THE INFLUENCE OF ALCOHOL ON PROTEID METABOLISM. By R H. CHITTENDEN. Reprinted from the Journal of Physiology. Vol. XII. No. 3, 1891. [From the Journal of Physiology. Vol. XII. No. 3, 1891.] THE INFLUENCE OF ON PROTEID META- BOLISM. By R. H. CHITTENDEN, Professor of Physiolo- gical Chemistry in Yale fJjriv&rsity. (From experiments made hy Messrs Charles Norris Jr, and E. E. Smith, Assistant in Physiological Chemistry.) Although much work has been done with a view to ascertaining the influence*of alcohol on nutrition, there is still great lack of unanimity of opinion as to its influence on the metabolism of proteid matter. Many observers have reported a diminished excretion of nitrogen during the administration of alcohol, thus implying a diminution of proteid metabolism, while others have found the elimination of urea or nitrogen wholly unchanged. While there is a general impression that alcohol tends to lower the nitrogen output, or in other words to check the metabolism of proteid matter, and that wholly irrespective of the amount taken, the facts at our disposal are hardly sufficient to warrant such an assumption. As has been well pointed out by Warren1 and Reichert2 few, if any, of the old experiments have much value now. The older observers rarely went further than to determine the daily excretion of urea, wholly ignoring the residual nitrogen and the nitrogen of the feces. Furthermore, the necessity of having the body in a con- dition of nitrogenous equilibrium, when studying the influence of a substance on nutrition, was not as fully appreciated then as at the present day. Of the more recent experiments those made by Munk3 appear to be the most trustworthy. This observer experimented with dogs of 18—20 kilos, body weight, in a condition of nitrogenous equilibrium, giving 1 Boston Med. and Surg, Journal, July, 1887. 2 “ The action of alcohol on animal heat functions.” Therapeutic Gazette, Feb. 1890. 3 Verhandl. d. Physiol. Gesellsch. Berlin, Jan. 3, 1879. Also Jahresbericht filr Thier- chemie fiir 1878. p. 310. ALCOHOL AND PROTEID METABOLISM. 221 alcohol in small or large doses for three to five days and comparing the excretion of nitrogen by the urine and faeces during this period with a like period in which no alcohol was given. The results appear to show that while smaller doses, 25 c.c. absolute alcohol, tend to diminish slightly the total nitrogen output, larger doses of 40—50 c.c. of absolute alcohol per day decidedly increase the elimination of nitrogen. In this connection it is to be remembered that v. Boeck and Bauer1 found that with small doses of alcohol there was a diminished excretion of carbonic acid and inflow of oxygen, while larger doses led to an increased consumption of oxygen and excretion of carbonic acid. Hence, Munk concludes that in general, moderate doses of I—l|-c.c. of absolute alcohol per kilo, lessen the decomposition of proteid matter to the extent of 6—7 per ceut., while larger doses of 2 c.c. absolute alcohol per kilo, of body weight increase proteid metabolism 4to 10 per cent. Munk also noticed that after giving large doses of alcohol, the further administration of small doses failed then to produce any diminution in the consumption of proteid matter, or only to a slight extent. Biess2, on the other hand, experimenting with men and giving 3—5 grams of absolute alcohol per kilo, of body weight found both the urea and uric acid of the urine diminished 15—16 per cent, during an alcohol period of 13 days, thus implying diminished proteid metabolism, but the men experimented with were apparently not in nitrogenous equilibrium. Further, in experiments published last year, Keller3, experimenting on himself and taking a single dose of 150 c.c. of 96 per cent, alcohol (2’4c.c. per kilo, body weight), found a slight diminution in the nitrogen of the urine, but as the nitrogen of the faeces was not determined and there is no evidence that the body was in nitrogenous equilibrium this result is likewise of doubtful value. With herbivora, Weiske has shown that small doses of alcohol (about 1 c.c. per kilo, body weight) exert no influence on proteid metabolism, when the animal receives his ordinary food. Further, Weiske and Flechsig4 have found that much the same result is obtained when the animal is fed upon a very rich nitrogenous diet. Thus, in an experiment covering 32 days a sheep of 40 kilos, body weight took daily 60 grams of alcohol diluted to 1 litre, with food containing 22 24 grams of nitrogen. The total excretion of nitrogen 1 Zeitschrift fiir Biologic. Band x. p. 336. 