Ancel Keys
Encyclopedia
Ancel Benjamin Keys was an American scientist who studied the influence of diet on health. In particular, he hypothesized that different kinds of dietary fat
had different effects on health.
He examined the epidemiology
of cardiovascular disease
(CVD) and was responsible for two famous diets: K-ration
s formulated as balanced meals for combat soldiers in World War II
and the Mediterranean diet
, which, with his wife Margaret, he popularized. Science, diet, and health were central themes in his professional and private lives.
struck. Shortly after the disaster, his family relocated to Berkeley where he grew up. His intellect was well-known ever since a young age as Lewis Terman
, noted psychologist and inventor of the Stanford-Binet IQ Test
identified Keys as one of the 1528 intellectually "gifted" students that he studied at Stanford
. During his youth, he left high school to pursue odd jobs such as shoveling bat guano in Arizona, working as a powder monkey
in a Colorado mine, working in a lumber camp and even working as a crewmember on a ship to China. He eventually finished his secondary education and was admitted to the University of California at Berkeley in 1922.
, where he initially studied chemistry, but was dissatisfied and took some time off to work as an oiler
aboard the S.S. President Wilson (1st)
which traveled to China
. He then returned to Berkeley, switched majors and graduated with a B.A. in economics
and political science
(1925), an 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
and in 1930, received his Ph.D. in oceanography
and biology
. 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).
to determine the weight of fish from their length, a pioneering use of biostatistics
at the time. Once in Copenhagen (1931), he would continue 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 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 John 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 that worked at high altitudes. 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 and then 5 weeks at altitudes of 15,000 to 20,000 feet. He noted that 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. 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 things as blood pressure and resting heart rate were considered immutable.
where he would continue to carry out his studies in physiology. He only lasted a year there, citing an intellectually stifling environment where research was secondary to clinical "doc business" and playing bridge
. In 1937, he would leave the Mayo Foundation for the University of Minnesota to teach physiology and eventually found the Laboratory of Physiological Hygiene. His earlier research on human physiology eventually 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 soldiers to determine its feasibility as a temporary and mobile foodsource. 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 initial suggestions made it to the final product. The rations weighed only 28 oz (793.8 g), but provided 3200 calories per day and though a few 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.
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 the 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 from Civilian Public Service
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 3 months, study the physical and mental effects of starvation on the volunteers for 6 months and then study the physical and mental effects of different refeeding protocols on them for 3 months. The participants would first be placed on the 3 month baseline diet of 3200 calories after which their calories were reduced to 1800 calories/day while expending 3009 calories in activities such as walking. The final 3 months were a refeeding period where the volunteers were divided into 4 different groups. 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.
, 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), culminating in what came to be known as the Seven Countries Study
.
Keyes 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. In order to do this, Keys collected data on deaths from coronary heart disease and fat consumption from 22 countries. Despite the fact that 22 countries provided statistics, Keys cherry-picked the data from the 7 countries which supported his theory that animal fat was the main cause of coronary heart disease in order to publicize his opinions. The results of what later became known as the “Seven Countries Study” appeared to show that serum cholesterol was strongly related to coronary heart disease mortality both at the population and at the individual level.[26] As a result, in 1956 people representing the American Heart Association appeared on television to inform people that a diet which included large amounts of butter, lard, eggs and beef would lead to coronary heart disease. This resulted in the American government recommending that people adopt a low fat diet in order to prevent heart disease. Interestingly, this idea still prevails despite the fact that there is not a shred of scientific evidence to prove it.
