The sequence of events that produced the greatest scam in the history of modern medicine.
Table 1 describes the sequence of 70 events that I will argue were critical in directing an unquestioning global acceptance of Keys’ unproven hypotheses and then its subsequent disproof. In that table I simply outline each event in its barest detail. In the coming sequence of columns I expose the meaning of each scientific event and how the most damaging of the scientific findings were skillfully managed by a core of like-thinking scientists to ensure that the real truth could not emerge.
The ideas and arguments I present are not original in that I am not their original source. Rather they have been covered in compelling detail in the four iconic books (1-4), and in a number of others that confine themselves to what has become known as the Cholesterol Scam or the Cholesterol Con (5-9). That list is not all-inclusive.
Re-reading Smith and Pinckney, Moore, Taubes and Teicholz’s books brings home to me just how brilliantly exceptional they are. If this series drives yet more to read any or all of those books, the series will have been successful. So my goal here is perhaps twofold. First to introduce and direct the diligent reader to the original sources of all this material. And second, to bring a comprehensive focus on the full nature of the ingenious scam to which we have all been exposed – at great cost. Included is my interpretation of the reasons why that scam has succeeded. So far. Perhaps my real hope is that by once more re-telling the story of how this scam unfolded over the past century, we may come a little closer to the day when the medical and nutrition professions will be forced to admit that, yes, they finally acknowledge what is now obvious.
That this has been the greatest scam in the history of modern medicine. Who knows? One day they might even apologize.
Table 1: Historical sequence of the significant events leading to the global adoption of the Diet-Heart and Lipid Hypotheses as proven dogmas, despite an absence of definitive proof and in the face of multiple disproofs.
|1. 1910||Future Nobel Laureate German Chemist Adolph Windaus detects the presence of cholesterol in arterial plaque (atherosclerosis).||The natural assumption will become that the cholesterol in the arterial plaque originated from the blood stream crossing into the arterial wall to cause “artery clogging” – the Lipid Hypothesis.|
|2. 1910||With the help of German chemist, E.C.Kayser, soap and candle makers in Cincinnati, Ohio, William Procter and James Gamble produce an hydrogenated oil from cottonseed. They subsequently form the company Procter and Gamble (P&G).||The commercial product, Crisco, produced by this hydrogenation process is promoted to US housewives as a healthier and cheaper alternative to usual animal fats used in cooking. Cleverly promoted as a superior substitute for butter, lard and tallow, the sales of Crisco increase 40-fold in 4 years. The false perception is created that industrially-produced foods are much healthier for humans than are the foods our human ancestors have eaten for millions of years – like meat, fish, eggs, and animal fats including lard and tallow and those from brains and bone marrow and, more recently, from dairy produce.|
|3. 1913||Russian scientist Nikolai Anichkov (Anitschkow) feeds herbivorous rabbits a mixture of cholesterol and sunflower oil, and produces a form of atherosclerosis, not unlike that found in human.||The logical conclusion becomes that, provided the blood cholesterol concentration is sufficiently high, the same outcome – the development of severe atherosclerosis – will apply to all creatures including humans. Eminent Ancel Keys’ Lipid Hypothesis acolyte, Daniel Steinberg MD, concludes that Anichkov’s finding is the equal of William Harvey’s 1628 discovery of the circulation. He argues that Anichkov should have been awarded the Nobel Prize in Medicine/Physiology.|
|4. 1939- 1945||Mortality from coronary heart disease (CHD) falls sharply in a number of European countries during World War II. There is no such effect in the US.||Since consumption of animal-based products was dramatically reduced over the same time period in the affected European countries, the logical conclusion becomes that animal foods are the direct cause of coronary atherosclerosis and CHD.|
|5. 1945||US President Franklin Delano Roosevelt dies suddenly from a cerebral stroke at age 63.||Roosevelt had suffered from malignant hypertension (high blood pressure) for some years but the medical treatment then available was ineffective. US national (and medical) pride is challenged to better understand heart disease so that, in future, the disease can be treated more effectively and, in the long term, hopefully prevented.|
|6. 1948||US President Roosevelt’s successor, President Harry Truman, signs The (US) National Heart Act into law.||The National Heart Act creates the National Institutes of Health including the National Heart Institute (NHI) and makes available substantial funding for heart disease research in the USA. The first $500 000 is provided for what becomes known as the Framingham Heart Study.|
|7. 1948||The Procter & Gamble (P&G) company donates all the funds it raises from its “Truth or Consequences” radio program to the American Heart Association (AHA). The amount is $1.74 million (or $17 million in 2014 dollars).||As a result, the AHA hires its first professional fund-raiser “to raise money and let Americans know that heart disease was the country’s number one killer” (4, p.48). The AHA soon becomes the largest not for profit group of any kind in the USA. “By 1960, the AHA was investing hundreds of millions of dollars in research” (4, p.48). Essentially all this money would be spent promoting an unquestioning acceptance of Keys’ Twin Hypotheses.|
|8. 1948 –present||The Framingham Heart Study (FHS) is launched.||The goal of the FHS is to “determine the factors predisposing to the development of disease through clinical and laboratory examination and long term follow up”. These factors will become known as risk factors. The management of these supposed risk factors makes every person a potential “at risk” patient and will have a major influence on the manner in which medicine is practised, not just in the US but globally. It provides the opportunity for the discovery and marketing of a new class of pharmaceutical agents to treat “risk factors”, at the same time exposing humans to the potential for harm produced by those new chemical agents.|
|9. 1950||John Gofman MD uses an ultracentrifuge technique to separate and identify the different blood lipoprotein particles. He becomes the first to propose the Diet-Heart and Lipid Hypotheses. Ancel Keys will ultimately steal Gofman’s ideas and present them as his own.||Dr Gofman identifies himself as the scientist best equipped to lead future research of factors causing the heart disease “epidemic” then developing in the US and elsewhere. Most importantly he understands that high carbohydrate diets raise lipoproteins in the Sf o 20-400 lipoprotein band on ultracentrifuge and that elevations of this lipoprotein band is associated with CHD. He warns that “Neglect of (the carbohydrate factor) can lead to rather serious consequences… by allowing certain individuals sensitive to the carbohydrate action to take too much carbohydrate as a replacement for some of the animal fats” (3, p,156-157). But Gofman is too great a threat to Keys and his acolytes, so he is muscled out. He changes his research direction and moves on. In the end his contribution has been written out of history (as have the contribution of others!).|
|10. 1952||Laurance W. Kinsell MD discovers that the substitution of animal fats with vegetable fats, lowers blood cholesterol concentrations.||The importance of this study, which antedates the formulation of Keys’ Twin Hypotheses, is that it establishes a dietary change that reliably lowers blood cholesterol concentrations. Indirectly it supports Keys’ soon-to-be-stated hypothesis eating animal produce raises the blood cholesterol concentration which must then be the direct cause of increased rates of coronary heart disease (CHD), according to his Diet-Heart and Lipid hypotheses. The supposition is that replacing dietary animal fats with a more plant-based diet and the liberal substitution of all saturated fats with processed hydrogenated polyunsaturated fats in “vegetable” oils will guarantee the opposite outcome.|
|11. 1953||Autopsies of young US soldiers killed in the Korean war shows presence of advanced (“gross”) coronary atherosclerosis in 77%.||The finding is overstated; the truth was not as dire as the article suggested. Yet the article reinforces the search for the coronary risk factors, initiated by the Framingham Heart Study, that can be detected ante-mortem (before death) and which predict those at greater risk of developing CHD in the future. The assumption is that reversal of these factors will (obviously) prevent the development of symptomatic CHD in middle age. The MRFIT, MONICA and LookAHEAD studies (see subsequently) amongst many others including the Helsinki Businessmen Study, effectively proves that this is, at best, wishful thinking. But this fact will be successfully hidden from succeeding generations of medical students and doctors.|
