January 1, 1899
Elliott P. Joslin
A Centennial Portrait
Dr Joslin describes how his mother's Type 2 Diabetes could be put into remission if she followed his low carb diet. She was able to live for 13 more years.
- Case #8:
Dr. Joslin's Mother
The first was 73 years old and was Dr. Joslin's mother. The second was 16 years old and the youngest daughter of Dr. James Jackson Putnam, who had been Dr. Joslin's principal mentor in the first year of his practice and his teacher in the medical school. Dr. Putnam was the austere, brilliant and path-finding neurologist whose name is now inscribed on the chair in Neurology at the Harvard Medical School.
It is said that Dr. Joslin specialized in diabetes to help his mother with her disease. While this is not correct, he certainly remained highly interested in her progress as well as in her type of diabetes, hee proudly noted in his later writing that a remission or two occurred in her diabetes when she carefully followed the restraints of a good meal plan. In the first edition of his textbook on diabetes, published in 1916, EPJ described his mother's case, thinly disguised under the topic "Is the tendency of the diabetic glycosuria to increase?"
A woman showed the first symptoms of diabetes in the spring of 1899 at 60 years of age and 5% of sugar was found in June. She had gradually lost during the preceding fifteen years, twenty pounds and weighed 165 pounds when the diagnosis was made. Under rigid diet, the urine promptly became sugar-free, the tolerance rose to 130 grams and safe for very brief intervals and remained so for nine years until 1908. In 1909, a carbuncle appeared. With prompt surgical care, vaccines, the restriction of carbohydrates and the temporary utilization of an oatmeal diet, the sugar disappeared and the carbuncle healed promptly, but the urine did not remain permanently sugar-free, although only about 30 grams of sugar was excreted. Residence in the hospital for a few days in September of 1912, in order to have a few teeth removed, lowered the sugar to 0.8%.
Except for brief periods of illness due to the carbuncle and pneumonia, the patient remained well during all these years and was unusually strong and vigorous for a woman of 73 until she finally succumbed to a lingering illness subsequent to a hemiplegia and death finally occurred due to a terminal pneumonia in 1913.
With his mother's case. Dr. Joslin described the most common presentation of diabetes. When she was diagnosed with diabetes, she was overweight and probably inactive. Had she been born a decade later, Mrs. Joslin might have enjoyed a life lengthened by the use of insulin in the 1920s and antibiotics in the 1930s.
As an aside: Dr. Joslin's inheritance from his mother, Sara Proctor Joslin, left Dr. Joslin a millionaire several times over by today's standards. Sara Proctor, her sisters and one brother were the heirs to a very large fortune derived from their father Abel's leather tanning trade. Sara Proctor became the second wife of Dr. Joslin's father Allen, who was a shoe manufacturer in the town of Oxford. This connection with the Proctor leather tanning business guaranteed the success of the Joslin shoe factory. EPJ was fond of noting that he was a direct descendant of John Proctor of Salem, who had been hanged for defending his principles in the witch trials of 1692.
EPJ's lifestyle, in line with his upbringing and religion, always understated his affluence. However, it afforded him the means to aid family and associates with education and travel, as well as the ability to acquire the property needed to gradually expand his clinic. He underwrote Priscilla White's training in 1928 at the leading pediatric center in Vienna, a typical act of generosity to his co-workers.
December 1, 1927
Dietary Factors that Influence the Dextrose Tolerance test - A preliminary study - by J. Shirley Sweeney, M.D.
Sweeney studies healthy young people to see how feeding them a certain macronutrient influences the results of a glucose tolerance test, and proves that carbohydrates sensitize the body to future carbohydrates, while fat and starving create an insulin resistance effect where blood sugar stays high after a sudden assault of glucose.
The current explanation of this phenomenon (Macleod) is that the first dose of glucose sensitizes the insulin-secreting mechanism, so that in response to the second dose the islet cells secrete insulin more readily and more abundantly at a lower level of hyperglycaemia. On the basis of this explanation Sweeney, in 1927, attempted to explain the variations in sugar tolerance found in normal subjects on different diets. Using the ordinary glucose tolerance test as a guide, he investigated the sugar tolerance of healthy individuals during starvation, on a fat diet, on a protein diet, and on a carbohydrate diet. He found that protein had little effect; that fat diets and starvation diminished sugar tolerance; and that carbohydrate diets improved sugar tolerance. Sweeney considered that the diminished sugar tolerance was due to the impaired sensitivity of the insulin-secreting apparatus, consequent upon the absence of the stimulus of carbohydrate ingestion, and that the improved tolerance was the result of the increased sensitivity of this mechanism, owing to greater stimulation.
