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Legacy of Nutritionist Ancel Keys

      To the Editor:
      A diet high in saturated fat increases risk for heart disease and stroke. We know this, but few can recall who first uncovered the connection. It was Ancel Keys — a name to note and remember. Some 60 years ago, he was a luminary in medical science with a reputation that reached ordinary Americans. In 1961, his image graced the cover of TIME magazine. He was the first to promote the health benefits of the Mediterranean diet. An esteemed professor at the University of Minnesota, Ancel Keys was brilliant, bold, and worldly.
      A life full of adventures and discoveries, his story is extraordinary.
      • Keys A.
      Adventures of a Medical Scientist.
      Health Revolutionary: The Life & Work of Ancel Keys. University of Minnesota Libraries, University Archives, 2002.
      • Brody J.
      Dr Ancel Keys, 100, Promoter of Mediterranean Diet, Dies. New York Times, November 23.
      Born to teenagers in 1904, Ancel was raised in Berkeley, California, where the family struggled. Growing up, he worked unusual jobs for a city boy: as a gofer in a lumber camp, powder monkey in a Colorado gold mine, and guano shoveler in an Arizona bat cave. In 1922, he started at the University of California at Berkeley. The summer after his first year he signed on as an oiler on a steamship to Asia, learning Chinese on the side. After 3 months at sea, he returned to campus and completed his undergraduate degree in 2 years. After a brief stint at a Woolworth store — where “the work soon became intolerably dull” — he returned to UC-Berkeley, found topics that interested him, and, with his substantial intellect, breezed through, earning a PhD in biology in 1930.
      • Keys A.
      Adventures of a Medical Scientist.
      A 2-year fellowship took him to Copenhagen to work under August Krogh, a Nobel laureate in physiology. Next, he went to the University of Cambridge, and, under mentor Joseph Barcroft, became intrigued with studying how the human body adapts to extreme conditions; in 1936 he was awarded a second PhD (in physiology). Then L.J. Henderson, director of the acclaimed Harvard Fatigue Laboratory, cabled him with an offer, so off he went to join D.B. Dill, the lab’s research leader, and his elite cadre of physiologists and biochemists. This led to his pioneering work on the oxygen-carrying capacity of blood. At the age of 29 years, Ancel Keys, polymath and venturous researcher, organized a high-altitude expedition to South America and spent 6 months on the slopes of the Andes. Incredibly, he spent 10 frigid and harrowing days above 20,000 feet measuring its effects on his own blood.
      In 1939, he was recruited to the University of Minnesota, where he would stay until retirement in 1975. He established the Laboratory of Physiological Hygiene, which became an internationally recognized research center for human physiology and nutrition. One of his first projects was for the War Department, which had heard of his field research in the Andes; he was asked to develop pocket-size, balanced meals for paratroopers. The result was the K ration, named for its developer. Loathed by most troops, the food rations were a salvation for stranded soldiers.
      His next major study was groundbreaking and controversial — the Minnesota starvation experiment. He knew during the war and in its aftermath civilian starvation would be rampant. This prompted him to study the effects of starvation and how best to re-feed the famished. Volunteers were 36 young men — conscientious objectors, primarily from the Mennonite, Brethren, and Quaker faiths. Six months on a subsistence diet (1800 calories per day from root vegetables, bread, and simple starchy foods) was a grueling experience. The men became emaciated (losing 25% of their weight), depressed, irritable, weak, and obsessed with thoughts of food. Three months of nutritional rehabilitation followed. Comprehensive findings were detailed in his two-volume Biology of Human Starvation (1950), a classic in the field.
      • Keys A.
      • Brozek J.
      • Henschel A.
      In the early 1950s, he began the landmark Seven Countries Study, which followed 12,000 healthy middle-aged men living in Italy, Greece, Yugoslavia, the Netherlands, Finland, Japan, and the United States.
      Seven Countries Study.
      The genesis of this project was his theory that the increase in heart attacks among Americans was associated with changes in eating and lifestyle following World War II. He questioned the common medical wisdom that atherosclerosis was an inevitable consequence of aging. His observation that some countries had much lower rates of heart disease than the United States indicated the potential for population-level prevention. A finding of lasting importance was that a Mediterranean diet — rich in fruits, vegetables, pasta, and olive oil, with small portions of meat, fish, and dairy products — appeared to be protective against heart disease. Japan, where vegetables, rice, and fish were the mainstays, also had a very low rate of heart disease. But in the United States and Finland, diets rich in saturated fats were associated with heart attack rates 10-fold higher.
      To translate his research findings into practical advice for a general audience, Keys and his wife Margaret wrote three books, two became best sellers: Eat Well & Stay Well (1959)
      • Keys A.
      Eat Well & Stay Well.
      and How to Eat Well and Stay Well the Mediterranean Way (1975).
      • Keys A.
      • Keys M.
      How to Eat Well and Stay Well the Mediterranean Way.
      Professor Keys continued to write, travel, and lecture into his 90s. He died in 2004; 2 months shy of reaching 101 years. Ever the rigorous scientist, when asked on his 100th birthday whether his diet had contributed to his long life, he answered, "Very likely, but no proof."
      • Sullivan P.
      Heart Disease Researcher, Inventor of K Rations. Washington Post, November 24.
      In the ensuing half-century since Keys proposed his diet–heart disease theory, major advances in molecular biology dramatically improved our understanding of the intricacies of cardiovascular diseases including the role of serum cholesterol, lipoprotein subfractions, and specific apolipoproteins. His original theory evolved into a complex multifactorial model. In recent years, a few scientists and journalists have harshly criticized the Seven Countries Study, causing a stir primarily in social media and online outlets; their major criticisms have been debunked by a careful review of Keys’ published papers.
      • Pett K.D.
      • Willett W.C.
      • Vartiainen E.
      • Katz D.L.
      The seven countries study.
      Remarkably, most of Keys’ practical recommendations on diet remain valid today. A recent expert-panel concludes: (1) most evidence continues to suggest risk of heart disease is reduced by replacing saturated fat with polyunsaturated fats; and (2) the focus of dietary advice should be on consumption of foods and overall dietary patterns, not on single nutrients.
      • Forouhi N.G.
      • Krauss R.M.
      • Taubes G.
      • Willett W.C.
      Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance.
      Similarly, the most recent American College of Cardiology/American Heart Association clinical practice guideline states that a healthy diet emphasizes intake of vegetables, fruits, legumes, nuts, whole grains, and fish, while replacing saturated fat with polyunsaturated fats and minimizing intake of processed meats, refined carbohydrates, and sweetened beverages.
      • Arnett D.K.
      • Blumenthal R.S.
      • Albert M.A.
      • et al.
      2019 ACC/AHA guideline on the primary prevention of cardiovascular disease.
      All recommendations align with those of Keys. (Both papers also recommend trans fats be avoided, but this issue arose decades after the Seven Countries Study.)
      Ancel Keys pioneered the field of quantitative human biology, combining research in physiology, nutrition, and public health. An experimentalist and epidemiologist, he made lasting theoretical and practical contributions across diverse topics on health. He showed characteristics once considered to be genetically set — such as cholesterol levels, blood pressure, body weight, and responses to stress — are largely modifiable by changes in diet and lifestyle. His research accomplishments laid a foundation on which thousands have built.