|12. 1953||Searching for a new research direction, Ancel Keys PhD discovers a World Health Organization (WHO) document showing an association between dietary fat intake and CHD mortality rates in 22 countries. The USA is the worst affected country, Japan the least.||Keys publishes his original “arm chair” “scientific paper” based on the data from just 6 of the 22 countries for which the WHO data were available. Scientist will subsequently accuse Keys of “cherry-picking” only the most convenient data that supported his evolving hypothesis. Although Keys knows that such associational epidemiological studies cannot prove causation, yet he never deviates from actively promoting his unproven hypotheses as if they are already proven. The problem is evidently Keys’ personality. For he begins his “scientific” quest certain of his correctness. So he writes in 1953: “No other variable in the mode of life besides the fat calories in the diet is known which shows anything like such a consistent relationship to the mortality rate from coronary or degenerative heart disease”. And: “..there is no longer any doubt that one central item is the concentration, over time, of cholesterol and related lipids, and lipoproteins in the blood serum. No other etiological influence of comparable importance is as yet identified” (10, 1399-1400). Keys and his equally solipsistic acolytes would spend the rest of their lives convincing the world that they alone are correct.|
|13. 1955||President Dwight Eisenhower suffers his first heart attack during the final year of his first term of office in the White House. Dr Paul Dudley White is one of the cardiologists who assists in the medical management of the President. Eisenhower recovers and is re-elected US President for a second term. He becomes a staunch advocate of Ancel Keys’ unproven dietary theories and a formidable ally of the American Heart Association (AHA) and National Heart Institute (NHI) research programs. The main focus of these research programs are to “prove” that Keys’ Twin Hypotheses are correct.||With Paul Dudley White’s approval, Ancel Keys places Eisenhower on his experimental “heart-healthy, low-fat, prudent diet”. The outcomes are not good as Eisenhower develops type 2 diabetes mellitus (T2DM), suffers a stroke, has multiple heart attacks, and dies from intractable heart failure in 1969. The autopsy shows that he has advanced obstructive coronary artery disease – the very condition Keys’ unproven, experimental diet is meant to prevent or reverse. Today we now know that incorrectly-treated T2DM is a key determinant of chronic heart failure. Thus Keys’ “heart healthy” diet contributed significantly to the death of President Eisenhower. But this connection is never made public.|
|14. 1955||Seminar of the World Health Organization (WHO) Study Group on Atherosclerosis and Ischemic Heart Disease.||Keys’ presentation at this seminar of his 1953 WHO epidemiological associational data is heavily criticised by Jacob Yerushalmy MD and Herman Hilliboe MD who point out that associational studies cannot prove causation, except in exceptional circumstances. Keys takes this criticism as a public humiliation and vows to prove to the world that he is correct. His solution is to begin planning the Seven Countries Study (SCS). But the SCS is just another associational study, even though it is very expensive. Critically the SCS began with the manifest pre-conceived bias of its principal investigator. It was designed and run as an experiment to vindicate Ancel Keys’ Twin hypotheses. That is how it would be marketed to the scientific and medical communities even though, as an associational study, it failed to provide much support for any of Keys’ biases. Importantly, the key measurement in the study – the diets of persons living in the different countries – is so poorly conducted that meaningful conclusions cannot be drawn. But this fact is skilfully hidden by Keys and his co-workers.|
|15. 1956||The US Public Health Service funds Ancel Keys’ Seven Countries Study.||Using his growing national and international status as the diet doctor for President Eisenhower, Keys manages to convince key members of the US Public Health Service to fund that study that will become known as the Seven Countries Study.|
|16. 1957||A nutrition committee representing the AHA rejects Keys Diet-Heart and Lipid Hypotheses concludes that: “Perhaps the best that can be said (about Keys’ evidence – my addition) is that there is an association that has statistical value, but that it is not an obligatory association either in small groups or, and much less so, in an individual” (11, p.174).||The AHA rules that Keys’ hypothesis is not supported by hard scientific evidence and thus cannot be used to mandate specific dietary changes: “Thus the evidence at present does not convey any specific implications for drastic dietary changes, specifically in the quantity or type of fat in the diet of the general population, on the premise that such changes will definitely lessen the incidence of coronary or cerebral artery disease (11, p.175).
So that: “In the opinion of the authors of this review, there is not enough evidence available to permit a rigid stance on what the relationship is between nutrition, particularly the fat content of the diet, and atherosclerosis and coronary heart disease. We are certain of one thing: the evidence now in existence justifies the most thorough investigation. This should be done soon, thoroughly, and uncompromisingly” (11, p.164).
|17. 1957||Edward “Pete” Ahrens MD publishes a review of dietary factors, especially different dietary fats, that influence blood cholesterol concentrations.||Even though he remains a Keys sceptic all his life – “it has not been demonstrated in man that lowered levels of serum lipids will alter his susceptibility to atherosclerosis (12, p.1911)”- he concludes the paper with the advice that “patients with existent or threatening atherosclerosis may be justifiably advised to eat high portions of unsaturated fats” (12, p.1911). This statement was not evidence-based (then or now) but indicates the extent to which the low-fat dietary bias had already infected even the most sceptical thinkers of the day.|
|18. 1957- 1972||The New York Diet and Coronary Heart Disease study of Norman Jolliffe MD, subsequently known as The Anti-Coronary Club Program, is initiated.||This was perhaps the first study to evaluate the effects of the “Prudent Diet” that limited the consumption of animal fats, replacing especially saturated fats with polyunsaturated fatty acid-enriched margarines and “vegetable” oils in the dietary management of persons who had suffered a heart attack. Although the study was marketed as proof that this diet beneficially improved long-terms health outcomes in persons with heart attack, hidden in the data was evidence that there were more deaths in the group randomized to the Prudent Diet. The authors did their best to hide this inconvenient evidence. Also, most unfortunately, during the trial the principal investigator Dr Jolliffe, died suddenly from a heart attack.|
|19. 1957||The initial results from the Framingham Heart Study (FHS) are reported||Although the FHS finds that elevated blood cholesterol concentrations are weakly predictive of future CHD risk, its key but hidden findings are that the nature of the diet predicts neither the blood cholesterol concentration nor the risk of death from CHD. This disproves Keys’ Diet-Heart hypothesis. As a result the report of the finding had to be hidden. The report was consigned to a vault in the NHI buildings in Washington, DC. The subterfuge was ultimately revealed by a former director of the FHS, George Mann MD, who resigned from the study group when he realized that those controlling the FHS would not allow all its true findings to be disclosed.
The finding that an elevated blood HDL-cholesterol concentration was a better predictor of a (reduced) future CHD risk than was an elevated total or LDL-cholesterol concentration for an (increased) CHD risk was also written out of history because it conflicts with the Diet-Heart hypothesis.
Ultimately the finding that an elevated HDL-cholesterol concentration is protective against CHD, led to the finding that insulin resistance, high blood triglyceride and low HDL-cholesterol concentrations are the more important predictors of CHD risk.
The FHS also finds, inconveniently, that those with low blood cholesterol concentrations are at increased risk for developing cancer.
