Ancel Keys early in his career

Meet Monsieur Cholesterol

University of Minnesota Update, Winter 1979
by William Hoffman

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"There's a little hotel in Brussels that my wife and I stop at now and then, and every time I go in there the maitre d', a lady in her sixties, says, 'Ah, Monsieur Cholesterol!'"

Ancel Keys no longer totes his statistics tables to prove a point, or at least he doesn't need to anymore. His theory on the connection of diet, blood cholesterol levels, and heart disease is widely recognized now.

But if the great cholesterol controversy of the 1950s and '60s has waned, Keys plainly has not. His retirement home on the Mediterranean south of Naples is perhaps more a way station than a seaside retreat.

"I was invited to give two lectures at the International Congress on Nutrition in Rio de Janeiro. So we left the Twin Cities for New York last summer -- we like to spend July and August in Minnesota -- and flew to Rio. Then we flew to Lisbon, Zurich, Milan, Naples, and home for a rest. Then we went to Athens, Bangkok, Singapore, where I lecture, Hong Kong, Japan, where I gave the inaugural lecture for the Noboru Kimura Foundation for Medical Research, back to Italy and then back to the Twin Cities. That's about 40,000 miles by air."

Professor emeritus in the School of Public Health and former director of the University's Laboratory of Physiological Hygiene, Keys has spent a fair portion of his life between stops. His first experience of traveling, when he was only two years old, was as a refugee from the devastation following the San Francisco earthquake of 1906. Some 20 years later he traveled to China aboard ship, and roughly 10 years after that trip he scaled a peak in the Chilean Andes in midwinter. Since then he has traveled the world over -- a number of times -- as a leading authority on diet and cardiovascular disease.

Still spry and voluble at 75, Keys has had a number of diverse occupations. As a boy he worked in a lumber camp for a while, then shoveled bat guano in an Arizona cave. He served as a powder monkey in a Colorado gold mine and later as a clerk in a Woolworth store. Many years later, as a physiologist and nutritionist, he developed K rations (K for Keys) for army combat troops, and then instigated and directed the first scientific study of human starvation.

He is a former chairman of the International Society of Cardiology and has been a consultant to the World Health Organization and the Food and Agriculture Organization for almost 30 years. He is a member of countless medical science organizations and has written hundreds of articles. And he is a friend of many peoples.

"I'm fully in favor of Minnesota, except for the winters," said Keys, who lived in St. Paul for 35 years. "But I wouldn't want to live in a tropical area either, though Singapore is lovely. In Italy we have snow in the mountains. Winters are mild. I noticed the temperature in Rome this morning was 59 degrees and a couple days ago it was 61. We're a little warmer than that near Naples, but it gets down into the 40s at night."

Keys revealed his characteristic blunt manner of speaking when sitting in his office at Health Sciences Unit A, a new building on the Twin Cities campus. "This building is antiseptic. No charm or character at all. But I suppose it works after a fashion. Still, it's too cold in the summer, too hot in the winter.

"The old lab was below the football stadium, you know. It was strictly a temporary proposition back in the early '40s, then it was extended. We borrowed and stole and cheated to fix it up a bit, but at least is had some character. The facilities here are very good indeed, as far as I can make out. But the building itself is sterile."

Keys retired in 1972 after 36 years at the University, 26 of them as director of the Laboratory of Physiological Hygiene, where most of his pioneering research on cholesterol and heart disease was conducted, along with other research designed to "find out before people get sick why they get sick."

Shopping around

As an only child, Keys was born in Colorado Springs, Colorado, in 1904. His family moved to San Francisco and, after the earthquake, to Los Angeles and finally settled in Berkeley, where Keys attended school. After his experiences in the lumber camp, cave, and mine, he entered the University of California at Berkeley in 1922.

"I started out in chemistry. The department of chemistry at Berkeley at that time was perhaps the leading one in the country, with many students. I did about two-thirds of the chemical stuff, but I wanted to get out of school in a hurry so I checked into the idea of switching majors. Another reason was that at the end of my freshman year they offered a scholarship, and I was only runner-up for it. So I was a little disillusioned."

