114. Her principal food was coffee, of which she took daily as many

as forty small cups. She was jovial and a boon table companion, and used black coffee in quantities that would have surprised an Arab. Her coffee-pot was always on the fire, like the tea-pot in an English cottage (Lejoncourt, p. 84; Chemin, p. 147). The entire matter resolves itself into one of individual tolerance, resistivity, and constitution. Numerous examples of young abstainers who have died and coffee drinkers who have still lived on can be found, and _vice versa_, the preponderance of instances being in neither direction. Bodies of persons killed by accident have been painstakingly examined for physiological changes attributable to coffee; but no difference between those of coffee and of non-coffee drinkers (ascertained by careful investigation of their life history) could be discerned.[216] In the long run, it is safe to say that the effect of coffee drinking upon the prolongation or shortening of life is neutral. _Coffee in the Alimentary Tract_ When coffee is taken _per os_ it passes directly to the stomach, where its sole immediate action is to dilute the previous contents, just as other ingested liquids do. Eventually the caffein content is absorbed by the system, and from thence on a stimulation is apparent. Considerable conjecture has occurred over the difference in the effects of tea and coffee, the most feasible explanation advanced being one appearing in the London _Lancet_.[217] The caffein tannate of tea is precipitated by weak acids, and the presumption is that it is precipitated by the gastric juice and, therefore, the caffein is probably not absorbed until it reaches the alkaline alimentary tract. In the case of coffee, however, in whatever form the caffein may be present, it is soluble in both alkaline and acid fluids, and, therefore, the absorption of the alkaloid probably takes place in the stomach. This theory, if true, goes far toward explaining the more rapid stimulation of coffee. The statement has sometimes been made that milk or cream causes the coffee liquid to become coagulated when it comes into contact with the acids of the stomach. This is true, but does not carry with it the inference that indigestibility accompanies this coagulation. Milk and cream, upon reaching the stomach, are coagulated by the gastric juice; but the casein product formed is not indigestible. These liquids, when added to coffee, are partially acted upon by the small acid content of the brew, so that the gastric juice action is not so pronounced, for the coagulation was started before ingestion, and the coagulable constituent, casein, is more dilute in the cup as consumed than it is in milk. Accordingly, the particles formed by it in the stomach will be relatively smaller and more quickly and easily digested than milk _per se_. It has been observed that coffee containing milk or cream is not as stimulating as black coffee. The writer believes that this is probably due to mechanical inclusion of caffein in the casein and fat particles, and also to some adsorption of the alkaloid by them. This would materially retard the absorption of the caffein by the body, spread the action over a longer period of time, and hence decrease the maximum stimulation attained. In a few instances, a small fraction of one percent of coffee users, there is a certain type of distress, localized chiefly in the alimentary tract, caused by coffee, which can not be blamed upon the much-maligned caffein. The irritating elements may be generally classified as compounds formed upon the addition of cream or milk to the coffee liquor, volatile constituents, and products formed by hydrolysis of the fibrous part of the grounds. It may be generally postulated that the main causation of this discomfort is due to substances formed in the incorrect brewing of coffee, the effect of which is accentuated by the addition of cream or milk, when the condition of individual idiosyncrasy is present. Without enlarging upon his reason, Lorand[218] concludes that neither tea nor coffee is advisable for weak stomachs. Nalpasse,[219] however, believes that coffee taken after meals makes the digestion more perfect and more rapid, augmenting the secretions, and that it agrees equally well with people inclined to embonpoint and heavy eaters whose digestion is slow and difficult. Thompson[220] also observes that coffee drunk in moderation is a mild stimulant to gastric digestion. Eder[221] reported, as the result of an inquiry into the action of coffee on the activity of the stomachs of ruminants, that coffee infusions produced a transitory increase in the number and intensity of the movements of the paunch, but that the influence exercised was very irregular. An elaborate investigation of the action of tea and coffee on digestion in the stomach was made by Fraser,[222] in which he found that both retard peptic digestion, the former to a greater degree than the latter. The digestion of white of egg, ham, salt beef, and roast beef was much less affected than that of lamb, fowl, or bread. Coffee seemed actually to aid the digestion of egg and ham. He attributed the retarding effect to the tannic acid of the tea and the volatile constituents of the coffee--the caffein itself favoring digestion rather than otherwise. Tea increased the production of gas in all but salt foods, whereas coffee did not. Coffee is, therefore, to be preferred in cases of flatulent