Future

25 Cholesterol Confusion 8 A Large and Fluffy Distraction 

I’m back to talking about Robert Lustig again with this video. Lustig is, as I said, a master at speaking with certitude about issues he apparently doesn’t understand.

Here he is on Tom Ashbrook’s NPR show talking about – what else? – sugar.

LUSTIG: It causes all of the peripheral metabolic diseases that we know about: heart disease, type-2 diabetes, probably cancer and dementia as well, hypertension. This is now costing the United States $147 billion a year. The bottom line is we wouldn’t need health care reform if we had obesity reform and we could do obesity reform with sugar reform alone.

Yes, sugar causes all this. Nothing else does. He can say this categorically, with no qualifications. The implication of this wild-eyed claim is that other factors in nutrition and lifestyle are innocent. Meat and fat don’t cause cancer or heart disease or diabetes, no matter what the epidemiology says, to say nothing of smoking. Sugar alone taxes the medical system. Usually scientists tend to avoid absolute and overly broad statements because they don’t want to be taken for fools. Lustig isn’t worried about that.

LUSTIG: People have, you know, demonized saturated fat for the last fifty years. It turns out saturated fat is pretty neutral in this entire story.

Saturated fat is neutral. Bad people have demonized it. Good people demonize sugar. Lustig is an authority who speaks with authority. He must know what he is talking about.

He expressed his opinions about sugar in an attention-seeking article published in Nature as well. He wants it regulated somehow. Don’t ask me how that would work. Most medical professionals no longer think fat is the primary culprit in heart disease, he wrote. There is no citation for this statement. I think this was probably just a feeling he has.

Those audio clips came from a radio broadcast that also featured Mark Bittman of the New York Times, who was there to correct Lustig as he spoke. He just didn’t.

BITTMAN: I’m a supporter of Rob. I think that he hasn’t said anything so far that I would disagree with.

I can’t blame people for being confused when people of such prominence in food and nutrition display ignorance on this scale. At least Bittman has gotten other things right.

Durianrider is a funny and interesting guy who comments about issues in nutrition on his YouTube channel. He found an amazing video clip of Lustig and I’m totally jealous of him for that. Here is a short excerpt from his discussion of it.

DURIANRIDER: Robert Lustig is an endocrinologist in California. So this guy’s not just off the street. He’s “academically qualified.” Now, he … pick the basic mistakes he makes. Listen carefully.

LUSTIG: … Fruits. Coconut. Olive. Avocado. Have no carbohydrate. There is no foodstuff on this planet that has both fat and carbohydrate at the same time. It’s one or the other, because that’s evolution, that’s nature, that’s what God did.

DURIANRIDER: So did you spot Robert Lustig’s mistake? Now this ...

Of course, Durianrider goes on to have some fun with this.

He points out that a man who is putting himself forth as an expert in nutrition says that no natural food has both fat and carbs. This is obviously completely false. You can see that both avocados and coconuts both contain carbohydrate. I want to bang my head against a wall when I hear a man calling himself a scientist explain this false statement by saying, “That’s evolution. That’s nature. That’s what God did.” Just try to unpack those three ideas at the same time. God acted through evolution to perfectly segregate carbs from fats in every possible natural substance that might somehow wind up in Robert Lustig’s belly. This is a professional level of foolishness. You won’t be able to match him at this so don’t even try. Once again, we have a low carber dealing with science at an ideological level.

Lustig also appeared on NPR’s Science Friday. He didn’t talk for long before he said something way out there.

LUSTIG: Because all food is inherently good. It’s what you do to the food afterward.

All food is inherently good. That does have a certain ring of truthiness, doesn’t it? Don’t think about that too hard, though. For one thing, food in one culture may be seen as disgusting in another culture. Food isn’t that easily defined. Humans the world over eat substances like clay, for example. Next, some normal foods are toxic unless you process them. Think of mushrooms or kidney beans here. Moreover, there is no reason any independent organism from us would evolve to be good for us to eat. How would a plant, for example, evolve to be healthy for us? Other than plants that produce fruits to entice the fruit eater to spread their seeds, I don’t know how that would work. We have cultivated plants to make them better for us. We have made them as good to eat as they are. But never mind all that. Childish beliefs seem so convincing coming from a scientist.

