The Great Cholesterol Myth: Part 2

The Great Cholesterol Myth: Part 2

Turned Tables

It’s spring again, and it’s raining. Keys’ deep, sharp eyes follow his pen as he writes at a desk in Magdalen College, Oxford.


Dear Dr. Moschcowitz:


Your letter dated February 25 finally reached me by the devious route: St. Paul-Minneapolis-Oxford-Naples-Oxford. We are just back from a month’s work at Naples and expect to spend May doing research in Madrid.

It is with pleasure that I feel able to accept the invitation to deliver a lecture at the Mount Sinai Hospital in the coming winter. Something to do with atherosclerosis would appeal to me as suitable for the topic and the title might be: Atherosclerosis, a Problem in a Newer Public Health… During the current year I am on Sabbatical leave with a Fulbright Senior Research Award, attached to Magdalen College, Oxford.


Sincerely yours,

Ancel Keys


In 1951, Keys had accepted an invitation from a generous and brilliant Oxford nutritionist, Professor Hugh MacDonald Sinclair. The offer was a part in a study on “[the] deposition of cholesterol in EFA deficiency”, and included a position as visiting professor.   The two men had met back in 1942 when Sinclair visited the lab at the University of Minnesota. He had since been absorbed in studying the effect of essential fatty acid deficiency on atherosclerosis and, impressed with the multifaceted way Keys approached his work, had invited him onto his team.  Yet the partnership only lasts for one of the agreed upon two years. The academics aren’t seeing eye to eye. The point of contention is the results from Sinclair’s studies show a deficiency in fatty acids causes cholesterol to build up in the arterial tissues, while Keys “...considered that all fats raised plasma cholesterol equally,” Certain of his new position, he spends what’s left of his academic sabbatical travelling to the Netherlands, Spain, and Italy.


His suspicions of Fat had resurfaced with two developments. The first was during a 1951 malnutrition conference in Rome. Dr. Gino Bergami, Professor of Physiology at the University of Naples, informed him that coronary heart disease had barely reaped from the  working class, but hadn’t been so gracious to the wealthy.  During dinner with well-to-do Neapolitans, he noted, “The pasta was loaded with meat sauce and everyone added heaps of parmesan cheese. Roast beef was the main course. Dessert was a choice of ice cream or pasty. I persuaded a few of the diners to come for examination, and Margaret [his wife] found their cholesterol levels were much higher than the workmen.”


The second factor in Keys changing his mind was a 1950 paper by Swedish internist, Dr. Haqvin Malmros. The paper was titled, “The relation of nutrition to health; a statistical study of the effect of the war-time on arteriosclerosis, cardiosclerosis, tuberculosis and diabetes.” It included several charts detailing the mortality rates and the egg and milk consumption of four different countries, showing a drop both in dietary animal fat and deaths from atherosclerosis in Sweden, Finland, and Norway during WWII. His conclusion was that we “ought to avoid all luxury consumption of high-cholesterol food stuffs. Especially the combination of eggs and cream, butter and other fats would seem to be risky… There is much which goes to show that in Denmark, Sweden and the U.S.A. the consumption of… animalic fats is at present too high and may involve serious risks for public health.”


Although incredulous of some of Malmros’ claims, Keys nevertheless publishes another paper, boldly asserting that there is “no longer any doubt that one central item is the concentration, over time, of cholesterol and related lipids and lipoproteins in the blood serum” and charges back into the investigation with this newfound position. He begins by accepting the invitation of Dr. Eli Moschcowitz to lecture at Mount Sinai Hospital on January 7th, 1953. His presentation is an overview of predicting and preventing heart disease, and includes graphs charting the relationship between dietary fat percentage and heart disease deaths in different countries between the years 1948-1949. The audience is receptive, and the hospital publishes a summary of the talk in their small medical journal.


A few months later, Keys publishes a paper that would become infamous: “Atherosclerosis: a Problem in Newer Public Health.” In it, he lays out four points:


“1) It is a fact that, compared with healthy persons of the same age, patients with definite angina pectoris or who have survived a myocardial infarction tend to have blood serum characterized by high cholesterol and certain lipoprotein concentrations, a high cholesterol-phospholipid ratio, and a larger proportion of the cholesterol in the beta lipoprotein fraction.

