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 1970 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] Describing online comments on his review of a book about the Atkins diet, T. Colin Campbell wrote in 2014 that "...an irrationality...infuses both sides of this debate (better characterized as a shouting match)."[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 the results of larger studies that reported earlier on the predictive value for heart attack of several characteristics measured in health, 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] Keys's 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 USA, with 75% and highest in one of the Japanese cohorts, with 100%.[8] The Seven Countries Study has continued for more than 50 years.

Major findings

The Seven Countries Study showed that the risk and rates of heart attack and stroke cardiovascular risk both at the population level and at the individual level was directly and independently related to the level of total serum cholesterol. It demonstrated that the association between blood cholesterol level and coronary heart disease (CHD) risk from 5 to 40 years follow-up is found consistently across different cultures. Cholesterol and obesity were associated with increased mortality from cancer.[9][10][11]

Objective data on CVD health in relation to the Mediterranean diet originated from the Seven Countries Study. 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. When investigated further, the importance of the eating pattern characterized as the Mediterranean diet became clear.[12][13][14][15][16] What exactly is meant by "Mediterranean Diet" today, and its benefits, was detailed by Antonia Trichopoulou and Anna Ferro-Luzzi. 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.[17][18][19][20][21][22]

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 increases risk of heart disease.[23][24] 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.[25]

The Seven Countries Study, along with other important large studies, e.g. the Framingham Heart Study, Nurses' Health Study, Women's Health Initiative, confirmed not only the importance of healthy diet, but also of not being overweight or obese, and of regular exercise, in maintaining good general health. It also showed that regular exercise and dietary fibre strongly influence body fat levels . These and other research findings made it possible to calculate the probability of an individual developing coronary heart disease in the future.[26][27][28][29]

The Seven Countries Study demonstrated that elevated blood pressure (hypertension) increases risk of coronary heart disease and stroke. It showed that the mortality rate after a coronary heart disease event or stroke can be influenced by the level of hypertension. In several cohorts of the study, stroke deaths exceeded deaths from coronary heart disease.[30][31]

The Seven Countries Study showed that differences in overall mortality between the different regions of the world are largely accounted for by the variation in cardiovascular mortality.[15]

The Seven Countries Study confirmed 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 important studies about smoking, e.g. the Framingham Heart Study and the British Doctors Study.[32][33][34][35]

The Seven Countries Study revealed the importance of good cardiovascular health in avoiding 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.[36]

Criticism

Early criticism

Scientists differed on the best predictors of heart disease. In the history according to Gary Taubes, in 1950 in Science, John Gofman described separating lipoproteins into different densities in the University of California, Berkeley, ultracentrifuge.[37] In 1952 as part of a panel with Keys, Gofman agreed that reducing fat in the diet might help some heart patients[38] (and in this same issue of Circulation Keys explained that dietary cholesterol is not a factor in humans[39]). In 1956 Gofman wrote that an atherogenic index (the combined levels of LDL and VLDL) predicted atherosclerosis and heart disease.[40] 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."[41]

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".[42] In 1957 a distinguished pioneer in lipid research, Edward H. "Pete" Ahrens, Jr., 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."[43]

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, 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.[44] In 1957 when they published their critique,[45] 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".[46] 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.[47]

Contemporary criticism

Several scientists stepped forward at the time to disagree with Keys's conclusions. Published in 1973 and including his critique of Keys's work,[48] Raymond Reiser found methodological and interpretational errors in a review of forty trials.[49] 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.[50] Although he is widely misquoted to this day (for example in Breitbart[51]), George V. Mann did not say in the New England Journal of Medicine (NEJM) in 1977 that the lipid theory is "the greatest scam in the history of medicine".[52][53] 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.[54] In NEJM in 1977, he dismissed Keys's work of 1953, "The naïveté... is now a classroom demonstration."[53]

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.[55] The next year Yudkin retired to write Pure, White and Deadly.[56]

Debate since 2000

In 2000, Uffe Ravnskov published his book The Cholesterol Myths and went on to found The International Network of Cholesterol Skeptics.[57]

