Rejecting the lipid hypothesis with a cholesterol of 278 mg/dl and a smile

When it comes to evaluating how likely you are to have a heart attack, the most accurate diagnostic—the gold standard—is the calcium score. The reason why it’s the most accurate is because it’s calculated from an actual 3D image of the heart and the blood vessels around it. A computerised tomography (CT) scan is done, and from it the amount of plaque buildup in all the places where it appears because of the high density of the calcium it contains is measured and summed to give the total calcium score.

3d_image_of_my_heart

3D volume rendering of my heart seen from the top.

Even though it has been estimated that approximately half of heart attacks are caused by non-calcified lesions, this is the closest thing we have to a direct measurement of the amount of plaque in the network of arteries around the heart. From doing this to thousands of people, we know that plaque usually begins to accumulate after the age of 35. Why isn’t the calcium score test done systematically on everyone above 40 in order to assess their immediate risk, but also to track their individual cardiovascular evolution, showing, with a reliable reference each year, how quickly or slowly arterial plaque is growing? Because it’s too expensive. Therefore, it’s only prescribed to people who are deemed to be at high risk based on other so-called “risk factors”. You know the list: overweight, sedentary, smoking, stressed, etc. But the clincher in this list of risk factors, the one factor that has pretty much eclipsed all the other ones, at least for the past few decades, is high cholesterol.

The focus on cholesterol was, over time, shifted to LDL, the “bad” cholesterol, and later on the ratio between it and HDL, the “good” cholesterol, terms introduced by the pharmaceutical industry to convince us that there is a battle between a good guy and a villain that must be stopped, which they can help with by providing us cholesterol lowering statins, even if with each passing year, the evidence exonerating cholesterol and lipoproteins from any wrong-doing in the genesis and progression of cardiovascular disease has been accumulating. Still, for people and for doctors, it’s really hard to overcome the several decades of conditioning we’ve suffered holding cholesterol as the main culprit for heart disease.

Fortunately, this knowledge and information have been shared and available for as long as the first experiments that set us on this damning direction in thinking and mindset. For my part, I first read a clear expose on the function of cholesterol and lipoproteins from Ron Rosedale over 10 years ago. Then I read it from Uffe Ravnskov, then from Anthony Colpo, then from Malcolm Kendrick who has and to this day continues to investigate the topic and share his findings on his blog, and then from Gary Taubes. All of this has taught me that cholesterol, HDL, and LDL, are not only not dangerous, but that they are essential and crucial for optimal health. This, I shared with you in But what about cholesterol? and shaped my diet to maintain healthy levels: I restricted carbohydrates and polyunsaturated oils, and have gotten most of my calories from minimally processed saturated fats from grass fed animals fats, coconut oil, butter, and olive oil. In this endeavour to maintain strong cholesterol and lipoprotein levels, as you can see below, I have succeeded.

The following plot shows all the measurements of total cholesterol I have ever gotten made from blood tests over the past decade. What you can see is that in late 2007—a time before which I ate mostly complex carbohydrates and polyunsaturated seed oils while avoiding animal and saturated fats—my total cholesterol was below 150 mg/dl. Since then, it has been generally around or above 200 mg/dl with a slight upward trend over the years.

ts_total

My own total cholesterol levels in mg/dl measured from late 2007 to mid 2018.

If we look at the concentration of low and high density lipoproteins LDL and HDL, we also see consistently high levels, with LDL typically 10-30 mg/dl higher than HDL levels. Unsurprisingly, the same general shape and trend are is seen in these measurements as are seen in those of the total cholesterol.

ts_hdl_ldl

My own LDL and HDL levels in mg/dl measured from late 2007 to mid 2018.

Many of you have been reading this blog for a while, and I trust that you have therefore also known for a while that cholesterol is good for you, and that we should strive to have robust levels of HDL, LDL, and total cholesterol. Whether you have managed to overcome the conditioning we have all been subject to over our lifetimes about the purported but never-substantiated dangers of cholesterol and saturated fats, I cannot know. But I hope that I have at least helped a little in that respect.

In any case, I have for several years, every since I first read about the calcium score, wanted to get this test done, and see where I actually stood on the arterial calcification scale. I’ve never had fears or apprehension about it because even when I first read about it, I felt that I had a pretty good idea of the process by which cardiovascular disease evolved, and was following a regime that I knew would minimise the likelihood of atherosclerosis. But still, there is a big difference between having confidence that something is the case, and actually knowing that it is by seeing observational, quantitative, measured evidence for it. Finally, this spring, I was able to get a calcium score done.

