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Nutrition Past and Future

23 Cholesterol Confusion 6 Dietary Cholesterol (And the Magic Egg) 

Recently this study made the news. The authors asked people having the plaque in their carotid artery measured to complete a questionnaire. The questionnaire asked them what their egg-eating habits had been over the years. The authors used that information to calculate something they called "egg-yolk years," which gave them a way to measure what their exposure to egg yolks had been as a function of time. They then compared their egg-yolk years scores to the results of their plaque scans to see if there was a relationship between them. The idea here was that they wanted to see if the cumulative effect of more egg-yolk eating over the years resulted in more plaque in their carotid arteries.

This study was discussed on a podcast that I really like. The person you will hear doing most of the talking in the clip I'm about to play is Steven Novella, and as my channel viewers know, I am a fan of his. Unfortunately, I think he made some errors in reasoning as he interpreted this study. Listen and see if you agree. I've edited his comments a bit to save time.

STEVEN NOVELLA: Are eggs good for you or bad for you? What’s the bottom line?

JAY(?) NOVELLA: Eggs overall are good for you and I don’t care what you say.

EVAN BERNSTEIN: I think they’re a good source of protein and other nutrients.

JAY NOVELLA: And riboflavin.

EVAN BERNSTEIN: Right, well, like anything that’s, well, almost anything, it’s not without its negatives but I think the positives outweigh the negatives.

STEVEN NOVELLA: They, yeah, that’s basically what I would say, they – cholesterol in eggs actually doesn’t increase your serum cholesterol. This seems a little counterintuitive.

JAY NOVELLA: Is that because of the nature of cholesterol in the eggs or the nature of cholesterol itself?

STEVEN NOVELLA: I think it’s the nature of cholesterol itself. Eating cholesterol in general doesn’t raise your serum cholesterol. The type of fat – the saturated fats and the trans fats – those are the bad ones.

Everyone in on this discussion likes eggs and thinks they are mostly good for us. These are their a priori beliefs. Dr. Novella thinks it is counterintuitive but true that the cholesterol in eggs doesn't raise your blood cholesterol. He does grant that saturated fat will raise your cholesterol. With his views on eggs out of the way, he then talked specifically about this study measuring egg-yolk years.

STEVEN NOVELLA: They’re starting with people who have all had studies of their arteries to see how narrowed they are … Then they came up with this measure they’re calling “egg-yolk years,” “egg-yolk years,” which is the number of eggs per week times the number of years you’ve consumed those eggs, which is similar to – you know, when we take a smoking history we usually record it in “pack years,” how many packs per day times how many years you’ve been smoking as sort of a rough estimate of your total, you know, risk or burden from smoking … They’re using just a survey data. There’s just potentially many confounding factors in here … To me, this is the killer for this study. They looked at total cholesterol, triglycerides, HDL, and LDL. And guess what they found.


STEVEN NOVELLA: No freakin’ difference at all. No difference! So the eating eggs did not increase your total cholesterol, it did not increase triglycerides, did not lower HDL good cholesterol, did not increase LDL or bad cholesterol.

JAY NOVELLA: But doesn’t that break any possible connection?

STEVEN NOVELLA: Well, yeah! Right? Doesn’t that argue sorta strongly? … So what’s the mechanism then? So eggs cause atherosclerosis but not by affecting the lipid profile in any way?

You can hear they are a little exasperated with the conclusions of the study authors. Those results did not match with their understanding of diet-heart. Therefore the results must be wrong. These podcasters think the authors really goofed by publishing a study that they couldn't understand. Novella's cursory review of the research on dietary cholesterol left him believing it is harmless. Everyone leaves the discussion of this study with their prior conceptions intact. Eggs are harmless.

Because they found a superficially plausible reason to reject this study, they didn't have to think too hard about the fact that egg yolks are loaded with saturated fat. Novella did say saturated fat raises cholesterol, didn't he?