2) It is a fact that, on the average, persons afflicted with diabetes, myxedema and nephrosis tend to have high cholesterol and the other peculiarities mentioned above. Among these patients there is a high incidence of atherosclerosis and degenerative heart disease.

3) It is a fact that in animal experiments those measures, such as high cholesterol diets and thyroid suppression, which produce high levels of cholesterol and allied substances in the serum, are also productive of atherosclerosis.

4) It is a fact that a major characteristic of the atherosclerotic artery is the presence of abnormal amounts of cholesterol in that artery. The atherosclerotic plaque consists of 40 to 70 per cent cholesterol. It is extremely probable that most or all of this cholesterol is derived from the blood. The cholesterol in the blood does not exist as a simple solution of free and ester cholesterol; it is carried in lipoprotein complexes.”


For the next year, Keys conducts informal explorations. He hosts conferences with various groups of doctors, looking for partners and the funding to launch a large-scale study of his hypothesis. A meeting is called in Naples to lay more formal plans, and it’s here that Keys meets a particularly influential and respected cardiologist from Boston… Dr. Paul Dudley White. If this one invitation had not been accepted, it is likely that the medical field, and the world, would be a very different place. The partnership that is forged between these men becomes the biggest force in the study of heart disease. Keys is about to take on the world, and Dr. White will be his only hope of survival.


In September of 1955, a committee of experts from the World Health Organization meet in Geneva. The discussion is on the Pathogenesis of Atherosclerosis, and Keys is expected to present. The panel members include some of his supportive colleagues, Drs. Haqvin Malmros, James Watt, and Johannes Groen, but it also includes those yet to be convinced; Oxford educated Sir George Pickering in particular, who would later describe the meeting as “lively, tending to tangents and tirades.”  Keys commences his presentation as he did at Mt. Sinai Hospital, drawing correlations between dietary fat and atherosclerosis, offering a particularly famous figure. In it, six countries are graphed out along a plane of heart disease deaths and percentage of total fat calories in diet, the data having been gathered between 1948 and ‘49. The United State crowns the chart, sitting at the intersection of forty percent of caloric intake and seven-thousand deaths. The committee members are wary. Halfway through a sentence, Pickering speaks up.


“Tell us, Professor Keys, if you would be so kind, what is the single best piece of evidence you can cite in support of your thesis about diet and coronary heart disease?”


The answer Keys gives is so far lost to history, but whatever it is supplies the challenging Professor of Medicine what he needs to shut Keys down. The others in the room eventually dismiss the evidence as simply corollary and nothing more, certainly not definitive, and the meeting is adjourned.


Most people would probably wish to dissolve into oblivion after failing such an eminent audience so conspicuously. Not Keys. There was a killer out there on the loose, and he was certain he knew who it was. Failure here simply gives him the motivation to convince everyone else, and he was about to gain the stage to do it.


Crime & Punishment

A 64 year old man is halfway through his second round of golf on a Friday afternoon. He’s on a business trip in Denver with his family, and is taking his free time to practise his favourite sport at the Cherry Hills Golf Club. He’s a fit man, average height. A ‘Type A’ personality with a temper, but aside from that he carries stress well and is generally optimistic. Smoking was the only substance vice in his life, but he stopped six years ago and has never faltered. He normally follows the advice of his doctors and a healthy diet, but today he allowed himself to enjoy a hamburger with onions before setting out to finish this second round. As he tees up for the ninth hole, however, something doesn't feel right. Was it the onions? Too much sun? To be safe, he ends the game and spends a quiet evening and dinner at home before going to bed at ten.


But he’s up at 1.30am. There’s a sharp pain in his chest. Assuming it’s indigestion, he asks his wife Mary to get him some milk of magnesia. While she does so, she decides it would be wise to ring his doctor, Maj. General Howard Snyder. The doctor arrives in a half an hour and administers the patient two doses of morphine. He sleeps until 11am, but wakes up still in pain. Four hours and two more doctors later, he is admitted to the Fitzsimmons General Hospital.