1870. 2 Zeitschrift fiir klin. Medicin. 2. 1. 3 Zeitschrift fiir physiologische Chcmie. 1889. Band xm. p. 128 4 J.f. Landwirthschaft. xxxvix. p. 327. 222 R H. CHITTENDEN. through the urine and fseces amounted during the fore period to 22'2 grams per day, while the daily output during the alcohol period was 22'4 grams, and in the after period 21’88 grams of nitrogen. Thus, from this experiment it would appear, that with herbivora, at least, alcohol does not protect the consumption of proteid matter like carbohydrates, but rather increases it. It is plainly evident from these several results that we are not yet in a position to state definitely the action of alcohol upon proteid metabolism. Quite probably, as indicated by Munk’s experiments, the action varies with variations in the conditions, but unfortunately many of the experiments hitherto tried have been lacking in some one respect to such an extent that the results need to be accepted with caution. In the present study of the question, the experiments have been confined wholly to dogs, and in the administration of the alcohol we have followed Munk in the size of the doses, so that the conditions might be favourable for obtaining confirmation of his results. The diet used throughout the experiments was a mixture of desic- cated beef and milk crackers or biscuit. The meat was prepared by taking large quantities of lean beef (sufficient to last through an entire experiment), freeing it from fat and tendon, passing it through a hashing machine and then drying it at 45—50° 0. until it had lost about 75 per cent, of its weight. The entire quantity was ground to a coarse powder, thoroughly mixed, and preserved in tightly closed jars. A sufficient amount of dry milk biscuit was likewise prepared by simply grinding it to a coarse powder. The percentages of nitrogen in both meat and biscuit were determined in sampled portions by the Kjeldahl method, thus giving us exact data on which to calculate the daily income of nitrogen. First Experiment. In this experiment, the dog used weighed a little over 16 kilos. He was confined in a suitable cage, lined with galvanized iron, adapted for the collection of the excreta. The meat employed as food contained 12-87 per cent, of nitrogen and the crackers or biscuit I*Bl per cent, of nitrogen. The daily rations consisted of 96 grams of the prepared beef and 80 grams of biscuit, mixed with 850 c.c. of water; one-half being given at 9 a.m., the other half at 5 p.m. The daily nitrogen income amounted therefore to 13 79 grams. The animal was confined in the cage and fed upon this diet for two weeks before the excretions were ALCOHOL AND PROTEID METABOLISM. 223 analyzed, at the end of which time it was assumed that the animal had become habituated to the diet and his surroundings. The extent of nitrogenous metabolism wTas measured by daily determinations of the nitrogen of the urine, using the Kjeldahl method, and by determina- tions of total sulphur and phosphorus. The nitrogen of the fseces was likewise determined by Kjeldahl’s method, whenever the animal defecated. Owing to the highly nutritive character of the food, however, this usually occurred only once in five days. Each day’s urine repre- sents the quantity excreted from 9 a.m. of one day to 9 a.m. of the following day, the date given in the tables being the day on which the 24 hours ended. Consequently, alcohol given on the 4th of April, for example, would have no effect on the