In his 2009 video Sugar: The Bitter Truth, Robert Lustig says his purpose is to debunk the prior thirty years of nutrition research, specifically Keys.[58] 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.[59]

Controversy continues about the study itself, 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][61] Reigniting the debate[62] was a meta-analysis in 2014 finding that "current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats".[63] However, this meta-study has also met with controversy and was corrected, with Willett continuing to defend reduced saturated fat in the diet.[64]

James J DiNicolantonio, one of the associate editors of BMJ's Open Heart, authored or co-authored a number of papers in 2014 with scientists who believe a diet including saturated fat does no harm to human hearts.[65][66][67] Lustig, Yudkin, and DiNicolantonio mention Keys by name[56][59][66] and most mention the Seven Countries Study, as do recent books by two journalists, Gary Taubes and Nina Teicholz.

Taubes wrote two bestsellers, Good Calories, Bad Calories in 2007[68] followed by Why We Get Fat in 2010–2011.[69] Part I of Good Calories, Bad Calories relates how we came to believe dietary fat causes heart disease (Part II offers that carbohydrates cause the chronic diseases of civilization, and Part III explains obesity and calories).[70] Adding interviews, Teicholz's The Big Fat Surprise closely follows Taubes Part I, urging a second look at the idea that saturated fat causes heart disease.

Taubes became a regular contributor to The New York Times opinion pages[71] and twice the paper gave Taubes a lead feature story in its Sunday magazine: "What if It's All Been a Big Fat Lie?" (2002)[72] and "Is Sugar Toxic?" (2011).[73]

Campbell, who mentions the Seven Countries Study and recounts meeting Keys twice,[74] calls Taubes "by far, the most eloquent and influential present-day spokesperson for the low-carb movement."[75] In his book, The Low-Carb Fraud (2014), Campbell says that Taubes was right to "demolish" the counting calories myth, and that his history of the past five decades of nutrition science is well done (although later termed a distortion[76]).[77] An advocate for a whole food plant-based (WFPB) diet, Campbell points out that Taubes uses "a bit of sleight of hand" to say that, "refined sugar is bad, therefore all foods that contain sugars (i.e. carbs) are bad."[78]

In September 2014, Frank Hu led the 2015 Dietary Guidelines Advisory Committee's report on saturated fat and cardiovascular disease. 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.[79] 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."[62]

As of 2016, WebMD and the Mayo Clinic both recommended that its readers avoid or minimize saturated fats and replace them with polyunsaturated or monounsaturated fats.[80][81]