I was very lucky to be referred to a young (45), well-informed, and open-minded cardiologist who also does research and has led trials on a group of several thousands of people who work at the Santander Bank campus near Madrid. He also happens to be the head of the cardiology imaging unit of the Clinical Hospital San Carlos in Madrid, a post he has held for more than 6 years now. So, he’s not just any cardiologist: he’s one of the best, and most importantly, one of the very best in cardiology imaging, which was exactly the purpose of consulting with him in the first place. I could not have been in better hands.

On our first appointment, after the initial conversation and questions regarding medical and health history, his assistant helped do an ECG, which looked “perfectly normal”, he said. Then he did the ultrasound with Doppler imaging that allows to see the heart pumping and the blood flowing with a colour coding of red and blue for the blood flowing away and towards the probe. To the trained eye of the imaging cardiologist, the Doppler ultrasound shows how the heart moves, how the cross-sections of the arteries pulsate with the heart beats, how the valves open and close, how flexible the tissues are, and how impeded or unimpeded the flow is. After a thorough examination, from one side and then from the other, he said everything looked very good.

At the end of the appointment he wrote a prescription for the CT scan to be able to get my calcium score, and another for a set of blood tests to which he willingly allowed me to request any additional one I wanted to have done. Before leaving the clinic, the assistant was able to arrange to have the blood test and the scan on the same day one week later: the blood test would be done in house first thing in the morning, and the scan would be done afterwards at the best medical imaging facility in the city.

The day before the scan, I read up on the test, how it’s done, how the measurements are made, and what the score means. I found out that, first, that the measuring of the amount of plaque buildup was done by eye, meaning that the experience and know-how of the cardiologist doing it was quite important. Second, I found out that the scale was not normalised like a scale from 1 to 10 or 0 to 100; that it was from 0 to whatever, which could be 400, 1000 or 4000. Although I was surprised and a little disappointed at first—we all love to get a score that can be immediately compared to everyone else’s, and gives us a sense of where we stand with respect to the rest of the population—I quickly realised that this made good sense given that it is not a relative but instead an absolute measure of plaque buildup in the arteries: naturally, this can go from no plaque to a little bit, to a lot, and to a ton of plaque. One could imagine estimating a maximum amount—say the amount needed to completely fill up the arteries—and use that as the normalising factor representative of 100%, and expressing every other result with respect to this. For now, this hasn’t been done, and the guidelines for interpreting your calcium score suggest values as follows:

  • 0 — No identifiable plaque. Risk: Very low, generally less than 5 percent.
  • 1 – 10 — Minimal identifiable plaque. Risk: Very unlikely, less than 10 percent.
  • 11 – 100 — Definite, at least mild atherosclerotic plaque. Risk: Mild or minimal coronary narrowing likely.
  • 101 – 400 — Definite, at least moderate atherosclerotic plaque. Risk: Mild coronary artery disease highly likely, significant narrowings possible.
  • 401 or Higher — Extensive atherosclerotic plaque. Risk: High likelihood of at least one significant coronary narrowing.

I got the blood test results back before the calcium score: everything looked good. Because most of my blood markers have been stable for years, especially the metabolic markers related to glucose and fat metabolism, the ones I am most interested in are those I need to monitor: things like B12, folate, homocysteine, and D, all of which need to be controlled and their levels adjusted with supplements; those that show my hormonal status, especially for the thyroid and sex hormones; and finally the markers of systemic inflammation which should always be as low as possible. The cholesterol panel is the one that for me has the least importance. But we are here considering cholesterol and lipoproteins in relation to cardiovascular risk assessed by means of the calcium score. So, these were the measured values: total cholesterol was 278 mg/dl, HDL was 122 mg/dl, LDL was 145 mg/dl, VLDL was 11 mg/dl (ref: <40), lipoprotein(a) was 4.40 mg/dl (ref: <30), and the ratios of total/HDL and LDL/HDL labelled atherogenesis indices were 2.28 (ref: <4.5) and 1.19 (ref: <3.55), values which are all deemed very good, of course.

A few days later I got my calcium score back. What do you think it was? You know I’m currently 45 and that calcification begins to grow after the age of 30-35, and has definitely progressed by the age of 40. You also know that—from what we are told by most doctors and health authorities—that plaque buildup and calcification is an inevitable part of ageing, that no matter what we do or eat or not eat, even if we might be able do things to slow it down, plaque accumulates and calcification progresses in only one direction: upward and onward. With this in mind, what would you guess my calcium score was?

