The Cause of Coronary Artery Disease


The conventional theory of the cause of coronary artery disease has been driven by the so called “Diet Heart Hypothesis.” This was the idea that diets that were high in saturated fats raised blood cholesterol which caused atherosclerotic blockage of arteries. This was started by several flawed studies. The first was done by Nikolai Anichkov in 1913. He found that when he fed rabbits diets that were high in cholesterol, that they developed coronary atherosclerosis. This was and still is considered a groundbreaking study proving the role of cholesterol in heart disease. The problem was that rabbits are herbivores, not accustomed to eating cholesterol as there is no cholesterol in plant foods. Hence their bodies were not adapted to consuming dietary cholesterol. When the same experiments were done using dogs which are carnivores, no such coronary lesions developed.  Furthermore, when it was eventually agreed that dietary cholesterol played no role in atherosclerosis in humans, the American Heart Association and USDA eventually dropped the 30 year old recommendation that all Americans should restrict dietary cholesterol. So why didn’t they drop the recommendations to limit saturated fat? Well, the other early study that was influential an that was also flawed was the Seven Countries Study by a physiologist named Ancel Keyes where he looked at incidence of heart disease in various countries and compared it with the incidence of heart disease in those countries. The problem with his study was that he hand picked the seven countries that fit his hypothesis and ignored those that didn’t, namely France and Switzerland which have among the highest saturated fat intake and the lowest incidence of heart disease. None the less he was able to convince the scientific community that his hypothesis was correct and subsequently convinced the US government to formulate guidelines telling people to limit saturated fat intake. What happened in studies that tested the hypothesis that reduction in saturated fats reduced CAD?  Several have been done. Two of the most notable studies where polyunsaturated fats were substituted for saturated fats were the Minnesota Coronary Experiment and the Sydney Diet Heart Study. The Minnesota Coronary Experiment was done by Ancel Keys’ own staff at the University of Minnesota. I D Frantz Jr et al. (1989). Arteriosclerosis 9 129-35 doi:10.1161/01.ATV.9.1.129 There, long term residents in psychiatric hospitals were put on regular vs diets where saturated fats were replaced by polyunsaturated vegetable fats. The results were the opposite of what was expected. The experimental group had more deaths due to heart disease as well as total deaths. For every 30 point reduction in total cholesterol, there was a 20% increase in deaths. The authors waited 15 years to publish these results. When author Gary Taubes asked the principle investigator why he waited to long, the response was that they were disappointed with the results. The Sydney Diet Heart Study showed similar results ie higher coronary and all cause mortality in the group that ate the diet where polyunsaturated fats were substituted for saturated fats.  The results of this study also laid dormant in storage until they were recently discovered and published.  The problem with the diet heart hypothesis is that not only does saturated fat, which can raise total cholesterol, but also raises HDL or good cholesterol, not correlate with heart disease, but that blood cholesterol itself doesn’t correlate with heart disease either. A landmark ongoing study of diet, cholesterol and heart disease that has been going on since 1948 is the Framingham Heart Study. There 5,200 residents of the town of Framingham in Massachusetts have been followed since 1948. The initial much heralded finding was that serum cholesterol correlated with heart disease. However as the study went on it later turned out that total cholesterol had weak correlation with heart disease in men only below the age of 50 and no correlation with heart disease after 50. In women there was no correlation with heart disease before 50 and a reverse correlation after 50. That is after the age of 50, the higher a woman’s cholesterol, the longer she lived.
Another damning study is the “UCLA Study” where 137,000 patients who were admitted for heart disease from 541 hospitals were studied for 5 years. They found that over 75% had LDL cholesterol levels below 130, considered to be a good level, and 50% had levels below 100, a level considered to be ideal and well below normal. A meta analysis published in BMJ in 2016 looked at 19 studies involving 68,000 patients and found an inverse relationship between LDL cholesterol and death in patients over 60, similar to Framingham findings above.
So if there is no data that high total or in particular LDL cholesterol correlates with heart, disease why is there still belief of it’s role in causing heart disease? Enter statins and the medical industrial complex. When belief was high that blood cholesterol correlated with heart disease, the search was on to find classes of drugs that would lower blood cholesterol. The most powerful class discovered was the statin class. Statins inhibit production of cholesterol which causes liver LDL receptors to increase which increases removal of cholesterol. Several studies were done by the manufacturers that showed reduction in cardiac events, however reduction in total mortality was weak. And when analyses were done of long term benefits it was found that they might prolong live by only 3-4 days. A recent study of 100,000 Medicare patients who had suffered a myocardial infarction showed that those that were intolerant of statins ie could not and did not take them had slightly higher incidences of heart events but lower overall mortality.
So when it became apparent that LDL itself had basically no correlation with heart disease, investigators stared to look at subgroups of lipid particles such as small dense LDL and apoB which is a marker of total LDL particles. It turns out that increased levels of small dense LDL and apoB particles do correlate with incidence of CAD.  So it was then believed that if a person has a high number of small dense LDL particles ie high apoB count, and since these particles do correlate with heart disease, that these particles must cause atherosclerosis by getting into the walls of arteries and triggering atherosclerosis.  Ok, so, finally, a study of one of the new potent LDL lowering drugs, PCSK9 inhibitors, evolocumab, was recently published, the FOURIER TRIAL.
This drug lowered LDL significantly to very low levels. It also raised HDL and lowered triglycerides. Basically, all the lipid parameters and particle numbers were “fixed” to all be in what would be considered ideal ranges. LDL cholesterol was reduced to 30. Apo B was reduced by 49%. Other lipid parameters were fixed as well. Lp(a) was reduced by 27%. HDL was increased by 8.4%. Apo A1 was increased by 6.5%. Triglycerides were reduced by 16%. Basically all the numbers were in as good a range as could be hoped for. They were basically “perfect.”  So how did the patients do?  In the patients on the drug, the incidence of events over the two year period was 9.8% compared to 11.3% in the control group. This is hardly earth shattering.  So, in these patients who had as “good” a total lipid profile as could possibly be imagined, the incidence of events was 10% over two years, which is still considered extremely high as far as percent risk scores go. According to the Framingham risk calculator, a 20% ten year risk of coronary events is the highest category for cardiac risk.  These patients had a 10% incidence of cardiac events in only two years.  That is, these patients still suffered cardiac events at what is considered an extremely high rate.  Cardiac events were not reduced any where close to what would be considered a low cardiac risk category. What’s more, you guessed it, the subjects on this powerful LDL lowering drug had higher total mortality. So, again, you can basically fix all the lipid particle numbers of at risk patients to what would be considered perfect lipid profiles, yet they still had a high incidence of cardiac events. Maybe lipid moieties or particles, ie LDL, apo B, apo A ratios, HDL have no causative role in coronary artery disease whatsoever, rather they are merely markers of a condition that is the real cause of coronary artery disease, ie insulin resistance and what is probably the real cause of atherosclerosis, high circulating insulin levels.

