The combined role of atheroma, cholesterol, platelets, the endothelium and fibrin in heart attacks and strokes

Medical

Hypotheses

15:

305-322,

1984

THE COMBINED ROLE OF ATHEROMA, CHOLESTEROL, PLATELETS, THE ENDOTHELIUM AND FIBRIN IN HEART ATTACKS AND STROKES Wayne Martin.

PO Box 1133, Fairhope, AL 36532,

USA.

ABSTRACT In 1920 the typical American diet was rich in cholesterol and fat, especially saturated animal fat, with one-third the polyunsaturated vegetable fat as now; yet in that year, death from myocardial infarction (MI) in the United States was so rare that it had no name or medical recognition. In 1960, when MI deaths in the United States had soared to an alarming rate of 600,000, orthodox medicine concluded that cholesterol and saturated animal fat in food caused elevated cholesterol in blood, which caused cholesterol in atheroma, which in turn caused death from MI and strokes. It is suggested that human atheroma is made up mostly of fibers of either collagen or fibrin, smooth-muscle cells or dead smooth-muscle cells, that it contains but little cholesterol, and that it is present in both men and women and in populations having little or no MI as well as in those where MI is the greatest cause of death. It is suggested that Ml is largely caused by coronary blood clots formed at the site of a break in the coronary artery endothelium; that the introduction of a new, unnatural dietary fatty acid - trans-trans linoleic acid - in margarine and refined vegetable oils in the 192Os, by induc ing a deficiency of beneficial prostaglandin Et (PGE1) while greatly increasing harmful thromboxane A2 (TXA2), caused vasoconstriction while the clumping of platelets was greatly increased, giving rise to the coronary blood clots that either cause or are part of the fatal process of MI. It is suggested that in fostering the increase of dietary trans-trans linoleic acid in polyunsaturated vegetable fats at the expense of saturated animal fat, orthodox medicine is fostering a principle cause of Ml as the cure.

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INTRODUCTION Were one to take a poll of 10,000 doctors today, asking as to the role of cholesterol and atheroma in heart attacks and strokes, the vast majority of them would say that cholesterol causes atheroma, which causes heart attacks and strokes; that cholesterol, a yellow, waxlike substance, clogs the arteries, causing both coronary and cerebral ischemia, giving rise to both heart attacks and strokes. We propose to present a case that, with the exception of the few of us who suffer from familial hypercholesterolemia, cholesterol cannot be demonstrated to have a major role either in human atheroma or in heart attacks.

WHAT IS HUMAN ATHEROMA? ___In 1913 Anitschkow fed cholesterol to rabbits, and they quickly developed yellow, waxlike plaques in their arteries.1 No one in medicine paid much attention to Anitschkow then one reason being that whereas today we will have 550,000 deaths this year in the United States from the type of heart attack called a myocardial infarction (Ml), in 1913 this type of heart attack had no name or medical recognition and must have been exceptionally rare. By 1953-forty years later- this type of heart attack did have the name “myocardial infarction” and each year was causing over 400,000 deaths in the United States. It was then that Katz and Stamler published their work on atherosclerosis. 2 They fed cholesterol to chickens, and very quickly their chickens, like Anitschkow’s rabbits, developed plaques of yellow, In their 1953 book, “Experimental Atherosclerosis,” waxlike cholesterol in their arteries. they have a footnote questioning if what happens with chickens has any bearing on human atherosclerosis. In the conclusion to their book they felt that what they had done with chickens was relevant to human atheroma, yet they closed with saying, “Certainly much basic clinical and laboratory research lies ahead before a solution is reached.” Notwithstanding the doubts and qualifications of Katz and Stamler, orthodox medicine accepted an unqualified dogma that cholesterol in blood clogged arteries, causing atherosclerosis, which caused heart attacks. In 1955 Duguid and Robertson examined human atheroma and said that it was made up of They at once had detractors who said the fibers that Duguid and fibrin, not cholesterol.3 Robertson wereseeing were not fibrin but fibers of collagen; however, in late 1955, Levene, using an electron microscope, showed that the fibers of human atheroma were indeed fibrin.4 Neither Duguid and Robertson nor Levene took any note of cholesterol in human atheroma. By 1960 orthodox medicine had refined its dogma about cholesterol, atheroma and heart attacks to incriminate saturated fat. Saturated fats such as in butter caused elevated cholesterol in blood, which caused more cholesterol in atheroma, which caused more heart attacks. The polyunsaturated fatty acid, linoleic acid, in diet would reduce cholesterol in blood, which would reduce cholesterol in atheroma, which would reduce the risk of death from a heart attack. SO went the dogma which decreed polyunsaturated linoleic acid to be the good, life-saving fatty acid. In Holland, 86ttcher eta/ in 1960 ran a chemical analysis of human atheroma, and to the concern of a few doctors, found that as atheroma became more severe, the amount of “good” linoleic acid in it increased. Further, they found that the cholesterol content of 306