The resulting "cholesterol controversy" revealed sharp divisions in post-war scientific culture over whether the statisticians'
"strong associations" could provide scientific certainty. In its simplest form, the debate over cholesterol, dietary saturated fat and CVD pitted "interventionists" against those calling for further studies—preferably clinical or laboratory studies. The role of cholesterol in CVD was cemented in the minds of many when huge studies with powerful cholesterol-lowering drugs seemed to show a correlation between lowering LDL cholesterol and reduced risk of cardiovascular disease. (Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun 28;326(7404):1423. www.bmj.com/cgi/content/full/326/7404/1423). However, one of the largest studies in their meta-analysis(Heart Protection Study, Lancet. 2002 Jul 6;360(9326):7-22) used rather questionable methods: all prospective subjects were given the investigative drug (simvastatin) for 6 weeks, and anyone showing signs of abnormal responses to the drug was excluded from the formal study. These exclusions were far stricter than standard management of statin therapy, and resulted in fully two-thirds of the initial pool of subjects being ineligible for the study. This would have grave implications for clinical practice, but was not mentioned in the conclusions or discussion section of the primary research article. Not dissimilar to the dishonesty of which Dr Keys was accused, this has incited far less criticism, but the significance of dietary saturated fat intake for cholesterol and CVD remains an area of heated debate.
However, already in the 1960s Keys was able to convince a sizable part of the US public that replacing saturated by unsaturated fat would reduce blood cholesterol and the incidence of coronary heart disease. The resulting changes in the composition of food fats led to a doubling of the proportion of the unsaturated fatty acid, linoleic acid, in the body fat of Americans between 1960 and 1975 Mortality rate from coronary heart disease in the US began to fall from 1968 onwards, and about half of the decline was ascribed to changes in lifestyle including diet.
Keys had concluded that saturated fats as found in milk and meat have adverse effects opposite to the beneficial effects of the unsaturated fats found in vegetable oils. These same unsaturated fats and oils are however, found in meats and to a larger extent than Dr. Keys ever gave these foods credit for in any of his work. 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 (Prentice RL, Sheppard L. Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Causes Control. 1990 Jul;1(1):81-97). The idea began to be called into question in the late 1990s due to research that did not support a link between fat and cancer and an obesity epidemic in the face of reductions in fat intake (Katan MB, Grundy SM, Willett WC. Should a low-fat, high-carbohydrate diet be recommended for everyone? Beyond low-fat diets. N Engl J Med. 1997 Aug 21;337(8):563-6; discussion 566-7).
With the advent of ever-more powerful cholesterol lowering drugs, high cholesterol has ceased to be a major cause of premature heart disease in affluent countries. Its place has been taken by obesity and the subsequent type 2 diabetes, problems for which the diets developed by Keys offer no solution, though he appreciated the connection between obesity and cardiovascular disease (Circulation 1952:5; 115-118).
Keys also popularized the use of the body mass index
(BMI) as a measure of body fat, following a 1972 paper.
Keys was always considered an interventionist. He generally shunned food fads and vigorously promoted the benefits of the "reasonably low-fat diets" he contrasted with "the North American habit for making the stomach the garbage disposal
unit for a long list of harmful foods."http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4830a1box.htm Keys' studies and recommendations have had a substantial impact on changes in the U.S. diet that may have caused a downward trend in CVD.http://www.cdc.gov/nchs/data/hus/hus05.pdf#036. Several recent studies have vindicated Keys' thesis that unsaturated oils are more effective at improving markers of CVD than high-carbohydrate low-fat foods. Because of his influence in dietary science, Keys was featured on the cover of the January 13, 1961 issue of Time magazine.
Ancel Keys died on November 20, 2004, two months before his 101st birthday
. A year earlier, he had left Pioppi
, his beloved village in Southern Italy
where he had spent 28 years of his life.
amongst others for having selection bias when supporting his conclusions. Ravnskov examined the data that Keys used and found no correlation to back up Keys' findings.
A University of Minnesota study in the late 1940s injected 11 public service employee volunteers with malaria, then starved them for five days. Some were also subjected to hard labor, and those men lost an average of 14 pounds. They were treated for malarial fevers with quinine sulfate. One of the authors was Ancel Keys.
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
had different effects on health.
