Editing Ancel Keys

{{short description|American physiologist (1904–2004)}}
{{Use mdy dates|date=November 2024}}
{{Infobox scientist
| image             = Ancel-Keys.jpg
| image_size        =
| alt               =
| caption           = Keys in 1945
| birth_name        = Ancel Benjamin Keys
| birth_date        = {{birth date|1904|01|26}}
| birth_place       = {{nowrap|[[Colorado Springs, Colorado]], U.S.}}
| death_date        = {{death date and age|2004|11|20|1904|01|26}}
| death_place       = [[Minneapolis]], Minnesota, U.S.
| fields            = {{hlist|[[Human nutrition]]|[[public health]]|[[epidemiology]]}}
| workplaces        = [[University of Minnesota]]
| education         = {{ubl|[[University of California at Berkeley]] (B.A., M.S., Ph.D.)}}
| doctoral_advisor  =
| academic_advisors = [[August Krogh]]
| doctoral_students =
| notable_students  =
| known_for         = {{hlist|Human nutrition|[[K-ration]]|[[Mediterranean diet]]}}
| author_abbrev_bot =
| author_abbrev_zoo =
| influences        =
| influenced        =
| awards            =
| signature         = <!--(filename only)-->
| signature_alt     =
| footnotes         =
| relatives         = [[Lon Chaney]] (uncle)
| spouse            = {{marriage|Margaret Haney|1939}}
}}

'''Ancel Benjamin Keys''' (January 26, 1904&nbsp;– 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]] reduced [[cardiovascular diseases]].<ref name="montani2021">{{cite journal | vauthors = Montani JP | title = Ancel Keys: The legacy of a giant in physiology, nutrition, and public health | journal = Obesity Reviews | volume = 22 | issue = S2 | date = January 2021 | pages = e13196 | pmid = 33496369 | doi = 10.1111/obr.13196 | doi-access = free }}</ref><ref name="sparling2020">{{cite journal | vauthors = Sparling PB | title = Legacy of Nutritionist Ancel Keys | journal = Mayo Clinic Proceedings | volume = 95 | issue = 3 | pages = 615–617 | date = March 2020 | pmid = 32138891 | doi = 10.1016/j.mayocp.2019.12.012 | url = https://www.mayoclinicproceedings.org/article/S0025-6196(19)31088-2/fulltext#:~:text=Remarkably%2C%20most%20of%20Keys%E2%80%99%20practical%20recommendations%20on%20diet%20remain%20valid%20today.%20A%20recent%20expert-panel%20concludes%3A%20(1)%20most%20evidence%20continues%20to%20suggest%20risk%20of%20heart%20disease%20is%20reduced%20by%20replacing%20saturated%20fat%20with%20polyunsaturated%20fats | doi-access = free }}</ref> Modern dietary recommendations by health organizations,<ref name="aha2017">{{cite journal | vauthors = Sacks FM, Lichtenstein AH, Wu JH, Appel LJ, Creager MA, Kris-Etherton PM, Miller M, Rimm EB, Rudel LL, Robinson JG, Stone NJ, Van Horn LV | title = Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association | journal = Circulation | volume = 136 | issue = 3 | pages = e1–e23 | date = July 2017 | pmid = 28620111 | doi = 10.1161/CIR.0000000000000510| s2cid = 367602 | doi-access = free }}</ref><ref>{{cite web |url=https://apps.who.int/iris/bitstream/handle/10665/275990/9789241514873-eng.pdf | title = Global Nutrition Policy Review 2016–2017 | page = 55 | publisher = [[World Health Organization]] | access-date = September 23, 2019}}</ref> and national health agencies<ref>{{cite web |url=https://food-guide.canada.ca/en/healthy-eating-recommendations/make-it-a-habit-to-eat-vegetables-fruit-whole-grains-and-protein-foods/choosing-foods-with-healthy-fats/ | title = Choosing foods with healthy fats | publisher = [[Health Canada]] | access-date = September 23, 2019}}</ref><ref>{{cite web |url=https://health.gov/dietaryguidelines/2015/resources/DGA_Cut-Down-On-Saturated-Fats.pdf | title = Cut Down on Saturated Fats | publisher = [[United States Department of Health and Human Services]] | access-date = September 23, 2019}}</ref><ref>{{cite web |url=https://www.nhs.uk/live-well/eat-well/different-fats-nutrition/ | title = Fat: the facts | date = April 27, 2018 | publisher = United Kingdom's [[National Health Service]] | access-date = September 23, 2019}}</ref><ref>{{cite web |url=https://www.eatforhealth.gov.au/food-essentials/fat-salt-sugars-and-alcohol/fat | title = Fat | date = September 24, 2012 | publisher = Australia's [[National Health and Medical Research Council]] and [[Department of Health and Ageing]] | access-date = September 23, 2019}}</ref><ref>{{cite web |url=https://www.healthhub.sg/live-healthy/458/Getting%20the%20Fats%20Right | title = Getting the Fats Right! | publisher = Singapore's [[Ministry of Health (Singapore)|Ministry of Health]] | access-date = September 23, 2019}}</ref><ref>{{cite web | url = https://www.nhp.gov.in/healthlyliving/healthy-diet | title = Health Diet | publisher = India's [[Ministry of Health and Family Welfare]] | access-date = September 23, 2019 | archive-date = August 6, 2016 | archive-url = https://web.archive.org/web/20160806032305/https://www.nhp.gov.in/healthlyliving/healthy-diet | url-status = dead }}</ref><ref>{{cite web |url=https://www.health.govt.nz/your-health/healthy-living/food-activity-and-sleep/healthy-eating/making-healthier-food-choices | title = Making healthier food choices | publisher = New Zealand's [[Ministry of Health (New Zealand)|Ministry of Health]] | access-date = June 3, 2021}}</ref><ref>{{cite web |url=https://www.chp.gov.hk/en/static/100023.html | title = Know More about Fat | publisher = Hong Kong's [[Department of Health (Hong Kong)|Department of Health]] | access-date = September 23, 2019}}</ref> 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-ration]]s, 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 Benjamin Keys was born in [[Colorado Springs, Colorado|Colorado Springs]] on January 26, 1904, the son of Benjamin Pious Keys (1883–1961) and Carolyn Emma Chaney (1885–1960), the sister of actor and director [[Lon Chaney]] (1883–1930).<ref name='Brody2004'>{{cite news | first = Jane E. | last = Brody | title = Ancel Keys, 100, Promoter of the Mediterranean Diet, Dies | date = November 23, 2004 |url=https://www.nytimes.com/2004/11/23/obituaries/23keys.html | work = [[The New York Times]] | access-date = February 5, 2011}}</ref> In 1906 they moved to San Francisco before the [[1906 San Francisco earthquake]] struck.<ref name='Sullivan2004'>{{cite news | first = Patricia | last = Sullivan | title = Ancel Keys, K Ration Creator, Dies | date = November 24, 2004 |url=https://www.washingtonpost.com/wp-dyn/articles/A7213-2004Nov23.html | newspaper = [[The Washington Post]] | access-date = February 5, 2011}}</ref> Shortly after the disaster, his family relocated to [[Berkeley, California|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".<ref name ='Sullivan2004'/> 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]].<ref name='Hoffman1979'>{{cite web |url=http://mbbnet.umn.edu/hoff/hoff_ak.html | title = Meet Monsieur Cholesterol | access-date = February 5, 2011 | last = Hoffman | first = William | year = 1979 | work = [[University of Minnesota]] | publisher = University of Minnesota}}</ref> He eventually finished his secondary education and was admitted to the University of California at Berkeley in 1922.<ref name=Hoffman1979/>