urine of that date, but its influence would be looked for on the day following. The method employed in the determination of total sulphur and phosphorus was to evaporate a given volume of the urine (50—100 c.c.) in a commodious silver crucible with pure potassium hydroxide and nitrate, igniting the residue until it was completely oxidized and treating the salts with water. For sulphur, the solution was acidified with hydrochloric acid, evaporated to dryness, the residue again dissolved, the solution filtered and precipitated after the usual method with barium chloride. For phosphorus, the solution was acidified with nitric acid, evaporated to dryness, the residue again dissolved and the solution precipitated first with molybdic solution and lastly with magnesia mixture. From the weight of magnesium pyrophosphate, the phosphorus was readily calculated. The experiment extended through twenty-eight days and was divided into three periods; a fore or normal period of twelve days, during which no alcohol was given, an alcohol period of ten days during which 290 c.c. of absolute alcohol were administered, and lastly a short after period of six days. As seen from the table of results, the average daily output of nitrogen by the urine and fseces for the normal period amounted to 1331 grams, while the daily income was 1379 grams. The animal lost considerable hair which would account for a portion of the deficit in nitrogen, while the remainder must be attributed to the slight gain in body weight and in part to the ordinary losses in ana- lytical work. First Experiment. Date Body weight Volume urine Sp. gr. Reaction Nitrogen Sulphur Phos- phorus Absolute alcohol taken March kilos. c.c. grams gram gram c.c. 24 16-1 810 1016 acid 12-973 0-862 0-609 0 25 16-1 800 1017 13-000 6-850 0-630 26 16-2 850 1016 13-080 0-854 0-632 27 16-1 820 1017 13-087 0-877 0-910 28 16-3 745 1016 11-012 0-720 0-603 29 16-2 780 1016 11-052 0-735 0-611 30 16-3 955 1019 16-866 1-081 0-995 31 16-2 860 1017 53 13-873 0-880 0-784 April 1 16-4 915 1016 13-993 0-881 0-822 2 16-3 805 1017 13-600 0-897 0-762 3 16-4 820 1017 5? 13-567 0-874 0-778 4 16-5 700 1014 33 9-267 0-699 0-496 ►—4 r— o o Daily average 821 1016 12-947 0-850 0-719 March 28. 113 gram feces 2-510 April 3. 92 „ 35 1-890 Daily average nitrogen 13-314 Date Body weight Volume urine Sp. gr. Reaction Nitrogen Sulphur Phos- phorus Absolute alcohol taken April kilos. c.c. grams gram gram c.c. fl5 115 5 16-2 820 1017 acid 12-511 0-721 0-682 6 16-3 850 1020 ?> 16-317 1-192 1-024 [15 115 7 16-6 840 1016 J7 12-602 0-879 0-763 fl5 15 8 16-8 850 1016 J? 12-565 0-997 0-726 1 f!5 U5 0 16-8 775 1016 )> 12-632 0-732 0-795 fl5 115 10 16-7 800 1016 5? 13-121 0-840 0-730 ■ fl 5 115 11 16-6 780 1017 13-322 0-860 0-736 15 115 12 16-8 810 1016 ?? 12-816 0-771 0-776 ] fl 5 Ll 5 13 17-0 870 1016 5? 13-278 0-853 0-772 Q5 115 . 14 16-8 740 1018 12-626 0-795 0 718 0 Total alcohol Daily average 813 1016 13-179 0-864 0-772 290 A] .ril 8. 96 grams fseces 2-020 , 13. 98 „ 2-140 Daily average Nitrogen 13-595 ALCOHOL AND FROTH ID METABOLISM. 225 Date Body weight Volume urine Sp. gr. Eeaction Nitrogen Sulphur Phos- phorus Absolute alcohol taken April kilos. c. c. grams gram gram 15 16-8 800 1018 acid 13-108 0-810 0-790 0 16 16-8 830 1016 13-161 0-820 0-793 17 16-9 839 1017 13-586 0-850 0-761 18 16-8 , 831 1016 13-749 0-889 0-762 19 16-9 820 1017 13-542 0-889 0-782 20 17-0 735 1018 33 10-982 0-686 0-639 Daily average 809 1017 13-021 0-824 0-754 April 20. 