He examined the epidemiology
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
of cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
(CVD) and was responsible for two famous diets: K-ration
K-ration
The K-ration was an individual daily combat food ration which was introduced by the United States Army during World War II. It was originally intended as an individually packaged daily ration for issue to airborne troops, tank corps, motorcycle couriers, and other mobile forces for short durations...
s formulated as balanced meals for combat soldiers in World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
and the Mediterranean diet
Mediterranean diet
The Mediterranean diet is a modern nutritional recommendation inspired by the traditional dietary patterns of southern Italy, Crete and much of the rest of Greece in the 1960s....
, which, with his wife Margaret, he popularized. Science, diet, and health were central themes in his professional and private lives.
Early life
Ancel Keys was born in Colorado Springs in 1904 to teenage parents and in 1906, they moved to San Francisco before the 1906 San Francisco Earthquake1906 San Francisco earthquake
The San Francisco earthquake of 1906 was a major earthquake that struck San Francisco, California, and the coast of Northern California at 5:12 a.m. on Wednesday, April 18, 1906. The most widely accepted estimate for the magnitude of the earthquake is a moment magnitude of 7.9; however, other...
struck. Shortly after the disaster, his family relocated to Berkeley where he grew up. His intellect was well-known ever since a young age as Lewis Terman
Lewis Terman
Lewis Madison Terman was an American psychologist, noted as a pioneer in educational psychology in the early 20th century at the Stanford University School of Education. He is best known as the inventor of the Stanford-Binet IQ test...
, noted psychologist and inventor of the Stanford-Binet IQ Test
Stanford-Binet IQ test
The development of the Stanford–Binet Intelligence Scales initiated the modern field of intelligence testing and was one of the first examples of an adaptive test. The test originated in France, then was revised in the United States...
identified Keys as one of the 1528 intellectually "gifted" students that he studied at Stanford
Genetic Studies of Genius
The Genetic Studies of Genius, today known as the Terman Study of the Gifted, is a still-running longitudinal study begun in 1921 to examine the development and characteristics of gifted children into adulthood...
. During his youth, he left high school to pursue odd jobs such as shoveling bat guano in Arizona, working as a powder monkey
Powder monkey
Powder monkeys were a part of warships' crews during the Age of Sail that carried bags of gunpowder from the powder magazine in the ship's hold to the gun crews. Powder monkeys were usually boys or young teens selected for the job for their speed and height — they were short and would be...
in a Colorado mine, working in a lumber camp and even working as a crewmember on a ship to China. He eventually finished his secondary education and was admitted to the University of California at Berkeley in 1922.
Higher Education
Keys attended the University of California, BerkeleyUniversity of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...
, where he initially studied chemistry, but was dissatisfied and took some time off to work as an oiler
Oiler (occupation)
An oiler is a worker whose main job is to oil machinery. In previous eras there were oiler positions in various industries, including maritime work , railroading, steelmaking, and mining...
aboard the S.S. President Wilson (1st)
American President Lines
American President Lines Ltd. is the world's seventh-largest container transportation and shipping company, providing services to more than 140 countries through a network combining intermodal freight transport operations with IT and e-commerce...
which traveled to China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
. He then returned to Berkeley, switched majors and graduated with a B.A. in economics
Economics
Economics is the social science that analyzes the production, distribution, and consumption of goods and services. The term economics comes from the Ancient Greek from + , hence "rules of the house"...
and political science
Political science
Political Science is a social science discipline concerned with the study of the state, government and politics. Aristotle defined it as the study of the state. It deals extensively with the theory and practice of politics, and the analysis of political systems and political behavior...
(1925), an M.S. in zoology
Zoology
Zoology |zoölogy]]), is the branch of biology that relates to the animal kingdom, including the structure, embryology, evolution, classification, habits, and distribution of all animals, both living and extinct...
(1928). For a brief time, he took up a job as a management trainee at Woolworth's
F. W. Woolworth Company
The F. W. Woolworth Company was a retail company that was one of the original American five-and-dime stores. The first successful Woolworth store was opened on July 18, 1879 by Frank Winfield Woolworth in Lancaster, Pennsylvania, as "Woolworth's Great Five Cent Store"...
