Seven Countries Study

The Seven Countries Study is an epidemiological longitudinal study directed by Ancel Keys at what is today the University of Minnesota Laboratory of Physiological Hygiene & Exercise Science (LPHES). Begun in 1956 with a yearly grant of US$200,000 from the U.S. Public Health Service, the study was first published in 1978 and then followed up on its subjects every five years thereafter.[1]

As the world's first[2] multicountry epidemiological study, it systematically examined the relationships between lifestyle, diet, coronary heart disease and stroke in different populations from different regions of the world. It directed attention to the causes of coronary heart disease and stroke, but also showed that an individual’s risk can be changed.

As of 2016, heated scientific debate continues. Project officer Henry Blackburn wrote in 1975, "Two strikingly polar attitudes persist on this subject, with much talk from each and little listening between."[3] Ian Leslie quotes a sympathetic colleague at the University of Minnesota who said Keys was "critical to the point of skewering”.[4]

History

In the 1940s, a University of Minnesota researcher, Ancel Keys, postulated that the apparent epidemic of heart attacks in middle-aged American men was related to their mode of life and possibly modifiable physical characteristics. He first explored this idea in a group of Minnesota business and professional men (executives aged 45 to 55) that he recruited into a prospective study in 1947, the first of many cohort studies eventually mounted internationally. The U.S. Public Health Service agreed to fund the study (and then set up and proceeded to fund the Framingham Heart Study on a larger scale). The Minnesota men were followed through 1981 and the first major report appeared in 1963 after the fifteen-year follow-up study.[5][6]

The study contributed much to survey methods and confirmed larger studies that reported earlier on the predictive value for heart attack of several characteristics, the now-traditional risk factors of blood pressure and blood cholesterol level and cigarette smoking. Keys traveled widely with his wife Margaret who tested people's serum cholesterol. They sent their samples back to Minnesota for analysis. In 1952, Keys's hypothesis that coronary heart disease could be related to diet was first published in Voeding in The Netherlands.[7] His work in post-wartime Naples led him to seek organization and funding for studies of different populations, as did his subsequent work in Uganda; Cape Town, South Africa; Sardinia; Bologna; and Ilomantsi, Finland; and with Japanese men living in Hawaii and in Japan. He decided to concentrate on men living in villages, rather than those in cities where the population moved around frequently.[6]

In the mid-1950s, with improved methods and design, Keys recruited collaborating researchers in seven countries to mount the first cross-cultural comparison of heart attack risk in populations of men engaged in traditional occupations in cultures contrasting in diet, especially in the proportion of fat calories of different composition, the Seven Countries Study still under observation today.

The Seven Countries Study was formally started in fall 1958 in Yugoslavia. In total, 12,763 males, 40–59 years of age, were enrolled as 16 cohorts, in seven countries, in four regions of the world (United States, Northern Europe, Southern Europe, Japan). One cohort is in the United States, two cohorts in Finland, one in the Netherlands, three in Italy, five in Yugoslavia (two in Croatia, and three in Serbia), two in Greece, and two in Japan. The entry examinations were performed between 1958 and 1964 with an average participation rate of 90%, lowest in the US, with 75% and highest in one of the Japanese cohorts, with 100%.[8] The study has continued for more than 50 years.

Major findings

The Seven Countries Study suggested that the risk and rates of heart attack and stroke (CVR), both at the population level and at the individual level, correlated directly and independently to the level of total serum cholesterol, in seven sampled out countries. It demonstrated that the correlation between blood cholesterol level and coronary heart disease (CHD) risk from 5 to 40 years follow-up is found consistently across different specially selected cultures in these seven countries. Cholesterol and obesity correlated with increased mortality from cancer.[9][10][11] The Seven Countries Study suggested that elevated blood pressure (hypertension) was correlated with risk of coronary heart disease and stroke. It showed that the mortality rate after a coronary heart disease event or stroke was associated with the level of hypertension. In several cohorts of the study, stroke deaths exceeded deaths from coronary heart disease.[12][13] It hinted that differences in overall mortality between the different regions of the seven countries are largely associated with variation in cardiovascular mortality.[14] Coronary deaths in the United States and Northern Europe greatly exceeded those in Southern Europe, even when controlled for age, cholesterol, blood pressure, smoking, physical activity, and weight.

