The limits of scientific evidence and the ethics of dietary guidelines

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  • Skeaff and Miller from the local University of Oswego.
  • “ Almost nobody took me seriously,” says Keys. By 1952 Keys was arguing that Americans should reduce their fat consumption by a third, while simultaneously acknowledging that his hypothesis was based more on speculation than data: "direct evidence on the effect of the diet on human arteriosclerosis is very little,” he wrote, “and likely to remain so for some time."
  • “ Almost nobody took me seriously,” says Keys. By 1952 Keys was arguing that Americans should reduce their fat consumption by a third, while simultaneously acknowledging that his hypothesis was based more on speculation than data: "direct evidence on the effect of the diet on human arteriosclerosis is very little,” he wrote, “and likely to remain so for some time."
  • Keys is quoted in Time Magazine saying the report was an “acceptable compromise” with “some undue pussy-footing.”
  • A single paragraph in a four page story notes that that Keys’s hypothesis is “still questioned by some researchers with conflicting ideas of what causes coronary disease.”
  • Can’t dot the I’s, can’t cross the t’s.
  • Particularly important in the diet heart debate, because people’s lives are on the line Preventive medicine targets those of us who believe ourselves to be healthy, only to tell us how we must live to remain healthy. It rests on the presumption that any recommendation is based on the “highest level” of evidence that the proposed intervention will do more good than harm. The method of science is the method of bold conjectures and ingenious and severe attempts to refute them. Karl Popper
  • Between 1957 and 1960 framingham investigators had assessed the diet of 1000 subjects. Notice the length of the citation. 24th volume of 27. Framingham study wasn’t the only one that failed to reveal any correlation between the fat consumed and either cholesterol levels or heart disease. This was true in virtually every study in which diet, cholesterol and heart disease were compared within a single population, be it in Framingham, Puerto Rico, Honolulu, Chicago, Tecumseh, Michigan, Evans County, Georgia, or Israel. Proponents of Keys’s theory insisted that the diets of these populations were too homogenous, and so everyone ate too much fat. The only way to show that fat was responsible, they argued, was by comparing entirely different populations, those with high-fat diets to those with low-fat diets. This might have been true, but perhaps fat just wasn’t the relevant factor.
  • Between 1957 and 1960 framingham investigators had assessed the diet of 1000 subjects. Notice the length of the citation. 24th volume of 27. Framingham study wasn’t the only one that failed to reveal any correlation between the fat consumed and either cholesterol levels or heart disease. This was true in virtually every study in which diet, cholesterol and heart disease were compared within a single population, be it in Framingham, Puerto Rico, Honolulu, Chicago, Tecumseh, Michigan, Evans County, Georgia, or Israel. Proponents of Keys’s theory insisted that the diets of these populations were too homogenous, and so everyone ate too much fat. The only way to show that fat was responsible, they argued, was by comparing entirely different populations, those with high-fat diets to those with low-fat diets. This might have been true, but perhaps fat just wasn’t the relevant factor.
  • Navajo Indians: Page et al. 1956. Irish immigrants: Trulson et al. 1964. African nomads: Mann et al. 1964. Swiss farmers: Gsell and Mayer 1962. Monks: Groen et al. 1962. Keys rationalizations: Keys 1963; Keys 1975.
  • The Ni-Hon-San study (but not really) Men living at a research station in Antarctica Tarhumara Indians in the Mexican highlands Infants with a history of breast-feeding.
  • Turned a negative study into a positive study A sleight of hand, a magic trick?
  • Only two studies. Already known at the time that low-fat diets would be high-carb diets and so would raise triglycerides...
  • “ The first comprehensive statement by any branch of the Federal Government on risk factors in the American diet.”
  • The precautionary principle
  • THE ABILITY TO IGNORE NEGATIVE EVIDENCE IS KEY INCONVENIENT TIMING: RESULTS COME OUT THREE DAYS AFTER MCGOVERN’S PRESS CONFERENCE, ANNOUNCING the “Dietary Goals for the United States,” AND advocating low-fat, high-carbohydrate diets for all Americans. If the New York Times account of the proceedings is accurate, the AHA and the assembled investigators went out of their way to ensure that the new evidence would not cast doubt on Keys’s hypothesis or the new dietary goals. Rather than challenge the theory that excess cholesterol can cause heart disease, the Times reported, “the findings re-emphasize the importance of a fatty diet in precipitating life-threatening hardening of the arteries in most Americans,” which is precisely what they did not do .
  • Studies reported as positive, even when negative: Four of these studies tried to establish relationships between dietary fat and health within populations — in Honolulu, Puerto Rico, Chicago (Stamler and Shekelle’s second Western Electric study) and Framingham, Massachusetts. None of them succeeded. In Honolulu, the researchers followed 7,300 men of Japanese descent and concluded that the men who developed heart disease seemed to eat slightly more fat and saturated fat than those who didn’t, but the men who died seemed to eat slightly less fat and slightly less saturated fat than those who didn’t. This observation was made in Framingham and Puerto Rico as well. In 1981, investigators from the three studies published an article in the journal Circulation discussing the problem. They said it posed a dilemma for dietary advice, but not an insurmountable one. Because the men in Puerto Rico and Honolulu who remained free of heart disease seemed to eat more starches this suggested that it might be a good idea to recommend that we all eat more starch, as McGovern’s “Dietary Goals” actually had. And because the advice should never be to eat more calories, we would have to eat less fat to avoid gaining weight.