dyspepsia. Hutchinson, in his _Food and Dietetics_, opines: As regards the practical inferences to be drawn from experiences and observations, it may be said that in health the disturbance of digestion produced by the infused beverages (tea and coffee) is negligible. Roberts, indeed, goes so far as to suggest that the slight slowing of digestion which they produce may be favored rather than otherwise, as tending to compensate for too rapid digestibility which refinements of manufacture and preparation have made characteristic of modern foods. Regarding increase in secretory activity, Moore and Allanston[223] report that in their experience meat extracts, tea, caffein solution, and coffee call forth a greater gastric secretion than does water, while with milk the flow of gastric juice seems to be retarded. Cushing[224] and others support this statement. This action is partially explained by Voit on the grounds that all tasty foods increase gastric secretion, the action being partly psychological; but Cushing observed the same effects upon introducing coffee directly into the stomachs of animals. In general, a moderate amount of coffee stimulates appetite, improves digestion and relieves the sense of plenitude in the stomach. It increases intestinal peristalsis, acts as a mild laxative, and slightly stimulates secretion of bile. Excessive use, however, profoundly disturbs digestive function, and promotes constipation and hemorrhoids.[225] There is much evidence to support the view that "neither tea, coffee, nor chicory in dilute solutions has any deleterious action on the digestive ferments, although in strong solutions such an action may be manifest."[226] After conducting exhaustive experiments with various types of coffee, Lehmann[227] concluded that ordinary coffee is without effect on the digestion of the majority of sound persons, and may be used with impunity. _Coffee in the Dietary--Food Value_ There are three things to be considered in deciding upon the inclusion of a substance in the dietary--palatability, digestibility without toxicity or disarrangement, and calorific value. Coffee is as satisfactory from these viewpoints as any other food product. The palatability of a well-made cup of good coffee needs no eulogizing; it speaks for itself. It adds enormously to the attractiveness of the meal, and to our ability to eat with relish and appetite large amounts of solid foods, without a subsequent uncomfortable feeling. Wiley[228] says that the feeling of drowsiness after a full meal is a natural condition incidental to the proper conduct of digestion, and that to drive away this natural feeling with coffee must be an interference with the normal condition. However, if by so doing, we can increase our over-all efficiency without material harm to our digestive organs (and we can and do), the procedure has much in its favor both psychologically and dietetically. The fact that coffee favors digestion without eventual disarrangement has been demonstrated above. On the subject of the relative agreement with the constitution of foods of daily consumption, Dr. English[229] said: It is well known that there is no species of diet which invariably suits all constitutions, nor will that which is palatable and salutary at one time be equally palatable and salutary at another time to the same individual. I think the most natural food provided for us is milk; yet I will engage to show twenty instances where milk disagrees more than coffee. Further in this regard, Hutchinson[230] considers that ninety percent of the "dyspepsias" attributed to coffee are due to malnutrition, or to food simultaneously ingested, no disease known to the medical profession being directly attributable to it. No one cognizant of the facts will contend that a cup of black coffee has any direct food value; but not so with the roasted bean. This has quite an appreciable content of protein and fat, both substances of high calorific value. The inhabitants of the Island of Groix eat the whole roasted coffee bean in considerable quantity, and seem to obtain considerable nourishment therefrom. Also, the Galla, a wandering tribe of Africa, make large use of food balls, about the size of billiard balls, consisting of pulverized coffee held in shape with fat. One ball is said to contain a day's ration; and, because of its food content and stimulating power, serves to sustain them on long marches of days' duration. When an infusion, or decoction, of roasted coffee is made, about 1.25 percent of the extracted matter is protein, it being accompanied by traces of dextrin and sugar. The same dearth of extraction of food materials occurs upon infusing coffee substitutes. This small amount can have but little dietetic significance. However, upon addition of sugar and of milk or cream, with their content of protein, fat, and lactose, the calorific value of the cup of coffee rises. Lusk and Gephart[231] give the food value of an ordinary restaurant cup of coffee as 195.5 calories, and Locke[232] gives it as 156. Mattei[233] found that 8 cc. of an infusion of roasted Mocha coffee of five-percent strength suppressed incipient polyneuritis in pigeons within a few hours' time. Their weight did not improve, but otherwise they were completely restored to health. However, in from four to six weeks after the apparent cure, the symptoms rapidly returned and the pigeons perished, with symptoms of paralysis and cerebral complications. The temporary cure was probably due to caffein stimulation and secondary actions of the volatile constituents of coffee, which may be related to the vitamines; for it is not likely that the vitamines would withstand the heat of roasting. If B-vitamine does occur in roasted coffee, it is present only in traces.