|20. 1958||The Oslo Secondary Prevention Trial (OSPT) is initiated||CHD death rates dropped steeply in Norway during the latter years of WWII but increased again in the post-war years. The increase was associated with an increased consumption of trans fat-laden margarines which were government subsidized. The OSPT was a study of the effects of a diet high in polyunsaturated fats on recurrence of CHD in men who had suffered a first heart attack. It was therefore similar to New York’s Anti-Coronary Club study.|
|21. 1959-1965||Margaret Albrink MD and Evelyn Man MD reported that blood triglyceride concentrations are more likely than blood cholesterol concentrations to be elevated in persons with CHD and in those with T2DM.||Albrink and Man also noted that, in persons with T2DM, the main dietary change in the previous 30 years had been an increased dietary carbohydrate intake and a reduced dietary fat intake. This change was associated with increased blood triglyceride concentrations but without noticeable change in blood cholesterol concentrations. In an historically important editorial in the Annals of Internal Medicine in June 1965 Albrink concludes that humans evolved as hunters eating high-fat high-protein diets with relatively little carbohydrate. As a result human metabolism evolved in a low carbohydrate state: “The habitual diet of prehistoric man would have been low in carbohydrate and high in fat and protein and as such would promote his ability to conserve carbohydrate” (13, p.1331). She suggested that exposing humans that had evolved in this way to conserve any ingested carbohydrates to high carbohydrate diets, following the development of agriculture 12-18000 years could be harmful: Thus: “…the common modern diseases of diabetes, atherosclerosis, and obesity and associated hyper(tri)glyceridemia may be the present day manifestations of the effect of affluence on a once useful genetic trait, the ability to conserve carbohydrate” (13, p.1332).|
|22. 1960||The NIH establishes an Executive Committee on Diet and Heart Disease. The Committee proposes a National Diet Heart Study (NDHS).||The resulting pilot study established (i) that it is not possible to complete a double-blind dietary intervention in which foods are provided to the subjects and (ii) that a long-term study of the effects of a low-fat dietary intervention on CHD outcomes would be too expensive to undertake. Nina Teicholz concludes that the pilot NDHS “could reasonably be viewed in part as an industry-driven effort to broaden the market for its commodity oil. Companies contributing to the study included nearly every major food corporation in the country including the vegetable oil giant Anderson, Clayton & Company, Carnation, The Corn Products Company, Frito-Lay, General Mills, H.J.Heinz, the Pacific Vegetable Oil Corporation, Pillsbury, and Quaker Oats, among others” (4, p.91).|
|23. 1961||A new AHA committee “strengthened” by the addition of Keys’ principal acolyte, Jeremiah Stamler MD, reversed its 1957 decision that there was no strong evidence that dietary fat, especially saturated fat intake, is a key driver of the evolving CHD “epidemic”. Instead it put its financial, scientific and academic weight behind Keys’ Twin Hypotheses which it endorsed as the sole scientific option that it was prepared to support.||This acceptance was not based on any new scientific evidence from long-term randomized controlled trials. Rather it was more likely influenced by that generous $1.74 million “gift” from P&G to the AHA in 1948. The evidence is the conclusion in the 1961 AHA publication that lowering the blood cholesterol concentration “may lessen the development or extension of atherosclerosis and hence the risk of heart attacks or strokes” (14, p. 389). As a result, “the reduction or control of fat consumption under medical supervision with reasonable substitution of poly-unsaturated fats for saturated fats, is recommended as a possible means of preventing atherosclerosis and decreasing the risk of heart attacks and strokes” (14, p.390).|
|24. 1962-1989||The National Heart Institute provided funding for the Minnesota Coronary Experiment (MCE). Ancel Keys PhD was promoted as the principal investigator.||With the MCE, Ancel Keys initiated the first randomized controlled trial of his Diet-Heart and Lipid Hypotheses. Subjects partially replace dietary saturated fat with linoleic acid from corn oil. The study was extremely well controlled so that subjects in the intervention and control groups were provided with foods exactly according to the experimental protocol. Although the original findings were available in 1976, the final results were reported only in 1989. The reasons for the delay only become apparent when the data were recovered, re-analysed and republished by independent scientists in their Recovered Minnesota Coronary Experiment (RMCE). The findings of the RMCE disproved Keys’ Twin Hypotheses (see later) and so, once more, they had to be “buried”. The main conclusion from the study is that removing saturated fat from the diet causes harm so that it is unethical to prescribe this dietary approach to any patient.|
|25. 1965||On July 1st 1965, the Sugar Research Foundation sent its Director of Research, John Hickson, on a covert mission to the Harvard University School of Public Health. There he met with Harvard’s Professor Mark Hegsted MD to discuss ways in which the Harvard Medical School might be able to assist the sugar industry in deflecting attention away from an accumulating body of evidence clearly documenting the negative health consequences of sugar consumption.||Hickson’s mandate was to limit the potential damage resulting from 4 scientific papers published in the June 1965 issue of the Annals of Internal Medicine. All four articles provided evidence that either sugar or carbohydrates likely play a significant role in the causation of CHD. Hickson contracts Professors Frederick Stare MD and Mark Hegsted MD to write an editorial in the New England Journal of Medicine (NEJM). To ensure that they convey the “correct” message he pays the duo the equivalent of $50 000 in today’s money. Two years later the Editorial appears in the NEJM. It presents the false argument that there is no evidence linking sugar to CHD. It concludes that “increasing the proportion of polyunsaturated acids and reducing the level of dietary cholesterol are the dietary changes most likely to be of benefit (in the prevention of CHD)” (15, p.246)). The Editorial essentially ends any future interest in (or reference to) the possibility that carbohydrate-sensitive hypertriglyceridemia is a significant cause of CHD, thereby burying the novel work of Albrink and Man and Kuo from the 1950s. Thus whereas until 1965 there were two competing theories of which dietary macronutrient – carbohydrate or fat – is the more likely cause of CHD, after the publication of the Editorial, there remains only one – fat and especially saturated fat from the consumption of animal products. Key’s Diet-Heart hypothesis had won the argument even in the absence of a trace of definitive proof. All future research and teaching on this topic in medicine and in the nutrition sciences would have to reflect this industry-directed, false messaging.|
|26. 1965||The World Health Organization (WHO) funded the Co-operative Trial in the Primary Prevention of Ischaemic Heart Disease using the drug, Clofibrate.||This was the first study to evaluate the effects of a drug that lowers blood cholesterol concentrations on CHD outcomes. 15 745 males aged 30-59 in three European cities were randomized to intervention and control groups and followed for 5 years. The intervention group receives the cholesterol-lowering drug, clofibrate. Although the study found a significant reduction in the number of non-fatal heart attacks in the intervention group taking clofibrate, the total number of deaths in that group was significantly increased. The study establishes the principle that it cannot be assumed that a drug intervention, however well intended, is without risk to those in the intervention group. It is a rule that will be frequently ignored in the pursuit of developing novel drugs, like statins, that are prescribed to healthy people in the hope that some benefit might accrue in the long-term.|
|27. 1966||The National Heart Lung and Blood Institute initiated the Coronary Drug Project.||This study evaluated the effects of 5 different drugs, including niacin and clofibrate, most of which lower blood cholesterol concentrations, on CHD outcomes in 8341 US men aged 30-64. None of the drugs was effective and all produced worrying side-effects. The study confirmed the results of the 1965 WHO Co-operative trial using clofibrate: No drug that effectively lowers the blood cholesterol concentrations is without potentially harmful side-effects.|
|28. 1966-2013||The Sydney Diet Heart Study was initiated||458 men who had suffered a recent heart attack were randomized to control and dietary intervention groups. Those in the dietary intervention group replaced some dietary saturated fat with the polyunsaturated fatty acid, linoleic acid, from safflower and sunflower oil. The first outcomes reported in the 1970s showed an excess of deaths in the dietary intervention group. But this finding was hidden in the original publication and the data were essentially lost. The full extent of the harm caused by the replacement of dietary saturated fat with linoleic acid would only be revealed in 2013 with the publication of the Recovered Sydney Diet Heart Study, discussed subsequently.|
|29. 1967||Peter Kuo MD identified carbohydrate-sensitive hypertriglyceridemia (CSHT) as the most common lipid abnormality in patients with CHD.||Albrink and Man’s finding that hypertriglyceridemia, not hypercholesterolemia, appears to be the most common abnormality in persons with CHD was confirmed by Peter Kuo MD. He also confirmed their speculative conclusion that the hypertriglyceridemia is caused by dietary carbohydrates, not dietary fats. The effect of this finding was essentially nullified by the New England Journal of Medicine Editorial that appears in the November 1967 issue of that journal. From that moment, any potential role of CSHT in the causation of CHD was effectively written out of the medical consciousness. The effect has been so long lasting that even today the potential role of hypertriglyceridemia and of carbohydrates in the causation of CHD is fastidiously ignored in the teaching and practice of medicine.|
|30. 1967||Donald Fredrickson MD, Robert Levy MD and Robert Lees MD developed a novel classification of blood lipid abnormalities that predispose to CHD.||Donald Fredrickson and colleagues performed electrophoresis on blood samples and developed a simpler classification of the common blood lipid abnormalities found in persons with CHD – the Fredrickson Classification. Since electrophoresis is a laboratory method more widely available than the ultracentrifugation technique necessary for the Gofman classification, this classification soon began to enjoy widespread support. The classification includes a Type IV pattern that is essentially carbohydrate-sensitive hypertriglyceridemia. Thus the Fredrickson Classification clearly identifies dietary carbohydrate as one potential driver of CHD. However, with time, the Fredrickson Classification fell out of favour to be replaced by the simplistic model in which initially only blood total cholesterol concentrations were considered important. Fredrickson’s concerns about the role of carbohydrates in the genesis of CHD would be progressively forgotten and his contribution, like those of Gofman, Albrink, Man and Kuo, are written out of history.|
|31. 1968||The first results from the Oslo Secondary Prevention Trial were reported||The study found that whilst there were fewer fatal heart attacks in the dietary intervention group, overall mortality was unaffected. Thus the study found that whilst lowering the blood cholesterol concentration might reduce the clinical expression of one form of CHD, it must be causing increased deaths from other causes (since total mortality was not reduced). This would become a recurring theme in studies of blood cholesterol-lowering interventions. It would emphasize the concept that the most important measure of any intervention aimed at improving health outcomes, is the effect that intervention has on total (all-cause) mortality. Unfortunately this critical point continues to be ignored in any drug trial in which total mortality is not reduced In the intervention group – as occurs for example in the vast majority of clinical trial of the statin drugs. The data are simply not reported – as if they do not matter.|
|32. 1968||The first findings of the Los Angeles Veterans trial of the “effects of a diet high in unsaturated fat in preventing complications of atherosclerosis” were reported.||846 middle-aged elderly men living in a Los Angeles Veterans Administration Hospital were randomly assigned to a control and diet intervention group. The diet replaced saturated fats with a diet high in polyunsaturated fats. The intervention failed to reduce total all-cause mortality and increased deaths from cancer. Yet it was sold to the world as proof that a low-fat diet high in polyunsaturated fatty acids can prevent CHD. It would become one of four such studies – The Anti-Coronary Club Trial; the LA Veterans Hospital Study; The Finnish Mental Health Study; and The Oslo Secondary Prevention Trial – none of which showed a benefit of the diet, but which would be marketed for the next 50 years as definitive proof of the value of replacing dietary saturated fat with polyunsaturated fats from hydrogenated “vegetable oils” high in trans fats (and other manufactured chemicals, the long-term effects of which on the human body remain unknown even to this day).|
|33. 1969||The National Institutes of Health established a Review Panel to determine whether or not it is practical to initiate a trial of the Diet-Heart hypothesis.||This committee under the leadership of Edward “Pete” Ahrens concluded that a test of the Diet-Heart hypothesis would be too expensive and too impractical to be undertaken. Yet this did not hinder either the AHA or the NHI from continuing to promote, in the absence of any reasonable evidence, dietary interventions to lower blood cholesterol concentrations as if these interventions have already been proven to be beneficial and without risk of harm. Yet the evidence for potential harm had already been clearly established by the LA Veterans Hospital Study.|
|34. 1970||The results from Keys’ Seven Countries Study (SCS) were reported.||The study has significant problems that are seldom mentioned. First it was an associational study that cannot prove causation. Second the selection of the Seven Countries for study was not performed randomly. Third many of the studied countries were recovering from the debilitating effects of WWII. Fourth, the collection of the dietary data was hopelessly inept. The singular finding was a significant linear relationship between the median blood cholesterol concentrations in the different study populations and 10-year coronary deaths in those communities. Whilst there was a significant relationship between % calories from saturated fat and 10-year coronary death rates, there were a host of unexplained anomalies in death rates between communities eating either quite different or quite similar diets. Most importantly, as in the Framingham Heart Study, differences in blood cholesterol concentrations between individuals could not be explained by any single dietary factor including the amount of saturated fat in the diets. A host of other studies have since confirmed that, compared to a host of still unidentified factors, diet has a very marginal effect on blood cholesterol concentrations. Thus like the Framingham study, the SCS disproves the foundational prediction of Keys’ Diet-Heart Hypothesis which is that dietary animal fat consumption is the sole determinant of the blood cholesterol concentration.
