Ancel Keys’ Cholesterol Con. Part 10 – 1978-1979

1978. The identification of dietary trans fats as uniquely damaging to human health.

When in 1 Proctor and Gamble employed the German chemist E.C.Kayser to produce the hydrogenated “vegetable” oil from cotton seeds, a product that would become known as Crisco (1), they had no legal requirement to prove that their novel industrially-produced food product was in fact safe for human consumption. Instead they claimed, without evidence, that it was healthier than the traditional fats that humans had always eaten including butter, lard and suet. The false assumption seems to have been that an industrially-produced product was logically superior to the natural foods that humans had eaten for millennia. 

But by 1968 the AHA had become aware of concerns about the safety of trans fats and was preparing to release this statement: “Partial hydrogenation of polyunsaturated fats results in the formation of trans forms which are less effective than the cis, cis forms in lowering cholesterol concentrations. It should be noted that many currently available shortening and margarines are partially hydrogenated and may contain little polyunsaturated fat of the natural cis, cis form” (2, p.22). 

Indeed 150 000 pamphlets containing this statement were printed by the AHA but were never released. Why? Because Fred Mattson, then in charge of P&G, convinced Campbell Moses, then medical director of the AHA, to pulp them. Instead the AHA document that was released contained the usual Keysian recommendations – restrict calories, substitute polyunsaturated fats for saturated fats, and reduce cholesterol in the diet. This would be the advice promoted in the 1977 McGovern Senate Committee that gave us the 1977 US Dietary Goals for Americans (3), discussed in an earlier column (4). 

When a young graduate student at the University of Maryland, Dr Mary Enig PhD, read the McGovern Committee’s report, she identified a number of false statements (2). 

First, the Committee’s claim that the consumption of animal fats was on the increase, was false; consumption of animal fats was on the decline in the US at that time (5-7). Whilst it was true that total fat intake had increased (figure 1), this was due in the main to an increase in consumption of unsaturated fats from “vegetable” oils with 50% of the increase coming from liquid “vegetable” oils and about 41% from margarines made from vegetable oils” (2, p.23) (figure 1).

Legend to Figure 1: Individual daily intake (grams) of different fats in the US between 1909 and 1972. Note that the increase in total fat consumption after 1939 was due to an increase in “vegetable” fat consumption, including linoleic acid which is extracted from flax, hemp, poppy, safflower and sunflower seeds as well as from corn and soybean oils. The adverse consequences of replacing dietary saturated fat with “vegetable” fats including linoleic acid has been established by a number of randomized controlled trials described in these columns. Reproduced from reference 7.

Figure 1 confirms that the claim by Senator McGovern’s Senate Committee (3) that the intake of saturated fats from animal sources had increased for some time before the coronary heart disease “epidemic” had taken off in the 1930s-1940s is clearly nonsensical and is further disproved by an analysis of the % contribution of the different fats to what US citizens were consuming between 1909 and 1972 (figure 2).

Figure 2 shows a dramatic and progressive reduction in the % contribution that animal fats made to the American diet from 1909 to 1972 with a progressive increase in “vegetable” oil consumption across the entire time period.

Legend to Figure 2: The daily individual consumption of fats from different sources expressed as a percentage of total daily fat intake. Not that whereas animal fat consumption and saturated fat consumption has been in decline since 1909, “vegetable” fat consumption has increased from about 20% of daily fat calories to >40% in 1972. That contribution has very likely increased even further after 1972 – see figure 4. Reproduced from reference 7.

Enig’s conclusion was: “Retrospective analysis is useful for providing clues to the etiology of diseases. If there is a relationship between dietary fat and cancer, our analysis indicates that processed vegetable fats should be more carefully investigated (my emphasis)” (7, p.2219)

A related study (8) that analysed changes in carbohydrate and fat consumption by US citizens from 1909 to 1961 on the basis of retail food market sales showed that the greatest change during that period was a 40% increase in consumption of polyunsaturated fats causing a 30% increase in the ratio of polyunsaturated to saturated fatty acid intake (P:S ratio) (figure 3). 

Legend to Figure 3: Percent changes in polyunsaturated fatty acid consumption, in the polyunsaturated fat to saturated ratio (P:S ratio), in total fat consumption and in cholesterol and saturated fatty acid consumption by US citizens from 1909 to 1961, based on retail market sales. Note that the P:S ratio, which Keys’ Twin Hypotheses predicts will prevent CHD (as endorsed by the McGovern Senate Committee – reference 4), increased by 40% at the exact time that the CHD “epidemic” was taking hold in the US. Reproduced from figure 4 in reference 8.

Of course this dramatic increase in the P:S ratio was the exact change the McGovern report had proposed, on the basis of Keys’ Twin Hypotheses, that would be essential to reverse the CHD “epidemic”. Yet already by 1961, 16 years before the McGovern Committee published its report, that change had essentially already happened (my added emphasis). 

So far from protecting against coronary heart disease, the increase in the P:S ratio happened at the exact time that the CHD “epidemic” was taking hold in the US. Thus a more logical conclusion would be that the increase in the P:S ratio especially after 1932, has to be considered as a possible factor contributing to that epidemic. 

Interestingly the “bought” (9) 1961 American Heart Association Advisory Statement (10) that reversed its previous opposition to the Diet-Heart hypothesis and instead promoted “the reasonable substitution of poly-unsaturated fats for saturated fats…as a possible means of preventing atherosclerosis and decreasing the risk of heart attacks and stroke” (10, p. 136) was profoundly influential in driving the subsequent consumption of polyunsaturated fats. This is shown in Figure 4 which quantifies the effect of the 1961 AHA Advisory Statement on the consumption of soybean oil in the US. 

Legend to Figure 4: The 1961 American Heart Association (AHA) Central Committee Advisory Statement (10) discussed in an earlier column (9) produced a dramatic increase in the consumption of the polyunsaturated fatty acid, linoleic acid, from soybeans. This increase continues to the present day. Note that the increased consumption of the polyunsaturated fatty acid, linoleic acid, would cause an even more dramatic increase in the P:S ratio after 1961 (figure 3). Reproduced from figure 10 in reference 11. 

In fact so large has been this change (Figures 1-4) that, with hindsight, we are forced to consider the possibility that the CHD “epidemic” was more likely caused, rather than prevented, by the dramatic increase in “vegetable” oil consumption in the US, consequent to Procter and Gamble’s manufacture of Crisco in 1913 and the “bought” 1961 AHA Advisory Statement. 

Whilst we cannot blame Keys for the manufacture of hydrogenated “vegetable” oils like Crisco, by ensuring that this best mate, Dr Jeremiah Stamler MD, was included on that 1961 AHA Committee, Keys played a central role in redirecting the 1961 AHA Advisory Statement to support his unproven hypotheses (9). And to promote his idea that the substitution of dietary saturated fat with polyunsaturated fats was healthy and desirable.

Yet Keys was not unaware of some undesirable consequences of the hydrogenation of seed oils. In a 1961 paper (12), his team has shown that the ingestion of hydrogenated safflower or hydrogenated corn oil increased blood cholesterol concentrations by between 21-25mg/dL (0.5mmol/L). 