DIETARY FACTORS THAT INFLUENCE THE DEXTROSE TOLERANCE TEST - A PRELIMINARY STUDY
The dextrose tolerance test is now being extensively employed as a diagnostic procedure. It is most beneficially used in the differentiation of mild diabetes mellitus and renal diabetes. It is also being used, and is believed to be of diagnostic value, in many pathologic conditions, such as encephalitis, malignant tumor, pituitary and thyroid dysfunctions and nephritis.
Although it is definitely established as a diagnostic procedure, there is some diversity of opinion concerning what constitutes a normal response to the oral administration of dextrose. Some writers state that in a healthy person there may be a postprandial rise in blood sugar of from 14 to 16 per cent and a return to the normal within two hours. There are other writers who consider a postprandial hyperglycemia of 20 per cent within normal limits. It is generally believed that the persistence of the postprandial hyperglycemia is of more diagnostic significance than the degree of hyperglycemia. In early cases of diabetes the blood sugar curve rises higher, stays up for a longer time and does not return to normal for several hours. Macleod says that "slight deviations from the normal must not be given too much weight in diagnosis, since they may occur in other diseases or even in perfectly normal persons." All who have studied dextrose tolerance curves have noted the variability exhibited by normal persons, to say nothing of those who are diseased. These variations have been discussed and explained in different ways.
It occurred to me that perhaps the character of the food and the amount of water that a person had been consuming for a few days prior to the time the tolerance test was made might be factors that would influence the dextrose tolerance curve. If these factors should prove to be capable of altering a tolerance curve, they could be controlled. This would eliminate some of the confusing variability that is so frequently observed. It was these thoughts that lead to the following experiments.
Young, healthy, male medical students were used to study the effect of different preceding diets. Four groups were formed. The subjects in one group were given a protein diet, those in another a fat diet, those in a third a rich carbohydrate diet, and those in the fourth group were not given any food—the starvation group. Those on the protein diet received only lean meat and the whites of eggs. The students on the fat diet received only olive oil, butter, mayonnaise made with egg yolk, and 20 per cent cream. Those in the group fed on carbohydrates were allowed sugar, candy, pastry, white bread, baked potatoes, syrup, bananas, rice and oatmeal. These diets were followed for two days. Meals were taken at the usual hours, and eating between meals was allowed, provided the diets were followed. Those in the starvation group did without food for two days.
On the morning of the third day, each student was given by mouth 1.75 Gm. of dextrose per kilogram of body weight, on an empty stomach. Determinations of blood sugar were made from samples of venous blood removed immediately before the dextrose was given, and at 30, 60 and 120 minute intervals following its administration. I made all determinations of blood sugar by the Folin-Wu method.
A better comparison of these groups is obtained by examining table 5 and chart 5 in which are contained the average or type curves of each group. It will be noted that those students who were on the carbohydrate diet exhibited a marked increase in sugar tolerance and those on a protein diet a slight decrease in tolerance, while those who were placed on the fat diet and those who were starved manifested a definite decrease in sugar tolerance. The differences in the average fasting blood sugars are noteworthy. The blood sugar in those of the protein and starvation groups was distinctly lower than that of the members of the fat and carbohydrate groups.
Because of the great difference in these groups, those students on the fat diet and those in the starvation group who showed the most extreme responses were placed on the carbohydrate diet. Similiarly, those in the carbohydrate group who showed an extreme response were placed on starvation restriction. This was obviously done to determine whether the curve of a person could be changed significantly by diet. The results are presented in table 6 and in charts 6 and 7.
Comparison of the curves of these five students is striking. The curves of all who had been placed on carbohydrate diets manifested a definite increase in their sugar tolerance. When three of these (the three most extreme) were placed on starvation restrictions, the curves were notably abnormal ; there was a marked postprandial hyperglycemia. which persisted at the end of two hours ; in other words, what was an increased sugar tolerance following the carbohydrate diet became a definitely decreased tolerance following two days of starvation. The remaining two persons who were placed on the fat diet showed a similar decreased tolerance. It should be stated that an interval of at least one week was allowed between the tolerance tests performed on the same subject.