===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 (occupation)|oiler]] aboard the [[American President Lines]] ship SS ''President Wilson'', which traveled to [[China]].<ref name=Hoffman1979/> 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).<ref name=Hoffman1979/>

For a brief time, he took up a job as a management trainee at [[F. W. Woolworth Company|Woolworth's]], but returned to his studies at [[Scripps Institution of Oceanography]] in [[La Jolla, California|La Jolla]] on a [[scholarship|fellowship]].

In 1930, he received his Ph.D. in [[oceanography]] and [[biology]] from UC Berkeley.<ref name=Hoffman1979/> He was then awarded a [[United States National Research Council|National Research Council]] fellowship that took him to [[Copenhagen, Denmark]] to study under [[August Krogh]] at the Zoophysiological Laboratory for two years.<ref name=Hoffman1979/><ref name='Zadunaisky1969'>{{cite book | last1 = Zadunaisky | first1 = JA | title = Fish Physiology | chapter = The Chloride Cell: The Active Transport of Chloride and the Paracellular Pathways | volume = 10 | editor1= William Stewart Hoar |editor2=David J. Randall | publisher = Academic Press | year = 1969 | pages = 130–136 | chapter-url=https://books.google.com/books?id=8fuEB7O3IqIC&q=ancel%20keys%20willmer&pg=PA130 | access-date = February 5, 2011 | isbn = 978-0-12-350430-2 | quote = Ancel Keys was a fellow of the National Research Council of America, who did the perfusion experiment leading to the observation of chloride secretion in the Zoophysiological Laboratory in Copenhagen, Denmark, under the direction of August Krogh.}}</ref> During his studies with Krogh, he studied fish physiology and contributed numerous papers on the subject.<ref name=Zadunaisky1969/>

