American Medical Association

A Critique of Low-Carbohydrate Ketogenic Weight Reduction Regimens:
A Review of Dr. Atkins’ Diet Revolution
Journal of the American Medical Association 224(1974):1415.
Journal of the American Medical Association

This statement has been unanimously accepted for publication by the American Medical Association Council on Foods and Nutrition—Philip L. White, ScD, Secretary. Reprint requests to AMA Council on Foods and Nutrition, 535 N Dearborn St, Chicago 60610 (Dr. White).

There has been a rekindling of public interest in the low-carbohydrate ketogenic diet touted as a “miraculous” and “revolutionary” approach to weight reduction. A recent example is the publication and extensive promotion of a book, Dr. Atkins’ Diet Revolution.[1] The Council on Foods and Nutrition of the American Medical Association evaluated the claims made by Dr. Atkins and considered certain general questions concerning the “low-carbohydrate diet.”

History of Low-Carbohydrate Diets

The low-carbohydrate diet approach to weight reduction is neither new nor innovative. About a century ago, an English surgeon, William Harvey[2] devised a diet for obesity that specifically interdicted sweet and starchy foods, while permitting meat ad libitum. One of his portly patients, William Banting[3] attested to the efficacy of Harvey’s diet in A Letter on Corpulence, Addressed to the Public. During the last 20 years, there has been a cyclical recrudescence of similar diets having in common the following major features: (a) a low to very low carbohydrate content, (b) no restriction of protein and fat, and © 11 unrestricted calories.” Variants of the diet have been described in 1953 by Pennington[4, 5] (“Treatment of Obesity with Calorically Unrestricted Diets”), in 1960 as the Air Force diet,[6] in 1961 by Taller7, in 1964 as The Drinking Man’s Diet,[8] in 1967 by Stillman,[9] and, most recently, by Atkins1.

Over the years, starting with the “Banting Diet,” such regimens have been awarded. a succession of eponyms and, from the very beginning, have been proclaimed to the public in glowing terms, If such diets are truly successful, why then, do they fade into obscurity within a relatively short period only to be resurrected some years later in slightly different guise and under new sponsorship. Moreover, despite the claims of universal and painless success for such diets, no nationwide decrease in obesity has been reported.

Physiological Effects

An examination of the claims associated with advocacy of low-carbohydrate diets suggests that, in some instances, the authors found a way of circumventing the first law of thermodynamics, namely: “The energy of an isolated system is constant and any exchange of energy between a system and its surroundings must occur without the creation or destruction of energy.”“, For example, claims have been made that an unlimited calorie intake (excluding carbohydrate) is associated with a consistent and physiologically advantageous loss of weight (which presumably continues as long as the diet is maintained).

Most of the diets focus on diet composition, placing special emphasis on carbohydrate restriction while ignoring the calorie content of the diet. Some of the authors appear to believe that low-carbohydrate diets generate sufficient ketone bodies (eg, “incompletely burned” fat) to cause urinary losses of ketones in amounts sufficient to account for remarkable rates of weight loss in the face of high calorie intake. Dietary carbohydrate, particularly sugar, is considered by some advocates to be a nutritional “poison” that promotes “hypoglycemia,” diabetes, atherosclerosis, and, of course, obesity.

To understand how diets induce changes in body weight, it is necessary to consider their effect on body composition -notably, fat, lean tissue, and water. Obesity is defined as an accumulation of fat in undesirable excess. Such fat can be lost only when calorie expenditure exceeds calorie intake. When water is retained in the body, weight may remain stable or increase even though fat is being lost. When lean tissue is broken down, weight loss may be rapid; however, this kind of weight loss is generally thought to be undesirable. Thus, short-term changes in weight on any diet have little meaning unless the composition of the weight loss is known.

While it is widely understood that calories are obtained from food, it is not as well comprehended that calories (energy) are lost from the body as heat, as excreta and detritus (urine, stools, sweat, etc), in the breath, and as metabolic and mechanical work (the body’s metabolic processes and physical activity). There are no other significant pathways of energy loss and no weight reducing regimen can operate without utilizing these channels. No weight reducing diet, including the low-carbohydrate ketogenic diet, can be effective unless it provides for a decrease in energy intake or somehow increases energy losses.

