The ‘Deadly Dangers of Saturated Fat’ & the ‘Superlative Safety of Statins’

Part 1

Although these myths were thoroughly discredited recently, it is important to know how they originated and why they have persisted despite lack of proof and abundant evidence to the contrary Dr Paul J Rosch

The twin myths of the deadly dangers of saturated fat and the superlative safety of statins were thoroughly discredited recently (see [1, 2] Low Fat and Low Saturated Fat Diet Bad for Health and Statins for the Healthy are Harmful, SiS 66). Nevertheless, it is important to know how they originated and why they have persisted despite abundant evidence to the contrary.

Irrelevant animal experiments and false conclusions

It began with some irrelevant animal experiments and false conclusions. The presence of cholesterol in blood as well as atherosclerotic plaque had been known since 1850. In 1910, Adolf Windaus, a German physician and chemist, who later received a Nobel Prize for Chemistry, reported that atheroma in human aortas contained 6 times more free cholesterol than healthy arteries, and over 20 times more cholesterol ester [3].  A few years later Nikolai Anitschkow showed that feeding rabbits purified cholesterol obtained from egg yolks for two or three months produced lipid laden lesions in the aorta and other arteries [4].  However, there was little clinical interest in these observations as coronary heart disease was uncommon at the time.

That changed in 1950 when John Gofman, who had been impressed with Anitschkow’s experiments repeated them and replicated his results.  He was convinced that serum cholesterol and/or its dietary sources contributed to coronary atherosclerosis but knew this was not a direct effect as the cholesterol molecule was too large to pass through the arterial wall.  Little was known about how cholesterol was transported to different body sites to make vitamin D, testosterone, estrogen and other steroid hormones and Gofman was uniquely qualified to investigate this. Prior to receiving his medical degree in 1946, he obtained a Ph.D. in physics at Berkeley, where he studied under Nobel Laureates Ernest O. Lawrence and Glenn T. Seaborg.  Lawrence was awarded the 1939 Physics Nobel Prize for inventing the cyclotron, a device that accelerates charged particles.  Seaborg received the 1951 Chemistry Nobel Prize for using the cyclotron to discover uranium, plutonium, neptunium and other new elements and their isotopes, especially as uranium-235 was required to make the atomic bombs that ended the war with Japan.

Gofman learned of a new analytic ultracentrifugation device that had been developed in Sweden, and because of his superb background in physics and chemistry, immediately saw how it could be used to study cholesterol transport. He obtained one for his laboratory and found that the hypercholesteremic serum samples of his cholesterol-fed rabbits could be separated into two distinct compartments based on their density. The layer at the top of the serum sample was designated low-density lipoprotein cholesterol (LDL) and the deposit at the bottom of the test tube was called high-density lipoprotein cholesterol (HDL) [5].  As LDL appeared to be particularly proatherogenic, he proposed that it promoted the rapid progression of coronary disease in humans and later developed an atherogenic index based on lipoprotein values and ratios [6].   This stimulated myriad investigations, including the research of Michael S. Brown and Joseph L. Goldstein [7], who received the 1985 Nobel Prize in Physiology or Medicine “for their discoveries concerning the regulation of cholesterol metabolism' that led to the development of statins [8].  Gofman believed that avoiding animal fats and cholesterol would help prevent coronary disease, as indicated in his Introduction to The Low Fat, Low Cholesterol Diet: What To Eat And How To Prepare It, a 1951 book co-authored by his pediatrician wife, Dr Helen Gofman and others at Berkeley [9].