human atheroma was a very minor constituent but that it did increase somewhat as atherosclerosis became more severe, and most of it was present as the cholesterol ester of linoleic acid;5 however, the accumulation of the cholesterol ester of linoleic acid in atheroma may be the body’s way of removing cholesterol from atheroma. Morrison and Johnson analyzed the cholesterol content of coronary arteries of patients who had died of heart attacks as well as of patients who had died of other causes. They found a mean average of 20.4 mg per gram dry weight in the heart attack patients, but a mean average of only 5.1 mg per gram in patients who had died of other causes.6 This would seem to imply some connection between cholesterol and heart attacks; however, it demonstrated also that on a hydrated coronary artery basis, the amount of cholesterol present was too small to support the concept that yellow, waxlike cholesterol clogged the arteries. The cholesterol concept of atheroma has continued to remain in force since then, notwithstanding its being factually devastated in 1977 when Benditt, using an eleciron microscope, showed that human atheroma is composed of new cell growth, that human atheroma is beHe also noted that the fibers discussed by Duguid, Robertson and nign tumorneoplasia. Levene are collagen, not fibrin- but like them, he found little or no yellow, waxlike cholesterol.7 In the October 14, 1978 issue of The Lancet, the editor discussed the fact that atheroma is indeed benign tumor and suggested that it is caused by a virus.8 In 1983 Melnick eta/ have found antigen to cytomegalovirus (CMV) in 25% of the samples of atheroma obtained in blood-vessel surgery. They suggest that CMV may act to cause smooth-muscle cells of the media of arteries either to proliferate into the intima, giving rise to the swelling and enlargement of the plaque of atheroma or that CMV causes smooth-muscle cells to migrate from the media into the expanding intima. They suggest that if the involvement of CMV in atheroma formation can be confirmed, a vaccine against CMV may offer protection against the formation of human atheroma.9 Dot-land2 Illustrated Medical Dictionary, 25th edition, in 1974 defined atheroma as “being The intima is composed of a mass of plaque of degenerated, thickened arterial intima.” composed of a matrix of longitudinal collagen fibers. This definition has remained unchanged in Dorland’s for the past fifty years, so the medical consultants to OorlandS seem to have been unconvinced as to yellow, waxlike cholesterol being a major constitutent of Dorland’s fifty-year-old definition fits well with Benditt’s electron human atheroma. microscope observation of 1977, except for his saying that the fibers are monoclonal and neoplastic.

Mitchinson in 1983 suggested that macrophages cause the formation of plaques of atheroma, that atherosclerosis is an auto-immune disease. He suggests that part of the aging process is that smooth muscle cells in the media migrate into the intima, causing the intimal thickening of the first stage of atheroma formation. Then macrophages move into the thickened intima, releasing oxidized fatty acids. Macrophages, according to Mitchinson, kill bacteria by releasing hydrogen peroxide and other deadly oxidizing substances, oxidized fatty acids being one such killing substance. These oxidized fatty acids kill smooth-muscle cells as well as other cells in the intima. These macrophage-killed cells then contribute to the bulk of the plaque of atheroma, and they render the plaque non-reversible. This condition is made more severe in Vitamin E deficiency and presumably is preventable in part by increased Vitamin E in diet.63

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This is not a new concept. J.C. F. Poole and Sir Howard Florey in 1958 wrote of the role of the macrophages in atheroma formation.64 This is all a far cry from yellow, persists.

waxlike

cholesterol

clogging arteries - but the dogma still

THE ROLE OF CHOLESTEROL? There is a circumstantial connection between cholesterol and Ml. Among populations where there is little or no Ml, serum cholesterol is usually found to be in a range of about 150-180 mg percent, whereas in developed nations where MI is the greatest single cause of death, serum cholesterol is in a range of 200-300 mg percent.10 A specific example is a study in Uganda in 1959 by Shaper and Jones. The Indian population of Kampala, Uganda, had serum cholesterol in a range of 200-300 mg percent, and the same high death rate from Ml as in the United States. The black population there had serum cholesterol in a range of 150-180 mg percent and a nil incidence of Ml.11 In this study it was noted that the Indian population with the high death rate from MI had dietary fat that contained much more linoleic acid than the MI-free black population had in diet. It could be that the circumstantial connection between serum cholesterol and Ml is a weak one. Certainly a thirteen-year, multi-nation test on the cholesterol-reducing drug, clofibrate, ended showing no benefit insofar as Ml was concerned- and much harm otherwise.12 An editorial in The Lancer, commenting on the fact that this drug did lower serum cholesterol but otherwise was of no benefit in preventing Ml, said, “The treatment was successful, but unfortunately the patient died.“13 The high death rate among patients taking clofibrate is presumed, however, to have been due to the toxic nature of this drug66 rather than due to its lowering of serum cholesterol. In this editorial in The Lancet (October 14, 1978), commenting on Benditt’s work showing that human atheroma is mostly composed of benign tumor, it is noted that human atheroma often shows no cholesterol accumulation, that the fatty streaks composed of fat-filled cells that are found in human arteries may have no connection with the massive, occlusive fibrous plaques of atheroma, and while there still may be some doubt if the fibrous plaques are neoplastic, there is no doubt that the occlusive nature of human atheroma is for the most part due to fibers of something rather than to waxlike cholesterol. The editorial also notes that “the overwhelming emphasis placed on cholesterol and lipoproteins in atherogenesis has diverted effort away from other lines of research for nearly two decades”8 The decade of the 1960s was the decade of the testing of cholesterol-reducing, linoleic acidbearing diets, none of which showed any marked improvement in reducing death from Ml.14, 15. 16 In the March 21, 1981 issue of The Lancet the editor, reviewing the work on cholesdiets have not convinced clinicians of terol and Ml to that date, wrote, “. . . polyunsaturated A new approach is needed.“17 their efficacy or patients of their practicability. It could be that the cholesterol connection with Ml is a happenstance, just as was the presumption that estrogen would prevent Ml. Young women who are free from Ml produce much more estrogen than coronary prone men, so under the egis of the Coronary Drug Project in the United States, coronary-prone men were given estrogen. The result was a near disaster, ending with the conviction that estrogen causes Ml rather than preventing it.18