The Seven Countries Study was investigated further in regard to an eating pattern loosely characterized as the Mediterranean Diet.[15][16][17][14][18] What exactly is meant by "Mediterranean Diet" today, was detailed by Antonia Trichopoulou (wife of Dimitrios Trichopoulos),[19] and Anna Ferro-Luzzi.[20] The diet was publicized and popularized by Greg Drescher of the Oldways Preservation and Exchange Trust and by Walter Willett of the Harvard School of Public Health.[21][22][23][24][25][26]

The Seven Countries Study also showed that the slowly changing habits of a population in the Mediterranean region, from a healthy, active lifestyle and diet, to a less active lifestyle and a diet influenced by the Western pattern diet, significantly correlated with increased risk of heart disease.[27][28] Meanwhile, it has been confirmed by other researchers that there is an inverse association between adherence to the Mediterranean Diet and the incidence of fatal and non- fatal heart disease in initially healthy middle-aged adults in the Mediterranean region.[29]

The Seven Countries Study, along with other studies, e.g. the Framingham Heart Study, and the Nurses' Health Study, showed the importance of overweight, obesity, and regular exercise as health issues.[30][31][32][33] It showed a correlation between good cardiovascular health and dementia in the general population. It also showed that cardiovascular risk factors in mid life are significantly associated with increased risk of dementia death later in life.[34] It indicated that cigarette smoking is a highly significant predictor of the development of coronary heart disease, leading to excess rates of angina pectoris, myocardial infarction (MI), and coronary death, along with other studies about smoking, e.g. the Framingham Heart Study and the British Doctors Study.[35][36][37][38]

Criticism

Early criticism

Scientists differed on the best predictors of heart disease. In 1950 in Science, John Gofman described separating lipoproteins into different densities in the ultracentrifuge.[39] In 1952 as part of a panel with Keys, Gofman agreed that reducing fat in the diet might help some heart patients[40] (and in this same issue of Circulation Keys explained that dietary cholesterol is not a factor in humans[41]). In 1956 Gofman wrote that an atherogenic index (the combined levels of LDL and VLDL) predicted atherosclerosis and heart disease.[42] In 1958 he wrote, "The serum cholesterol measurement can be a dangerously misleading guide in evaluation of the effect of diet upon the serum lipids."[43]

Some offered hypotheses opposed to Keys. In 1966, based on their work and writing since 1956, George Campbell and Thomas L. Cleave published Diabetes, Coronary Thrombosis and the Saccharine Disease. They argued that the chronic Western diseases such as diabetes, heart disease, obesity, peptic ulcers and appendicitis are caused by one thing: "refined carbohydrate disease".[44] In 1957, Edward H. Ahrens Jr., a pioneer in lipid research, warned of oversimplifying the problem of diet and heart disease, saying the cause could be fat and cholesterol or it could be carbohydrates and triglycerides. Until evidence was produced, he questioned "the wisdom of prescribing low-fat diets for the general population."[45]

Even before the study had begun, there had been criticism of its methods. Jacob Yerushalmy and Herman E. Hilleboe pointed out that, for an earlier study demonstrating this association (Atherosclerosis, a problem in newer public health), Keys had selected six countries out of 21 for which data were available. Analysis of the full dataset made the analysis between fat intake and heart disease less clear.[46]

In 1957 when they published their critique,[47] Yerushalmy and Hilleboe seemed to some to be lecturing, "the association between the percentage of fat calories... and mortality from... heart disease is not valid" and then they call Keys's work a "tenuous association".[48] Keys, who was one of the first nutrition epidemiologists, wrote in every journal article that "causal relationships are not claimed". His reaction was to mount the Seven Countries Study, the first multicountry epidemiological study ever done.[49]

Contemporary criticism

Several scientists disagreed with Keys's conclusions at the time. Published in 1973 and including his critique of Keys's work,[50] Raymond Reiser found methodological and interpretational errors in a review of forty feeding trials of the relationship between saturated fat and circulating lipoproteins, notably confounding with trans-fatty acids.[51] Ahrens found separately with Margaret Albrink that triglycerides mattered in coronary disease more than total cholesterol, and came to think that carbohydrates cause heart disease and not fats.[52] George V. Mann, writing in the New England Journal of Medicine in 1977, dismissed Keys's 1953 Mt. Sinai address about the ecologic correlation of diet fat and coronary disease as exhibiting "naïveté ... [that] is now a classroom demonstration.",[53] he did not say that the lipid theory is "the greatest scam in the history of medicine"[53][54]). Mann studied the mainly meat diet of Alaskan Eskimos, Congolese pygmies, and the Maasai of Tanzania and Kenya, and thought other factors like lack of exercise were responsible for heart disease.[55] Yet contrary to Mann's assertion that despite wide official recommendations for dietary change “the [coronary heart disease (CHD)] epidemic continues unabated, cholesteremia in the population is unchanged, and clinicians are unconvinced of efficacy”,[53] the age-specific CHD death rate in the United States had by that time been on a steady 3% annual decline since the late 1960s.[56]