They were also sufficiently pleased with their knee-jerk reaction to this study that they didn't feel any special obligation to try to explain its actual results. Why did this association appear? The authors must have overlooked something. That's all there is to it. Let's move on. This reaction is very similar to the usual hand-waving reaction we see from low carbers when the latest epidemiological study comes out that they don't like. Confounders! Epidemiology is a pseudoscience! Next topic!

I am using this study and that audio because this incident gives us a chance to sort through a bunch of sources of cholesterol confusion all mixed together. This was all too good to pass up, despite the significant downside for me of criticizing Dr. Novella. The guy is brilliant so that makes this risky, and I like him so that makes this unpleasant. Counterbalancing all that is that one of the study authors is the great David Jenkins, whom I am happy to defend, and the fact that the topic of dietary cholesterol is so important.

This egg-yolk-years study reminds me of this other study that I mentioned in my Pesky Facts video. Animal fat, saturated fat, and cholesterol were all found to be associated with carotid intima medial thickness. The egg-yolk-years study is in line with prior research, but the prior research has been forgotten. The cycle of confusion about - and rationalizations for - fatty animal foods repeats itself and nothing is ever learned.

Let's look beyond the abstract of the egg yolk study. The people receiving the scans and filling out the questionnaires were there at the clinic because they had referrals to the clinic. Have you had a referral for a measurement of your carotid intima media thickness? I sure haven't. But I'm not at risk of stroke, though. Since 2000, the referrals at their clinic were scheduled on an urgent basis. Those people with the urgent referrals were the people who filled out these questionnaires.

The U.S. Preventive Services Task Force recommends against the use of this screening procedure in the general population. It carries risks and costs that make it of questionable benefit for even those at risk of stroke. It is almost certain that these people in this study were in effect systematically selected based on their vulnerability to cardiovascular disease. How many vegans do you think were in that group?

If we look at the table from the study with the cholesterol scores, we can see that Novella is indeed correct. There is no upward trend in LDL scores with the number of egg-yolk years.

However, if we look at the age at first visit, there is a clear upward trend. This is the major clue we need to understand this study.

Novella saw this and he remarked that egg yolk consumption was associated with age at first visit. Age is a risk factor for atherosclerosis. To him, this means that age acts separately from cholesterol, all by itself, to create atherosclerosis, which is a disease characterized by arterial plaques jammed full of cholesterol. We can cleanly separate the effects of both risk factors because they have nothing to do with each other. As you know by now if you've watched these videos in order, it is the cumulative exposure to cholesterol over time that largely explains why age is such a big risk factor. Novella noted that they controlled for age. He decided that there must have been another factor for which they didn't control. But what factor?

What factor would associate with egg-yolk years and plaque volume so well that it could create a false relationship that looks so good on paper? This reminds me of the overuse of the "correlation isn't causation" line. Saying that allows people to feel good about not having to think too hard. Here we have an association. The association is biologically plausible. There is no better explanation. But it is just an association so we can simply discard it. Notice how much we have to swallow down to accept his interpretation. Saturated fat doesn't raise cholesterol. Dietary cholesterol doesn't raise cholesterol. Something else that causes plaques tracks exactly along with egg-yolk years, but it is not egg-yolk years. If Novella didn't like eggs, do you think such a bright and skeptical person would not notice himself painting himself into a corner like this?

You know, Dr. Novella, it is amazing how well cholesterol tracks with deaths from heart disease in the old research. That mysterious confounder of cholesterol that causes heart disease really shadows cholesterol closely. I wish we could decipher what it is. This is one big riddle, isn't it?

Here's an old study with one man going on and off cholesterol supplementation from egg yolks. Once again, this mysterious confounder stalks cholesterol with eerie precision. How could egg yolks have been so cursed that they should have such a dastardly and persistent confounder? Pity the poor egg yolks. Some dark force has concealed their pure innocence through these many years. But we will nonetheless believe that they are good for us and do not raise cholesterol. That confounder will be discovered one day!

Let's think about this very simply. Were the egg yolk years scores lower for the people with lower egg-yolk years mostly because they didn't eat as many egg yolks each week? Or was their egg-yolk years score lower because they were younger? Is this starting to click?