August 2, 1950
Blood lipids and human atherosclerosis
Dr John Gofman created the original diet-heart and lipid hypothesis, but included carbohydrates as a factor driving cardiovascular disease.
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)
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.
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)
January 1, 1954
The Significance of Ketosis Produced by a High Meat-Fat Ration under Arctic Conditions.
On the basis of the presented data it may be concluded that from a physiological standpoint the all-carbohydrate ration offered no significant advantage over the high meat ration under the conditions of the study.
With the increasing human activities in circumpolar areas in recent years, the problem of an adequate and physiologically suitable ration with high caloric density has been the subject for much dispute among physiologists and nutritionists. Although a high protein diet has been successfully used by Eskimos and arctic travellers for generations, both as trail diet and emergency rations, there has been a tendency in recent years to emphasize the desirability of an all-carbohydrate ration ( Mellinger, 1948, Roth, 1948, Dyme, 1950). One of the main arguments in favor of the carbohydrate ration has been its antiketogenic effect, assuming harmful effect of slight ketosis even during the short periods of survival in question under arctic conditions.
With reference to these questions a study was designed, the purpose of which was to consider a high-carbohydrate versus a high-protein diet, with reference to physiological adequacy and an evaluation of the physiological and clinical significance of ketosis under strenuous arctic field conditions during midwinter in Alaska.
It is clearly realized that the determination of ketone bodies is subject to considerable inaccuracy. However, the reported data indicate that under the conditions of the test the excretion of urinary acetone in the meat group never exceeded 1 g per day. The highest figure recorded was 8 66 mg which is a very small amount.
According to Peters and Van Slyke (1946), ketones are regularly found in the urine of healthy persons leading a normal life. Van Slyke found as much as 280 mg ketones per 1000 ml urine. Others have reported figures between 7 and 125 mg daily.
Under conditions such as total starvation when all energy is derived from protein and fat, the production of ketone bodies by the liver is accelerated and the excretion of ketones in the urine increases. In normal adults the appearance of gross ketonuria, according to Peters and Van Slyke (1946), does not reach its height until 3 to 5 days of the fast have elapsed. As starvation proceeds ketosis gradually diminishes. He states that in the normal male, ketosis of starvation does not reach serious proportions because sufficient carbohydrate is derived from protein and oxidized, and the levels of blood ketones are not high enough to tax severely the mechanism for the preservation of acid-base equilibrium. In one subject about 6 g of ii-hydroxybutyric acid were excreted daily in the urine for the last two weeks of a 31-day fast. In diabetic acidosis ketonuria may reach values 10 times higher than this.
Compared with these figures the amounts of acetones excreted in the urine in our subjects on the meat ration are insignificant, and it appears that this slight ketonuria observed under these conditions for the periods considered likely as the duration of a survival situation would have no appreciably harmful effect.
Exercise greatly increases the ketosis, and a 10-mile walk in the morning without breakfast will produce distinct ketonuria in a healthy person who otherwise is living on a normal diet (Courtice and Douglas, 1936).
A number of evidences indicate a mechanism of adaptation to ketosis. In our Eskimo studies it is observed that the degree of ketonuria is less than what is normally observed in Whites on a similar diet. On the other hand, an Eskimo soldier who had lived for several months on the normal Army mess rations excreted the same amounts of acetone as the normal white soldiers when given a "ketogenic" diet. In the subjects studied by McClellan and DuBois (1930) the ketonuria diminished after several months on a carbohydrate-free diet.
Deuel and Oulick (1932) have demonstrated that ketosis develops more rapidly and attains greater intensity in women than in men.
It has been repeatedly observed that ketosis frequently occurs under strenuous field conditions regardless of the diet, and Sargent and Consolazio (1951) showed that the ketosis is reduced when the same subject undergoes repeated field tests, indicating some evidence of adaptation.
In an Arctic bivouac at Fort Churchill the approximate caloric expenditure was 4000 calories per day. The caloric intake was about 3600. Under these conditions all the men showed trace quantities of urinary ketones almost every day, starting on the third day in the bivouac (Molnar et al., 1942).