My calcium score—based on 3D imaging of the heart and the region around it, and calculated by the one of best imaging cardiologist in Spain—was 0. It wasn’t 10 or 20. It wasn’t even 1, or 2, or 3. It was zero.

In our scientific training we learn that theories can never be proven—that they can only be disproven, and that hypotheses can never of accepted—that they can only be rejected. We also learn that to disprove or reject a theory or hypothesis, what is needed is a single contradicting piece of evidence, a single contradicting observation. The lipid hypothesis—that elevated blood cholesterol leads to atherosclerosis of the arteries, and that therefore decreasing blood cholesterol concentration significantly reduces cardiovascular risk—has been ingrained into our psyche more solidly than almost anything else that we collectively believe. But faced with this evidence, even if it is from one person only, of having maintained “elevated” fasting cholesterol levels consistently for a decade while in spite of this having gotten a perfect calcium score at the age of 45, the hypothesis must surely be rejected.

Even if we didn’t have any other evidence at all, according to the scientific principle that one contradicting piece of evidence is sufficient to reject a hypothesis, this single instance of my history of high total cholesterol together with a calcium score of zero is enough to reject the hypothesis that having elevated blood cholesterol levels over a long time leads to atherosclerosis and therefore to cardiovascular disease.

And we can be sure I’m not the only one. In fact, I’m willing to bet anything that most people in the low carb community who have been low carbers for as long as I have will have high cholesterol levels and low calcium scores. But still, to change the mindset of several generations of doctors, journalists, and people everywhere—hundreds of millions of educated people conditioned from decades of misinformation—will take years, probably decades. That’s how we are as social animals: stubborn in our beliefs.

In any case, I hope you, at least are, if you weren’t already, are now convinced that having high cholesterol does not cause atherosclerosis. Are you now curious to find out what your calcium score is? If you do get it done, please share.

For my part, I feel even more confident than I did. Even if I assured you more than five years ago in the spring of 2013 in At the heart of heart disease that you could be entirely free from cardiovascular disease by following some basic guidelines I listed regarding our eating, drinking, and living habits, there is nothing like observational evidence. And now we have it.

 

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Six eggs per day for six days: cholesterol?

In What about cholesterol we saw how important cholesterol is for so many essential bodily functions and in so many important ways, that there should never have been a shadow of a doubt in anyone’s mind that cholesterol is anything but essential and vital to our health and our life. And that, therefore, it is ridiculous to even have to say that cholesterol is good for us. However, it is more than completely absurd, non-sensical, and outright dangerous to claim that it is bad for us. Let me assume you are now well convinced of this.

There is something we didn’t go into that relates to the fact that we’ve been told—and continue to be told—that we should minimise our intake of dietary cholesterol. The crazy thing about that recommendation is that the amount needed by the body of this vital substance depends solely on the body’s needs for it. And thus, the normally functioning liver, supplied with adequate amounts of the essential building blocks, produces cholesterol in the amount that is necessary for proper bodily function—whatever that amount happens to be at a particular time. What this means is that in a healthy individual, the amount of cholesterol you eat should not really affect the amount of cholesterol in the blood, estimated by the concentration of the lipoproteins that transport it to and from tissues.

Even though this obvious consequence of considering the body’s physiological function should just be accepted as a plain fact, unfortunately, most people—including health professionals—don’t. We continue to believe that cholesterol is bad, and we continue to try to minimise dietary cholesterol in order to lower lipoprotein concentrations, completely ignoring the fact that cholesterol and lipoprotein production is an exceedingly refined and well regulated mechanism that responds directly to the body’s needs.

It is certainly possible that if dietary cholesterol intake decreases, the liver produces more, and if dietary cholesterol intake increases, then the liver produces less; to what extent certainly depends on the physiological circumstances, and specific needs for cholesterol depend on many factors, all related to the state of the body. But it is pretty well established that the body produces more or less the same amount of cholesterol regardless of the dietary cholesterol intake because it much prefers to use the kind of cholesterol the liver produces, which is free or un-esterified cholesterol, rather than having to de-esterify the dietary cholesterol that comes primarily as cholesterol ester. Therefore, much of the dietary cholesterol is used in bile and excreted through the intestines.