Some observers have suggested that the excretion of large quantities of ketones in the urine might account for the extra weight loss alleged to occur in association with low-carbohydrate ketogenic diets. However, when ketone excretion incident to such diets actually has been measured, it has been found to range between 0.5 and 10 gm/24 hr.[11,12] Studies carried out on starving nondiabetic persons indicate that at most about 20 gm of ketones per day may be excreted in the urine.[13,14] And, as Folin and Denis- have shown, the total acetone excretion with the breath is quantitatively insignificant; at most, 1 gm/day. Since the caloric value of ketones is about 4.5 kcal/gm, it is clear that, in subjects on ketogenic diets, ketone losses in the urine rarely, if ever, exceed 100 kcal/day, a quantity that could not possibly account for the dramatic results claimed for such diets.

Another claim made by proponents of the low-carbohydrate high-fat diet has been based on observations by Kekwick and Pawan[16] in 1956 that obese patients on extremely high-fat diets of 1,000 kcal (90% of calories from fat) lost weight more rapidly over an eight- to ten-day period than when they were on an isocaloric diet containing a similar proportion of carbohydrate. To explain their findings, these authors suggested that “obese patients must alter their metabolism in response to the contents of the diet.” However, when Pilkington and associates” studied the effect of similar diets for periods of 18 to 24 days, rate of weight loss was the same for both diets.

During the first few days of their study, Pilkington et al did observe differences in rate of weight loss similar to those reported by Kekwick and Pawan; however, they concluded that these temporary differences were due chiefly to changes in water balance. Olesen and Quaade,[18] conducting similar studies, reported observations and conclusions similar to those of Pilkington et al. Finally, it should be mentioned that some years earlier, Werner[19] studied subjects on the Pennington version of the low-carbohydrate diet and found that, apart from transient changes in water balance, the rate of weight loss in obese subjects on the low-carbohydrate diet that restricted calories was similar to that of a “balanced” diet of equal caloric value.

The excretion of sodium and water from the body can be inhibited by dietary carbohydrate.[20,21] Bloom[22] has shown that the weight loss of fasting can be decreased or abolished by the sodium and water retention that occur after ingestion of 600 kcal of carbohydrate. This effect on weight occurs even while the subject remains in negative caloric balance. It should also be pointed out that diets devoid of or very low in carbohydrate tend to promote a temporary sodium loss from the body. In addition, a diet very high in protein content places an extra solute load on the kidneys necessitating an increase in excretion of urinary water; thus a low-carbohydrate diet, by several mechanisms, may cause dehydration, if suitable precautions are not taken. Patients whose renal function is already compromised may have difficulty in handling the extra burden placed on their kidneys by such a diet.

Basis for Weight Loss

No scientific evidence exists to suggest that the low-carbohydrate ketogenic diet has a metabolic advantage over more conventional diets for weight reduction. The fact remains, however, that some patients have lost weight on the low-carbohydrate diet “unrestricted in calories.” Why is this so? Yudkin and Carey[23] have reported experiments that provide an adequate explanation of the long-term weight loss that can occur when a “ketogenic” diet is consumed. These workers studied six obese adults who were carefully instructed in the weighing and recording of their complete diets. They were told to eat their usual food for two weeks. At the end of this time, they were asked to reduce the carbohydrate in their diets to about 50 gm/day for an additional two weeks and to eat as much protein and fat as they liked. Specifically, the subjects were told that they could eat unlimited amounts of such foods as meat, fish, eggs, cheese, butter, margarine, and cream. The intake of calories, protein, fat, and carbohydrate from the daily dietary records was then calculated.

In all subjects, there was a reduction in calories ranging from 13% to 55% during the time they were consuming the low-carbohydrate diet. Interestingly, none of the six subjects ate more fat, and three of them showed a significant reduction of fat intake, ranging from 22 to 35 gm/day. It was concluded that weight lost on such diets was principally due to the consumption of fewer calories.

When obese patients reduce their carbohydrate intake drastically, they are apparently unable to make up the ensuing deficit by means of an appreciable increase in protein and fat. This is especially noteworthy when one considers the fact that carbohydrates comprise 45% or more of the average American’s diet.[24] It is difficult to unbalance a diet to this extent and continue to consume the same calories as before. However, for persons who are adapted to a diet virtually devoid of carbohydrate it is not hard to maintain body weight. Tolstoi[25] and McClellan and DuBois[26] studied two normal men who maintained their usual weight for one year on a diet that consisted exclusively of lean and fat meat. The two men consumed about 120 to 130 gm of protein and enough fat to provide a total intake of 2,000 to 3,000 kcal/day. Thus, the weight reduction that occurs in obese subjects who are shifted to a low-carbohydrate diet seems to refleet their inability to adapt rapidly to the marked change in dietary composition. There appears to be no inherent reason why body weight can not be maintained on a diet devoid of carbohydrate if the other essential nutrients are provided.