112 grams feces 2-350 Daily average Nitrogen 13-413 During the alcohol period, in which T9 c.c. of absolute alcohol per kilo, of body weight were given daily for nine consecutive days, the average daily output of nitrogen amounted to 13'59 grams, an increase of about 2 per cent, over the average daily excretion of the normal period. The excretion of sulphur and phosphorus was likewise increased during the alcohol period to a corresponding extent. In the third or after period the excretion of all three elements fell back approximately to the normal. The alcohol administered during the alcohol period was given in two distinct doses daily, mixed with the water of the food, and in no case did it apparently disagree with digestion. Unlike most previous experiments there was here no noticeable diuretic action, the average daily volume of urine being essentially the same during all three periods. The doses of alcohol were sufficiently large to produce drowsiness and a tendency towards stupor, the animal sleeping a great portion of the time during the alcohol period. There was further a slight weakness of the hind legs noticeable at times, particularly just after the doses of alcohol were given. The results of this experiment may perhaps be taken as confirmatory of Munk’s observations that fairly large doses of alcohol tend to increase somewhat the nitrogen output, thus implying increased metabolism of proteid matter. Our results certainly show a slightly increased excretion of nitrogen during the alcohol period, and this is confirmed by a corresponding increase in the excretion of sulphur and phosphorus. Considering, however, the size of the doses and the length of the alcohol period, it would seem as if a more decisive result might naturally be expected, if the substance experimented with is possessed of any very pronounced effect upon proteid metabolism. 226 R. H. CHITTENDEN. Second Experiment. In this experiment a somewhat smaller dog was employed, of about 13 kilos, body weight. The diet was of the same order as that made use of in the first experiment. The prepared meat contained 12 83 per cent, of nitrogen, as determined by the Kjeldahl method, and the biscuit IT6 per cent, of nitrogen. The quantity of food given daily throughout the experiment consisted of 70 grams of prepared beef and 50 grams of milk biscuit with 500 c.c. of water. Hence the daily income of nitrogen amounted to 9'56 grams. This was fed to the animal at one time, instead of dividing it as in the first experiment, always at the same hour, viz, 10 a.m. Likewise, when the alcohol was given, the entire daily dose was mixed with the food and thus adminis- tered at one time. In view of the possibility of alcohol exerting some special influence upon the elimination of either urea or uric acid, without necessarily affecting the excretion of total nitrogen, it was decided in this experi- ment to estimate not only the amount of nitrogen eliminated, but also the urea and uric acid. Phosphoric acid was also determined, but estimation of total sulphur and phosphorus was omitted. Uric acid was determined gravimetrically by E. Salkowski’s well-known silver method1. Phosphoric acid by titration with a standard solution of uranyl nitrate. Urea, by titration with a standard solution of mercuric nitrate, after removal of the phosphates by baryta mixture and of chlorine by standard solution of silver nitrate. The standard mercury solution was prepared as recommended by Pfluger, and in the titra- tion the acidity of the mixture was neutralized by a solution of sodium carbonate of 1053 specific gravity, after the method recommended by Pfliiger. Total nitrogen in both the urine and faeces was determined by the Kjeldahl method. The experiment was divided into three periods of ten days each. In the first or normal period, the average daily excretion of nitrogen through the urine and fmces amounted to 9'098 grams. This shows a deficit of 0’46 gram of nitrogen when compared with the daily nitrogen income ; a deficiency due doubtless in part to loss of nitrogen by shedding of hair, and in part to the animal not being absolutely in nitrogenous equilibrium. The deficit, however, is not a large one and would mean at the most a laying up of 2'87 grams of proteid matter per day, or for the ten days’ period of 28-7 grams proteid matter. In harmony with this, the animal appears to have gained slightly in weight. 1 See Salkowski and Leube. Die Lehre vom Earn. pp. 96-97. ALCOHOL AND FROTH ID METABOLISM. 