For a lot more details, you can check out Peter Attia’s essential points to remember on his series The straight dope on cholesterol, even if I don’t really agree with the points linking LDL with atherosclerosis, simply because lipoprotein concentration, particle number, size distribution and everything else are all secondary or even further removed consequences of other dietary and metabolic factors upstream. In fact, I believe we should not even have started measuring lipoprotein concentrations and cholesterol in the first place. What we should have always focused on are uric acid levels and tracers of inflammation. And on another note, Peter is categorical that dietary cholesterol is not absorbed and all excreted. However, a couple of review papers I read about lipid absorption state that about 50% of intestinal cholesterol is, in fact, absorbed. The truth is that it is almost certainly dependent on a whole slew of factors and that, as for all things, the body absorbs and excretes in accord with its needs.

A viral infection, for example, will generally lead to the increase of lipoprotein concentration because these are the molecules that can most effectively gobble up and destroy viruses. Dehydration leads to a scarcity of water at the cellular level. As a consequence, each cell’s survival relies on producing more cholesterol in order to more effectively seal in the precious water it depends on for life that appears to be so scarce. Hence, dehydration also leads to higher cholesterol. A diet high in sugar—simple and starchy carbohydrates—naturally leads to a much greater amount of damage to cells and tissues throughout the body, but especially to the blood vessels themselves, from the highly damaging presence of insulin, the result of glycation of proteins and fats by higher concentrations of circulating glucose, and several other related factors. To repair the damaged cells, cholesterol is needed, and thus, in this case also, lipoprotein concentrations rise accordingly.

Although the fact that the amount of dietary cholesterol does not affect blood lipoprotein concentrations much is not debated by people in-the-know about issues pertaining to cholesterol, I just wanted to see this for myself what would happen. So, I devised a simple self-experiment: compare the lipoprotein concentrations in my blood when following my low-card, high-fat, high-nutrient diet, to those after eating 6 eggs per day for 6 days in a rowwhere I basically just added to my diet more eggs, usually raw in smoothies. That’s a lot of eggs… But before I present the results, I think it’s important to go through a few numbers relevant to this discussion.

lotsofeggs

Eggs: An average organic egg of 50 g supplies 70 calories, and contains 5 g of fat (all in the yolk), 6 g of protein (all in the egg white), less than 0.5 g of carbohydrates and 215 mg of cholesterol. This means that 6 eggs supply a total of 1300 mg of cholesterol. For me, 6 eggs per day is 3 times my usual consumption of 2 eggs per day on average—a 300% increase.

Blood volume: The blood in our body accounts for about 7% of its mass (Ref). For a weight of 100 kg, there is 7 kg of blood (about 7 litres); if you weight 50 kg, then there is 3.5 kg of blood or about 3.5 litres. And therefore, for a 57-58 kg person like me, this makes almost exactly 4 kg, and thus about 4 litres or 40 decilitres.

Lipoproteins: Cholesterol is not water-soluble, and thus has to be transported by lipoproteins. Different lipoproteins carry a different amount of cholesterol. The bulk of it, however, is found in LDL and HDL molecules. The percentage of cholesterol by weight in LDL is about 40%, and in HDL it is between 20 and 35% (Ref). To keep our calculation simple, we’ll take this to mean that LDL is half cholesterol by weight, and HDL is one quarter cholesterol.

Here are the results of the blood tests from December 16 and 22, 2011, both taken in the late afternoon after nearly 24 hours of fasting (I do this every week, so it was nothing unusual). And please don’t worry about the boldface: it appears automatically if the numbers are not in the “recommended” range, which for cholesterol is below 200 and for glucose 65-110 mg/dL. And don’t worry about the spelling: it’s spanish because I live in Spain.

Now, looking at the results, can you guess which one is which: which is the result of the blood test before one week of 6 eggs per day, and which one is after?

The answer is that the first table is from the blood test done on Dec 16, and the second table is from the blood test done on Dec 22:

After one week of eating 6 eggs per day, the LDL decreased from 110 to 95 mg/dL, the HDL increased from 106 to 112 mg/dL, the “total cholesterol” decreased from 224 to 213, and the triglycerides decreased from 41 to 29 mg/dL.

About the lipoprotein concentrations, you may recall from this graph I linked to in my first post on cholesterol, and in which was compiled all the available data found by its author, that included mortality rates and what is referred to as “total cholesterol” (but is in fact total lipoproteins), the ideal range for which is labelled “Colesterol total” in the above test results is 200-240 mg/dL, and the minimum all-cause mortality is found for concentrations of 220 mg/dL. That’s right where my numbers happen to be.