Keys switched to economics and political science, then left school temporarily to sign as an oiler aboard the S. S. President Wilson, bound for China. "The diet was mainly alcohol," the nutritionist told Time magazine in 1961. "I don't remember eating anything." Upon his return he went back to the University of California, where he received a bachelor's degree in 1925.

"I didn't know what I wanted to do, so I went back to the university and talked to the one professor in political science and economics who had impressed me. His name was Paul Cadman, and he was quite a character in practical economics, you might say. He was an adviser to several banks in San Francisco, that sort of thing.

"He had impressed me a good deal with his course, which reminds me very much of John Kenneth Galbraith's book The Age of Uncertainty. The course was on the history of economics and political thought. Anyway, Cadman listened to me for a while and then he said, 'Look, I think you ought to see my friend Professor Kofoid.' I'd never heard of Kofoid, but it turned out he was head of zoology."

Although he had not taken a biology course since high school, Keys finished his mater's degree in zoology in six months by "sort of tripling up on course work," and in 1928 was on his way to the Scripps Institute of Oceanography in La Jolla. "They got me a fellowship down there. I had been hard up for some years, so this was great. Big money. A hundred dollars a month and I lived in a nice little redwood bungalow on the cliff." He was granted a Ph.D. in oceanography and biology two years later.

A National Research Council fellowship for two years of study in Europe took him to Copenhagen to work under Professor August Krogh, a Nobel laureate in physiology. Next he went to the University of Cambridge, where he did research, lectured, and earned a Ph.D. in 1936.

"It was fairly common in those days to move around a lot. Not so much nowadays, perhaps, but it used to be -- shopping around from one school to the other as a postdoctoral fellow. If you had the wherewithal to hold body and soul together, that's what you did. I was just about to accept a permanent job at Cambridge, however, when I got a cable from Harvard. So I said to myself, 'Okay, go to Harvard and see what's happening in the States.' I taught biochemistry at Harvard and stayed for three years.

"Before this, I had been thinking about questions of high altitude adaptation, things like that. So I very quickly planned an expedition an spent six months in the Andes. Coming back and writing it up accounted for half my time at Harvard."

Keys's boss at Cambridge, John Barcroft, had climbed to the top of Tenerife, the largest of the Canary Islands, "about 12,000 feet, not all that high actually." Barcroft's book on his high-altitude study inspired Keys and a friend to conduct a major high-altitude study in the Andes. He thought findings of the expedition would have practical import for the Chilean copper miners living and working at great heights. And at Harvard money was available for such research.

"I took a small group down there to make preparations. We stayed at about 9,500 feet for two months and made a base. The actual work at higher altitudes took about five weeks -- at successive altitudes from about 15,000 up to 20,000 feet or a little over. Sir Brian Matthews and I did the highest work because we stood the altitude better. We were up over 20,000 feet for about 10 days.

"It was awfully damned cold constantly, because it was midwinter. We had expected to go to the Himalayan region in Asia at a latitude of 25 or 30 degrees north. Instead we ended up being 22 degrees south in July, which is the middle of winter. In the cold, you easily lose your breath, but you just pace yourself. We got along.

"We had a little snow shelter -- put up a few poles and blankets over them -- and crawled in there to get out of the wind and cold. At night the temperature dropped to 50 below. We didn't do much cooking, of course. Through it all I lost a little weight but wasn't sick in any important sense, though of four others who came up from time to time two were very sick. One of them was John Talbott, who later was editor of the Journal of the American Medical Association for many years. We had an awful time getting him down. He was not blue but black -- gas pain, retching. We thought he was going to die. You see, Brian and I had the advantage of having lived at 10,000 feet for a couple of months beforehand."

K rations and starvation

Several months later Keys accepted a job offer from the University of Minnesota's Mayo Foundation in Rochester. "They offered me twice my miserable salary at Harvard and an opportunity to set up a new division of biochemical research on human beings, human physiology and biochemistry. But after I'd been there a year I found it a little confining. With my background, it just seemed to me awfully provincial, if you don't mind my saying so. All the docs talked nothing but doc business and the evenings were devoted to bridge."