John Yudkin thought that sugar, not fat, was at the root of heart disease and other human ills. Keys wrote and promoted his disagreement in 1971.[57] The next year Yudkin retired to write Pure, White and Deadly.[58]

Debate since 2000

Controversy continues about the study itself,[59] and about the strength and causality of the association between dietary fat and heart mortality, particularly as the study of cholesterol has become more sophisticated.[60]

In 2000, Uffe Ravnskov (MD, PhD) published his book The Cholesterol Myths[61] and went on to found The International Network of Cholesterol Skeptics.[62]

In a 2001 article in Science magazine entitled Nutrition: The Soft Science of Dietary Fat, Gary Taubes wrote "it is still a debatable proposition whether the consumption of saturated fats above recommended levels (..) by anyone who's not already at high risk of heart disease will increase the likelihood of untimely death (..) [n]or have hundreds of millions of dollars in trials managed to generate compelling evidence that healthy individuals can extend their lives by more than a few weeks, if that, by eating less fat".[63][64] A New York Times Magazine article entitled "What if It's All Been a Big Fat Lie?" followed in 2002.[65] A further critical analysis of the Seven Countries Study was undertaken by Taubes in his bestselling book Good Calories, Bad Calories (2007)[66] which was followed by Why We Get Fat in 2010.[67] In Good Calories, Bad Calories, Taubes wrote that the Seven Countries Study "was fatally flawed (..) Keys chose seven countries he knew in advance would support his hypothesis (..) [that] coronary heart disease is strongly influenced by the fats in the diet (..) [n]o consideration was given to alternative hypothesis."[68] In his 2016 book The Case against Sugar, Taubes states that "of all the factors measured in these populations, the two that tracked best with heart disease—as Yudkin might have predicted—were sugar and saturated fat (..) and because populations in the study that ate a lot of one tended also to eat a lot of the other, Keys now suggested that this was ″adequate to explain the observed relationship between sucrose and [coronary heart disease] without recourse to the idea that sucrose″ (..) caused it. This was speculation (..) researchers typically assumed that if Keys was right, Yudkin was wrong, and vice versa (..) [w]hen researchers realized that the French had relatively low rates of heart disease despite a diet that was rich in saturated fats, they wrote it off as an inexplicable ″paradox,″ and ignored the fact that the French traditionally consumed far less sugar than did populations—the Americans and British, most notably—in which coronary disease seemed to be a scourge."[69]

In his 2009 "viral video" Sugar: The Bitter Truth,[70] Robert Lustig (MD, PhD) criticized Keys' Seven Countries Study.[71] Lustig gave details in his book Fat Chance: that Keys cherry-picked seven of 22 countries; consumption of trans-fat peaked in the 1960s and Keys failed to separate them out; results for Japan and Italy could be explained by either low saturated fat consumption or by low sugar consumption; and Keys wrote that sucrose and saturated fat were intercorrelated but failed to perform the sucrose half of his multivariate correlation analysis.[72] However, in his later monograph of 1980, Keys included multivariate regressions in which sugar is added to the regression and saturated fat is controlled for. In this regression, Keys found that sugar was not statistically significantly related to incidence of heart disease when dietary saturated fat was controlled for.[8] Today, sugar intake is known to increase the risk of diabetes mellitus, and increased dietary intake of sugar is known to be associated with higher blood pressure, unfavorable blood lipids and cardiometabolic risks.[73][74] However, a 2010 conference debate of the American Dietetic Association expressed concern over the health risks of replacing saturated fats in the diet with refined carbohydrates, which carry a high risk of obesity and heart disease, particularly at the expense of polyunsaturated fats which may have health benefits.[75]

In September 2014, Frank Hu led the 2015 Dietary Guidelines Advisory Committee's report on saturated fat and cardiovascular disease, and Alice H. Lichtenstein said that the consensus is that a low-fat diet is "probably not a good idea" and that it might induce dyslipidemia. She said that the guidelines had changed (formerly recommending low fat, and now moderate fat) in 2000, and that the American Heart Association and the National Heart, Lung, and Blood Institute had revised guidelines as of 2000.[76] The group's Scientific Report of the 2015 Dietary Guidelines Advisory Committee says the average person in the U.S. consumes too much saturated fat. "Sources of saturated fat should be replaced with unsaturated fat, particularly polyunsaturated fatty acids."[77][78]