While the doctors and staff work to stabilise his condition, other doctors are called in for consultation. Someone suggests that a civilian heart specialist should be one of them, and none other than Dr. Paul White is decided upon. He arrives on Sunday at 1.10pm and examines the man, affirming the diagnosis of the other doctors, and prescribes two or three weeks of bed rest, Coumadin for blood clotting, Quinine to regulate heart rhythm, and a “light diet”.


4.12pm. A bulletin is released to the media: “...a moderate attack of coronary thrombosis, without complications. His present condition is satisfactory.” In English, Dwight D. Eisenhower has had a heart attack.


While doctors and scientists have been noting the health trends for years, it isn’t until this event that the public takes note. Now coronary heart disease is on everyone’s mind as their country’s leader is confined to a hospital bed. Suddenly not just experts, but the public wanted answers. What causes heart disease? Can it be stopped? What do we do? In the spirit of not letting a serious crisis go to waste, Dr. White takes charge. The Monday after Eisenhower’s attack, and frequently over the next six weeks, he and other doctors begin to catechize the American public during press conferences on cholesterol and heart disease, emphasising the important factor of diet.


Keys keeps working. After his humiliation at the WHO conference, he travelled to Spain, South Africa, Japan, and Finland, conducting preliminary informal surveys. On a September day in 1958, a collection of medical experts, spouses, and dignitaries gather in one of the dining rooms of the Hotel Jadran in Makarska, Yugoslavia. Its brutalist grid backs up against the mountain Sveti Jure, and a little life breathes in through the windows from the Adriatic at its feet. The party has gathered to christen the start of their biggest project yet. Beginning tomorrow, at the direction of Ancel Keys, the Seven Countries Study (SCS) will commence. The objective is to document the percentage of fat in the diet of each country and the corresponding serum cholesterol levels, and measure their association to heart disease. Apart from Yugoslavia, teams have been deployed to Finland, Netherlands, Italy, Greece, and Japan, and a group stays behind in Minnesota to conduct a study specifically on men in the Railroad workforce.


Amid field work, Keys and his biochemist wife Margaret publish a cookbook, “Eat Well, Stay Well”, outlining their ideas of how heart-healthy Mediterraneas eat based on some of their experiences during their travels. In it they note that “It is still not provided by rigorously controlled large-scale experiments on statistically impeccable samples of the American population that the kind of dietary adjustment suggested in this book will actually prevent or lessen the risk of heart attacks. The extraordinary difficulties of such experiments may mean the ultimate, irrefutable proof can never be provided… We now know that the likelihood of future coronary heart disease rises steeply with the level of cholesterol in the blood. And we know that the level of cholesterol in the blood rises with the amount of saturated fat in the diet.” They proceed to sell 120,000 hard-back copies.


As Keys continues to rise in the eyes of the public, an ever deepening shadow stretches over Fat. His time is short. The climax of the hunt is inevitable. Some continue to fight for his honour, but his fate was about to be sealed. January of 1961 comes with Keys’ face on the cover of TIME magazine. The article is titled “Medicine: The Fat of the Land” and begins by detailing America’s woes with health and food: the fads, the diets, tonics, vitamins, even pink protein cocktails, and the $900,000,000 America spends on said products. “...a big part of the public wants to know facts about diet and health, and a big group of U.S. scientists wants to supply them. The man most firmly at grips with the problem is the University of Minnesota’s Physiologist Ancel Keys… Keys’s findings, though far from complete, are likely to smash many an eating cliché.” It follows with the main messages of Keys’ campaign:


Ҧ Americans eat too much. The typical U.S. daily menu, says Dr. Keys, contains 3,000 calories, should contain 2,300. And extra weight increases the risk of cancer, diabetes, artery disease and heart attack.


“¶ Americans eat too much fat. With meat, milk, butter and ice cream, the calorie-heavy U.S. diet is 40% fat, and most of that is saturated fat—the insidious kind, says Dr. Keys, that increases blood cholesterol, damages arteries, and leads to coronary disease.”


The topics of Key’s personal disgust for obesity, the psychology of food, and dieting on grown-up formula then segway into his charges against cholesterol. 


