Diet-Heart Hypothesis

https://www.crossfit.com/health/ancel-keys-cholesterol-con-part-4

Dr Tim Noakes:

In a previous column (3), I described how already in 1950, John Gofman, MD, had formulated the diet-heart and lipid hypotheses (4) two years before Keys would commandeer the ideas as his own.

Gofman posed as a double challenge for Keys and his future disciples. First, Gofman was far more qualified than Keys to undertake research into the dietary and other factors causing heart disease. But perhaps more importantly, Gofman’s diet-heart hypothesis gave equal weight to dietary fats and dietary carbohydrates as the factors driving atherosclerosis and the development of CHD.

According to Gofman:

What is solidly established is that the Sf° 20-400 lipoprotein levels [i.e., blood triglyceride or VLDL concentrations] on the average, can be raised by increasing the dietary carbohydrate intake and can be lowered by decreasing it. … Furthermore, many individuals who are characterized habitually by some type of error in their metabolism that makes their Sf° 20-400 lipoproteins habitually extremely high will experience a marked reduction in the blood levels of these lipoproteins when the carbohydrate intake is lowered. (5, p. 123, my addition)

Gofman continues:

These same lipoproteins are essentially unaffected, in the average case, by changing from animal to vegetable fats. This information is extremely crucial, for in many individuals the risk of coronary heart disease comes primarily from the Sf° 20-400 lipoproteins [VLDL or triglycerides]. For such individuals, any attempt to lower heart attack risk by shifting from animal fat to vegetable fat in the diet would be illogical. There would be no reason whatever to expect any benefits since one would be changing the diet in a manner directed toward affecting the Sf° 0-20 [LDL] lipoproteins, which is not the problem at hand for these persons. For such individuals, the preventive efforts would have to be directed toward lowering the carbohydrate intake, which will, on the average reduce the Sf° 20-400 lipoprotein levels. With respect to the effect of carbohydrates on the Sf° 20-400 lipoproteins, it is a matter of the amount of carbohydrate that is eaten rather than the total number of calories ingested. For example, if one maintains individuals at exactly the same number of calories per day, so that they do not alter the weight in any way, but takes out some of the carbohydrates in their diet and replaces them by vegetable oil, one finds that the Sf° 20-400 lipoprotein levels will fall. Achievement of this result of lowering the Sf° 20-400 lipoproteins requires neither any alteration in caloric intake nor any alteration in body weight. (5, p. 124, my additions and emphasis)

Subsequently, in 1958 Gofman pointed out a key logical flaw that has since been ignored (6). He noted that a number of studies had found increasing the dietary intake of vegetable oils produced a fall in blood cholesterol concentrations, and this has been interpreted as beneficial. But the addition of vegetable oils also reduced total carbohydrate intake, and since carbohydrate increases the Sf° 20-400 lipoprotein levels, which contain approximately 13% of cholesterol by weight, the shift from a higher- to a lower-carbohydrate diet might be the real reason why increasing the intake of vegetable oils causes a reduction in blood cholesterol concentrations.

Thus, Gofman warned: “No consideration was given by them to the possibility that the lowering of cholesterol levels might have been the result of the simultaneous removal of a large amount of carbohydrate from the diet” (6, p. 277).

Gofman next describes the effects of a low-carbohydrate (100 g/day) diet in a 65-year-old male subject with a previous myocardial infarction (Figure 2).

Figure 2: The effects of a low-carbohydrate diet in a myocardial infarction survivor. Note the low-carbohydrate diet produced a very large decrease in the Sf° 20-400 lipoprotein levels, now known as the VLDL-lipoproteins, which transport predominantly triglycerides. Total blood cholesterol concentration was unaffected by this dietary change. Despite this, the patient’s atherogenic index (AI) had fallen, placing him in a more favorable metabolic state according to Gofman’s understanding. Reproduced from data on Table V in reference 6, p. 279.