  • Studies reported as positive, even when negative: Four of these studies tried to establish relationships between dietary fat and health within populations — in Honolulu, Puerto Rico, Chicago (Stamler and Shekelle’s second Western Electric study) and Framingham, Massachusetts. None of them succeeded. In Honolulu, the researchers followed 7,300 men of Japanese descent and concluded that the men who developed heart disease seemed to eat slightly more fat and saturated fat than those who didn’t, but the men who died seemed to eat slightly less fat and slightly less saturated fat than those who didn’t. This observation was made in Framingham and Puerto Rico as well. In 1981, investigators from the three studies published an article in the journal Circulation discussing the problem. They said it posed a dilemma for dietary advice, but not an insurmountable one. Because the men in Puerto Rico and Honolulu who remained free of heart disease seemed to eat more starches this suggested that it might be a good idea to recommend that we all eat more starch, as McGovern’s “Dietary Goals” actually had. And because the advice should never be to eat more calories, we would have to eat less fat to avoid gaining weight.
  • 12,000 middle-aged men (culled from 362,000) with cholesterol > 290 Interventions: cholesterol-lowering diet, blood pressure medication, smoking cessation programs After seven years, more deaths in the intervention group than in the controls 41.2/1000 (Intervention) vs. 40.4/1000 in controls
  • 3,800 middle-aged men (culled from half a million) with cholesterol > 265. -Intervention: cholestyramine, a cholesterol-lowering drug. -cholesterol levels in drug group drop by 18% to 25 % (according to Time) 71 men die in control group vs. 68 in intervention. 38 by heart attack vs. 30 "It is now indisputable that lowering cholesterol with diet and drugs can actually cut the risk of developing heart disease and having a heart attack.” Basil Rifkin, NIH director of the LRCCPT in Time
  • 3,800 middle-aged men (culled from half a million) with cholesterol > 265. -Intervention: cholestyramine, a cholesterol-lowering drug. -cholesterol levels in drug group drop by 18% to 25 % (according to Time) 71 men die in control group vs. 68 in intervention. 38 by heart attack vs. 30 "It is now indisputable that lowering cholesterol with diet and drugs can actually cut the risk of developing heart disease and having a heart attack.” Basil Rifkin, NIH director of the LRCCPT in Time
  • The LRC findings are extrapolated from a drug to a diet
  • Peter Ahrens called this extrapolation “unwarranted, unscientific and wishful thinking.” Thomas Chalmers, an expert on clinical trials who would later become president of the Mt. Sinai School of Medicine in New York, described it to Science as an “unconscionable exaggeration of all the data.” In fact, the investigators acknowledged in their JAMA article that their attempt to ascertain a benefit from diet alone had failed Steinberg is chair of the consensus panel, co-PI of LRCPPT.
  • Peter Ahrens called this extrapolation “unwarranted, unscientific and wishful thinking.” Thomas Chalmers, an expert on clinical trials who would later become president of the Mt. Sinai School of Medicine in New York, described it to Science as an “unconscionable exaggeration of all the data.” In fact, the investigators acknowledged in their JAMA article that their attempt to ascertain a benefit from diet alone had failed Steinberg is chair of the consensus panel, co-PI of LRCPPT. Why’d they exaggerate: Basil Rifkind: 20 years trying to prove it. ''It's an imperfect world. 'The data that would be definitive is ungettable, so you do your best with what is available.''
  • All three reports were front page news in the NYT and the WP. All written effectively by the same half dozen individuals , who had been behind this for a dozen years. The chapter linking dietary fat to heart disease had been contracted out to the same administrators at the National Heart Lung and Blood Institute who had organized the NIH consensus conference and founded the National Cholesterol Education Program. In Diet and Health , the chapter assessing the hazards of fat had been drafted by three old hands in the dietary fat controversy: Henry Blackburn, a protégé of Ancel Keys at Minnesota; Richard Shekelle, who had co-authored more than forty papers with Jeremiah Stamler, and DeWitt Goodman, who had chaired the National Cholesterol Education Program panel that had drafted the 1987 guidelines.
  • 19 541 [40%] randomized to intervention group; 29 294 [60%] to free-living controls.
  • After 8.1 years, for the above After 7.5 years, women lost one pound compared to controls, but their waist size increased.
  • One of the first of them.