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M. F. Oliver, who organized the failed clofibrate test in 1964, wrote in The Lancet for November 14, 1981, saying that once a patient is known to suffer from ischemic heart disease, reducing serum cholesterol is of little or no benefit- although he still felt that cholesterol He did note, however, that had something to do with the beginning of human atheroma. Scotland, with one of the highest death rates in the world from Ml, had a moderately low national serum cholesterol level of 219 mg percent.19 There can be little doubt that the one in 500 of us who suffers from familial hypercholesterolemia with serum cholesterol in the range of 1,000 mg percent has a vascular tree devasted by cholesterol deposits in arteries (but not in veins), and does suffer death from Ml, often at an early age. Now the Lipid Research Clinics Program in the United States has completed a ten-year testing program among the small percent of men in whom total serum cholesterol was between 265 and 1,000 mg percent -with the average for the group at 294 mg percent. With half this test group, serum cholesterol was reduced by 8.5 percent by diet and by the use of the drug, cholestyramine, 24 grams daily, the side effects of which were nausea, pain, constipation and flatulence. In this test, fatal and non-fatal episodes of Ml were combined, and in the treated group there were 155 such episodes as compared to 187 among the controls - for a reduction in MI of 19 percent; however, total deaths in both groups were nearly the same 171 in the controls and 68 in the treated group).67 The editor of The Lancet, commenting on this test in the February 11, 1984 issue, wrote: “Most of the attributable cases of cardiovascular heart disease in the population arise from the large number of people whose cholesterol values are around average, not from the few in So in this ten-year test among the few whom the concentration is conspicuously high.“68 men with above-average serum cholesterol, a reduction in serum cholesterol from an average of 294 to 277 mg percent resulted in a reduction of fatal and non-fatal episodes of Ml of 19 percent, with no reduction in mortality. In the March 17, 1984 issue of The Lancet, Chandra Pate1 made a critical review of these results. He noted that in England and Wales, to apply these results to the population, by spending 140 million pounds a year for cholestyramine, the annual number of fatal and nonfatal events of Ml could be reduced by 480 compared to 152,000 CHD deaths recorded each year. He concluded with, “We should stop fooling ourselves and look for radically new approaches.”

It is to be regretted that there is no record of serum cholesterol among similar men in the United States in 1923, when Ml was so rare that it had no name or medical recognition; however, in 1923 when dietary fats were mostly cholesterol-bearing and highly saturated butter and lard, the average serum cholesterol in our population must have been higher than it is today. THE ROLE OF PLATELETS In 1882 Bizzozero discovered platelets in blood and said quite correctly that platelets start all blood clots. His concept about platelets was rejected out of hand, and until 1925 platelets were considered by orthodox medicine to be a myth and were, in fact, called the mythical Bizzozero cells.20 In 1926 Tait and Burke showed that platelets did exist, that they did start all blood clots by forming a white or platelet thrombus at the site of a wound and that only after a white or platelet thrombus has been formed will a red or fibrin thrombus form on top qf it. They also showed that with different individuals, platelets have a greater or

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lesser degree of adhesiveness, and the greater the adhesiveness of platelets, the greater the likelihood of a blood clot to form.21 In 1925 Sir John McNee described a form of heart attack now called Ml as being caused by one or more blood clots in coronary arteries .22 By 1926 orthodox medicine accepted the existence of this new form of heart attack; mostly it was called coronary thrombosis, but some doctors used the term “coronary thrombosis and ischemic necrosis.” About 1949 the name of this by-then relatively new form of heart attack was changed to myocardial infarction. For forty years after 1926, as death from MI changed from a very rare happening to the greatest single cause of death in our Western World, great concern was shown by doctors about coronary blood clots, but the fact that these fatal clots were all started with a platelet thrombus was ignored in toto. In 1965 Owren clearly defined the role of platelets in coronary thrombosis,23 but he was ignored, and it was not until 1972 that many orthodox doctors began to consider that coronary blood clots were indeed initiated by platelets and that aspirin, by reducing platelet adhesion, might reduce the risk of death from Ml.24 In 1978 Dyerburg eta/ reported that eicosapentaenoic acid in fish oil is converted to prostaglandin I3 (PGl3) in the body, which greatly reduces platelet adhesion -which in turn is responsible for the near freedom from death from Ml among Greenland Eskimos.25 In 1976 Sean Moore added further knowledge of platelet thrombi and MI. He showed that oftentimes a shower of platelet thrombi will block the microcirculation of the heart, causing micro infarcts that can initiate the fatal arrhythmias that follow Ml.26 In 1977 Vane, Moncada and Higgs found that arachidonic acid, largely from meat and dairy products, is converted to prostacyclin (PGI2) and to thromboxane A2 (TXAz), the former of which greatly reduces the aggregation of platelets and acts as a vasodilator, with the latter causing platelets to aggregate into platelet thrombi while acting as a potent vasoconstrictor. 27