At the other extreme, a majority of human beings, particularly those in., Asia and Africa, remain lean on diets extremely high in carbohydrate (by American standards) and correspondingly low in fat.[27,28] Thus, there is’ equally no inherent reason to associate a diet rich in carbohydrate with obesity.

Potential Hazards

What are the potential hazards of a diet very low in carbohydrate and rich in fat? Perhaps the greatest danger is related to hyperlipidemia, which may be induced by such a regimen. Hypercholesterolemia and hypertriglyceridemia are associated with an increased risk of developing coronary heart disease.[29,30] A diet rich in cholesterol and saturated fat could be responsible for accelerating artherosclerosis, particularly in susceptible persons. The two subjects reported on by Tolstoi[25] developed a visible lipemia on their all-meat (low-carbohydrate) diets, and their plasma cholesterol rose to high levels (in one subject up to 800 mg/100 ml).

Ketogenic diets also may cause a significant increase in the blood uric acid concentration. It appears that, by competing with uric acid for renal tubular excretion, elevated blood ketones can promote hyperuricemia. In patients with a gouty diathesis, the increment in hyperuricemia induced by such a regimen could exacerbate the underlying disease.

Bloom and Azar[31] have reported that all of the subjects whom they studied on “carbohydrate- free diets” complained of fatigue after two days on the diet. “This complaint was characterized by a feeling of physical lack of energy [and] was brought on by physical activity. The subjects all felt that they did not have sufficient energy to continue normal activity after the third day. This fatigue promptly disappeared after the addition of carbohydrate to the diet.”

Another observation made by Bloom and Azar was that the subjects on the low-carbohydrate diets developed postural hypotension. The average systolic pressure fell 30 mm Hg and the diastolic 15 mm Hg when the subjects assumed an upright position after being supine.

Evaluation of Dr. Atkins’ Diet Revolution

In light of these facts, some of the claims in Dr. Atkins’ Diet Revolution can be examined. It is alleged that “… carbohydrates-not fat-are the principal elements in food that fatten fat people. They do this by preventing you from burning up your own fat and by stimulating your body to make more fat…. Protein and fat combinations alone do not do this.”[1, p7]

How does this thermodynamic miracle take place? It is stated that the diet promotes the production of “fat mobilizing hormone” (FMH) “… and the production of FMH is the whole purpose of this diet-and the reason it works when all other diets fail.”[1, p16] But, according to Dr. Atkins, “FMH releases energy into your bloodstream by causing the stored fat to convert to carbohydrate. Thus, the fatigue clears without having to call upon the defective insulin mechanism.”[1, p13] Accordingly, “… this is the diet revolution; the new chemical situation in which ketones are being thrown off-and so are those unwanted pounds, all without hunger.”[1, p13]

As for a “fat mobilizing hormone” (FMH), no such hormone has been unequivocally identified in man. Fat is mobilized when insulin secretion diminishes.[32] Also, it is recognized that growth hormone and catecholamines stimulate fatty acid mobilization from the fat depots; however, neither of these substances is known to physicians and scientists as “FMH.” Thus, the existence and physiological role of a putative FMH in man remain to be established.

The assertion that carbohydrates are the principal elements in food that fatten is, at best, a half-truth. In point of fact, human subjects can gain weight by increasing their intake of fat, the most concentrated source of calories available. This was the rationale for the successful use of oral fat emulsions in the treatment of underweight persons.[33] Also, obesity is prevalent in North America, where the proportion of fat in the diet is higher than that in most other countries,[34] whereas obesity is relatively rare in large areas of the world where the “hidden sugar” of rice starch comprises a very high proportion of the total daily food intake.[35]

Body fat is burned in increasing quantity when total calorie intake is inadequate-regardless of the quantity of carbohydrate in the inadequate diet. Body fat is made from dietary fat as well as from dietary carbohydrate. This fact is obvious when one considers that the linoleic acid in the body’s fat depots (usually 10% to 12%) cannot be made in the body but is derived entirely from the diet. Indeed, the fatty acid pattern of fat in the body’s adipose stores tends to reflect the pattern of fatty acids in the diet.[36]

The notion that sedentary persons, without malabsorption or hyperthyroidism, can lose weight on a diet containing 5,000 kcal/day is incredible. No reliable nutritional studies have been reported to support such a claim. Nor is it possible to explain the alleged weight loss in the presence of a high calorie intake on the basis of ketonuria.[11-15]

With respect to ketosis, it is of particular interest to consider the experience of the Canadian Army during World War II with pemmican (dehydrated prime beef with added suet) as an emergency ration for infantry troops. In the Canadian study,[37] the pemmican derived 70% of its calories from fat and 30% from muscle. Thus, the ration was essentially free of carbohydrate.

