Low Carb Against the World

BUFFALO, Sept. 3 (P), Sugar is "fuel' for cancer, and its regulation in diet essential for cancer treatment, the American Chemical society was told yesterday. The report came from the cancer research department of the University of Pennsylvania, from work done by Gladys E. Woodward and Edith G. Fry, under direction of Dr. Ellice McDonald. 

"In cancer," said Dr. McDonald, in explaining the technical report, "the essential difference between tumor tissue and normal tissue is the ability of cancer to digest the animal sugar (or glycogen) in a different and more expeditious way than normal. "The greater the amount of sugar there is in the blood of cancer patients, the shorter is the expectation of their lives. There is a greater growth of the cancer when there is a large amount of sugar in the blood. The tumor grows faster, and there are a greater number of dividing cells. Cancer patients with a low blood sugar respond well to treatment and have a better chance of survival, with slow growth of the tumor.

"The amount of the sugar in the blood of cancer patients should be periodically measured, particularly before and after any treatment, for if the blood sugar increases after any treatment of the tumor, this should be corrected before any further treatment is instituted, and any new treatment should be based on the results of the tests. 

"The general conclusion is that cancer patients, particularly those with a high level of blood sugar, should be put on a low carbohydrate diet which should contain little or no sugar."

Physicians were slow to appreciate that insulin allowed the proportion of carbohydrate in the diet to be increased, for, as Himsworth said, ‘a well-founded theory directs that the carbohydrates in the diabetic’s diet must be curtailed if health is to be preserved’. On the other hand, as he continued, ‘a brilliant piece of clinical empiricism produces irrefutable proof that a liberal allowance of carbohydrate acts favourably on the diabetic’s health’ [17]. This empiricism began in 1926, when a high carbohydrate diet was first shown to improve glucose tolerance in healthy individuals [18].

https://link.springer.com/article/10.1007/s00125-008-1203-9

Himsworth recommended a high-carbohydrate diet to treat diabetes. Professor Edwin Gale has noted:

He demonstrated that injected insulin produced a greater hypoglycaemic response in individuals treated with the high carbohydrate diet, thus demonstrating that diet could influence insulin sensitivity. The high carbohydrate diet worked because it allowed the flow of glucose to the tissues to be maintained at a lower head of pressure by making people more sensitive to their own insulin.[5]

HIGH CARBOHYDRATE DIETS AND INSULIN EFFICIENCY 

BY H. P. HIMSWORTH, M.D., M.R.C.P. BEIT MEMORIAL RESEARCH FELLOW; ASSISTANT, MEDICAL UNIT, UNIVERSITY COLLEGE HOSPITAL, LONDON 

During the last four years the use of diets containing a relatively large quantity of carbohydrate has become more and more common in the treatment of diabetes mellitus. When these diets were first introduced they were received with many theoretical objections, but their undeniable success rapidly compelled their serious consideration and encouraged their increasing acceptance. This divergence between theoretical objection anid practical success is no minor discrepancy capable of easy adjustment after careful revision of the data, but a definite conflict between two diametrically opposed conclusions. 

On the one hand, a well-founded theory directs that the carbohydrates in the diabetic's diet must be curtailed if health is to be preserved; whilst, on the other, a brilliant piece of clinical empiricism produces irrefutable proof that a liberal allowance of carbohydrate acts favourably on the diabetic's health. At present it may be said that the thepretical objections are securely established, not only on a logical sequence of experimental results, but also on the accumulated clinical experience of diabetes mellitus before the introduction of insulin whilst the beneficial effects attending the use of high carbohydrate diets are inexplicable either by any known physiological or pathological mechanism, or on the basis of previous clinical experience. A probable clue as to the nature of the discrepancy is suggested by a consideration of the chronological relation of the conflicting views. The good results following the use of high carbohydrate diets were not discovered until after the introduction of insulin treatment. This suggests that there exists in the body a mechanism capable of stimulating the utilization of carbohydrate, but which cannot exert its action in the absence of an adequate supply of insulin. It was with the object of searching for this mechanism that the present work was undertaken, and the employment of healthy men as subjects for the search was dictated by the supposition that it would only be possible to detect the unknown mechanism in subjects possessing the normal supply of insulin. 