[234] The inclusion of coffee in the average dietary is warranted because of its evident worth as an aid to digestion and for its assimilating power, thus earning its characterization as an "adjuvant food." _Action of Coffee on Bacteria_ The employment of coffee as an aid to sanitation has been but little considered. Coffee, when freshly roasted and ground, is deodorant, antiseptic, and germicidal, probably due to the empyreumatic products developed during the process of roasting. An infusion of 0.5 percent inhibits the growth of many pathogenic organisms, and those of 10 percent kill anthrax bacteria in three hours, cholera spirilla in four hours, and many other bacteria, including those producing typhoid, in two to six days.[235] The maintenance of a low rate of contraction of typhoid fever has often been attributed to drinking of coffee instead of water, the action of the coffee being partly due to the bactericidal effect of the caffeol and partly to the boiling of the water before infusion. The stimulating tendency of the caffein to sustain and to "tide over" those of low vitalities is also evidenced. _Use of Coffee in Medicine_ Coffee has been employed in medicinal practise as a direct specific, as a preventive, and as an antidote. The _United States Dispensatory_[236] summarizes the uses of caffein and coffee as follows: Caffein is a valuable remedy in practical medicine as a cerebral and cardiac stimulant and as a diuretic. In undue _somnolence_, in _nervous headache_, in _narcotism_, also, at times when the exigencies of life require excessively prolonged wakefulness, caffein may be used as the most powerful agent known for producing wakefulness. In a series of experiments, J. Hughes Bennett found that within narrow limits there is a direct physiological antagonism between caffein and morphine. Coffee and caffein in narcotic poisoning are of value as a means of keeping the patient awake, and of stimulating the respiratory centres. As a cardiac stimulant, caffein may be used in any form of heart failure; the indications for its use are those which call for the employment of digitalis. It is superior to digitalis in never disagreeing with the stomach, in having no distinctive cumulative tendency, and in the promptness of its action. It is pronouncedly inferior to digitalis in the power and certainty of its action, and in the permanence of its influence once asserted. As a diuretic it is superior; it is very valuable in the treatment of _cardiac dropsies_, and is often useful in _chronic Bright's disease_ when there is no irritation of the kidneys. On account of its tendency to produce wakefulness, it is usually better to mass the doses early in the day, at least six hours being left between the last dose and the ordinary time for sleep. From eight to fifteen grams (of caffein) may be given in the course of a day in severe cases. If tried, it would probably prove a useful drug in cases of _sudden collapse_ from various causes. Good effects of coffee are recounted by Thompson.[237] It removes the sensation of fatigue in the muscles, and increases their functional activity; it allays hunger to a limited extent; it strengthens the heart action; it acts as a diuretic, and increases the excretion of urea; it has a mildly sudorific influence; it counteracts nervous exhaustion and stimulates nerve centers. It is used sometimes as a nervine in cases of migraine, and there are many persons who can sustain prolonged mental fatigue and strain from anxiety and worry much better by the use of strong black coffee. In low delirium, or when the nervous system is overcome by the use of narcotics or by excessive hemorrhage, strong black coffee is serviceable to keep the patient from falling into the drowsiness which soon merges into coma. In such cases as much as half a pint of strong black coffee may be injected into the rectum. Strong coffee with a little lemon juice or brandy is often useful in overcoming a malarial chill or a paroxysm of asthma. It is a useful temporary cardiac stimulant for children suffering collapse. Dr. Restrepo,[238] of Medellin, Colombia, claims to have cured many cases of chronic malaria and related diseases with infusion of green coffee, after quinine had failed. Wallace[239] states that tincture of green coffee is a natural and efficacious specific for cholera, and that she knows of more than a thousand eases of cholera and diarrhea which have been treated with it without an isolated case of failure. Landanabileo has been quoted as using raw coffee infusion in hepatic and nephritic diseases, venal and hepatic colics, and in diabetes. In the Civil War, surgeons utilized coffee in allaying malarial fever and other maladies with which they had to contend, often under the most trying conditions, and with severely limited means of combating disease.[240] Its effect is to counteract the depressant action of low and miasmatic atmospheres, opening the secretions which they have checked. Travelers from the colder climes soon find that the fragrant cup of coffee is a corrective to derangements of the liver resulting from climatic conditions.