In 1980 David Horrobin reviewed how prostaglandin Et (PGEt ), derived from cis-cis linoleic PGEt also restricts the acid, also reduces platelet adhesion while acting as a vasodilator. formation of pro-aggregating TXA2 while permitting prostacyclin to be freely converted from arachidonic acid. He also suggested that the unnatural fatty acid, trans-trans linoleic acid, which was first introduced into diet in large amounts in the late 1920s in margarines, blocks the conversion of cis-cis linoleic acid to PGEt and that the new disease, Ml, which became pandemic in the Western World in the late 1930s is at least in part caused by a deficiency of PGE1. He also showed that gamma linolenic acid in evening primrose oil and in human milk can be converted by the body to PGE1 in the presence of trans-trans linolenic acid.28 In 1983 Renaud and Nordoy showed that alpha linolenic acid - which is in wheat, rye, soybeans, walnuts, rapeseed and flaxseed - is converted to PGI3, which greatly reduces the aggregatability of platelets.29

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THE ROLE OF THE ENDOTHELIUM In 1979 Moncada and Vane, writing on the interaction between platelets and the blood vessel wall, said, “Platelets do not adhere to the healthy vascular endothelium.” They gave no references, but stated it either as a new discovery or as a well-known fact.30 Macfarlane in 1948 clearly stated that before a vascular blood clot can be initiated, first the endothelium must break or ulcerate or rupture or be damaged, and only then will platelets adhere to sub-endothelium tissue to initiate a platelet thrombus and the beginning of a vascular blood clot.31 In 1955 Willis told of the requirement of a damaged endothelium to produce a dangerous vascular blood clot, and he suggested that Vitamin C, by giving strength to the endothelium, could prevent fatal blood clots.32 In 1965 Owren clearly stated the role of the endothelium and platelets in vascular blood clots, in that only after the endothelium had been ruptured can a platelet thrombus form at the site of the rupture.23 Benditt, when he used an electron microscope to determine that human atheroma is largely composed of benign tumor, took note of bits of broken endothelium and platelets in atheroma. He suggested that while the major portion of the plaque of atheroma is benign tumor, the plaque is enlarged and thickened by the endothelium breaking from time to time. When this happens, the blood’s fibrinolytic activity will lyse most of the clot, and new endothelium will cover the site of the break, but bits of old endothelium and a few platelets will be added to the plaque of atheroma.7 Katz and Stamler in their 1953 work on experimental atherosclerosis, were striving to find a solution to Ml, but in their entire work they make no mention of platelets, and only once do they mention the endothelium - in that to say that with chickens, the yellow, waxlike cholesterol forms under the endothelium. So even with their chickens, cholesterol did not settle out of the blood, clogging the arteries.2 Between 1925, when it was decided that coronary blood clots either caused or were involved in Ml, and the early 197Os, orthodox doctors disregarded the roles of both the endothelium and platelets in myocardial infarction. The endothelium is only one cell thick, but it is an all-important, albeit fragile, lifeline. Moncada and Vane have shown that the endothelium protects itself from blood clots forming on it by producing PGI2, which reduces platelet adhestion to a degree that platelet thrombi can never form on it as long as it remains unbroken.27

THE ROLE OF FIBRINOLYSIS As soon as the endothelium in a coronary artery ruptures and a platelet thrombus forms with the subsequent fibrin red clot, the fibrinolytic enzyme, plasmin, begins to lyse the fibrin portion of the clot. The endothelium protects itself not only from blood clots by producing PG12, but as Astrup in 1956 suggested, the endothelium also protects itself by producing plasmin to lyse fibrin,33 however, Astrup had platelets involved in a vascular 311

blood clot, but only after fibrin had formed. Even as late as 1971, Todd supported this concept of the endothelium’s ability to prevent blood clots, without any mention of the role of platelets.3 Men who have survived MI have been shown to have lower fibrinolytic to men who never suffered from Ml.35 Exercise increases fibrinolytic eating onions,37 while something other than alcohol in beer, wine and apples or grapes reduces fibrinolytic acitify, as do lactones in heated margarine.39

HISTORY OF MYOCARDIAL

activity as compared activity,36 as does vinegar made from fats such as in

INFARCTION

In a press conference on September 1, 1983, Senator Henry Jackson, on return from a tiring overseas mission, spoke in great anger, excoriating the Russians who had just shot down a Korean passenger aircraft. He then went home, where he died suddently of Ml. Sixty years earlier, in August, 1923, President Warren Harding received the shocking news of the Teapot Dome scandal and died suddenly, no doubt like Senator Jackson, of Ml; however, as no one in medicine in 1923 had any knowledge of Ml, history records that he died of a mysterious form of sudden death. In late 1925, Cowan and Bramwell reviewed the case histories of twenty-four patients who had died of bundle branch block with fibrillation and speculated as to the cause of death. The description of two case histories were of Ml; however, no mention was made of it, displaying a lack of knowledge of Ml.40

In 1920 when death from myocardial infarction must have been most rare, dietary fats were Diet was rich in cholesterol, devoid of the liquid unsaturated fats, butter, lard and tallow. and in the so-called midwestern goiter belt of the United States, very little seafood was consumed. How, then, in 1960 did orthodox medicine accept the dogma that the typical of 1920 was the cause of the pandemic of Ml?