Imagine this. What if every person in this bunch of patients at risk for stroke or who may have actually been suffering some sort of occlusion all had exactly the same egg-eating habits? What if every person in Canada ate, say, 14 eggs a week. How would that be represented in a table showing egg-yolk years matched with age? The answer is that the people with fewer egg-yolk years would have fewer egg-yolk years simply because they were younger. And that isn’t so far from what we have here. Now I realize this chart is showing the age of first referral, not simply the age of the patient. We are missing that other information. However, I think that without that information we can assume reasonably that this does reflect age to some degree. There are all sorts of things I can think of that would complicate that relationship, but let’s not get into that. The simple interpretation here makes sense and there is no reason we should reject it given the information. People at risk of dangerous levels of plaque in their arteries are more likely than not to be people who have over some number of years sometime in the past had high cholesterol, and eggs do raise your cholesterol. I’ll have more on that in a moment.

You may be wondering how I explain the fact that blood cholesterol was the same across their categories of egg-yolk years. Well, here is where we get into all the other sources of confusion. Older patients were more likely to be on statins, especially if they were getting urgent referrals for these scans. That would lower their cholesterol. You also have seen in my Primordial Prevention video that cholesterol tends to fall in men over 50 or 60 in high-fat societies. That would confuse things as well. Recall what I showed you in my autopsy video. Some of these people in this study may not be have been that far from the autopsy table themselves, no offense. Remember, we saw that there is no reason to think that cholesterol measured right at the end of life is representative of cholesterol levels over the preceding decades.

Dr. Novella, age is a risk factor for cardiovascular disease. You are right about that. Your mistake was in ignoring how age affects cholesterol levels. The literature you read told you how age affected the risk of adverse events. It didn’t tell you how age affects biomarkers like cholesterol. A helpful supporter of my efforts here named Richard found this quote, which explains this idea nicely.

Dr. Novella, you may not be familiar with this phenomenon but it really is true. This epidemiologist expressed exasperation that this factor has been repeatedly observed and then forgotten about and later rediscovered. This is just like the amnesia we've seen over past decades among the researchers in diet heart that kept a zombie controversy going for no good reason. Unfortunately, you are now re-animating this zombie.

Furthermore, egg yolk consumption has also been associated with diabetes, and diabetics sometimes have an LDL risk that is better quantified by LDL particle number than LDL cholesterol.

All this leads to what I think is the biggest flaw in Novella’s reasoning. That would be the map-territory problem I’ve told you about. He is equating the biomarker with the disease. That is wrong. They are not the same things. This study, in my opinion, brilliantly bypassed the map-territory problem by simply looking at the question that really interests us: does egg consumption relate closely to the severity of atherosclerosis? We learned that it does. All the rest is just moving the goalposts. We look at LDL because we care about plaque, not the other way around.

Novella reviewed the recent research on dietary cholesterol and concluded that it doesn't affect lipids very much. This is understandable. Recent reviews have overlooked a lot of valuable old experiments, allowing their authors to declare dietary cholesterol to be innocent. Not all recent reviews have reached this wrong conclusion, though. This review from 2001 found that dietary cholesterol adversely affects the lipid profile. More recent research sometimes clouds the issue. I'll show you what I mean now.

Another smart guy to find fault with this study is Dr. David Katz, the director of the Yale Preventive Research Center. He has performed his own research on dietary cholesterol. He said the study we are talking about only showed association, not cause and effect. He must think eggs are magical. They have special properties that keep their saturated fat and cholesterol from hurting you. He thinks that this study only shows us that eggs associate with the foods that really do hurt us like sausage and bacon. That's called confounding, he says. Meats have saturated fat and cholesterol that are bad, unlike eggs which have saturated fat and cholesterol that are good.

He also suspects that the researchers in the egg-yolk years study were biased. That bias allowed them to find whatever they were looking for in their observational study. He thinks you can find associations for anything if you look hard enough. If he is so convinced of this, then I have a challenge for him. Dr Katz, I want you to get a study through peer review that finds an association between raw fruit consumption and arterial plaque volume. I dare you. I think you can't do it. The ball's in your court now, smart guy. Associate away.

