Exploring “The Great Cholesterol Myth”
I have a strong interest the prevention of heart disease. I believe healthy nutrition and lifestyle are the key to our health and well being. In my early career as a cardiologist, working in the hospital setting, I was fascinated by the diagnosis and treatment of heart disease. Don´t misunderstand me, I still am. However, as the years have passed I have become more and more interested in disease prevention. Helping people stay healthy and avoid disease is very different from diagnosing and treating. However, although prevention is important, it is not always easy to practice and the results are hard to measure. It´s time consuming, you don´t see the results immediately and it deserves both patience and persistence. Therefore, it´s not surprising that doctors are often less interested in prevention than treating and curing. As Dr. Bernard Lown recently put it so elegantly on his blog, The Lown Conversation: “Diligent prevention unfortunately plays second fiddle to heroic cures.”
The most powerful tool to cut the burden of heart disease in our community is education. Let me quote the remarkable Maya Angelou: “When you know better you do better”. One of the most important roles for doctors and other medical professionals is educating people about healthy lifestyle, nutrition, exercise and other measures to prevent disease. However, to educate is not always a simple task. Furthermore, bad education is often worse than no education. There are so many books written today on lifestyle, exercise, diet and nutrition, and there is an overflow of information on the internet. Obviously, some of it is good and some of it is bad. In many cases, education and information is driven by a product line designed to enrich the bank account of the author. Obviously, such information may be misleading.
Many books and articles have been written on the role of cholesterol in heart disease. Elevated cholesterol has traditionally been considered a risk factor for cardiovascular disease. Lowering cholesterol, low density lipoprotein (LDL) cholesterol in particular, is generally considered important. Recently however, the role of cholesterol in heart disease has been debated. A few weeks ago a ran into a new book on the subject, called “The Great Cholesterol Myth written by nutritionist Jonny Bowden, PhD, and cardiologist Stephen Sinatra, MD. At first sight I wasn´t interested in the book. There are so many similar books I thought: The Cholesterol Myths by Uffe Ravnskog, The Great Cholesterol Con by Malcolm Kendrick, The Great Cholesterol Con by Antonio Colpo and The Great Cholesterol Lie by Dwight Lundell. Sounds pretty boring. However I decided to give Bowden´s and Sinatra´s book a chance. Although, I thought I already knew what their hypothesis was about, I was quite curious to find out how they present their data and how they argument their theories.
In the field of cardiology, the role of cholesterol in atherosclerosis and cardiovascular disease is often debated. In my opinion, the so-called lipid hypothesis is an oversimplification of a complex disorder. Sometimes we debate because we disagree on how to simplify complex mechanisms. Cholesterol is just one of many players in the atherosclerotic process. The main reason it has become such a popular player is that it is easy to measure, not because it plays the main role. However, medical debates are often quite interesting, and they may actually have some positives. They often provoke lively discussions, and they may stimulate scientific research. The downside is that if you have already chosen a side, you run the risk of neglecting, or not choosing to accept scientific results or arguments that don´t support your own opinion.
There are different ways for authors to present a hypothesis they believe is true. You can choose to present all available data, and then make an argument for the data you believe support your hypothesis. Such a balanced, informative approach is honest, and it gives the reader a chance to make up his own mind. However, it doesn´t necessarily catch the attention of the news media or make the headlines.
If you are absolutely convinced that you have a lock on the truth, you may prefer to predominantly present data that reinforce your own beliefs. In my opinion, the recent book by Bowden and Sinatra is an example of this approach. Their book is a perfect example of how to convince you have the truth at your proposal. You may have the feeling while reading, that somehow the authors have managed to unlock the hidden truth, and you may admire how fearlessly they expose, what they call the misinformation fed by the scientific community. Let me quote the first sentence of the first chapter: “The two of us came together to write this book because we believe that you have been completely misled, misinformed, and in some cases directly lied to about cholesterol”. Certainly an interesting book, quite fun to read and provoking. Because of the controversy, such a book is likely to get media attention, I presume that´s a part of the procedure. Strangely, people often like to read about how they have been cheated and mislead. If you manage to convince them they have been cheated, they are also more likely to believe your own theories and arguments.
While reading “The Great Cholesterol Myth”, I had this strong urge that I had to play the devil´s advocate. It´s not necessarily because I dislike the book or disagree with everything the authors write. On the contrary, I think they have some great tips on healthy lifestyle and diet. It´s just because I believe people have the right to hear both sides of the story, and then make up their own mind. I´m not a book critique, so whether I liked the book or not is irrelevant. However, taking on the role of the devil´s advocate I want to bring forward some of my thoughts while reading the book.