  • “ A bitter pill to swallow”
  • 322 workers at Israeli research center, BMI > 27 Low Fat Diet: < 30 % fat, Calorie-restricted ,Grains, vegetables Mediterranean Diet <35% fat Calorie restricted, Add fish, nuts, olive oil Low Carb Diet <20 g/day carbs initially, Increase to max 120 g/day,
  • 322 workers at Israeli research center, BMI > 27 Low Fat Diet: < 30 % fat, Calorie-restricted ,Grains, vegetables Mediterranean Diet <35% fat Calorie restricted, Add fish, nuts, olive oil Low Carb Diet <20 g/day carbs initially, Increase to max 120 g/day,
  • Statins lower LDL cholesterol and reduce CVD risk -- particularly secondary prevention and people with very high cholesterol. after that it gets murky. Saturated fat increases LDL cholesterol -- Ergo saturated fat must increase heart disease risk
  • The limits of scientific evidence and the ethics of dietary guidelines

    1. 1. The Limits of S cientificSubtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Evidence and the Ethics of Dietary Guidelines Working Draft - Last Modified 1/29/2010 2:11:49 PM S ixty years of Ambiguity Peter Attia, M.D. Printed 7/3/2008 12:12:08 PM Pres ident, Nutrition S cience Initiative June 20, 2012 * Footnote Source: Source
    2. 2. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Printed 7/3/2008 12:12:08 PM * Footnote Source: Source 2
    3. 3. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Premature death Working Draft - Last Modified 1/29/2010 2:11:49 PM Insulin resistance Cancer Type 2 diabetes Asthma Fatty liver disease Sleep apnea Atherosclerosis Obesity Osteoarthritis Hypertension Neurodegeneration Printed 7/3/2008 12:12:08 PM Stroke Gall bladder disease Metabolic diseases * Footnote Source: Source
    4. 4. U.S. obesity ratesSubtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 34% Working Draft - Last Modified 1/29/2010 2:11:49 PM Printed 7/3/2008 12:12:08 PM 1 5%1 971 201 031 milion peopl l * Source: e Footnote Source 1 1 1 milion peopl l e
    5. 5. U.S. diabetes ratesSubtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 8% Working Draft - Last Modified 1/29/2010 2:11:49 PM Printed 7/3/2008 12:12:08 PM2%1 970 201 04.2 milion peopl l e 21 .1 milion peopl l e * Footnote Source: Source
    6. 6. 46 Subtitle, 1 6 pt bold, delete if not used UnitU.S. consumption of food not used of measure, 1 6 point plain, delete if since U.S. obesity rates since 1 960, by 1 970 age P ercent P ercent Working Draft - Last Modified 1/29/2010 2:11:49 PM Printed 7/3/2008 12:12:08 PM For men aged 20-74, from National Health and Nutrition Examination Surveys (NHANES) * Footnote Source: Source
    7. 7. 900Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 800 81 8% 700 Working Draft - Last Modified 1/29/2010 2:11:49 PM Healthcare spending 600 500 5x difference 400 Printed 7/3/2008 12:12:08 PM 300 200 Economic growth 1 68% 100 0 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 * Footnote Source: Source
    8. 8. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Fat and Saturated Fat? Recommendations Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    9. 9. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used “Intakes of dietary fatty acids and cholesterol are maj or determinants of cardiovascular disease (CV and Type-2 D) Working Draft - Last Modified 1/29/2010 2:11:49 PM diabetes (T2D), two maj causes of morbidity and mortality in or A mericans… In order to reduce the population’s burden from CV D and T2D and their risk factors, the preponderance of the evidence indicates beneficial health effects are associated with Printed 7/3/2008 12:12:08 PM several changes in consumption of dietary fats and cholesterol. These include limiting saturated fatty acid intake to less than 7 percent of total calories… ” D iet G uid el ary ines Ad visory C ommit ee, 201 0 t * Footnote Source: Source
    10. 10. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Fat and Saturated Fat? The Evidence Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    11. 11. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM “The available evidence from cohort and randomized controlled trials is unsatisfactory and unreliable to make judgment about and substantiate the effects of dietary fat on risk of CHD.” Printed 7/3/2008 12:12:08 PM FAO / O Expert C onsul at background paper, 2009 WH t ion * Footnote Source: Source Skeaff, Miller, 2009. Annals of Nutrition and Metabolism. Sept. 1 5: 1 73-201 .