Of the great variety of physical fitness tests (Cureton, 1947), the Treadmill Test was selected for practical reasons. It should be emphasized, however, that physical fitness is exceedingly difficult to evaluate, not only because the meaning of physical fitness is far from clear, but also because the result of the test is greatly dependent upon a number of factors beyond the control of the observer.
In all cases we observed an improvement at the end of the field phase, most marked in the carbohydrate group, associated with approximately 10-pound weight loss (7.5 %).
It should be noted that the subjects had been living on a caloric deficit of the order of 2000 calories a day, and performing daily route marches of 10 miles.
In the case of untrained personnel in poor physical condition, one would expect an improvement in physical fitness during the field phase. Our subjects, however, were all well trained and in excellent physical condition at the onset of the experiment. The factor of physical training therefore can hardly explain the difference in the physical fitness scores.
On the other hand, it appears that the weight loss may be the most important factor in explaining the observed difference. The subjects started off probably slightly overweight and the loss of 7 per cent of their body weight would tend to increase their physical performance, since there is less weight to carry during the exercise. This is in conformity with general experience under similar conditions. It is observed that the carbohydrate group, which had the greatest weight loss, also showed the greatest improvement of physical fitness scores. The purpose of the experimental phase was to study the effect of the experimental diet on various physiological functions as compared with the levels during the normal conditions in the standardization phase. The results indicate the following effect: Both in the carbohydrate group and in the meat group, there was an increase of the physical fitness scores, most pronounced in the carbohydrate group. The basal heat production was 13 per cent higher at the end of the experimental phase than during the standardization phase in the meat group, while a reduction of 7 per cent occurred in the carbohydrate group. This difference is probably due to the specific dynamic action of protein. During the experimental phase the meat group consumed 300 ml more fluid per day than the carbohydrate group. While all subjects in the meat group were in a positive nitrogen balance, the subjects in the carbohydrate group showed a negative balance of 6.3 g on an average. Ketonuria occurred in all meat subjects and in three of the carbohydrate subjects.
During the field phase the factor of climatic stress was added to the experimental conditions, and the following results were obtained:
No significant difference was observed in the physical performance of the subject on the meat ration, the carbohydrate ration, or on the meat-and-carbohydrate ration during the actual field phase. The physical fitness scores were improved in all three groups at the end of the field phase, and this improvement was greatest in the carbohydrate group which also had the greatest weight loss. The psychiatric evaluation revealed no distinct differences between the three groups. There was no significant deterioration in morale, but an increase in carelessness, irritability and desire to sleep which occurred in all three groups. The weight loss was 7.0 per cent in the meat group, 7.5 per cent in the carbohydrate group, and 6 per cent in the group receiving both meat and carbohydrate. There was an increase in the basal heat production of 9 per cent in the meat group and 7 per cent in the meat-carbohydrate group, while the carbohydrate group showed a reduction of 7 per cent in the BMR. The water consumption was 1500 ml in the meat group, 850 ml in the carbohydrate group, and 1200 ml in the meat-carbohydrate group. All three groups showed negative nitrogen balance, which was most pronounced in the carbohydrate group, where it was approximately 7 g, as against approximately 2 g in the meat group. Ketonuria occurred in all three groups, most pronounced in the meat group.
On the basis of these findings, and in view of the fact that water supply, as a rule, does not present any problem in the Arctic, it may be concluded that the carbohydrate ration offered no significant advantage under conditions of arctic survival as stimulated in the present study. In terms of heat production and nitrogen balance, the high meat ration is preferable. It is evident from this study that under survival conditions, which necessitate caloric expenditure, between 2500 and 3000 calories per man per day, including travel of approximately 10 miles a day, 1000 calories per man per day is sufficient for a period of at least 10 days.
It would therefore seem logical that survival rations developed for arctic use should consist of protein, fat, and carbohydrate in proportions which would serve to utilize the specific dynamic action of a high protein diet, the high caloric density of fat, and the physiological advantages of carbohydrates. Protein-fat rations with high caloric density such as various types of pemmican, have already been successfully used for more than half a century by arctic travellers.
It would appear advisable to base future arctic survival rations on the principle of a high meat-fat ration as the main meal of the day prepared in the evening, and an all-carbohydrate component of the ration to be consumed in the middle of the day while on the trail.