In the first two chapters the role of cholesterol in heart disease is discussed. The authors believe that cholesterol numbers are a poor predictor of heart disease. They point out that more than half of the people hospitalized with heart attacks have what they call “perfectly normal cholesterol levels”. The importance of cholesterol for different bodily functions is underlined. The message is; because cholesterol is essential for life it can´t be bad. Let me quote the book: “Both of us became skeptical of the cholesterol theory at different points in our careers, traveling different pathways to arrive at the same conclusion: Cholesterol does not cause heart disease.”
The second chapter bears the name “Cholesterol is harmless“. The people who write the special reports and guidelines, meant to help doctors make treatment decisions, get a fierce amount of critique. A quote from the book: “When the National Cholesterol Education Program lowered the optimal cholesterol levels in 2004, eight of the nine people on the panel had financial ties to the pharmaceutical industry, most of them to the manufacturers of cholesterol-lowering drugs who would subsequently reap immediate benefits from these same recommendations”.
Atherosclerosis is the underlying cause of cardiovascular disease. It leads to the building of plaques within the walls of our arteries. These plaques are composed of several substances, among them is cholesterol. Atherosclerosis typically affects the coronary arteries, the vessels supplying blood to the heart muscle. In medical school I was taught that the exact cause of atherosclerosis was unknown. However, there were certain risk factors, which if present increased the likelihood of developing atherosclerosis and coronary artery disease. The main risk factors were family history, smoking, high blood cholesterol, high blood pressure, diabetes and obesity. None of these risk factors was considered to be the cause of heart disease. However, by modifying the risk factors, the likelihood of developing heart disease could be reduced.
I have never believed that cholesterol is the cause of heart disease. However, it is certainly involved, and it is quite clear that cardiovascular disease as we know it would not exist if cholesterol was not present. Is a tsunami caused by water? No, but it won´t happen without it. Is heart disease caused by cholesterol? No, but it won´t happen without it.
The fact that cholesterol is a very important biologic substance and essential to life, does not prove that high levels may not promote a disease process. There are many examples of this phenomenon. Iron for example has important biologic functions. However high levels of iron in the body can cause a disease called haemochromatosis. Insulin is essential for our metabolism, however research indicates that high levels are undesirable and may promote obesity. A certain level of blood glucose is essential for life. If we don´t get glucose through our diet, the body produces it. However, high blood levels of glucose are undesirable and associated with the disease we call diabetes. So, although cholesterol is an important biologic substance, high levels could certainly be associated with disease.
In animal models, atherosclerosis does not occur in the absence of greatly elevated blood cholesterol. Furthermore, heart attacks have been shown to be uncommon in humans with very low plasma levels of LDL cholesterol due to a sequence variation in the PCSK9 gene. In cell cultures, according to Nobel prize winners Brown and Goldstein, cellular needs for cholesterol can be met with an LDL cholesterol level of 25 mg/dl (0.65 mmol/L). Human newborns have an LDL cholesterol in the range of 40-50 mg/dl (1.1-1.3 mmol/L). Healthy adult levels are 3-4 times higher. The normal LDL cholesterol range is 50 to 70 mg/dl (1.3-1.5 mmol/L) for native hunter-gatherers, healthy human newborns, free-living primates, and other wild mammals, all of whom do not develop atherosclerosis. Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl (1.8 mmol/L). No major safety concerns have surfaced in studies that lowered LDL to the range of 50 to 70 mg/dl.
Familial hypercholesterolemia (FH) is a disorder characterized by high cholesterol levels, specifically levels of LDL-cholesterol. Many individuals with this disorder die prematurely of atherosclerotic cardiovascular disease. I have found no mention of this disorder in Bowden´s and Sinatra´s book. The most common problem in FH is the development of coronary artery disease at a much younger age than would be expected in the general population. So, try telling a thirty year old woman with FH, and an acute heart attack, that cholesterol is harmless. Statin drugs have improved prognosis and quality of life in patients with FH.