Once his fellowship ended, he went to [[University of Cambridge|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).<ref name ='Hoffman1979'/>

==Scientific work==

===Early physiology studies===

While doing fish research at Scripps, Keys would use statistical [[regression analysis|regressions]] to estimate the weight of fish from their length, at that time a pioneering use of [[biostatistics]].<ref name='Blackburn1998'>{{cite web |url=http://mbbnet.umn.edu/firsts/blackburn_h.html | title = Ancel Keys | access-date = February 5, 2011 | last = Blackburn, MD| first = Henry | year = 1998 | work = [[University of Minnesota]] | publisher = University of Minnesota}}</ref> 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.<ref name=Zadunaisky1969/><ref name='Keys1932'>{{cite journal | title = 'Chloride secreting cells' in the gills of fishes, with special reference to the common eel | first2 = EN | journal = The Journal of Physiology | last2 = Willmer | year = 1932 | first1 = Ancel | last1 = Keys | volume = 76 | issue = 3 | pages = 368–380| pmid = 16994355 | doi = 10.1113/jphysiol.1932.sp002932 | pmc = 1394694}}</ref><ref name='Keys1931'>{{cite journal | title = The determination of chlorides with the highest accuracy | journal = Z. Vergl. Physiol. | year = 1931 | first = Ancel | last = Keys | volume = 15 | issue = 2 | pages = 352–363| doi = 10.1007/BF00339114 | s2cid = 28971898 }}</ref> He would also use this perfusion method to study the effects of [[adrenaline]] and [[vasopressin]] ("pitressin") on gill fluid flow<ref name='BatemanKeys1932'>{{cite journal | doi = 10.2307/1537248 | title = Branchial Responses to Adrenaline and to Pitressin in the eel | journal = Biological Bulletin | year = 1932 | first = Ancel | last = Keys |author2=J.B. Bateman | volume = 63 | issue = 2 | pages = 327–336|url=http://www.biolbull.org/cgi/reprint/63/2/327.pdf | access-date = February 5, 2011| jstor = 1537248 }}</ref> and osmotic regulation in fishes.<ref name='Keys1933'>{{cite journal | title = The Mechanism of Adaptation to Varying Salinity in the Common Eel and the General Problem of Osmotic Regulation in Fishes | journal = Proceedings of the Royal Society B | year = 1933 | first = Ancel | last = Keys | volume = 112 | issue = 776 | pages = 184–199 | jstor=81638 | doi=10.1098/rspb.1933.0002| bibcode = 1933RSPSB.112..184K | doi-access =  }}</ref> He also designed an improved [[Kjeldahl method|Kjeldahl apparatus]], which improved upon Krogh's earlier design, and allowed for more rapid determination of nitrogen content in biological samples.<ref name='Keys1940'>{{cite journal | title = A Rapid Micro-Kjeldahl Method | journal = The Journal of Biological Chemistry | year = 1939 | first = Ancel | last = Keys | volume = 132 | pages = 181–187|url=http://www.jbc.org/content/132/1/181.short | access-date = February 5, 2011 | quote = A micro-Kjeldahl method is described. The method is more rapid than the ordinary macro-Kjeldahl procedure and is not appreciably less accurate | issue=1| doi = 10.1016/S0021-9258(18)73407-8 | doi-access = free }}</ref> This would prove useful for activities as diverse as determining the protein content in grasshopper eggs<ref>{{cite journal | doi = 10.2307/1537901 | title = Nitrogen content and distribution in eggs of Melanoplus differentialis during embryonic development | journal = Biological Bulletin | year = 1940 | first = Carolyn | last = Trowbridge |author2=Joseph Hall Bodine | volume = 79 | issue = 3 | pages = 452–458|url=http://www.biolbull.org/cgi/reprint/79/3/452.pdf | access-date = February 5, 2011| jstor = 1537901 }}</ref> and anemia in humans.<ref>{{cite journal | doi = 10.1172/JCI103087 | title = The anemia of liver disease: observations on its mechanism. | journal = Journal of Clinical Investigation | year = 1955 | first = James H. | last = Jandi | volume = 34 | issue = 3 | pages = 390–404| pmid = 14354009 | pmc = 438641}}</ref>

While at Harvard's Fatigue Laboratory, he was inspired by his Cambridge mentor [[Joseph Barcroft]]'s ascent to the top of [[Tenerife|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.<ref name=Hoffman1979/> He was given the go-ahead and, in 1935, assembled a team to study the effects of high altitude on the body,<ref name=Sullivan2004/> such as how it affects blood pressure.<ref name=Brody2004/> 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.).<ref name=Hoffman1979/>