Once again, this inconvenient finding is not condoned in the teaching of medicine or nutrition/dietetics.
|35. 1970||The National Heart Lung and Blood Institute (NHLBI) formed an expert Panel on Hyperlipidemia and Atherosclerosis. This would become the 1971 NIH Task Force on Atherosclerosis.||The Task Force concluded that definitive testing of Keys’ Diet-Heart hypothesis would be too expensive as it would cost upward of $1 billion. Instead it agreed to spend $250 million on two trials – the Lipid Research Clinics Coronary Prevention Trial (LRC CPPT) and the Multiple Risk Factor Intervention Trial (MRFIT) – neither of which tested the role of diet in CHD.
Thus by 1970 the NHLBI clearly had no intention of evaluating the effects of Keys’ low-fat diet on long term health outcomes. Yet this did not stop their hubristic promotion of that diet as the key component of their strategy to prevent CHD. The point perhaps is that the NHLBI had long since decided that theirs was the appropriate strategy and it did not require any scientific proof to justify their promotion of that preventive approach.
|36. 1971||The World Health Organization (WHO) initiated the European Collaborative Trial of Multifactorial Prevention of Coronary Heart Disease.||The trial recruited 60 881 men aged 40-59 from 80 factories in the UK, Belgium, Italy and Poland. One half received advice on physical activity, on eating a cholesterol-lowering diet, on smoking cessation, and on control of body weight and of blood pressure. The control group were left to their own devices. At the time it was the largest randomized trial of CHD prevention ever attempted. The trial outcomes were first reported in 1980.|
|37. 1971||The Multiple Risk Factor Intervention Trial (MRFIT) was initiated||12 888 persons presumed to be at the very highest risk for future CHD were recruited from a population of 361 662 screened individuals. The group was then split in two. The control group continued to follow its usual behaviours; the intervention group was exposed to intensive educational and behavioural interventions, unmatched in scope before or since. The initial findings from the study were first published in 1982.|
|38. 1971||Initiation of the The Helsinki Policeman Study of the role of glucose intolerance/insulin resistance/T2DM in the development of CHD.||1259 of the original participants in a 1966 study of Helsinki and National Police Force members were recruited to evaluate the role of glucose intolerance in the development of CHD. This was the first study specifically investigating the role of insulin resistance (with our without T2DM) on the future development of CHD. It therefore addressed the relationship first suggested by Albrink and Man in 1959 and Kuo in 1967. The initial results were first reported in 1979.|
|39. 1972||The results of the AHA National Cooperative Pooling Project were reported.||The AHA organized that the directors of 5 major US studies pooled their data in order to evaluate any possible relationships between supposed CHD risk factors and subsequent development of CHD. The data showed a “strong relationship” between risk factors and subsequent CHD development. However the predictive value of especially an elevated blood cholesterol concentration was, at very best, marginal. Thus an elevated blood cholesterol concentration above 249mg/dL (6.4mmol/L) increased risk of a first coronary event/sudden death for any individual from 0.0045/year to 0.0067/year. Thus according to those data, knowing one’s blood cholesterol concentration was without any value in predicting the probability of suffering a heart attack in the near future.|
|40. 1973||The Lipid Research Clinics (LRC) Coronary Primary Prevention Trial (CPPT) was planned.||3810 men were randomized to control and intervention groups both of which were placed on a cholesterol-lowering diet. The intervention group were treated with the cholesterol-lowering drug, cholestyramine, and followed for 7 years. The results of the study were first reported in 1984.|
|41. 1973||The first results of the NiHonSan (Nagasaki-Hiroshima/Honolulu/San Francisco Japanese ancestry) study were reported.||One of the unsolved paradoxes confronting the Diet-Heart hypothesis is that persons of Japanese ancestry living in Japan have very low CHD rates but higher rates of stroke than persons living in the US. The diet-heart hypothesis alone cannot explain this finding. The NiHonSan study sought to determine the role of environmental factors in explaining different CHD and stroke rates in persons of Japanese ancestry resident in either Japan or in two cities in the US.
The clearest finding from the NiHonSan study was that differences in the health of Japanese living in different parts of the world cannot be explained solely by lower or higher intakes of saturated fat and lower or higher blood cholesterol concentrations. Instead the key measure of overall health – total mortality – was (once more) not different between any of these groups despite many lifestyle differences and differences in blood cholesterol concentrations.
In short, the NiHonSan study failed to support Keys’ Twin Hypotheses.
|42. 1974||The Helsinki Businessmen study was initiated.||1222 initially healthy middle-aged men but with established coronary risk factors were randomized to intervention and control groups. The study lasted 5 years during which the intervention group received multiple interventions aimed at lowering their risk for future development of CHD. They were advised to stop smoking; to achieve a normal body weight with the adoption of a prescribed diet and to moderate their alcohol intakes. In addition those with hypertension or hypercholesterolemia were treated with appropriate prescription drugs.
The initial results were reported in 1991
|43. 1977||The McGovern Senate Select Committee on Nutrition and Human Needs released its Dietary Goals for the United States.||Senator George McGovern’s Senate Committee, faced with the threat of redundancy and loss of funding, decides it will dictate to the US, and subsequently the world, the foods everyone should be eating to remain healthy. At the time, Senator McGovern is himself experimenting with the zero-fat Pritikin diet. The committee is later described as “a bunch of kids, who just thought, Hell, we should say something on this subject before we go out of business” (3, p.45). The final report is compiled by a vegetarian, Nick Mottern, who had no formal training in the nutritional sciences. The report is heavily criticized as not being evidence-based. In response to the request from concerned senior scientists that the Committee should rather wait for more research “before we make announcements to the American public”, Senator McGovern famously responded that “Senators don’t have the luxury that the research scientist does of waiting until every last shred of evidence is in.”
By refusing to wait for that “every last shred of evidence”, Senator McGovern’s Committee inadvertently pushed the world into the global obesity/diabetes epidemic. It will be perhaps the single greatest medical/scientific failure of the past century.
