Malcolm Kendrick

Heart disease has nothing to do with eating saturated fat, nor does it have anything to do with cholesterol in the bloodstream.

The most likely place for atherosclerotic plaques to be found is within the arteries that supply blood to the heart. The coronary arteries.

The diet-heart/cholesterol hypothesis –

  1. Saturated fat in the diet raises cholesterol.
  2. Raised cholesterol causes CVD.

The single most important event in the demonisation of saturated fat: Senator McGovern’s Dietary Committee of 1977.

Diet guidelines were taken up enthusiastically around the world despite a complete lack of any real evidence. A fact highlighted by an article, published in the BMJ, entitled: “Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis.” The researchers looked at all the evidence available to those who created the dietary guidelines at the time. They found that there was exactly, and precisely… none. “CONCLUSION: Dietary recommendations were introduced for 220 million US and 56 million UK citizens by 1983, in the absence of supporting evidence from RCTs” 

Today, we know virtually everything there is to know about fat metabolism, and it is now beyond doubt that saturated fat consumption cannot raise LDL levels. It is not simply unlikely, it is impossible. There is no mechanism within the body for it to do so. Yes, a rather bold, hubristic statement. But I have seen nothing to contradict it, and it is supported by the science.

What happens when we eat saturated fat?

  1. It binds to bile salts in the bowel.
  2. Once bound with bile salts, it’s absorbed into the gut wall and packed into a chylomicron.
  3. The chylomicron travels through the thoracic duct and released directly into the bloodstream.

It does not, at any point, pass through the liver.

As chylomicrons travel around the body, they are stripped of their fat content by cells they encounter (primarily fat cells). They continue to shrink in size until they are about the size of a LDL molecule, at which point they are called chylomicron remnants. These remnants are absorbed back into the liver. Which means that only a very small percentage of the fat that you eat can end up in the liver. This is what happens to all types of fatty acids: saturated, polyunsaturated, or monounsaturated.

Nothing in the absorption, transport, and storage of dietary fat, saturated or otherwise, has anything to do with LDL a.k.a. ‘bad cholesterol’ in any way shape or form.

Where do LDL’s come from?

The liver makes VLDL’s (also called triglycerides). The role of VLDL is to transport fatty acids and deliver them to fat cells. A LDL molecule is simply what is left of VLDL once it has been stripped of most of its fat content.

VLDL –> shrinks –> IDL –> shrinks –> LDL

Most LDL molecules are pulled out of circulation by the liver, though a certain amount does remain free in the blood. They can deliver cholesterol to cells that need it.

In whatever way you view these lipoproteins, the key takeaway fact is that VLDLs are the only source of LDLs. Thus, for the LDL level to rise, the VLDL level must go up first. Which leads to the next question. What makes VLDL levels go up? Well, as I hope is now clear, it is not, and never could have been saturated fat consumption.

Instead, what causes VLDL levels to rise is eating carbohydrates.

Therefore, in whatever form you choose to eat your carbohydrates, they are all broken down within the gut into their constituent simple sugar building blocks – largely glucose and fructose. These molecules, and any other form of sugar, are transported directly into the liver. The liver will then decide upon their fate.

The liver has 3 choices about what to do with it –

  1. Store it as glycogen.
  2. Release it gradually into circulation.
  3. Convert it into fat (de novo lipogenesis).

The liver can pack away about 500 calories of glycogen, or thereabouts. Once this 500 calorie limit has been reached, the liver is full. If you keep on eating carbohydrates, what happens next? What happens next is the only thing that can possibly happen. Which is that the liver is forced to convert the excess glucose into fat.

One further thing I need to mention here is that all new fats synthesized in the liver are saturated fats, and only saturated fats (mostly palmitic acid C16:0). The liver does not make unsaturated fats. The most important fact here is that, if you eat a lot of fat, the liver reduces its fat synthesis This, in turn, means that the VLDL level will fall. On the other hand, if you eat carbohydrates the VLDL level rises.

Key points –

  • Eating more fat/saturated fat reduces VLDL production.
  • Eating more carbohydrate increases VLDL production.

If carbohydrates raise VLDL levels, which they do, why does this not greatly increase LDL levels? More VLDL must mean more LDL. This would be true, except for the fact that the liver monitors LDL levels, and if they rise, it simply removes excess LDL from circulation. This is the process of homeostasis in action. Doing what it does.

For example, a major dietary trial was done, between 1968 and 1973. It was called the Minnesota Coronary Experiment (MCE). It was large scale, with over 9,000 participants, it was even a randomised controlled trial (RCT). Yes, the gold standard. As found in earlier studies, replacing saturated fats with polyunsaturated fats reduced the cholesterol level. However, and this is key, it had precisely no impact on cardiovascular disease.

More disturbingly, the greater the fall in the cholesterol level, the more people died. Yes, you did just read that. For each 1% fall in cholesterol there was a 1% increase in the risk of death.

“Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid [a polyunsaturated fat] effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes.”

Increased polyunsaturated fat intake → reduced cholesterol levels→ increased risk of death.

The Sydney Diet Heart Study was considerably smaller, but still a randomised controlled study. Again, the researchers replaced saturated fats with polyunsaturated fats. Again, the cholesterol levels fell (but all cause mortality and cardiovascular mortality increased).