Lustig gets goofy talking about evolution a bit later.

FLATOW: Why is it, then, that we evolved for eating fruits and honey and things that do contain sugar like that?

LUSTIG: That's a great question, and I can't tell you the absolute answer, but let me give you a little piece of evolutionary interest. We as human beings really only had sugar available to us one month a year, it's called harvest time. And the fruit would fall to the ground, we'd gorge on it, consume it like crazy. That would increase our adiposity, it would increase our fat stores very specifically. And then what would come after that? Four months of winter, no food at all. And so putting on those extra pounds in advance of a four-month famine was actually adaptive and actually let us make it through winter so that we could repeat the cycle all over again. It was actually metabolically and evolutionary adaptive.

The problem is that we now have a maladaptive situation because sugar is available 24/7, 365 in amounts that has never been known to man previously. How do we know this is true? Because the orangutans in Papua New Guinea have what are known as masting fruit orgies every January when harvest time comes, and the food falls to the ground, and they do exactly the same thing. We assume that this must be the reason sugar was put here for us in the first place.

Sugar was put here for us in the first place? This is his piece of “evolutionary interest”? Sugar was put here, people. That’s just science! And did he say that our ancestors went four months of the year eating nothing at all? “No food at all,” he said! What the hell is he talking about? He also said we only had sugar available one month per year. Didn’t Ira Flatow just ask him about fruit and honey?

The Hadza are an ancient people from the place where we actually did most of our evolving and they are able to collect fruit for a few months and then collect honey for at least a few months after that. There is no one-month harvest of sugary foods.

In fact, between honey and fruits, sweet foods are available continuously to the Hadza through both the wet and dry seasons.

Our chimpanzee and bonobo relatives are frugivores and they have to eat more than one month per year. Different fruits become available at different times. Go to your local farmers market and do your own research on that. As of this moment, it’s my apple season. My favorite figs and watermelons and pawpaws are gone, and before they were gone I was eating peaches. They were all put here by God for me to eat, right? Never mind that I put myself where I live, and, oh, never mind. What else did he say?

Yes, orangutans. Didn’t he say that orangutan feeding behavior is the proof that fruit and sugar make us fat? And didn’t he say that all natural food is good for us? Now he is saying that fruit makes orangutans fat? Where is the consistency? Anyway, orangutans have specific metabolic adaptations to help them put on fat. It’s important for their survival. Where they live the food supply isn’t steady.

You can see a graphic here showing you that they are not like us. They have a much lower basal metabolic rate. Chimpanzees, who are also frugivores, have higher metabolic rates than us.

We might expect that any animal that experiences seasonal variation in food availability will be able to vary its body fat reserves. Dr. Lustig could easily have chosen a carnivore to illustrate this, like the arctic fox. Do you see, Dr. Lustig, this clear evolutionary evidence of meat specifically causing an animal to pack on fat?

Anyway, here is his comment that is my topic in this video.

LUSTIG: … dietary fat does raise your LDL - that's true - but there are two LDLs, not one. There's one called large buoyant, and there's one called small dense. When you measure your LDL levels in your blood, you measure both at the same time. It turns out the large buoyant has nothing to do with cardiovascular disease. They float. They go along inside your blood vessels. They're too large to get under the surface of the cells that line the arterial wall. They don't cause anything. The small dense ones, though, those are the ones that are driven up by carbohydrate, and they are small enough to get under the surface of endothelial cells. They're the ones that start the foam cell process. They're the ones that start atherogenesis, and they're the ones that have gone through the roof, because when we took the fat out, the food tasted like cardboard. We had to substitute something. We substituted carbohydrate. So, yes, our percent fat went down, and our percent carbohydrate went up astronomically, and that drove hyperinsulinemia, drove liver fat, drove all the processes I've mentioned before, and that's how we got into this mess. We have to get out of it.

