Ancel Keys

Ancel Benjamin Keys (January 26, 1904 – November 20, 2004) was an American physiologist who studied the influence of diet on health. In particular, he hypothesized that replacing dietary saturated fat with polyunsaturated fat reduces cardiovascular heart disease. Modern dietary recommendations by health organizations, systematic reviews, and national health agencies corroborate this.

Keys studied starvation in men and published ''The Biology of Human Starvation'' (1950), which remains the only source of its kind. He examined the epidemiology of cardiovascular disease and was responsible for two famous diets: K-rations, formulated as balanced meals for combat soldiers in World War II, and the Mediterranean diet, which he popularized with his wife Margaret.

Early life

Ancel Keys was born in Colorado Springs in 1904 to Benjamin Pious Keys (1883–1961) and Carolyn Emma Chaney (1885–1960), the sister of actor and director Lon Chaney. In 1906 they moved to San Francisco before the 1906 San Francisco earthquake struck. Shortly after the disaster, his family relocated to Berkeley where he grew up. Keys was intelligent as a boy; Lewis Terman, a noted psychologist and inventor of the Stanford-Binet IQ Test, described him as intellectually "gifted". During his youth, he left high school to pursue odd jobs, such as shoveling bat guano in Arizona, being a powder monkey in a Colorado mine, and working in a lumber camp. He eventually finished his secondary education and was admitted to the University of California at Berkeley in 1922.

Higher education

At the University of California, Berkeley, Keys initially studied chemistry, but was dissatisfied and took some time off to work as an oiler aboard the American President Lines ship SS ''President Wilson'', which traveled to China. He then returned to Berkeley, switched majors, and graduated with a B.A. in economics and political science (1925) and M.S. in zoology (1928).

For a brief time, he took up a job as a management trainee at Woolworth's, but returned to his studies at Scripps Institution of Oceanography in La Jolla on a fellowship.

In 1930, he received his Ph.D. in oceanography and biology from UC Berkeley. He was then awarded a National Research Council fellowship that took him to Copenhagen, Denmark to study under August Krogh at the Zoophysiological Laboratory for two years. During his studies with Krogh, he studied fish physiology and contributed numerous papers on the subject.

Once his fellowship ended, he went to Cambridge but took some time off to teach at Harvard University, after which he returned to Cambridge and earned a second Ph.D. in physiology (1936).

Scientific work

Early physiology studies

While doing fish research at Scripps, Keys would use statistical regressions to estimate the weight of fish from their length, at that time a pioneering use of biostatistics. Once in Copenhagen (1931), he continued to study fish physiology and developed techniques for gill perfusion that provided evidence that fish regulated their sodium by controlling chloride excretion through their gills. He would also use this perfusion method to study the effects of adrenaline and vasopressin ("pitressin") on gill fluid flow and osmotic regulation in fishes. He also designed an improved Kjeldahl apparatus, which improved upon Krogh's earlier design, and allowed for more rapid determination of nitrogen content in biological samples. This would prove useful for activities as diverse as determining the protein content in grasshopper eggs and anemia in humans.

While at Harvard's Fatigue Laboratory, he was inspired by his Cambridge mentor Joseph Barcroft's ascent to the top of Tenerife's highest peak and his subsequent reports. Keys wrote up a proposal for an expedition to the Andes, suggesting the study could have practical value for Chilean miners who worked at high elevations. He was given the go-ahead and, in 1935, assembled a team to study the effects of high altitude on the body, such as how it affects blood pressure. He spent a couple of months at 9,500 feet (3,000 m.), and then five weeks at elevations of 15,000 to 20,000 feet (4,500 to 6,000 m.).

He noted there was no good way of predicting how well humans might adapt to high altitude, even if they adapted well to medium altitudes, which would be a problem for potential pilots in a time before pressure control had become practical. It was from these studies that he outlined the phenomenon of human physiological adaptation to environmental changes as a predictable event, a novel idea in a time when such parameters as blood pressure and resting heart-rate were considered immutable characteristics of individuals.

Development of K-rations

In 1936, Keys was offered a position at the Mayo Foundation in Rochester, where he continued his studies in physiology. He left after a year, citing an intellectually stifling environment where research was secondary to clinical "doc business" and playing bridge.

In 1937, he left the Mayo Foundation to teach physiology at the University of Minnesota, where he founded the Laboratory of Physiological Hygiene. His earlier research on human physiology led to an assignment with the Army Quartermaster Corps, where they worked to develop a more portable and nonperishable ration that would provide enough calories to sustain soldiers (such as paratroopers) in the field for up to two weeks.

This development did not begin without some turbulence. His colleague, Dr. Elsworth Buskirk, notes:

Once the basic design had been completed, the Navy, through the National Research Council, funded the testing of the K-rations on its sailors to determine their feasibility as a temporary and mobile food source. The initial ingredients of the K-ration were procured at a local Minneapolis grocery store—hard biscuits, dry sausage, hard candy, and chocolate. The final product was different from Keys' original ingredients, but most of Keys' suggestions made it to the final product. The rations weighed only , but provided 3200 calories per day. Though several sources claim the name was unrelated to Keys, many historical references support the claim that the K-ration was indeed named after him. The K-ration became such a success that it was often used for more than temporary sustenance, becoming a major staple of military nutrition.

