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The Cholesterol Myths by Uffe Ravnskov, M.D., Ph.D.

References

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2. Craig WE, Palomaki GE, Haddow JE. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. British Medical Journal 1989;298:784-788.

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6. Pocock SJ and others. High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men. British Medical Journal 1986;292:515-519.

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8. Pocock SJ, Shaper AG, Phillips AN. Concentrations of high density lipoprotein cholesterol, triglycerides, and total cholesterol in ischaemic heart disease. British Medical Journal 298, 998-1002, 1989.

9. National Research Council. Diet and health. Implications for reducing chronic disease risk. Washington D.C.: National Academy Press, 1989, page 166

10. Medalie JH and others. Five-year myocardial infarction incidence-II. Association of single variables to age and birthplace. Journal of Chronic Diseases 1973;26:329-349.

11. Gordon T. and others. High density lipoprotein as a protective factor against coronary heart disease. American Journal of Medicine 1977;62:707-714.

12. Watkins LO and others. Racial differences in high-density lipoprotein cholesterol and coronary heart disease incidence in the usual-care group of the multiple risk factor intervention trial. American Journal of Cardiology 1987;57:538-545.

13. The Expert Panel. Report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Archives of Internal Medicine 1988;148:36-69.

14. Kannel WB and others. Optimal resources for primary prevention of atherosclerotic diseases. Atherosclerosis study group. Circulation 1984;70:157A-205A.

15. Grundy SM. Cholesterol and coronary heart disease: a new era. JAMA 1986;256:2849-2858.

16. Hulley SB, Rhoads GG. The plasma lipoproteins as risk factors: comparison of electrophoretic and ultracentrifugation results. Metabolism 1982;31:773-777.

17. The Multiple Risk Factor Intervention Trial (MR.FIT), the Newcastle trial, the Lipid Research Clinic's trial, and the Helsinki Heart Study.

18. Yaari S and others. Associations of serum high density lipoprotein and total cholesterol with total, cardiovascular, and cancer mortality in a 7-year prospective study of 10000 men. The Lancet 1981;1:1011-1015.
- Ancel Keys. Seven Countries. A multivariate analysis of death and coronary heart disease. Harvard University Press 1980.

19. Rhoads GG, Gulbrandsen CL, Kagan A. Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. New England Journal of Medicine 1976;294:293 298.
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20. Conference on the health effects of blood lipids: Optimal distributions for populations. Workshop report: Epidemiological section. Preventive Medicine 1979;8:612. No LDL data were presented in that report either.

21. Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Annals of Internal Medicine 1979;90:85 91.

22. Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Scientific American 1984;251:52-60.

23. For more details, read the papers by William Stehbens

24. Ravnskov U. An elevated serum cholesterol is secondary, not causal, in coronary heart disease. Medical Hypotheses 1991;36:238-41.

25. Landé KE, Sperry WM. Human atherosclerosis in relation to the cholesterol content of the blood serum. Archives of Pathology 1936;22:301-312.

26. Epstein FH, Ostrander LD. Detection of individual susceptibility toward coronary disease. Progress of Cardiovascular Diseases 1971;13:324-342. ”An association between cholesterol concentration and coronary atherosclerosis was also recognized among individuals without the extreme manifestations of typical hyperlipidemia or hypercholesterol-emia”, the authors wrote, a statement in conflict with the data and the conclusions of the paper.

27. Paterson JC, Armstrong R, Armstrong EC. Serum lipid levels and the severity of coronary and cerebral atherosclerosis in adequately nourished men, 60 to 69 years of age. Circulation 1963;27:229-236.

28. Mathur KS, and others. Serum cholesterol and atherosclerosis in man. Circulation 1961;23:847-852.

29. Marek Z, Jaegermann K, Ciba T. Atherosclerosis and levels of serum cholesterol in postmortem investigations. American Heart Journal 1962;63: 768-774.

30. Méndez J, Tejada C. Relationship between serum lipids and aortic atherosclerotic lesions in sudden accidental deaths in Guatemala City. American Journal of Clinical Nutrition 1967;20:1113-1117.

31. Cabin HS, Roberts WC. Relation of serum total cholesterol and triglyceride levels to the amount and extent of coronary arterial narrowing by atherosclerotic plaque in coronary heart disease. American Journal of Medicine 1982;73:227-234.