References

Notes

  1. ↑ Taubes, p. 31.
  2. ↑ Teicholz, p. 36.
  3. ↑ Gary Taubes quotes Blackburn in Good Calories, Bad Calories p. 22, from: Blackburn, Henry, MD. Contrasting Professional Views on Atherosclerosis and Coronary Disease. N Engl J Med 1975; 292:105-107 January 9, 1975 doi:10.1056/NEJM197501092920214
  4. ↑ Campbell, T. Colin, PhD (October 6, 2014). "Low Carb Hot Air—Again, again and again!". T. Colin Campbell Center for Nutrition Studies. Retrieved June 13, 2015.
  5. ↑ Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E., "Coronary Heart Disease among Minnesota Business and Professional Men Followed Fifteen Years", Circulation 28:381-95 (Sept 1963).
  6. 1 2 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.
  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. ↑ D. Kromhout, "Serum cholesterol in cross-cultural perspective: The Seven Countries Study" Acta Cardiological 54:3:155-8 (June 1999)
  10. ↑ A. Menotti, M. Lanti, D. Kromhout, H. Blackburn, D. Jacobs, A. Nissinen, A. Dontas, A. Kafatos, S. Nedeljkovic, H. Adachi, "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 (Dec 2008)
  11. ↑ D.B. Panagiotakos, C. Pitsavos, E. Polychronopoulos, C. Chrysohoou, A. Menotti, A. Dontas, C. Stefanadis, "Total serum cholesterol and body mass index in relation to 40-year cancer mortality (the Corfu cohort of the seven countries study)" Cancer Epidemiology, Biomarkers and Prevention 14:7:1797-801 (July 2005)
  12. ↑ Epidemiological studies related to coronary heart disease: characteristics of men aged 40-59 in seven countries. 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. Acta Med Scand Suppl. 1966;460:1-392.
  13. ↑ Coronary heart disease in seven countries. Keys A (Ed). Circulation. 1970 Apr;41(4 Suppl):I 1-200.
  14. ↑ 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.
  15. 1 2 Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries. Menotti A, Keys A, Aravanis C, Blackburn H, Dontas A, Fidanza F, Karvonen MJ, Kromhout D, Nedeljkovic S, Nissinen A, et al. Ann Med. 1989 Jun;21(3):175-9.
  16. ↑ Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA. JAMA. 2004 Sep 22;292(12):1433-9.
  17. ↑ Teicholz, chapter 7.
  18. ↑ Health implications of Mediterranean diets in light of contemporary knowledge. 1. Plant foods and dairy products. Kushi LH, Lenart EB, Willett WC. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1407S-1415S.
  19. ↑ Health implications of Mediterranean diets in light of contemporary knowledge. 2. Meat, wine, fats, and oils. Kushi LH, Lenart EB, Willett WC. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1416S-1427S.
  20. ↑ The Mediterranean diet: science and practice. Willett WC. Public Health Nutr. 2006 Feb;9(1A):105-10.
  21. ↑ Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women. Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB. Circulation. 2009 Mar 3;119(8):1093-100.
  22. ↑ 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
  23. ↑ Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: the Seven Countries Study. Kafatos A, Diacatou A, Voukiklaris G, Nikolakakis N, Vlachonikolis J, Kounali D, Mamalakis G, Dontas AS. Am J Clin Nutr. 1997 Jun;65(6):1882-6.
  24. ↑ Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study. Menotti A, Keys A, Kromhout D, Blackburn H, Aravanis C, Bloemberg B, Buzina R, Dontas A, Fidanza F, Giampaoli S, et al. Eur J Epidemiol. 1993 Sep;9(5):527-36.
  25. ↑ Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort. Martínez-González MA, García-López M, Bes-Rastrollo M, Toledo E, Martínez-Lapiscina EH, Delgado-Rodriguez M, Vazquez Z, Benito S, Beunza JJ. Nutr Metab Cardiovasc Dis. 2010 Jan 20.
  26. ↑ Underweight and overweight in relation to mortality among men aged 40-59 and 50-69 years: the Seven Countries Study. Visscher TL, Seidell JC, Menotti A, Blackburn H, Nissinen A, Feskens EJ, Kromhout D. Am J Epidemiol. 2000 Apr 1;151(7):660-6.