The performance of the troops using pemmican and tea as the sole components of their ration deteriorated so rapidly as to incapacitate them in three days. When carbohydrate was added to the ration the men recuperated to a reasonably high level of performance.

While on the carbohydrate-free diet, the men complained of nausea and several of them vomited. Pathologic fatigue was evident. On the morning of the fourth day of the diet, physical examination disclosed a group of listless, dehydrated men with drawn faces and sunken eyes, whose breath smelled strongly of acetone. Because of anorexia and water loss the men had lost weight rapidly.

Throughout Dr. Atkins’ book, the statement is made that fat is readily converted to carbohydrate; this is biochemically incorrect. Available biochemical evidence indicates that the even-numbered carbon chain fatty acids stored in adipose tissue triglycerides cannot be used for appreciable net synthesis of carbohydrate.[38] Essentially all stored fat is composed of even-numbered carbon acids. The glycerol released during hydrolysis of triglyceride is potentially available for carbohydrate synthesis; however, glycerol is not a fat. In addition, glycerol in adipose tissue is derived entirely from circulating glucose. It comprises about 10% of the calories available when triglycerides are broken down and their components oxidized. There is no evidence that the fatty acid released from stored triglyceride “… stabilizes the gyrations in your blood sugar level.”’[1, p73]

The book vigorously condemns carbohydrates as being nutritionally pernicious. Dr. Atkins states that “It is important, then, to understand that sugar has antinutrient properties…. Starch is the major source of hidden sugar.”[1, p57] To describe starch as the major source of hidden sugar is naive. All carbohydrates in the diet must be converted to “sugar” by the digestive processes prior to their absorption by the intestine. To refer to sugar as having “antinutrient properties” is inaccurate. Although the thiamin (vitamin B1) requirement increases somewhat when dietary carbohydrate increases, this does not mean that sugar is an “antinutrient” any more than is linoleic acid, a dietary constituent that may increase the body’s requirement for vitamin E.

The book also puts great stress on “hypoglycemia” and its alleged relationship to obesity: “Hypoglycemia is undersuspected and underdiagnosed to an extent without parallel in medicine.”[1, p71] Dr. Atkins’ position on hypoglycemia should be considered in the light of the following statement:[39] recently published Feb 5 (223:682, 1973) in THE JOURNAL.

Recent publicity in the popular press has led the public to believe that the occurrence of hypoglycemia is widespread in this country and that many of the symptoms that affect the American population are not recognized as being caused by this condition. These claims are not supported by medical evidence. Because of the possible misunderstanding about the matter, three organizations of physicians and scientists (the American Diabetes Association, the Endocrine Society, and the American Medical Association) have issued the following statement for the public concerning the diagnosis and treatment of hypoglycemia:

“Hypoglycemia means a low level of blood sugar. When it occurs, it is often attended by symptoms of sweating, shakiness, trembling, anxiety, fast heart action, headache, hunger sensations, brief feelings of weakness, and, occasionally, seizures and coma. However, the majority of people with these kinds of symptoms do not have hypoglycemia; a great many patients with anxiety reactions present with similar symptoms. Furthermore, there is no good evidence that hypoglycemia causes depression, chronic fatigue, allergies, nervous breakdowns, alcoholism, juvenile delinquency, childhood behavior problems, drug addiction or inadequate sexual performance… .”

It is curious that hypoglycemia does not appear to be a problem in parts of the world where carbohydrate provides up to 80% of dietary calories. Indeed, it is of interest that in those same high-carbohydrate areas diabetes mellitus is less common than in the United States .27 Also, it has been shown 41 that diabetic patients consuming a diet low in cholesterol (100 mg/24 hr), high in carbohydrate (64% of total calories), and low in fat (20% of total calories) maintained good to excellent regulation without an increase in insulin requirements and with a decrease in plasma cholesterol levels. Plasma triglycerides did not increase.