A meta-analysis in March 2014 met with controversy and was corrected, it found that "current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats", with Walter C. Willett continuing to defend reduced saturated fat in the diet.[79][80] As of 2017, the American Heart Association recommends that saturated fat be reduced or replaced by products containing monounsaturated and polyunsaturated fats to reduce the risk of cardiovascular diseases.[81]

On August 1, 2017, True Health Initiative released a 65-page white paper correcting historical inaccuracies and errors that low-carb advocates have perpetuated "Ancel Keys and the Seven Countries Study: An Evidence-based Response to Revisionist Histories"[82] They refute four false ideas: Countries were selected and excluded based on desired outcome (as posited by Robert Lustig in his viral video); France was purposefully excluded; Dietary data in Greece taken during Lent introduced a distortion; Sugar was not considered as a possible contributor to coronary heart disease.

Notes
  1. Taubes, p. 31.
  2. Teicholz, p. 36.
  3. Gary Taubes quotes Blackburn in Good Calories, Bad Calories p. 22, from: Blackburn Henry (1975). "Contrasting Professional Views on Atherosclerosis and Coronary Disease". N Engl J Med. 292 (2): 105–107. doi:10.1056/NEJM197501092920214. PMID 1109429.
  4. Leslie, Ian. "The sugar conspiracy" "The Guardian", London, 7 April 2016. Retrieved on 9 April 2016.
  5. Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E (1963). "Coronary Heart Disease among Minnesota Business and Professional Men Followed Fifteen Years". Circulation. 28 (3): 381–95. doi:10.1161/01.cir.28.3.381. PMID 14059458.
  6. Keys, Ancel in Kromhout, Daan, Menotti, Alessandro, and Blackburn, Henry (eds.) (1993). "ISBN is invalid: 90-6960-048-x". The Seven Countries Study: A Scientific Adventure in Cardiovascular Disease Epidemiology. Utrecht, The Netherlands: printed by Brouwer Offset bv. pp. 16–25.CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link)
  7. Keys, A. (1952). "The Cholesterol Problem". Voeding (13): 539–555.
  8. Ancel Keys (ed), Seven Countries: A multivariate analysis of death and coronary heart disease, 1980. Cambridge, Mass.: Harvard University Press. ISBN 0-674-80237-3.
  9. Kromhout, D (June 1999). "Serum cholesterol in cross-cultural perspective. The Seven Countries Study". Acta Cardiologica. 54 (3): 155–8. PMID 10478272.
  10. Menotti, A; Lanti, M; Kromhout, D; Blackburn, H; Jacobs, D; Nissinen, A; Dontas, A; Kafatos, A; Nedeljkovic, S; Adachi, H (December 2008). "Homogeneity in the relationship of serum cholesterol to coronary deaths across different cultures: 40-year follow-up of the Seven Countries Study". European Journal of Cardiovascular Prevention and Rehabilitation. 15 (6): 719–25. doi:10.1097/HJR.0b013e328315789c. PMC 2642008. PMID 19050437.
  11. Panagiotakos, DB; Pitsavos, C; Polychronopoulos, E; Chrysohoou, C; Menotti, A; Dontas, A; Stefanadis, C (July 2005). "Total cholesterol and body mass index in relation to 40-year cancer mortality (the Corfu cohort of the seven countries study)". Cancer Epidemiology, Biomarkers & Prevention. 14 (7): 1797–801. doi:10.1158/1055-9965.EPI-04-0907. PMID 16030119.
  12. van den Hoogen PC, Feskens EJ, Nagelkerke NJ, Menotti A, Nissinen A, Kromhout D (Jan 2000). "The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world". N Engl J Med. 342 (1): 1–8. doi:10.1056/nejm200001063420101. PMID 10620642.
  13. Menotti A, Jacobs DR Jr, Blackburn H, Kromhout D, Nissinen A, Nedeljkovic S, Buzina R, Mohacek I, Seccareccia F, Giampaoli S, Dontas A, Aravanis C, Toshima H (Mar 1996). "Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes". Stroke. 27 (3): 381–7. doi:10.1161/01.str.27.3.381. PMID 8610299.CS1 maint: multiple names: authors list (link)
  14. Menotti A, Keys A, Aravanis C, Blackburn H, Dontas A, Fidanza F, Karvonen MJ, Kromhout D, Nedeljkovic S, Nissinen A, et al. (Jun 1989). "Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries". Ann. Med. 21 (3): 175–9. doi:10.3109/07853898909149929. PMID 2765258.