32. Feinleib M, and others. The relation of antemortem characteristics to cardiovascular findings at necropsy. The Framingham study. Atherosclerosis 1979;34:145-157.

33. Pearson TA. Coronary arteriography in the study of the epidemiology of coronary artery disease. Epidemiol. Rev. 1984;6:140-166.
In his review Pearson mentions a number of angiographic studies which he claimed had found a relationship between blood cholesterol levels and degrees of atherosclerosis. But three of them found no relationship; one of them is reference 34, the other two are: Nitter-Hauge S, Enge I. Relation between blood lipid levels and angiographically evaluated obstructions in coronary arteries. British Heart Journal 1973;35:791-795, and Barboriak JJ, and others. Coronary artery occlusion and blood lipids. American Heart Journal 1974;87:716-721.
An unsupportive study was ignored by Pearson: Fuster V, and others. Arteriographic patterns early in the onset of the coronary syndromes. British Heart Journal 1975;37:1250-1255.

34. Cramér K, Paulin S, Werkö L. Coronary angiographic findings in correlation with age, body weight, blood pressure, serum lipids, and smoking habits. Circulation 1966;33:888-900.

35. Gore I, Hirst AE, Koseki Y. Comparison of aaortic atherosclerosis in the United States, Japan, and Guatemala. American Journal of Clinical Nutrition 1959;7:50-54.

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37. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterol concentration: time to think again. British Medical Journal 1991;303:953-957.

38. Shaper AG. Cardiovascular studies in the Samburu tribe of northern Kenya. American Heart Journal 1962;63:437-442.

39. Mann GV, Shaffer RD, Sandstead HH. Cardiovascular disease in the Masai. Journal of Atherosclerosis Research 1964;4:289-312.

40. Lapiccirella V., and others. Enquête clinique, biologique et cardiogra-phique parmi les tribus nomades de la Somalie qui se nourissent seule-ment de lait. Bulletin of the World Health Organization 1962;27: 681-697.

41. Day J, and others. Anthropometric, physiological and biochemical differences between urban and rural Maasai. Atherosclerosis 1976;23:357-361.

42. Nichols AB, and others. Daily nutritional intake and serum lipid levels. The Tecumseh study. American Journal of Clinical Nutrition 1976;29:1384-1392.

43. Weidman WH, and others. Nutrient intake and serum cholesterol level in normal children 6 to 16 years of age. Pediatrics 1978;61:354-359.

44. Frank GC, Berenson GS, Webber LS. Dietary studies and the relationship of diet to cardiovascular disease risk factor variables in 10-year-old children - the Bogalusa heart study. American Journal of Clinical Nutrition 1978;31:328-340.
- After having divided the children into three groups according to their blood cholesterol values the researchers found that the children with the lowest values ate less fat, both saturated and unsaturated, than the children with the intermediate and the highest cholesterol values. No difference was found between the two latter groups. The ratio between saturated and polyunsaturated fat was almost identical in all groups, however. This ratio, considered the best measure of the effect of dietary fat on blood cholesterol, was not calculated in the tables, nor was it mentioned in the text. Here the authors admitted on the one hand that the diet possibly played only a minor role in the development of atherosclerosis; on the other hand they said there was, ”as might be expected”, a relationship between saturated fat and blood cholesterol. And they added that ”such studies do reinforce the need for seriously considering general modifications of food patterns at a young age”.

45. Morris JN, and others. Diet and plasma cholesterol in 99 bank men. British Medical Journal 1963;1:571-576.

46. Kroneld R, and others. Hälsobeteende och riskfaktorer för hjärt- och kärlsjukdomar i östra och sydvästra Finland. Suomen Lääkärilehti 1990;45:735-739.

47. Kahn HA, and others. Serum cholesterol: Its distribution and association with dietary and other variables in a survey of 10,000 men. Israel Journal of the Medical Sciences 1969;5:1117 1127.
- Jeremyah Stamler's group performed a similar study on 1900 middle-aged men. This study is impossible for anyone but statisticians to evaluate, since absolute figures were absent, and not even simple correlation coefficients were given, except for the relationship between Keys'and Hegstedts formula. The relationship between the diet and the risk of dying from coronary heart disease after the age of 19 was also studied, but again without giving any figures. The amount of saturated fat in the diet did not show any relationship with the risk of dying from coronary heart disease, the authors admitted, but they added that it was not possible to draw conclusions from only one study; if their results were seen ”within the context of the total literature”, they supported the diet-heart idea. (Shekelle RB., and others. Diet, serum cholesterol, and death from coronary heart disease. The Western Electric Study. New England Journal of Medicine 1981;304:65-70.