In 1988, at the Banting lecture series, Gerald Reavens presented his discovery of insulin resistance and metabolic syndrome which he called “syndrome X.”  This syndrome consists of resistance of tissues, mainly the liver to effects of insulin causing the pancreas to secrete more and more insulin to maintain glucose homeostasis.  It is characterized by high resting and food stimulated insulin levels.  The insulin resistant condition or metabolic syndrome has other characteristic features, namely central obesity, hypertension, elevated blood sugar, lipid abnormalities, mainly elevated triglycerides and lowered HDL cholesterol and finally vascular disease.  Insulin resistance starts with the consumption of large amounts of sugar over long periods of time.  This sugar consumption has an affect on the liver whereby the liver can’t handle the large amounts of fructose in the sugar and converts it to fat within the liver which leads to insulin resistance within the liver.  The increase in hepatic or liver fat then progresses to fatty liver and eventually steatohepatis and occasionally cirrhosis.  Other organs can then become resistant to insulin as well. The pancreas compensates by secreting more and more insulin as the insulin resistance becomes worse and worse until eventually it can’t secrete enough insulin to keep glucose levels controlled and the blood glucose rises and a person is then identified as diabetic.  The whole time insulin levels are rising due to this sugar caused insulin resistance, but while blood glucose levels are still normal, the individual has what is called pre diabetes.  As Gary Taubes describes in “The Case Against Sugar,” sugar consumption in the US and throughout the world has gone up over 20 fold since the beginning of the 19th century and diabetes has paralleled this going up incidence over 8 fold over the past 100 years.  It is estimated that 50% of the US population has diabetes or pre diabetes.  25% of Americans have fatty liver.      Not only is insulin resistance associated with obesity, diabetes, and vascular disease, it is the cause of the vast majority of those conditions.  It is felt that over 80% of hypertensive patients and 80% of cardiac patients are either diabetic or pre diabetic and if one uses the insulin tolerance test developed by Robert Kraft, one could identify nearly all patients with coronary artery disease as diabetic or pre diabetic.  Recent studies have identified fatty liver as a stronger predictor of vascular disease than lipid markers.