  15. Keys A, Aravanis C, Blackburn HW, Van Buchem FS, Buzina R, Djordjević BD, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, Lekos D, Monti M, Puddu V, Taylor HL (1966). "Epidemiological studies related to coronary heart disease: characteristics of men aged 40-59 in seven countries". Acta Med Scand Suppl. 460: 1–392. PMID 5226858.
  16. Keys A "Coronary heart disease in seven countries." Circulation 1970 Apr;41(4 Suppl):I 1-200.
  17. The seven countries study: 2,289 deaths in 15 years. Keys A, Menotti A, Aravanis C, Blackburn H, Djordevic BS, Buzina R, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, et al. Prev Med. 1984 Mar;13(2):141-54.
  18. Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA (Sep 2004). "Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project". JAMA. 292 (12): 1433–9. doi:10.1001/jama.292.12.1433. PMID 15383513.
  19. Trichopoulou, Antonia; Costacou, Tina; Bamia, Christina; Trichopoulos, Dimitrios (26 June 2003). "Adherence to a Mediterranean Diet and Survival in a Greek Population". N Engl J Med. 348 (26): 2599–2608. doi:10.1056/NEJMoa025039. PMID 12826634.
  20. Willett, W.C.; Sacks, F.; Trichopoulou, A.; Drescher., G.; Ferro-Luzzi, A.; Helsing, E.; Trichopoulos, D. (June 1995). "Mediterranean diet pyramid: a cultural model for healthy eating". American Journal of Clinical Nutrition. 61 (6): 1402S–6S. doi:10.1093/ajcn/61.6.1402s. PMID 7754995. We present a food pyramid that reflects Mediterranean dietary traditions, which historically have been associated with good health. This Mediterranean diet pyramid is based on food patterns typical of Crete, much of the rest of Greece, and southern Italy in the early 1960s, where adult life expectancy was among the highest in the world and rates of coronary heart disease, certain cancers, and other diet-related chronic diseases were among the lowest.
  21. Teicholz, chapter 7.
  22. Kushi LH, Lenart EB, Willett WC (Jun 1995). "Health implications of Mediterranean diets in light of contemporary knowledge. 1. Plant foods and dairy products". Am J Clin Nutr. 61 (6): 1407S–1415S. doi:10.1093/ajcn/61.6.1407s.
  23. Kushi LH, Lenart EB, Willett WC (Jun 1995). "Health implications of Mediterranean diets in light of contemporary knowledge. 2. Meat, wine, fats, and oils". Am J Clin Nutr. 61 (6): 1416S–1427S. doi:10.1093/ajcn/61.6.1416s.
  24. Willett WC (Feb 2006). "The Mediterranean diet: science and practice". Public Health Nutr. 9 (1A): 105–10. doi:10.1079/phn2005931. PMID 16512956.
  25. Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB (Mar 2009). "Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women". Circulation. 119 (8): 1093–100. doi:10.1161/circulationaha.108.816736. PMC 2724471. PMID 19221219.
  26. Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating. By Walter C. Willett. Free Press. 2005. ISBN 0-7432-6642-0
  27. Kafatos A, Diacatou A, Voukiklaris G, Nikolakakis N, Vlachonikolis J, Kounali D, Mamalakis G, Dontas AS (Jun 1997). "Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: the Seven Countries Study". Am J Clin Nutr. 65 (6): 1882–6. doi:10.1093/ajcn/65.6.1882. PMID 9174487.
  28. Menotti A, Keys A, Kromhout D, Blackburn H, Aravanis C, Bloemberg B, Buzina R, Dontas A, Fidanza F, Giampaoli S, et al. (Sep 1993). "Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study". Eur J Epidemiol. 9 (5): 527–36. doi:10.1007/bf00209531. PMID 8307138.
  29. Martínez-González MA, García-López M, Bes-Rastrollo M, Toledo E, Martínez-Lapiscina EH, Delgado-Rodriguez M, Vazquez Z, Benito S, Beunza JJ (2010). "Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort". Nutr Metab Cardiovasc Dis. 21 (4): 237–44. doi:10.1016/j.numecd.2009.10.005. PMID 20096543.
  30. Visscher TL, Seidell JC, Menotti A, Blackburn H, Nissinen A, Feskens EJ, Kromhout D (Apr 2000). "Underweight and overweight in relation to mortality among men aged 40-59 and 50-69 years: the Seven Countries Study". Am J Epidemiol. 151 (7): 660–6. doi:10.1093/oxfordjournals.aje.a010260. PMID 10752793.
  31. Kromhout D, Bloemberg B, Feskens E, Menotti A, Nissinen A (Apr 2000). "Saturated fat, vitamin C and smoking predict long-term population all-cause mortality rates in the Seven Countries Study". Int J Epidemiol. 29 (2): 260–5. doi:10.1093/ije/29.2.260. PMID 10817122.