RATIONALE

American diet

ON MI

In his 1967 book, “Human Atheroma,” William Ashton stated what was then the general orthodox concept of atheroma as a cause of Ml,41 one which even today fits orthodox concepts, as follows: I) That human atheroma intimal layers;

is composed of yellow

lipid, mostly cholesterol,

deposited in the

2) That the intimal surface will ulcerate with resulting ischemic blood clotsmention of the endothelium; 3) That the degree of the severity of atheroma is proportional 41 That the stickiness of platelets may be a contributing and causing Ml; 312

this without

to the death rate from MI;

factor both in forming

atheroma

5) That in parts of Asia and Africa where death from MI is known to be rare, atheroma is also rare. {Ashton, however, noted that better information was needed about atheroma among people such as the Bantus of South Africa, who suffer from little or no Ml.) There have been challenges to the concept that atheroma causes MI and that in populations with little MI there is but little atheroma. Keeley and Higginson

in 1957 reported atheroma among the BantusP2 even though they

seemed to be free from Ml. They suggested that thrombi rather than atheroma may be the major cause of Ml. In 1959 Gore eta/ found the same degree of atheroma in Japan and in the United States. Gore and his group did not expect this result and asked what had gone wrong with their Japanese sample.43 In 1958 Strong eta/ reported on a worldwide study showing that atheroma is as prevalent among women as it is among men, and further, that all populations of the world suffer from atheroma to about the same degree, even among populations such as the Bantus, who are known to suffer from little Ml,44 In 1950 Thomas eta/ reported on a study in pathology, showing the black population of Uganda to be free from Ml; however, they did note that these blacks had atheroma.45 They, like Keeley and Higginson, said that it was high time more concern should be shown over the danger of thrombi and lessconcern about atheroma. Strong eta/ are continuing a study comparing atheroma in New Orleans, USA, and Tokyo, Japan, finding that in New Orleans, where the death rate from Ml was very high as of 1978, there was very little difference in atheroma as compared with Tokyo men, among whom MI is much lesscommon.70 In 1980 Sinclair noted that in Jamaica, where there is severe atheroma caused presumably by coconut oil in diet, atheroma does not seem to cause coronary thrombosis. Sinclair, in common with Thomas eta/ and Keeley and Higginson, stated that thrombosis and not atheroma is the major causal factor in Ml.71 There is now abundant evidence that man, worldwide, is afflicted with atheroma, but that many populations in Africa and Asia do co-exist with their atheroma without being afflicted with Ml. Prostaglandins and prostaglandin-like substances control vasodilation or vasoconstriction as well as the stickiness of platelets. The fatty acids in diet determine if beneficial or harmful prostaglandins will dominate. It is suggested that diet in the United States in 1920 must have been conducive to the proper prostaglandins to make Ml as rare then as it is among the Bantus today. In 1982 Simpson eta/ in England reported that Ml patients show a deficiency of linoleic acid in red-cell membrane phospholipids as compared to patients free from MI, indicating to them that Ml stands in an inverse ratio to dietary linoleic acid, with the more dietary linoleic acid, the less Ml.46 Also, Miettinen eta/ in Finland reported in 1982 that linoleic acid in diet was inversely proportional to Ml, with the more linoleic acid, the less Ml.47 In this prostaglandin era, it is as wrong to use the term linoleic acid without mention of its isomers as it would be to consider spring water and sea water as both being potable. In the 1920s when death from Ml in the United States was very rare, diet contained cis-cis linoleic acid in foods such as eggs, chicken and pork fat, as well as in grains such as corn,

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wheat and rye. There was also cis-trans linoleic acid in butter and beef fat. The new oil seed and hydrogenation industry in the mid1920s began to introduce into the American diet large amounts of the new and highly unnatural trans-trans linoleic acid along with other trans isomers of unsaturated fatty acids.72 The refined vegetable oils such as from corn, sunflower and cotton seed contain 50% of a mixture of trans-trans and cis-cis linoleic acid, while margarines contain from five to thirty percent trans-trans and cis-cis linoleic acid.48 These trans-trans linoleic acid-bearing fats were hardly available in 1920 at all. Enig eta/ in 1978 noted that in 1909 (when MI was so very rare) animal fat consumption averaged 104 grams per capita per day, whereas vegetable fat intake was only 21 grams per capita per day. By contrast, in 1972 when in the United States there were 600,000 deaths from Ml, animal fat consumption