The problem as he sees it is that David Jenkins is a vegan. That makes him biased. Vegans are biased against eggs.

People like him who eat eggs are not biased in favor of them. Why not? He went for a stretch not eating eggs. Now he eats them but not for breakfast. Therefore, his egg-eating doesn't bias him.

Everyone knows that the minority is biased and the majority is not biased, right everyone? Let's put that logic to a popular vote! That will prove that it's true!

Katz doesn't care for observational studies. He prefers intervention studies. His favorite studies are his own studies. It's funny how that works, isn't it? Since he has done studies that make eggs appear harmless, it would be pretty surprising if he said he liked a study that found them harmful. If he did that, we might wonder what was wrong with his studies. By the way, this sort of thinking is a huge source of the misinformation in the nutrition business. Of course, researchers like their own research best. Then they pay attention to other contemporary research. Then, after a while, that research gets a lot less interesting as the years pass. The worst thing that can happen to a good study is for its author to die. It becomes easily distorted and forgotten. That is Ancel Keys' problem. Now any fool with an internet connection can abuse his work with impunity. It was his fault that he only lived to be 100. He shouldn't have died if he really cared about helping people.

So what were the studies that Katz conducted that exonerated eggs? The first one looked at endothelial function. This one found that while eggs didn't raise cholesterol, oats lowered cholesterol. I suppose we are to assume that the starting cholesterol in his subjects was the right cholesterol for them and the oats did something weird by lowering it. It's all relative for Dr. Katz so he can say that eggs don't raise cholesterol, oats just lower it. There was no bias behind that interpretation, I'm sure. Yes, the thinking here really was that poor.

I guess he thought all the starting values here were right and proper. A BMI of 28 is overweight on the usual chart but for Dr. Katz I guess a BMI of 28 is just right because that's what they started with. Total cholesterol at around 200 is far above that of our ancestors but for Dr. Katz, that level is just right. As you will soon see, it matters what the starting value is for cholesterol. People with higher cholesterol than our ancestors won't be much affected by dietary cholesterol. But people with low cholesterol like our ancestors usually are affected by dietary cholesterol. It's all a matter of perspective, or perhaps one might say, bias.

Which brings us to his next study. Here he called his subjects hyperlipidemic, and as you see their LDL scores were terrible. This one involved first prepping his subjects with heart-damaging meals of either three whole eggs or a sausage and cheese sandwich. Then he fed them either whole eggs or egg substitutes and measured their endothelial function. We are not told what they ate for their other meals. They did eat other meals, right? Doesn't he want to control for that somehow?

He found that an egg substitute with no cholesterol or fat from egg yolks lowered LDL compared to whole eggs. Amazingly, from this, he concluded that "consuming eggs daily did not unfavorably influence serum cholesterol or other measures of the lipid profile." But they started out hyperlipidemic! That was your word, Dr Katz! Folks, I am not making this up. This is an actual study. Again, no bias here, right? But those vegans are so biased!

Look at the facts here. He took people with high cholesterol, fed them artery-clogging foods like sausage and eggs, and then  show us that egg substitute lowered their total and LDL cholesterol, and he is reporting that whole eggs don't adversely affect lipids.

He will tell you in this study that eggs are nutritious, though. And by gollie, Americans eat 'em and that makes 'em good! Now who the hell are these Canadian researchers coming along, trying to tell us Americans what to do? Yale must be proud of this clear-thinking and objective scientist.

He'll also add a plug for that sausage and egg sandwich in his study. At the bottom right, you see that sausage and egg sandwiches don't harm endothelial function according to him. Awesome! This is science, people! Those overweight folks with high cholesterol in this study were not hurt by sausage! Now that I see what sort of logic he likes, I have a suggestion for another trial he should try. He should take some hard drinkers from a local bar and put them in a study and show us how just a little extra splash of whiskey never hurt anybody. Or he could show us how long time cokeheads can handle just a quick hit no problem.