As Gofman wrote: “It can be seen from these data that a massive fall in the serum Sf° 20-400 lipoprotein levels occurs on the low-carbohydrate diet, without significant changes in the Sf° 0-20 lipoprotein levels. Accompanying this fall in lipoproteins is a highly marked and favourable reduction in the atherogenic index value” (6, p. 278-279).

Thus, the real originator of the diet-heart and lipid hypotheses stated that a low-carbohydrate, high-fat diet can be used in persons with established coronary atherosclerosis, presumably to reverse that disease.

He continued:

These same principles of carbohydrate restriction have been applied successfully in several types of extreme derangement of lipoprotein level control of the Sf° 20-400 lipoprotein class, namely, in xanthoma tuberosum, essential hyperlipidemia, and in diabetes mellitus … . For such a [post-myocardial infarction] patient, it is quite clear that management of the problem of coronary disease by dietary means involves the use of a low-carbohydrate diet, and not a low-fat, high-carbohydrate diet which is so often prescribed when attention is not paid to the lipoprotein findings. (6, p. 279-280, my emphasis)

The importance of this is that this evidence anticipated Peter Kuo’s “discovery” of carbohydrate-sensitive hyper(tri)glyceridemia (7) and its reversal with a low-carbohydrate diet by nine years (Figures 6 and 7 in reference 8).

In his conclusions Gofman wrote:

The increase in risk of future myocardial infarction associated with elevation of lipoproteins of the Sf° 20-400 lipoprotein classes provides the basis for a rational application of dietary measures in this disease … . Dietary carbohydrate intake is a prime factor controlling the serum level of the Sf° 20-100 and Sf° 100-400 lipoprotein classes. Restriction of dietary carbohydrates can provoke marked falls in the serum level of these lipoproteins … . The serum cholesterol measurement can be a dangerously misleading guide in evaluation of the effect of diet upon the serum lipids … . Rational management of patients with coronary heart disease or of individuals attempting to avoid coronary disease depends upon knowledge of the lipoprotein distribution in the individual patient. (6, p. 282-283)

Elsewhere Gofman wrote: “Neglect of [the carbohydrate factor] can lead to rather serious consequences, first in the failure to correct the diet in some individuals who are very sensitive to the carbohydrate action; and second, by allowing certain individuals sensitive to the carbohydrate action to take too much carbohydrate as a replacement for some of their animal fats” (9, p. 156-157).

In one of his last publications, a 1960 editorial, he again emphasized his concern about the carbohydrate factor:

Several investigators have shown that a low-fat high-carbohydrate diet produces opposite trends in the blood cholesterol and the blood lipid levels. The cholesterol level falls because the low fat diet depresses the level of the cholesterol rich Sf° 0-20 lipoproteins. The triglyceride level rises because the high carbohydrate intake elevates the level of the triglyceride-rich Sf° 20-400 lipoproteins. Both the triglyceride-bearing and cholesterol-bearing lipoproteins have been associated with the development of coronary disease. It therefore behoves the physician utilizing the dietary approach to understand the likelihood that a focus on the fat intake without an appreciation of the effect of carbohydrate intake will not lower all the blood lipids associated with the development of coronary heart disease. (10, p. 83)

Blood lipids and human atherosclerosis

"It was Ancel Keys himself who first discredited this notion[avoid eating cholesterol to reduce accumulation in body]. Although in 1952 he stated that there was "overwhelming evidence" for the theory, he then found that no matter how much cholesterol he fed to the volunteers in his studies, the cholesterol levels in their blood remained unchanged. He found that "tremendous" dosages of cholesterol added t othe daily diet--up to 3,000 milligrams per day (a single large egg has just under 200 mg)--had only a "trivial" effect and by 1955, he had already decided that "this point requires no further consideration."