5. Summary and Conclusions.
In a series of laboratory experiments followed by field experiments under strenuous arctic conditions, the physiological adequacy of low caloric arctic rations have been studied in groups of normal men under conditions which necessitate travel under various arctic conditions. The rations studied contained approximately 1000 calories per man per day and consisted of an all-carbohydrate ration and a high protein-fat ration. On the basis of the presented data it may be concluded that from a physiological standpoint the all-carbohydrate ration offered no significant advantage over the high meat ration under the conditions of the study.
June 24, 1961
The Canadian Medical Association - Experiences with the Pennington Diet in Management of Obesity
Leith M.D. uses a ketogenic diet with a restriction of 50 grams of carbs, fashioned after the Pennington Diet, with 48 obese subjects and found that twenty-eight were able to follow the diet and succeed in losing weight. The diet prevented hunger, which was the most important discovery.
Obesity in the human has been widely studied by such authorities as Newburgh and Rony. It is generally accepted that fat in excess will be laid down only if food intake exceeds energy output. The treatment of obesity has generally followed this premise. Diets deficient in calories have been prescribed so that caloric intake does not exceed energy output. Weight loss should automatically follow when the instructions are faithfully followed. Indeed formulae have been devised to predict the loss in weight on a measured low caloric intake of a candidate of known height and weight. These low caloric diets are made up so as to be deficient in fat and carbohydrate and with protein at approximately 1 g. per kg. of body weight. It has been shown that weight loss can be achieved in this manner. The diet is followed and the desired results are obtained. Unfortunately, it is difficult for most patients seen in clinical practice to follow a low caloric diet. The literaturre is replete with instances of diet failure on such a regimen. The difficulty is in part due to inability to control appetite. Anorectic agents such as amphetamine, phenmetrazine hydrochloride and bulk substitutites have been utilized as a means of controlling appetite. These are of some value in the clinical mangement of an obese patient. Methods other than those of controlling appetite have also been applied. These include the administration of thyroid extract, the effect of regular exercise and psychotherapy administered both individually and in groups. However, in spite of all these methods, the long-term management of obesity presents many disappointments. Patients often lose weight only to regain it after a short interval. In many, weight loss is never achieved.
Means other than the aforementioned have long been sought in the control of appetite. Appetite and satiety, i.e. the satisfaction of appetite, are complex problems. The latter, satiety, is dependent upon many variables. One of the chief factors is the production of body heat by the specific dynamic action of ingested food. Protein has much the highest index in this regard, while fat has the lowest." Rise in skin temperature and a resulting feeling of warmth are intimately correlated with the feeling of satiety. In fact, it has been suggested that the obese are slower in showing this rise, hence their desire for more food. Another theory relating to satiety is that of the arteriovenous (A-V) glucose difference and its regulation of glucoreceptors in the brain stem. Mayer feels that the glucoreceptors are the controlling centres of appetite and satiety. It is stated by others that satiety depends only on the body's caloric needs and the subsequent voluntary supply of calories. A most attractive hypothesis, well documented by physiological study, is that which proposes that satiety is experienced because the stomach is full. Nervous impulses are sent out to the brain when the stomach is filling or full and the sensation of satiety results. Satiety may then be related to many factors of the diet. If the bulk of food, its protein and its fat intake are increased, on the basis of some of these theories satiety may then more readily follow. Bulk, increased intake of fat and protein, and thus satiety, are not possible with the usual low caloric diet.
As a diet for achieving satiety while effecting weight loss, the low carbohydrate diet of Pennington shows some promise. This diet allows as much bulk as desired. It is high in both fat and protein. Such a diet meets many of the requirements for achievement of satiety. It provides plenty of protein to be used for heat production by the body. Calories are supplied by the high fat intake and filling of the stomach is achieved by the usual bulky nature of the diet. Pennington claims that his patients have lost weight on this diet with a caloric intake of 3000 calories. Another consideration is that of a fat-mobilizing hormone which has been reported to be present in the urine of patients on this type of diet. Urine extracts from such fasting patients have been shiown to produce weight loss when injected into mice. Unfortunately, verification of this work has not as yet been reported by others. One may anticipate that with such a diet hunger may be avoided, appetite satisfied and a measurable weight loss achieved. The diet is not easy to follow. Its most important requirement is the strict necessity of restricting carbohydrate intake to less than 50 g. per day. One may consume as much fat and protein as desired to produce satiety. Of course diets high in fat and protein, and therefore meats, are somewhat expensive. These may be out of the reach of some economic classes. Other ethnic groups long accustomed to high carbohydrate intakes, such as Italians and Chinese, may find such a diet highly unpalatable. However, most well-motivated patients are prepared to follow such a diet.
