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Nutrition Past and Future

21 Cholesterol Confusion 4 The Map Is Not the Territory 

Anyone who follows the latest news in cardiology knows about the failure of the AIM-HIGH trial. This was a trial based on the idea that patients with the characteristic high triglycerides and low HDL of the metabolic syndrome could be helped by using niacin to raise their HDL in combination with a statin. Statins are well-proven. There wasn’t a doubt that they would help the people taking part in this trial. The question under investigation was, would the niacin help them, too? It was found that the combination did what it was supposed to do for their biomarkers. HDL went up. Triglycerides went down. However, the group receiving niacin along with a statin didn’t do any better than a control group taking the statin alone. But didn't their HDL go up? Isn't that supposed to be good? What can be learned from this trial?

And what can be learned from that other finding that I mentioned in a previous video which showed that people who have higher HDL due to their genes don't seem to have any extra protection from heart disease? We’ve been told for many years that HDL is the good cholesterol. We’ve been told that people with high HDL have a lower risk for heart disease in ecological studies. Shouldn’t the higher HDL from niacin or the higher HDL from genetics provide some benefit?

Both of these findings confused a lot of smart people in cardiology. The people who study heart disease think a lot about biomarkers. Biomarkers provide a useful model for them to be able to understand how heart disease works. HDL particles do the work of reverse cholesterol transport, returning cholesterol to the liver. That’s why it is considered good cholesterol, and there is epidemiology to back that up. More HDL should mean lower risk.

Unfortunately, the HDL hypothesis has not yet produced anything a clinician can use. It seems HDL is too complicated for us to be able to say that more of it is better. I consider the disconnect between our expectations of HDL and the performance of HDL in these studies to be evidence of a problem with our conceptual model of heart disease. There is a saying that “the map is not the territory.” What this means is that a representation of a thing should never be confused with the thing itself. Maps are useful. They give us a model of reality that we can work with and understand. Biomarkers are a valuable representation of the real heart disease process. They are undoubtedly helpful. I wouldn’t dispute that for a moment. However, our representation of the reality of heart disease no longer serves us when we forget its limits. It isn’t helpful if it causes us to ignore important information. It fails us when we miss fine distinctions.

Read this slide and you will see that the low level inflammation that is so common in industrialized societies is practically non-existent in people living in the Ecuadorian Amazon. Biomarkers of inflammation are associated with heart disease in affluent societies. They are not associated with heart disease in those Ecuadorians. But why? Shouldn't the usual markers of the inflammation we see in heart disease work with them? Why should they be so different this way? The answer is that they are in a different situation.

Unfortunately, in epidemiology the easiest populations to study seem to get the most attention. It's relatively easy to collect data on people in affluent societies. Our doctors deal with patients living in these societies, and they read up on studies  looking at people just like them. But I ask you to consider that humans didn't always live like us. If we stay too focused on people just like ourselves, we might miss out on some important observations. If one were to try to look back at our ancestors, or to look around at other species, important insights about health and disease might be found. The latter idea of looking across the Animal Kingdom for new ideas in medicine is called One Health. One Health tries to build partnerships between doctors who work with animals who are humans with doctors who work with animals who are not humans. We animals have a lot in common with each other. This new effort to take advantage of that fact is an example of health professionals using creative ways to broaden their horizons and find new inspiration.

We need to recognize that most of our research into heart disease is done in the context of societies consuming high-animal-fat diets. This creates a bias in our observations. Another layer of bias is added by the fact that the people who are most often studied in medicine are the sick and dysfunctional. Much money is to be made for anyone who can find a new drug to deal with the obesity problem, for example, so the obese are the object of a lot of research. I believe this is a big part of the explanation for why carbs are so misunderstood today. As you will see in my Evolved Fuel System and How to Become Insulin Resistant videos, the loss of the ability to properly metabolize carbohydrates is probably not caused by eating too many health carbs. Instead, it is caused at least in part by consuming too much meat and fat along with refined carbs that we shouldn’t expect our bodies to cope with. And yet we hear over and over that carbs make us fat.

Sugar is an easy punching bag, but the problems with it are exaggerated. High saturated fat diets probably cause sugar to seem much more harmful than it really is. Sugar shouldn’t have to take all the blame for that.