After a year in Rochester, Keys was invited by Lotus D. Coffman, then president of the University, to come to Minneapolis and organize what was to become the Laboratory of Physiological Hygiene. Among Keys's early research projects were subsistence tests for the defense department. A study of the physical difference between athletes and nonathletes caused a writer for Life to call him "the only U.S. scientist whose work is supported on the budget of a University athletic association." In that study, Keys concluded that athletes' hearts are no larger than those of nonathletes, but they beat more slowly.

In 1941, serving as a special assistant to the secretary of war, Keys started working with the army to develop rations for troops in combat. The first K rations resembled a typical bag lunch and were tested by soldiers at Fort Snelling. "We bought the stuff down at Witt's, the best market in the Twin Cities in those days.

"Six months later, I went down to Fort Benning, Georgia, run to more elaborate trials. Then General McNair, the chief of infantry at the time, said that this was going to be the combat ration because it was easy to hand out. The logistics were simple, that's all. But I was surprised when I saw the packages start to roll in with 'K' on them. Then I got a letter for Colonel Logan of the Quartermaster Corps in Washington saying he hoped I wouldn't mind. Of course, it's all different now -- roast turkey and ice cream and who knows what else."

Toward the end of the war Keys began to realize that starvation "was going to be a huge problem" in war-torn countries. He consulted military and civilian authorities in Washington and then launched the "Minnesota starvation experiment" involving a first-rate research team and 36 conscientious objectors who volunteered for the experiment as a form of alternative service.

"They were a remarkable group of youngsters. One or two of them defected, so to speak, but in general they were really remarkable. Of course, we did a lot of screening because we found all the kooks in the world in that conscientious objector pot. But the Church of the Brethren and the Quakers mad sure we had good, decent, honest youngsters who were not simply trying to stay out of the war but wanted to do some service.

As for the rights of human research subjects, well, the Helsinki Declaration hadn't been signed at that time. But the volunteers were informed about what they were up against, and they were very carefully monitored."

For five months the volunteers received half the normal number of calories for adult males. Each man was required to keep a diary and to exercise regularly n the treadmill. The diet was designed to duplicate that of the occupied countries of Europe, so that "each volunteer would become the nutritional equivalent of a Pole or a Greek." After a while, the men became irritable and were obsessed with thoughts of food. Simple strength declined only about 10 percent, but endurance on the short, heavy tasks dropped by half. Keys noted that men who were initially most fit showed the greatest deterioration. The average weight loss was 25 percent per man.

Three months after the experiment, none of the men had regained his former weight or physical capacity. Keys learned that effective rehabilitation for an adult male requires that the daily calorie level be above the normal for several months, that the proportion of protein in the diet be increased, and that he take vitamin supplements. This information was sent to various national and international relief agencies at work in Europe. "Starved people cannot be taught democracy. To talk about the will of the people when you aren't feeding them is perfect hogwash."

Keys reported the results of the experiment in his two-volume Biology of Human Starvation, published by the University of Minnesota Press in 1950. He maintains that it is still the definitive work on the subject. "In Rio a couple of months ago the president of the nutrition foundation asked if I would consider doing a review of work along this line. He said we would bill the Minnesota experiment as one to which nothing else compares. I doubt another of its kind will ever be done."

Monsieur Cholesterol

Statistics from northern Europe showing that as food supplies became short the death rate from coronary heart disease dropped markedly led Keys to launch a long-range study to discover the factors involved in degeneration of the heart. For this task he recruited 286 Minneapolis and St. Paul businessmen, including such University notables as Owen Wangensteen and Bernie Bierman. At about the same time, he organized a metabolic research unit at the state hospital in Hastings.

Keys's early suspicion that fat produces high blood cholesterol was aroused when he examined a Wisconsin dairy farmer referred to him by the University of Wisconsin medical school. "He had big knobs on his and elbows and over his eyes, and when you opened them, it was just pure cholesterol inside. They had tried various things at Madison, including giving him thyroid extract to a point where he was shaking all the time.