He noted there was no good way of predicting how well humans might [[High-altitude adaptation in humans|adapt to high altitude]], even if they adapted well to medium altitudes, a problem for potential pilots in a time before pressure control had become practical.<ref name='Keys1936'>{{cite journal | title = The Physiology of Life at High Altitudes | journal = The Scientific Monthly | year = 1936 | first = Ancel | last = Keys | volume = 43 | issue = 4 | pages = 289–312| jstor = 16163| bibcode = 1936SciMo..43..289K }}</ref> 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.<ref name=Kalm_2005>{{cite journal |vauthors=Kalm L, Semba R |title=They starved so that others be better fed: remembering Ancel Keys and the Minnesota experiment |journal=J Nutr |volume=135 |issue=6 |pages=1347–1352 |year=2005 |pmid=15930436|doi=10.1093/jn/135.6.1347 |doi-access=free }}</ref><ref name='Keys1938'>{{cite journal | doi = 10.1098/rspb.1938.0043 | title = Individual Variations in Ability to Acclimatize to High Altitude | journal = Proceedings of the Royal Society B | year = 1938 | first1 = Ancel | last1 = Keys | first2 = Bryan H. C. |last2=Matthews |first3=W. H. |last3=Forbes |first4=Ross A. |last4=McFarland | volume = 126 | issue = 842 | pages = 1–24| jstor=82153| bibcode = 1938RSPSB.126....1K | s2cid = 128707808 | doi-access =  }}</ref>

===Development of K-rations===
{{Main|K-ration}}
[[File:KRation Dinner.JPG|thumb|left|An example of a [[K-ration]] dinner. All the components were intended to fit into a box which would fit into a soldier's pocket]]

In 1936, Keys was offered a position at the [[Mayo Foundation]] in [[Rochester, Minnesota|Rochester]], where he continued his studies in physiology.<ref name=Keys1936/> He left after a year, citing an intellectually stifling environment where research was secondary to clinical "doc business" and playing [[Contract bridge|bridge]].<ref name=Hoffman1979/>

In 1937, he left the Mayo Foundation to teach physiology at the University of Minnesota,<ref name='Reed2004'>{{cite news | first = Christopher | last = Reed | title = Ancel Keys The dietician who promoted the virtues of the Mediterranean diet | date = December 8, 2004 |url=https://www.theguardian.com/news/2004/dec/08/guardianobituaries1 | work = [[The Guardian]] | access-date = February 5, 2011}}</ref> where he founded the Laboratory of Physiological Hygiene. His earlier research on human physiology led to an assignment with the [[Quartermaster Corps (United States Army)|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.<ref name='Buskirk1992'>{{cite journal | title = From Harvard to Minnesota: Keys to our History | journal = Exercise and Sport Sciences Reviews | year = 1992 | first = ER | last = Buskirk | volume = 20 | pages = 1–26| pmid = 1623883  | quote = Based on an appeal from the Army Quartermaster Corps, experiments to design and test rations for the promotion and maintenance of combat effectiveness for paratroopers were undertaken. Neither Keys nor the military was particularly interested in vitamins, but rather they wanted to put calories into a small packet of nonperishable food&nbsp; ... the Keys or [[K-ration]] was designed in the Laboratory and at field test sites in both hot and cold areas on the North American continent. | doi=10.1249/00003677-199200200-00001| doi-access = free }}</ref>

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

{{blockquote|When it appeared that the U.S. would be in World War II, Keys went to the Quartermaster Food and Container Institute in Chicago to inquire about emergency rations. The story goes that he was told to go home and leave such things to the professionals. Undissuaded, he went to [[Wm. Wrigley Jr. Company|William Wrigley's]] office and secured $10,000 for the development of an emergency ration. Then, he went to the [[Cracker Jack|Cracker Jack Company]]. They couldn't supply money, but did provide the water-tight small box concept. The result was the K-ration in sealed Cracker Jack boxes.<ref name=Buskirk1992/>}}

