Diet-Heart Hypothesis

In 1910, as part of his pioneering studies of the role of cholesterol in human metabolism, German chemist Adolf Otto Reinhold Windaus discovered atheromatous arterial lesions (arterial plaques) contain six times as much free cholesterol and 20 times as much esterified cholesterol as do healthy arteries (2). Windaus would also later describe the pathways by which cholesterol is converted to vitamin D. For his work, he was awarded the Nobel Prize in chemistry in 1928.

The assumption at the time was, predictably, that the cholesterol in arterial plaques must arise from the cholesterol circulating in the bloodstream. In time, this finding gave rise to Gofman/Keys’ lipid hypothesis, which holds that elevated blood cholesterol concentrations (caused by eating a high-fat diet especially rich in “artery-clogging” saturated fats) drive cholesterol across the arterial lining, a single layer of cells known as the endothelium, and into the subendothelial space, causing the initiation of fatty streaks (Figure 1). These then progress to the development of more advanced atherosclerosis, termed arterial plaques (Figure 2), which among other complications can cause heart attacks and strokes.

Figure 1: This diagram explains the currently accepted theory of how endothelial damage, largely of unknown cause, allows LDL-cholesterol to cross the endothelium and enter a postulated and hypothetical acellular space, the subendothelial space. There, the LDL-cholesterol is taken up by macrophages, causing the development of the earliest form of atherosclerosis, known as the fatty streak. Note that for the atherosclerotic process to happen in this way, the tunica intima must be devoid of all cells other than the single layer of endothelial cells that coat its upper surface, separating it from the blood contained in the lumen of the artery. According to this model, the subendothelial space is essentially a wide-open vacant space waiting expectantly to accommodate these (complex) processes that produce atherosclerosis. Reproduced with additions from reference 4, p. 3.

The finer details in Figure 1 are not critical to the argument. What is important is the way in which the different cellular structures are depicted.

Here, the crucial point is that, according to the currently popular explanation of atherosclerosis (4), until the endothelium is damaged (by currently unknown biological events), allowing the unrestrained entry of LDL-cholesterol, the tunica intima is depicted as a single, thin layer of endothelial cells sitting on top of an acellular space (devoid of cells). This is an important consideration, since the presence of any cells in the subendothelial space must impede the entry of LDL-cholesterol directly from the bloodstream and will hinder the ability of the macrophages to detect and consume the cholesterol, as depicted in Figure 1.

Figure 2 depicts how this model explains the progression of the fatty streak to full-blown atherosclerotic plaque. Note again that the subendothelial space is devoid of cells before the hypothetical endothelial damage allows the free entry of LDL-cholesterol into this conveniently located anatomical space.

Figure 2: This figure shows how the fatty streak (Figure 1) progresses to the atherosclerotic plaque according to the lipid hypothesis. For the lipid hypothesis to be true, until after the initial “injury” to the endothelium has allowed the entrance of blood-derived LDL-cholesterol, the tunica intima must, as shown in this figure and in Figure 1, contain no cells other than the thin layer of endothelial cells on its upper surface. Notice that in this figure, smooth muscle cells (SMC) migrate from the tunica media into the tunica intima to further progress the development of the atherosclerotic plaque. Reproduced with additions from reference 4, p. 8.

In 1910, neither Windaus nor anyone else was aware that cholesterol cannot simply pass through healthy arterial walls, however hard it may be “shoved” (3). Currently, the most popular theory for atherosclerosis is that shown in Figures 1 and 2. This theory holds that the endothelial cells lining the lumen of the artery wall must first be damaged before the passing of cholesterol through the wall can happen. This is termed “endothelial cell dysfunction” (4), but the immediate cause of “endothelial cell dysfunction,” if this is indeed the mechanism, remains shrouded in secrecy even today, 110 years after Windaus’ discovery.

This theory also predicts that cholesterol enters damaged arteries down a concentration gradient, so the degree of a person’s arterial disease can be predicted quite simply as their average blood cholesterol concentration multiplied by the number of years the blood cholesterol concentration has been “elevated” (3, 5).

Also, still unknown then was that atherosclerosis is a patchy disease that selectively targets only specific areas of different arteries. This is exemplified by what happens in the coronary arteries supplying blood to the heart muscle (6).

It also was then unknown that in some populations, there may be advanced atherosclerosis in the cerebral (brain) arteries with minimal involvement of the coronary (heart) arteries (7, 8). In such cases, a person is at greater risk of stroke than heart attack. In other cases, as is more prevalent in the U.S., the opposite applies.