Theoretical Objections to High Carbohydrate Diet 

Before discussing the present research it is first necessary to glance at the work upon which the theoretical objections to the use of high carbohydrate diets in diabetes are based. For a long time it has been known that the excessive consumption of carbohydrate by the diabetic results in deterioration of his clinical condition. It was not, however, -until a few years before the discovery of insulin that light was thrown, by the work of F. M. Allen and his collaborators, on the mechanism of this unfavourable clinical change. Allen studied the effect of diet upon the health of partially depancreatized dogs, and summed up his results by saying:

"Dogs which have lost a certain amount of pancreatic tissue will become diabetic irrespective of diet. Dogs which retain a sufficient amount of pancreatic tissue will never become diabetic irrespective of diet. But between these two groups is an intermediate group. On an Eskimo diet they may be found to live in health. On a Hindu diet they soon go down to fatal diabetes." 

Thus if sufficient pancreas is removed from a dog so that it is on the borderline of pancreatic diabetes the animal lives, if it receives a low carbohydrate diet, and the blood sugar remains low and glycosuria does not occur. But if such an animal is given a diet rich in carbohydrates the full clinical and chemical picture of pancreatic diabetes appears, and the animal rapidly dies. Allen further confirmed the work of other investigators, showing that, as a general rule, once pancreatic diabetes has been induced in these dogs by excessive intake of carbohydrates, then a return to the low carbohydrate diet will not cure the condition. It would appear that ingestion of excess of carbohydrate overstrained the remaining pancreatic tissue so as to produce a permanent degree of degeneration. In the partially depancreatized dogs which died of the diabetes thus induced, histological examination of their pancreatic tissue revealed hydropic degeneration of the ,B cells of the islets of Langerhans, and Allen emphasized that this was also found in the pancreas of the patient dying in diabetic coma. As by this time the probability of the insular tissue's secreting an "anti-diabetic hormone" was generally accepted, conclusions from Allen's work were easily drawn. In the partially depancreatized dog excess of dietary carbohydrate, by producing a raised blood sugar, causes overstrain of the islets in the remaining pancreatic tissue; under this strain the cells break down and eventually are unable to secrete sufficient hormone to prevent the development of pancreatic diabetes. At death the /B cells of the islets are in a state of hydropic degeneration; the pancreas from the diabetic dead of his disease shows similar lesions; therefore to preserve life in the diabetic the islet cells must be guarded against overstrain by maintaining the blood sugar at a low level by restriction of carbohydrates in the diet. The Allen diet--and the theoretical objections-are based on these conclusions.