According to Dr. Atkins, most overweight people are hypoglycemic. A majority of physicians probably would not agree with this statement since it is well known that obese patients tend to be resistant to their own insulin. Moreover, there is no sound evidence to suggest that Dr. Atkins’ recommendations of “… megadoses of B-complex, C, and especially E vitamins”[1, p153] will help keep blood sugar at an even level. The blood sugar remains remarkably stable without the help of unphysiologic doses of vitamins.

The diet encourages a high intake of saturated fats and cholesterol. The possible hazards of this practice are shrugged off with statements such as: “Studies have shown that you cannot absorb more cholesterol than is in two eggs each day.”[1, p282] This is not entirely correct. It is not impossible to increase the plasma cholesterol level somewhat further by increasing the intake of egg cholesterol beyond this quantity.[41-44] More to the point, when they are added to a low cholesterol diet, two egg yolks per day can cause an undesirable increase in the plasma cholesterol concentration. Moreover, a rise in plasma cholesterol is not necessarily “compensated for” by a concurrent decrease in triglycerides. Indeed the most ominous type of hyperlipidemia, from the standpoint of coronary heart disease, is the form in which the plasma cholesterol concentration is elevated while the triglyceride level is normal (Type II).[45]

When a person consumes a diet very high in fat, he tends to develop an exaggerated alimentary lipemia.[46, 47] Some persons may already suffer from an inability to clear fat properly. There is also preliminary evidence to suggest that elevated levels of free fatty acids (such as would occur in patients consuming a lowcarbohydrate ketogenic diet) may promote both vascular thrombosis and cardiac arrhythmias.[48-55]

An elevation of the plasma uric acid level is a frequent, if not invariable, concomitant of the low-carbohydrate ketogenic diet. If it becomes necessary to prescribe a drug like allopurinol to counteract such diet-induced hyperuricemia, then the risk of untoward side effects from the drug[56] is added to the nausea, anorexia, and fatigue that so often occur during adaptation to a diet virtually devoid of carbohydrate.

In summary, the approach to treatment of obesity recommended by Dr. Atkins is to restrict carbohydrate intake to less than 40 gm/day thus inducing a state of ketonuria as measured by means of a dipstick.

Summary of Critique of Dr. Atkins’ Diet Revolution

The material cited appears to be more than sufficient to make the following points clear:

  1. The “diet revolution” is neither new nor revolutionary. It is a variant of the “familiar” low carbohydrate diet that has been promulgated for many years.

  2. The rationale advanced to justify the diet is, for the most part, without scientific merit. Furthermore, no evidence is advanced that controlled studies were ever carried out to validate the observation that weight can be lost by sedentary subjects who consume a carbohydrate-poor diet providing 5,000 kcal/day.

  3. The Council is deeply concerned about any diet that advocates an “unlimited” intake of saturated fats and cholesterol-rich foods. In persons who respond to such a diet with an elevation of plasma lipids and an exaggerated alimentary hyperlipemia, the risk of coronary artery disease and other clinical manifestations of atherosclerosis may well be increased-particularly if the diet is maintained
    over a prolonged period.

  4. Any grossly unbalanced diet, particularly one which interdicts the 45% of calories that is usually consumed as carbohydrates, is likely to induce some anorexia and weight reduction if the subject is willing to persevere in following such a bizarre regimen. However, it is unlikely that such a diet can provide a practicable basis for long-term weight reduction or maintenance, ie, a life-time change in eating and exercise habits.

  5. It is unfortunate that no reliable mechanism exists to help the public evaluate and put into proper perspective the great volume of nutritional information and misinformation with which it is constantly being bombarded. The Council believes that, in the absence of such a mechanism, members of the media and publishers as well as authors of books and articles advising the public on diet and nutrition have a unique responsibility to ensure that such information and advice are based on scientific facts established by responsible research. Bizarre concepts of nutrition and dieting should not be promoted to the public as if they were established scientific principles. If appropriate precautions are not taken, information about nutrition and diet that is not only misleading but potentially dangerous to health will continue to be conveyed to the public.

  6. Physicians should counsel their patients as to the potentially harmful results that might occur because of adherence to the “ketogenic diet.” Observations on patients who suffer adverse effects from this regimen should be reported in the medical literature or elsewhere, just as in the case of an adverse drug reaction.