Today 43 years later, the scientific world is still awaiting the publication of “every last shred of evidence” that proves the value of the low-fat Prudent diet.
|44. 1978||Dietary trans fats were first identified as being uniquely damaging to human health.||When P&G promoted the development of Crisco after 1913, it was unaware that the hydrogenation of seed oils produced a novel group of fatty acids known as trans fatty acids. By the 1960s, trans fatty acids contributed as much as 50% of the fatty acid content of products containing these hydrogenated fatty acids. Two scientists in the US, Drs Mary Enig and Fred Kummerow were the first to propose that trans fat are uniquely unhealthy. Dr Enig suggested that trans fatty acids might be linked to the development of cancers whilst Dr Kummerow presented evidence that trans fats may be uniquely involved in the causation of atherosclerosis. Thus the ultimate irony: Polyunsaturated fats in “vegetable” oils promoted by Keys and his acolytes as the key method to lower blood cholesterol concentrations to prevent CHD according to Keys’ Diet-Heart Hypothesis, might have contributed to the dramatic rise in CHD which began in the 1920s exactly when hydrogenated polyunsaturated fatty acids full of trans fats were first developed and marketed by P&G.|
|45. 1979||The Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project was initiated.||A group of European epidemiologists led by Professor Hugh Tunstall-Pedoe MD sensed a research opportunity in the 1970s when it became clear that rates of CHD were falling rapidly in many countries across the globe. They proposed a research project involving 21 countries spanning 4 continents to determine whether the falling CHD and stroke rates in these countries could be explained by changes in CHD “risk factors”. The results were reported in 1994.|
|46. 1979||The first results from the Helsinki Policemen study of insulin resistance as a predictor of CHD risk were reported||The results found that 5-year incidence of CHD deaths and non-fatal heart attacks was significantly related to elevated blood glucose concentrations measured 1-hr post-glucose ingestion. Ten year mortality as well as CHD deaths and non-fatal heart attacks were also higher in those with the highest fasting, 1-hr and 2-hr post-glucose-ingestion blood glucose concentrations. The authors concluded that the area-under-the-curve blood insulin concentrations post glucose ingestion were at least as strong a predictor of future CHD risk as was the blood cholesterol concentration.
Subsequently a number of more recent studies have proposed that “insulin resistance is the most important single cause of coronary artery disease” (16, p.1449).
|47. 1980||The inconvenient results of the WHO European Collaborative Trial of Multifactorial Prevention of Coronary Heart Disease were released.||This study of 60 881 middle-aged men employed in 80 factories in the UK, Belgium, Italy and Poland found that reducing the key risk factors reduced, but not significantly, total mortality, non-fatal heart attacks and fatal CHD. In only one country, Belgium, was the reduction in all these outcome measurements statistically-significant. The study is usually touted as further evidence that coronary risk factor intervention trials significantly reduce future CHD risk. But this study like many others (MRFIT; Helsinki Businessmen Study; The Women’s Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT)) failed to achieve that outcome.|
|48. 1980||The Food and Nutrition Board of the National Academy of Sciences released Towards Healthful Diets.||The publication of the US Department of Agriculture Dietary Goals for Americans (USDADGA) was heavily criticized by many members of the National Academy of Sciences, most especially its President Philip Handler. The organization’s response was to publish a contrary and more conservative opinion entitled Toward Healthful Diets (17). The review argued that the USDADGA was basing its recommendations in the absence of any scientific evidence that those guidelines would do good and with no risk of harm. The review made six dietary recommendations, none of which promoted the low-fat high-carbohydrate diet for disease prevention. Thus:
“Select a nutritionally adequate diet from the foods available, by consuming each day appropriate servings of dairy products, meats or legumes, vegetables and fruits, and cereal and breads” (17, p.16).
|49. 1982||The inconvenient findings of the MRFIT study were published||This large study of more than 12 000 subjects provided the gold-standard test of an intervention that radically altered for the better, the “health” behaviours of those in the intervention group. Subjects in that group greatly reduced their dietary fat and cholesterol intakes; their blood cholesterol concentrations fell by 5-7%; their smoking rates fell by 50%; and 67% of subjects with hypertension normalized their elevated blood pressures. These changes were sustained for 7 years.
But all to no avail as the trial “failed miserably”. There were no measurable health benefits from these favourable reductions in “risk factors”.
Thus after spending $115 million in a trial that lasted 10 years, the researchers had conclusively proved that multiple interventions that substantially modify what are considered to be the most important CHD risk factors (smoking, high blood pressure and elevated blood cholesterol concentrations) had absolutely no effect on the measured health outcomes.
This study is never mentioned by the advocates of the Diet-Heart hypothesis.
Nor is it mentioned that T2DM was clearly the strongest risk factor for future CHD events in this population.
One possibility is that the change to a low-fat diet negated the expected beneficial effects of reduced rates of smoking and of hypertension in the intervention group. This too is never mentioned. Nor is it mentioned that the incidence of lung cancer was increased in the intervention group.
|50. 1984||The results of the Lipid Research Clinics Cholesterol Primary Prevention Trial (LRC CPPT) were published||The LRC CPPT trial tested the effects of the cholesterol-lowering drug cholestyramine on CHD outcomes during 7 years of follow up. Prior to the start of the experiment the researchers had agreed that, because of the extraordinary importance of the study – it would establish for the first time whether or not lowering the blood cholesterol concentration was harmful or helpful – they would accept, as significant, only a finding that the study had a less than 1% probability that any positive findings were the result of chance alone. But when the results were not significant at the 1% level, the researchers simply moved the statistical goal posts. This allowed them to claim that the study had produced a statistically-important finding. In fact the only “significant” finding was that the annual risk of heart attack fell by 0.2% in the intervention group. Once again, however, the truly important measurement – total all-cause mortality – was not different between groups.
In a classic example of scientific fraud, This failed study was then used as the definitive proof that lowering blood cholesterol concentrations by a low-fat dietary intervention would also reduce CHD risk. When the chief investigator was asked how he could possibly justify this clearly fraudulent interpretation he responded: ‘It’s an imperfect world. The data that would be definitive is ungettable, so you do your best with what is available’” (3, p. 58).
In other words when the data do not support your preconceived biases you simply bury the evidence by lying to the world. So much for the need for an independent, impartial body of scientific evidence.
|51. 1984||The 1984 NIH organized The National Consensus Development Meeting||Once Keys’ acolytes at the NIH had decided that the LRC CPPT study had provided the definitive evidence that lowering blood cholesterol concentrations by whatever means – by drugs or by diet – would reverse the CHD epidemic, they needed to ensure that the fake findings of that study would never be questioned. So they convened a National Consensus Development Meeting run over 3 days. The reality is that the goal of all Consensus Meetings is to present the illusion of consensus when it is clear that no such consensus exists. The meeting was chaired by one of Keys’ most stalwart supporters Dr Daniel Steinberg MD who had written the consensus document even before the meeting began. The meeting simply endorsed his personal biases as if they were a National Consensus. The meeting resolved that “Saturated fat increases LDL cholesterol, a major cause of atherosclerosis and CHD, and replacing it with polyunsaturated or monounsaturated fat decreases LDL cholesterol”. As a logical extension it came up with “a simple set of numbers that satisfied everyone. We proposed ‘desirable’ (blood cholesterol) levels of <200 (mg/dL) for persons younger than 20 years; <220 for those 30 to 39 years; and <240 for those older than 40 years, and we proposed the same guidelines for men and women” (18, p.10). Thirty-six years later and still without definitive supportive evidence, these guidelines remain entrenched in the teaching of medical practice around the globe.
At the time the Consensus was vigorously opposed by a number of senior scientists. Today they would simply be dismissed as “cholesterol sceptics”.
|52. 1987||The National Cholesterol Education Program (NCEP) was launched in the US||The NIH National Consensus Development Meeting, actually the Steinberg Consensus, entrenched elevated blood cholesterol concentrations as the major driver of CHD and established the (urgent) need for all to lower their elevated blood cholesterol concentrations. But at the time in 1984, the majority (61%) of US Physicians did not share this certainty; they did not believe that cholesterol was the key driver of CHD. The NIH therefore decided that this would have to change.
The goal of the NCEP was to give scientific credibility to a nation-wide program of blood cholesterol testing in all but infants, so that those with elevated blood cholesterol concentrations could receive appropriate management to reduce their future risk for developing CHD. In their zeal to promote this program, few questioned the extraordinary costs that such a program would entail.
Also hidden was the fact that the major beneficiaries of the NCEP would not be the health of the US public. Rather the key beneficiaries of the NCEP would be the pharmaceutical industry (in providing medications to lower elevated blood cholesterol concentrations); the laboratories involved in measuring blood cholesterol levels in hundreds of millions of US citizens; and the tens of thousands of medical practitioners involved in sampling their patients’ blood (for cholesterol testing).
In reality the NCEP was little more than a targeted intervention by the US pharmaceutical industry to prepare the US public and their physicians for the introduction of a novel group of prescription drugs – the cholesterol-lowering statin drugs then still in development – that it hoped would provide the industry with an unprecedented financial windfall.