[241] Dr. Guillasse, of the French Navy, in a paper on typhoid fever, says: Coffee has given us unhoped for satisfaction, and after having dispensed it we find, to our great surprise, that its action is as prompt as it is decisive. No sooner have our patients taken a few tablespoonfuls of it, than their features become relaxed and they come to their senses. The next day the improvement is such that we are tempted to look upon coffee as a specific against typhoid fever. Under its influence the stupor is dispelled, and the patient arouses from the state of somnolency in which he has been since the invasion of the disease. Soon all the functions take their natural course, and he enters upon convalescence.[242] Also it has been reported that in extreme cases of yellow fever, coffee has been used most effectively by many physicians as the main reliance after all other well known remedies have been administered and failed. According to Lorand,[243] the use of coffee in gout is strictly prohibited by Umber and Schittenhelm; but he considered it a mistake absolutely to forbid coffee, as, when a person has good kidneys, the small amount of uric acid furnished by the caffein can readily be eliminated. A curious remedy for gout and rheumatism, the efficacy of which the writer scouts, is said to be[244]--a pint of hot, strong, black coffee, which must be perfectly pure, and seasoned with a teaspoonful of pure black pepper, thoroughly mixed before drinking, and the preparation taken just before going to bed. If this has any value, it is probably purely psychological in its function. Several writers[245] attribute amblyopia and other affections of the sight to coffee and chicory, without giving much conclusive experimental data. Beer,[246] a Vienna oculist, however, held that the vapor from pure, hot, freshly-made coffee is beneficial to the eyes. Coffee and caffein are physiologically antagonistic to the common narcotics, nicotine, morphine, opium, alcohol, etc., and are frequently used as antidotes for these poisons. Binz found that dogs that have been stupified with alcohol could be awakened with coffee. It may thus be prescribed for hard drinkers to counteract the baleful excitability produced by alcohol; in fact, many topers taper off after a long debauch with coffee containing small amounts of alcoholic beverages. Considering its ability to counteract the slow intoxication of tobacco, it may be inferred that coffee is indispensable for hard smokers. In general, the medicinal value of coffee may be said to be directly attributable to its caffein content, although its antiseptic properties are dependent upon the volatile aromatic constituents. Its function is to raise and to sustain vitalities which have been lowered by disease or drugs. Although some of the cures attributed to it are probably purely traditional; still, it must be admitted, that by utilizing its stimulating qualities in many illnesses the patient may be carried past the danger point into convalescence. _Physiological Action of "Caffetannic Acid_" It has been demonstrated in chapter XVII that there is no definite compound "caffetannic acid," and that the heterogeneous material designated by this name does not possess the properties of tanning. Further substantiation of this contention, and more evidence of the innocuous character of the tannin-like compounds in coffee, are contained in the testimony of Sollmann.[247] "Tannins precipitate proteins, gelatine, and connective tissue, and thus act as astringents, styptics, and antiseptics. The different tannins are not equivalent in these respects. Some (which are perhaps misnamed) such as those of coffee and ipecac, are practically non-precipitant.... On the whole, one may say that the small quantities of tannin ordinarily taken with the food and drink are not injurious, but that large quantities (excessive tea drinking) are certainly deleterious. The tannin of coffee is scarcely astringent, and, therefore, lacks this action," which is proven by the fact that it does not precipitate proteins. "It has been claimed that 'caffetannic acid' injures the stomach walls, but there is no evidence that this is so."[248] Wiley,[249] in reporting some of his experiments, says: "Apparently the efforts to saddle the injurious effects of coffee-drinking upon caffetannic acid in any form in which it may exist in the coffee-extract are not supported by these recent data." The fact that tannins retard intestinal peristalsis, whereas coffee promotes this digestive action, lends further proof to the non-existence of tannin in coffee. These statements by eminent authorities may be consolidated into the verity that there is no tannin, in the true sense of the term, in coffee; and that the constituents of the coffee brew which have been so designated are physiologically harmless. _Physiological Action of Caffeol_ The evidence regarding the physiological action of caffeol is contradictory in many cases. J. Lehmann found in 1853, that the "empyreumatic oil of coffee, _caffeone_," is active; but more recent investigations have yielded results at variance with this. Hare and Marshall[250] believe that they proved it to be active. E.T. Reichert,[251] however, found it inactive in dogs, excepting in so far that, when given intravenously, it mechanically interfered with the circulation. With it Binz[252] was able to produce in man only feeble nervous excitement, with restlessness and increase in the rate and