Once the basic design had been completed, the Navy, through the [[National Research Council (United States)|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.<ref name=Sullivan2004/> The final product was different from Keys' original ingredients, but most of Keys' suggestions made it to the final product.<ref name=Hoffman1979/> The rations weighed only {{convert|28|oz|abbr=on}}, but provided 3200 calories per day.<ref name=Reed2004/> Though several sources claim the name was unrelated to Keys,<ref name=Quartermaster-1>{{cite conference|url=http://qmfound.com/history_of_rations.htm |contribution=Rations: The History of Rations |access-date=February 6, 2011 |archive-url=https://web.archive.org/web/20110208042157/http://www.qmfound.com/history_of_rations.htm |archive-date=February 8, 2011 |publisher=The Quartermaster School |via=U.S. Army Quartermaster Museum |date=January 1949 |title=Conference Notes prepared for the Quartermaster General }}</ref> many historical references support the claim that the K-ration was indeed named after him.<ref name=Hoffman1979/><ref name=Buskirk1992/><ref>{{cite journal | title = Olaf Mickelsen (July 29, 1912 to August 8, 1999)  | journal = Journal of Nutrition | year = 2001 | first = Rachel | last = Schemmel |author2=Simin Vaghefi |author3=Barbara Bowman  | volume = 131 | issue = 2 | pages = 205–210| pmid = 11160534  | quote = During World War II, I worked with Dr. Ancel Keys on the K ration. This emergency ration was named after Dr. Keys because of the pioneering work he did in getting our country conscious of the fact that a ration of this type would be surely needed if we became embroiled in war.| doi = 10.1093/jn/131.2.205 | doi-access = free }}</ref> The K-ration became such a success that it was often used for more than temporary sustenance, becoming a major staple of military nutrition.<ref name=Hoffman1979/><ref name=Buskirk1992/>

===Starvation study===
{{main|Minnesota Starvation Experiment}}

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 [[methyltestosterone|testosterone]] on muscle work<ref name='Samuels1942'>{{cite journal | title = Influence of Methyl Testosterone on Muscular Work and Creatine Metabolism in Normal Young Men | journal = Journal of Clinical Endocrinology and Metabolism | first = Leo | last = Samuels |author2=Austin Henschel |author3=Ancel Keys  | volume = 2 | issue = 11 | pages = 649–654 | year = 1942| doi =  10.1210/jcem-2-11-649 |url=http://jcem.endojournals.org/cgi/content/abstract/2/11/649 | access-date = February 6, 2011}}</ref> and vitamin supplementation as a performance enhancer on adequately fed soldiers,<ref name='Keys1943'>{{cite journal | title = The performance of normal young men on controlled thiamine intakes | journal = Journal of Clinical Nutrition | year = 1943 | first = Ancel | last = Keys |author2=Austin Henschel |author3=Olaf Mickelsen |author4=Josef Brozek  | volume = 26 | issue = 4 | pages = 399–415|url=http://jn.nutrition.org/cgi/reprint/26/4/399.pdf | access-date = February 6, 2011}}</ref><ref name='Keys1942'>{{cite journal | title = Vitamin supplementation of US Army rations in relation to fatigue and the ability to do muscular work | journal = Journal of Clinical Nutrition | year = 1942 | first = Ancel | last = Keys |author2=Austin Henschel | volume = 23 | issue = 3 | pages = 259–269|url=http://jn.nutrition.org/cgi/reprint/23/3/259.pdf | access-date = February 6, 2011}}</ref> 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.<ref name=Buskirk1992/>

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.<ref name=Kalm_2005/><ref name=Buskirk1992/> The original pool of 400 responders was reduced to 36 selectees, of whom 32 would go on to complete the study.<ref name='Keys1950'>{{cite book | last1 = Keys | first1 = Ancel | author-link1 = Ancel Keys | title = The Biology of Human Starvation | publisher = University of Minnesota Press | year = 1950 | location = Minneapolis | pages = 262}}</ref> 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.<ref name=Kalm_2005/> 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.<ref name=Kalm_2005/>

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<ref name=Hoffman1979/> and, by 1950, he completed publication of his two-volume 1385-page ''Biology of Human Starvation''.<ref name=Kalm_2005/><ref name=Buskirk1992/>

===Seven Countries Study===
{{Main|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).<ref name=Keys_1963>{{cite journal |vauthors=Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E |title=Coronary heart disease among Minnesota business and professional men followed 15 years |journal=Circulation |volume=28 |issue= 3|pages=381–395 |date=September 1, 1963|pmid=14059458 |doi=10.1161/01.cir.28.3.381|doi-access=free }}</ref> At a 1955 expert meeting at the World Health Organization in Geneva, Keys presented his diet-lipid-heart disease hypothesis.<ref>{{cite web|title=Famous Polemics on Diet-Heart Theory|author=Henry Blackburn|publisher= School of Public Health, University of Minnesota|url=http://www.epi.umn.edu/cvdepi/essay.asp?id=33|archive-url=https://web.archive.org/web/20140327233831/http://www.epi.umn.edu/cvdepi/essay.asp?id=33|archive-date=March 27, 2014}}</ref><ref name=Keys_1980>{{cite book | last = Keys | first = Ancel| title = Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease |url=https://archive.org/details/sevencountriesmu0000keys | url-access = registration | publisher = Harvard University Press | year = 1980 | isbn = 978-0-674-80237-7 }}</ref> 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.<ref>{{Cite journal|last=Keys|first=A.|date=July 1953|title=Atherosclerosis: a problem in newer public health|journal=Journal of the Mount Sinai Hospital, New York|volume=20|issue=2|pages=118–139|issn=0099-9695|pmid=13085148}}</ref> His rationale and conclusions were heavily critiqued by two other epidemiologists.<ref>{{Cite journal|last1=Yerushalmy|first1=J.|last2=Hilleboe|first2=H. E.|date=July 15, 1957|title=Fat in the diet and mortality from heart disease; a methodologic note|journal=New York State Journal of Medicine|volume=57|issue=14|pages=2343–2354|issn=0028-7628|pmid=13441073}}</ref>