48. Balogh M, Kahn HA, Medalie JH. Random repeat 24-hour dietary recalls. American Journal of Clinical Nutrition 1971;24:304 310.

49. Keys A. Atherosclerosis: a problem in newer public health. Journal of Mount Sinai Hospital NY 1953;20:118-39.

50. Yerushalmy J, Hilleboe HE. Fat in the diet and mortality from heart disease. A methodologic note. New York State Journal of Medicine 1957;57:2343-54.

51. Keys A. Coronary heart disease in seven countries. Circulation 1970;41 (suppl 1):1-211.

52. Jacobs D, and others. 1992. Report of the conference on low blood cholesterol: mortality associations. Circulation 1992;86:1046-60.

53. Grundy SM. Multifactorial etiology of hypercholesterolemia. Implications for prevention of coronary heart disease. Arteriosclerosis 1991;11:1619-.

54. Marmot MG, Booth M, Beral V. International trends in heart disease mortality. Atherosclerosis Reviews 1982;9:19-27.

55. Guberan E. Surprising decline of cardiovascular mortality in Switzerland: 1951-1976. Journal of Epidemiology and Community Health 1979.;33:114-20.

56. Yudkin J. Diet and coronary thrombosis. Hypothesis and fact. The Lancet 1957;2:155-62.

57. Slattery ML, Randall DE. Trends in coronary heart disease mortality and food consumption in the United States between 1909 and 1980. American Journal of Clinical Nutrition 47;1060-70.

58. Sytkowski PA, Kannel WB, D’Agostino RB. Changes in risk factors and the decline in mortality from cardiovascular disease. New England Journal of Medicine 1990;322:1635-41.

59. Marmot MG, and others. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: prevalence of coronary and hypertensive heart disease and associated risk factors. American Journal of Epidemiology 1975;102:514-25.

60. Marmot MG, Syme SL. Acculturation and coronary heart disease in Japanese-Americans. American Journal of Epidemiology 1976;104:225-47.

61. Paul O and others. A longitudinal study of coronary heart disease. Circulation 1963;28:20-31.

62. Medalie JH and others. Five-year myocardial infarction incidence-II. Association of single variables to age and birthplace. Journal of Chronic Diseases 1973;26: 329-49.

63. Yano K and others. Dietary intake and the risk of coronary heart disease in Japanese men living in Hawaii. American Journal of Clinical Nutrition 1978;31:1270-1279.

64. Garcia-Palmieri MR and others. Relationship of dietary intake to subsequent coronary heart disease incidence: the Puerto Rico heart health program. American Journal of Clinical Nutrition 1980;33: 1818-1827.

65. Gordon T, and others. Diet and its relation to coronary heart disease and death in three populations. Circulation 1981;63;500-515.

66. McGee DL and others. Ten-year incidence of coronary heart disease in the Honolulu heart program. Relationship to nutrient intake. American Journal of Epidemiology 1984;119:667-676.

67. Kromhout D, Coulander CDL. Diet, prevalence and 10-year mortality from coronary heart disease in 871 middle-aged men. American Journal of Epidemiology 1984;119:733-741.

68. Kushi LH and others. Diet and 20-year mortality from coronary heart disease. The Ireland-Boston diet-heart study. New England Journal of Medicine 1985;312: 811-818.

69. Khaw K, Barrett-Connor E. Dietary fiber and reduced ischemic heart disease mortality rates in men and women: a 12-year prospective study. American Journal of Epidemiology 1987;126:1093-1102.

70. Posner BM and others. Dietary lipid predictors of coronary heart disease in men. Archives of Internal Medicine 1991;151:1181-7.

71. Zukel WJ and others. A short-term community study of the epidemiology of coronary heart disease. A preliminary report of the North Dakota study. American Journal of Public Health 1959;49:1630-1639.

