Frederick Hoelzel

Apparent prolongation of the life span of rats by intermittent fasting.

When a sufficient amount of choice food is available, labora tory rats, like many humans, eat enough to become more or less obese. As a consequence, the life span of rats feeding ad libitum, like the life span of their human counterparts, is presumably shortened. This inference is supported by the repeated findings of McCay and his associates (†42 a, b; †43) that the life span of rats can be considerably prolonged by a drastic restriction in their allowance of food. The findings of McCay and his associates practically constitute an experi mental confirmation of the claims of Cornaro (Butler, †05) who attributed a considerable prolongation of his life to a rigid restriction of his food intake. However, since the time of Cornaro (1464—1566)no similarly prolonged and rigid voluntary restriction of the human food intake appears to have been recorded. Obviously, Cornaro †s prolonged prac tice of food restriction has not been widely followed because a normal appetite tends to impel its more or less complete appeasement at reasonably frequent intervals, when sufficient palatable food is easily obtainable. Only short periods of food restriction, such as the religiously interdicted periods of food restriction or fasting of the past, would seem to be practical.

Relation of diet to diverticulosis of the colon in rats.

Summary Observations made on 252 rats fed various diets in life span studies indicated that diverticulosis of the colon in ageing rats is produced by the lack of a suitable kind and amount of roughage in the diet. Bulk-formers including more or less hemicellulose in the form of psyllium seed husks were found to prevent the development of colonic diverticulosis.

Production of peptic ulcers in rats and mice by diets deficient in protein

Ulceration of the prostomach and main stomach of rats and mice and ulceration of the duodenum of mice but not of rats was found to occur as a result of starvation or diets deficient in protein or in essential amino-acids.

Production of ulcers in the prostomach of rats by protein restriction.

Büchner, Siebert and Molloy 1 found that marked ulceration could be produced in the prostomach of rats by stimulating the gastric secretion with histamine on starvation days. Some ulceration also occurred in rats starved every other day during a period of 17 days, without histamine. Bürkle-de la Camp 2 confirmed these results with histamine but did not observe ulcers in the prostomach of rats after short periods of simple starvation. The question of ulceration following starvation was of particular interest because irritation of the parapyloric region by the gastric secretion was believed to explain a peculiar and intense hunger sensation that repeatedly developed with starvation or protein restriction in the senior author of the present report (Hoelzel and Kleitman 3 ). Moreover, the observation that protein restriction led to an increase in the fasting gastric acidity (Hoelzel 4 ) made it appear that, if ulcers would develop in the prostomach of rats with starvation, ulceration might also occur as a result of protein restriction alone. We first starved 35 rats every other day or during alternate 2-day periods and gave diets differing in their protein content to the various rats on feeding days. As a result, some rats seemed to develop ulcers in the prostomach regardless of the type of diet, but practically all rats that were intermittently starved and were fed diets low in protein for more than 2 weeks developed ulcers. No ulcers were found in the prostomach of any of 175 control rats. The experimentation was therefore extended to determine the effect of more prolonged starvation, of protein restriction without starvation, and of adding salt, spices, alcohol, HCl or ant-acid salts to various diets.

Use of non-nutritive materials to satisfy hunger.

Evidence is presented indicating that, although non-nutritive materials dispel the desire to eat only transiently by filling the stomach, they tend to dispel the desire to eat more thoroughly by filling the intestines. It is believed that relatively pure cellulosic bulk-formers which resist breakdown in the digestive tract serve the purpose best.

An explanation of appetite

In a self-study of appetite, particularly the appetite for protein-rich foods, it was found that the basal gastric or gastro-duodenal secretory and motor activity as well as epigastric sensations varied with the protein intake or reserve. The involved relations to protein needs seem to explain the physiologic regulation of the protein intake, ft was further found that the protein. carbohydrate, salt and water intakes or reserves are interrelated in affecting basal gastro-duodenal functioning and appetite. Buccal factors in appetite are affected by changes in nutrition in parallel with the gastro-duodenal factors but the common reference of the appreciation of food mainly to taste and smell merely seems to be due to a greater awareness of the flavor and aroma of foods than of the more basic satisfying characteristics of relatively bland food constituents, such as, many proteins, fats and starches.

Gastric acidity, nutritional hydration and appetite.

Data secured during a period of undernutrition and of re-alimentation revealed a relation between the fasting gastric acidity and the degree of general hydration. Such a relation also explains changes in gastric acidity which were found to occur in connection with short fasts, prolonged fasts and variations in the protein intake. A relation between gastric acidity and hydration likewise explains decreases in appetite and in food tolerance which were found to be produced by restricting the food intake too much or by too frequent fasting.

Production of intestinal lesions by feeding karaya gum and other materials to rats.

When fed diets including granular karaya gum, bran or a poor grade of psyllium material, hooded rats proved to be more susceptible than albino rats to the development of lesions in the lower bowel. Serious intestinal lesions were found in 3 of 5 hooded rats fed large amounts of karaya gum for from 396 to 711 days.

Experimental production of polyposis of the colon in rats

Various degrees of polyposis of the colon were produced in 86 (34%) of a group of 250 rats fed diets including pulverized inert materials (kaolin, barium sulphate, talcum powder and pulverized cellulose). Bleeding of the colon occurred in about 90% of the 250 rats.

Nutritional edema and its relation to the incidence of common colds

In the course of 20 years of personal experimentation with fasting and various diets, edema was frequently manifested. It often occurred after periods of undernutrition but was most prominent after prolonged fasting. Edema has also been observed in others after fasting. It is apparently similar to the starvation edema (Hungerödem) which developed among the undernourished masses of Europe during the late war. The European studies of this “war edema” made it clear that nutritional factors and not impairment of the circulation or of kidney function were responsible. But the detailed analysis of the nutritional factors was complicated by the fact that the dietary of the afflicted individuals was not only insufficient in quantity but was also inadequate in other respects. Thus, some investigators were led to attribute the edema mainly to an excessive salt and vegetable intake while others considered it a consequence of deficiency in vitamins or fat. The edema observed in the subject of the present study occurred independent of some of the factors which complicated the European studies. Hence, it is possible to say definitely that vitamin deficiency, fat starvation or an excessive salt intake were not fundamental factors in the development of this edema. Instead, the observations in this study indicate that protein starvation is the primary factor in giving rise to this type of hydration. The finding of Kohman 1 is hereby supported. However, the gross manifestation of nutritional edema seems to be possible only when the diet contains sufficient salt or carbohydrate or both. Water taken alone is not stored and water restriction only creates thirst without removing the cause of the edema. Data concerning the state of hydration before, during and after a 33-day fast were secured with the intradermal salt solution test Qf hfcclure and Aldrich 2 by Dr. Kunde. 3 Further observations were made later in connection with a 41-day fast.