, but returned to his studies at Scripps Institution of Oceanography
Scripps Institution of Oceanography
Scripps Institution of Oceanography in La Jolla, California, is one of the oldest and largest centers for ocean and earth science research, graduate training, and public service in the world...
in La Jolla on a fellowship
Scholarship
A scholarship is an award of financial aid for a student to further education. Scholarships are awarded on various criteria usually reflecting the values and purposes of the donor or founder of the award.-Types:...
and in 1930, received his Ph.D. in oceanography
Oceanography
Oceanography , also called oceanology or marine science, is the branch of Earth science that studies the ocean...
and biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
. He was then awarded a National Research Council
United States National Research Council
The National Research Council of the USA is the working arm of the United States National Academies, carrying out most of the studies done in their names.The National Academies include:* National Academy of Sciences...
fellowship that took him to Copenhagen, Denmark to study under August Krogh
August Krogh
Schack August Steenberg Krogh FRS was a Danish professor of Romani background at the department of zoophysiology at the University of Copenhagen from 1916-1945...
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
University of Cambridge
The University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
but took some time off to teach at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
, after which he returned to Cambridge and earned a second Ph.D. in physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
(1936).
Early Physiology Studies
While doing fish research at Scripps, Keys would use regressionsRegression analysis
In statistics, regression analysis includes many techniques for modeling and analyzing several variables, when the focus is on the relationship between a dependent variable and one or more independent variables...
to determine the weight of fish from their length, a pioneering use of biostatistics
Biostatistics
Biostatistics is the application of statistics to a wide range of topics in biology...
at the time. Once in Copenhagen (1931), he would continue to study fish physiology and developed techniques for gill perfusion
Perfusion
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuser" meaning to "pour over or through."...
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 pitressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
on gill fluid flow and osmotic regulation in fishes. He also designed an improved Kjeldahl apparatus
Kjeldahl method
The Kjeldahl method or Kjeldahl digestion in analytical chemistry is a method for the quantitative determination of nitrogen in chemical substances developed by Johan Kjeldahl in 1883.- Method :...
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 John Barcroft's ascent to the top of Tenerife's
Tenerife
Tenerife is the largest and most populous island of the seven Canary Islands, it is also the most populated island of Spain, with a land area of 2,034.38 km² and 906,854 inhabitants, 43% of the total population of the Canary Islands. About five million tourists visit Tenerife each year, the...
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 that worked at high altitudes. 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 and then 5 weeks at altitudes of 15,000 to 20,000 feet. He noted that 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. 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 things as blood pressure and resting heart rate were considered immutable.
Development of K Rations
In 1936, Keys was offered a position at the University of Minnesota's Mayo Foundation in RochesterRochester, Minnesota
Rochester is a city in the U.S. state of Minnesota and is the county seat of Olmsted County. Located on both banks of the Zumbro River, The city has a population of 106,769 according to the 2010 United States Census, making it Minnesota's third-largest city and the largest outside of the...
where he would continue to carry out his studies in physiology. He only lasted a year there, citing an intellectually stifling environment where research was secondary to clinical "doc business" and playing bridge
Contract bridge
Contract bridge, usually known simply as bridge, is a trick-taking card game using a standard deck of 52 playing cards played by four players in two competing partnerships with partners sitting opposite each other around a small table...
. In 1937, he would leave the Mayo Foundation for the University of Minnesota to teach physiology and eventually found the Laboratory of Physiological Hygiene. His earlier research on human physiology eventually 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 soldiers to determine its feasibility as a temporary and mobile foodsource. 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 initial suggestions made it to the final product. The rations weighed only 28 oz (793.8 g), but provided 3200 calories per day and though a few 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 Studies
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 testosteroneMethyltestosterone
Methyltestosterone is a 17-alpha-alkylated anabolic steroid used to treat men with a testosterone deficiency. It is also used in women to treat breast cancer, breast pain, swelling due to pregnancy, and with the addition of estrogen it can treat symptoms of menopause...