      References

        • Keys A.
        Adventures of a Medical Scientist.
        Self-published memoir, 1999
      1. Health Revolutionary: The Life & Work of Ancel Keys. University of Minnesota Libraries, University Archives, 2002.
        ([37-min video] Accessed September 19, 2019)
        • Brody J.
        Dr Ancel Keys, 100, Promoter of Mediterranean Diet, Dies. New York Times, November 23.
        2004
        • Keys A.
        • Brozek J.
        • Henschel A.
        Biology of Human Starvation. Minne ed. Edition. University of Minnesota Press, South Minneapolis, MN1950
      2. Seven Countries Study.
        sevencountriesstudy.com/
        Date accessed: September 19, 2019
        • Keys A.
        Eat Well & Stay Well.
        Doubleday, New York, NY1959
        • Keys A.
        • Keys M.
        How to Eat Well and Stay Well the Mediterranean Way.
        Doubleday, New York, NY1975
        • Sullivan P.
        Heart Disease Researcher, Inventor of K Rations. Washington Post, November 24.
        2004
        • Pett K.D.
        • Willett W.C.
        • Vartiainen E.
        • Katz D.L.
        The seven countries study.
        Eur Heart J. 2017; 38: 3119-3121
        • Forouhi N.G.
        • Krauss R.M.
        • Taubes G.
        • Willett W.C.
        Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance.
        BMJ. 2018; 361: k2139
        • Arnett D.K.
        • Blumenthal R.S.
        • Albert M.A.
        • et al.
        2019 ACC/AHA guideline on the primary prevention of cardiovascular disease.
        Circulation. 2019; 140: e596-e646