-Nina Teicholz - Big Fat Surprise - Page 23

"Keys confidently drew a direct line of causation from fat in the diet to serum cholesterol in the blood to heart disease. In a 1952 presentation at Mt. Sinai in New York, Keys formally introduced this idea, which he called his "diet-heart hypothesis." His graph showed a close correlation between fat intake and death rates from heart disease in six countries."

​

Nina Teicholz - Big Fat Surprise - Page 27

4. Discussion. 

Since hypertension in man has been stated to be typically associated with increased incidence and severity of atherosclerosis (Katz and Stamler, 1953), it would be of interest to compare the incidence of hypertension in Eskimos with that of Whites although the interrelationship between hypertension and atherosclerosis is by no means clear. In a survey of 104 Alaskan Eskimos the author found that both the systolic and diastolic blood pressures were lower in Eskimos than in Whites of corresponding age. Eighty per cent of the recorded systolic blood pressures were below 116 mm Hg. and no systolic blood pressure higher than 162 mm was ever recorded in our "normal" Eskimo subjects. In a series of 117 Eskimo patients, only one of the patients had systolic blood pressure above 145 mm (a 60-year old woman having a blood pressure of 200/80 mm) (Rodahl, 1954). It may be noted in this connection that Alexander (1949) found hypertension to be practically non-existent among Aleuts, and his electrocardiographic and clinical examination of 296 Aleuts, including 23 above the age of 60, revealed almost no cardiovascular disease. 

Gotman et al. (1950) have found that some hypertensives show elevated plasma concentrations of Sf 10-20 lipoproteins even if the blood cholesterol concentration is normal, although these changes in the "giant molecule" levels are not correlated with the degree of hypertension. 

Very little is known regarding the plasma lipids in Eskimos, and the plasma lipid studies in Eskimos so far reported have yielded inconsistent data. This may not be surprising when considering the wide range of conditions, dietary and otherwise, encountered in the different groups of Eskimos. Corcoran and Rabinowitch (1937) who studied two groups of Canadian Eskimos, one group subsisting on a meat diet and one group subsisting on a mixed diet, found in both groups lower concentrations of plasma lipids and of cholesterol than the normal values for Whites, and the meat group had slightly higher plasma lipid levels than the group on a mixed diet. In this connection it may be noted that serum cholesterol in Whites is decreased in severe caloric undernutrition (Keys, 1953-b). Periods of semi-starvation may occur among the Eskimos, which thus may affect the blood lipid levels. Sinclair et al. ( 1949) have reported plasma lipid findings in the Canadian Eskimos that are similar to the figures considered normal in Americans. Wilber and Levine (1950) found moderately elevated plasma lipid levels of Alaskan Eskimos. It may also be noted that Alexander (1949) found mean plasma cholesterol levels of 176-197 mg/l 00 ml in two groups of Aleuts. 

In view of the small number of Eskimos examined in the present study no definite conclusion can be drawn from this limited material. These preliminary investigations indicate, however, that while some Eskimos, such as the Nunamiuts, may have very high cholesterol intakes, the average figures for dietary cholesterol and fat for the four Eskimo groups examined are comparable to those of the average American man; their blood cholesterol levels are the same, while the Sf 12-20 lipoproteins (Gofman fraction) were lower in concentration than Whites of corresponding age. If it were convincingly demonstrated that the Eskimos in reality have a lower incidence of cardiovascular disease than Whites, it would appear that these findings support Gofman's postulates that the high concentration of the cholesterol-bearing protein molecules are associated with atheroclerosis. 

It should be noted, however, that very little exact information is available regarding the occurrence of arteriosclerosis in Eskimos. None of the 16 Eskimos analyzed here showed any evidence of arteriosclerosis by clinical or roentgenological examination, and cardiovascular disease was extremely rare among the large number of Eskimo patients examined by the author during a two-year period in Alaska. Similarly, Dr. Paul Haggland, who has operated on a large number of Eskimos in Alaska during the last 15 years, has never seen arteriosclerosis or atherosclerosis in Eskimos (personal communications). He had the occasion to perform autopsy on one female and two male Eskimos, aged 60-65 years, and found no arteriosclerosis. Dr. Earl Albrecht, Territory Commissioner of Health, states that arteriosclerosis is rare in Eskimos, based on clinical evidence (personal communications). 