"We checked this fellow's serum cholesterol level, and the first reading was 1,000. His brother, who came with him, had a reading of 600. The average level in the United States is about 220 or 230, so of course this was sky high. So we put them over in the laboratory, fed them there for a week, and bang! Their cholesterol levels dropped down to 500 and 300. Essentially we put them on a fat-free diet. Wasn't very tasty.

"Then we got thinking about the possibility of giving them some fat. We gave them some vegetable margarine and their cholesterol levels shot back up again. That led us to think it was just the fat. We didn't realize that the vegetable margarine in those days was made of saturated fat. The saturated story didn't come up till some years after that. Anyway, that got me thinking, furiously, and it was the testing of these ideas about the diet and fat that led us to Hastings."

Cholesterol, named from Greek words meaning solid bile, is a yellowish waxy substance. Synthesized primarily by the liver, it is an important element in brain cells and nerve tissue, and it carries fatty acids in the bloodstream. But when it builds up in the arteries over a period of time, "it looks as if someone dumped Cream of Wheat in them. A heart attack occurs when the blood clots or when a blockage forms in the congested arteries."

But Keys discovered that the amount of fat in food, not the amount of cholesterol, has the greatest effect on the serum cholesterol level in the blood. Later he traced cholesterol buildup to saturated fats -- fat molecules with a full load of hydrogen atoms -- found mainly in meat and dairy products.

From this point on, Keys concentrated on dietary factors and lipid metabolism with the idea of preventing cardiovascular disease rather than curing it. Time and again he was criticized by various commercial interests for his findings, particularly by the meat and dairy industries. "There'll always be commercial interests involved in matters like this, but most of their arguments have gone by the wayside. The important thing is to make people aware of the dangers.

"People nowadays are wondering if, at the advanced stage of heart disease, dieting is helpful. I say it is helpful, in the psychological sense if nothing else. If you tell someone there's nothing to be done, it's hopeless. But if you say, 'Well, here's a diet. You can eat this, and that and the other thing,' that helps them a lot emotionally. We can bring serum cholesterol down that way. Not as much as we'd like, because people don't like to give up their habits."

In 1950 Keys went to Rome as chairman of the World Health Organization's first joint commission on food and agriculture, and the following year he took a sabbatical to Oxford as a senior Fulbright fellow. His interest in epidemiology was stimulated by exploratory surveys done in Italy, Spain, and England.

"I went down to Naples, and a friend of mine arranged for one of the young doctors to assist me. He got some volunteers from the fire department -- it was just across the street from the medical school -- and we took their blood pressure, blood samples, height and weight, and we asked them a few questions about their diet.

Later that year I was invited to lecture in Madrid, and I arranged to make a similar study of people in the poor quarter there. Then I asked my sponsor, who was number one in medicine in Spain at the time, about patients with coronary heart disease, and he said he saw a lot of them in his practice. These were all rich people, of course." Keys's conclusion was that the difference in diet between poor people and rich people accounted for the greater incidence of heart disease among the wealthy.

The Naples firemen and Madrid poor had a significantly lower blood cholesterol levels than Americans, and fat represented a smaller percentage of their daily diets. But 50 professional men in Madrid, all of whom had diets comparable to the diets in the United States, had cholesterol levels comparable to those of their American counterparts. High-fat diets in England and New Zealand also were reflected in a correspondingly high rate of heart disease.

It was in 1954 that Keys "really began more serious study of cardiovascular epidemiology" with help from President Eisenhower's heart specialist, Paul Dudley White.

"Paul at that time was president of the International Congress on Cardiology, and he asked me to organize a symposium on epidemiology for a meeting in Washington. It produced the biggest overflow crowd of the session. We had the biggest room, 800 capacity, and there were more than 1,200 people jammed in there. That was the beginning of cardiovascular epidemiology."

In 1955 Keys had his wife, Margaret, a biochemist, went to South Africa to begin systematic work on the Bantus, Cape Coloreds, and Europeans. "She did all the fieldwork," Keys said. The highly publicized findings showed that the calorie intake of fat varied widely in the diets of the three groups, and blood cholesterol counts and the incidence of heart disease correlated with diet -- lowest for Bantus and highest for Europeans. The following year Keys studied Japanese men living in Japan, Hawaii, and Los Angeles. Again, cholesterol levels and incidence of heart disease were closely tied to fat consumption: all were lowest in Japan and highest in the United States.