    12. 12. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used “A meta-analysis of prospective epidemiologic studies showed Working Draft - Last Modified 1/29/2010 2:11:49 PM that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CV D.” Printed 7/3/2008 12:12:08 PM Siri-Tarino et al. American Journal of C l inical Nut ion, 201 0 rit * Footnote Siri-tarino et Source 0. AJC N. Mar; 502-509. Source: al. 201
    13. 13. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM A History Lesson 1 951 -1 961 Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    14. 14. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 951 Working Draft - Last Modified 1/29/2010 2:11:49 PM Ancel Keys and his wife Margaret visit Naples, Italy. They assess the cholesterol and fat content of the diet among workers (no heart disease) and the Printed 7/3/2008 12:12:08 PM wealthy (heart disease). Margaret Keys measures cholesterol levels. * Footnote Source: Source
    15. 15. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM 1 952 Keys presents his hypothesis at a WHO meeting in Amsterdam: “fatty diet, raised serum cholesterol, Printed 7/3/2008 12:12:08 PM atherosclerosis, myocardial infarction.” * Footnote Source: Source
    16. 16. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 961 Working Draft - Last Modified 1/29/2010 2:11:49 PM The American Heart Association A 4-page A report from an ad-hoc committee that now HA includes Keys concludes that “the best scientific evidence Printed 7/3/2008 12:12:08 PM of the time” strongly suggests that A mericans would reduce their risk of heart disease by reducing the fat in their diets, and replacing saturated fats with polyunsaturated fats. * Footnote Source: Source
    17. 17. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 961 Working Draft - Last Modified 1/29/2010 2:11:49 PM The Press Keys tells Time that the ideal Printed 7/3/2008 12:12:08 PM heart-healthy diet should be almost 70% carbohydrate and only 1 5% fat. * Footnote Source: Source
    18. 18. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM The competing philosophies Printed 7/3/2008 12:12:08 PM Proponents * Footnote Source: Source
    19. 19. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used “ We don’t have the luxury of Working Draft - Last Modified 1/29/2010 2:11:49 PM time to find the truth before making policy…” Printed 7/3/2008 12:12:08 PM --The McGovern Report * Footnote Source: Source
    20. 20. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM The competing philosophies Printed 7/3/2008 12:12:08 PM Opponents/ skeptics * Footnote Source: Source
    21. 21. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Without definitive evidence, we don’t know if we’re right. Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    22. 22. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Selection bias 1 957-1 970 Each new research adds detail, reduces areas of Printed 7/3/2008 12:12:08 PM uncertainty, and, so far, provides further reason to believe. Ancel Keys, 1 957 * Footnote Source: A . ug. Source Keys, 1 957. J MA A 24:1 91 2-1 91 9
    23. 23. Subtitle, 1 6 pt bold, delete if not used Unit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Framingham Heart Study Positive data: Framingham “links” cholesterol to heart disease. Printed 7/3/2008 12:12:08 PM Negative data: In women over 50 “cholesterol had no predictive value.” * FootnoteKannel etSource: Source Med. J al. Ann Int an;74(1 ):1 -1 2.
    24. 24. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Framingham Heart Study [Unpublished] negative data: Framingham compares the diets of men with cholesterol over 300 to those of men with cholesterol under 1 70 and finds no associat with the amount or type ion Printed 7/3/2008 12:12:08 PM of fat consumed.Kannel, W.B., and T. Gordon. 1 968. The Framingham D iet S tudy: D iet and Regul ion of S erum C hol erol Section 24 of The Framingham at est .Study. An Epidemiol * Footnote ogical Investigat of C ardiovascul D isease. Bethesda, MD: U.S. Department of Health, Education, and Welfare, Public ion arHealth Service, and National Institutes of Health. Source: Source
    25. 25. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Framingham Heart Study “There is considerable range of serum cholesterol within the Framingham Study Group. Something explains this inter-individual Printed 7/3/2008 12:12:08 PM variation, but it is not diet (as measured here).”Kannel, W.B., and T. Gordon. 1 968. The Framingham D iet S tudy: D iet and Regul ion of S erum C hol erol Section 24 of The Framingham at est .Study. An Epidemiol * Footnote ogical Invest ion of C ardiovascul D isease. Bethesda, MD: U.S. Department of Health, Education, and Welfare, Public igat arHealth Service, and National Institutes of Health. Source: Source
    26. 26. Subtitle, 1 6 pt bold, delete if not used Unit of measure, 1 6 point plain, delete if not used More negative evidence Working Draft - Last Modified 1/29/2010 2:11:49 PM Studies of Benedictine and Trappist monks, Navaj Indians, o Irish immigrants to Boston, Swiss A lpine farmers and Maasai and other A frican pastoralists report no association of saturated fat to heart disease. Printed 7/3/2008 12:12:08 PM Keys rejects them as having “no relevance to diet-cholesterol- CHD relationships in other populations.”Groen et *al. 1 962. AJC N. Jun:456-70., Page et al. 1 956. C ircul ion. May: 675-9. , Trulson et al. 1 964. JAD A. 225-9. , Mann et al. 1 964. J Footnote atAtherosclSource: Source J ug: 289-31 2, Keys. 1 975. At erosis Res. ul-A heroscl erosis, Sep-Oct;22(2):1 49-92.