So what about lipids?  Numerous studies have identified HDL and triglycerides as the strongest predictors of heart disease as far as lipid markers go.  As stated above small dense LDL and high apoB to apoA ratios also correlate with heart disease.  However, what all these so called atherogenic lipid marker patterns have in common is that all are characteristic of the metabolic syndrome.  In fact the most “atherogenic” patterns of lipids ie high triglycerides, low HDL, high apoB, small dense LDL are all only seen in metabolic syndrome, strongly implicating metabolic syndrome in the cause of atherosclerosis.  So is it these lipid particles patterns that all the researchers and drug companies have focused on for so long that are the atherogenic trigger of vascular disease by metabolic syndrome?  Or is it something else?  As the FOURIER trial described above showed, when all these particles were normalized by drugs, there was still an extremely high level of cardiac events.  You have all these lipid particles brought to ideal levels yet there was still a high level of cardiac events.  So if it is not the lipid patterns characteristic of the metabolic syndrome that causes vascular disease, what is it?  I would propose that there is a strong case that insulin itself and high insulin levels of the metabolic syndrome are the primary drivers of vascular atherosclerotic disease and that all the lipid particles and particle patterns associated with the metabolic syndrome are nothing more than markers of the syndrome and have no causal roll in the promotion of atherosclerosis.  The true feature of metabolic syndrome that damages the lining of arteries leading to atherosclerosis is not the so called atherogenic lipid particles, but rather the effects of a high insulin level itself on the walls of arteries that causes them to develop atherosclerosis.

To be continued…..


What about cholesterol?