Event Rich Text

The results of analyses of Eskimo foods are presented in Table 1. On the basis of nutritional surveys with individual food weighings in different families from four Eskimo settlements in Alaska and the above-mentioned results of cholesterol determinations in Eskimo foods, supplemented by figures available for the cholesterol content of nonEskimo foods (Okey, 1945; Pihl, 1952), the cholesterol intake of Eskimos has been estimated (Tables 2, 3). From these calculations it is observed that the mean caloric consumption of the 45 adult male and female Eskimos was about 2,700 calories, the fat consumption was 105 g and the mean cholesterol intake was roughly 340 mg daily, varying from 150 mg to 700 mg per day. It should be noted that these cholesterol figures may be considered as minimum values because several of the food items ingested could not be included in the calculation since the cholesterol content was unknown. It may also be noted that the cholesterol intake varies greatly from one Eskimo group to another, depending on the different dietary habits. Thus, it was observed that among the inland Eskimos, the Nunamiuts at Anaktuvuk Pass, some of the men consumed as much as 70 grams or more of boiled brain from mountain sheep in a single evening meal yielding almost 600 mg cholesterol from this food item alone. 

It is thus evident that some Eskimos have fairly high cholesterol intakes compared with healthy American white men, although the mean intake for the 45 Eskimos studied is in the order of 2.5 g per week (varying from 1 to 5 g) . This corresponds to the group of moderate habitual cholesterol intakes reported for normal American men (Keys, 1949) while in the Inland Eskimos the mean figure is in the order of 4 g cholesterol per week, which corresponds to the group of highest habitual cholesterol intakes for normal American men, reported by Keys (1949). 

Keys (1950) has estimated that the American diet varies with regard to cholesterol content from a low of 200-300 mg daily to 700-800 mg, depending on the food consumed. Gubner and Ungerleider ( 1949) have given the figure 200--360 mg for daily cholesterol intake on a mixed diet. 

It thus appears that the estimated mean figures for cholesterol intakes in Eskimos may be comparable to those of Whites on a mixed diet. 

The average figure for the daily fat consumption in the 45 Eskimo subjects reported here was only about 105 g (377 of the calories), while in a larger survey the average daily fat consumption in Alaskan Eskimos was 139 g (40 % of the calories). In normal white men living in Alaska the fat consumed represented 37.5 %( of the calories ingested. 

In the Eskimo subjects the mean serum cholesterol concentration was 203 mg per 100 ml (Table 4) which is about the same as is found in normal Whites. Thus L. J. Milch (personal communications) found an average level of 207 mg cholesterol per 100 ml serum in Whites 30-35 years old. 

On the other hand, the Eskimo serum concentration of Sf 12-20 lipoproteins was 20 mgl100 ml as against 28 mgl100 ml in Whites of similar age, observed by Milch (personal communications). For Whites under 25 years of age Milch found 24 mg/lOO ml, and for Whites 40-45 years of age 38 mg/l 00 m!.

Official History:

The AHA Reorganizes: The AHA reorganizes, transforming from a scientific society to a voluntary health organization composed of volunteers and supported by professional staff. Support for the AHA’s mission becomes much more visible, with fundraising activities taking hold in communities and businesses.

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"Founded in 1924 at the outset of the heart disease epidemic, the AHA was a scientific society of cardiologists seeking to better understand this new affliction. For decades, the AHA was small and underfunded, with virtually no income. Then in 1948, it got lucky: Proctor & Gamble (P&G) designated the group to receive all the funds from its "Truth or Consequences" content on the radio, raising $1,740,000, or 17 million in 2014 dollars. At a luncheon, P&G executives presented a check to the AHA president, and "suddenly the coffers were filled and there were funds avaliable for research, public health progress and development of local groups--all the stuff that dreams are made of!" according to the AHA's official history. The P&G check was the "bang of big bucks" that "launched" the group. Indeed, one year later the group opened seven chapters across the country and collected $2,650,000 from donations.

The new funds in 1948 allowed the group to hire its first professional director, a former fund-raiser for the American Bible Society, who unfolded an unprecedented fund-raising campaign across the United States. There were variety shows, fashion shows, quiz programs, auctions, and collections at movie theaters, all meant to raise money and let Americans know that heart disease was the country's number one killer."

-Nina Teicholz - The Big Fat Surprise - Page 48

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Instead, what happened was that after the diet-heart hypothesis became adopted by the AHA and NIH, Keys’s bias was institutionalized. These two organizations set the agenda for the field and controlled most of the research dollars, and scientists who didn’t want to end up like Mann had to go along with the AHA-NIH agenda.

The AHA and NIH were parallel, entwined forces from the start. In 1948, when the AHA was launched as a national, volunteer-run organization, one of its first tasks was to establish a “heart lobby” in Washington, DC, to convince President Eisenhower to set up the National Heart Institute—which he did, also in 1948.

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NHI morphed over the years into the National Heart, Lung, and Blood Institute (NHLBI) that exists today. And every step of the way, this new institute moved in concert with its close sibling, the AHA.

In 1950, for instance, the two jointly held the first national conference on heart disease, in Washington, DC.