    27. 27. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Selection bias Revisit Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    28. 28. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 957 Oglesby Paul and colleagues study 5,400 male employees Working Draft - Last Modified 1/29/2010 2:11:49 PM of the Western Electric Company. They compare the 1 5 percent of men who reported eating the fattest diets to the 1 5 percent who reported eating the Printed 7/3/2008 12:12:08 PM leanest. “Worthy of comment, is the fact that of the 88 coronary cases, 1 4 have appeared in the high-fat intake group and 1 6 in the low-fat group.” * Footnote Source: Source
    29. 29. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 981 Working Draft - Last Modified 1/29/2010 2:11:49 PM Shekelle, Stamler et al. return to Western Electric They compare heart disease morbidity and mortality to the fat content of the diet in 1 957. Printed 7/3/2008 12:12:08 PM “The amount of saturated fatty acids in the diet was not significantly associated with the risk of death from CHD.” * Footnote Source: Source
    30. 30. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 981 Shekelle, Stamler et al. rationalize: Working Draft - Last Modified 1/29/2010 2:11:49 PM “Although most attempts to document the relation of dietary cholesterol, saturated fatty acids, and polyunsaturated fatty acids to serum cholesterol Printed 7/3/2008 12:12:08 PM concentration in persons who are eating freely have been unsuccessful, positive results have been obtained in [four] investigations besides the Western Electric Study.” * Footnote Source: Source
    31. 31. Subtitle, 1 6 pt bold, delete if not used 1 981Unit of measure, 1 6 point plain, delete if not used Shekelle, Stamler et al. rationalize further: Working Draft - Last Modified 1/29/2010 2:11:49 PM “If viewed in isolation, the conclusions that can be drawn from a single epidemiologic study are limited. Within the context of the total literature, however, the present Printed 7/3/2008 12:12:08 PM observations support the conclusion that the [fat] composition of the diet affects the level of serum cholesterol and the long-term risk of death from CHD in middle-aged A merican men.” * Footnote Source: Source
    32. 32. Subtitle, 1 6 pt bold, delete if not used 1 981Unit of measure, 1 6 point plain, delete if not used Enter the media... Working Draft - Last Modified 1/29/2010 2:11:49 PM Washingt P ost on “The new report strongly reinforces the view that a high- fat, high-cholesterol diet can clog arteries and cause heart disease.” Printed 7/3/2008 12:12:08 PM Shekelle in the New York Times “The message of these findings is that it is prudent to decrease the amount of saturated fats and cholesterol in your diet.” * Footnote Source: Source
    33. 33. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 990 The denouement... Working Draft - Last Modified 1/29/2010 2:11:49 PM The A and NHLBI co-author a report called HA “The Cholesterol Facts.” Printed 7/3/2008 12:12:08 PM The Western Electric study is included as one of seven “epidemiologic studies showing the link between diet and CHD [that] have produced particularly impressive results” and “showing a correlation between saturated fatty acids and CHD” -- precisely what it did not do. * Footnote Source: Source
    34. 34. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM State of the Evidence The 1 970s Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    35. 35. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM 1 970 A A n merican Heart A ssociation committee recommends low- saturated-fat diets (less than 1 0% of calories) for every American, including “infants, children, adolescents, lactating Printed 7/3/2008 12:12:08 PM and pregnant women, and older persons.”Inter-Society Commission for Heart Disease Resources. 1 970. C ircul ion. J 55-95. at * Footnote Source: Source uly;A
    36. 36. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 975 “Two strikingly polar attitudes persist on this subj with much ect, Working Draft - Last Modified 1/29/2010 2:11:49 PM talk from each and little listening between.” --Henry Blackburn, New E ngl and Journal of Medicine 1 978 Printed 7/3/2008 12:12:08 PM “It must still be admitted that the diet-heart relation is an unproved hypothesis that needs much more investigation.” --Thomas Dawber, New E ngl and Journal of Medicine * Footnote Source: NEJM. J 9; 1 05-7., Dawber, 1 978. NEJM. A 31 ; 452-8.Blackburn, 1 975.Source an ug
    37. 37. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Clinical Trials P re-1 977 Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    38. 38. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Low-fat diets? Working Draft - Last Modified 1/29/2010 2:11:49 PM 1 963 Hungarian researchers report a benefit of consuming a maximum of 1 .5 ounce of fat per day. 1 965 Printed 7/3/2008 12:12:08 PM British researchers report no benefit of consuming a maximum of 1 .5 ounces of fat per day: “A low-fat diet has no place in the treatment of myocardial infarction.” * FootnoteKorányi,Source: Ther H ung. 1 1 :1 7, Research Committee, 1 965. Lancet Sep 1 1 ; 501 -4. 1 963. Source .
    39. 39. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Cholesterol-lowering diets? Working Draft - Last Modified 1/29/2010 2:11:49 PM 1 973* Minnesota Coronary Study 9,000 men and women: 269 deaths in intervention [low SF, cholesterol] group. Printed 7/3/2008 12:12:08 PM 206 deaths in control group. * Results go unpublished for 1 6 years. Why? “We were disappointed in the way they turned out.” (Frantz) * Footnote Frantz et al, 1 989. A Source: Source rteriosclerosis. J an-Feb; 1 29-35.