The main problem that mainstream medicine and cardiologists have with low carb high fat diets is concern that “eating all that fat” will increase risk for heart disease. This concern was so great that Atkins was called before a senate committee where witnesses said that his diet was malpractice and was like mass murder. The problem is that the “cholesterol, diet, heart” hypothesis was adopted without any substantiating proof. What lead to the diet heart hypothesis was that there is cholesterol in the atherosclerotic lesion in arteries so researchers therefore believed that dietary cholesterol caused these lesions. In 1915 a researcher named Nikolai Anitschkow did a study where he fed rabbits diets high in cholesterol and they developed atherosclerotic lesions in their arteries. The problem was that rabbits are herbivores and not physiologically adapted to eating cholesterol since plants don’t contain. When they fed high cholesterol diets to dogs/wolves which are carnivores, they do not develop atherosclerosis. In the 1950’s a physiologist named Ansel Keys also believed that dietary fat and cholesterol caused heart disease. To “prove” this he documented the diet patterns of seven countries and concluded that the people in the countries that had the highest total and saturated fat intake also had the highest incidence of heart disease. The problem was that he chose to exclude those countries that had the opposite findings, namely France and Switzerland which had the highest saturated fat intake also had the lowest incidence of heart disease. At the same time a physician named John Yudkin in England theorized that dietary sugar was the real cause of vascular disease and when he looked at Keys’ own data he showed that sugar tracked more closely to heart disease than fat did in the countries Keys picked. Keys went on a mission, however, to convince the world that eating fat, and saturated fat in particular should be limited to avoid heart disease. He apparently was very persuasive as he had little trouble convincing the US government of his theory So, 1980 with the first USDA dietary guidelines for Americans, total fat, cholesterol, and saturated fat were advised to be avoided and complex carbohydrates were recommended to be eaten preferentially. No mention was made for sugar restriction. At this same time, besides Yudkin warning about sugar as the cause of heart disease, the leading lipidologists in the US including Pete Ahrens of Rockefeller University were studying lipid patterns and heart disease and discovered that triglycerides and HDL were more strongly correlated with heart disease than LDL cholesterol, and that diets low in fat and high in carbohydrate, although they might lower LDL cholesterol, worsened triglycerides and HDL and worsened risk for heard disease. Plus they found that LDL cholesterol itself had very little correlation with heart disease. When they presented this argument to George McGovern’s senate committee looking into diet and health, Senator McGovern said to Ahrens, “You mean I can eat all fat and cholesterol I want and it won’t hurt me?” When Ahrens said, “Yes,” McGovern said “Well that’s not what my cardiologist says.” Unfortunately the government bought the “cholesterol, diet, heart hypothesis” as well as the American Heart Association and it has been the mainstay of dietary guidelines ever since.
AFTER the government decided to adopt these guidelines, they then went about funding studies that they felt would prove it correct with three large studies totaling nearly a billion dollars in tax payer money, LRC-CPPT, MRFIT, and Women’s Health Initiative. They failed. None showed convincing evidence of benefit of the diet. The largest, the women’s health initiative, followed 50,000 women for 8 years, half followed a low cholesterol, low fat diet. After 8 years there was no benefit in any parameters of weight, heart disease, or cancer. Nonetheless the government and AHA stuck to their belief.
The reason that diets that lower cholesterol failed to prevent heart disease is because total cholesterol has nothing to do with causing heart disease. Numerous studies have failed to show a correlation between total cholesterol or even total LDL and heart disease, in fact in women over 50, all studies show that the higher the cholesterol, the longer they live. A large study done at UCLA found that the average LDL of acute heart attack patients was less than 100 and a third were less than 70. The national average LDL cholesterol at the time was 140. So why did these studies fail? It turns out Yudkin was correct. It is sugar via the metabolic syndrome that is the cause of heart disease along with basically all the other chronic diseases of civilization namely obesity, diabetes, hypertension, heart disease, stroke, and cancer. As Gary Taubes so eloquently illustrates in his recent book, “The Case Against Sugar,” excess sugar and in particular the fructose part of sugar induces a physiologic state called insulin resistance which causes insulin levels to rise, both at baseline and especially after consuming glucose containing food. This state of fructose induced insulin resistance with high insulin levels is called metabolic syndrome and is a precursor of diabetes and is the substrate for the chronic diseases of modern civilization. It was first described by a Stanford diabetologist, Gerald Reaven. It is associated with numerous physiologic changes in the body including high insulin levels, truncal and visceral obesity, elevated blood pressure, high triglycerides, low HDL levels, elevated blood sugar, change in size of LDL particles to small dense character, increased leptin level from leptin resistance as well. It is this metabolic syndrome with it’s elevated insulin level which is associated with vascular disease, coronary artery disease, stroke, as well as cancer, not cholesterol. There is much debate going on as to what feature or features of the metabolic syndrome actually cause vascular disease. Most researchers are still focused on lipids so they are studying the various lipid particles, LDL, large vs small, Apo B particles, Apo A particles, HDL, large vs small HDL, trying to see which particles “cause” vascular disease as well as what change in the lipid particles associated with the metabolic syndrome are responsible for vascular disease. The fact that metabolic syndrome is associated with a higher LDL particle count and that those LDL particles are smaller and more dense leads some to believe that the high number of small dense LDL particles overwhelm the vascular endothelium and cause plaque to form. The trouble is that some studies show that the total number of these particles actually doesn’t correlate with incidence of heart disease any more than the fact that they are small and dense as caused by metabolic syndrome (1).  Looking at individuals and groups there is no more evidence that various lipid particles “cause” vascular disease beyond being markers that an individual has insulin resistance and metabolic syndrome and that that something about insulin resistance, metabolic syndrome itself is the actual cause of the vascular lesions of atherosclerosis. I personally believe it is the high insulin level itself that does the damage to the walls of vessels that makes them vulnerable to plaque formation and that various lipid particles and their sizes are nothing more than markers of insulin resistance and metabolic syndrome with it’s chronic elevated insulin levels. There is data to suggest this. When rabbits are fed cholesterol they do develop atherosclerosis as stated above. However when researchers make rabbits diabetic by treating the pancreas to not make insulin, and these rabbits are fed high cholesterol diets, they don’t get atherosclerosis until they are given high doses of insulin. Studies by Robert Stout, in England, showed insulin enhanced transport of cholesterol and fat into cells of the arterial wall just as insulin enhances transport of fat into fat cells in adipose tissue. Insulin is also induces tissue growth including stimulating growth of arterial smooth muscle cells.
As Gary Taubes argues in The Case Against Sugar, dietary sugar appears to be the main culprit in causing metabolic syndrome and the diseases associated with it namely obesity, diabetes, hypertension, heart disease, stroke, and cancer.  Societies that don’t or didn’t have sugar, don’t have any of these diseases. This includes the Inuit in the arctic where the diet was all animal products which included mostly cariboo, fish, and marine mammal blubber. Their diet was 80% fat and 20% protein. They had none of those diseases of western society including obesity, diabetes, hypertension, heart disease, and cancer. After the first explorers studied the Inuit and made these observations, they were studied closely and observed for the development of these diseases. The first case of breast cancer didn’t appear until 1966 and by 1975 there were only two more. Now the Inuit have the same incidence of all these diseases as they have adopted the modern western diet with it’s high sugar consumption. The same goes for the native peoples in America where early military physicians noted the same thing, as well as Albert Schweitzer in Africa where he worked with native peoples for 40 years. He noted the remarkable absence of those diseases. George Campbell, another physician who came after Schweitzer worked with the Zulu in South Africa. He had clinics in the bush where the Zulus ate their natural diet as well as an urban clinic in Durban. He noted again none of the above diseases of western civilization in the clinic in the bush but all of them in the city where the diet was western type. In his meticulous records, he noticed that it took a diet containing 70 lb of sugar per year for 20 years for the above diseases to start showing up. This appears to be holding up in current observations. The current average per capita sugar consumption in the US now is 120 lb per person per year. In all societies where sugar consumption has been tracked, there have been a dramatic increases in consumption after they became westernized or from the general dramatic increase in world consumption the past 140 years. In the US annual per capita sugar consumption rose from 10 lb per capita per year in the early 1800’s to, to 80 lb per year in 1900, to 100 pounds per year in 1920. It peaked at 150 lb per person per year in 1995. Now it is about 120 lb per person per year. In every case the dramatic rise in sugar consumption was associated with a similar dramatic rise in obesity and diabetes in all societies.