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 the 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 from Civilian Public Service
Civilian Public Service
The Civilian Public Service provided conscientious objectors in the United States an alternative to military service during World War II...
as test subjects in the Minnesota Starvation Experiment
Minnesota Starvation Experiment
The Minnesota Starvation Experiment, also known as the Minnesota Semi-Starvation Experiment, the Minnesota Starvation-Recovery Experiment and the Starvation Study, was a clinical study performed at the University of Minnesota between November 19, 1944 and December 20, 1945...
. At the time, conscientious objectors were being placed in virtual concentration camps with a few functioning like the Civilian Public Service
Civilian Public Service
The Civilian Public Service provided conscientious objectors in the United States an alternative to military service during World War II...
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 3 months, study the physical and mental effects of starvation on the volunteers for 6 months and then study the physical and mental effects of different refeeding protocols on them for 3 months. The participants would first be placed on the 3 month baseline diet of 3200 calories after which their calories were reduced to 1800 calories/day while expending 3009 calories in activities such as walking. The final 3 months were a refeeding period where the volunteers were divided into 4 different groups. 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 cardio-vascular disease (CVD) was prompted, in part, by seemingly counterintuitive data: American business executives, presumably among the best-fed persons, had high rates of heart diseaseHeart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
, while in post-war Europe, CVD rates had decreased sharply in the wake of reduced food supplies. Keys postulated a correlation between cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
levels and CVD and initiated a study of Minnesota businessmen (the first prospective study of CVD), culminating in what came to be known as the Seven Countries Study
Seven Countries Study
The Seven Countries Study is an important epidemiological study. It is a large longitudinal study. It was the first study to systematically examine the relationships between lifestyle, diet, coronary heart disease and stroke in different populations from different regions of the world...
.
Keyes 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. In order to do this, Keys collected data on deaths from coronary heart disease and fat consumption from 22 countries. Despite the fact that 22 countries provided statistics, Keys cherry-picked the data from the 7 countries which supported his theory that animal fat was the main cause of coronary heart disease in order to publicize his opinions. The results of what later became known as the “Seven Countries Study” appeared to show that serum cholesterol was strongly related to coronary heart disease mortality both at the population and at the individual level.[26] As a result, in 1956 people representing the American Heart Association appeared on television to inform people that a diet which included large amounts of butter, lard, eggs and beef would lead to coronary heart disease. This resulted in the American government recommending that people adopt a low fat diet in order to prevent heart disease. Interestingly, this idea still prevails despite the fact that there is not a shred of scientific evidence to prove it.
The resulting "cholesterol controversy" revealed sharp divisions in post-war scientific culture over whether the statisticians'
Statistics
Statistics is the study of the collection, organization, analysis, and interpretation of data. It deals with all aspects of this, including the planning of data collection in terms of the design of surveys and experiments....
"strong associations" could provide scientific certainty. In its simplest form, the debate over cholesterol, dietary saturated fat and CVD pitted "interventionists" against those calling for further studies—preferably clinical or laboratory studies. The role of cholesterol in CVD was cemented in the minds of many when huge studies with powerful cholesterol-lowering drugs seemed to show a correlation between lowering LDL cholesterol and reduced risk of cardiovascular disease. (Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun 28;326(7404):1423. www.bmj.com/cgi/content/full/326/7404/1423). However, one of the largest studies in their meta-analysis(Heart Protection Study, Lancet. 2002 Jul 6;360(9326):7-22) used rather questionable methods: all prospective subjects were given the investigative drug (simvastatin) for 6 weeks, and anyone showing signs of abnormal responses to the drug was excluded from the formal study. These exclusions were far stricter than standard management of statin therapy, and resulted in fully two-thirds of the initial pool of subjects being ineligible for the study. This would have grave implications for clinical practice, but was not mentioned in the conclusions or discussion section of the primary research article. Not dissimilar to the dishonesty of which Dr Keys was accused, this has incited far less criticism, but the significance of dietary saturated fat intake for cholesterol and CVD remains an area of heated debate.