Through the late 1950s and early '60s, the Keyses were constantly on the go. "There were some big contrasts along the way. We went to Japan in the spring of 1956, and this was a fascinating experience. But to go three months later to Finland, the absolute opposite, was really something." In Finland, Keys noticed that the farmers and woodcutters, many of whom were lean and muscular yet suffered from heart disease, buttered their cheese. He launched a long-range research program to study the effects of dietary fat consumption on the incidence of heart disease, and followed with similar programs in Italy, the Netherlands, Greece, and Yugoslavia.

Keys accompanied White on a goodwill tour to the Soviet Union in 1956, and after an interview with Stalin's doctor reported that the former premier apparently died of natural causes, rumors to the contrary notwithstanding. At that time, Keys noticed, "the friendliness -- the freedom with which everybody talked to us" and predicted a break in the cold war, at least on the scientific front."

Meanwhile, the American press and broadcast media were paying more notice to the Minnesota physiologist. Newspaper and wire services often carried stories about him and his ideas. In a 1956 Associated Press story, Keys remarked that, generally speaking, "the higher your income, the more fat you eat. "But after you're earning $200 a week, you probably can't do any more harm. You probably can't eat any more fat."

"Americans have Sunday dinner every day," Keys told Time magazine in 1959. At another time he was quoted as attributing heart disease to "the North American habit for making the stomach the garbage disposal unit for a long list of harmful foods." He once charged that television was "doing a disservice to the nation and the individual" because viewers tend to eat a lot and remain inactive. "If we could find some way to make people do push-ups during commercials, then we'd all be strong as lions -- the commercials are so long."

In his many talks, public and private, he announced "new remedies" for heart disease, namely proper diet, exercise, emotional stability, and no smoking. And he argued that obesity, in an of itself, is not necessarily a major heart risk unless it is extreme.

While in Yugoslavia in 1958, Keys and his wife corrected proofs of their book Eat Well and Stay Well, which became a best-seller/ Readers were advised to "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." Margaret Keys supplied 200 low-fat recipes.

For the next few years, Chinese restaurants nationwide exhibited "window streamers and counter cards plugging Dr. Ancel Keys's book." Eventually it was translated into Finnish, Spanish, Italian, German, Japanese, and Portuguese. Minneapolis Tribune columnist Will Jones lamented the loss of the "mad, carefree past -- the world as we knew it before Ancel Keys came along." Keys admitted that "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."

Staying on top

Keys's continuing interest in high-altitude experiments took him to White Mountain, California, in 1962. He and five other scientists from the Andes expedition -- now ranging in age from 58 to 72 -- tested the ability of older men to function at an altitude of 14,850 feet.

Keys has always believed in the benefits of regular exercise -- he walks and swims a lot in Italy -- but he has no intention of joining up with the joggers. The director of the Florida Heart Association, who was 48, recently dropped dead while jogging. "I've seen just too many cases like that."

"To take up a fairly vigorous thing like jogging at older ages when you've never done anything like it at earlier ages is just asking for trouble. A friend of mine at a Los Angeles university who is a big mover in this business told me last year that he personally had been in on the obits of four people in one month who had dropped dead while jogging. And one of our ambassadors in Europe just dropped dead while jogging. I try to persuade people to have some pleasurable, safe exercise, preferably useful, when they are older."

And dieting can be dangerous, too. "Diet fads are for the birds, if you don't like birds. My friend Ed Rynearson -- he was in charge of the division of metabolism at the Mayo Clinic -- pointed out that we're overridden with diet fads. His particular peeve was Adele Davis. She's dead now, and I shouldn't speak ill of the dead. But her books are just full of hogwash. She has a variety of diets, but no great sense to them at all -- lots of natural things, which I suppose is all right. The health food stores have stacks of her books. She made a pot of money, I'm sure.