  27. ↑ Saturated fat, vitamin C and smoking predict long-term population all-cause mortality rates in the Seven Countries Study. Kromhout D, Bloemberg B, Feskens E, Menotti A, Nissinen A. Int J Epidemiol. 2000 Apr;29(2):260-5.
  28. ↑ Physical activity and dietary fiber determine population body fat levels: the Seven Countries Study. Kromhout D, Bloemberg B, Seidell JC, Nissinen A, Menotti A. Int J Obes Relat Metab Disord. 2001 Mar;25(3):301-6.
  29. ↑ Probability of middle-aged men developing coronary heart disease in five years. Keys A, Aravanis C, Blackburn H, Van Buchem FS, Buzina R, Djordjevic BS, Fidanza F, Karvonen MJ, Menotti A, Puddu V, Taylor HL. Circulation. 1972 Apr;45(4):815-28.
  30. ↑ The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group. van den Hoogen PC, Feskens EJ, Nagelkerke NJ, Menotti A, Nissinen A, Kromhout D. N Engl J Med. 2000 Jan 6;342(1):1-8.
  31. ↑ Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes. 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. Stroke. 1996 Mar;27(3):381-7.
  32. ↑ 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. Menotti A, Lanti M, Nedeljkovic S, Nissinen A, Kafatos A, Kromhout D. Int J Cardiol. 2006 Jan 13;106(2):157-63.
  33. ↑ Cigarette smoking and mortality risk: twenty-five-year follow-up of the Seven Countries Study. Jacobs DR Jr, Adachi H, Mulder I, Kromhout D, Menotti A, Nissinen A, Blackburn H. Arch Intern Med. 1999 Apr 12;159(7):733-40.
  34. ↑ Mortality in relation to smoking: 50 years' observations on male British doctors. Doll R, Peto R, Boreham J, Sutherland I. BMJ. 2004 Jun 26;328(7455):1519.
  35. ↑ The health risks of smoking. The Framingham Study: 34 years of follow-up. Freund KM, Belanger AJ, D'Agostino RB, Kannel WB. Ann Epidemiol. 1993 Jul;3(4):417-24.
  36. ↑ Cardiovascular risk factors and dementia mortality: 40 years of follow-up in the Seven Countries Study. Alonso A, Jacobs DR Jr, Menotti A, Nissinen A, Dontas A, Kafatos A, Kromhout D. J Neurol Sci. 2009 May 15;280(1-2):79-83.
  37. ↑ Taubes, pp. 153–154.
  38. ↑ Allen, EV (ed.) Katz, LN, Keys, A, and Gofman, JW. Atherosclerosis. A Symposium: Introduction. Circulation. 1952; 5: 98–100 doi:10.1161/01.CIR.5.1.98
  39. ↑ Keys, A. Human Atherosclerosis and the Diet. Circulation. 1952; 5: 115–118 doi:10.1161/01.CIR.5.1.115
  40. ↑ Gofman, JW et al. and 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. 1956; 14: 689–741 doi:10.1161/01.CIR.14.4.689
  41. ↑ Gofman, JW. February 1958. Diet in the prevention and treatment of myocardial infarction. The American Journal of Cardiology. Volume 1, Issue 2, Pages 271–283. doi:http://dx.doi.org/10.1016/0002-9149(58)90058-4
  42. ↑ Taubes, p. 112
  43. ↑ Taubes, p. 158.
  44. ↑ Yerushalmy J, Hilleboe HE. Fat in the diet and mortality from heart disease. A methodologic note. NY State J Med 1957;57:2343–54.
  45. ↑ Weaver Jr., Warren (July 16, 1957) "2 Doubt Fat's Tie to Heart Disease" The New York Times, retrieved February 19, 2015.
  46. ↑ Blackburn, Henry. "Famous Polemics on Diet-Heart Theory" Regents of the University of Minnesota, retrieved February 19, 2015
  47. ↑ Teicholz, pp. 44, 72, 36.
  48. ↑ Reiser, Raymond (May 26, 1973). "Saturated fat in the diet and serum cholesterol concentration: a critical examination of the literature" (PDF) Am J Clin Nutr (American Society for Nutrition), pp. 524-555, retrieved February 21, 2015.
  49. ↑ 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
  50. ↑ Teicholz, p. 58–59.
  51. ↑ Delingpole, James (February 11, 2015). "So butter is good for you. Just like global warming, then." Breitbart, retrieved February 17, 2015
  52. ↑ Mann, George V. M.D. (April 7, 1977). "Diet and Obesity", N Engl J Med (Massachusetts Medical Society) 296:812 doi:10.1056/NEJM197704072961411, retrieved February 17, 2015