    40. 40. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM The Tipping Point January,1 977 Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    41. 41. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not usedRecommendation #I Working Draft - Last Modified 1/29/2010 2:11:49 PMIncrease carbohydrate consumptionto 55 to 60% of caloriesRecommendation #2Reduce fat consumption to 30% Printed 7/3/2008 12:12:08 PMof calories * Footnote Source: Source
    42. 42. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM he Fallback Position? he Precautionary Principle Printed 7/3/2008 12:12:08 PM The question to be asked is not why should we hange our diet but why not? There are [no risks] hat can be identified and important benefits can be * Source: Footnote Source
    43. 43. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Cohort Studies 1 977-1 984 Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    44. 44. Total cholesterol does not predictSubtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used future heart disease Working Draft - Last Modified 1/29/2010 2:11:49 PM High LDL is a “marginal risk factor” Low HDL is a 4-fold better predictor of risk than LDL and the only reliable predictor of risk for men or women over 50. Printed 7/3/2008 12:12:08 PM Caveats: Saturated fat raises HDL. Carbohydrates lower HDL. * FootnoteCastelli Source: et al, 1 977. C ircul ion. Source at May; 767-72., Gordon et al, 1 977. Am J Med. May;707-1 4.
    45. 45. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 981 Working Draft - Last Modified 1/29/2010 2:11:49 PM Honolulu, Framingham and Puerto Rico Saturated fat and total fat negatively associated with risk of heart attack Printed 7/3/2008 12:12:08 PM Saturated fat and total fat positively associated with longevity Gordon et Footnote . C ircul ion. Mar;500-1 5. Feinleib, 1 981 . Am J Epi. J * al, 1 981 at ul;5-1 0. Source: 983. C ancer Res. May; 2503s-2507s. Feinleib,1 Source
    46. 46. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 981 -3 Working Draft - Last Modified 1/29/2010 2:11:49 PM Low serum cholesterol (< 1 60 mg/ associated with a dl) higher risk of cancer. Observed in every cohort study with 3 exceptions (all Printed 7/3/2008 12:12:08 PM Chicago cohorts studied by Jeremiah Stamler) Gordon et Footnote . C ircul ion. Mar;500-1 5. Feinleib, 1 981 . Am J Epi. J * al, 1 981 at ul;5-1 0. Source: 983. C ancer Res. May; 2503s-2507s. Feinleib,1 Source
    47. 47. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Authors concluded: Things that raise HDL should be considered Printed 7/3/2008 12:12:08 PM to reduce the risk of CVD * Footnote Source: Source
    48. 48. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Why ignore HDL and triglycerides for 20 years? Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    49. 49. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used 1 982 The Multiple Risk Factor Intervention Trial (MRFIT) Working Draft - Last Modified 1/29/2010 2:11:49 PM Cost: $1 1 5,000,000 7 year mortality: 41 .2/ ,000 (intervention) vs. 40.4/ ,000 (controls) 1 1 Printed 7/3/2008 12:12:08 PM Wal S t l reet Journal “Heart attacks, a test collapses.” * Footnote Source: JAMA. MRFIT, 1 982. Source Sep 24;1 465-77.
    50. 50. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used J anuary, 1 984 Working Draft - Last Modified 1/29/2010 2:11:49 PM The Lipid Research Clinics Primary Prevention Trial Cost: $1 50,000,000 1 0 year mortality 35.8/ ,000 (intervention) vs. 37.3/ ,000 (controls) 1 1 Printed 7/3/2008 12:12:08 PM Time Magazine “Sorry, it’s true. Cholesterol really is a killer.” * Footnote LRC Source: Source Program , 1 984. JAMA. J 20; 351 -64, 365-74. an
    51. 51. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used The authors conclude Working Draft - Last Modified 1/29/2010 2:11:49 PM “Caution should be exercised before extrapolating the LRCPPT findings to cholesterol lowering drugs other than bile acid sequestrants.” Printed 7/3/2008 12:12:08 PM “The LRCPPT was not designed to assess directly whether cholesterol lower by diet prevents CHD.” * Footnote LRC Source: Source Program , 1 984. JAMA. J 20; 351 -64, 365-74. an
    52. 52. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM “It is now indisputable that lowering cholesterol with diet and drugs can actually cut the risk of developing heart disease and having a heart attack.” --Basil Rifkind, NIH director of the LRCPPT, in Time Printed 7/3/2008 12:12:08 PM * Footnote LRC Program Source JAMA. J 20; 351 -64, 365-74. Source: , 1 984. an
    53. 53. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM The Tipping Point Tips 1 984 Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    54. 54. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PMThe LRC results “strongly indicate that the more youlower cholesterol and fat in your diet, the more youreduce your risk of heart disease.” --Basil Rifkind, NIH director of the LRCPPT, in Time Printed 7/3/2008 12:12:08 PM * Footnote LRC Program Source JAMA. J 20; 351 -64, 365-74. Source: , 1 984. an