had decreased to 97 grams per day while vegetable fat consumption

had in-

creased almost threefold, to 69 grams per day. They noted that by 1972 the average American consumed 12.1 grams of trans-trans linoleic acid per day. They noted that in margarine, up to 47% of the linoleic acid was as the trans-trans isomer, that vegetable shortening, used so widely in bread and baked goods, has up to 53% of the linoleic acid,as the transtrans isomer, while in liquid vegetable oils up to 17% is as the trans-trans isomer.49 In 1983 Enig eta/ reported that partially hydrogenated vegetable oils contain a far greater amount of these unnatural trans isomers than do the more fully hydrogenated fats. In this more recent work they reported that vegetable shortening contains from 8.7 to 35.4% trans fatty acids. Stick margarine contains from 15.9 to 31%. One grade of corn snack chips contain 25% trans fatty acids, and French fried potatoes contain from 7 to 35% of trans fatty acid in their fat. The fat in crackers contains up to 30% trans fatty acids. Pastries made of iard contain no trans fatty acids, but when made of vegetable shortening they contain up to 32% trans fatty acids. The fats in bread contain up to 23% trans fatty acid when vegetable shortening is used, but only 0.2% when hydrogenated lard is used as shortening.72 In the United States today, where we will have 550,000 deaths from Ml this year, the population has three times as much linoleic acid as was present in the American diet in the 1920s. Today’s linoleic acid, however, is a mixture of the trans-trans, cis-trans and cis-cis isomers, whereas in 1920 such little linoleic acid as was in diet was made up of the cis-cis and cistrans isomers in the almost complete absence of the trans-trans isomer. The blacks of Uganda, who are free from Ml, have only 15% dietary fat calories11 and as such have in their diet only about 10% as much linoleic acid as does anyone living today in the United States, England and Finland; however, all of the small linoleic acid content of the Ugandan diet is the cis-cis isomer. Horrobin has clarified the relationship of the isomers of linoleic acid to Ml. Cis-cis linoleic acid under the influence of the enzyme, delta-6-desaturase (D6D), is converted to gamma linolenic acid (G LA). G LA then is converted to dihomogamma linolenic acid, which is then converted to prostaglandin El (PGE1). PGE1, like PG12, acts as a vasodilator and rePGEl also prevents harmful vascular blood clots in another duces platelet aggregation. way. It influences in a most favorable manner the ratio of PG12 to thromboxane A2 (TXA2), derived from arachidonic acid in both meat and dairy products, so that much beneficial PG12 is formed with little TXA2; however, the conversion of cis-cis linoleic acid to GLA is blocked by dietary trans-trans linoleic acid.28 It could be that in 1920 when death from Ml was so very rare in the United States, the relatively small amount of dietary cis-cis linoleic acid was converted in toto to PGEl, which was adequate to prevent the blood clots of Ml, whereas today, with three times as much dietary linoleic acid in the form of the mixed isomers, we suffer from a severe deficiency of PGEl, with the result that we have far

314

too rinuchTXA2, which causes Ml and strokes by both vasoconstriction and increased aggregation of platelets. Keeley and Higginson in 1957 and Thomas eta/ in 1960 said it was time that lessthought should be devoted. to atheroma and more to vascular blood clots as a cause of Ml. Streptokinase will lyse the fibrin portion of a blood clot. Streptokinase has been used with success within three hours of the onset of the pain of Ml. Nineteen of 24 Ml patients treated with intracoronary streptokinase had coronary perfusion re-established, and they benefited by lesspain.50 In another such test with streptokinase in which streptokinase was administered six hours after the first pain of Ml, 12 of 20 patients had coronary circulation re-established, but these patients benefited little otherwise.51 These streptokinase tests demonstrate that in the vast majority of Ml cases, coronary blood clots and not atheroma are the cause of the disaster; and further, that if such coronary blood clots are not lysed within three hours of the beginning of the thrombus, the myocardium undergoes irreversible damage due to infarction. There seem to be four prostaglandin pathways to the prevention of Ml, the first being cis-cis linoleic acid being converted to PGE1. In this respect, as we grow older we produce less of the enzyme D6D and hence are able to convert less cis-cis linoleic acid to GLA.52 Horrobin suggeststhat the way to avoid this roadblock to a proper amount of PGEl is to take as a dietary supplement evening primrose oil, which contains nine percent by weight of G LA. It is no doubt the cis-cis linoleic acid to PGET pathway that prevents Ml among the Ugandan black population. The second pathway is via eicosapentaenoic acid in fish oil to PGl3. It is through this pathway that the Greenland Eskimos no doubt derive their freedom from Ml.25 The third pathway is via alpha linolenic acid- in grains such as rye, wheat and millet, in soybeans and in nuts such as chestnuts and walnuts - being converted in small part to PGl3.29 PGl3 must act in all respects like PGEl. The fourth prostaglandin pathway has to do with the oils of onions and garlic, which contain methylallyltrisulfide, which, like PGEt , restricts the formation of harmful TXA2.75 The Japanese, who have a low death rate from Ml, benefit from three prostaglandin pathways. They have cis-cis linoleic acid in rice and soy food, which converts to PGEt . They have alpha linolenic acid in soy food, which converts to PGl3, and they have eicosapentaenoic acid in fish, which converts to PGl3. Also, they have but little trans-trans linoleic acid in their low-fat diet, as hydrogenated margarines are seldom used in Japan. It is easy to reason that as the Ugandan black population has little dietary saturated fat and very low serum cholesterol, then it follows that a combination of high dietary saturated fats and high serum cholesterol causes Ml; however, there are dramatic exceptions. Malhotra has shown that the north Indian population around Udaipur has a very low death These rate from MI while living on a high-fat diet in which nearly all the fat is outterfat.53 Indians have in their diet a dish calledpokara, which consists of onions fried in butter.