In the end, the strategy worked perfectly as the statin drugs, first marketed a few years later, would become one of the most financially-successful drugs ever produced. This would usher in an era of unmatched profits for the pharmaceutical industry.
|53. 1989||The initial results of Keys’ Minnesota Coronary Experiment (MCE) were reported||Thirteen years after the results of the MCE first became available to the study scientists, they were finally published in a relatively obscure medical journal. This initial (1989) report claimed that the replacement of dietary saturated fat with the polyunsaturated fatty acid, linoleic acid, was neither beneficial nor harmful. The reality was that when Keys’ acolytes discovered that their original MCE data did not support Keys’ Diet-Heart Hypothesis, in their embarrassment, they chose to bury the data. But the publication of the Recovered MCE results, discussed subsequently, showed that the low-fat dietary intervention not only failed to produce any benefits; in reality it caused harm. Had these findings been honestly reported in 1976, they would likely have prevented the publication of the USDA Dietary Guidelines of Senator McGovern’s Committee in 1977 and would have forestalled the global damage caused by the acceptance of those guidelines that promote the low-fat diet (and which were in any case, disproven by Keys’ own MCE study).|
|54. 1989||The results of Dr Robert Knoop’s Dietary Alternatives Study and of the Boeing Employees Fat Intervention Trial (BeFIT) were published||By 1977 it had become clear to the Framingham Heart Study (FHS) researchers (and others) that an elevated blood cholesterol concentration was a very weak predictor of future CHD risk. Instead, for a brief period (1977-1979), those researchers published a series of papers showing that a low blood HDL-cholesterol concentration was a much better predictor of CHD risk. However after 1979 those same researchers, perhaps warned that this “unorthodox” opinion would harm their careers and future funding prospects should they persist, just as quickly reverted to their original opinion by embracing the conventional AHA/NIH party line: “serum total cholesterol makes ‘a significant contribution to….coronary heart disease in persons older than 50 and practically up into the eighties’” (19).
Working with employees of the Boeing Company in Seattle, Washington, Dr Robert Knoop and his colleagues would spend the years between 1989-2005 studying the effects of diets differing in their fat and carbohydrate contents on blood LDL- and HDL-cholesterol concentrations. The overriding conclusions were that: (i) diets lower in fat cause blood HDL-cholesterol concentrations to fall; and (ii) that this effect is greater in women than in men. Since they believe that lowering blood HDL-cholesterol concentrations is unlikely to be a healthy outcome, they began to question whether any woman should ever be placed on a low-fat diet. Naturally their work is ignored since it establishes a potentially important negative consequence of the promotion of low-fat diets for everyone.
|55. 1991||The results of the Helsinki Businessmen Study (HBS) were reported||The goal of this study was to determine whether lifestyle modification, in particular stopping smoking, achieving an ideal weight through adoption of a “healthy” diet, moderation of alcohol use, and active drug treatment of those with hypertension or hyperlipidemia that did not respond to diet, would reduce the subsequent development of CHD in this group of Helsinki businessmen.
The study, like the MRFIT study, produced a seriously inconvenient finding. Although the intervention group succeeding in reducing their CHD risk factors by 46%, yet their rates of CHD events during the follow-up were significantly higher than in the control group who had made no special attempt to modify their “risk factors”.
This paper has also been forgotten by history since it refutes what would otherwise appear to be common sense. Reversing coronary risk factors must reduce coronary risk.
But both the MRFIT and the HBS, like the Women’s Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT), dispute this logically obvious (and appealing) prediction.
|56. 1993||The Women’s Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was initiated||The goal of the Women’s Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was to determine whether a population of older women who adopted the USDA Dietary Guidelines for Americans would reduce their risks of colo-rectal and breast cancers and suffer less from coronary heart disease.
For the study 48 835 post-menopausal women were randomized to one of two groups. The control group was encouraged to continue eating their usual diet whereas the intervention group adopted the USDA Dietary Guidelines by reducing their fat intake and eating more vegetables and grains. Women in the intervention group also received an “intensive behavioural modification program” comprising 18 group sessions in the first year followed by quarterly maintenance sessions for the next 7 years. The control group received only a copy of Dietary Guidelines for Americans. As a result any positive outcomes in the intervention group could not be ascribed purely to dietary change since the intervention group received additional interventions not shared by the control group.
The first results of the study were reported in 2005.
|57. 1993||Harvard University’s Professor Walter Willett MD invented the Mediterranean Diet.||Beginning in the 1980s scientists in the three nations – Greece, Italy and Spain – that produce much of the world’s olive oil, began to wonder if perhaps it was olive oil in especially the diet of the Cretans that explains their low rates of CHD (as identified by Keys’ Seven Countries Study). Funded in part by support from those three governments between 1993 and 2004, about 50 olive-oil sponsored conferences were held around the world, promoting the idea that the “Mediterranean” diet, especially if it contained liberal amounts of olive, oil was especially healthy for humans. At the very first conference, Professor Walter Willett presented his (unique) Mediterranean Diet Pyramid. The key differences from the Food Pyramid promoted by the 1977 US Dietary Goals for Americans, were that beans and legumes are the main source of protein with fish, poultry and eggs to be eaten only once weekly and red meat at most “monthly”. This conforms to Professor Willett’s personal choice as someone who eats a predominantly plant-based diet.
Paradoxically over the past 30 years meat consumption in France, Italy, Spain and even amongst the Cretans, the Swiss and the Japanese, has increased substantially. Despite this, heart disease rates have continued to fall in all those countries even though average blood cholesterol concentrations, especially in the Japanese, have increased.
These findings do not support Willett’s interpretation that the Mediterranean diet is uniquely healthy because it limits the consumption of animal produce to, at most, once weekly and meat only once monthly.
|58. 1994||The findings of the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study are reported.||The MONICA study was initiated in 1974 with the goal of measuring trends in cardiovascular mortality and coronary heart disease and stroke morbidity in 21 countries and to assess the extent to which these trends could be explained by changes in known risk factors, daily living habits, health care, or major socioeconomic features measured at the same time in those participating countries. The assumption was that falling rates of CHD in those countries would be explained by changes in the “classical” risk factors.
The findings of the study were that perhaps as little as 15% of the variance in coronary-event rates in women and 40% in men could be “explained” by trends in the “classic” coronary risk, indicating that the so-called classic risk factors explain less than a half to three-quarters of the real factors explaining CHD.
The findings are therefore in line with those from the MRFIT study, the WHO European Collaborative Trial of Multifactorial Prevention of Coronary Heart Disease, the Helsinki Businessmen Study and the The Women’s Health Initiative Randomized Controlled Dietary Modification Trial.
|59. 2003||The LookAHEAD (Action for Health in Diabetes) Trial was planned.||The primary objective of the LookAHEAD clinical trial was to assess the long-term effects (up to 11.5 years) of an intensive weight loss program conducted over 4 years with overweight and obese individuals with T2DM.
Approximately 5000 male and female participants with T2DM, aged 45-74 years with elevated body mass index, were randomized into one of two groups – an intensive lifestyle intervention group or the control group.
The goal of the intensive lifestyle intervention was to produce a sustainable weight loss through decreased caloric intake and increased physical activity. The control group received diabetes support and education alone. The primary study outcome was the time to the development of the first major cardiovascular disease (CVD) event.
The first results were reported in 2014.
|60. 2003 – 2013||The Prospective Urban Rural Epidemiology (PURE) study was initiated.||Between January 1st 2003 and March 31st 2013 the Prospective Urban Rural Epidemiology (PURE) study enrolled and finally studied 135 335 individuals aged 35-70 years living in 628 urban and rural communities in 18 countries on five continents. The study included three high-income (Canada, Sweden, and United Arab Emirates), 11 middle-income (Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, occupied Palestinian territory, Poland, South Africa, and Turkey) and four low-income countries (Bangladesh, India, Pakistan, and Zimbabwe). On entry to the study, participants completed standardized questionnaires that collected information about their socioeconomic status, lifestyle, health history, medication use and physical activity. Food intake was assessed using validated, country-specific food frequency questionnaires. Follow up occurred at 3, 6 and 9 years. The initial goal of the study was to determine whether the burden of risk factors and the incidence of cardiovascular disease was “higher in low- and middle-income countries than in high-income countries, whether mortality after a cardiovascular event is higher in low- and middle-income countries than in high-income countries, or whether both are true”. In time the study would evolve into the most thorough epidemiological evaluation of the Diet-Heart and Lipid hypotheses ever undertaken, dwarfing everything that had gone before and most especially Keys’ error-ridden Seven Countries Study.|
|61. 2005||The inconvenient results of the Women’s Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) were reported.||The published results of the WHIRCDMT found that the low-fat “heart healthy” diet failed to reduce risk for developing cancers of the colon, rectum or breast; it also failed to influence CHD outcomes. In fact the sole significant finding of the study and the one that the original scientific publication managed unsuccessfully to hide, was that the health of postmenopausal women who began the trial with either CHD or T2DM worsened if they ate the low-fat diet. The study would become the first in the trinity of studies (the WHIRCDMT; the Recovered MCE; and the Recovered SDHS) all of which establish that the removal of saturated fat from the diet causes harm. Thus the prescription of low fat diets that remove saturated fat from the diet are unethical because they are now known to cause harm. In medical practice it is unethical to promote any practice that is known to cause harm.