Bertelsen (1940) is, on the other hand, of the opinion that arteriosclerosis is fairly common in Greenland, particularly if one considers the average span of life for the Greenland Eskimos. Hoygaard (1941) writes with regard to the Angmagssalik Eskimos, Southeast Greenland, that "arteriosclerosis was frequently found even in persons below 40". 

Brown (1951) states with regard to the Southampton Island Eskimos and the Igloolik Eskimos: "We have found well-marked general arteriosclerosis and also coronary heart disease proved by electrocardiogram and, in one case, by post mortem. Some of the cases of coronary heart disease were in congestive failure." 

During our study of the patho-physiology of the Alaskan Eskimos from 1950 to 1952, x-rays were taken of the chest and extremities of 84 Eskimos, using a portable x-ray apparatus. All chest x-rays were taken at a distance of 180 cm; all x-rays of the limbs (left arm and left leg) were taken at a distance of 90 cm. Professor Johan Torgersen, Institute of Anatomy, Oslo University, has very kindly examined all these roentgenograms, with a particular reference to possible roentgenological evidence of arteriosclerosis and other cardiovascular abnormalities. He finds, as a typical feature of all roentgenograms examined, that the bone structure in the Eskimo is unusually massive with sharply defined, well-calcified bone lamellae. The muscle attachments are as a rule very large. The occurrence of arthritis deformans is no less frequent in these Eskimos than in Whites of similar age (:5 cases in 84 Eskimos, 51 males and 33 females, with an average age of 28 years). Four Eskimo subjects at Barter Island had cartilaginous exostoses on the tibia (fig. 2). 

From this material (see Table 5) it appears that the occurrence of roentgenological evidence of arteriosclerosis in these Eskimos is neither more nor less than what one would expect to find in Whites of similar age groups. Out of 9 Eskimos over 47 years of age, roentgenological evidence of atherosclerosis of the arch of the aorta was detected in 3 cases, 2 males and 1 female. Of the entire material one Eskimo showed calcium deposits in the arteries (see fig. 1). In one 60-year old Eskimo woman with a blood pressurc of 200/80, thcre was slight enlargemcnt of the left ventricle of the heart. It is thus evident that further studies are necessary in order to settle the question of arteriosclerosis in the Eskimo and the relation between dietary cholesterol, serum cholesterol levels and cardiovascular disease ill these people.

5. Summary and Conclusions. 

The cholesterol content of some common Eskimo foods has been determined and the serum cholesterol level as well as the serum concentration of Sf 12-20 lipoproteins in 16 healthy Alaskan Eskimos are reported. On the basis of these preliminary data it appears that some Eskimos have high cholesterol intakes compared with healthy American men, but that their blood cholesterol levels are the same. On the other hand, the Sf 12-20 lipoproteins in Eskimos are lower in concentration than in Whites of corresponding age. From the available evidence it appears that the incidence of cardiovascular disease among the Alaskan Eskimos may be lower than in whites. A more complete analysis of this problem is in progress.

Keys used the same disparaging arguments to dismiss observations of Inuit in the Arctic. Like Mann, Vilhjalmur Stefansson had also seen for himself how good health and a high-fat diet could go hand in hand; the Inuit diet, as we’ve seen, was at least 50 percent fat. And in 1929 Stefansson conducted that yearlong experiment of eating only meat and fat. Optimistically, he expected that these efforts would lead to “a path of garlands for the high-fat regimens” laid down by admiring colleagues. He was thus unprepared for his fall from grace. “And what a fall!” he wrote. “The first cloud in the sky was no bigger than a man’s hand, in fact no larger than a brief and friendly personal note from Dr. Ancel Keyes [sic]” in 1954.