Thus already in 1956 Keys had advised that in adopting a low-fat diet “emphasis should be placed on reducing the consumption of margarine, hydrogenated shortenings, butterfat, and meat fats” (13, p.376). Interestingly, Keys was also not then, nor ever did he become, an advocate of what would become Walter Willett’s very-little-meat Mediterranean Diet Pyramid (14) for he wrote: ”The great nutritional values of milk and meat should be maintained, and increased (my emphasis) by favouring skim milk, cottage cheese, and lean meat” (13, p.376). Perhaps his understanding of the importance in the diet of meat and cheese, and avoidance of margarine and “hydrogenated shortenings” explains why Keys, like Jeremiah Stamler and Fred Kummerow, all lived to >100 years of age.

The analysis of retail market food sales by Antar et al (8) also included a measure of the other great dietary change that also happened during this period – a dramatic 120% increase in the consumption of sugars and syrups and total simple sugars, associated with a reduction in total carbohydrate consumption and the consumption of complex carbohydrates. As a result the ratios of complex to simple carbohydrate consumption fell by close to 70% (figure 5).

Legend to figure 5. Percentage change in source of carbohydrates consumed by US citizens between 1889 and 1961. Note the dramatic 120% increase in sugars and syrups and the ~70% reduction in the ratio of complex to simple carbohydrates consumed. Reproduced from figure 1 in reference 8. 

Others (15,16) have confirmed these changes in the nature of the carbohydrates consumed by US citizens during this period. As a result Antar et al. (8) concluded: “The increase in (the consumption of) polyunsaturated fatty acids has surpassed the increase in the saturated ones and consequently the ratio has increased about 37% since 1909. Obviously these data do not fit the hypothesis that low ratios of polyunsaturated to saturated fatty acids in the food supply contribute to the increased incidence of coronary heart disease in the United States. The changes which have occurred in the type of dietary carbohydrates, however, may be a factor” (8, p.177). 

Interestingly Antar and colleagues did not raise the obvious elephant in the room. What if it was the increased consumption of polyunsaturated fats in the last century that was the real driver of the subsequent CHD epidemic, perhaps ignited by the contemporaneous change in the amount and nature of carbohydrate consumption?   

One assumes that none of these findings was ever considered by the McGovern Senate Committee (3) in its deliberations. Instead I suspect that, like so much of the evidence that disproves Keys’ Twin Hypotheses, it was simply glossed over. And ignored.

The second error that Mary Enig recognized in the McGovern Report was the presence of a number of epidemiological studies that directly contradicted the McGovern Committee’s claim that “there is …. a strong correlation between dietary fat intake and the incidence of breast and colon cancer” (2, p.23). Instead it seemed to her that differences in geographical incidences of breast and colon cancer were better explained by differences in “vegetable” oil intakes. She argued that the use of “vegetable” oils was associated with higher rates of cancer whereas animal fats seemed to be protective (7). Accordingly Enig proposed that the industrially-produced trans fats present in hydrogenated “vegetable” oils might be the causative factor. She also identified examples of data manipulation that had allowed the McGovern Committee to arrive at its (false) conclusions. 

Enig’s lasting legacy is that she was the first to analyse and to draw attention to the trans fat contents of US foods (17,18). She calculated that in the 1990s the average daily trans fat intake of US citizens ranged between 1.6 to 38.7 grams/person/day (5). Subsequently she documented the presence of trans fats in the subcutaneous fat of Israeli citizens who also had very high linolenic acid content and polyunsaturated/saturated (P/S) fatty acid ratios (19).

The full story of Enig’s battle with the producers of “vegetable” oils had been faithfully described (2) and is also contained in two of her books (20,21). The final outcome was that industry buried Enig’s work, the importance of which continues to be ignored. Her concerns remain largely unanswered even today. 

An indication of the relevance of her work is shown in Figure 6 which compares the different trans fatty acid isomers in stick (hard) margarine compared to butter as analysed by Enig (5).

Legend to figure 6: The percentage of total fatty acids present in 16 different trans isomers in hydrogenated “stick” margarine (left panel) compared to butter (right panel). Note that 34% of the total fatty acids in stick margarine comprise trans fats whereas they constitute only 6% in butter. In addition naturally-occurring trans fats in dairy are not toxic to humans. Reproduced from reference 5, p. 44. 

The key point in Figure 6 is the extent to which the fats in butter and in hydrogenated “vegetable” oils differ with a much greater content of a range of trans fats in hydrogenated margarine derived from “vegetable” oils, than are present in butter.

Whilst these data are from the 1990s and the manufacturing processes for the production of “vegetable” oils has since changed, the reality is that, in the absence of long-term clinical trials which have yet to be performed (my emphasis), we currently have no idea whether or not modern industrially-produced “vegetable” oils are any less harmful for human consumption than were those produced before the 1960s. 

For it was in the 1960s that Fred Kummerow first began to draw attention of the high concentrations of trans fats in industrially-produced margarine and shortening. According to Kummerow, prior to 1968, margarine contained 44% trans fats and 8% linoleic acid whereas shortening contained 30% trans fats and 8% linoleic acid (22, p.58). Following his representation to the American Heart Association’s Medical Director, Dr Campbell Moses, the Institute of Shortening and Edible Oils subsequently moved to reduce the trans fats content of margarine to 28% and in shortening to 20% whilst increasing the linoleic contents of these products to 27% and 24% respectively. According to Kummerow, this large reduction in trans fats by 1968 may have been central to the fall in CHD rates in the US in the years thereafter.  

What we need to learn from this trans fat debacle is that we should never, ever assume that an industrially-produced food is healthier than is a natural food that has been eaten by humans for millennia, simply because that industrially-produced “fake” food favourable alters one biomarker considered (by the Keysian majority) to be important; in this case, the blood cholesterol concentration. Humans, we need to remember, are not simply a blood cholesterol measurement. Many other factors, most of them currently unknown, determine our future health.

Enig also provided a list of the extent to which trans fats existed as hidden fats in popular US foods between 1979 and 1990 (Table 1) (Table 3.3 in reference 5, p. 45).

Table 1. Typical trans fatty acid levels in US foods as analysed by Enig between 1979-1990.

                    Food items  Trans fats as % of total fat in food item
Shortening                          50
Cookies                         48
Crackers                         43
Candies                         39
French Fries (Chips)                         37
Imitation Cheese                         37
Margarine                         36
Pastries                         35
Potato Chips                         30
Frosting                         27
Salad Dressing                           5

Reproduced from reference 5, p. 45: Table 3.3

I reproduce this table for two reasons. First to show the extent to which hidden hydrogenated fats are present in common “snack” foods. Whether or not these industrially-produced fats still contain trans fats is largely irrelevant in my opinion. For there are no clinical trials to determine whether these hidden fats, now produced by a different chemical process that reduces their trans fat content, are indeed safe. My presumption is that they are not likely to be. Surely we do not have to repeat the same error twice?

Second it suggests that Dr Kummerow’s certainty that the level of trans fats has been decreasing in the US diet since 1968 appears overtly optimistic.

We turn next to a more detailed review of the work of Dr Kummerow who, at the time, was the only other scientist equally concerned about the potential negative health consequence of this quite sudden introduction of dietary trans fats into the human diet. 

Already in 1957 he had co-authored a paper showing the presence of trans fatty acids in considerable amounts in human adipose tissue, liver, heart, aortic tissue and in atheromatous plaques of humans who had died from the complications of atherosclerosis (23). He would spend the next 60 years of his life studying the effects of trans fats and oxidized cholesterol – a group of chemical compounds known as the oxysterols – on human health. He concluded that the dietary consumption of trans fats and polyunsaturated fatty acids that are easily oxidized producing the oxysterols, are the key dietary factors driving the development of human atherosclerosis (22,24-26).