I believe atherosclerosis is “caused” by disruption of the endothelial lining of arteries where there is injury which leads to the cascade of lipid deposition and atherosclerosis, but there has to be injury to the endothelium first. High cholesterol alone won’t cause this. In the vast majority of individuals that injury is caused, I believe, by high insulin levels caused by metabolic syndrome. Once the injury has occurred, high LDL may contribute to accelerating the process, possibly. The next most common cause of endothelial injury leading to atherosclerosis is hypertension and artery wall stress. An example of this is patients with coarctation of the aorta who have hypertension from a purely mechanical basis ie narrowing of the aorta above the heart, without any metabolic syndrome component to their hypertension. If not caught early and treated with surgery, they die in their 30’s of MIs. Again artery wall stress injures the artery lining and then inflammation sets in with atherosclerosis formation.
There are two more points to be covered in the argument that lipid particles don’t cause heart disease. First, proponents of the theory like to point to familial hypercholesterolemia where individuals have a genetic variation that causes high cholesterol levels. Homozygous individuals with two copies of the gene do indeed have extremely high cholesterol levels over 1,000 and die of myocardial infarctions early in life in their 30’s. But their cholesterol levels are extremely high and fortunately this is very rare. Homozygous individuals have high cholesterol, usually in the 300-500 range and have higher incidences of heart disease compared to the general population, before age 50, but no increase in heart disease rates after 50 despite still having the same high cholesterol levels (2). Ok, so if high cholesterol levels cause heart disease in these individuals why doesn’t it carry through their whole lives. Another interesting observation was made about heterozygote FH’s. Familial hypercholesterolemia can be traced back genetically through families. Such a study was done in a family pedigree in Holland. They traced the gene in a family back to the early 1800s. It turned out that FH heterozygotes had lower mortality rates in all decades of life through the 1800’s, but in the 1900’s they started showing increased mortality, right when the sugar/ diabetes epidemic started to take off (3).   So it appears again that without the injury to the lining of the artery caused by sugar and the metabolic syndrome, high cholesterol in these FH heterozygotes was harmless.
There is an animal model for this as well. Back to dogs. Researchers fed dogs high cholesterol diets plus removed their thyroid glands to make them hypothyroid which also raises cholesterol even higher. They didn’t develop coronary atherosclerosis until they were made hypertensive by creating surgical coarctations of their aortas (4).  Again it took the endothelial injury of the hypertension before the hypercholesterolemia could induce coronary artery disease, just as the hypercholesterolemic rabbits who were made diabetic didn’t develop vascular disease until they were given insulin to injure the the endothelial lining of their arteries.
The final argument in the cholesterol heart disease hypothesis is the reduction in cardiac events in patients given cholesterol lowering therapy. The most common such drug is the statin class which does lower cholesterol and is associated with lower incidence of cardiac events but dubious data on total all cause mortality. With statins, however the degree of LDL lowering does not correlate with the degree of cardiac event reduction suggesting it is some other action of statins that lowers cardiac events other than LDL lowering.  Some attribute it to coronary plaque stabilizing effects of statins rather than LDL lowering. The new class of cholesterol lowering drugs the PCSK9 blockers lower cholesterol dramatically and a recent study showed that getting further LDL lowering with one of these drugs caused a whopping 15% lowering in cardiac events from 11.3 % of patients having events to 9.8 % of individuals in each group having events, an actual absolute lowering of only about 1%. However, there was no reduction in total all cause mortality (5).  Same goes for statins. A recent study looked at 100,000 patients who were treated with statins after a heart attack. Those who could tolerate statins ie who stayed on them had a similar reduction in cardiac events compared to those who did not tolerate statins, however total all cause mortality was higher in those who stayed on statins than those who weren’t and came off them (6). To me these studies suggest that if you have a condition that CAUSES vascular disease by injuring endothelium such as hyperinsulinemia via metabolic syndrome, or hypertension, then a high LDL level particle count MIGHT accentuate the atherosclerotic process at best. But again aggressively lowering LDL in these individuals doesn’t bestow total all cause mortality benefits.