Forty-eight obese individuals were selected. These were patients attending a private practice, an industrial medical centre, or the outpatient clinic of a hospital. All expressed a desire to lose weight. A copy of the diet was given to each patient. The diet was made up to allow protein and fat ad libitunm. However, the carbohydrate component was carefully restricted to less than 50 g. per day. The object of the diet was to provide as much bulk as desired but at the same time to limit sharply the carbohydrate intake. These basic points were outlined to each patient. There were no other diet restrictions. Copies of the diet were mimeographed along with suggested menus for each meal. The patients were instructed regarding the approximate values of the usual daily foodstuffs. The high protein and high fat content foods were selected as being most useful for this type of diet. The whole regimen was reviewed with the patient after the diet had been followed for some weeks, so as to correct any misunderstanding that might have arisen. The patients at the outset found the concept of an ad libittum diet difficult to understand. However, with time they realized that the guiding principle of the extremely low carbohydrate intake (less than 50 g. daily) had first to be strictly maintained. They could then realize satiety by taking as much fat and protein as required. The patients' weights varied from 140 lb. in a young woman whose height was 58 in. to 274 lb. in an elderly woman 70 in. in height. The patients ranged in age from 16 to 62 years. They all fulfilled the true definition of obesity, being 20% more than the ideal (provided by the Metropolitan Life Insurance tables) weight for their height. Their weights were checked at monthly intervals for three months to one year. A small group, eight patients in all, were followed up for a two-year period. One patient was studied while in hospital and balance studies are available in this case (Fig. 1). The patients served as their own controls, since all had been on a low caloric diet without measurable success. At least half had used anorectic agents, seven patients had taken bulk substitutes, and eight had participated in group psychotherapy for a period of eight months. None of them showed a sustained loss of weight.
Forty-eight patients were seen initially. Of these, eight rapidly loist interest and did not wish to carry on with the diet after the first month. All of these patients complained, nonetheless, of the monotony of the diet, its constipating effect, the absence of taste and its failure to satisfy their desire for sweets. Of the remaining 40 patients, 12 felt that they were following instructions faithfully but did not lose weight. The remaining 28 patients achieved satisfactory weight loss during the period of at least six months in which the diet was followed. This loss varied from 10 to 40 lb., averaging 11/ lb. per week. Nine of the 28 patients who lost weight were able to reduce their weight to ideal chart indices.19 The others, although showing considerable weight losses during the period of study, did not reach this desired level. Results in the single case under balance study are shown in Fig. 1. The balance study was carried out on a woman (E.C.) who initially weighed 83 kg. (182 lb.). She was allowed a free diet, for the first seven days. It will be noted that the caloric intake was approximately 2800 calories and that little change in weight occurred. There was a substantial fall in weight from day 7 to day 15 when a low caloric diet of 1000 calories was taken. The high protein and fat diet of Pennington with only 50 g. of carbohydrate was followed for the final period from day 15 to day 24. The caloric value during this period was in the neighbourhood of 2000. There was a weight loss of at least 1 kg. (2.21 lb.) and, interesting to observe, a negative nitrogen balance and a positive sodium balance. The patients who did achieve weight loss showed a substantial fall as. illustrated by a representative case (Fig. 2). All patients, including those who dropped out of the study, expressed similar opinions regarding the diet. They agreed that it was monotonous and constipating. Many missed sweets and the oral satisfaction derived from sweets. However, none of the patients experienced hunger. since they were free to eat protein and fat at will. Hunger had been a factor to most of them on lowr caloric diets and they were quite familiar with this form of nagging discomfort. The new diet was preferred by them, if only for this reason. The eight patients followed up for two years maintained their weight loss w\hile following the diet. DIscussIoN The treatment of the obese patient has followxed a stereotyped pattern for the past 20 years. Prescribing a simple low caloric diet and sympathetic handling of the patient, the usual metlhod, had not been a rewarding form of clinical treatment. Usually, the patient was disturbed by a continual g,naving sense of hunger.0 Attempts to overcome the feeling of hlunger by the use of anorectic drugs and bulk substitutes have been found of value for limited periods.4 5 The use of food high in protein and fat