227 Second Experiment. Date Body wt. Yol. urine Sp. gr. Nitrogen Urea Uric acid Phospho- ric acid (P2O5) Nitrogen of faeces Absolute alcohol taken Jan. kilos. c.c. grams grams gram grams grams c.c. 13 12-6 530 1019 8-362 18-925 0-0402 1-109 14 12-6 497 1018 8-771 17-940 0-0365 0-943 15 12-8 475 1018 8-342 18-629 0-0377 1-216 16 13-0 525 1016 7-824 16-851 0-0330 1-044 17 12-9 615 1017 10-627 23-460 0-0286 1-494 0-558 18 12-8 430 1023 8-916 18-542 0-0126 0-968 0-665 19 12-9 510 1016 8-121 17-414 0-0339 1-204 20 12-8 665 1017 10-829 22-512 0-0372 1-629 21 12-8 420 1016 5-608 12-456 0-0271 0-871 1-773 22 12-9 495 1021 10-586 22-359 0-0364 1-337 200 Total 5162 87-986 189-088 0-3232 11-815 2-996 2-996 Total nitrogen, urine and faeces 90-982 Date Body wt. Yol. urine Sp. gr. Nitrogen Urea Uric acid Phospho- ric acid (P2o5) Nitrogen of faeces Absolute alcohol taken Jan. kilos. c.c. grams grams gram grams grams c.c. 23 12-8 585 1018 9-311 20-032 0-0570 1-257 25-6 24 12-9 480 1015 6-162 13-533 0-0480 0-955 25-8 25 12-9 470 1018 7-676 17-332 0-0277 1-014 25-8 26 130 550 1020 10-288 22-644 0-0690 1-304 26-0 27 130 535 1019 9-320 20-512 0-0570 1-205 0-280 32-5 28 13-0 575 1020 10-554 22-550 0-0449 1-473 32-5 29 13-1 450 1017 6-644 13-873 0-0277 0-992 32-8 30 13-1 550 1017 7-844 16-902 0-0358 1-099 39-3 31 13-0 550 1018 8-866 19-156 0-0393 1-249 1-572 39-0 Feb. 1 13-0 630 1019 10-843 22-679 0-0439 1-389 Total 5375 87-508 189-213 0-4503 11-937 0-852 299-3 1-852 Total nitrogen, urine and faeces 89-360 li. H. CHITTENDEN. Date Body \vt. Vol. urine Sp. gr. Nitrogen Urea Uric acid Phospho- ric acid (PA) Nitrogen of feces Absolute alcohol taken Feb. kilos. c.o. grams grams gram grams grams c.c. 2 13-0 650 1025 13-605 29-868 0-0487 1-817 0-075 0 3 13-0 520 1017 6-837 15-879 0-0216 1-117 4 12-9 560 1021 10-341 21-416 0-0218 1-450 5 12-9 540 1018 9-196 19-756 0-0219 1-322 6 12-9 540 1017 9-072 18-860 0-0230 1-135 n 1 12-9 500 1020 8-088 17-561 0-0230 1-238 0-917 8 12-8 610 1019 10-710 22-376 0-0229 1-505 9 12-6 570 1021 10-872 22-466 0-0316 1-460 10 12-6 635 1018 9-705 19-948 0-0273 1-436 1-073 11 12-7 525 1019 8-902 18-388 0-0297 1-276 Total 5650 97-328 206-518 0-2715 13-756 2-065 2-065 Total nitrogen, urine and fseces , 99-393 During the alcohol period of ten days, 299'3 cubic centimeters of absolute alcohol were given with a total excretion of 89'36 grams of nitrogen, as contrasted with the 90-98 grams of nitrogen of the normal period. This diminution in the excretion of nitrogen is very slight, and as it is accompanied by almost no change in the excretion of urea it cannot be considered as having any very decisive significance. The most noticeable result in the alcohol period is the decided increase in the elimination of uric acid. This commences immediately on the exhibition of the alcohol, continues throughout the alcohol period and the day following, and then suddenly drops to below the normal amount. The elimination of phosphoric acid during the alcohol period is not materially different from that of the fore period, neither is there any marked diuretic action under the influence of the alcohol. There is a slight increase in body weight. In the after period, following the administration of alcohol, the total nitrogen output for the ten days amounts to 99'39grams, which is a decided increase over the amount excreted during the fore period, and would at first glance indicate that the average daily excretion of nitrogen during the after period (9’93 grams) was greater than the daily income of nitrogen (9’56 grams). This, however, is not wholly true, for while the total nitrogen output in the after period is greater than the total nitrogen ingested, this is due to the very large amount of nitrogen eliminated on the first day of the after period, or the day following the ALCOHOL AND PROTEID METABOLISM. 