72. Finegan A and others. Diet and coronary heart disease: dietary analysis on 100 male patients. American Journal of Clinical Nutrition 1968;21:143-148.

73. Bassett DR and others. Coronary Heart disease in Hawaii: dietary intake, depot fat, "stress," smoking, and energy balance in Hawaiian and Japanese men. American Journal of Clinical Nutrition 1969;22:1483-1503.

74. Scrimshaw NS, Guzmán MA. Diet and atherosclerosis. Laboratory Investigations 1968;18:623-8.

75. Moore MC, Guzmán MA, Schilling PE, Strong JP. Dietary-atherosclerosis study on deceased persons. Journal of the American Dietician Association 1976;68:216-23.
- Sorlie PD, Garcia-Palmieri MR, Castillo-Staab MI, Costas R, Oalmann MC, Havlik R. The relation of antemortem factors to atherosclerosis at autopsy. The Puerto Rico Heart Health Program. American Journal of Pathology 1981;103:345-52.
- Reed DM, MacLean CJ, Hayashi T. Predictors of atherosclerosis in the Honolulu heart program. I. Biologic, dietary, and lifestyle characteristics. American Journal of Epidemiology 1987;126:214-25.
- Reed DM, and others. A prospective study of cerebral artery atherosclerosis. Stroke 1988;19:820-5.

76. Research committee. Low-fat diet in myocardial infarction. A controlled trial. The Lancet 1965;2:501-4.
- Rose GA, Thomson WB, Williams RT. Corn oil in treatment of ischaemic heart disease. British Medical Journal 1965;i:1531-3.
- Research committee to the medical research council. Controlled trial of soya-bean oil in myocardial infarction. The Lancet 1968;ii:693-700.
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- Woodhill JM, and others. Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Adv Exp Med Biol 1978;109:317-30.
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- Frantz ID, and others. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis 1989;9:129-35.

77. de Lorgeril M, and others. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. The Lancet 1994;343:1454-9.

78. Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitiative review of primary prevention trials. British Medical Journal 1990;301:309-314.

79. Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. British Medical Journal 1992;305:15-19.

80. Davey Smith G, Song F, Sheldon TA. Cholesterol lowering and mortality: the importance of considering initial level of risk. British Medical Journal 1993;306:1367-1373.

81. Bonneux L, Barendregt JJ. Ischaemic heart disease and cholesterol. There´s more to heart disease than cholesterol. British Medical Journal 1994;308:1038.
- Ravnskov U. Optimism about drug treatment is unjustified. British Medical Journal 1994;308:same issue.

82. Ravnskov U. Implications of 4S evidence on baseline lipid levels. The Lancet 1995;346:181.
- Massy ZA, Keane WF, Kasiske BL. Inhibition of the mevalonate pathway: benefits beyond cholesterol reduction? The Lancet 1996;347:102-103.
- Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. The Lancet 1996;348:1079-1082.

83. Hidaka Y, Eda T, Yonemoto M, Kamei T. Inhibition of cultured vascular smooth muscle cell migration by simvastatin (MK 733). Atherosclerosis 1992;95:87-94.

84. Meiser BM, and others. Simvastatin decreases accelerated graft vessel disease after heart transplantation in an animal model. Transplantation Proceedings 1993;25:2077-9.

85. Soma MR, and others. HMG CoA reductase inhibitors. In vivo effects on carotid intimal thickening in normocholesterolemic rabbits. Arteriosclerosis 13, 571-8, 1993.

86. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). The Lancet 1994;344:1383-1389.

87. Sacks FM and others. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New England Journal of Medicine 1996;335:1001-1009.

88. Shepherd J and others. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. New England Journal of Medicine 1995;333:1301-1307.

90. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA 1996;275:55-60.

91. Gurr MI. Dietary lipids and coronary heart disease: old evidence, new perspective. Progress of Lipid Research 1992;31:195-243.