It may well be that the demonization of carbs in the media and on bookshelves is the result of our narrow focus on the tiny fraction of humans in our long evolutionary history who have consumed high-calorie, high-meat, high-fat diets and then added refined sugar to that terrible mix. That tiny, deviant fraction of all humans to have walked the Earth is us.

An overweightlow carber might feel reassured because his triglycerides are under control. Carbs will raise your triglycerides, he'll say. However, chronically elevated triglycerides in an obese person aren't equivalent to somewhat elevated triglycerides in a healthy person. We shouldn't get too excited about triglycerides without some proper context.

Remember, Dean Ornish was able to demonstrate both a regression of arterial plaques and a reduction in adverse events using a low-fat, high-carb diet.

He managed that even though triglycerides went up for the people receiving his diet. This should cause us to be open to different interpretations of biomarkers that haven’t been proven to be closely connected to the disease process the way LDL cholesterol has been.
The fact is that atherosclerosis is primarily a condition of cholesterol build-up, not triglyceride build-up.

Triglycerides don’t seem to bear much relation to the degree of atherosclerosis when measured at autopsy. This is one version of the atherosclerosis at autopsy argument you won’t hear Gary Taubes make. He hasn’t exposed his ideas about triglycerides to the same skeptical treatment he has applied to cholesterol. He has not pursued the truth, but rather fame, money, and influence. Consequently, he has found those, but he hasn't found the truth about heart disease.

Mark McCarty wrote a very good article on this topic. On the right, you can read how he draws important distinctions between the raised triglycerides seen in healthy people who eat carbs and the pathologically elevated high triglycerides of the insulin resistant and obese. One must understand how these two conditions are different, just as the conditions of the Ecuadorians in the Amazon and the conditions of the affluent are different.

I’ll add that even if we decide that triglycerides are important to keep on the low side, and with that I would not disagree, vegan diets seem better than omnivorous diets for this purpose. Healthy vegan diets generally outperform any other diet for nearly any biomarker related to heart disease or diabetes that you can think of.

When people develop abdominal obesity and live sedentary lives, they are in a different metabolic condition than people who are active and slender. We are less active and fatter than humans of the past. It is against that backdrop that new biomarkers for heart disease are investigated. Researchers want better ways of identifying those people who are at risk of heart disease but who don't have unusual levels of LDL cholesterol. It is from this type of  thinking that misinformation has arisen about large and fluffy LDL. This is supposed to be an exciting new biomarker that tells us more than just LDL cholesterol. I’ll deal with that red herring in a later video.

For now, I'll just say that if you want to talk about biomarkers, there is something you should remember. LDL cholesterol is the best studied and most validated risk factor of them all. ApoB or some other measurement may turn out to be better, but at this point it must be acknowledged that that doesn’t have the pedigree of LDL cholesterol. ApoB hasn’t been studied for fifty years. It hasn’t been proven to be predictive in a variety of cultures the way that LDL cholesterol has been. LDL cholesterol has been shown to be predictive over multi-decade time scales. Notice that the other well-known biomarkers that have been recently floated as risk factors are still are basically a part of the LDL story. They are just embellishments of the link between LDL cholesterol and heart disease. I consider newer ideas like focusing on small, dense LDL or particle numbers to be just the usual LDL cholesterol story with a twist of metabolic syndrome. Nothing fundamental has changed.

Here’s a question I’d like you to ponder. Every time a new study comes out stating that a particular biomarker was the most predictive one within a particular group of patients over a particular period of time in some particular place, does that mean we need to rethink our basic understanding of how heart disease works? Of course not. We’d be forever chasing our tails if we did that. Yet the bloggers and broscientists, who can't be sued for malpractice for the nonsense they publish, will tell you that they are on the cutting edge of medical knowledge and you should listen to them over the so-called mainstream. Their irresponsibility is appalling.

The makeup of the patient population has changed over time. Today doctors are dealing with a lot of obese, insulin resistant, and diabetic patients. Therefore, these patients and their problems have received a lot of attention from the research community. It must not be forgotten, however, that they are different from the rest of us. For example, this important study found that the artery walls of diabetics are far more permeable to LDL than those in healthy controls. Risk factors didn’t show any difference between these diabetics and the non-diabetics. And yet they were different.