False association between animal fats, cholesterol and heart disease

Anitschkow also got a big boost from Ancel Keys, who chaired the 1951 conference of the UN’s Foodand Agriculture Organization in Rome. He asked the audience aboutdiet as it related to the heart attack epidemic in middle-aged men that was sweeping across the US.  Prior to 1920, less than 10 percent of all US deaths were due to heart disease,but by 1950, this had escalated toover 30 %. A University of Naples professor told him there was no such problem in his or nearby cities, which Keys personally verified.  The only exception he found was asmall class of wealthy people who dined on meat daily. The general public had meat once or twice a week and mostly ate pasta, fruits and vegetables. He also found that except for the meat eaters, the average cholesterol levels were low, and concluded that there was an association between a high fat diet, elevated serum cholesterol and coronary heart disease rates, just as Anitschkow proposed. Within a few years, Keys identified six countries where there were similar findings [10], and subsequently embarked on his extensive Seven Countries study in healthy middle-aged men that appeared to confirm these cause-effect relationships [11].

Strong support for Anitschkow also came from the Framingham study, which had been initiated by the National Heart Institute in 1948 to identify factors thatcontributed to heart disease [12]. Residents of this small manufacturing town near Boston were periodically investigated for anything that might conceivably influence the development of coronary heart disease, including blood levels of sugar, cholesterol and other chemicals, fat consumption, smoking, degree of obesity, physical activity and exercise habits. Their 6-year follow-up analysis of over 4 000 healthy men and women aged 31-65 found that serum cholesterol measured at the start was significantly higher among those who experienced coronary events during this period. The Framingham study went on to identify other modifiable risk factors such as smoking, hypertension, obesity, diabetes and lack of exercise, which had additive effects.  Nevertheless, the major culprit was elevated cholesterol from dietary fat. This was reinforced by the 1977 McGovern Senate Committee on Nutrition report that advised avoiding saturated fats to lower cholesterol levels and prevent heart disease [13].

Official government policy established on cholesterol as the culprit

This became official government policy with the establishment of the National Cholesterol Education Program in 1985, and is ongoing.  September has been designated National Cholesterol Education Month, during which everyone is urged to have their cholesterol and lipoprotein levels measured.  That’s not surprising as the role of cholesterol and LDL now seemed to be indisputable. In a 1958 editorial, Dr. William Dock, a renowned cardiologist and Chairman of the Department of Pathology at Stanford University Medical School, wrote [14]: “Thus the early work of Anitschkow bears comparison with that of Harvey on the circulation and of Lavoisier on the respiratory exchange of oxygen and carbon dioxide.” Dock also compared the significance of Anitschkow’s research to Koch’s discovery of the tubercle bacillus. And a more recent ranking of “Cardiology's Ten Greatest 20th Century Discoveries” [15] listed the top three as 1) The Electrocardiogram, 2) Preventive Cardiology and the Framingham Study, and 3) The “Lipid Hypotheses” and Atherosclerosis.

How could we have been so wrong for so long?

Note that the last author used the term “Lipid Hypotheses” to include both the saturated fat diet-heart disease theory as well as the belief that elevated cholesterol was the cause of coronary atherosclerosis. But neither of these hypotheses has ever been proven. With respect to Antischkow's monumental discovery, rabbits are herbivorous and cholesterol is a foreign substance they cannot utilize or metabolize.  In addition, although serum cholesterols were often over 1 ooo mg/L (26mmol/L), the lipid deposits in arteries consisted mainly of macrophage derived foam cells rather than the fibrous and atheromatous plaques found in patients with symptomatic coronary atherosclerosis [16]. More importantly these findings could not be reproduced when the experiments were repeated in rats, dogs and other meat eaters, so they should not be extrapolated to people.