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 artery disease|coronary heart disease]] mortality both at the population and individual levels.<ref>Kromhout D: "Serum cholesterol in cross-cultural perspective. The Seven-Countries Study". ''Acta Cardiol'' 1999;54:155–158</ref><ref name=Katan>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</ref>

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. Keys stated that of the 12,000 men in seven countries studied in 1960, those least likely to develop cardiovascular disease lived in [[Crete]].<ref>[http://www.nytimes.com/1998/02/10/science/personal-health-pass-the-wine-and-olive-oil-and-other-lessons-from-crete.html "Personal Health; Pass the Wine and Olive Oil, and Other Lessons From Crete"]. nytimes.com. Retrieved May 4, 2024.</ref>

After Keys' retirement from the [[University of Minnesota]] in 1972, his protege Henry Blackburn, MD became director of the Laboratory of Physiological Hygiene.<ref>{{cite web |title=Blackburn, Henry « Heart Attack Prevention |url=http://www.epi.umn.edu/cvdepi/bio-sketch/blackburn-henry/ |website=University of Minnesota |access-date=March 28, 2020}}</ref>  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.

===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.<ref>{{cite web|url=https://www.lipid.org/sites/default/files/images/mwall/Ancel_Keys.pdf|title=Ancel Keys, PhD (1904–2004)|publisher=National Lipid Association|access-date=August 15, 2016}}</ref><div style="margin:1em;>
:Change in serum cholesterol concentration

:{{math|1=(mmol/L) {{=}} 0.031(2D<sub>sf</sub> − D<sub>puf</sub>) + 1.5{{sqrt|D<sub>ch</sub>}}}}

:where D<sub>sf</sub> is the change in percentage of dietary energy from saturated fats, D<sub>puf</sub> is the change in percentage of dietary energy from polyunsaturated fats, and D<sub>ch</sub> is the change in intake of dietary cholesterol.<ref>{{cite journal|volume=320|issue=7230|pages=301–5|date=January 29, 2000|journal=BMJ|title=Exploring a fiscal food policy: the case of diet and ischaemic heart disease|author=Marshall, Tom|pmc=1117490|pmid=10650031|doi=10.1136/bmj.320.7230.301}}</ref></div>

===BMI and other contributions===
In a 1972 article, Keys and his coauthors promoted{{citation needed|date=June 2022}} [[Adolphe Quetelet]]'s [[body mass index]] (BMI) as "preferable over other indices of relative weight on [correlation with height and measures of body fatness] as well as on the simplicity of the calculation and, in contrast to percentage of average weight, the applicability to all populations at all times",<ref>{{cite journal|title=Reprints and Reflections: Indices of relative weight and obesity|author1=Ancel Keys |author2=Flaminio Fidanza |author3=Martti J Karvonen |author4=Noburu Kimura |author5=Henry L Taylor |journal=Int. J. Epidemiol.|year=2014|volume=43|issue=3|pages=655–665 first published online April 1, 2014|doi=10.1093/ije/dyu058|pmid=24691951 |doi-access=free |quote=Reprint of Keys A, Fidanza F, Karvonen MJ, Kimuru N, Taylor HL. "Indices of relative weight and obesity". ''J Chron Dis'' 1972. Vol. 25. pp. 329–343. }}</ref> which the U.S. [[National Institutes of Health]] then popularized in 1985.<ref>{{cite news|title=Beyond BMI|author=Singer-Vine, Jeremy|date=July 20, 2009|url=http://primary.slate.com/articles/health_and_science/science/2009/07/beyond_bmi.html|publisher=The Slate Group|newspaper=Slate|access-date=February 10, 2016|archive-url=https://web.archive.org/web/20160216130711/http://primary.slate.com/articles/health_and_science/science/2009/07/beyond_bmi.html|archive-date=February 16, 2016}}</ref><ref>{{cite web|url=https://consensus.nih.gov/1985/1985Obesity049html.htm|title=Health Implications of Obesity|date=February 11, 1985|access-date=February 10, 2016|publisher=National Institutes of Health, U.S. Department of Health and Human Services}}</ref>

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."<ref>[https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4830a1box.htm Ancel Keys, Ph.D.], Morbidity and Mortality Weekly Report, [[Centers for Disease Control and Prevention]]</ref> Because of his influence in dietary science, Keys was featured on the cover of the January 13, 1961, issue of [[Time magazine|''Time'' magazine]].