After a life time of study, his conclusion is that “plasma cholesterol levels do not cause coronary heart disease” (26, p. 74). Instead he postulates that the oxidation of circulating blood cholesterol by (unstable) dietary polyunsaturated fatty acids is the cause. The result is that oxidized polyunsaturated fats change the composition of the cell membranes within the coronary arteries increasing the probability that they will develop atherosclerosis (27,28). 

Trans fats act in a similar way: “Our bodies handle manufactured trans fats differently from natural trans fats (in dairy). The natural trans fats, such as in butterfat, operate in the body in the same way as unsaturated cis fats in vegetable oils and thus are safe to eat. They do not interfere with the making of cell membranes. However, the manufactured trans fats do change the way cell membranes are made in the body including the cell membrane composition of arteries and veins (28). They cause changes in the fatty acids by incorporating trans acids and by changing the phospholipid composition, i.e., increased sphingomyelin (content), in the cell membranes so that calcium could infiltrate the cells. Remember more sphingomyelin shows up in those with heart disease” (24, p.47). 

“We replicated these results in the laboratory dish….(29)…(30)….(31)….(32)” (24, p.47-48).

Kummerow’s research on the development of atherosclerosis has seldom been properly exposed outside of the highly technical scientific journals in which his work has been published. Instead it has lain hidden, in part because it is more complex than Keys’ simplistic (and wrong) “cholesterol clogs arteries” that is so easy for all to understand. Over the past 63 years Kummerow’s research (22,24,25) has established the following:

  1. He has developed a model of coronary atherosclerosis in pigs (33,34) that is very similar to the human disease. Yet reference is seldom made to this in the scientific, especially cardiological literature. Instead the experiments of Nikolai N. Anichkov (Anistschkow)  are remembered and glorified (1). 
  2. Kummerow and his team have shown that pigs fed a diet of corn oil, free of cholesterol and saturated fats, developed atherosclerosis similar to that found in humans (33,34). This did not require that the pigs develop elevated blood cholesterol concentrations (hypercholesterolemia) (33). This is a key finding since the original Anistschkow model of animal atherosclerosis requires that blood cholesterol levels must be markedly elevated for the atherosclerosis to develop. 
  3. His team then developed a biological model to explain how this happens at a cellular level. 
  4. As in humans, age is an important factor predicting more severe atherosclerosis in pigs. 
  5. Aging is associated with the greater accumulation of the phospholipid, sphingomyelin, in the cells of the coronary arteries of older pigs (25).
  6. Sphingomyelin may be an important factor driving the development of coronary atherosclerosis because it facilitates entry of calcium into the cells of the coronary arteries thereby contributing to the development of more rigid, atherosclerotic arteries (29).
  7. This accumulation of calcium is increased in the presence of trans fatty acids (30).
  8. Support for the sphingomyelin hypothesis comes from the established observation that non-branching sections of human arteries are less prone to atherosclerosis than are the branch points in those same arteries (35). 
  9. The evidence is that higher sphingomyelin concentrations were found in the branching segments of human arteries at sites known to be more prone to the development of atherosclerosis (25,29) (Figure 7).

Legend to figure 7. Sphingomyelin content of arteries, collected at autopsy in men and women, was higher in non-branching areas of those arteries than it was at the branching (bifurcation) points known to be more likely to develop atherosclerosis. Reproduced from figure 1 in reference 25.  

  1. Subsequent studies have confirmed that the sphingomyelin content of human arteries increases with age. At birth it constitutes less than 10% of the total phospholipids; it is increased in arteries from persons with coronary artery disease (36) reaching more than 60% of the total phospholipid content of arterial (atherosclerotic) plaques (figure 8). 

Legend to figure 8. The sphingomyelin content of different arteries. The umbilical cord arteries of the newborn contain little sphingomyelin which increases in veins recovered from the hearts of persons who have undergone coronary artery bypass grafting (CABG). But the highest sphingomyelin contents and the lowest content of the other phospholipids is found in established coronary artery plaques. Reproduced from figure 2 in reference 25. Original data from reference 28.

  1. The theory predicts that since sphingomyelin activates calcium entry into the cell, arteries with higher sphingomyelin content should also have higher calcium content. Which they do (28,36); calcium content in areas of plaque with high sphingomyelin content was more than four-times higher than in control areas (28).
  2. Oxysterols increase the uptake of calcium into cultured endothelial cells. 
  3. When exposed to the blood of patients with documented coronary atherosclerosis, arterial (endothelial) cells grown in culture increased their uptake of calcium significantly more than when exposed to blood from healthy controls (37). But when commercially-produced oxysterols were added to the blood of healthy control subjects, the cultured endothelial cells acted as if the blood had come from those with documented coronary artery disease. increasing their calcium uptake to equal that in response to blood from diseased patients (37). 
  4. Exposure of cultured endothelial cells to the oxysterols, 25-, 26-, or 27-hydroxycholesterol, increased cellular production of sphingomyelin and was associated with an increased intra-cellular calcium uptake (38-40). 
  5. Kummerow concludes that the presence of increased concentrations of oxysterols in the blood of persons with documented coronary atherosclerosis alters the phospholipid composition of the arterial cells (28) by increasing sphingomyelin content at the expense of the other phospholipids (figure 8). The higher sphingomyelin content increases the uptake of calcium into those cells (25). 
  6. In concert, all these changes then produce the atherosclerotic plaque (25). 

The next challenge for Kummerow and his team was to determine whether, and which, dietary factors might be involved in driving this process. 

The team began with the knowledge that oxidized LDL-cholesterol is toxic to cell cultures (41) and that blood oxidized LDL-cholesterol concentrations are much better predictors of future CHD risk than is LDL-cholesterol (42,43). Thus it is known that, compared to healthy controls, plasma levels of oxidized LDL-cholesterol are significantly elevated in patients with stable angina pectoris, in patients with unstable angina pectoris, and in patients with acute myocardial infarction (25). Oxidized LDL-cholesterol concentrations are also increased in persons with the metabolic syndrome (25). Persons with the metabolic syndrome are at greatly increased risk of developing CHD. So the first challenge was to determine whether Kummerow and colleagues could confirm that finding. 

  1. Accordingly Zhou and colleagues from Kummerow’s laboratory (37) found that the concentration of 7 different oxysterols were increased in the blood of persons with established coronary artery disease (figure 9). 

Legend to figure 9. The concentration of 7 individual oxysterols were increased in patients with established coronary artery disease undergoing coronary artery bypass surgery. As a result the blood content of 7 oxysterols was greater in patients than in controls, both younger and older than 60 years of age. Reproduced from figure 3 in reference 25 from data collected in reference 37. 

  1. Another study of 1200 patients undergoing cardiac catheterization found that the blood concentration of oxysterols increased with the severity of the coronary artery disease (44) whereas blood cholesterol concentrations were unrelated to the degree of arterial disease. Thus the authors concluded that: “These data indicate that the concentration of the oxidation products rather than the concentration of cholesterol in the plasma identified stenosis in cardiac catheterization patients” (p.188).
  2. A study of patients undergoing cardiac transplantation for either advanced coronary artery disease or for other cardiac diseases unrelated to coronary atherosclerosis, found that the severity of the coronary atherosclerosis was predicted by blood concentrations of oxidized cholesterol (figure 10).