in order to overcome hunger does not at first glance appear to be a likely treatment for obesity. However, such a diet, high in protein and fat but low in carbohydrate, has been suggested by Pennington, who has reported that weight loss can be achieved by such means.16 17 Pennington also has submitted the following theory in an attempt to show that fat and carbohydrate are metabolized in a different manner by obese as compared to normal subjects. A partial block in carbohydrate metabolism at the pyruvic acid level is postulated. Pyruvic acid becomes converted to fat. Glucose intake is increased in an attempt to overcome the block. Obesity results because of the increased intake and consequent fat deposition. By inhibiting glucose intake in the obese, Pennington feels that energy will be derived not from glucose but from fat (ketogenesis). Weight loss in the obese on such a diet is achieved through fat breakdown. The evidence for this theory is hardly complete. Our results do show that satisfactory weight loss may be accomplished by a full caloric, low carbohydrate diet. The patients ingested protein and fat as desired. Careful attention was paid to keeping carbohydrate intake to a minimum. It has been suggested that the diet was unpalatable and the caloric intake was unconsciouslv restricted for this reason, although the builk may have appeared to be sufficient. Another criticism might be that even if the total bulk and caloric intake were ingested, complete absorption may not have taken place. The answer to these points may be discussed in the light of the vork of Kekwick and Pawan,20 who have shown that obese patients will lose weight with diets of 1000 calories. Surprisingly, the rate of weight loss was increased when the composition of the diet was altered from the usual low caloric one to one predominantly made up of fat or protein. They also showed that more liberal diets, of approximately 2000 calories, sufficient to maintain an even weight in obese patients, would result in weight loss if this same caloric intake was altered to a high fat or high protein content of similar caloric value. Balance studies performed during the period showed that complete absorption occurred during the period of high fat or protein ingestion. They suggested that some aspects of metabolism are different in the obese as compared to the normal and that alteration in composition of food may alter energy output in the obese. Our results are compatible with these findings. The same studies have been extended by Pilkington,21 whose group has shown that obese patients on 1000 calorie diets consisting mainly of fat or protein, for long periods of time, lost weight at a constant rate. They found that after an initial rapid weight loss a steady state was achieved if the diet was continued for a sufficiently long period, usually months. The weight loss paralleled that seen in the usual isocaloric 1000 calorie diet consisting mainly of carbohydrate. One mtust bear in mind that these vere 1000 and not 2000 calorie diets. The detailed study on the single patient described in this report shows that weight loss occurred on a full caloric intake, consisting of high fat and protein and low carbohydrate content. The sodium balance was positive and the nitrogen balance negative during the periods of free diet and low caloric diet. However, while on the Pennington diet the sodium balance was negative and the nitrogen balance was positive. Although one is tempted to attempt it, it is not possible to interpret these findings decisively. Shifts in mineral balances are commonly observed phenomena in the obese when the caloric intake is manipulated. The patients who were successful in losing weight all did so on a liberal diet which prevented hunger and provided for satiety. All the other methods of weight reduction mentioned earlier have been utilized by the author in the past. The diet discussed was found to be the most satisfactory of all these methods in our hands. Weight reduction occurred dramatically with a rapid fall early and then proceeding slowly but surely. Only nine of the 28 were able to reach ideal weight indices.'9 The others did not do so well but did achieve significant weight losses. It is our feeling that the usual low isocaloric diet would be necessary to bring these remaining 18 subjects down to ideal weight indices, but this is not an established fact. As stated, the patients found this method of losing weight superior to others. They did not suffer from hunger, felt satisfied most 'of the time and were free to reach for food at any time. They found this to be of immeasurable comfort and thus they were able to lose weight to a greater degree and for a longer period of time than they had heretofore realized. The results reported indicated that a greater number of patients will follow such a diet for a long period with satisfactory achievement levels.
SUMMARY Twenty-eight of 48 patients succeeded in losing weight on a liberal caloric diet high in protein and fat and low in carbohydrate, as proposed by Pennington. The results are discussed in the light of recent metabolic studies in obesity by Kekwick and Pawa.