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Stare eta/, in their Irish Brothers Study, have shown that brothers living in Ireland and eating one pound of butter a week suffer from less MI than do their brothers in Boston, who have in diet more linoleic acid and less saturated fats.54 The circumstantial evidence associating MI with hydrogenated, trans-trans linoleic acid-con. taining margarines and fats is strong. In 1920 in the United States, when death from Ml was rare, there was very little trans-trans linoleic acid in diet. Then in the late 193Os, as margarines to a large extent replaced butter in diet, death from MI became pandemic. In Norway during and following World War II, as margarine consumption decreased by half, death from Ml decreased by one-third. Then between 1945 and 1955, as margarine consumption tripled, death from Ml doubled.23

THE RELATIONSHIP

OF THE MARGARINE

INDUSTRY

TO Ml

The margarine industry, circa 1910, was founded by the meat-packing industry as a means of utilizing waste animal fats in producing human food. For many years margarine was called oleomargarine, the o/e0 from oleostearin, derived from tallow. At the same time, in the southern United States where swine were fed peanuts, pork fat was semi liquid and could not be sold as lard. At that time the creamery industry discarded much by-product buttermilk. The meat-packing industry imported palm, coconut and fish oil, to blend with waste animal fat, to produce oleomargarine.55 About ten percent of the early oleomargarine was made up of waste milk solids discarded by the creamery industry. The early oleomargarines contained a little linoleic acid as cis-trans linoleic acid from tallow and some cis-cis linoleic acid from soft pork fat; however, most oleomargarines of that day contained no pork fat. Figures are not available, as no one was concerned with the isomers of linoleic acid then, but it is likely that these early margarines contained no trans-trans linoleic acid. The early margarines were made up mostly of tallow, palm oil and coconut oil, and as the fatty acids in these fats were for the most part saturated, they were not hydrogenated. Literary Digest, a widely read American magazine in the 192Os, took the side of the margarine industry against the restrictive legislation against margarine which had been passed by both state and federal governments in behalf of the dairy industry. In 1923 the Literary Digest gave margarine figures in the United States as being 114,000,000 pounds in 1914, with an increase to 400,000,000 pounds by 1923, notwithstanding restrictive legislation.56 This amounted to about one pound per person per year in the United States in 1914 and four pounds per person per year in 1923. There was much opposition on the part of American farmers to the importation of so much foreign fish, palm and coconut oil; so beginning in 1925, there was a great proliferation of soybean and cottonseed extraction plants. By the mid-1930s margarine in the United States had changed from being a waste animal-fat product containing also the highly saturated fatty acids in palm and coconut oils to a product made up largely of soy and cottonseed oils, which oils contained between 40 and 50 percent cis-cis linoleic acid as compared to none in Hydrogenation of these high-linoleic-acid oils produced margarpalm and coconut oil.57 ines with a relatively high content of trans-trans linoleic acid. Owren in 1965 showed that consumption of this newer type of margarine in Norway had, by 1939, reached 40 pounds per year per person, and by 1955 consumption had increased 316

further

to 53 pounds

in our Western

half to 18 pounds that country increased

per person

World;

per person

decreased

from

die of it and no one could with

pounds

very

linoleic

had become 53 pounds

endemic,

Between

By 1939, when about

per year, death

fats in butter, of margarine

atheroms greatly

increased.

Meanwhile,

in 1960 at about

600,000

ing the infusion bearing liquid

liquid

into fats;

unsaturated

from

constant,

basis, death

soybeans,

sunflower,

at that

the dogma

figure

unsatu-

and cotton

seed

States plateaued

for ten years,

notwithstand-

of these “good,”

linoleic

the consumption

MI began to decrease.

Ml in the United

the

prevent

of liquid

safflower

Ml in the United

of pounds from

to

causes Ml, and that

and corn oil in diet would

rate from

death

from

MI

proportions,

in toto accepted which

in the decade of the 197Os, while

fats remained

on a population-corrected

from

had increased

IN Ml?

establishment

constant

fats

acid-containing

per year, death

pandemic

was

saturated

consumption

cause atheroma,

diet of millions

States could

mostly

1958 and 1970 the consumption

and remained

however,

DECLfNE

death

MI in

consumption

consumption

linoleic

per person

MI had reached

corn,

the annual

the American

of the United

then contained

oils such as safflower

between

rated fats such as the oils derived

deaths from

MI, margarine

the new trans.trans

medical

and liquid

from

this new margarine

lard and tallow

Accordingly,

and Ml.

rationing,

Ml doubled.22

40 pounds

from

1958 and 1960 the orthodox

substitution

from

per year, and mtirgarine

WHY THE ______

that saturated

War II food

epidemic

by more than

1945 and 1955 as margarine

it was death

and by 1955 when

per person

World

per year, death

had reached

MI had become decreased

Ml was so rare that the president

acid.

consumption

from

consumption

and between

be aware that

per person

little

margarine

per year during

per capita

So in 1923 when death but four

as margarine

by one-third,

to 53 pounds

By 1939 death

per year.

yet in Norway,

acid-

of these By the 1980s

States had decreased

by about

21 percent.58

In the January noted

that

26, 1980 issue of The Lancet,

there

had been a substantial

men in the United middle-aged

States,

men smoked

use of anti-hypertensive reducing

Ml;

yet one could cigarettes

that

now.