Legend to figure 10. The study of Holvoet et al. (45) found that blood LDL-cholesterol concentrations (left panel ) were unrelated to the severity of coronary atherosclerosis in those with cardiac diseases requiring transplantation for medical conditions that are unrelated to coronary atherosclerosis (and who showed no or minimal atherosclerosis – Grade 0) or in those with increasing degrees of coronary atherosclerosis (Grade I and Grade II). But blood oxidized LDL-cholesterol concentrations increased linearly in patients undergoing cardiac transplantation for conditions causing increasing degrees of coronary atherosclerosis (right panel). Redrawn from figure 1 and relevant data in reference 45. 

Once again blood LDL-cholesterol concentrations were not different between groups (figure 10, left panel). Nor, rather surprisingly were blood triglyceride or HDL-cholesterol concentrations different. 

However in another study the authors found that the odds ratios that persons with the highest levels of oxidized LDL-cholesterol would have markers of the metabolic syndrome were the following: 

Table 2: The Odds Ratios (OR) that otherwise healthy elderly in the Healthy, Aging and Body Composition study (46) who had the highest oxidized LDL-cholesterol concentrations would also have other markers of the Metabolic Syndrome.

                    Measurement                          OR 
Blood triglyceride/HDL-cholesterol ratio                         3.88 (reference 45).
Blood triglyceride concentrations                         3.12
Blood HDL-cholesterol concentrations                         3.10
Blood glucose concentrations                          2.03
Blood insulin concentrations                          1.98
Waist circumference                          1.48
Blood pressure                          1.27

Thus in as much as blood concentrations of oxidized LDL-cholesterol are a marker of severity of atherosclerosis (figure 10), they are also an indicator of the extent to which the individual has features of the metabolic syndrome. And the best maker of both is the blood triglyceride/HDL-cholesterol ratio.

  1. Thus these data established that blood oxysterols concentrations are indeed elevated in patients with coronary atherosclerosis and so could be one of the causes of their advanced coronary atherosclerosis according to Dr Kummerow’s theories. In all these studies, blood LDL-cholesterol concentrations were unrelated to the extent of coronary atherosclerosis. 

One of the critical missing links in Keys’ Diet-Heart and Lipid Hypotheses is that neither can explain how coronary thrombosis develops, the critical event that converts the presence of coronary atherosclerosis into the clinical events of heart attack or sudden death. Recall that this problem has been addressed by both Ahrens (47) and Jolliffe (48) (figures 4 and 5 in reference 49).  But Kummerow’s team offer a biological solution that fits their model.

  1. Two chemicals – prostacyclin and thromboxane – are secreted respectively by the cells lining the arteries (endothelial cells) or by platelets. They induce competing biological effects that regulate (i) the tendency for platelets to adhere to each other causing a blood clot and (ii) the tendency of arteries, more correctly arterioles, to either dilate or constrict. Prostacyclin is a vasodilator that reduces the probability that platelet adherence and clotting will occur; thromboxane is a potent vasoconstrictor that promotes blood clotting. 
  2. Thus an overproduction of thromboxane in the face of reduced prostacyclin secretion favours the development of blood clotting and arterial vascoconstriction.
  3. In the coronary arteries this imbalance would predispose to the development of coronary thrombosis and its major clinical manifestations, heart attack and sudden death.
  4. Mahfouz and Kummerow (50,51) have shown that oxysterols at low concentrations increases thromboxane production and sensitizes platelets to the effects of thromboxane. LDL-cholesterol that had not undergone oxidation to produce oxysterols produced a significantly smaller effect. 
  5. Furthermore oxysterols (52) and trans fatty acids (53) inhibit prostacyclin release from endothelial cells.   

Additional studies from this group have shown that the anti-oxidant vitamins E and C can reduce the effects of oxysterols in the production of atherosclerosis in animal models (54, 55). Others have also addressed the role of antioxidants in the prevention of atherosclerosis (56).

Left unanswered is how does “good” cholesterol – the cholesterol in the unoxidized form (without added oxygen) that is found in animal produce and the trillions of human cells – turn into the “bad” cholesterol with an added oxygen molecule – the oxysterols.

Kummerow (22, p.34) notes that here are seven “lethal” oxysterols circulating in the blood of patients with coronary artery disease (see Figure 9). Two of these originate in the diet from fried foods and powdered egg yolks. The other five are produced by dysfunctional metabolism of cholesterol in the liver. This according to Kummerow can be reversed by a diet “with a proper amount of protein and fat, low in vitamin D, void of trans fat, and with proper amounts of vitamin B and magnesium” (22, p.39). A diet low in industrially-produced vegetable oils would also seem important.

As a result of his extensive experience over 6 decades (22,24,57-61), Kummerow has produced an Executive Summary (Table 3) that explains each of the biological steps in his hypothesis: 

Table 3:  Fred Kummerow MD synthesizes his knowledge gained over an extended life time studying the effects of trans fats and hydrogenated “vegetable” oils on mammalian arteries. Reproduced from reference 25, p.201.


Two lipids present in the diet, oxysterols and trans fats, and not cholesterol in the plasma are responsible for heart failure. 


  • Cholesterol is necessary for life; the liver makes approximately 2 g a day to provide enough for the body to use. If the body does not have enough cholesterol to make cells, there are negative health consequences. 
  • Oxidized cholesterol, called oxysterols, are synthesized both in the liver and derived from food. 
  • Heart failure (more correctly, Dr Kummerow probably means, atherosclerosis – my addition) can develop without cholesterol from the diet present. 
  • The cellular events that occur during the progression of heart failure (atherosclerosis – my addition) are as follows:
  1. Changes first occur at branching points;
  2. There is a significant increase of sphingomyelin at branching points of the arteries;
  3. Those with heart disease have an increase in sphingomyelin in their arterial walls.
  • Oxysterols increase sphingomyelin synthesis, which leads to calcium binding in the arterial wall. Eventually this causes the blockage of blood flow in the coronary arteries. 
  • Oxysterols are produced during excessive frying of food; cholesterol gets converted into oxysterols during that process. 
  • Oxysterols are responsible for an increase of thromboxane released from the platelets. Thromboxane is necessary for blood clotting, but too much can lead to sudden heart failure. 
  • The consumption of too much polyunsaturated fat can overtax the liver. The excess polyunsaturated fat trips the mechanism that turns cholesterol into oxysterols. 
  • Polyunsaturated fats contain two essential fatty acids, linoleic and linolenic acids, which are needed to synthesize prostacyclin. Prostacyclin keeps the blood flowing, also an important factor in heart failure. 
  • Trans fatty acids inhibited the conversion of linoleic acid to arachidonic acid, thus preventing the synthesis of prostacyclin. 
  • Trans fats come from the diet; they are not made in the body, but rather created by partially hydrogenating vegetable oil. 
  • The exact composition of partially hydrogenated vegetable oil was not known until 1952. 
  • Partially hydrogenated oil had different properties than the fatty acids in animal fat or vegetable oil. 
  • Margarines and shortenings over the decades have contained trans fats in varying amounts up to 50%. 
  • In 1968, these sources of fat were reformulated to have less trans and more linoleic acid. However, they did not go far enough to make the fats ‘safe’ for consumption. 
  • The US FDA proposed a ban on trans fat on 7 November 2013. It should be instituted fully. 