This is the LDL subclass argument. Large buoyant LDLs cannot penetrate the vascular wall, he says. This is totally false. Of course, if you believed that you need foods to be fatty so that they will not taste like cardboard, you might fall for this one, too.

You also might fall for it if you were an Atkins Foundation-funded researcher. He is just towing the company line here.

Lustig has cast his lot with the agenda-driven fat-promoters at Atkins.

He says Atkins works. Works for what? Works at causing systemic inflammation? Works at damaging your carbohydrate metabolism? Works at selling misleading books to a confused public? Maybe that’s what he meant here.

As you know by now if you’ve seen my Lipidologist Lost video, this speculative claim about LDL subclass isn’t even endorsed by a low-carb lipidologist. It’s a flimsy speculation based on ignorance, which makes it perfect fodder for the Paleo broscientists as well. Here is Mark Sisson implying that it is only the small, dense LDLs which are problematic. Even Mark Sisson won’t directly say in his book that the larger LDLs are innocent.

Robb Wolf doesn’t mind saying that, though. The large LDLs are benign. Small LDLs are caused by carbs. The government doesn’t keep up with the latest broscience, and so they appear to be trying to kill you even if that isn't their intent. When a broscientist casts himself as an enlightened source of responsible health advice and the legitimate scientists funded by the NIH as dummies who are unwittingly harming you, you should mentally translate this language into, “I want your money and I will say whatever is necessary to get it.” Most everyone in the field of nutrition understands that good carbs lower cholesterol in comparison to saturated fat and are associated with improved insulin sensitivity and better cardiovascular health. Wolf pretends that everyone is insulin resistant because he knows that the metabolically broken are his best customers.

Here is the bottom line on LDL phenotype. This is a distraction. It is a novel biomarker that people got a bit too excited about which is not holding up as a good way to identify people at risk. This measure was never intended to be used for promoting a low-carb diet. It is a huge and unwarranted leap to declare that large LDLs are not atherogenic simply because diabetics and the insulin resistant display a particular phenotype in their LDLs.

This is why the low-carbers make this claim. High-fat diets do skew the distribution of LDLs toward larger sizes. This is what high-fat-feeding does, so in their minds, it must be a good thing.

This study was well-controlled so a conclusion can be drawn from this that dietary fat caused the change in phenotype to larger LDLs.

The primary reason low-carb increases the overall LDL size is because low-carb causes LDLs to be jammed with more cholesterol esters, which are dangerous because they are difficult to remove once deposited in the artery wall.

Diabetics and those with metabolic syndrome have a characteristic lipid profile characterized by high triglycerides…

Low HDL, and small, dense LDL. The insulin resistant and diabetic are at increased risk of heart disease and they make up more of our population now than in the past, so they have overly influenced the perception of the way heart disease works for some.

Diabetics are special. Their vascular walls are more permeable. They and other dyslipidemic individuals will tend to have excess small, dense LDLs which are relatively depleted of cholesterol but these LDLs still have ApoB particles, making them atherogenic for all the reasons the promoters of this hypothesis say. If you have a lot of them, that is definitely a bad thing. But if you have metabolic syndrome or diabetes, you should already know that you have a reason to be concerned about heart disease without knowing your LDL phenotype. Knowing that your LDLs are generally smaller doesn’t necessarily help you that much. It's up to your doctor to figure out what drugs you need to manage that risk. I don’t disagree with any of the claims that the Paleo promoters or anyone else make about small LDLs. What I object to is the claim that these are the only LDLs that cause heart disease. There is no reason that this issue should create confusion about saturated fats, and there is no reason to associate these LDLs with healthy carbs.

When novel biomarkers are debated, this happens in the context of identifying who is at the highest risk of events in the late stages of heart disease. We must not let this confuse us about how heart disease works over many decades. Even when evaluated in its appropriate context, the LDL phenotype idea has its problems. There has been a lack of standardization over testing methods and definitions, as well as the issue of the cost associated with the tests that are needed to measure this.

Moreover, because the LDL phenotype idea is so closely associated with metabolic syndrome, it hasn’t proven its value as a biomarker beyond the usual biomarkers that identify metabolic syndrome.