229 last dose of alcohol. Thus the average daily nitrogen output for the last nine days of the after period is 953 grains against 9'56 grams ingested. The body weight during the after period is seen to gradually fall back to that of the first few days of the fore period. In the light of the three periods of this series it seems fair to conclude that the alcohol has given rise to an increase in the excretion of uric acid and at the same time has diminished slightly the elimination of total nitrogen. Third Experiment In this experiment the same animal was made use of as in the preceding one. The daily diet was changed slightly, the animal receiving 67 grams of prepared beef, 50 grams of sampled biscuit and 600 cubic centimeters of water. The meat used throughout the expe- riment contained IS’SS per cent, of nitrogen, the biscuit o’sB per cent.; hence the animal received each day 9'52 grams of nitrogen. This experiment was somewhat shorter than the others, extending through twenty-four days, divided into three periods of eight days each. In the fore or normal period, the total nitrogen income for the eight days amounted to 76T6 grams, while the total nitrogen output, through the urine and faeces amounted to 76'84 grams, thus showing a good condition of nitrogenous equilibrium. The body weight likewise re- mained constant. Third Experiment. Date Body \vt. Vol. urine Sp. gr. Nitrogen Urea Uric acid Phospho- ric acid (p2o5) Nitrogen of feces Absolute alcohol taken Feb. kilos. c.c. grams grams gram grams grams c.c. 19 12-7 530 1019 9-528 19-915 0-0228 1-342 20 12-6 690 1018 11-637 24-603 0-0210 1-489 21 12-6 590 1017 9-141 19-667 0-0227 1-179 22 12-6 495 1016 6-803 14-400 0-0208 1-021 23 12-7 560 1019 9-944 21-382 0-0258 1-303 24 12-5 590 1018 10-245 22-408 0-0271 1-367 25 12-6 495 1018 8-637 18-681 0-0213 1-133 26 12-6 530 1019 9-676 20-158 0-0209 1-337 1-232 31-5 T otal 4480 75-611 161-214 0-1824 10-171 1-232 1-232 Total nitrogen, urine and faeces 76-843 R. 11. CHITTENDEN. 230 Date Body wt. Vol. urine Sp. gr. Nitrogen Urea Uric acid Phospho- ric acid (PA) Nitrogen of fasces Absolute alcohol taken Feb. kilos. c.c. grams grams gram grams grams c.c. 27 12-6 570 1016 8-118 17-646 0-0459 1-187 31 -5 28 12-7 425 1017 6-635 14-285 0-0410 0-977 31-8 Mar, 1 12-8 470 1018 7-857 16-675 0-0501 1-010 32-0 2 12-7 630 1020 12-271 25-819 0-0545 1-436 0-682 38-1 3 12-7 640 1018 9-915 21-008 0-0154 1-237 38-1 4 12-7 525 1016 7-448 15-840 0-0457 0-985 38-1 5 12-7 580 1017 8-719 19-039 0-0487 1-224 38-1 6 12-7 495 1018 8-221 17-368 0-0465 1-110 0-802 0 Total 4335 69-184 147-680 0-3778 9-166 1-484 279-2 1-484 Total nitrogen, urine and faeces 70-668 Date Body wt. Vol. urine Sp. gr. Nitrogen 1 Urea Uric acid Phospho- ric acid (P.Os) Nitrogen of fasces Absolute alcohol taken Mar. kilos. c.c. grams grams gram grams grams c.c. 7 12-6 710 1024 14-387 29-656 0-0412 1-678 0 8 12-6 520 1019 8-293 17-631 | 0-0234 1-156 9 12-6 625 1018 10-089 21-499 0-0384 1-413 1-033 10 12-5 618 1019 10-436 22-655 0-0386 1-409 11 12-6 470 1017 7-659 16-167 1 0-0310 1-115 12 12-7 452 1016 6-678 14-837 1 0-0289 1-047 13 12-7 575 1019 11-292 23-678 | 0-0405 1-462 14 12-7 510 1020 10-378 21-402 j 0-0388 1-268 0-738 Total 4480 79-212 167-575 0-2808 10-548 1-771 1-771 Total nitrogen, urine and faeces 80-983 During the alcohol period of eight days, 279'2 cubic centimeters of absolute alcohol were administered. The total amount of nitrogen eliminated during this period was 70’66 grams, being a decrease of over 6 grams in the eight days, or an average diminution of about three- fourths of a gram per day. The excretion of urea was correspondingly diminished during the alcohol period and likewise that of phosphoric acid. In conformity with this tendency towards diminished proteid metabolism there is to be noticed a slight increase in the body weight. ALCOHOL AND P ROTE ID METABOLISM. 