  32. Kromhout D, Bloemberg B, Seidell JC, Nissinen A, Menotti A (Mar 2001). "Physical activity and dietary fiber determine population body fat levels: the Seven Countries Study". Int J Obes Relat Metab Disord. 25 (3): 301–6. doi:10.1038/sj.ijo.0801568. PMID 11319625.
  33. Keys A, Aravanis C, Blackburn H, Van Buchem FS, Buzina R, Djordjevic BS, Fidanza F, Karvonen MJ, Menotti A, Puddu V, Taylor HL (Apr 1972). "Probability of middle-aged men developing coronary heart disease in five years". Circulation. 45 (4): 815–28. doi:10.1161/01.cir.45.4.815. PMID 5016014.
  34. Alonso A, Jacobs DR Jr, Menotti A, Nissinen A, Dontas A, Kafatos A, Kromhout D (May 2009). "Cardiovascular risk factors and dementia mortality: 40 years of follow-up in the Seven Countries Study". J Neurol Sci. 280 (1–2): 79–83. doi:10.1016/j.jns.2009.02.004. PMID 19251275.CS1 maint: multiple names: authors list (link)
  35. Menotti A, Lanti M, Nedeljkovic S, Nissinen A, Kafatos A, Kromhout D (Jan 2006). "The relationship of age, blood pressure, serum cholesterol and smoking habits with the risk of typical and atypical coronary heart disease death in the European cohorts of the Seven Countries Study". Int J Cardiol. 106 (2): 157–63. doi:10.1016/j.ijcard.2004.12.092. PMID 16321686.
  36. Jacobs DR Jr, Adachi H, Mulder I, Kromhout D, Menotti A, Nissinen A, Blackburn H (Apr 1999). "Cigarette smoking and mortality risk: twenty-five-year follow-up of the Seven Countries Study". Arch Intern Med. 159 (7): 733–40. doi:10.1001/archinte.159.7.733. PMID 10218754.CS1 maint: multiple names: authors list (link)
  37. Doll R, Peto R, Boreham J, Sutherland I (Jun 2004). "Mortality in relation to smoking: 50 years' observations on male British doctors". BMJ. 328 (7455): 1519. doi:10.1136/bmj.38142.554479.ae. PMC 437139. PMID 15213107.
  38. Freund KM, Belanger AJ, D'Agostino RB, Kannel WB (Jul 1993). "The health risks of smoking. The Framingham Study: 34 years of follow-up". Ann Epidemiol. 3 (4): 417–24. doi:10.1016/1047-2797(93)90070-k. PMID 8275219.
  39. Taubes, pp. 153–154.
  40. Katz LN, Keys A, Gofman JW (1952). "Atherosclerosis. A Symposium: Introduction" (PDF). Circulation. 5: 98–100. doi:10.1161/01.CIR.5.1.98.
  41. Keys A (1952). "Human Atherosclerosis and the Diet" (PDF). Circulation. 5: 115–118. doi:10.1161/01.CIR.5.1.115.
  42. Gofman JW, Andrus EC, et al. (1956). "Evaluation of Serum Lipoprotein and Cholesterol Measurements as Predictors of Clinical Complications of Atherosclerosis: Report of a Cooperative Study of Lipoproteins and Atherosclerosis". Circulation. 14: 689–741. doi:10.1161/01.CIR.14.4.689.
  43. Gofman JW (1958). "Diet in the prevention and treatment of myocardial infarction". The American Journal of Cardiology. 1 (2): 271–283. doi:10.1016/0002-9149(58)90058-4.
  44. Taubes, p. 112
  45. Taubes, p. 158.
  46. Yerushalmy J, Hilleboe HE (1957). "Fat in the diet and mortality from heart disease. A methodologic note". NY State J Med. 57: 2343–54.
  47. Weaver Jr., Warren (July 16, 1957) "2 Doubt Fat's Tie to Heart Disease" The New York Times, retrieved February 19, 2015.
  48. Blackburn, Henry. "Famous Polemics on Diet-Heart Theory" Regents of the University of Minnesota, retrieved February 19, 2015
  49. Teicholz, pp. 44, 72, 36.
  50. Reiser Raymond (1973). "Saturated fat in the diet and serum cholesterol concentration: a critical examination of the literature" (PDF). Am J Clin Nutr. 26 (5): 524–555. doi:10.1093/ajcn/26.5.524. PMID 4573412.
  51. De Meester, Fabien, Sherma Zibadi and Ronald Ross Watson (June 7, 2010). Modern Dietary Fat Intakes in Disease Promotion, Springer Science & Business Media via Google Books. ISBN 1603275711, p. 110, retrieved February 19, 2015
  52. Teicholz, p. 58–59.
  53. Mann George V (1977). "Diet-Heart: End of an Era". N Engl J Med. 297 (12): 644–650. doi:10.1056/NEJM197709222971206. PMID 197407.
  54. Mann George V (1977). "Diet and Obesity". N Engl J Med. 296 (14): 812. doi:10.1056/NEJM197704072961411. PMID 840281.
  55. "George V. Mann: Obituary". Legacy.com, retrieved February 17, 2015
  56. Blackburn, Henry. "George Mann's Editorial on 'Diet-Heart: End of an Era?' A Reply". Heart Attack Prevention: A History of Cardiovascular Disease Epidemiology. Regents of the University of Minnesota. Retrieved 17 April 2017.