==Later years and death==
[[File:Eat Well Stay Well 1963.png|thumb|''Eat Well Stay Well'', 1963]]

When Keys was hired at the Mayo Foundation in 1936, he hired Margaret Haney (1909–2006) as a medical technologist.<ref name=Buskirk1992/> In 1939 they married and had three children: Carrie D'Andrea, Henry Keys, and Martha McLain.<ref name='Cohen2006'>{{cite news | first = Ben | last = Cohen | title = Chemist, author, diet researcher Margaret Keys was 97 | date = December 18, 2006 |url=http://www.startribune.com/obituaries/11603901.html | work = [[Star Tribune]] | access-date = February 6, 2011 | archive-url=https://web.archive.org/web/20111208163753/http://www.startribune.com/obituaries/11603901.html | archive-date = December 8, 2011 }}</ref> 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.<ref>{{cite book|page=211|last=Tucker, Todd|publisher=University of Minnesota Press|isbn=978-0-8166-5161-0|first=2006 Simon & Schuster|year=2007|title=The Great Starvation Experiment: Ancel Keys and the Men Who Starved for Science}}</ref>

Together, Margaret and Keys co-authored three books, two of them bestsellers.<ref name=Brody /> 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.<ref>Tucker 2006. p. 207.</ref><ref name="theflorentine2011">{{cite web |title=Ancel Keys |url=https://www.theflorentine.net/2011/06/01/ancel-keys/ |publisher=The Florentine |date=June 1, 2011 |access-date=May 2, 2021}}</ref> 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.<ref name=Hoffman1979/> 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.<ref name="theflorentine2011"/><ref name="museum">{{cite web |title=Living Museum of the Mediterranean Diet |url=https://tenutaducamarigliano.it/en-gb/portfolio-item/living-museum-mediterranean-diet/ |publisher=Tenuta Duca Marigliano |access-date=May 2, 2021}}</ref>

Keys appeared on the ''[[To Tell The Truth]]'' game show as the inventor of K-Rations, fooling  two of the four panelists.<ref>{{cite web |title=To Tell The Truth |url=https://www.youtube.com/watch?v=1MDpFyhm_lk | archive-url=https://ghostarchive.org/varchive/youtube/20211211/1MDpFyhm_lk| archive-date=December 11, 2021 | url-status=live|website=You Tube | date=February 29, 2016 |publisher=CBS Television |access-date=August 19, 2019}}{{cbignore}}</ref>

Keys received three notable awards: Commander, [[Order of the Lion of Finland]] (1963), the McCollum Award from the [[American Society for Nutrition|American Society of Clinical Nutrition]] (1967), and an honorary doctor of science from the University of Minnesota (2001).<ref name=UofMbio>{{cite web|title=Ancel Keys, MS, PhD|url=http://www.epi.umn.edu/cvdepi/bio-sketch/keys-ancel/|publisher=Regents of the University of Minnesota|access-date=January 9, 2019}}</ref>

On January 26, 2004, Keys celebrated his [[Centenarian|100th birthday]].

Keys died on November 20, 2004, in Minneapolis, two months before his 101st birthday.<ref name="theflorentine2011"/><ref name="Obit">{{cite press release|title=Ancel Keys. |url=http://www.the-aps.org/membership/obituaries/ancel_keys.htm |publisher=The American Physiological Society |year=2004 |access-date=November 13, 2007 |archive-url=https://web.archive.org/web/20070927031550/http://www.the-aps.org/membership/obituaries/ancel_keys.htm |archive-date=September 27, 2007 }}</ref><ref name=Brody>{{cite news|last1=Brody|first1=Jane E. |title=Dr. Ancel Keys, 100, Promoter of Mediterranean Diet, Dies|url=https://www.nytimes.com/2004/11/23/obituaries/dr-ancel-keys-100-promoter-of-mediterranean-diet-dies.html|work= The New York Times|date= November 23, 2004|access-date= July 28, 2016}}</ref>

Keys was an atheist.<ref>{{cite book|title=The Great Starvation Experiment: Ancel Keys and the Men Who Starved for Science|year=2008|publisher=U of Minnesota Press|isbn=978-0-8166-5161-0|author=Todd Tucker|page=146|quote=Max's advocates made up a diverse cast of characters, from the Jewish Peace Fellowship leader Rabbi Isador Hoffman to the atheist Ancel Keys, who wrote the committee that Max "proved to be a highly reliable and conscientious man who comported himself well under the most rigorous and demanding circumstances."}}</ref>