As for the glucose, well, you already know I try to keep it as low as possible, and by the way, I had no signs of hypoglycemia when my blood glucose was 60 mg/dL. In fact, I never do, even during three-day fasts, cycling to and from work, and doing resistance training at lunchtime. This demonstrates that the state of hypoglycemia can not be defined by a fixed threshold of glucose concentration below which we are considered to be in that state, but rather is based upon the individual’s metabolic function. This should be obvious since some people feel the consequence of hypoglycemia quite regularly and at glucose levels that would be exceptionally high for others, who on the contrary never feel them, simply because their metabolism has been trained to use fats for the body’s energy needs efficiently, and in fact, almost exclusively—to function in ketosis—as is my case. I plan to revisit this topic in greater detail in the future. But for now, let’s come back to the blood test results.

Firstly, we see that the sum of LDL and HDL compared to the “total cholesterol” is 216 vs. 224 (Dec 16) and 207 vs. 213 (Dec 22). This tells us that the VLDL (very low density lipoproteins) and CM (chylomicrons) together account for 8 mg/dL on Dec 16, and 6 mg/dL on Dec 22. They are, and we’ll not discuss these lipoproteins any further in this post.

Secondly, we note that the small difference in the very low concentrations of triglycerides (three fatty acids attached to a glycerol backbone), considered to be “normal” up to 150 mg/dL, mirrors the small difference in the lipoproteins that carry most of the triglycerides: the CM (90% triglycerides) and VLDL (62% triglycerides). Low triglyceride levels with low glucose and insulin levels equate to efficient metabolic use of fats.

And thirdly, we find that for 4 litres of blood, if we assume simple rounded figures of 100 mg/dL of LDL and 100 mg/dL of HDL, the total amount of cholesterol being carried around in the bloodstream is about 3000 mg: 40 dL*(50%*100 mg/dL + 25%*100 mg/dL). This is just 3 grams in the entire blood supply for a body weight of 58 kg! And an additional 1300 mg of cholesterol per day—almost half of the cholesterol in the bloodstream—from eating 6 eggs, and this for 6 consecutive days that supplied a total of 7800 mg of cholesterol, did not affect the lipoprotein concentration.

This leads us back to the hypothesis presented in the first paragraphs: the amount of cholesterol you eat should not really affect the amount of cholesterol in the blood. And although a quick experiment on a single person is far from being definitive proof of anything, this one clearly indicates, at least for me, that increasing intake of dietary cholesterol by an amount that is close to half of the total cholesterol circulating in the bloodstream, and doing this each day for 6 days in a row, does not raise lipoprotein concentrations (in this case, they went down slightly) when comparing the values measured at the same time in the late afternoon after a 24 hour fast once at the start of the week and 7 days later.

Furthermore, based on the sensible assumption that cholesterol synthesis by the liver is a response to the body’s needs, but also ability to manufacture it, if absorption of intestinal cholesterol is not nil but varies depending on the body’s needs, then supplying more dietary cholesterol may help ease the requirements on the liver for manufacturing the quantities needed. Therefore, this “help” to the liver can only be viewed as favourable considering the extreme importance of this organ for good health. It could also be that most or even all the additional dietary cholesterol was simply excreted in the stools. But in any case, it is absolutely certain that eating this huge amount of cholesterol every day did not affect lipoprotein concentrations in the blood after the period of fasting.

What I would like to do is to evaluate dietary cholesterol absorption on me, a 40-year old man in excellent health, by adopting an extreme diet of eating only eggs and water (this will remove the influence of other foods and nutrients and therefore reduce significantly the number of variables that can influence cholesterol synthesis and absorption), and take minimal blood samples at regular time intervals such as every hour or every couple of hours. By evaluating the changes in cholesterol transporters we would be able to estimate how much is absorbed because we know that lipids from the intestines are transported to the blood mostly by CM and VLDL, whereas HDL and LDL are mostly responsible for transport to and from the liver.

In any case, as we have seen here, but also as I mentioned in my opening sentences that we have known for a rather long time, dietary cholesterol does not influence blood cholesterol much. So please, when you hear someone say that we should avoid eating too much cholesterol because they have “high cholesterol”, you don’t need to say anything if you don’t want to, but remember at least this: cholesterol is so important and so good for us, that the liver and cells themselves will always do everything to supply the all the cholesterol that is needed, whatever that is at a particular time, and no matter how little or how much we get from our food. And maybe it is even the case that eating more cholesterol actually helps the liver and cells meet the body’s continuous demands throughout the day and night of this vital substance.