The insensible perspiration decreased from day to day during the period of thirsting, and increased again during the after-period when drinking was resumed. During the thirst-period, and particularly during the first days of the after-period, Dennig discovered perversions of the nitrogen and the fat-absorption, particularly of the latter.

During the time when water was withheld and during the days immediately following (i.e., during the first days of the after-period), the excretion of nitrogen was relatively and absolutely greater than during the fore-period. Dennig draws the following conclusion from this finding: "There is undoubtedly destruction of albumen, and a portion of the degradation products derived from this process are not flushed out until water-drinking is resumed."

In a second series of investigations performed on the same subject the effect of thirsting upon the destruction of albumen did not, by the way, become apparent, and Dennig attributes this to habituation.

In still another very exhaustive communication Dennig (35) reports on the effect of water-withdrawal, particularly on obese subjects. In general, the results corresponded to those reported above. It appeared, however, that fat persons could tolerate thirsting better. No disturbances of absorption were found in such subjects. The loss of albumen during the thirst period was considerably smaller than in lean subjects, occasionally almost nil.

Dennig expresses himself as follows in regard to the effect of thirsting upon metabolism: "The water that the organism gives off during the thirst-period must be replaced by dehydration of the tissues, in particular by the combustion of fat and the destruction of albumen"; in another place he emphasizes the fact that not all of the nitrogen that is excreted in increased quantity during the period of thirsting need be derived from the disassimilation of tissue-albumen, "for human adipose tissue, according to A. W. Volkmann, contains 0.45 per cent, of nitrogen, so that a large portion of the nitrogen that is excreted in excess, about 30 per cent., may be derived from the disassimilation of fat."

The last of the larger investigations that are concerned with the questions under discussion is the communication by Spiegler (36); here some of the details of the nitrogen-excretion during periods of thirsting are chiefly discussed.

In many of the experiments reported by the different authors the urinary nitrogen excretion was found to fall in the beginning of the thirst period and then gradually to rise to values that were above normal. In many instances, even, the increased nitrogen-excretion was not noted until the first day of the afterperiod. Thus, e.g., in one investigation reported by Dennig, in which the N-intake and the absorption of the food remained constant, the urinary N-output assumed the following values:

Fore-Period

10

19.38

11

19.98

12

19.99

Main-Period

13

18.62

14

17.32

15

18.48

16

18.96

18

19.39

19

19.62

After-Period

19

21.70

20

22.06

21

24.36

22

19.53

23

20.03

24

20.00

Landauer interpreted the initial fall of the N-excretion during the thirst-period to signify that the destruction of albumen, while increased during this period, still did not lead to an increased N-excretion, because the nitrogenous waste that was formed in excess was retained owing to the fact that too little water was available to readily flush it out of the system. We know, for instance, that normally a large excess of water will flush out a certain quantity of retained nitrogenous material from the tissues, - Meyer, Oppenheim, von Noorden, Neumann (37), - and thus lead to an increase of the urinary nitrogen.

Dennig interprets the fact that the highest values for the N-excretion are found in the first days of the after-period in the same way, and attributes this phenomenon to flushing out of retained nitrogenous waste. Straub, who in a previous publication also advocated this view, expresses himself somewhat differently in the paper referred to above; here he maintains that the increased N-excretion during the days following the thirst-period must be attibuted to a continuation of the increased destruction of albumen, because, he argues, during these first days the organism is still partially dehydrated and must first replace the water that was lost during the period of water-withdrawal.

Spiegler is inclined to explain the drop in the N-excretion at the beginning of the thirst-period by assuming that the absorption of food is retarded. The striking fact that the highest values for nitrogen are found in the after-period he explains by a resumption of the absorptive function in the bowel and a resulting rapid assimilation of the food material accumulated in the gastro-enteric tract.

Spiegler arrived at these conclusions from short series of investigation with only one thirst-day. His views may be correct for such short periods, but their application to investigations extending over longer periods of time is doubtful and combatable. This is not, however, the place to argue the pros and cons of the different views held by all these investigators. It is probable that the course of the N-excretion during the period of thirsting is the resultant of the various factors enumerated above.

Spiegler has also furnished a contribution to the inquiry whether or not more fat than normal is destroyed during the thirsting period. He fed two dogs of the same litter, that were from 6 to 7 weeks old, with boiled meat. One dog was used as a control and received every morning, together with his meat or soon after eating it, all the water he wished to drink. The other dog never received any water with his meat, but only at noon or in the evening; at these times, however, too, in any desired quantity; this dog, one might say, therefore, was "Schweningering."

In the course of this investigation, that extended over three months, the difference in the weight of the two dogs, that originally was 960 g. in favor of the control-animal, rose to 2441, and Spiegler attributed this to a greater destruction of proper tissues on the part of the experiment-dog as compared to the control-dog. Spiegler declares himself justified in excluding the possibility of a greater loss of water on the part of the first animal, and attributes the difference in weight to a greater destruction of albumen and probably also of fat, as the experiment-dog looked exceedingly thin and lean. In rebuttal of Straub's finding that the C02-excretion did not increase on withdrawal of water, Spiegler called attention to the possibility that a young, growing animal reacted differently to the withdrawal of water - as far as the destruction of fat is concerned - than an adult animal.

It is clear that this experiment is open to criticism on many counts and that it is unsuited to solve the various questions under discussion. In the first place, the difference of 970 g. in the weight of the two young dogs of the same litter is not insignificant, and one could readily imagine that the experiment-dog might have spontaneously failed to gain as much weight as the control-animal. In the second place, no information is given in the article in regard to the important question whether the absorption of the food was as good in the experiment-dog as in the control-dog.

We see, therefore, that the statements made by different investigators in regard to the increased destruction of fat in thirsting animals and human subjects are highly contradictory. One thing, however, is established, viz.: Very great restriction of liquids, leading to torturing thirst, is followed both in man and animals by an increased excretion of nitrogen. We regard this as a manifestation of toxic tissue destruction. The toxins that are formed in process of metabolism are not properly eliminated, and are consequently retained in the tissues and poison the protoplasm of the cells. Consequently we witness an increased excretion of N and of P205, that becomes manifest either at once or later (dependent upon certain circulatory conditions and the eliminative powers of the kidneys) in the urine.

In order to produce this unquestionably dangerous and unfavorable influence upon albumen catabolism, it is necessary, however, to restrict the ingestion of liquids to a point that is far below the measure allowed obese subjects and others for therapeutic purposes. The water in the diet used in the clinical experiments of Jurgensen and Dennig amounted to only 300 to 500 c. c. Oertel never went below about 1 liter of water (including the water incorporated in solid and semi-solid articles of diet.) Practical experience extending over the intervening twenty years has definitely taught us in the meantime that one cannot and should not go below 1000 to 1200 c. c. of liquid (not including the water contained in the solid food) in reduction cures for obesity.

The results obtained in regard to the destruction of fats vary, as we have seen. The study of Landauer, performed with methods that are open to criticism, and the experiment of Spiegler, that is not free from ambiguity, seem to decide in favor of the theories of Oertel and Schweninger. The more exact series of investigations that Straub performed in animals seem to decide against these theories. So far no experiments have been made in human subjects that can form the basis for scientifically accurate conclusions in regard to the effect of water-restriction upon metabolism.

We have attempted to approach this question by studying the respiratory interchange of gases in healthy and obese subjects. These studies will now be reported.