    55. 55. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Why’d they exaggerate? Working Draft - Last Modified 1/29/2010 2:11:49 PM “It’s an imperfect world. The data that would be definitive is ungettable, so you do your best with what is available.” Printed 7/3/2008 12:12:08 PM --Basil Rifkind, 2002 * Footnote LRC Program, 1 984. JAMA. J 20; 351 -64, 365-74. Source: Source an
    56. 56. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Consensus Building 1 987 -1 989 Working Draft - Last Modified 1/29/2010 2:11:49 PM In sciences t are based on supposit hat ion Printed 7/3/2008 12:12:08 PM and opinion, t obj is t command he ect o assent not mast t t , er he hing it f. sel --Francis Bacon, Novum O rganum, 1 620 * Footnote Source: Source
    57. 57. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used December, 1 984 Working Draft - Last Modified 1/29/2010 2:11:49 PM The NIH consensus conference Conclusion There is “no doubt” that a low-fat diet “will afford significant Printed 7/3/2008 12:12:08 PM protection against coronary heart disease” to every A merican over the age of two. * Footnote Consensus conference, 1 985. JAMA. A 1 2;253(1 4):2080-6. Source: Source pr
    58. 58. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used December, 1 984 Working Draft - Last Modified 1/29/2010 2:11:49 PM The NIH consensus conference Caveat Printed 7/3/2008 12:12:08 PM If there had been a true consensus, says Dan Steinberg (chair of the consensus panel, co-PI of LRCPPT), “you wouldn’t have had to have a consensus conference.” * Footnote Consensus conference, 1 985. JAMA. A 1 2;253(1 4):2080-6. Source: Source pr
    59. 59. Subtitle, 1 6 pt bold, delete if not used 1 989Unit of measure, 1 6 point plain, delete if not used National Academy of Sciences D iet and H eal h: Impl ions for Red ucing t icat Working Draft - Last Modified 1/29/2010 2:11:49 PM C hronic D isease Risk (1 ,300 pages) Printed 7/3/2008 12:12:08 PM “Highest priority is given to reducing fat intake, because the scientific evidence concerning dietary fats and other lipids and human health is strongest and the likely impact on public health the greatest.” * Footnote Source: SourceUSDHHS 1 988.
    60. 60. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Evidence, post-consensus 1 990 - t ay od Printed 7/3/2008 12:12:08 PM * Footnote Source: Source
    61. 61. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Lifestyle Heart Trial (1 990) 28 patients in treatment arm, Working Draft - Last Modified 1/29/2010 2:11:49 PM 20 patients received no intervention 1 year interventionTreatment: smoking cessation, low-fat (1 0% max) vegetarian diet, Printed 7/3/2008 12:12:08 PM no flour, no sugar, stress management, vigorous exercise Treatment group showed a significant reduction in angiographically documented coronary atherosclerosis * Footnote Source: 1 990. Lancet 336:1 29-1 33 Ornish et al, Source
    62. 62. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Meta-Analyses (2001 ) Cochrane Collaboration: “Reduced or Modified dietary fat for Working Draft - Last Modified 1/29/2010 2:11:49 PM preventing cardiovascular disease” 27 well-controlled randomized trials1 0,000 subj ects followed for an average of three years each. Printed 7/3/2008 12:12:08 PM No effect on longevity. No “significant effect on cardiovascular events.” * Footnote Source:al,Source . Hooper et 2001 C ochrane D atabase S yst Rev. (3):CD0021 37
    63. 63. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Meta-Analyses (2006) Cochrane Collaboration: “Multiple risk factor interventions for Working Draft - Last Modified 1/29/2010 2:11:49 PM primary prevention for coronary heart disease” Multiple interventions include lowering blood pressure and cholesterol1 0 well-controlled trials 900,000 patient years of observation Printed 7/3/2008 12:12:08 PM“The pooled effects suggest multiple risk factor intervention has no effect on mortality.” * FootnoteEbrahim et al.Source Cochrane Database Syst Rev. Oct 18;CD001561. Source: 2006.
    64. 64. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Women’s Health Initiative (2006) Working Draft - Last Modified 1/29/2010 2:11:49 PM 48,835 post-menopausal women randomized to a low-fat diet or a control diet A six years, total fat consumption was reduced by fter Printed 7/3/2008 12:12:08 PM 8.2% ; saturated fat was reduced by 2.9% . “Modest” increases in fruits, vegetables and whole grains * Footnote Source: Source