This paragraph is a rundown of some of the possible reasons for this result. These all assume that the condition of the diabetic’s arteries is different than that of a normal person’s.

As I said earlier, high triglycerides in the diabetic and obese are different than slightly elevated triglycerides in a health person eating a high-carb diet. Low carb diets tend to lower triglycerides in the insulin resistant because of the shift in metabolism that they cause from glucose oxidation to fat oxidation. But the question I have for the low carbers is, how does low carb solve the underlying problem of insulin resistance? Isn’t low carb just an attempt to get by with a broken metabolism? Doesn’t it lock the low carber into an inflamed state as the body stresses itself working with a second-rate fuel supply all the time?

The body does what it can to deal with whatever you throw at it. It’s job is to maintain homeostasis. It will find a way to deal with a low carb diet. However, it is not smart to unnecessarily stress the body. The body will break down in time on its own. There is no need to rush the process.

Triglycerides are atherogenic when they get too high. I am not saying otherwise. However, the importance of them may be more as an indicator of an underlying dysfunction. High triglycerides are representative of the broken carbohydrate metabolism of the metabolic syndrome.

Unfortunately, a few doctors will misinterpret the latest research and latch onto pet theories because they haven't considered the big picture. They may not understand the results of epidemiological studies because they haven’t thought seriously about what normal looks like in societies unlike their own.

Add to that source of confusion those Atkins-sponsored trials that do not make clear the nutritional quality of the food they are calling “carbohydrate” and you have laid the groundwork for a lot of misunderstanding. You’ll see how big a problem the issue of carbohydrate quality in diet trials is in my Cherry Picked Research videos.

I have tried to give real examples of these various sources of confusion in action in all these Cholesterol Confusion videos and this one will be no different. Here I’ll be picking on someone who is very smart and who I respect a lot. I’m talking about Richard Kones, a doctor I referenced in my How Much LDL? video. Here he is writing about low-carb diets. He starts out with a frank admission. “Nearly everyone is baffled about why nothing ‘works’ and (is) desperate for answers.” He then points out that very few low-carbers are actually successful at losing weight. His candid statement of bafflement tells me that, no surprise, Dr Kones has not looked at the literature from a vegan perspective. If he did, he might see that vegans are highly successful as a group at maintaining a healthy BMI.

Kones makes some key observations about heart disease which I wish more people understood. He says that even if most of us have a low short-term risk for heart disease, we still have a high long-term risk. He is aware that few of us are succeeding at limiting our long term exposure to risk.

Kones expresses support for primordial prevention. He understands that the scientific support for diets low in meat and high in fruits and vegetables is overwhelming. I think these are some of the most important concepts in heart disease for the public to understand. It is after this promising setup that he discusses low-carb diets.

He has seen the studies showing some of the serious downsides of the low-carb approach. I read through this article and thought that he was going to conclude it with an unequivocal rejection of the low-carb strategy. How could a responsible person look past such serious causes for concern as the ones you see here?

Yet in the end, the many studies showing weight reduction for people on low-carb diets without their risk factors going completely out of whack convinced him that there is a place for low-carb in heart disease risk management. I think Kones took false comfort in biomarkers. He has confused the map with the territory. He apparently didn’t understand that any diet that produces weight loss should either improve or at least not make worse those biomarkers. The effects of weight loss are what he was seeing, not the effects of carb-restriction. He doesn’t seem to have read about all the controlled trials showing how protein and saturated fat produce an insulin resistant state. He has not critically looked at the low-carb weight loss trials the way I will in my Cherry Picked Research videos.

He seems to be saying that for the patient who is probably already insulin resistant, a diet that worsens insulin resistance might be appropriate. That makes no sense to me. I hope Dr Kones changes his mind about low-carb diets one day and condemns them. All responsible people in medicine should speak clearly about how risky low carb is.

Dr Kones was one of my references in a past video in which I showed you how little LDL we need to be healthy. The low levels you truly need are important to keep in mind when you read claims by the confusionists, who say that you should not worry about high cholesterol because cholesterol is necessary for life. Of course it is. And just a little cholesterol is plenty. That is a dumb argument but it needs to be dealt with and that’s what I’ll do in the next video.