As noted in [1], although Keys had data on 22 countries, he cherry picked the seven that best supported his theory. When all the countries were included, there was no fatty diet-heart disease link [17], and had he selected Israel, Sweden, Germany and France, he would have concluded that the more saturated fat and cholesterol consumed, the lower the incidence of coronary heart disease. Despite that, Keys was featured on the cover of Time magazine, and his claim that saturated fats in the diet clogged arteries and caused heart disease was now supported by so many prestigious organizations and authorities that it was viewed as gospel. It was severely criticized by others, such as Russell Smith, a psychologist with a strong background in mathematics and physiology. He meticulously reviewed over 2 000 studies on the links between dietary fat, cholesterol and heart disease and came to this conclusion [18]:

“The word “landmark” has often been used to describe Ancel Keys Seven Countries Study, commonly cited as proof that the American diet is atherogenic. The dietary assessment methodology was highly inconsistent across cohorts and thoroughly suspect. In addition, careful examination of the death rates and associations between diet and death rates reveal a massive set of inconsistencies and contradictions. . . . It is almost inconceivable that the Seven Countries study was performed with such scientific abandon. It is also dumbfounding how the NHLBI/AHA alliance ignored such sloppiness in their many “rave reviews” of the study. . . . . In summary, the diet-CHD relationship reported for the Seven Countries study cannot be taken seriously by the objective and critical scientist.”

George Mann, the highly respected Professor of Medicine and Chemistry at Vanderbilt and a co-director of the Framingham study at the time, was even more vitriolic [19]:

“Saturated fat and cholesterol in the diet are not the cause of coronary heart disease. That myth is the greatest scientific deception of this century, perhaps of any century. The diet-heart hypothesis has been repeatedly shown to be wrong, and yet, for complicated reasons of pride, profit and prejudice, the hypothesis continues to be exploited by scientists, fund-raising enterprises, food companies and even governmental agencies. The public is being deceived by the greatest health scam of the century.”

“The greatest health scam of the century”

Observational studies can show a statistical correlation but not causation. Keys repeatedly tried several times to demonstrate significant changes in serum cholesterol by altering dietary fat intake with no success [20]. Decades later, he wrote [21]: “Dietary cholesterol has an important effect on the cholesterol level in the blood of chickens and rabbits, but many controlled experiments have shown that dietary cholesterol has a limited effect in humans.”

He was even more emphatic in a subsequent Internet magazine interview [22]: “There’s no connection whatsoever between cholesterol in food and cholesterol in blood. And we’ve known that all along. Cholesterol in the diet doesn’t matter at all unless you happen to be a chicken or a rabbit.”  However, by this time, most of the country was on a low fat or Prudent Diet that not only restricted saturated fat, but also increased polyunsaturated liquid vegetable fats such as corn oil.

The first report on the Prudent Diet was from the Joliffe Anti-Coronary Club in Manhattan, which had as controls a group of healthy middle-aged men who followed their usual diet of lots of eggs, butter, cheese and red meat. The Prudent Diet cohort strictly avoided these and substituted a special margarine rich in polyunsaturated fats for butter. After four years, although serum cholesterol was reduced in those following the Prudent Diet, eight had died from a myocardial infarction, compared to none in the control group [23].

Numerous other attempts to reduce coronary disease by limiting saturated fat intake also failed and several observational studies similarly found that saturated fat restriction was associated with increased risk of coronary heart disease deaths [24-28]. As Sylvan L Weinberg, a past president of the American College of Cardiology, warned in a subsequent editorial [29]:

“The low-fat–high-carbohydrate diet, promulgated vigorously by the National Cholesterol Education Program, National Institutes of Health, and American Heart Association since the Lipid Research Clinics-Primary Prevention Program in 1984, and earlier by the U.S. Department of Agriculture food pyramid, may well have played an unintended role in the current epidemics of obesity, lipid abnormalities, type II diabetes, and metabolic syndromes. This diet can no longer be defended by appeal to the authority of prestigious medical organizations or by rejecting clinical experience and a growing medical literature suggesting that the much-maligned low-carbohydrate–high-protein diet may have a salutary effect on the epidemics in question.”