    65. 65. Subtitle, 1 6 pt bold, delete if not used Unit of measure, 1 6 point plain, delete if not used Women’s Health Initiative (2006) “The intervention did not reduce risk of CHD or stroke.” Working Draft - Last Modified 1/29/2010 2:11:49 PM “A low-fat dietary pattern did not result in a statistically significant reduction in the risk of invasive breast cancer...” “There is no evidence that a low-fat dietary pattern intervention reduces colorectal cancer risk...” Printed 7/3/2008 12:12:08 PM “A low-fat dietary pattern among generally healthy postmenopausal women showed no evidence of reducing diabetes risk...”Howard et al. 2006. JAMA. Feb 8:655-666. Prentice et al. 2006. JAMA. Feb 8:629-642. * FootnoteBeresford Source: 2006. JAMA. Feb 8:643-654. Tinker et al. 2008. Arch Int Med. J 28:1 500-1 51 1 . et al. Source ul
    66. 66. Subtitle, 1 6 pt bold, delete if not used Diet trials (2003)Unit of measure, 1 6 point plain, delete if not used Low-carbohydrate/ high-fat vs. low-calorie, low-fat Working Draft - Last Modified 1/29/2010 2:11:49 PM Conventional LOW-FA HIGH-CA diet T, RB instruction Women: 1 200-1 500 calories/ d Men: 1 500-1 800 calories/ d 63 obese 60 % carbs, 25 % fat, 1 5 % protein men and R Printed 7/3/2008 12:12:08 PM women HIGH-FA LOW-CA diet instruction T, RB First two weeks < 20 g carbs/ d Then gradually increase until stable weight * Footnote Source: 2003. NEJM. Foster et al. Source May 22;2082-90
    67. 67. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used TGs TC Working Draft - Last Modified 1/29/2010 2:11:49 PMDiet trials (2003) Foster et al Printed 7/3/2008 12:12:08 PM LDL HDL Low carb/ conventional low fat * Footnote Source: 2003. NEJM. Foster et al. Source May 22;2082-90
    68. 68. Subtitle, 1 6 pt bold, delete if not used Diet trials (2007)Unit of measure, 1 6 point plain, delete if not used A TO Z Trial 2 MONTHS Group n kcal/ d CHO PRO FAT Weight LDL Trig HDL DBP Working Draft - Last Modified 1/29/2010 2:11:49 PM Atkins 77 1 381 ~ 62g 97 84 -4.3 kg +2.3 -52.3 -0.4 -2.9 Zone 79 1 455 1 52 87 57 -2.0 kg -5.3 -24.8 -0.5 -2.1 LEARN 79 1 476 1 80 73 49 -2.8 kg -7.3 -1 7.2 -3.8 -1 .4 Ornish 76 1 408 220 60 33 -2.8 kg -1 0.1 -1 0.9 -5.3 -0.4 Printed 7/3/2008 12:12:08 PM 1 2 MONTHS Group n kcal/ d CHO PRO FAT Weight LDL Trig HDL DBP Atkins 77 1 599 ~ 1 40g 84 78 -4.5 kg +0.8 -29.3 +4.9 -4.4 Zone 79 1 594 1 79 80 62 -1 .5 kg 0 -4.2 +2.2 -2.1 LEARN 79 1 654 1 94 79 61 -2.5 kg +0.6 -1 4.6 -2.8 -2.2 Ornish 76 1 505 1 95 68 50 -2.4 kg -3.8 -1 4.9 0 -0.7 * Footnote Gardner et al. 2007. JAMA. March 7;969-77 Source: Source
    69. 69. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Diet trials (2008) Workplace Diet Trial Printed 7/3/2008 12:12:08 PM * FootnoteShai et al. 2008. NEJM. J Source: Source ul 1 7;229-41
    70. 70. Subtitle, 1 6 pt bold, delete if not used Diet trials (2008)Unit of measure, 1 6 point plain, delete if not used Workplace Diet Trial Test Low Fat Mediterranean Low Carb Working Draft - Last Modified 1/29/2010 2:11:49 PM Systolic BP, mm Hg -4.3 -5.5 -3.9 Diastolic BP, mm Hg -0.9 -2.2 -0.8 LDL-C, mg/ dl -0.05 -5.6 -3.0 HDL-C, mg/ dl 6.3 6.4 8.4 Printed 7/3/2008 12:12:08 PM Triglyceride, mg/ dl -2.8 -21 .8 -23.7 T Chol : HDL ratio -0.6 -0.9 -1 .1 Hemoglobin A c, % 1 -0.4 -0.5 -0.9 C-reactive protein, mg/ l -0.6 -0.9 -1 .3 Red denotes p< 0.05 for within-group change from baseline. Blue denotes p< 0.05 for comparison of Low Carb vs. Low Fat. * FootnoteShai et al. 2008. NEJM. J Source: Source ul 1 7;229-41
    71. 71. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Why the confidence? P re-1 984 Printed 7/3/2008 12:12:08 PM Populations with very low cholesterol levels have a low incidence of heart disease * Footnote Source: Source
    72. 72. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Working Draft - Last Modified 1/29/2010 2:11:49 PM Why the confidence? P ost 984 -1 Printed 7/3/2008 12:12:08 PM Cholesterol-lowering drugs work (statins, in particular) * Footnote Source: Source
    73. 73. Subtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Caveat Working Draft - Last Modified 1/29/2010 2:11:49 PM Drugs and diets are not comparable. Drugs have multiple actions as do diets. Printed 7/3/2008 12:12:08 PM “Saying that statins reduce heart disease risk by lowering cholesterol, is like saying that aspirin reduces heart disease risk by reducing headaches.” --Kronmal * Footnote Source: Source
    74. 74. President John F. KennedySubtitle, 1 6 pt bold, delete if not usedUnit of measure, 1 6 point plain, delete if not used Yale University commencement address June 11, 1962 Working Draft - Last Modified 1/29/2010 2:11:49 PM “ For the greatest enemy of truth is very often not the lie Printed 7/3/2008 12:12:08 PM – deliberate, contrived and dishonest – but the myth – persistent, persuasive, and unrealistic. Too often we hold fast to the clichés of our forebears. We subject all facts to a prefabricated set of interpretations. We enjoy the comfort of opinion without the discomfort of thought.” * Source: Footnote Source

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