  53. 1 2 Mann, George V., Sc.D., M.D. (September 22, 1977). "Diet-Heart: End of an Era" N Engl J Med (Massachusetts Medical Society) 297:644-650 doi:10.1056/NEJM197709222971206, retrieved February 17, 2015
  54. ↑ "George V. Mann: Obituary". Legacy.com, retrieved February 17, 2015
  55. ↑ Keys, A. Sucrose in the diet and coronary heart disease. Atherosclerosis. September–October, 1971 Volume 14, Issue 2, pp. 193–202. doi:http://dx.doi.org/10.1016/0021-9150(71)90049-9
  56. 1 2 Yudkin, John. (2012 [1972]). Pure, White and Deadly. Penguin [Davis-Poynter]. ISBN 978-0-241-96528-3
  57. ↑ Teicholz, p. 45.
  58. ↑ Lustig, Robert (July 30, 2009). "Sugar: The Bitter Truth", University of California Television (UCTV) via YouTube, retrieved February 20, 2015
  59. 1 2 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.
  60. ↑ Taubes, Gary. Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health. Anchor, 2008.
  61. ↑ Uffe Ravnskov. A hypothesis out-of-date: The diet–heart idea. Journal of Clinical Epidemiology 55 (2002) 1057–1063. PII: S0895-4356(02)00504-8. http://www.ravnskov.nu/A%20hypothesis%20out%20of%20date.pdf accessed 18 March 2014
  62. 1 2 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
  63. ↑ Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. Rajiv Chowdhury, MD, PhD; Samantha Warnakula, MPhil; Setor Kunutsor, MD, MSt; Francesca Crowe, PhD; Heather A. Ward, PhD; Laura Johnson, PhD; Oscar H. Franco, MD, PhD; Adam S. Butterworth, PhD; Nita G. Forouhi, MRCP, PhD; Simon G. Thompson, FMedSci; Kay-Tee Khaw, FMedSci; Dariush Mozaffarian, MD, DrPH; John Danesh, FRCP*; and Emanuele Di Angelantonio, MD, PhD. Annals of Internal Medicine. 2014;160(6):398-406-406. doi:10.7326/M13-1788
  64. ↑ Kupferschmidt, Kai (March 24, 2014) "Scientists Fix Errors in Controversial Paper About Saturated Fats", Science Insider, Science, retrieved February 22, 2015.
  65. ↑ DiNicolantonio, James J, and Sean C Lucan (December 10, 2014). The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease. Open Heart, BMJ Publishing Group Ltd & British Cardiovascular Society, retrieved February 22, 2015.
  66. 1 2 DiNicolantonio, James J (2014). The cardiometabolic consequences of replacing saturated fats with carbohydrates or Ω-6 polyunsaturated fats: Do the dietary guidelines have it wrong?, Open Heart. doi:10.1136/openhrt-2013-000032
  67. ↑ Harcombe Z, Baker JS, Cooper SM, et al (accepted December 2, 2014). Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. OpenHeart 2015; 2:e000196. doi:10.1136/openhrt-2014-000196, retrieved February 22, 2015.
  68. ↑ Taubes (2007)
  69. ↑ Taubes, Gary. (2010–2011). Why We Get Fat. Anchor Books (Random House). ISBN 978-0-307-47425-4
  70. ↑ Taubes, p. xxiii.
  71. ↑ Taubes, Gary. (January 27, 2008). "What’s Cholesterol Got to Do With It?", and (June 2, 2012). "Salt, We Misjudged You", and (June 30, 2012). "What Really Makes Us Fat", and (February 8, 2014). "Why Nutrition Is So Confusing". The New York Times. Retrieved March 10, 2015.
  72. ↑ Taubes, Gary. (July 7, 2002). "What if It's All Been a Big Fat Lie?". The New York Times. Retrieved March 10, 2015.
  73. ↑ Taubes, Gary. (April 13, 2011). "Is Sugar Toxic?". The New York Times. Retrieved March 10, 2015.
  74. ↑ Campbell, pp. 31–32.
  75. ↑ Campbell, p. 12.
  76. ↑ Campbell, p. 38.
  77. ↑ Campbell, pp. 13, 15.
  78. ↑ Campbell, pp. 19, 69.
  79. ↑ 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
  80. ↑ Paturel, Amy (2014). "Is Butter Back? The Truth About Saturated Fats". WebMD. Retrieved June 12, 2015.
  81. ↑ Mayo Clinic Staff (February 2, 2016). "Dietary fats: Know which types to choose". Mayo Foundation for Medical Education and Research. Retrieved February 13, 2016.

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