Conclusion & future perspective 

  • The most effective way to prevent coronary heart failure is to eat moderate amounts of food, particularly avoiding commercially fried foods and too many polyunsaturated fats. 
  • The banning of partially hydrogenated fat would eliminate trans fatty acids from human consumption. 
  • The FDA should further mandate that soybean oil be fully hydrogenated and diluted with soybean oil that has been extracted by pressing that will include vitamin E, an antioxidant. 

Naturally any evidence that hydrogenated “vegetable” oils might be a cause of, rather than a cure for coronary atherosclerosis could not be tolerated by those promoting Keys’ Twin Hypotheses. As a result the work of Enig and Kummerow has largely been ignored as remains the case today. 

But importantly Dr Kummerow offers an explanation that is absent from Keys’ Twin Hypotheses. His mechanism explains how diet increases the probability of plaque rupture with the development of arterial (coronary) thrombosis.

In retrospect the resistance to acknowledging Kummerow’s work is remarkable. For already in 1981, Elson and colleagues (62) had reported that swine fed a diet with an increased amount of trans fats had higher blood cholesterol concentrations and, perhaps more alarmingly, a higher fat content in their aortas than did swine fed a diet high in saturated fats.

This anticipated the findings of Mensink and Katan (63) that: “The effect of trans fatty acids on the serum lipoprotein profile is at least as unfavourable as that of cholesterol-raising saturated fatty acids, because they not only raise LDL cholesterol levels but also lower HDL cholesterol levels” (p. 439). 

This finding should never have been dismissed out of hand, by those driving the Lipid Hypothesis. For If elevated blood LDL-cholesterol concentrations cause heart disease and if hydrogenated “vegetable” oils containing trans fats cause LDL-cholesterol levels to rise, then it was difficult to continue the argument that the consumption of hydrogenated “vegetable” oils is healthy.

Another finding that should not have been ignored, but was and is, is that arterial plaque contains both polyunsaturated (64) and trans fats (65).  But, inconveniently, no saturated fatty acids! 

But the final realization that dietary trans fats are most probably harmful occurred only when Walter Willett MD, the omnivorous nutritional epidemiologist who promotes a strong vegan/vegetarian dietary agenda and has very firm opinions on the dangers of meat eating (66,67), showed that the consumption of trans fats was associated with higher CHD rates in the longitudinal Nurses’ Health Study (68). 

Thus: “Intakes of foods that are major sources of trans isomers (margarine, cookies [biscuits], cake and white bread) were each significantly associated with higher risk of CHD. The findings support the hypothesis that consumption of partially hydrogenated vegetable oils may contribute to the occurrence of CHD” (68, p. 581).

In time legislation was introduced to remove trans-fats from the food chain (22,24,60,69) as the hydrogenation process was changed. But it was replaced by a novel intervention – interesterification (69, p.273). Yet the long-term health effects of this new method of hydrogenating seed oils is simply not known.

Nina Teicholz writes: “interesterification is akin to hitting someone with a sledgehammer, because you randomly distribute all the fatty acids on the glycerol. It produces a lot of new triglycerides’, many of which we know nothing about…Leveille and others are therefore nervous about the health implications: ‘We just don’t know,’ he judges. ‘It could be another trans lurking: we really need to look at it and understand it.’ And of course, in the same way that consumers didn’t know that they were eating trans fats, they now don’t know they’re eating interesterified fats, because they are listed on the food label simply as ‘oil’ (usually ‘soybean oil’)” (69, p.273). 

But on the assumption that the ingestion of any industrially-produced fat that lowers the blood LDL-cholesterol concentration, must be healthier that the animal fat it replaces, “vegetable” oils, whether produced by hydrogenation or interesterification, continue to get a free health pass. Despite zero evidence that these oils, however produced, are safe for long-term human consumption. And the clear evidence from three studies – the Women’s Health Initiative Randomized Controlled Dietary Modification Trial (70), the Recovered Sydney Diet Heart Study (71), and the Recovered Minnesota Coronary Experiment (72) – that the partial replacement of dietary saturated fat with “vegetable” oils produces harm.

The point is that the safety of this industrial extraction of “vegetable” oils and subsequent hydrogenation was not determined by P&G when they developed Crisco. But commercial success allowed the industry to purchase massive influence with and ultimately control over the American Heart Association. Once that goal had been achieved, there would be no questioning the long-term health effects of “vegetable” oils. Or if there was, it would be effectively muted by a group of influential nutrition scientists who allegiance to the value of dietary “vegetable” oils remains resolute and obdurate. 

So leading nutrition scientists including Walter Willett MD and Frank Hu MD at Harvard (73) and Dariush Mozzafarian MD (74) at Tufts, all of whom are enthusiastic supporters of the Diet-Heart and Lipid Hypotheses and the value of replacing dietary saturated fat with “vegetable” oils, were natural targets for funding support from large manufacturers of these products including Unilever, the world’s largest producer of “vegetable” oils. Willett’s numerous conflicts of interest have been carefully documented (75) as is the evidence that he is reluctant to acknowledge those conflicts in his published works, for example: “WCW(illett) has no competing interests to declare” (76, p.10). 

Indeed the list of “supporters” of the Harvard Chan School of Public Health where Willett works, runs to 12 pages just for funding provided for one 12 month period of 2018-2019 (77). At the head of the list is an (annual) donation of $10 000 000 “and above” from the Bill and Melinda Gates Foundation.

The challenge that Willett, Hu and Mozzafarian face is that whilst their nutritional epidemiological research is highly attractive to corporate funders, since epidemiological research can usually come up with one or other attractive findings for its sponsors, it is not about the truth. When Willett and Hu contacted the Editor of the Journal of the American Medical Association, Christine Lane, requesting that she retract a series of articles, discussed subsequently (78), that finally dismiss Willett and others’ concerns about the dangers of meat consumption discussed subsequently, she curtly responded: “Some of the researchers have built their careers on nutritional epidemiology. I can understand it’s upsetting when the limitations of your work are uncovered and discussed in the open” (67, p.E1). 

Perhaps the person who has most exposed the limitations in the nutritional epidemiological approach adopted by Willett, Hu and Mozaffarian is Professor John Ioannidis from Stanford University. His contribution is detailed in a subsequent column (78).

Dr Mozaffarian’s list of personal conflicts of interest is just as extensive: “Dr Mozaffarian reports ad hoc honoraria or consulting for Bunge, Haas Avocado Board, Nutrition Impact, Amarin, AstraZeneca, Boston Heart Diagnostics, GOED, and Life Sciences Research Organization. Dr Mozaffarian has served on scientific advisory boards for Unilever North America and Elysium Health” (79, p.e596). Interestingly the International Life Sciences Research Organization, more commonly ILSI, works or has worked with Phillip Morris, Kellogg, Monsanto, Dannon, the Calorie Control Council and Procter and Gamble. The influence of ILSI in controlling the global dietary guidelines is well documented (80-85). 

Their influence of Willett and Mozaffarian has been to advance “vegetable” oils as the new health food even though there is no definitive evidence that they are safe. This judgement is based purely on Keys unproven hypothesis that dietary saturated fat is “bad” so that anything that replaces a “bad” fat must be inherently “good” even in the absence of established proof of safety. 

So industrially-extracted, chemically-treated “vegetable” oils (extracted from seeds) became the new health food. And no one thought it incumbent on the manufacturers of these products to prove that they are indeed healthier than the natural products like butter, tallow and lard, that has been eaten by humans for eons, but which have now been replaced in the human diet, by products, the long-term health effects of which are simply not known. 

