Posted by: Joseph Dixon | May 17, 2014

Science: Unintended Consequences; Ancel Keys, Cholesterol, and the Transition to an Obese Society; Part VI, Ancel Keys’ Career, Part 2: Implementing The Seven Countries Study

One of the major criticisms of Dr. Ancel Keys is that he intentionally left out data from other countries that would have destroyed the strength of his main observation that CHD was correlated with cholesterol concentrations across the seven countries. This criticism is just nonsense. A later study of 40 countries completely supported Dr. Keys’ observations in the Seven Countries Study and I will address this below. If you read the comments of the investigators who were associated with the Seven Countriesstudy, there is no indication that subsets of data were eliminated from the study.

At the time of Dr. Keys’ 100th birthday. Prof. Mario Mancini of the Universitfldi Napoli, Napoli, Italy, wrote of his early association with Dr. Keys and how the results from the Seven Countries study were important in the establishment of a high blood cholesterol as a risk factor for CHD.

M. Mancini and J. Stamler; Diet for preventing cardiovascular diseases: Light from Ancel Keys, Distinguished Centenarian Scientist.  Nutr Metab Cardiovasc Dis (2004) 14:52-57

Prof. Mancini described how, in 1954, Dr. Keys organized a meeting in Naples, Italy to discuss with leading investigators a study that would investigate the role of diet and life style on the incidence of CHD in middle aged males across a spectrum of countries. The countries to be enrolled included Finland, Greece, Italy, Japan, The Netherlands, U.S. and Yugoslavia.

If you read the early chapters in Seven Countries, Dr. Keys explained how the different groups of men were chosen and described the methods that were used to study them. The cohorts selected were men, 40 to 59 years old, usually from a well defined area where all men in that area were asked to participate in the study. The response rate for most of the groups asked to participate was over 90%, which is an excellent rate. Although seven countries were involved, more than one area was studied in most of the countries, so the total number of cohorts numbered sixteen, of which eleven were from rural regions. The particular countries used in the study were chosen because a group of researchers was available to participate in the country and the countries represented a wide range of dietary intakes. The areas within each were chosen because they represented defined areas with an apparently stable population of men. The group of men recruited in the US were comprised of railroad workers, both office workers and more active switchman, from the area outlined by Green Bay, Wisconsin; St. Louis, San Francisco, and Seattle. To make a direct comparison with the American cohort, a similar group of railroad workers was identified and recruited in Italy. One has to remember that the study was started in the 1950s, before the advent of personal computers, excel spreadsheets, the internet, and commercial jet aircraft.

The results of the Seven Countries study were described in Part I of this book. The purpose of reviewing how the study was started is to show, for that time period, that this was a brilliant, out of the box study that was conceived by a curious scientist who wished to find an answer to a serious problem.

In order to counter the argument that Dr. Keys gerrymandered the results by leaving out data from other countries, I would like to discuss a later study that was comprised of data from forty countries.

S M Artaud-Wild, S L Connor, G Sexton and W E Connor;  Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.  Circulation. 1993;88:2771-2779

The authors of this study (referred to as the Connor study) investigated health statistics and food intake (40 dietary variables) data from forty countries that spanned many levels of socioeconomic status. The authors also used a simple Cholesterol-Saturated Fat Index (CSI) that allowed for comparisons against the combined intakes of cholesterol and saturated fat. When the data were analyzed, CHD mortality was highly correlated with the CSI across all of the countries, except for France and Finland. This correlation is shown in the figure presented below.

Correlation with CSI in Connor 1993

Although all of the data were derived from national health statistics, the large range of data accumulated allows a strong level of confidence concerning the results. The figure shows that deaths from CHD were highly correlated with the intake of saturated fat and cholesterol over 38 countries. France was off the correlation curve due to the fact that there was much less CHD for a high CSI, and Finland was off the curve because there was much more CHD for a high CSI value than expected. The authors noted these abnormalities and called them a paradox. They analyzed the dietary data for these two countries and found that Finns consumed much more milk and butterfat (fat from milk, cream, cheese, and butter) than the French. On the other hand, the French consumed more vegetables and vegetable oils than the Finns. Interestingly, the Connor study pointed to milk fat as a potent pro-CHD factor. On the whole the results of this study completely replicated the results obtained by Dr. Keys and his colleagues in the Seven Countries study.

The Connor study even observed a similar paradox as was observed by Keys. In the Seven Countries study there was a large disparity between Finland and Crete, which had widely different rates of CHD at similar fat intakes. In the Connor study, there was a large disparity between Finland and France, which had widely different rates of CHD at similar fat intakes. Of course, these disparities were probably due to the protective effects of the Mediterranean diet in Crete and France. Overall, the Connor study closely replicated the results of the the Seven Countries study but did so using data from forty countries. This study blows apart the common criticism of the Seven Countries Study that Ancel Keys did not include data from other countries and thus he altered the results concerning the roles of cholesterol and saturated fat in the development of CHD. Furthermore, we must ask the question, why would Ancel Keys alter the results? The Connor study, and many others that followed, have definitely supported the results obtained in the Seven Countries study, and my final conclusion must be that Dr. Ancel Keys was an accurate and truthful scientist.

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