But didn't he say that egg yolks only looked bad in that biased vegan study because they associate with sausages? Look at this. The man actually referred to sausage! I thought his own research showed that sausage sandwiches do not harm endothelial function in overweight people!

Katz really gets silly when he says, "It is, in a word, illogical that the human body would be harmed by something to which it is long adapted.... To say otherwise would be like saying bamboo is bad for pandas. He says, "Science is generally at its best when it is bounded by" bias, I mean, "sense." I guess I read that wrong. Appeal to nature, anyone? Do they know that fallacy at Yale? Feel free to use your imagination about past diets, Dr. Katz. Such personal gut checks for truthiness are the core of good science. If you take a moment to think critically about this, the real question, sir, is whether or not we are adapted to high blood cholesterol. I say we are not. Moreover, a basic concept in evolution is that natural selection is about the propagation of genes. That happens with reproduction. Evolution doesn't care if you have a stroke at age 60. Sorry that doesn't agree with your feelings about eggs. You have to love it when a guy talks about logic while comparing humans eating eggs to pandas eating bamboo. Ok, here's another idea for a study, Dr Katz. You are really inspiring my creativity today.

Let's go all in on your logic. Since pandas eat bamboo almost exclusively, lets do a study where we feed humans eggs exclusively. Same deal, right? Eggs to humans are just like bamboo to pandas, correct? I'll predict that eating an all-egg diet will raise cholesterol. I'll bet an all-egg diet will raise cholesterol even if you once again study people with high cholesterol. That would be a cool study if you can get past the ethics of it, wouldn't it? Do you care to predict what it would show, Dr Katz? Just how magical do you think eggs are?

By the way, there once was a guy who ate eggs about as much as a panda eats bamboo. Somehow he had average cholesterol anyway. Genes are weird.

The reaction of Dr. Katz to the vegan David Jenkins got me thinking about this story, also on the Huffington Post. To Marion Nestle, a top source of quotes to the media on all things nutrition, vegetarian science is biased science. You just can't trust those meat-free people to do nutrition research. The people with normal diets, who are most like everyone else, are the clear thinkers because you just know they question and think critically about everything and they aren't afraid to do what everyone else does. That's the sort of mind that does good science. The herd mentality has always led to new discoveries, right, Dr. Nestle? Smart people don't think different.

I'll explain the sources of confusion regarding dietary cholesterol for our doctors. As Ancel Keys wrote in 1988, as dietary cholesterol is increased, it has less effect on blood cholesterol.

[Reference: “One point to emphasize is that the relation between serum cholesterol and dietary cholesterol is curvilinear; the relative effect on the serum progressively decreases as the amount of cholesterol in the diet is increased.”

Keys, A. (1988). Diet and blood cholesterol in population surveys--lessons from analysis of the data from a major survey in Israel. The American journal of clinical nutrition, 48(5), 1161-1165.]

Dietary cholesterol also tends to affect blood cholesterol more if the person receiving the dietary cholesterol starts with lower cholesterol. Dietary cholesterol has been shown to increase blood cholesterol in controlled studies when the participants are healthy. Dr. Dayspring should note that dietary cholesterol also increases the number of atherogenic particles.

This study of cholesterol absorption is valuable because the subjects in it were semi-vegetarian. They weren't vegans. They did ordinarily consume eggs, fish, and dairy. For these people who had lower than average cholesterol, dietary cholesterol did raise their blood cholesterol.

The authors thought this study would be interesting because they knew that when someone has a high baseline cholesterol level, that won't be changing so much if they consume cholesterol.

Embedded in this study was the interesting observation that cholesterol levels in these vegetarians did not track closely with age. Normally cholesterol rises with age but not for these semi-vegetarians. This should remind us of hunter gatherers and the people Ancel Keys studied in Naples.

Here you see that going in to this study the semi-vegetarians had much lower cholesterol than the controls, although they still weren't very low in my estimation. That LDL here converts to about 107 milligrams per deciliter.