So whatever Willett and Mozzafarian and their sponsors including Unilever and Procter and Gamble amongst others, might want us to believe, replacing dietary saturated fats with mono- or polyunsaturated fats has not been shown to produce clearly beneficial outcomes (86-92). 

Instead I argue that three long-term randomized controlled trials finally (70-72) prove that it is unethical to encourage anyone to replace saturated fat with “vegetable” oils since this change will produce harm in some. 

It is time that Dr Kummerow’s work should be more widely appreciated and its potential importance recognized.

  1. 1979-1995. The Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project is initiated.

The Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project was initiated in 1979. According to the principal investigator, Hugh Tunstall-Pedoe MD, the study funded by the World Health Organisation was inspired in turn by the Framingham Heart Study (FHS) and the Seven Countries Study (SCS) (93). The FHS, he enthused, had proven that certain personal factors were “powerful and consistent indicators of increased coronary heart disease. The concept of risk factors was born” (93, p.1).  He noted that the most potent of these risk factors – “the classic risk factors” – were cigarette smoking, blood pressure and blood cholesterol concentrations. Other factors, he argued, were less common – T2DM; less consistent – obesity and exercise; or less readily measured (diet, alcohol, and psychosocial factors). 

In fact, as I showed in a previous column (94), blood cholesterol concentrations were a marginal risk factor in the Framingham study (Figure 1 in reference 94) whereas insulin resistance, a precursor and necessary companion of T2DM, was a much more potent predictor (Figure 6 in reference 94). 

He continued in the same breathless manner explaining the importance of the SCS which had apparently shown that “obesity and physical exercise accounted for little (of the variation in CHD incidence across the Seven Countries), as did cigarette smoking. Blood pressure was of some significance, but the determinant role went to cholesterol. The average blood cholesterol concentration varied significantly across populations. It correlated with the amount and type of fat in the diet and correlated strongly with population coronary disease rates” (93, p.2). 

The statement that the SCS proved that the blood cholesterol concentration was determined by the amount and type of fat in the diet is patently false as I showed earlier (95). The SCS did not prove that diet is even a minor determinant of the blood cholesterol concentration. The academic scientist Tunstall-Pedoe fell squarely into the sly trap carefully laid by the Keys’ acolytes (Figure 10 in 95). For if a high fat diet does not determine the blood cholesterol concentration, then Keys’ Diet-Heart Hypothesis has no foundation.

Tunstall-Pedoe then described that the sharp reduction in CHD rates in the US, described conveniently at a 1978 conference organized by the US NHLBI in Washington by another Keys acolyte Frederick Epstein (96), had generated “considerable excitement”. Which is perhaps predictable since this finding would naturally have to be explained and this would generate the opportunity for yet more research funding for the chosen few. 

The discussion then led to the initiation of the MONICA study (97) which was ultimately undertaken in 21 participating countries spanning four continents, running in parallel with similar studies in the US (98,99), all in progress in the 1980s and 1990s. 

The objectives of the MONICA study were: To measure the trends in cardiovascular mortality and coronary heart disease and stroke morbidity and to assess the extent to which these trends are related to changes in known risk factors, daily living habits, health care, or major socioeconomic features measured at the same time in defined communities in different countries.

In other words the MONICA study became a test of what is known about the role of coronary risk factors in the “causation” of CHD. For our purposes the results of the MONICA study should have established the extent to which our understanding of CHD risk factors explain the reduction in CHD rates around the world after the late 1950s.

The study was eventually restricted to 38 populations in 21 countries, mostly in Europe but with three each in Australia and Asia, and two in North America.  The study population was restricted to residents of both sexes living in those communities and aged between 35-64 years. Coronary risk factors were measured in these populations at the beginning and end of the 10-year study period; in some populations a third measurement was made in the middle of the experimental period. Coronary events were registered continuously throughout the 10-year experimental period. 

Importantly the study began in the period when there was great enthusiasm and no little certainty in the value of “risk factors” in the prediction of future heart attack risk. In other words the belief was strong that risk factor are factors causing CHD. 

But recall that proof of causation requires that removal of the so-called “risk factor” does not simply reduce the prevalence of the disease of interest. When the supposedly causal factor is removed, the disease must disappear completely. For as Claude Bernard wrote in 1878: “Indeed, proof that a given condition always precedes or accompanies a phenomenon does not warrant concluding with certainty that a given condition is the immediate cause of that phenomenon. It must still be established that when this (causal) condition is removed, the phenomenon will no longer appear” (100).

Or as W.E. Stehbens (101,102) has written rather more recently: “…differentiation between cause and non-causative factors is essential…Reduction in incidence rather than elimination of the disease precludes a causal relationship….Elimination of the cause eradicates the disease”.

If like the MRFIT (103) removal of so-called “risk factors” failed to eradicate the disease in MONICA, then risk factors are not causal for CHD.

The findings would begin to be reported after the mid-1990s by which time the National Consensus Conference (NCC) and the National Cholesterol Education Program (NCEP) had already essentially decided that especially an elevated blood cholesterol concentration is the key “cause” of CHD.

The question would become: Would the MONICA study support the certainty of the NCC and the NCEP?