  57. Keys A (1971). "Sucrose in the diet and coronary heart disease". Atherosclerosis. 14 (2): 193–202. doi:10.1016/0021-9150(71)90049-9. PMID 4940760.
  58. Yudkin, John. (2012 [1972]). Pure, White and Deadly. Penguin [Davis-Poynter]. ISBN 978-0-241-96528-3
  59. Taubes (2007)
  60. Ravnskov (2002)
  61. Uffe Ravnskov (MD, PhD)Cholesterol Myths lecture via YouTube, retrieved October 31, 2017
  62. Teicholz, p. 45.
  63. Taubes (2001) Gary Taubes on Cholesterol and Science Practices; interview via YouTube, retrieved October 31, 2017
  64. Taubes, Gary (2001). Nutrition: The Soft Science of Dietary Fat
  65. Taubes, Gary. (July 7, 2002). "What if It's All Been a Big Fat Lie?". The New York Times. Retrieved March 10, 2015.
  66. Taubes (2007) Good Calories, Bad Calories; Talks at Google via YouTube, retrieved October 31, 2017
  67. Taubes, Gary (2010) Why We Get Fat; Santa Cruz County Office of Education via YouTube, retrieved October 31, 2017
  68. Taubes (2007) pp.31-3, p.22, p.160
  69. Taubes (2016) p.166ff
  70. Schomer, Stephanie. "The Sweet Lowdown: Exposing the Unhealthy Truth About Sugar What the doctor leading the charge against one of our biggest dietary enemies—sugar—wants you to know". Ophra.com. HARPO PRODUCTIONS, INC. Retrieved 31 October 2017.
  71. Lustig, Robert (July 30, 2009). "Sugar: The Bitter Truth", University of California Television (UCTV) via YouTube, retrieved February 20, 2015
  72. Lustig, Robert, M.D., M.S.L. (2012). Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease, Plume (Penguin), ISBN 978-0-14-218043-3, pp. 110-111.
  73. Te Morenga, L. A.; Howatson, A. J.; Jones, R. M.; Mann, J. (2014). "Dietary sugars and cardiometabolic risk: systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids". American Journal of Clinical Nutrition. 100 (1): 65–79. doi:10.3945/ajcn.113.081521. ISSN 0002-9165. PMID 24808490.
  74. Howard, B.V; Wylie-Rosett, J. (2002). "Sugar and cardiovascular disease: A statement for healthcare professionals from the Committee on Nutrition of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association". Circulation. 106 (4): 523–7. doi:10.1161/01.cir.0000019552.77778.04. PMID 12135957.
  75. Zelman K (2011). "The Great Fat Debate: A Closer Look at the Controversy—Questioning the Validity of Age-Old Dietary Guidance". Journal of the American Dietetic Association. 111 (5): 655–658. doi:10.1016/j.jada.2011.03.026. PMID 21515106.
  76. Frank Hu and Alice Lichtenstein (September 16–17, 2014) in 2015 Dietary Guidelines Advisory Committee Meeting 5 (event starts at 4:14) and Day 1 Meeting Summary (PDF). U.S. Department of Health and Human Service and U.S. Department of Agriculture. Retrieved March 12, 2015
  77. Millen, Barbara E. (chair) (February 2015). Scientific Report of the 2015 Dietary Guidelines Advisory Committee, Office of Disease Prevention and Health Promotion, p. 17 line 626, 640., and Part D, p. 11, line 407, and "Part A. Executive Summary" p. 9 line 347-8., retrieved February 22, 2015
  78. Paturel, Amy (2014). "Is Butter Back? The Truth About Saturated Fats". WebMD. Retrieved June 12, 2015.
  79. Chowdhury Rajiv; et al. (2014). "Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis". Annals of Internal Medicine. 160 (6): 398–406. doi:10.7326/M13-1788. PMID 24723079.
  80. Kupferschmidt, Kai (March 24, 2014) "Scientists Fix Errors in Controversial Paper About Saturated Fats", Science Insider, Science, retrieved February 22, 2015.
  81. Sacks, Frank M.; Lichtenstein, Alice H.; Wu, Jason H.Y.; Appel, Lawrence J.; Creager, Mark A.; Kris-Etherton, Penny M.; Miller, Michael; Rimm, Eric B.; Rudel, Lawrence L.; Robinson, Jennifer G.; Stone, Neil J.; Van Horn, Linda V. (15 June 2017). "Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association". Circulation. 136 (3): e1–e23. doi:10.1161/CIR.0000000000000510. PMID 28620111.
  82. Pett, Kahn, Willett, Katz (2017). "Ancel Keys and the Seven Countries Study: An Evidence-based Response to Revisionist Histories" (PDF). True Health Initiative. Retrieved August 29, 2018.CS1 maint: multiple names: authors list (link)