Starvation study

During World War II, Keys produced various studies related to human physical performance that were of interest to the military, such as studying the effects of testosterone on muscle work and vitamin supplementation as a performance enhancer on adequately fed soldiers, among many other similar studies. It was during the war that Keys and fellow researchers recognized the importance of knowing how to properly treat widespread starvation, since simple overfeeding for so many would be imprecise and there was a potential that the refeeding would fail.

To gain insight into the physiology of starvation, in 1944 Keys carried out a starvation study with 36 conscientious objectors as test subjects in the Minnesota Starvation Experiment. At the time, conscientious objectors were being placed in virtual concentration camps, with a few functioning like the Civilian Public Service, so that recruiting them would prove easier than seeking out volunteers in the general population. The original pool of 400 responders was reduced to 36 selectees, of whom 32 would go on to complete the study. The main focus of the study was threefold: set a metabolic baseline for three months, study the physical and mental effects of starvation on the volunteers for six months, and then study the physical and mental effects of different refeeding protocols on them for three months. The participants would first be placed on the three-month baseline diet of 3200 calories after which their calories were reduced to 1800 calories/day while expending 3000 calories in activities such as walking. The final three months were a refeeding period where the volunteers were divided into four groups, each receiving a different caloric intake.

The war came to an end before the final results of the study could be published, but Keys sent his findings to various international relief agencies throughout Europe and, by 1950, he completed publication of his two-volume 1385-page ''Biology of Human Starvation''.

Seven Countries Study

His interest in diet and cardiovascular disease (CVD) was prompted, in part, by seemingly counter-intuitive data: American business executives, presumably among the best-fed people, had high rates of heart disease, while in post-war Europe CVD rates had decreased sharply in the wake of reduced food supplies. Keys postulated a correlation between cholesterol levels and CVD and initiated a study of Minnesota businessmen (the first prospective study of CVD). At a 1955 expert meeting at the World Health Organization in Geneva, Keys presented his diet-lipid-heart disease hypothesis. As part of his argument, he presented a correlation between deaths from heart disease and percentage of fat in the diet that featured six countries. His rationale and conclusions was heavily critiqued by two other epidemiologists.

After observing in southern Italy the highest concentration of centenarians in the world, Keys hypothesized that a Mediterranean-style diet low in animal fat protected against heart disease and that a diet high in animal fats led to heart disease. This finding helped Keys initiate a long-term observational study, known as the Seven Countries Study, which appeared to show that serum cholesterol was strongly related to coronary heart disease mortality both at the population and at the individual level.Katan MB, Beynen AC. "Linoleic acid consumption and coronary heart disease in U.S.A. and U.K." ''Lancet''. 1981 Aug 15;2(8242):371

Keys had concluded that saturated fats as found in milk and meat have adverse effects, while unsaturated fats found in vegetable oils had beneficial effects. This message was obscured for a 20-year period starting around 1985, when all dietary fats were considered unhealthy. This was driven largely by the hypothesis that all dietary fats cause obesity and cancer. A 2015 systematic review and meta-analysis by the Cochrane Collaboration, an organisation which promotes evidence-based medicine, found that reducing saturated fat intake reduced the risk of cardiovascular disease, concluding: "Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturated fats."

After Keys' retirement from the University of Minnesota in 1972, his protege Henry Blackburn, MD became director of the Laboratory of Physiological Hygiene. Blackburn continued research on the role of lifestyle including diet in the cause and prevention of heart disease. The department played an active role in multicenter trials of the 1970s–80s and population strategies of surveillance and preventive interventions in Minnesota.

Minnesota Coronary Experiment

In 1968, about ten years after the beginning and two years after the first publication of the results of the ''Seven Countries Study'', Keys and Ivan Frantz initiated a large randomized control trial, replacing saturated fats by food items with naturally high or artificially raised content of linoleic acid in an ''intervention group''.

The randomized and blinded experiment ended in 1973. Results were not published until only much later in form of smaller excerpts as part of conference talks or doctoral theses. The raw data and analysis were discovered in 2013 in the estate of the principal investigator, Ivan Frantz.

The study shows no positive effects of the altered dietary intake. Cardiovascular mortality of patients over 65 years of age increased by the replacement of saturated fats.

The 2016 paper ''"Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment"'' concludes:

Keys equation

The Keys equation predicts the effect of saturated and polyunsaturated fatty acids in the diet on serum cholesterol levels. Keys found that saturated fats increase total and LDL cholesterol twice as much as polyunsaturated fats lower them.

Pure, White and Deadly'' was published, written by John Yudkin for a lay readership. Its intention was to summarize the evidence that the over-consumption of sugar was leading to a greatly increased incidence of coronary thrombosis, and that in addition it was certainly involved in dental caries, probably involved in obesity, diabetes and liver disease, and possibly involved in gout, dyspepsia and some cancers.