The study also found that the risk for developing T2DM was increased in women who were prescribed cholesterol-lowering statin drugs. And that the low fat diet did not increase weight loss compared to the usual American diet.
All these findings are particularly inconvenient for the Diet-Heart Hypothesis.
This explains why the true findings of this study were also conveniently buried.
|62||Publication of a study comparing Weight Loss on Low-Carbohydrate, Mediterranean, or Low-Fat Diets.||For this two-year trial, 322 moderately obese subjects, with an average age of 52 years were randomly assigned to one of three diets:
A low-fat, restricted-calorie diet.
A Mediterranean, restricted-calorie “rich in vegetables and low in red meat, with poultry and fish replacing beef and lamb”. This diet is essentially the Willett “Mediterranean” diet.
A low-carbohydrate, non-restricted-calorie diet – 25 g of carbohydrate/day for the first 2 months with a gradual increase to 120g/day. Intake of total calories, protein, and fat were not limited. The diet is that described by Atkins.
This study established two irrefutable facts.
First that the American Heart Association prescribed low fat-diet performed dismally and was substantially worse than the Atkins low-carbohydrate diet. This has since been shown repeatedly. Yet it is as if the evidence simply does not exist. This is important since in defending their disproven diet, the AHA has wasted much effort vilifying the Atkins diet.
Second that the Mediterranean diet was no better and in some case, not as effective as the Atkins diet. This key fact has also been rigorously suppressed since the new but still unproven dogma is that the “Mediterranean” diet is the optimum diet to lower CHD risk. Yet in all relevant measures in this study, the Atkins Diet outperformed this example of a “Mediterranean” diet.
|63. 2013||The results of the Recovered Sydney Diet Heart Study were published||The original findings of the Sydney Diet Heart Study (SDHS) which began in 1966 were reported in 1978 as the following: “Survival was slightly better in the second (dietary intervention) group. Multivariate analysis showed that none of the dietary factors were significantly related to survival”. But even then the data did not support that conclusion. Rather the data showed that the intervention group that had replaced dietary saturated fats with an increased ingestion of polyunsaturated fatty acids, actually did worse. But the extent of that “worseness” was buried as the results were incompletely analysed and were published in a relatively obscure medical journal. The authors would have considered their actions justifiable since their findings disproved Keys’ Diet-Heart Hypothesis and were therefore entirely unacceptable.
But when the original data were “recovered” and subjected to independent analysis 35 years later, a rather different result emerged. Thus: “The intervention group had (significantly) higher rates of death than controls” (20). These higher death rates in the intervention group occurred in all important categories – all cause; cardiovascular disease; and coronary heart disease.
Had these findings been properly analysed and honestly reported in 1978 they would have been accepted as disproof of Keys’ Diet-Heart hypothesis and the world would not have been subjected dietary guidelines based on a false and now frequently disproven hypothesis.
|64. 2014||The LookAHEAD trial was terminated prematurely.||This trial sought to use the conventional Calories In Calories Out (CICO) model of weight control to reverse obesity in persons with T2DM and so reduce the development of T2DM complications.
On October 2012, the planned 11.5-year study was terminated as “futile” after 9.6 years when it was established that these interventions were no more effective in slowing the progression of arterial damage than was doing nothing.
This very expensive and well conducted study confirms that T2DM will not be beaten by encouraging persons with T2DM to exercise more and to eat a diet rich in blood glucose- and blood insulin-raising, obesogenic carbohydrates.
|65. 2016||The results of the Recovered Minnesota Coronary Experiment (RMCE) were published.||On the death of his father, Ivan Franz II who had been the principal investigator of the MCE, his son, Ivan Franz III, discovered the original data for the MCE trial. He submitted the recovered computer files for analysis to those who had reported the Recovered Sydney Diet Heart Study (RSDHS).
The recovered data confirmed that the original MCE report had misrepresented and significantly underplayed the true findings of the study by implying that there were no differences in CHD outcomes between the control and intervention groups in that original study.
In contrast the RMCE established that no age group benefitted from the intervention but survival was significantly worsened in those over 65 who were placed on the intervention “heart-healthy” prudent diet. In addition “there was a 22% higher risk of death for each 30mg/dL (0.78mmol/L) reduction in serum cholesterol (concentration)” (21).
Thus the evidence from the WHIRCDMT, the Recovered MCE and the Recovered SDHS is unequivocal. Removing saturated fat from the diet causes harm to both men and women.
It is therefore unethical ever to advise anyone to follow this dietary practice. Since the first ethical rule in Medicine is: First do no harm.
|66. 2017||A report of the association of food consumption, blood cholesterol concentrations and cardiovascular disease in 42 European countries||A group of scientists from the Czech Republic used international statistics to search for associational (non-causal) relationship between nutritional factors and the prevalence of cardiovascular disease in 42 European countries. The mortality data were derived from the European Cardiovascular Disease Statistics whereas the nutritional information came from the FAOSTAT website which reports the “total quantity of foodstuffs produced in a country added to the total quantity imported and adjusted to any change in stocks that may have occurred during the reference period” (22).
The overall conclusion from these associational relationships was that eating more animal fat and protein and less carbohydrate was associated with higher blood cholesterol concentrations and a lower prevalence of hypertension and cardiovascular disease.
Whilst associational studies cannot prove causation, they can perhaps show what is unlikely to be true. Which in this case are Keys’ Twin Hypotheses.
The clearest evidence to refute Keys’ Lipid Hypothesis were the data showing an inverse relationship between actual CVD mortality rates in the 42 countries and the prevalence of raised blood cholesterol concentrations in those countries.
The authors concluded: “Our results do not support the association between cardiovascular disease (CVDs) and saturated fat which is still contained in official dietary guidelines. Instead, they argue with data accumulated from recent studies that link CVD risk with the high glycemic index/load of carbohydrate-based diets. In the absence of any scientific evidence connecting saturated fat with CVDs, these findings show that current dietary recommendations regarding CVDs should be seriously reconsidered” (22, p.1).
|67. 2017||The first results from the Prospective Urban Rural Epidemiology (PURE) study are published.||The key findings from this large study of 135 335 individuals aged 35-70 years living in 628 urban and rural communities in 18 countries on five continents, were that those living in countries with high carbohydrate intakes had higher rates of total mortality whereas total fat and individual types of fat intake were associated with lower total mortality. Total fat intake and types of fat eaten were also not associated with cardiovascular disease, heart attack or death from cardiovascular disease but saturated fat intake predicted lower rates of stroke.
The authors concluded that: “Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk” (23, p.776).
The principal investigator in this study is Professor Salim Yusuf PhD who is one of the world’s most respected medical scientists. Yusuf was one of the few who were critical of the recommendations of the 1984 National Cholesterol Consensus Development Conference. In 2011, he was rated the world’s second-most cited researcher, in part for his conduct of large-scale clinical trials that have had a significant impact on the treatment and prevention of cardiovascular and cerebrovascular disease. From 2015-16 he served as President of the World Heart Federation and it was during that time that Professor Yusuf dropped the findings of the PURE study on an unsuspecting world. Predictably his apparent desertion of the Keys’ Diet-Heart hypothesis was not universally appreciated by those medical and scientific colleagues who saw little value in the tentative conclusion he and his team had drawn from an epidemiological associational study. Yet they apparently had few qualms that Keys’ Twin Hypotheses are also based on epidemiological associational studies of much poorer quality. In particular the dietary analyses in the PURE study were exceptionally well conducted – the opposite of the case in Keys’ Seven Countries Study.
|68. 2017||The first results of the Virta Health Study were reported.||In 2014 Finnish entrepreneur Sami Inkinen teamed up with two of the original and most respected low-carbohydrate diet investigators, Stephen Phinney MD and Jeff Volek PhD to form the new company, Virta Health, located in San Francisco. The goal was to advance the work of Atkins, Westman, Phinney and Volek and to determine whether T2DM might be “reversed” by a ketogenic low-carbohydrate diet. Inkinen’s genius was to realise that T2DM is ultimately a behavioural disease caused by poor dietary choices in those with insulin resistance. He realized that its reversal cannot be achieve by the prescription of therapeutic drugs through occasional visits to medical specialists. Instead it requires that the patient with T2DM must receive continuous feedback, advice and encouragement on a moment-to-moment basis. Inkinen and his team appreciated that this could only be achieved through a radical new medical model – the Virta Health Clinic model which “has reinvented the diabetes care model by providing patients with continuous, technology-enabled remote care from Virta medical providers who are experts in safely reducing and eliminating diabetes medications”.