There have been a number of studies that have not found LDL phenotype to be predictive of the degree of atherosclerosis or hard endpoints.

The best known study to raise doubts about the importance of small, dense LDL as a predictor of the degree of atherosclerosis was this one. This study showed that both of the basic phenotypes of LDL are atherogenic and if anything, the large LDLs are worse.

This study found that large LDLs predicted coronary events. Large LDLs are not benign.

This recent systematic review said that measurements of LDL phenotype are not ready for routine clinical use. There have been other studies showing that the LDL phenotype idea doesn’t work well but my purpose here is not to tell cardiologists how to do their jobs. I am only interested in giving you the information you need to understand that the claims in the low-carb world about LDL size are flat-out bogus.

Here you see the sizes of the major lipoproteins. Look at the inner column called “Particle diameter”. The measurement unit is nanometers. You can see that LDLs here go up to 25 nm.

Here you see that LDLs can be as large as 27.5 nm.

Now consider this paragraph. The larger particles called VLDLs and even smaller chylomicrons can enter the subendothelial space, which means that Lustig is wrong. Much larger particles than large LDLs can enter the artery wall, all the way up to diameters of 70 nanometers.

The largest LDLs are much smaller than 70 nm.

In experiments on vascular tissue from rabbits, IDLs and VLDLs were shown to be able to penetrate the artery wall, although not as easily. If those bigger particles can get in, large LDLs should have no problem causing trouble.

My earlier slide that said “Chapter 17” at the top referenced this study. This showed that VLDLs and their remnants do make their way under the surface of the artery. VLDLs are larger than the largest LDLs. If VLDLs are atherogenic, how can anyone say that large LDLs are not?

Read some scholarly articles that discuss LDL size and you will see the same few ideas and references repeatedly appear in a single boilerplate paragraph. It's almost as if all these authors cut-and-pasted the same paragraph and then made a few alterations. Read enough papers on this subject and you'll see what I mean. Small LDLs don’t bind as easily to the LDL receptor. They are more attracted to proteoglycans. They are more easily oxidized. Fine, but so what? Why would we conclude from this that other LDLs are benign?

Cholesterol-rich large LDLs are especially attracted to the LDL receptor, but your cells can only incorporate so much cholesterol.

You can see that all the way back in 1983 Brown and Goldstein had recognized that larger lipoproteins than LDLs were likely promoting disease in their familial hypercholesterolemia patients.

As Dr Dayspring has said, it is not valid to conclude that a distribution of LDL sizes favoring large LDLs indicates safety from heart disease. People with familial hypercholesterolemia tend to have just such a pattern and we know that FH is deadly.


This was the original paper to make this observation. FH patients had LDLs that were larger and less dense.

Moreover, larger LDLs may be packed with an ester called cholesteryl oleate, which may cause them to be more atherogenic.

In animal models, there have been inconsistent findings regarding LDL size and atherosclerosis. This editorial makes reference to a study that showed small, dense LDLs to be less atherogenic.

When Mark Sisson says that you are safe if you have few or no small, dense LDLs in your blood, he is displaying his ignorance on this topic.

Everyone has all the different sizes of LDL. Mark Sisson has small LDLs, guaranteed.

All the different sizes of LDLs are atherogenic in excess because they are all packing cholesterol. This was an excellent article by Frank Sacks and Hannia Campos on this issue.

They covered some of the studies up to 2003 that contradicted this hypothesis.

They also disputed the importance of LDL oxidation in atherosclerosis. I will talk about this topic in a later video.

Despite all this, you may still believe in the importance of this issue and continue to eat a low carb favorite like beef. Let’s take a look at a study funded by the beef industry and see what it says about LDL size.

This study looked at two low carb diets loaded with beef. One was higher in saturated fat than the other. Saturated fats were added to the high-fat diet through the use of fatty dairy products.

Small, dense LDL concentrations were reduced during the low-saturated fat diet. More saturated fat meant more scary small, dense LDLs. Moreover, total cholesterol, LDL-C, non-HDL-C, and yes, Dr. Dayspring, apoB were all reduced by a diet with less saturated fat. Adding dairy fat made all these worse.