  1. Noakes TD. Ancel Keys’ Cholesterol Con: Part 3. Crossfit Health.
  2. Enig MG, Fallon S. The Oiling of America. Part 1. Nexus December 1998-Jauary 1999:6(1):19-23;80-82. Available at:
  3. United States Senate Select Committee on Nutrition and Human Needs. Dietary Goals for the United States. US Government Printing Office. Washington DC, February 1977.
  4. Noakes TD. Ancel Keys’ Cholesterol Con: Part 9. The  Noakes Foundation.
  5. Enig MG. Diet, serum cholesterol, and coronary heart disease.  Chapter 3: In Coronary Heart Disease: The Dietary Sense and Nonsense. An evaluation by Scientists. Mann GV, Ed. Janus Publishing Company, London, England, 1993; 36-60.
  6. Rizek RL, Friend B, Page L. Fat in today’s food supply – level of use and sources. J Am Oil Chem Soc 1974;51:244-250. 
  7. Enig MG, Munn RJ, Keeney M. Dietary fat and cancer trends – a critique. Fed Proc 1978;37:2215-2220.
  8. Antar MA, Ohlson MA, Hodges RE. Changes in retail market food supplies in the United States in the last seventy years in relation to the incidence of coronary heart disease, with special reference to dietary carbohydrates and essential fatty acids. Am J Clin Nutr 1964;14:169-178. 
  9. Noakes TD. Ancel Keys’ Cholesterol Con: Part 6. The Noakes Foundation.
  10. 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.
  11. Blasbalg TL, Hibbeln JR, Ramsden CE, et al. Changes in the consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 2011;93:950-962.
  12. Anderson JT, Grande F, Keys A. Hydrogenated fats in the diet and lipids in the serum of man. J Nutr 1961;75:388-394.
  13. Keys A. The diet and the development of coronary heart disease. J Chron Dis 1956;4:364-380.
  14. Noakes TD. Ancel Keys’ Cholesterol Con: Part 13. Crossfit Health.
  15. Ohlson MA. Dietary patterns and effect on nutrient intake. World Rev Nutr Dietetics 1969;10:13-43.
  16. Ohlson MA. Dietary patterns and effect on nutrient intake. Ill Med J 1962 (November); 461-466.
  17. Enig MG, Atal S, Keeney M, et al. Isomeric trans fatty acids in the U.S. diet. J Am Coll Nutr 1990;9:471-486.
  18. Enig MG, Pallansch LA, Sampunga J, et al. Fatty acid composition of the fat in selected food items with emphasis on trans components. J Am Oil Chem Soc 1983;60:1788-1795.
  19. Enig MG, Budowski P, Blondheim SH. Trans-unsaturated fatty acids in margarines and human subcutaneous fat in Israel. Hum Nutr Clin Nutr 1984;38C:223-230.
  20. Enig MG. Know your fats: The complete primer for understanding the nutrition of fats, oils and cholesterol. Bethesda Press, Bethesda MY, 2000.
  21. Enig MG, Fallon S. Eat Fat, Lose Fat. The Healthy Alternative to Trans Fats. Penguin Books, London, UK, 2005.
  22. Kummerow FA, Kummerow JM. Cholesterol is not the culprit. A guide to preventing heart disease. Spacedoc Media LLC, 2014. 
  23. Johnston PV, Johnson OC, Kummerow FA. Occurrence of trans fatty acids in human tissue. Science 1957;126:698-699.
  24. Kummerow FA, Kummerow JM. Cholesterol won’t kill you but trans fats could. Seperating scientific fact from nutrition fiction in what you eat. Trafford Publishing, Victoria, BC. 2008.
  25. Kummerow FA. Two lipids in the diet, rather than cholesterol, are responsible for heart failure and stroke. Clin Lipidol 2014;9:189-204.
  26. Kummerow FA. Good health and well-being. My diet. World Nutrition 2015;6:72-78
  27. Zhou Q, Smith TL, Kummerow FA. Cytotoxicity of oxysterols on cultured smooth muscle cells from human umbilical arteries. Proc Soc Exp Biol Med 1993;202:75-80.
  28. Kummerow FA, Cook LS, Wasowicz E, et al. Change in phospholipid composition of the arterial wall can result in severe atherosclerotic lesions. J Nutr Biochem 2001;12:602-607.
  29. Kummerow FA, Przybylski R, Wasowicz E. Changes in arterial membrane lipid composition may precede growth factor influence in the pathogenesis of atherosclerosis. Artery 1994;21:63-75
  30. Kummerow FA, Zhou Q, Mahfouz MM. Effect of trans fatty acids on calcium influx into human arterial endothelial cells. Am J Clin Nutr 1999;70:832-838.
  31. Kummerow FA, Mahfouz MM, Zhou Q. Trans fatty acids in partially hydrogenated soybean oil inhibit prostacyclin release by endothelial cells in presence of high levels of linoleic acid. Prostaglandins 2007;84:138-153.
  32. Kummerow FA, Wasowicz E, Smith Y, et al. Plasma lipid physical properties in swine fed margarine or butter in relation to dietary magnesium intake. J Am Coll Nutr 1993;12:125-132. 
  33. Taura S, Taura M, Imah H, et al. Coronary atherosclerosis in normocholesterolemic swine. Artery 1978;4:395-407.
  34. Taura S, Taura M, Kummerow FA. Human arterio- and atherosclerosis: identical to that in 6 and 36 month old swine fed a corn soy diet free of cholesterol and saturated fat. Artery 1978;4:100-106.  
  35. Ross R. The pathogenesis of atherosclerosis – an update. N Engl J Med 1986;314:488-500.
  36. Yia-Herttuala S, Sumovuori H, Karkola K, et al. Atherosclerosis and biochemical composition of coronary arteries in Finnish men. Comparison of two populations with difference incidences of coronary heart disease. Atherosclerosis 1987;65:109-115. 
  37. Zhou Q, Wasowicz E, Handler B, et al. An excess concentration of oxysterols in the plasma is toxic to cultured endothelial cells. Atherosclerosis 2000;149:191-197.
  38. Zhou Q, Smith TL, Kummerow FA. The effect of 25-hydroxycholesterol accumulation on intracellular calcium. Cell Calcium 1991;12:467-476.
  39. Zhou Q, Kummerow FA. Alterations of Ca++ uptake and lipid content in cultured human arterial smooth muscle cells treated with 26-hydroxycholesterol. Artery 1994;21:182-192. 
  40. Zhou Q, Kummerow FA. Effects of 27-hydroxycholesterol on cellular sphingomyelin synthesis and Ca++ content in cultured smooth muscle cells. Biomed Environ Sci 1997;10:369-376.
  41. Hessler Jr, Morel DM, Lewis J, et al. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Atherosclerosis 1983;3:215-222.
  42. Yia-Herttuala S. Macrophages and oxidized low density lipoproteins in the pathogenesis of atherosclerosis. Ann Med 1991;23:561-567.
  43. Holvoet P. Oxidized LDL and coronary heart disease. Acta Cardiol 2004;59:479-484. 
  44. Kummerow FA, Olinescu RM, Fleischer L, et al. The relationship of oxidized lipids to coronary artery stenosis. Atherosclerosis 2000;149:181-190.
  45. Holvoet P, Stassen J-M, Van Cleemput, et al. Oxidized low density lipoproteins in patients with transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 1998;18:100-107.
  46. Holvoet P, Kritschevsky SB, Tracy RP, et al. The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the Health, Aging, and Body Composition Cohort. Diabetes 2004;53:1068-1073.
  47. Ahrens EH, Hirsch J, Insull W, et al. Dietary control of serum lipids in relation to atherosclerosis. JAMA 1957;164:1905-1911.
  48. Jolliffe N. Fats, cholesterol and coronary heart disease. A review of recent progress. Circulation 1959;20:109-127.
  49. Noakes TD. Ancel Keys’ Cholesterol Con: Part 4. The Noakes Foundation. 
  50. Mahfouz MM, Kummerow FA. Oxysterol and TBARS are among the LDL oxidation products which enhance thromboxane A2 synthesis by platelets. Prostaglandins Lipid Mediators 1998;56:197-217.
  51. Mahfouz MM, Kummerow FA. Oxidized low-density lipoprotein (LDL) enhances thromboxane A2 synthesis by platelet, but lysolecithin as a product of LDL oxidation has an inhibitory effect. Prostaglandins Lipid Mediators 2000;62:183-200.
  52. Mahfouz MM, Kummerow FA. Oxidized low density lipoprotein inhibits prostacyclin generation by rat aorta in vitro: A key role of lysolecithin. Prostaglandins Lipid Mediators 2001;66:283-304.
  53. Kummerow FA, Mahfouz MM, Zhou Q, et al. Effects of trans fats on  prostacyclin production.  Scand Cardiovasc J 2013;47:377-382.
  54. Smith TL, Kummerow FA. Effect of dietary vitamin E on plasma lipids and atherogenesis in restricted ovulator chickens. Atherosclerosis 1989;75:105-109.