depth of respirations. The general effects, as summated by Sollmann[253] are, for _small doses_, pleasant stimulation; increased respiration; increased heart rate, but fall of blood pressure; muscular restlessness; insomnia; perspiration; congestion; for _large doses_, increased peristalsis and defecation; depression of respiration and heart; fall of blood pressure and temperature; paralytic phenomena. It is doubtful whether the quantities taken in the beverage cause any direct central stimulation. Investigations have also been conducted with the various known constituents of this "coffee oil." Erdmann[254] found that in doses of between 0.5 and 0.6 gram per kilo of body weight, furane-alcohol kills a rabbit by respiratory paralysis; and that the symptoms of poisoning are a short primary excitement, salivation, diarrhea, respiratory depression, continuous fall of the body temperature, and death from collapse with respiratory failure. In man, doses of from 0.6 to 1 gram of furane-alcohol increased respiratory activity without producing other symptoms. However, man is not as susceptible to these compounds as are the smaller animals. But even if their relative susceptibility be assumed to be the same, the lethal dose given the rabbit is equivalent to giving a 140-pound man one dose containing the furane-alcohol content of over 5,000 cups of coffee. Thus, in view of the very apparent minuteness of the quantity of this compound present in one cup of coffee, together with the fact that it is not cumulative in its physiological action, the importance of its toxic properties becomes very inconsequential to even the most profuse and inveterate coffee drinkers. Burmann[255] reported the volatile principle to have a reducing action on the hemoglobin; a depressing effect on the blood pressure; a depressant action on the central nervous system, disturbing the cardiac rhythm; and an action on the respiratory centers, causing dyspnea. The report of Sayre[256] regarding the minimum lethal dose of the concentrated combined active principles of coffee obtained from dry distillation is, for frogs, administered intraperitoneally and subcutaneously, 0.03 cubic centimeters per gram of body weight; for guinea pigs per stomach, 7.0 cc. per kilogram of body weight, and administered intravenously and intraperitoneally, about 1.0 cc. per kilogram. This evidence regarding the physiological action of caffeol can not in any wise be construed to indicate a harmfulness of coffee. The percentage of these volatile substances in a cup of coffee infusion is so low as to be relatively negligible in its action. And, again, the caffein content of the brew, as will be seen, tends to counteract any possible desultory effects of the caffeol. _General Physiological Action of Caffein_ More attention has been given to the study of the physiological action of caffein than to that of the other individual constituents of coffee. Since certain of the effects of coffee drinking have been attributed to this alkaloid, a brief presentment of the pharmacology of caffein will be given as an exposition of the many statements made regarding it. According to the _British Pharmaceutical Codex_[257]: Caffein exerts three important actions: (1) on the central nervous system: (2) on muscles, including cardiac: and (3) on the kidney. The action on the central nervous system is mainly on that part of the brain connected with psychical functions. It produces a condition of wakefulness and increased mental activity. The interpretation of sensory impressions is more perfect and correct, and thought becomes clearer and quicker. With larger doses of caffein the action extends from the psychical areas to the motor area and to the cord, and the patient becomes at first restless and noisy, and later may show convulsive movements. Caffein facilitates the performance of all forms of physical work, and actually increases the total work which can be obtained from muscle. On the normal man, however, it is impossible to say how much of the action on the muscle is central and how much peripheral, but, as fatigue shows itself first by an action on the center, it is probable that the action of caffein in diminishing fatigue is mainly central. Caffein accelerates the pulse and slightly raises blood pressure. It has no action in any way resembling digitalis; by increasing the irritability of the cardiac muscle, its prolonged use rather tends to fatigue than to rest the heart. Caffein and its allies form a very important group of diuretics. The urine is generally of a lower specific gravity than normal, since it contains a lesser proportion of salt and urea; but the total excretion of solids, both as regards urea, uric acid, and salts, is increased. Caffein, by exciting the medulla, produces an initial vaso-constriction of the kidneys, which tends at first to retard the flow of urine. So in recent years, other drugs have been introduced, allies of caffein, which act like it on the kidneys, but are without the stimulant action on the brain. Theobromine is such a drug. Another authority states that[258]: One of the most constant symptoms produced in man by over-doses of caffein is excessive diuresis, and experiments made upon the lower animals show that caffein acts as a diuretic not only by influencing the circulation, but also by directly affecting the secreting cells, the probabilities being in favor of the first of these theories of action. According