Triglycerides were also worsened by the high-saturated fat diet.

I was very pleased to see that the authors considered the problem of heme iron in beef in their commentary. I think this is a very important concern. I’ll talk more about this in my Ancestral Cholesterol videos.

If you are fixated on this issue for some reason, one diet that has demonstrated its success with changing LDL subclass in the preferred direction is the healthy low-fat diet of Dean Ornish. Ornish’s approach succeeds on so many levels, I’m not sure why any intelligent person would disregard it.

It is very hard to find a published journal article that tries to back up the claim that there are LDL sizes that are not atherogenic, yet low-carb bloggers will say that large LDLs are innocent anyway, as if it were a fact. I was able to find just such an article, though. Here you see it. The claim is made that the larger sizes of LDL do not fulfill the criteria of atherogenicity. The authors, led by Stanislav Oravec of Bratislava, Slovakia, have hereby declared the existence of a newly described type of hypercholesterolemia, a non-atherogenic hyperbetalipoproteinemia LDL 1,2. This seems like a big announcement of a condition with a big name. They are saying they have found people with high cholesterol that is not atherogenic because they have the right LDL phenotype.

This is a really interesting paper. They found 145 people with this newly discovered condition. How many people did they screen to find these special 145? They did not say. It does seem odd that just in Slovakia they found 145 people with any medical condition that has never been described by anyone else before this. You see how they determined they had no atherosclerosis. There are no scans or any other pictures in this article. You’ll need to take their word for all this. As you see, they said there was simply no impairment of the circulation in these people with their fancy new phenotype. And by the way, they did have some atherosclerosis after all. Apparently this special condition is at least semi-atherogenic, which sorta ruins the specialness of it all.

Fortunately, Oravec has put out a better paper since then. Here he clearly tells us that in young people, he and his colleagues found that large and intermediate LDLs were associated with premature heart attacks and small, dense LDLs were not. Yes, you heard me right, low carbers. Read it for yourselves. So much for non-atherogenic familial hyperbetalipoproteinemia 1,2. They said that small, dense LDLs are probably an age-related phenomenon.

That’s not the only study of younger people to shoot holes in the small, dense LDL hype of the low-carbers. Here, obese boys were fed meals with different levels of carbs and fat. A high-fat meal increased the number of small, dense LDLs. The high-fat meal also decreased HDL. The authors found that shifting a meal’s contents from fats to carbs created a better-looking lipid profile. I wonder how a broscientist would explain this one.

This study also looked at young people, in this case Finns, over a six-year period. These authors did not find any evidence that small LDL particle size was associated with increased LDL oxidation or metabolic syndrome. What is a modern caveman to do with this information? Adapt, perhaps?

I’ll close this video with the words of Evan Stein, whom you have heard from before in my videos. He has written, and this is pretty great:

“For the practicing clinician, however, the major argument for extending measurement of subclasses into the mass market is the hypothesis that one subclass is more atherogenic than another. Because evidence clearly indicates that all Apo B–containing particles are atherogenic, this reasoning is akin to the argument that an Uzi submachine gun is more deadly than an M16 or an AK47. Obviously all are potentially lethal, and although this assertion may interest gun aficionados, it matters little to law enforcement or to general public safety if the sole objective is disarmament!”

“Subclass studies have proliferated over the last few years, but many of these studies were funded or subsidized either by suppliers of the assays as a method to expand their use and move them into mainstream practice, or by pharmaceutical companies in an attempt to claim some advantage over other therapeutic agents, especially when the LDL-C or Apo B reducing ability of their drug was less competitive. Although these studies have created more heat, they provide little additional light.”

There is nothing I can say that is better than that on this topic. Evan Stein is a true expert and he isn’t writing diet books. Two other true experts who only deal in respectable science are Michael Brown and Joseph Goldstein. The time has come to look more closely at their work. They won the Nobel Prize. But did you know they were "wrong"? That’s what at least one doctor says. You can decide if he’s right after you watch the next video.