The Framingham study, which established cholesterol as the most important risk factor for coronary heart disease, was never able to prove this or to show that saturated fat increased serum cholesterol or coronary disease. During the early 1950s, detailed information on dietary habits had been obtained on a thousand participants.  A follow-up analysis in 1971 found no connection between diet andserum cholesterol and the authors concluded [30]: “These findings suggest a cautionary note with respect to hypotheses relating diet to serum cholesterol levels. There is a considerable range of serum cholesterol levels within the Framingham Study Group. Something explains this inter-individual variation, but it is not diet.” The senior author William Kannel was then Director of the Framingham study, and this report was never published for obvious reasons.  However, over two decades later, William Castelli, who succeeded Kannel as Director, wrote [31]:

“In Framingham, Massachusetts, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower people’s serum cholesterol...we found that the people who ate the most cholesterol, ate the most saturated fat, ate the most calories weighed the least and were the most physically active.”  And a 30-year follow-up revealed that [32] 'For each 1 mg/dl drop of cholesterol there was an 11 % increase in coronary and total mortality.”

Saturated fat-heart disease hypothesis thoroughly discredited

The Tecumseh Community Health Study, which utilized data on the composition of over

2 700 foods, found that cholesterol and triglyceride levels were unrelated to quality, quantity, or proportions of fat, carbohydrate, or protein consumed [33]. Participants who ate the least cholesterol also had the highest blood cholesterol levels.

The World Health Organization’s Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) epidemiologic project was undoubtedly the largest study ever designed to explore the relationship between risk factors and cardiovascular disease.  It began in 1971 as a collaborative effort involving 32 centers in 21 countries that monitored approximately 10 million men and women aged 25-64 for ten years. It thoroughly discredited the saturated fat–heart disease hypothesis. All the countries in the top eight for saturated fat consumption had lower death rates for heart disease than all of the eight countries that consumed the least fat. The French consumed three times as much saturated fat as the Azerbaijani but had one-eighth the rate of heart disease deaths. Heart disease mortality in Finland was four times greater than in Switzerland, even though saturated fat consumption was similar [34].

Although such epidemiologic studies cannot prove or disprove causal relationships, no large scale interventional trial has ever demonstrated that restricting saturated fat reduces the risk of coronary disease [35, 36]. This was true even when combined with reducing other risk factors like hypertension and cigarettes as evidenced by the $115 million Multiple Risk Factor Intervention Trial (MRFIT). This involved 28 medical centers and 250 researchers who screened 361 662 men and deliberately chose those who were at the highest risk in order to increase the power of the test.

Compared to matched controls, cholesterol intake was cut by 42 %, saturated fat consumption by 28 %, total calories by 21 %, and there was a significant reduction in hypertension and cigarette smoking after 8 years. Although there was a modest fall in serum cholesterol, there was no effect on coronary heart disease and the disappointing conclusion was [37]: “The overall results do not show a beneficial effect on Coronary Heart Disease or total mortality from this multifactor intervention.”

The Women's Health Initiative (WHI) study was established by NIH in 1991 to address the most common causes of death, disability and impaired quality of life in postmenopausal women. This 15-year $625 million project involved 161 808 healthy postmenopausal women followed at 40 clinical centers that included three interventional clinical trials; Hormone Therapy, Calcium/Vitamin D supplementation and Dietary Modification. The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of CHD, breast and colorectal cancers. Study participants followed either their usual eating habits or the dietary regimen noted above. The results indicated that despite some reduction in cardiovascular risk factors such as blood lipids and diastolic blood pressure, there was no significant reduction in the risk of coronary heart disease or stroke in the cohort that restricted fat and increased fruit, vegetables and grain [38, 39].

As William James, the father of modern psychology noted, “There is nothing so absurd that it cannot be believed as truth if repeated often enough.” Although many more articles could be cited, most people still believe that saturated fatcauses heart attacks. Other reasons for this will be explored in Part 2, whichwill haveafocus on statin safety and efficacy, why figures don’t lie but liars can figure, why measuring cholesterol is a waste of time and money, and what really causes heart disease; so stay tuned!

Article first published 24/06/15

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