  55. Mahfouz MM, Kawano H, Kummerow FA. Effect of cholesterol-rich diets with and without added vitamins E and C on the severity of atherosclerosis in rabbits. Am J Clin Nutr 1997;66:1240-1249.
  56. Heinecke JW. Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis 1998;141:1-15.
  57. Kummerow FA. Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease. Am J Clin Nutr 1979;32:58-83.
  58. Kummerow FA. Dietary recommendations to reduce cholesterol consumption may have undesireable consequences. Paroi Arterielle 1981;7:3-5.
  59. Kummerow FA. Viewpoint on report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. J Am Coll Nutr 1993;12:2-13.
  60. Kummerow FA. The negative effect of hydrogenated trans fats and what to do about them. Atherosclerosis 2009;205:458-465.
  61. Kummerow FA. Interaction of sphingomyelin and oxysterols contributes to atherosclerosis and sudden death. Am J Cardiovasc Dis 2013;3:17-26.
  62. Elson CE, Benevenga NJ, Canty DJ, et al. The influence of dietary unsaturated cis and trans and saturated fatty acids on tissue lipids of swine. Atherosclerosis 1981;40:115-137.
  63. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high-density and low-density lipoprotein cholesterol levels in healthy subjects. NEJM 1990;323:439-445.
  64. Felton CV, Crook D, Davies MJ, et al. Dietary polyunsaturated fatty acids and composition of human aortic plaques. Lancet 1994;344:1195-1196.
  65. Stachowska E, Dolegowska, Chlubek D, et al. Dietary trans fatty acids and composition of human atherosclerotous plaques. Eur J Nutr 2004;43:313-318.
  66. Zimmerman E. Tell me about the planetary health diet. The Cut, February 8th 2019.
  67. Rubin R. Backlash over meat dietary recommendations raises questions about corporate ties to nutrition scientists. JAMA 2020. Published online January 15th 2020. Available at
  68. Willett WC, Stampfer MJ, Manson JE, et al. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 1993;341:581-585.
  69. Teicholz N. The Big Fat Surprise. Why butter, meat and cheese belong in a heathy diet. Simon and Schuster, New York, NY. 2014. 
  70. Howard BV, Van Horn L, Manson JE et al. Low-fat dietary pattern and risk of cardiovascular disease. The Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:655-666.
  71. 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.
  72. 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..
  73. Willett WC. The role of dietary n-6 fatty acids in the prevention of cardiovascular disease. J Cardiov Med 2007;8Suppl1:S42-S45.
  74. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: A systematic review of meta-analysis of randomized controlled trials. PLOS Medicine 2010. Published March 23rd 2010. Available at:
  75. Anonymous. Dr Walter Willett: Numerous potential conflicts of interest.
  76. Forouhi NG, Krauss RM, Taubes G, Willett . Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance. BMJ 2018;361:k2139
  77. Harvard T.H. Chan School of Public Health. Supporting the Harvard Chan School. Institutional Partnerships and Matching Gift Companies. Available at:
  78. Noakes TD. Ancel Keys’ Cholesterol Con: Part 14. Crossfit Health.
  79. Singh GM, Micha R, Khatibzadeh S, et al. Response to letter regarding article, “Estimated global, regional and national disease burdens related to sugar-sweetened beverage consumption in 2010”. Circulation 2016;133:e596.
  80. Raycheva M. New report condemns ILSI’s influence on DGAC, calls to block group from food policy decisions. Food Chemical News 23 April 2020. Accessible at:
  81. Anon. Partnership for an unhealthy planet: How big business interferes with global health policy and science. Published by Corporate Accountability 2020;1-36. Available at:
  82. Nutrition Coalition. The 2020 Dietary Guidelines Committee: Who will stand up for rigorous science over industry interests and – really – religion? March 6 2019. Available at:
  83. Steele S, Ruskin G, Sarcevic L, et al. Are industry-funded charities promoting “advocacy-led” studies or “evidence-based science”?: a case study of the International Life Sciences Institute. Globalization Health 2019;15:36.
  84. Dyer O. International Life Sciences Institute is advocate for food and drink industry, say researchers. BMJ 2019;365:14037.
  85. Steele S, Ruskin G, Stuckler D. Pushing partnerships: corporate influence on research and policy via the International Life Sciences Institute. Pub Health Nutr doi:10.1017/S1368980019005184 Published 25 November 2019
  86. Ravnskov U, DiNicolantonio JJ, Harcombe Z, et al. The questionable benefits of exchanging saturated fat with polyunsaturated fat. Mayo Clin Proc 2014;89:451-453.
  87. DiNicolantonio JJ. The cardiometabolic consequences of replacing saturated fats with carbohydrates or Ω-6 polyunsaturated fats: Do the dietary guidelines have it wrong? Open Heart 2014;1:e00032.
  88. Hamley S. The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomized controlled trials. Nutrition J 2017;16:30
  89. Taubes G. Vegetable oils, (Francis) Bacon, Bing Crosby, and the American Heart Association. Available at:
  90. Hannon BA, Thompson SV, An R, et al. Clinical outcomes of dietary replacement of saturated fatty acids with unsaturated fat sources in adults with overweight and obesity: A systematic review and meta-analysis of randomized controlled trials. Ann Nutr Metab 2017;71:107-117.
  91. Chang LF, Vethakkan SR, Nesaretnam K, et al. Adverse effects on insulin secretion of replacing saturated fat with refined carbohydrate but not with monounsaturated fat: A randomized controlled trial in centrally obese subjects. J Clin Lipidol 2016;10:1431-1441.
  92. Teng K-T, Chang LF, Vethakkan SR, et al. Effect of exchanging carbohydrate or monounsatured fat with saturated fat on inflammatory and thrombogenic responses in persons with abdominal obesity: A randomized controlled trial. CIin Nutr 2017;36:1250-1258.
  93. Tunstall-Pedoe H. Background, development and organization of MONICA. #1. Background to the WHO MONICA Project. In: MONICA Mongraph and Multimedia Sourcebook. World’s largest study of heart disease, stroke, risk factors and population trends 1979-2002. Tunstall-Pedoe H, Ed. WHO 2003. Avaiable at: 
  94. Noakes TD. It’s the insulin resistance, stupid? Part 9. CrossFit Essentials (Please complete this reference). 
  95. Noakes TD. Ancel Keys’ Cholesterol Con: Part 7. The Noakes Foundation.
  96. Epstein FH. Preventive trials and the “diet-heart” question. Wait for results or act now? Atherosclerosis 1977;26:515-523. 
  97. WHO MONICA Project Principal Investigators. The World Health Organization MONICA project (Monitoring Trends and Determinants in Cardiovascular Disease): A major international collaboration. J Clin Epidemiol 1988;41:105-114.
  98. The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study. Design and Objectives. Am J Epidemiol 1989;129:687-702
  99. Rosamond WD, Folsom AR, Chambless LE, et al. Coronary heart disease trends in four United States communities. The Atherosclerosis Risk in Communities (ARIC) Study 1987-1996. Int Epidemiol Assoc 2001;30:S17-S22.
  100. Bernard C. An introduction to the study of experimental medicine. The MacMillan Company, New York, NY, 1927.
  101. Stehbens WE. Basic precepts and the Lipid Hypothesis of Atherogenesis. Med Hypoth 1990;31:105-113.
  102. Stehbens WE. Causality in medical science with particular reference to heart disease and atherosclerosis. Perspect Biol Med 1992;36:97-119.
  103. Noakes TD. Ancel Keys’ Cholesterol Con: Part 11. Crossfit Health.

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.

 A foundation to question The Science™️ 


Get the latest news & updates

Copyright (c) 2023 The Noakes Foundation™️ – Cape Town, South Africa. The Noakes Foundation is a trademark of The Noakes Foundation PBO, established in 2013. All rights reserved.

error: Content is protected !!