Yudkin ended the first chapter: "I hope that when you have read this book I shall have convinced you that sugar is really dangerous." This message was extremely unwelcome to the sugar industry and manufacturers of processed foods. The final chapter of ''Pure, White and Deadly'' lists several examples of attempts to interfere with the funding of his research and to prevent its publication. It also refers to the rancorous language and personal smears used by Ancel Keys to dismiss the evidence that sugar was the true culprit.

Keys wrote, for example:

It is clear that Yudkin has no theoretical basis or experimental evidence to support his claim for a major influence of dietary sucrose in the etiology of CHD; his claim that men who have CHD are excessive sugar eaters is nowhere confirmed but is disproved by many studies superior in methodology and/or magnitude to his own; and his "evidence" from population statistics and time trends will not bear up under the most elementary critical examination. But the propaganda keeps on reverberating ... Unfortunately, Yudkin's views appeal to some commercial interests with the result that this discredited propaganda is periodically rebroadcast to the general public of many countries.

The efforts to discredit the case against sugar were largely successful, and by the time of Yudkin's death in 1995 his warnings were, for the most part, no longer being taken seriously.

Yudkin's arguments and evidence for the dangers of sugar were the focus of several articles in the ''British Medical Journal'' of January 19, 2013.

In 2009, Robert Lustig, a pediatric endocrinologist of the University of California, San Francisco, Medical School who has a special interest in childhood obesity, made a video called ''Sugar: The Bitter Truth''. Lustig had independently re-discovered and confirmed Yudkin's findings and, pointing to "a hole as big as the one in the " in Keys' regression analysis of CHD versus fat and sugar, asked his audience, "Am I debunking?"

BMI and other contributions

In a 1972 article, Keys and his coauthors promoted Adolphe Quetelet's body mass index (BMI) as "preferable over other indices of relative weight on orrelation with height and measures of body fatnessas well as on the simplicity of the calculation and, in contrast to percentage of average weight, the applicability to all populations at all times", which the U.S. National Institutes of Health then popularized in 1985.

Keys was always considered an interventionist. He generally shunned food fads and vigorously promoted the putative benefits of the "reasonably low-fat diets" which he contrasted with "the North American habit for making the stomach the garbage disposal unit for a long list of harmful foods." Because of his influence in dietary science, Keys was featured on the cover of the January 13, 1961, issue of ''Time'' magazine.

Later years and death

When Keys was hired at the Mayo Foundation in 1936, he hired Margaret Haney (1909–2006) as a medical technologist. In 1939 they married and had three children: Carrie D'Andrea, Henry Keys, and Martha McLain. Carrie became a clinical psychologist and Henry became a physician and cancer researcher. Both are well respected contributors to their fields. Martha was shot dead by a thief in 1991 when she was 42.

Together, Margaret and Keys co-authored three books, two of them bestsellers. They earned enough royalties to build Minnelea, their villa in the seaside village of Pioppi, in the Cilento region on the southwest coast of Italy, where Keys lived and worked from 1963 to 1998. They also traveled the world, going to places like Japan and South Africa to record data for Keys's published works, such as the Seven Countries Study. The village of Pioppi became the location of the ''Living Museum of the Mediterranean Diet'', which houses a documentary, photograph and film archive regarding the historic, scientific, and cultural background of the Mediterranean diet.

Keys appeared on the '' To Tell The Truth'' game show as the inventor of K-Rations, fooling two of the four panelists.

Keys received three notable awards: Commander, Order of the Lion of Finland (1963), the McCollum Award from the American Society of Clinical Nutrition (1967), and an honorary doctor of science from the University of Minnesota (2001).

Keys died on November 20, 2004, in Minneapolis, two months before his 101st birthday.

Keys was an atheist.

Criticism

Some doctors and nutritionists have been critical of Keys' implications. His famous seven countries study, which led to the medical opinion regarding the dangers of cholesterol, fat and substances containing the same, has been criticized as ignoring the cases of Denmark, France and Norway (countries where the diet is rich in fat, but occurrence of heart disease is low) and Chile (where diet is low in fat, yet occurrence of heart disease is high).

On August 1, 2017, the True Health Initiative released a 65-page white paper, correcting what they felt were historical inaccuracies and errors that low-carb advocates have perpetuated: "Ancel Keys and the Seven Countries Study: An Evidence-based Response to Revisionist Histories".

They refute what they claim were four sources of errors: that countries were selected and excluded based on desired outcome; France was purposefully excluded; dietary data in Greece taken during Lent introduced a distortion; and that sugar was not considered as a possible contributor to coronary heart disease.Pett, Kahn, Willett & Katz (2017) p 22, 32, 37, 43

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{{DEFAULTSORT:Keys, Ancel
1904 births
2004 deaths
American atheists
American centenarians
American nutritionists
American people of World War II
American physiologists
Civilian Public Service
Diet food advocates
Men centenarians
Writers from Colorado Springs, Colorado
University of Minnesota faculty

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