References

  1. Atkins RC: Dr. Atkins’ Diet Revolution: The High Calorie Way to Stay Thin Forever. New York, David McKay Inc Publishers, 1972.
  2. Harvey W: On Corpulence in Relation to Disease. London, Henry Renshaw, 1872, pp 109, 122.
  3. Banting W: Letter on Corpulence, Addressed to the Public (London, 1S63) ed 2. London, Harrison, 1863, p 22.
  4. Pennington AW: An alternate approach to the problem of obesity. J Clin Nutr 1:100-106, 1953.
  5. Pennington AW: Treatment of obesity with calorically unrestricted diets. J Clin Nutr 1:343348, 1953.
  6. Air Force Diet. Toronto, Canada, Air Force Diet Publishers, 1960.
  7. Taller H: Calories Don’t Count. New York, Simon and Schuster Inc Publishers, 1961.
  8. Jameson G, Williams E: The Drinking Man’s Diet. San Francisco, Cameron and Co, 1964.
  9. Stillman IM, Baker SS: The Doctor’s Quick Weight Loss Diet. Englewood Cliffs, NJ, Prentice-Hall Inc, 1967.
  10. White A, et al: Principles of Biochemistry. New York, McGraw-Hill Book Co Inc, 1954, p 9.
  11. Grande F: Energy balance and body composition changes: A critical study of three recent publications. Ann Intern Med 68:467-480, 1968.
  12. Azar GJ, Bloom WL: Similarities of carbohydrate deficiency and fasting. II. Ketones, nonesterified fatty acids, and nitrogen excretion. Arch Intern Med 112:338-343, 1963.
  13. Lusk G: The Elements of the Science of Nutrition. New York, W. B. Saunders Co, 1906, p 63.
  14. Deuel HJ Jr, Gulick M: Studies on ketosis. 1. The sexual variation in starvation ketosis. J Biol Chem 96:25-34, 1932.
  15. Folin 0, Denis W: On starvation and obesity, with special reference to acidosis. J Biol Chem 21:183-192, 1915.
  16. Kekwick A, Pawan GLS: Calorie intake in relation to body weight changes in the obese. Lancet 2:155-161, 1956.
  17. Pilkington TRE, et al: Diet and weight reduction in the obese. Lancet 1:856-858, 1960.
  18. Olesen ES, Quaade F: Fatty foods and obesity. Lancet 1:1048-1051, 1960.
  19. Werner SC: Comparison between weight reduction on a high-calorie, high-fat diet andon an isocaloric regimen high in carbohydrate. N Engl J Med 252:661-665, 1955.
  20. Gamble JL, Ross GS, Tisdall FF: The metabolism of fixed base during fasting. J Biol Chem 57:633-695, 1923.
  21. Hervey GR, McCance RA: The effects of carbohydrate and sea water on the metabolism of men without food or sufficient water. Proc R Soc Biol) 139:527-545, 1952.
  22. Bloom WL: Inhibition of salt excretion by carbohydrate. Arch Intern Med 109:26-32, 1962.
  23. Yudkin J, Carey M: The treatment of obesity by the “high-fat” diet. The inevitability of calories. Lancet 2:939-941, 1960.
  24. Recommended Dietary Allowances, 7th ed, publication 1964. National Academy of Sciences, Washington, DC, 1968, pp 9-10.
  25. Tolstoi E: The effect of an exclusive meat diet on the chemical constituents of the blood. J Bi Ch - 81.,713-711, 1929.
  26. Ian WS, DuBois EF: Prolonged Modiets with a study of kidney function and ketosis. J Biol Chem 87:651-668, 1930.
  27. West KM, Kalblfleisch JM: Glucose tolerance nutrition, and diabetes in Uruguay, Venezuela, Malaya and East Pakistan. Diabetes 15:918, 1966.
  28. McLaren DS, Pellet PL: Nutrition in the Middle East, in Bourne GJ (ed): World Review of Nutrition and Dietetics, vol 12. Basel, Switzerland, S. Karger, 1970, pp 43-127.
  29. Kannel WB, et al: Serum cholesterol, lipoproteins, and the risk of coronary heart disease: The Framingham Study. Ann Intern Med 74:112, 1971.
  30. Brown DF, Kinch SH, Doyle JT: Serum triglycerides in health and in ischemic heart disease. IV Engl J Med 273:947-952, 1965.
  31. Bloom WL, Azar GJ: Similarities of carbohydrate deficiency and fasting. 1. Weight loss, electrolyte excretion, and fatigue. Arch Intern Med 112:333-337, 1963.