Clinical Significance of the Results 

The results recorded in this paper carry us on our way towards the explanation of Allen's glucose equivalent of insulin. The reason behind the observation that the more carbohydrate ingested the greater the amount retained in the body by each unit of insulin is that the more carbohydrate eaten the more sensitive the organism becomes to each unit. Hence the paradox of the glucose insulin equivalent. It will be remembered that Allen's experiments were carried out on depancreatized dogs, and thus demonstrate that such a dog under the stimulus of the administration of carbohydrate is capable of developing an increasing sensitivity to insulin. My results show that the giving of carbohydrate raises the efficiency of. both injected and pancreatic insulin in the normal subject. It only remains to prove that carbohydrate has the same action in the diabetic and the explanation of the beneficial effect of high carbohydrate diets in these patients has been achieved. Ellis has recently supplied this proof. To diabetics needing large doses of insulin he gave glucose by mouth and small doses of insulin every hour. A remarkable increase in insulin efficiency resulted. Despite the ingestion of constant large amounts of glucose the dose of insulin required to restrain the blood sugar within normal limits decreased progressively. These results show that some diabetics, though possibly not all, are capable of developing a heightened sensitivity to insulin under the stimulus of carbohydrate ingestion. Thus the improvement of diabetic patients on a high carbohydrate diet is to be ascribed not to the greater stimulation, and consequent overstrain, of their insulin-secreting tissue by the excessive intake of carbohydrate, but rather to the rendering of the diabetic more susceptible both to his pancreatic and the injected insulin. The result is that each unit of insulin available accounts for a greater amount of carbohydrate. This, necessarily, by allowing a more economical utilization of the insulin secreted, reduces the demand of the body for insulin, with a consequent easing of the strain on the diseased islet cells. By thus lighteing the burden on the cells which remain capable of function it is possible that we aid their conservation as healthy tissue, and save rather than squander the patient's own pancreatic resources. If the augmentation of a diabetic's sensitivity to insulln is of importance in the balanced state, it is of much greater importance in the state of coma. It is well known that hundreds of units of insulin may be given in this condition with little effect on the blood sugar, when in the same diabetic after recovery 20 or 30 units will produce hypoglycaemic symptoms. Many comatose and precomatose patients seem to be relatively insensitive to insulin, and any measure directed to raise their sensitivity would appear to be of benefit. To this end glucose should be administered in large doses. The success of treatment based on this principle I have recorded previously, and the method has since been strongly recommended by Lawrence." A growing number of cases of diabetes are being. reported in which the patients for no ascertainable reason are found to be resistant to insulin. In one such case doses as large as 1,600 units of insulin a day had no effect on the blood sugar. It is possible that these cases may be explained by an almost complete absence of the factor making for susceptibility. In contradistinction to' these insulin-resistant diabetics, cases of spontaneous hypoglycaemia in which no hypertrophy or tumour of the islet cells can be found are continually being recorded. In such patients it is theoretically possible that the hypoglycaemia may be the outcome not of hyperinsulinism, but of the development of a state of a greatly heightened susceptibility lo insulin secreted by the pancreas. Finally, I would suggest the possibility of the existence of a type of diabetes due not to diminished secretion of insulin by the pancreas, but to a greater or less impairment of the organism's susceptibility to insulin. In such a case, although the output of endogenous insulin may be normal in quantity, the diminution or absence of the factor which is concerned in rendering the patient susceptible to insulin would produce a result identical with that of impaired production of insulin-namely, the clinical picture of diabetes mellitus.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2444943/pdf/brmedj07161-0009.pdf

To the editor: It was with dismay that we read in The Journal, August 10, statements of Dr Edward Tolstoi at a conference of "the members of the Departments of Pharmacology and of Medicine of Cornell University Medical College and the New York Hospital, with the collaboration of other departments" regarding the treatment of diabetes. He said:

"We found that our experimental subjects were free from the symptoms of diabetes in spite of glycosuria when they were receiving a diet of 75 grams of protein, 60 grams of fat, and 200 grams of carbohydrate, and protamine zinc insulin in daily doses of 50 units."

Does it make common sense to say that an adult of average body build and activity receiving 1,640 calories, daily in the form of carbohydrate 200, protein 75, and fat 60 grams who is excreting 150 or even 100 grams of sugar in twenty four hours, thus leaving a net balance of 1,040 or 1,240 calories respectively, could maintain body weight and be in nitrogenous equilibrium for a prolonged period? Furthermore, is it sensible or economical to alow the wastage of so large a part of the food eaten?