The remote care Virta Clinic was developed beginning in 2015; shortly thereafter 262 subjects with T2DM aged between 21-65 years were recruited to participate in a 5 year study of the effects of the intervention on multiple health markers. To date, outcome results have been reported at 3, 12 and 24 months.
After one year 60% of subjects had “reversed” their T2DM by lowering their HbA1c values to below 6.5%, representing an average 1.3% reduction in HbA1c values (despite reduced medication use). Furthermore 94% of subjects had either reduced or eliminated insulin use. Subjects also lost an average of 12% of body weight, equivalent to 14 pounds.
Changes in conventional metabolic risk factors for coronary heart disease were also dramatic. When compared to subjects receiving conventional management for T2DM, those receiving the Virta intervention showed significantly greater beneficial improvements in increased ApoA1 and HDL-C concentrations; in reduced high sensitivity CRP values (a measure of inflammation); in reduced triglyceride/HDL-C ratios; in reduced ApoB/ApoA1 ratios; in reduced total LDL particle numbers and especially reduced in small, dense LDL particle numbers; in reduced large VLDL particle numbers; in reduced blood pressure and in reduced anti-hypertensive medication use; and in reduced white blood cell counts. As a result 10-year atherosclerotic cardiovascular disease (ASCVD) risk had decreased 12%.
Thus the study has established that T2DM is a reversible medical condition. However its reversal requires the prescription of a high-fat low-carbohydrate ketogenic diet – the opposite of Keys’ low-fat high-carbohydrate diet. The study also confirmed that the prescription of a high-fat diet “reverses“ all established metabolic risk factors for CHD with the exception of LDL-cholesterol which might increase modestly in some.
Thus the Virta Clinic study provides the final repudiation of Keys’ Diet-Heart hypothesis.
|69. 2019||Professor John Ioannidis declared that nutritional epidemiology is a scandal – “It should just go in the waste bin”.||John Ioannidis MD PhD is one of the world’s most influential medical scientists whose special interest is the quality of evidence used to make medical decisions. In the 1990s he turned his attention for the first time to nutritional epidemiological science. He showed that the nutritional sciences are especially weak because they lack hard evidence but have an overreliance on epidemiological associational studies with statistically weak outcomes that cannot prove causation. Thus “thousands of spuriously significant associations have already been produced and translated in heavily opinionated, debated recommendations. Getting another significant result in a field that is already saturated with so many significant results offers no information gain: we still (think we) know what (we thought) we knew. Conversely, ‘negative’ results offer high information gain, because they change our probably false beliefs about potentially effective interventions … we should hope to get more ‘negative’ results in the future” (24, p.1386). Essentially he suggests the need for a revolution in the manner in which nutritional research is conducted and how the results are interpreted. Most of that which has been done before needs to be thrown “in the waste bin”. This would include Keys’ Twin Hypotheses (although he does not personally advocate that).|
|A collection of 6 articles published in the Annals of Internal Medicine exonerates the consumption of red and processed meats as a significant cause of ill-health in humans.||The fundamental basis for Keys’ Twin Hypotheses was that the US diet had changed radically in the years before the outbreak of the CHD epidemic, beginning in the 1920s. The key change according to this logic was that US citizens (considered to be representative of population around the world) had exchange a diet high in cereals and grains for one full of animal fats, especially saturated fats. But actual data of what US citizens were eating in the 18th, 19th and early 20th century simply do not show that. Meat consumption had dropped progressively before beginning to rise again in the mid-20th century. Thus Keys’ Twin Hypotheses were based on a fundamental flaw in logic.
These studies confirm that replacing meat in the diet is not associated with measurable health benefits, the final disproof of Keys’ Twin Hypotheses.
On the basis of all this information it is extremely difficult, in fact impossible, to make any credible case to support Keys’ Twin Hypotheses. In the following 11 columns I provide the details behind each of these 70 events before providing a final summary of exactly what this multi-billion dollar research effort, the goal of which was to provide support for Keys’ Twin Hypotheses, did actually reveal.
It’s finally time to expose this evidence more widely, but especially to the medical and nutrition/dietetics professions, so that in 2020 we can give humans the appropriate dietary advice that will return us all to a state of optimum metabolic health.
- Moore TJ. Heart Failure: A Critical Inquiry into American Medicine and the Revolution in Heart Care. New York, NY: Simon and Schuster, 1989. [Also Moore TJ. The cholesterol myth. The Atlantic. 1989;264(September):37].
- Smith RL, Pinckney ER. The Cholesterol Conspiracy. Warren H Green Inc; St Louis MI, 1991.
- Taubes G. Good calories bad calories. Fats, carbs, and the controversial science of diet and health. Anchor Books, New York, NY. 2008.
- Teicholz N. The Big Fat Surprise. Why butter, meat and cheese belong in a heathy diet. Simon and Schuster, New York, NY. 2014.
- Ravnskov U. The Cholesterol Myths. Exposing the fallacy that saturated fat and cholesterol cause heart disease. New Trends Publishing, Washington, DC. 2000.
- Colpo A. The Great Cholesterol Con. LULU publishers, 2007.
- Kendrick M. The Great Cholesterol Con. The truth about what really causes heart disease and how to avoid it. John Blake, London, UK. 2007.
- Ravnskov U. Fat and cholesterol are good for you. GB Publishing, Sweden. 2009.
- Rosch PJ. Fat and cholesterol don’t cause heart attacks. And statins are not the solution. Columbia Publishing, UK. 2016.
- Keys A. Prediction and possible prevention of coronary disease. Am J Publ Health 1953;43:1399-1407.
- Page IH, Stare FJ, Corcoran AC, et al. Atherosclerosis and the fat content of the diet. Circulation 1957;16:163-178.
- Ahrens EH, Hirsch J, Insull W, et al. Dietary control of serum lipids in relation to atherosclerosis. JAMA 1957;164:1905-1911.
- Albrink MJ, Man EB. Serum triglycerides in coronary artery disease. Arch Intern Med 1959;103: 4-8.
- Central Committee for Medical and Community Program of the American Heart Association. Dietary Fat and Its Relation to Heart Attacks and Strokes. JAMA 1961;175:389-391.
- McGandy RB, Hegsted DM, Stare FJ. Dietary fats, carbohydrates and atherosclerotic vascular disease. NEJM 1967;277:186-192; (concluded) NEJM 1967;277:242-247
- Adeva-Andany MM, Martinez-Rodriquez J, Gonzalez-Lucan M et al. Insulin resistance is a cardiovascular risk factor in humans. Diab Metab Syndr:Clin Res Rev 2019;13:1449-1455.
- Anon. Toward Healthful Diets. Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington DC: 1980.
- Steinberg D. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it – almost. J Lipid Res 2006;47:1-14.
- Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease: New perspectives based on the Framingham Study. Ann Intern Med 1979;90:85-91.
- Ramsden CE, Zamora D, Leelarthaepin B, et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death. Evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013 Feb 4;346:e8707.
- Ramsden CE, Zamora D, Majchrzak-Hong S, et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ 2016;353:i1246.
- Grasgruber P, Sebera M, Hrazdira E, et al. Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries. Food Nutr Res 2016;60:394
- Dehghan M, Mente A, Zhang X, et al. Association of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet 2017;390:2050-2062; Mente A, Dehghan M, Rangarajan S, et al. Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study. Lancet 2017;390:774-787; Miller V, Mente A, Dehghan M, et al. Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study. Lancet 2017;390:2037-2049; Dehghan M, Mente A, Rangarajan S, et al. Association of dairy intake with cardiovascular disease and mortality in 21 countries from five countries (PURE): a prospective cohort study. Lancet 2018;392:2288-2297.
- Ioannidis JPA. We need more randomized trials in nutrition – preferably large, long-term, and with negative results. Am J Clin Nutr 2016;103:1385-1386.
About the Author
Professor Tim Noakes has dedicated his life to the pursuit of knowledge and undoing the last 50 years of ‘bad’ nutritional science. His aim is to fix the future outlook of human health, by changing the way people eat and the food policies to enable the change.
Prof. Noakes has published more than 750 scientific books and articles. He has been cited more than 19 000 times in scientific literature, has an H-index of 71 and has been rated an A1 scientist by the National Research Foundation of South Africa for a second 5-year term. He has won numerous awards over the years and made himself available on many editorial boards.