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Low Carb High Fat Diet to Treat Diabetes

Low Carbohydrate, High Fat, Atkins type diet should be the first step in treatment of all diabetics, both type one and two. Numerous studies and practice experience testimonies have confirmed this. See Eric Westman’s second video below. The most comprehensive review of the data supporting using LCHF to treat diabetes was cited in the tremendous article by R D Feinman PhD per this link:

RD Feinman PhD: Low Carbohydrate Restriction as First Approach in Diabetes Management

The LCHF diet consistently lowers glucose and A1C. Dr. Westman cites numerous cases where his patients were able to get off all medication including insulin within weeks and in one case in days, see his second video below.  The number emerging is that over half of all diabetics who go on the diet come off most if not all their diabetic medications. Although the diet is high in fat including saturated fat, the diet consistently lowers triglycerides and raises HDL, the two most important lipid markers correlating with risk for heart disease. Also contrary to what one would think it is diets that are low in fat and high in carbohydrate such as the American Heart Association Low Fat “Heart Healthy” diet that increase blood saturated fat levels, thus increasing cardiac  disease risk.  Low carb, high fat diets to the opposite ie lower blood saturated fat levels.  Phinney and Volek showed this.  See their videos and books cited below.   In addition, low fat diets lower HDL, “good cholesterol,” raise triglycerides, and even though they lower LDL, “bad cholesterol,” they convert most of that LDL cholesterol to the small dense or truly dangerous form of LDL cholesterol.  Low carbohydrate diets, on the other hand, which in some cases will raise total and LDL cholesterol, convert the LDL to the large, buoyant, harmless form of LDL cholesterol, thereby lowering risk of heart disease far greater than low fat diets will.  Dietary saturated fat consumption which will increase in most low carb diets also has never been shown to increase risk of heart disease in numerous studies.  All this is covered and referenced in detail in the above linked article, as well as in Nina Teicholz’ tremendous book, “Big Fat Surprise, Why Butter, Meat, and Cheese belong in an Healthy Diet,” as referenced below as well as linked to a video of hers below.