Also,

drugs in the United counter

speculated

in cigarette

counter

than

but again, one could

the editor

decrease

on this decline.

smoking

among

in the near Ml-free the editor

He

middle-aged

days of 1923,

suggested

more

that the aggressive

States in the decade of the 1970s was helpful that

in 1923,

hypertension

was not controlled

any means.

Again,

in the Mijrch

Evidence.“ studies

trying

negative

to prove

reports

writing

thrombosis

give impetus acid without

caused

1965.

In 1973,

the editor Study59

wrote

of replacing

saturated

that the Western

Now into

the benefits

on “Soft

and the fact that

fats in diet with of essential

Study fatty

Even as late at 1981, we see the editor mention of its isomersgood and bad fattv

is offered Anderson

acids in diet seemed to affect

as to the decrease postulated,

317

Fat-

Hard

in numerous

unsaturated

Electric

He did address the atheroma/thrombosis

Ml and that

a suggestion

Electric

ones.

to research

of prostaglandins.

As a hypothesis, ning after

positive

of Ml in a population.

on linoleic

sideration

the Western

the benefit

balanced

he said, it should preventing

14, 1981 issue of The Lancet,

Here he reviewed

fat,

was positive, acids in the

of The Lancet and without con-

issue and said that thrombosis.

in MI in the United

as has been suggested

States,

begin-

here, that the rapid

in by

growth of the oil seed industry in the 1920s may have caused the pandemic of Ml. He proposed that just as too little oxygen delivered by blood due to coronary arteries occluded by thrombi can cause Ml, so can too much oxygen (delivered as oxygen free radicals from lipid peroxides) make the myocardium susceptible to infarction and death from Ml. He reported that corn oil from which the antioxidants in the form of the tocopherols had been removed was highly cardiotoxic to small animals and would cause myocardial fibrotic foci, which in turn cause Ml.60 In making margarine, too many tocopherols prevent the hydrogenation process from working. Over half the tocopherols in the crude, unsaturated vegetable oils used in making margarine are removed in refining. In the refining of the liquid oils, such as corn oil, now so widely used, a substantial proportion of tocopherols are also removed. Anderson suggests as a hypothesis that in the absence of the tocopherols, the so-called “good” unsaturated fatty acids such as linoleic acid are oxidized in vivo to lipid peroxides, which damage the myocardium, thus causing MI. He suggests that the pandemic of Ml that occurred in our Western world after 1935 may have been caused by the entrance into our diet and our blood of the lipid peroxides from all the new, linoleic acid-bearing fats from which the antioxidants had been largely removed.60 There may be an even more compelling reason why these new, unsaturated liquid fats caused Ml. Vitamin E is alpha tocopherol, and Vitamin E reduces platelet adhesion.61, 62 It also increases anti-thrombin activity and thus prevents the deposition of fibrin on newly formed platelet thrombi.73,P.f By 1950 all the nation’s cottonseed, most of its soybean and sunflower seed and a substantial proportion of its corn crop went to the oil seed industry, which removed over half the tocopherols from their oils as a refining sludge, which went to the making of soap. In the mid-1950s, Evan Shute of the Shute Institute in London, Canada, waged a relentless campaign, holding that Vitamin E, 800 IU or more a day, was both preventive and curative in treating Ml; however, he met with total rejection from orthodox medicine.65 In 1953 the writer could not buy 200 IU Vitamin E capsules in the United States, so he ordered them from the Vitamin E Society in Canada. Orthodox medicine in the United States in that year persuaded the U.S. postal authorities that Vitamin E was an unproven remedy that that should be banned from the U.S. mail. Thereafter, this writer’s orders to the Vitamin E Society were returned, with a big FRAUDULENT stamped across the envelope. For several years thereafter, he smuggled in his Vitamin E capsules from Canada. While Shute never convinced orthodox medicine as to the value of Vitamin E in preventing By 1955 a sizeable industry was orMl, he did convince a large segment of the lay public. ganized, whereby all the hundreds of tons olI tocopherol sludge removed by the oil seed industry were recovered and sold, largely by the health food industry as Vitamin E capsules. By 1970, the supply of the natural d alpha tocopherol isomer of Vitamin E that could be had as a waste product from the oil seed industry could no longer supply popular demand. By 1975 the sale of the synthetic dl alpha tocopherol isomer of Vitamin E had exceeded the sale of the natural isomer. While not everyone takes Vitamin E capsules, the burgeoning Vitamin E industry in the United States has exactly coincided with the decrease in Ml that began sometime in the late 1960s and seems to be continuing.

318

CONCLUSION It would be well if it could be found how one could prevent the fibrous structure of human atheroma; however, until such time as this is known, it seems possible to co-exist with our atheroma and live essentially Ml-free lives by having in diet the proper fatty acids to insure ample levels of PGEl, PGl2 and/or PG13, with a restricted amount of harmful TXA2. Such a diet can vary all the way from the high-fat American diet of 1920, which contained much saturated animal fat and cholesterol and very little linoleic acid (but with almost no trans-trans linoleic acid), to the low-fat, low-linoleic acid, cholesterol-lowering, trans-trans linoleic-acid-free vegetarian diet of the Ugandan blacks, to the high-fat, fish-oil-bearing diet of the Greenland Eskimos.

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