What concerns him much more [than overeating] is the relationship of diet to the nation’s No. 1 killer: coronary artery disease, which accounts for more than half of all heart fatalities and kills 500,000 Americans a year… 


Cholesterol, the cornerstone of Dr. Keys’s theory, is a mysterious yellowish, waxy substance, chemically a crystalline alcohol. Scientists assume that cholesterol… is somehow necessary for the formation of brain cells, since it accounts for about 2% of the brain’s total solid weight… They suspect it plays a role in the production of adrenal hormones, and… believe it is essential to the transport of fats throughout the circulatory system. But they cannot fully explain the process of its manufacture by the human liver. Although the fatty protein molecules, carried in the blood and partly composed of cholesterol, are water soluble, cholesterol itself is insoluble, and cannot be destroyed by the body. “A remarkable substance,” says Dr. Keys, “quite apart from its tendency to be deposited in the walls of arteries.”… 


Ordinarily, the human liver synthesizes only enough cholesterol to satisfy the body’s needs—for transportation of fats and for production of bile. Even eggs and other cholesterol-rich foods, eaten in normal amounts, says Dr. Keys, do not materially affect the amount of cholesterol in the blood. But fatty foods do… 


Neither Keys nor anyone else claims to know the whole complex chemical-mechanical story of cholesterol deposition, but he regards the cause-and-effect relationship between cholesterol and heart disease as proved… 


Keys’s theory… is still questioned by some other researchers with conflicting ideas of what causes coronary disease. The main difference is that they variously blame hypertension, stress, smoking and physical inactivity, while Keys gives these causes only minor roles. But the army of Keys supporters is growing... Keys’s chief weapon has been the sheer weight of solid statistics. Says one Philadelphia physician: “Every time you question this man Keys, he says, ‘I’ve got 5,000 cases. How many do you have?’”...


Most fads are short-lived and harmless. Even the worst usually harms only a relatively few susceptible people. But fads encourage distrust of doctors and self-diagnosis. In such an atmosphere of skepticism, it is difficult for a physician to convince a patient who feels fine that he must give up something he likes, to preserve his health. Yet, says Dr. Keys, that is exactly what many Americans should do. The average blood cholesterol count among middle-aged (40-60) U.S. men, says Keys, is an uncomfortable 240. “People should know the facts,” he says. “Then if they want to eat themselves to death, let them.”...


The only sure way to control blood cholesterol effectively, says Keys, is to reduce fat calories in the average U.S. diet by more than one-third (from 40% to 15% of total calories), and take an even sterner cut (from 17% to 4% of total calories) in saturated fats. He also warns against confusing the blood cholesterol level with cholesterol actually deposited in the arteries. No known diet will remove deposited cholesterol, and the object of all diets is only to keep deposits from growing to the point that they cut off the heart’s blood supply.


His diet recommendations are fairly simple: “Eat less fat meat, fewer eggs and dairy products. Spend more time on fish, chicken, calves’ liver, Canadian bacon, Italian food, Chinese food, supplemented by fresh fruits, vegetables and casseroles.” Adds Keys: “Nobody wants to live on mush. But reasonably low-fat diets can provide infinite variety and aesthetic satisfaction for the most fastidious—if not the most gluttonous—among us.”


Other than being on T.V., which Keys had already done and would again later in March, there are few things more confirming of the public’s recognition than being on the cover of TIME. He was deified to ‘Guardian Angel’, and Fat demoted to ‘Demon’. 


Later that year, the gavel blow finally comes from academia. Dr. White asks Keys to join the newly formed Nutrition Board at the AHA. Heart Specialist Irvine Page and Nutritionist Frederick Stare draft up an organisational stance, and after thirty-seven years of refraining from publishing advice on preventing heart disease, the American Heart Association officially adopts Keys’ hypothesis as fact.


It was now almost fifteen years since Ancel Keys had first started asking questions, and he had finally been assured he was right. He blamed the delay in the acceptance of his hypothesis on physicians failing to realise that “the first heart attack is usually only a late result of underlying disease in the coronary arteries that began many years earlier. In a given patient it may be difficult to see any relation between his clinical condition and his current blood cholesterol level or his recent dietary history.” The case was closed. Fat had finally been tried, convicted, and sentenced not only by a scientific supreme court, but more importantly by the everyday people who had trusted him for so long. He was driven out of mother’s kitchen and the doctor’s office. Now marked as an alien, he was banished. 