However, already in the 1960s Keys was able to convince a sizable part of the US public that replacing saturated by unsaturated fat would reduce blood cholesterol and the incidence of coronary heart disease. The resulting changes in the composition of food fats led to a doubling of the proportion of the unsaturated fatty acid, linoleic acid, in the body fat of Americans between 1960 and 1975 Mortality rate from coronary heart disease in the US began to fall from 1968 onwards, and about half of the decline was ascribed to changes in lifestyle including diet.
Keys had concluded that saturated fats as found in milk and meat have adverse effects opposite to the beneficial effects of the unsaturated fats found in vegetable oils. These same unsaturated fats and oils are however, found in meats and to a larger extent than Dr. Keys ever gave these foods credit for in any of his work. 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 (Prentice RL, Sheppard L. Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Causes Control. 1990 Jul;1(1):81-97). The idea began to be called into question in the late 1990s due to research that did not support a link between fat and cancer and an obesity epidemic in the face of reductions in fat intake (Katan MB, Grundy SM, Willett WC. Should a low-fat, high-carbohydrate diet be recommended for everyone? Beyond low-fat diets. N Engl J Med. 1997 Aug 21;337(8):563-6; discussion 566-7).
With the advent of ever-more powerful cholesterol lowering drugs, high cholesterol has ceased to be a major cause of premature heart disease in affluent countries. Its place has been taken by obesity and the subsequent type 2 diabetes, problems for which the diets developed by Keys offer no solution, though he appreciated the connection between obesity and cardiovascular disease (Circulation 1952:5; 115-118).
Keys also popularized the use of the body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
(BMI) as a measure of body fat, following a 1972 paper.
Keys was always considered an interventionist. He generally shunned food fads and vigorously promoted the benefits of the "reasonably low-fat diets" he contrasted with "the North American habit for making the stomach the garbage disposal
Garbage disposal
A garbage disposal unit or waste disposal unit is a device, usually electrically powered, installed under a kitchen sink between the sink's drain and the trap which shreds food waste into pieces small enough—generally less than —to pass through plumbing.Garbage disposal units are widely used in...
unit for a long list of harmful foods."http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4830a1box.htm Keys' studies and recommendations have had a substantial impact on changes in the U.S. diet that may have caused a downward trend in CVD.http://www.cdc.gov/nchs/data/hus/hus05.pdf#036. Several recent studies have vindicated Keys' thesis that unsaturated oils are more effective at improving markers of CVD than high-carbohydrate low-fat foods. Because of his influence in dietary science, Keys was featured on the cover of the January 13, 1961 issue of Time magazine.
Ancel Keys died on November 20, 2004, two months before his 101st birthday
Centenarian
A centenarian is a person who is or lives beyond the age of 100 years. Because current average life expectancies across the world are less than 100, the term is invariably associated with longevity. Much rarer, a supercentenarian is a person who has lived to the age of 110 or more, something only...
. A year earlier, he had left Pioppi
Pioppi
Pioppi is an Italian hamlet of the municipality of Pollica , located in Cilento, Campania region. Its name means poplars in Italian language.-History:...
, his beloved village in Southern Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
where he had spent 28 years of his life.
Criticism
The research of Ancel Keys has been criticized by Uffe RavnskovUffe Ravnskov
Uffe Ravnskov is a Danish independent researcher, a member of various international scientific organisations, and a former private medical practitioner in Sweden...
amongst others for having selection bias when supporting his conclusions. Ravnskov examined the data that Keys used and found no correlation to back up Keys' findings.
A University of Minnesota study in the late 1940s injected 11 public service employee volunteers with malaria, then starved them for five days. Some were also subjected to hard labor, and those men lost an average of 14 pounds. They were treated for malarial fevers with quinine sulfate. One of the authors was Ancel Keys.