It is important to emphasize, that it is lipoproteins that interact with the arterial wall and initiate the cascade of events that leads to atherosclerosis. Cholesterol is only one of many components of lipoproteins. LDL, the major carrier of cholesterol in the circulation, is the most atherogenic lipoprotein. High levels of LDL in the blood may lead to increased transport of this substance into the vessel wall. When inside the arterial wall, LDL can undergo a variety of modifications including oxidation, uptake by white blood cells called macrophages, formation of so-called foam cells and the initiation of inflammation. This cascade of events may ultimately result in an atherosclerotic plaque within the vessel wall. Obviously, cholesterol is not the cause of all this, but it is always involved. So, could it be that atherosclerosis is more likely to occur if plasma concentration of LDL-cholesterol is high than if it is low. The answer is yes. A number of scientific studies indicate that this is definitively the case. However, this does not mean that cholesterol causes heart disease. That is an oversimplification.
The authors claim that inflammation is the true cause of heart disease. Let me quote the book: “So if cholesterol isn´t the cause of heart disease, what is? The primary cause of heart disease is inflammation”. The authors point out that chronic inflammation is a significant component of virtually every single degenerative condition, including heart sisease, Alzheimer´s, diabetes, obesity, arthritis, cancer, and many other diseases. They believe oxidation is an important contributor to inflammation and atherosclerosis.
Bowden and Sinatra consider the size of the atherogenic LDL particles to be important. Thus, the more of the large fluffy particles, the better. The more of the small dense particles, the higher your risk. They even suggest these parameters may be considered the “new good and bad” cholesterol, instead of the traditional HDL cholesterol and LDL cholesterol.
Nature is complex and so are biological mechanisms that control bodily functions. A disease often occurs during specific conditions that involve many different biological mechanisms. Of course environmental and genetic factors play a role as well. So, why should there be a one simple cause of heart disease such as chronic inflammation or cholesterol? Isn´t it more likely that lipoproteins, cholesterol, oxidation, inflammation and many other factors are all involved at the same time? So, again, we may disagree because our methods of simplifying complex mechanisms are different.
An association between LDL particle size and cardiovascular risk has been found in some studies. However, measurements reflecting the number of LDL particles appear to be a stronger predictor of risk than particle size in itself. LDL-P and apolipoprotein B reflect the number of LDL-particles. Interestingly, patients with FH usually have large LDL-particles, but their risk of heart disease is very high, and so is their LDL-particle number. It is likely that the association between small LDL and heart disease reflects an increased number of LDL particles in patients with small particles. Therefore, particle size in itself may be unimportant.
Bowden and Sinatra consider the benefits of statin drugs to have been widely exaggerated. Furthermore, they believe the side effects of these drugs to be much more common than previously thought. They point out that statin therapy may be associated with cancer and diabetes. Other common side effects may be memory problems, lack of energy and sexual dysfunction. They believe that much of the side effects of statin therapy may be traced to depletion of coenzyme Q-10. Dr. Sinatra only uses statin drugs for high risk middle aged men.
I share many of the authors thoughts on statin therapy. I think side effects are underreported and doctors should be much more alert on the possible effects on muscle, diabetes risk, energy, memory and cognitive function. However, in my opinion most people tolerate statin therapy quite well. Furthermore, I believe these drugs certainly reduce cardiovascular risk in patients with documented cardiovascular disease and in many high risk individuals without disease. However, in my opinion statins are used to often in low risk patients. We, doctors should take time to inform these low risk individuals about possible alternatives to statin therapy, such as diet, exercise and healthy lifestyle. Interestingly, the chapter on statin therapy ends with a final cautionary note, let me quote: “Look, there´s not much doubt that statin therapy can significantly reduce the incidence of coronary morbidity and mortality for those who are at great risks of developing coronary artery disease“. Here I definitively agree with Dr. Bowden and Dr. Sinatra, but I have to wonder whether they disagree with themselves.
The seventh chapter of the book bears the name “Help your heart with these supplements”, and deals, as the name suggests, with different nutritional supplements. There are a number of supplements the authors believe improve the health of our hearts. Among these are coenzyme Q10, which the authors call the spark of life, D-ribose, L-carnitine, magnesium, niacin, vitamin E, fish oils and Omega-3. Interesting list, but somehow I could not help thinking that, if the authors owned companies that were selling these products on-line, it would seriously affect the credibility of the book and reduce its educative value. However, keeping in mind the they believe that the lipid hypothesis is kept alive by medical professionals, getting paid by pharmaceutical companies, I will have to assume that Dr. Bowden and Dr. Sinatra have no conflict of interest.