The idea that high cholesterol levels in the blood are the main cause of CVD is impossible because people with low levels become just as atherosclerotic as people with high levels and their risk of suffering from CVD is the same or higher. The cholesterol hypothesis has been kept alive for decades by reviewers who have used misleading statistics, excluded the results from unsuccessful trials and ignored numerous contradictory observations.”

https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391

Here, for example, is the latest risk calculator for use in the UK called Qrisk3. It is more complex than previous risk calculators, and it asks you for information on 20 different factors. They are, in no particular order of importance:

Age • Sex • Smoking • Diabetes • Total cholesterol/HDL ratio • Raised blood pressure. • Variation in two blood pressure readings • BMI • Chronic kidney disease • Rheumatoid arthritis • Systemic Lupus Erythematosus (SLE) • History of migraines • Severe mental illness • On atypical antipsychotic medication • Using steroid tablets • Atrial fibrillation • Diagnosis of erectile dysfunction • Angina, or heart attack in first degree relative under the age of 60 • Ethnicity • Postcode

It is true that all of these factors are directly, or indirectly, associated with cardiovascular disease. The problem here is to try to explain how these very different things all cause the same disease. How does a history of migraines link to, say, chronic kidney disease?

The current solution to this is to state that cardiovascular disease is multifactorial. However, in the end, you cannot just bring a whole bunch of factors together, declare that the disease is multifactorial, and attempt to convince yourself that you have created a scientific hypothesis.

In the end, the thing that I call the ‘single factor paradigm’, even if no-one else does, has led us to a place of almost perfect irony. Unable to find the single necessary cause. By which I mean the factor, or agent, without which the disease cannot occur – it was decreed that cardiovascular disease is caused by multiple single factors.

So, instead of having a coherent model, we have just ended up with an ever-lengthening list of risk factors for cardiovascular disease. The mainstream view is encapsulated in this quote from the American Journal of Hypertension: “Coronary heart disease is clearly a multifactorial disease with risk factors that tend to cluster and interact in an individual to determine the level of coronary risk.”

Which means that the correct answer to the question, what causes CVD? Is that there is no answer to this question. The question is, and always should have been, what is the process of cardiovascular disease?

The alternative hypothesis – blood clots (the thrombogenic hypothesis)

The alternative hypothesis is that blood clots, and blood clotting, are the key players in cardiovascular disease. From start, to finish. By which I mean that atherosclerotic plaques, the thickenings and narrowings in arteries, are the remnants of blood clots, formed on the arteries themselves. Or to put it another way, blood clots that have been created on, then incorporated into, artery walls.

The process starts when the lining of the artery wall is damaged in some way. This stimulates the formation of a blood clot (thrombus) which covers over the area, rather like a scab does when you damage your skin. A new layer of arterial lining then grows over the top of the thrombus, which effectively draws it into the artery wall. In most cases, the remnant thrombus is then fully broken down and removed.

Over many years of growth, plaques can end up in a whole range of different forms. They can be tough and fibrous, known as fibroatheroma. They can develop an almost liquid core, like a boil, with a thin covering. These are often called ‘vulnerable’ plaques.

A bit of good news about plaques is that, after decades, they normally pass through the vulnerable stage and begin to calcify.

For instance, the idea that plaque ‘rupture’ creates a thrombus that can block an artery. This is pretty much unquestioned as the cause of most heart attacks.

It is also widely accepted that thrombus formation, on top of an already existing plaque, can make plaques suddenly jump in size.

However, the very idea, the very idea, that thrombi could possibly have a role in starting the plaque in the first place is dismissed, virtually out of hand. It is LDL which does this, and LDL alone. LDL infiltrates the arterial wall to start the process, then a gradual build-up of LDL keeps the plaque growing. It is only at the later stages when blood clotting may take over – or have some role to play.

The simple fact is that cells don’t allow anything to enter without a reason (we shall leave viruses out of this discussion as they hijack cell mechanisms to do this). Cells are extraordinarily careful about what they allow in, and what they don’t. There are receptors and gates and channels, each one designed to allow entry of one thing, and one thing only. Down to the size of individual atoms, such as sodium, or potassium.

If LDL molecules cannot simply pass straight through endothelial cells – and they can’t – what else can explain LDL getting into an artery wall? At present, although this is usually left fuzzy, the explanation is that LDL molecules can slip between endothelial cells, then into the artery wall beneath.

In the same way, if you want to get from one side of an endothelial cell to the other, you must pass through the cell. You cannot pass between cells. They are sealed together with things called tight junctions. A whole series of strong, interlinked, protein bridges. This, I should add, is not up for debate, it is simply scientific fact.

Plaques are full of cholesterol. This is simply a known fact, isn’t it? In truth, it is not.

It’s certainly true that there is cholesterol in a plaque, some plaques – possibly even most plaques. However, there are an awful lot of other things trapped in there as well, which are not cholesterol, and have absolutely no connection to LDL, or cholesterol, in any way, shape or form. There are red blood cells, fibrin, platelets, white blood cells, smooth muscle cells, calcium, collagen etc. etc. etc. How did they get in there?

Almost the only thing beyond any question is that a plaque is not just a big lump of cholesterol stuck inside the artery wall. Plaques, if you start picking away at them, are rather complicated and messy old things.

These were ‘end-stage’ plaques, and they consisted of:

  • fibrous tissue (87 ± 8%)
  • calcific deposits (7 ± 6%)
  • pultaceous debris (5 ± 4%) (having a soft consistency: pulpy)
  • foam cells (1 ± 1%)