  32. Cahill GF Jr. Physiology of insulin in man. Diabetes 20:785, 1971.
  33. Shoshkes M, et al: Fat emulsions for oral nutrition; use of orally administered fat emulsions as calorie supplements in man. J Am Diet Assoc 27:197-208, 1951.
  34. Obesity and Health. A Source Book of Current Information for Professional Health Personnel, publiq4tion 1485. Washington, DC, US Public Health Service, Division of Chronic Diseases, 1966.
  35. Insull W, Oiso T, Tsuchiya K: Diet and nutritional st#tus of Japanese. Am J Clin Nutr 21:753-777, 1968.
  36. Christakis G, et al: Effect of a cholesterol-lowering diet on fatty acid composition of subcutaneous fat in man. Circ 26:648, 1962.
  37. Kark RM, Johnson RE, Lewis JS: Defects of pemmican as an emergency ration for infantry troops. War Medicine 7:345-352, 1945.
  38. West ES, et al: Textbook of Biochemistry, ed 4. New York, The Macmillan Co Publishers, 1967, pp 1050-1052.
  39. Statement on hypoglycemia, editorial. JAMA 223:682, 1973.
  40. Stone DB, Conner WE: The prolonged effects of a low cholesterol, high carbohydrate diet upon the serum lipids in diabetic patients. Diabetes 12:127-132, 1963.
  41. Beveridge JMR, et al: Dietary cholesterol and plasma cholesterol levels in man. Canad J Biochem Physiol 37:575, 1959.
  42. Bronte-Stewart B: Lipids and atherosclerosis. Fed Proc 20 (pt III, suppl 7):127-134,1961.
  43. Connor WE, Hodges RE, Bleiler RE: The serum lipids in men receiving high cholesterol and cholesterol-free diets. J Clin Invest 40:894901, 1961.
  44. Inter-Society Commission for Heart Disease Resources, Atherosclerosis and Epidemiology Study Groups. Primary prevention of the atherosclerotic disease. Circ 42:A-55-A-95, 1970.
  45. Fredrickson DS, Levy RI, Lees RS: Fat transport in lipoproteins-An integrated ap.proach to mechanisms and disorders. N Engl J Med 276:34-42, 94-103, 148-156, 215-225, 273-281, 1967.
  46. Brunzell JD, Porte D Jr, Bierman EL: Evidence for a common saturable removal system for removal of dietary and endogenous triglyceride in man. J Clin Invest 50:15a, abstract #48, 1971.
  47. Connor WE: Effect of dietary lipids upon chylomicron composition in man. Fed Proc 18:473, abstract #1861, 1959.
  48. Grei:g HBW: Inhibition of fibrinolysis by alimentary lipaernia. Lancet 2:16-18, 1956.
  49. Merigan TC, et al: Effect of chylornicrons on fibrinolytic activity of normal human plasma in vitro. Circ Res 7:205-209, 1959.
  50. Philip RB, Wright HP: Effect of adenosine on platelet adhesiveness in fasting and lipaemic bloods. Lancet 2:208-209, 1965.
  51. Farbiszewski R, Worowski K: Enhancement of platelet aggregation and adhesiveness by beta lipoprotein. J Atheroscler Res 8:988-990, 1968.
  52. Oliver MT, Yates PA: Induction of ventricular arrhythmias by elevation of arterial free fatty acids in experimental myocardial infarction, in Moret P, Feifar Z, (eds): Metabolism of the Hypoxic and Ischaemic Heart. Basel, Switzerland, S. Karger, 1972, p 359.
  53. Oliver MF, Kurien VA, Greenwood TW: Relation between serum-free fatty acids and arrhythmias and death after acute myocardial infarction. Lancet 1:710-714, 1968.
  54. Hoak JC, Warner ED, Connor WE: Effects of acute free fatty acid mobilization on the heart, in Bajusz E, Rona G (eds): Myocardiology: Recent Advances in Studies of Cardiac Structure and Metabolism. Baltimore, University Park Press, 1972, vol 1, pp 127-135.
  55. Hoak JC, Connor WE, Warner ED: Toxic effects of glucagon-induced acute lipid mobilization in geese. J Clin Invest 47:2701-2710, 1968.
  56. AMA Drug Evaluations, ed 1. Chicago, American Medical Association, 1971, pp 196-197.