You can see quite clearly that cholesterol feeding did raise LDL bad cholesterol markedly in these semi-vegetarians.

There was another cholesterol study using vegetarians who weren't very serious about doing a plant-based diet. Many of them ate fish.

Nevertheless you can see that their cholesterol numbers were nice and low and they did not increase with age much at all. Dr. Novella should read the top line. These people were asked about their egg-eating behavior and the answers they gave associated very well with their serum cholesterol. Damn association again, right, Dr. Katz? Maybe these vegetarians were eating bacon with their eggs because bacon just goes with eggs and everybody knows that, even vegetarians. It's just logic.

All this echoes a slide I showed you already. It was known in 1957 that vegetarians who did not eat eggs and dairy had lower cholesterol than those who did. Somehow they avoided that evil confounder of eggs and cholesterol simply by not eating eggs.

The characteristics of your subjects in a study matter. In this study by Robert Knopp and his associates, egg yolks were fed to people who were separated into groups based on their insulin sensitivity and body mass. The people who were categorized as insulin sensitive had their LDL go up much more after egg feeding than the people who were called insulin resistant.

You can see that the insulin-sensitive group went into this study with lower cholesterol than the insulin resistant groups. I don't think that was just a matter of coincidence.

Here are the visuals so you can see how the different people compared. The white bar is the insulin-sensitive group. The gray is for the insulin-resistant. The black is for a group of obese insulin-resistant people. Clearly, the insulin-sensitive people were affected by dietary cholesterol the most. For healthy people, dietary cholesterol raises blood cholesterol. Maybe if Dr. Katz tried using some healthy people in a study he would understand that. Dr. Dayspring, look what eggs did to ApoB! You should ask Gary Taubes to explain to you how this happened since he is the cholesterol expert who explained your field to you. This was a double-blind, randomized, crossover trial but I'm sure he will find something to just "explain it away."

Overweight, insulin resistant, and diabetic people don't absorb much dietary cholesterol but they do have greater cholesterol synthesis when they eat it. They should avoid dietary cholesterol for this reason.

Diabetics seem to be more at risk from eating eggs. Epidemiological research has linked egg consumption to a greater likelihood for them of developing heart disease and of dying sooner.

Christopher Packard looked at the effects of egg consumption in a controlled trial back in 1983. This one created real contrast in the amount of cholesterol consumed in its two phases while minimizing the variation in protein and fat.

There you see that dietary cholesterol really was the only factor that varied a lot. You also see that these were young participants, so they were more likely to be healthy and insulin sensitive.

The egg feeding increased their cholesterol by 29%. That was the average. Importantly, the authors pointed out that individual responses to the eggs varied a lot. Dr. Dayspring, once again LDL particle number was increased by the eggs. Hmmm. You'd better call up Gary Taubes again.

Iodine labeling allowed them to determine that this increase in blood cholesterol was due to an increase in their own LDL synthesis.

It has been established that dietary cholesterol consumption down-regulates the activity of the LDL-receptor, so there is a plausible biological basis for concern about it. Watch my Brown and Goldstein video for more on this.

The effects of dietary cholesterol are variable. For one thing, saturated fat consumed with cholesterol causes it to be more effective at raising blood cholesterol. This study by Christopher Fielding in 1995 separately investigated the effects of dietary cholesterol and saturated fat. After first feeding his participants a diet low in cholesterol and high in polyunsaturated fats to lower their cholesterol, he separately fed subgroups diets with differing levels of saturated fat and cholesterol. He found that whereas an increase in saturated fat had only a small effect on blood cholesterol, dietary cholesterol significantly increased blood cholesterol when it was combined with higher levels of fat intake, particularly saturated fat. In effect, his study found that saturated fat potentiates dietary cholesterol's ability to raise blood cholesterol. Most people who eat dietary cholesterol eat it along with saturated fat.

There are also genetic differences among us that cause wide variation in the effects of dietary cholesterol on blood cholesterol. This variability among humans and within humans is another huge source of confusion in the cholesterol discussion. I'll tell you about this problem in the next video.