Like many, others, we believe in controlling the hyperglycemia of diabetes (1) because it is fundamentally an abnormal state, (2) because a high blood sugar is a constant stimulus for insulin secretion and allows no opportunity for rest and recuperation such as the pancreas of a healthy person enjoys between meals and at night and (3) because control of hyperglycemia and glycosuria proves utilization of the diet whereas their disregard leads, in our experience, to accessory annoyances such as polydipsia and polyuria, the attendant necessity for extra food to make up for the loss of calories in the urine and the obvious wear and tear on the system for ingestion, assimilation and excretion of this unutilized extra food, quite apart from needless cost and waste. A high percentage of sugar in the blood implies the same in the tissues ; we think it likely that, directly or indirectly, this conduces to lack of normal tissue repair and resistance to infection, predisposes to degenerative phenomena in arteries and nerves and leads to weakness, weariness and impotence, although we freely admit that positive proof is lacking that all these harmful effects are due to hyperglycemia per se. Unhesitatingly we maintain that the blood sugar should approach normal because it is an index of the control of the diabetic condition ; if normal, it is one assurance that the whole disease is being treated well. Hyperglycemia is the red light which the physician should no more disregard, although he cannot always explain its significance, than he should fail to heed the red signal at the railroad crossing because he cannot see the train around the corner. 

Dr. Tolstoi's advice for certain cases of diabetic acidosis follows : 

First, let us consider the one whose condition is not far advanced, the patient as we see him in the clinic. He may report a sore throat. Examination of the urine reveals a 4 plus acetone reaction and diacetic acid. The skin and the tongue are dry, there is dehydration and there are listlessness and the desire to be left alone. We tell the patient "Go home, take a tablet or two of tablé salt (1 Gm. of salt) every hour, and follow that with a glass of water; in addition, take all the hot salt broth you can." We teach him to examine his urine for acetone and tell him to do so every two hours, and as long as acetone is present to give himself insulin (regular soluble) after each urine examination until the acetone bodies disappear. The dosage of insulin is determined by the urine analyses for sugar. He is told to take 25 units if the result of the test is yellow or red, 15 units if the specimen is green, and the juice of an orange if the Benedict solution is unchanged after boiling. This simple rule also protects the patients against insulin overdosage. 

We condemn such advice. In our opinion it is dangerous to send home patients whose urine gives a 4 plus reaction for acetone and diacetic acid. Dr. Tolstoi does not even suggest that they keep under the supervision of their family physicians. If there is one thing we attempt to do as a result of our experience with patients in coma and near coma, with diabetic children and with diabetic patients in general, it is this—to train them, if any unusual symptoms occur, to call the doctor. A patient who exhibits "listlessness and the desire to be alone" is not likely to carry out intelligent, energetic self treatment. We believe in the orthodox treatment of diabetes. We are convinced that our patients and the patients of other physicians do the best who follow the rules. Differences in diets of from 50 to 75 Gm. of carbohydrate a day are immaterial. By no means can we keep all our patients sugar free, but we do strive to maintain them under as good control as possible, thereby, as we believe, protecting them from complications and progression of the disease. Furthermore, as will appear in the forthcoming (October) (seventh) edition of the "Treatment of Diabetes Mellitus," we have endeavored to support our convictions by recording the complications, the causes of death and the duration of life in 5,669 of our fatal cases between 1898 and 1940. Tables show the decrease of deaths due to coma from 64 per cent to 4 per cent, the steady increase in duration of life after onset from 4.9 to 12.5 years and the advance in the average age at death from 44.5 to 64.8 years. 

Elliott P. Joslin, M.D. 

Howard F. Root, M.D. 

Priscilla White, M.D. 

Alexander Marble, M.D. Boston.

(Image is of Edward Tolstoi)

Tolstoi was young enough to be EPJ's son. He displayed a brashness on the podium and on one occasion in 1944 was blatantly discourteous to EPJ in a joint discussion, practically dismissing EPJ's rebuttal. He commonly chided the Joslin group about the pseudo logic of linking sugar directly to most of the complications - like it was a "religion." 

He and many of his group at Cornell and like-minded schools would tell the Joslin group and the Chicago group, for example, that long tetm complications appeared even in the "rigidly" well-controlled diabetics and those with his "asymptomatic-only" level did not appear to have more problems. Dr. Root at first and then, principally and more patiently. Dr. Marble took up the position that those with the best control from date of diagnosis had the least problems. 

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