231 The most noticeable feature of the alcohol period, as in the last experiment, is the great increase in the excretion of uric acid. This increase commences on the first day following the exhibition of alcohol, and the average daily quantity eliminated amounts to more than double the quantity eliminated during the fore period. Further, in the after period, the amount excreted quickly drops to near the normal quantity. Again, in the third or after period, the excretion of total nitrogen, urea and phosphoric acid rises to a little more than that of the normal period, indicating plainly that the animal was in good condition throughout the entire experiment, and that the action of the alcohol had unquestionably brought about an inhibition in the excretion of nitrogen, urea, etc., thus implying a diminution in the metabolism of proteid matter. In this connection it is to be observed that the total nitrogen income for the entire period of twenty-four days amounted to 228*48 grams, while the total nitrogen output for the same period, through the urine and faeces, amounted to 228*49 grams, thus showing an exceptionally close correspondence and giving us positive assurance of nitrogenous equilibrium. It is to be further observed that, as in the preceding experiment, the first day of the after period shows a very striking increase in the elimination of nitrogen, urea and phosphoric acid. This might naturally be interpreted as meaning that in the sudden withdrawal of the alcohol the check upon the metabolism of proteid matter was loosened, and consequently the production and excretion of these substances temporarily rose far above the normal amount. In this experiment, as in the two preceding ones, there is no pro- nounced diuretic action noticeable. Conclusions. As a result of these three experiments we may conclude that alcohol, in the quantities employed by us, and in the case of dogs, has no very striking specific action upon the general metabolism of proteid matter. In this connection due weight must be attached to the length of the o o alcohol periods. In each case they extended through eight or ten days and under such conditions one would naturally expect a very pronounced result; one which would be independent of the minor fluctuations to be looked for in a shorter series, and which at the same time would be magnified by the length of the individual periods. Furthermore, the quantity of alcohol employed was large, rising to 2 5 cubic centimeters 232 R. 11. CHITTENDEN. of absolute alcohol per kilo, of body weight. Obviously, such a quantity given day after day should produce a decided result, if the substance is endowed with any special power to retard or stimulate tissue changes. Our results lead us to the conclusion that alcohol, so far as its general influence on proteid metabolism is concerned, acts in the main simply as a non-nitrogenous food. As such it would yield a certain amount of energy by its own oxidation and thus tend to protect slightly the consumption of proteid matter and hence conserve the tissues. This view would accord with the recent results obtained by Reichert1 in his study of the action of alcohol on animal heat functions. Assuming this view to be correct, one could net expect any very great diminution in the nitrogen output under the influence of alcohol; in fact, no greater than was observed in experiments 2 and 3, since it can save the tissues or the proteid food-stuff only to the extent of the energy which it can itself yield. At the same time it must be remembered that alcohol is a potent drug, and as such may exert at times some specific action upon metabolic changes. Possibly in this direction lies the explanation of the decided increase in the elimination of uric acid. Our results cer- tainly indicate that alcohol has a decided and specific action in this direction, increasing the excretion of uric acid a hundred per cent, and that at a time when the elimination of urea and total nitrogen are being diminished. Alcohol may then be considered as having the power to diminish somewhat the general metabolism of proteid matter, thus conserving the tissues ; a power which is dependent mainly upon its character as a non-nitrogenous food. At the same time it has some specific action upon nutrition, as manifested in its tendency to increase the excretion of uric acid. 1 Therapeutic Gazette, Feb. 1890.