==Criticism==

Keys has received criticism from the [[low-carbohydrate diet]] community, who have argued that his Seven Countries Study excluded countries that did not fit his hypothesis.<ref>{{cite journal |author=Pett, Katherine D |author2=Willett, Walter C |author3=Vartiainen, Erkki |author4=Katz, David L|year=2017|title=The Seven Countries Study|journal= European Heart Journal|url=|volume=38|issue=42|pages=3119–3121|doi=10.1093/eurheartj/ehx603|pmid=29121230|doi-access=free}}</ref><ref name="Pett 2017">{{citation|title=Ancel Keys and the Seven Countries Study: An Evidence-based Response to Revisionist Histories|last1=Pett |first1=K D |last2=Kahn |first2=J |last3= Willett |first3=W C |last4= Katz |first4=DL|year=2017|url=https://www.truehealthinitiative.org/wp-content/uploads/2017/07/SCS-White-Paper.THI_.8-1-17.pdf|publisher=True Health Initiative |access-date=August 29, 2018}}</ref> Critics raised four primary objections to the Seven Countries Study, including (1) countries were selected and excluded based on a desired outcome; (2) France, a high-fat, low-heart disease country, was purposefully excluded from the survey; (3) dietary data in Greece taken during [[Lent]] introduced a distortion; and (4) sugar was not considered as a possible contributor to [[coronary heart disease]]. In response to this criticism, on August 1, 2017, the True Health Initiative released a 65-page white paper entitled "Ancel Keys and the Seven Countries Study: An Evidence-based Response to Revisionist Histories," correcting what they felt were historical inaccuracies and errors that low-carb advocates had perpetuated.<ref name="Pett 2017"/><ref>Pett, Kahn, Willett & Katz (2017) p 22, 32, 37, 43</ref>

==Books==
* {{cite book|last1=Keys|first1=A.|last2=Brozek|first2=J.|last3=Henschel|first3=A.|last4=Mickelsen|first4=O.|last5=Taylor|first5=H. L.|title=The Biology of Human Starvation (2 volumes)|publisher=University of Minnesota Press|year=1950| isbn = 978-0-8166-7234-9}}
* {{cite book|author-mask=1|last1=Keys|first1=Ancel|last2=Keys|first2=Margaret|title=Eat Well and Stay Well|publisher=Doubleday|year=1959|lccn=59-6361}}
* {{cite book|author-mask=1|last1=Keys|first1=Ancel|last2=Keys|first2=Margaret|title=The Benevolent Bean|url=https://archive.org/details/benevolentbean00keys|url-access=registration|publisher=Doubleday|year=1967|lccn=67-12853}}
* {{cite book|author-mask=1|last1=Keys|first1=Ancel|last2=Keys|first2=Margaret|title=How to Eat Well and Stay Well the Mediterranean Way|publisher=Doubleday|year=1975|isbn=978-0-385-00906-5}}
* {{cite book|author-mask=1|last1=Keys|first1=Ancel|title=Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease |url=https://archive.org/details/sevencountriesmu0000keys|url-access=registration|publisher=Harvard University Press|year=1980|isbn=978-0-674-49788-7}}
* {{cite book|author-mask=1|last=Keys|first=Ancel|title=Adventures of a Medical Scientist: Sixty Years of Research in Thirteen Countries|year=1999|publisher=memoir, privately published | isbn = 978-0-9672072-0-9}}<ref name=UofMbio />

==References==
{{CDC|article=Morbidity and Mortality Weekly Report|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4830a1box.htm}}
{{Reflist|30em}}

==External links==
*{{commons category-inline}}
*[https://www.sevencountriesstudy.com/about-the-study/investigators/ancel-keys/ "Ancel Keys"] at Seven Countries Study
*{{cite web|url=http://mbbnet.umn.edu/firsts/blackburn_h.html|title=Ancel Keys|access-date=April 15, 2007|author=Blackburn, Henry|publisher=[[University of Minnesota]]}}
{{Authority control}}

{{DEFAULTSORT:Keys, Ancel}}
[[Category:1904 births]]
[[Category:2004 deaths]]
[[Category:American atheists]]
[[Category:American men centenarians]]
[[Category:American nutritionists]]
[[Category:American people of World War II]]
[[Category:American physiologists]]
[[Category:Civilian Public Service]]
[[Category:Lipid hypothesis researchers]]
[[Category:Mediterranean diet advocates]]
[[Category:University of Minnesota faculty]]
[[Category:Writers from Colorado Springs, Colorado]]