References
  • Yudkin, John (1972). Pure, White and Deadly: The Problem of Sugar. London: Davis-Poynter. ISBN 978-0706700565. OCLC 571307.
  • Taubes, Gary (2001). "NUTRITION: The Soft Science of Dietary Fat" (PDF). Science. 291 (5513): 2536–2545. doi:10.1126/science.291.5513.2536. Retrieved 26 October 2017.
  • Ravnskov, Uffe (2000). The Cholesterol Myths: Exposing the Fallacy That Cholesterol and Saturated Fat Cause Heart Disease. White Plains, MD: NewTrends Publishing. ISBN 978-0967089713.
  • Ravnskov, Uffe (2002). "A hypothesis out-of-date: The diet–heart idea" (PDF). Journal of Clinical Epidemiology. 55: 1057–1063. doi:10.1016/s0895-4356(02)00504-8.
  • Taubes, Gary (2007). Good Calories, Bad Calories: Challenging the Conventional Wisdom on Diet, Weight Control, and Disease. New York: Alfred A. Knopf. ISBN 978-1-4000-4078-0.
  • Phinney, Stephen D.; Volek, Jeff (2011). The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-Saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable. Beyond Obesity LLC. ISBN 978-0983490708.
  • Willett, Walter C. (2012). Nutritional Epidemiology (Monographs in Epidemiology and Biostatistics). Oxford: Oxford University Press. ISBN 978-0199754038.
  • Ottoboni, Alice; Ottoboni, Fred (2013). The Modern Nutritional Diseases: and How to Prevent Them. Vincente Books. ISBN 978-0915241057.
  • Lustig, Robert (2014). Fat Chance: The Hidden Truth About Sugar, Obesity and Disease. London: Harper Collins.
  • Moore, Jimmy; Westman, Eric (2014). Keto Clarity: Your Definitive Guide to the Benefits of a Low-Carb, High-Fat Diet. Victory Belt Publishing. ISBN 978-1628600070.
  • Teicholz, Nina (2014). The Big Fat Surprise: Why Butter, Meat & Cheese Belong in a Healthy Diet. New York: Simon & Schuster Paperbacks. ISBN 978-1-4516-2443-4.
  • Yudkin, John; Lustig, Robert (2016). Pure, White and Deadly: How Sugar Is Killing Us and What We Can Do to Stop It. London: Penguin Life. ISBN 978-0241257456.
  • Fung, Jason; Noakes, Timothy (2016). The Obesity Code: Unlocking the Secrets of Weight Loss. Vancouver: Greystone Books. ISBN 978-1771641258.
  • Taubes, Gary (2016). The Case Against Sugar. New York: Alfred A. Knopf. ISBN 978-1846276378.
  • Rosch, Paul J.; Harcombe, Zoë (2016). Fat and Cholesterol Don't Cause Heart Attacks and Statins are Not The Solution. Columbus Publishing. ISBN 978-1907797538.
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