And just like that, as had happened many times before, the detectives, heads raised and backs patted, strolled past the killer who had been there all along.

 

  1.  Keys, A. “Cover letter to Mt. Sinai re lecture to be given by Ancel Keys on January 7, 1953 before a small audience.” 1952? University of Minnesota Heart Attack Prevention Letters, Memo, & Documents www.epi.umn.edu/cvdepi/document/ancel-keys-1953-correspondence/  Accessed Oct. 24, 2024
  2.  Sinclair, H. M. (September 30, 1985) This Week’s Citation Classic: Deficiency of essential fatty acids and atherosclerosis, etcetera. garfield.library.upenn.edu/classics1985/A1985AQU5900001.pdf

  3.  Blackburn, H. “Hugh Sinclair: An Eccentric and His Theory on Essential Fatty Acids” University of Minnesota Heart Attack Prevention (date unknown) www.epi.umn.edu/cvdepi/essay/hugh-sinclair-an-eccentric-and-his-theory-on-essential-fatty-acids/

  4. Ibid., 22

  5.  Taubes, G.  Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health  New York, NY, Anchor Books/Random House, 2008, Pg. 3

  6.  Levenstein H., Fear of Food: A History of Why We Worry About What We Eat, London, U.K., University of Chicago Press, 2012.

  7.  Malmros H. (1950) The relation of nutrition to health; a statistical study of the effect of the war-time on arteriosclerosis, cardiosclerosis, tuberculosis and diabetes.  pubmed.ncbi.nlm.nih.gov/14789502/

  8.  Keys A. (November 1953) Prediction and possible prevention of coronary disease.  pubmed.ncbi.nlm.nih.gov/13104699/

  9.  Keys A. (Jul-Aug 1953) Atherosclerosis: a problem in newer public health. www.epi.umn.edu/cvdepi/wp-content/uploads/2014/03/Keys-Atherosclerosis-A-Problem-in-Newer-Public-Health.pdf

  10. Blackburn, Henry (2012) 20th-Century “Medical Marco Polos” in the Origins of Preventive

    Cardiology and Cardiovascular Disease Epidemiology, pg. 765, www.ajconline.org/article/S0002-9149(11)03212-7/pdf

  11.  Ibid., 17, pg. 134

  12.  Ibid., 18

  13.  Messerli, F.H., Messerli, A.W., Luscher, T.F. (September 22, 2005) Eisenhower’ billion-dollar heart attack – 50 years later., pubmed.ncbi.nlm.nih.gov/16177247/

  14.  Paul, O., Take Heart: The Life and Prescription of Paul Dudley White, the World’s Premier Cardiologist, Boston, MA, Harvard University Press, 1986.

  15.  Ibid., 22

  16.  Teicholz N. (December 8, 2022) A short history of saturated fat: the making and unmaking of a scientific consensus.  pmc.ncbi.nlm.nih.gov/articles/PMC9794145/#R2

  17.  Ibid., 23

  18.  Blackburn, H., On the Trail of Heart Attacks in Seven Countries, pg. 6  sph.umn.edu/site/docs/epi/SPH%20Seven%20Countries%20Study.pdf

  19.  “About the Study” Seven Countries Study  www.sevencountriesstudy.com/about-the-study/

  20.  Keys, A., Keys, M., Eat Well, Stay Well, Garden City, N.Y., Doubleday, 1959, 1963

  21.  Blackburn, H. “Eat Well, Stay Well” University of Minnesota Heart Attack Prevention  www.epi.umn.edu/cvdepi/multimedia/documents/ancel-keys-selected-letters/eat-well-stay-well/

  22.  “Medicine: The Fat of the Land” Time, (Jan. 13, 1961) time.com/archive/6624894/medicine-the-fat-of-the-land/

  23.  “To Tell the Truth - Inventor of K-rations; Miss Australia (Mar 6, 1961)” YouTube, uploaded by To Tell the Truth (CBS), 29 February, 2016, www.youtube.com/watch?v=1MDpFyhm_lk

  24.  Ibid., 35

  25.  Ibid., 15

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