"Most diet fads don't do a great deal of harm -- lamb chop and pineapple, that sort of thing. But such things as the Zen macrobiotic diet definitely are harmful. And about that liquid protein diet, I was asked to be a witness at the hearings and legal proceedings in Los Angeles a year ago. People from the Food and Drug Administration were in on that, but they couldn't make their case stick and so it's still on the market. I sent material, but I didn't testify."

The problem of rising medical costs in the United States is one that Keys concedes is out of hand, though "it's hard to put the blame on anyone for it." Socialized medicine is not necessarily the answer. "In Italy, everyone is covered by a type of social security, and there are various ways of paying into it. Everybody gets taken care of, but there are an incredible number of bureaucratic hurdles.

"I also know something about the situation in Sweden because my daughter lived there for five years, and one of her children was born there. She had wonderful prenatal care and she received a check for $300 from the government to buy a layette for the baby. Really socialized. But you're just plain sick, unless it's obvious that you're at death's door, you may have to wait months and months to see a physician. The quality of medical care is at least as good as it is here, I think probably better.

"I can't say the same for Italy. Some of it is very good, some very poor. Italy has three times as many doctors per capita as the United States, and many of them can't make a living. But a few of them make pots of money. A friend of mine in Rome won't see anybody for less than 100,000 lire. That's $110 just to walk in the door. On the other hand, the son of our village mayor, after long labors, got through medical school and specialization in orthopedics. He's 38 and well established but earns considerably less than a good tile setter."

Having spent half a century at educational institutions, Keys says that they are changing all over the world. Some of the changes he believes are detrimental, such as the lowering of language requirements for medical students at the University of Minnesota. "Now we're getting the backlash in that medical students don't know how to read and write, let alone how to do arithmetic.

Keys thinks Minnesota "has turned out to be a cross between a trade school and a university -- a place for kids to hang around while they decide what they'd like to do. I guess that's true of many places. In the Scandinavian countries that's not true. Students really work and have some real objectives -- some profession -- in mind."

In time, he expects less emphasis to be placed on "just going to college" and more on attending an institution of higher education for a particular purpose. "In Italy, if I had a private fortune, I'd like to put it to use in vocational training. We need plumbers and electricians. We don't need all these eggheads."

Keys is concerned about the unstable political conditions in Italy and particularly about the strikes. "When we started off on this last trip we had to get a young fellow to drive us to Rome because the railroad was on strike. The trip is about 180 miles on a very beautiful toll road. When we got to the end of it, even the toll collectors were on strike."

But life in Italy away from the cities is another matter. The Keys home is outside a fishing village. The townsfolk are friendly, and life is lived at a patient pace. "Just a few days before we left I went down with a big stack of mail and discovered I'd forgotten my wallet. The postmaster said, 'Forget it, pay me some other time.' We know everybody in town, though I'm sure I couldn't tell you the names of 90 percent of the people, or maybe just their first names or nicknames. And people bring us things -- a fish, a rabbit, a loaf of home-baked bread. They're not rich.

"We come back to Minnesota for July and August, primarily because our little village swells from 500 people to 4,500 during the tourist season. Two-thirds of the tourists are Italian and the rest are German, Austrian, Swiss, and French. Not so long ago, when we bought our house, the roads were poor and there were no hotels in the whole south of Italy. Now, of course, they're having all sorts of problems -- water shortage, an overloaded power system, and so on."

These days, besides traveling and lecturing, Keys is writing up the results of long-range studies on cardiovascular epidemiology, including a 10-year study of 12,600 men in several European countries. "That's the biggest single study I've conducted. The manuscript will be published by the Harvard University Press this year." Studies he initiated in Finland, the Netherlands, and Yugoslavia now are into their 20th year.

And he finds time for safe, useful exercise. "Margaret and I get lots of pleasure from working in our yard. We just started the olive harvest. We have 80 olive trees and 75 citrus trees. We have oranges, tangerines, apricots, pears -- lots of pears -- plums, and four apple trees that produced only one apple so far.

"Also we have kumquats and chinotto. You probably don't know about chinotto. It's a citrus fruit, redder than most tangerines, and it grows on a beautiful tree. Produces lots of wonderful fruit for marmalade."