Keys was intelligent as a boy; Lewis Terman, a noted psychologist and inventor of the Stanford-Binet IQ Test, described him as intellectually "gifted".

[16] 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.

[17] 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.

[17] 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.

[18][20][21] He would also use this perfusion method to study the effects of adrenaline and vasopressin ("pitressin") on gill fluid flow[22] and osmotic regulation in fishes.

[26] While at Harvard's Fatigue Laboratory, he was inspired by his Cambridge mentor Joseph Barcroft's ascent to the top of Tenerife's highest peak and his subsequent reports.

Keys wrote up a proposal for an expedition to the Andes, suggesting the study could have practical value for Chilean miners who worked at high elevations.

[27] 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.

[27] He left after a year, citing an intellectually stifling environment where research was secondary to clinical "doc business" and playing bridge.

His earlier research on human physiology led to an assignment with the Army Quartermaster Corps, where they worked to develop a more portable and nonperishable ration that would provide enough calories to sustain soldiers (such as paratroopers) in the field for up to two weeks.

His colleague, Elsworth Buskirk, recalled: 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.

[31]Once the basic design had been completed, the Navy, through the National Research Council, funded the testing of the K-rations on its sailors to determine their feasibility as a temporary and mobile food source.

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.

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.

[28] 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[17] and, by 1950, he completed publication of his two-volume 1385-page Biology of Human Starvation.

The 2016 paper "Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment" concludes: Results – The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline −13.8% v −1.0%; P<0.001).

There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001).

Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

[52]In a 1972 article, Keys and his coauthors promoted[citation needed] 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",[54] which the U.S. National Institutes of Health then popularized in 1985.

[60] 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.

[61][62] 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.