92. Mann GV. Diet-heart: end of an era. New England Journal of Medicine 1977;297:644-650.

93. Mann GV. Coronary heart disease - "Doing the wrong things." Nutrition Today 1985;July/August:12-14.

94. Oliver MF. Dietary fat and coronary heart disease. British Heart Journal 1987;58:423-428.

95. Oliver MF. Might treatment of hypercholesterolaemia increase non-cardiac mortality? The Lancet 1991;337:1529-1531.

96. Oliver MF. Consensus or nonsensus conferences on coronary heart disease. The Lancet 1985;1:1087-1089.
- Oliver MF. Dietary fat and coronary heart disease. British Heart Journal 1987;58:423-428.
- Oliver MF. Reducing cholesterol does not reduce mortality. Journal of the American College of Cardiology 1988;12:814-7.
- Oliver MF. Doubts about preventing coronary heart disease. Multiple interventions in middle aged men may do more harm than good. British Medical Journal 1992;304:393-394.
- Oliver MF. National cholesterol policies. European Heart Journal 1993;14:581-583.

97. Pinckney ER and Pinckney C. The Cholesterol Controversy. Sherbourne Press, Los Angeles 1973.

98. Reiser R. Saturated fat in the diet and serum cholesterol concentration: a critical examination of the literature. American Journal of Clinical Nutrition 1973;26:524-555.

99. Reiser R. A commentary on the rationale of the diet-heart statement of the American Heart Association. American Journal of Clinical Nutrition 1984;40:654-658.

100. Friedman M, Rosenman RH, Byers SO. Deranged cholesterol metabolism and its possible relationship to human atherosclerosis: a review. Journal of Gerontology 1955;10:60-85.

101. Rosenman RH. The questionable roles of the diet and serum cholesterol in the incidence of ischemic heart disease and its 20th century changes. Homeostasis 1993;34:1-43.

102. Smith RL. Diet, blood cholesterol and coronary heart disease: a critical review of the literature. Vector Enterprises. Vol. 1, 1989; vol. 2, 1991.
- Smith RL. The Cholesterol conspiracy. Warren H. Green. St. Louis, 1991.
- Smith RL. Dietary lipids and heart disease. The contriving of a relationship. American Clinical Laboratory 1989;Nov:26-33.

103. Stehbens W. An appraisal of cholesterol feeding in experimental atherogenesis. Progress in Cardiovascular Diseases 1986;29:107-128.

104. Stehbens WE. An appraisal of the epidemic rise of coronary heart disease and its decline. The Lancet 1987;1:606-611.

105. Stehbens WE. Serum cholesterol and atherosclerosis. New Zealand Medical Journal 1988;101:795-797.

106. Stehbens WE. Diet and atherogenesis. Nutrition Reviews 1989;47:1-12.
- Stehbens WE. The lipid hypothesis and the role of hemodynamics in atherogenesis. Progress in Cardiovascular Diseases 1990;33:119-136.
- Stehbens WE. Limitations of the epidemiological method in coronary heart disease. International Journal of Epidemiology 1991;20:818-820.
- Stehbens WE. The hypothetical epidemic of coronary heart disease and atherosclerosis. Medical Hypotheses 1995;45:449-454.

107. Werkö L. Risk factors and coronary heart disease - facts or fancy? American Heart Journal 1976;91:87-98.

108. Werkö L. Prevention of heart attacks. Annals of Clinical Research 1979;11: 71-79.
- Werkö L. Diet, lipids and heart attacks. Acta Medica Scandinavica 1979;206: 435-439.
- Werkö L. The enigma of coronary heart disease and its prevention. Acta Medica Scandinavica 1987;221:323-333.

109. Other critical papers:

110. The Lipid Research Clinic's coronary primary prevention trial results. 1. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-64.

111. Miettinen TA, and others. Multifactorial primary prevention of cardiovascular diseases in middle-aged men. JAMA 1985;254:2097-2102.

112. Marmot MG, and others. Epidemiologic studies of coronary heart disease and stroke in japanese men living in Japan, Hawaii and California: prevalence of coronary and hypertensive heart disease and associated risk factors. American Journal of Epidemiology 1975;102:514-525.

113. Marmot MG, Syme SL. Acculturation and coronary heart disease in Japanese-Americans. American Journal of Epidemiology 1976;104:225-247.

114. Gotto AM, and others. The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. Circulation 1990;81:1721-1733.

115. Anderson KM, Castelli WP, Levy D. Cholesterol and mortality. 30 years of follow-up from the Framingham study. JAMA 1987;257:2176-2180.

116. Ravnskov U. Quotation bias in reviews of the diet-heart idea. Journal of Clinical Epidemiology 1995;48:713-719.

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© Uffe Ravnskov March 1997