to Schroeder, not only the water but also the solids of the urine are increased. The question whether caffein has an influence upon tissue changes and the consequent nitrogenous elimination can not be considered as distinctly answered, though the most probable conclusion is that the action of caffein upon urea elimination and upon general nutrition is not direct or pronounced. While the therapeutic dose of caffein is broken up in the body with the formation of methylxanthin, which escapes with the urine, the toxic dose is at least in part eliminated by the kidney unchanged. The metabolism of the methyl purins, of which group caffein is a member, appears to vary with the quantity ingested. The manner in which the methyl group is liberated by the cell protoplasm is said[259] to determine the amount of stimulus which the tissues receive from these substances. The xanthin group is almost without any excitatory action, and its metabolic end products are constant. Perhaps the variation in the excretions of unchanged methylpurins is dependent upon the amount of total reactive energy they invoke. Baldi[260] found that caffein in small doses increases muscular excitability in dogs and frogs. The spinal and muscular hyperic excitability produced by caffein is, in his opinion, due to the methyl groups attached to the xanthin nucleus. Fredericq[261] states that caffein increases the irritability of the cardiac vagus and accelerates the appearance of pseudofatigue of the vagus which is produced by prolonged stimulation of the nerve. The action of caffein on the mammalian heart has also been investigated by Pilcher,[262] who found that, following the rapid intravenous injection of caffein, there is an acute fall of blood pressure; and with a maximal quantity of caffein, 10 milligrams per kilogram, the cardiac volume and the amplitude of the excursions are usually unchanged. With larger quantities, the volume progressively increases and the amplitude of the excursion decreases. Salant[263] found that the intravenous injection of 15 to 25 milligrams of caffein per kilogram in animals was followed by a fall of blood pressure amounting to 7 to 35 percent in most cases, which was transitory, although in some animals it remained unchanged. A moderate rise was rarely observed. Caffein aids the action of nitrates, acetanilid, ethyl alcohol and amyl alcohol, and increases the toxicity of barium chloride. In a very thorough study of the toxicity of caffein which he made with Reiger,[264] a greater toxicity of about 15 to 20 percent by subcutaneous injection than by mouth, and but about one-half this when injected peritoneally, was found. Intramuscularly the toxicity is 30 percent greater than subcutaneously. In making the tests on animals, they found that individuality, season, age, species, and certain pathological conditions caused variation in the toxic effect of the administered caffein. Low protein diet tends to decrease resistance to caffein in dogs, and a milk or meat diet does the same for growing dogs. Caffein is not cumulative for the rabbit or dog. As a result of experiments on the action of caffein on the bronchiospasm caused by peptone (Witte), silk peptone, B-imidoazolyl-ethylamin, curare, vasodilation, and mucarin, Pal[265] concluded that caffein stimulates certain branches of the peripheral sympathetic and is thus enabled to widen the bronchi or remove bronchiospasm. According to Lapicque[266], caffein produces a change in the excitability of the medulla of the frog similar to that produced by raising the temperature of the nerve centers. Schürhoff[267] has pointed out that the continued use of large quantities of caffein will produce cardiac irregularity and sleeplessness. Cochrane[268] cited three cases where caffein was hypodermically administered in cases of acute indigestion, etc., and concluded that the cases prove that caffein, or a compound containing it as a synergist, does indirectly make the injection of morphia a safe proceeding, and directly increases the force of the heart and arterial tension. However, Wood[269] found that medium doses of caffein do not produce any marked rise in blood pressure, and cause a reduction in pulse rate. He attributes the contradictory results which prior investigations gave, to employment of unusually large doses and to inaccurate experimental methods. Caffein was found by Nonnenbruch and Szyszka[270] to have a slight action toward accelerating the coagulation time of the blood, being active over several hours. It inhibits coagulation _in vitrio_. Its action in the body apparently rests on an increase of the fibrin ferment. There is no reason to believe that the behavior is dependent on a toxic action, but there is probably an action on the spleen; for in several rabbits from which the spleen was removed, no action was observed. Experiments conducted by Levinthal[271] gave no positive information as to the formation of uric acid from caffein in the human organism. The elimination of caffein has also been studied by Salant and Reiger[272], who found that larger amounts of caffein are demethylated in carnivora than in herbivora, and resistance to caffein is inversely as demethylation, caffein being much more toxic in the former class. In a similar investigation, Zenetz[273] observed that caffein is very slightly eliminated from the system by the kidneys, and that its action on the heart is cumulative; therefore he concludes that it is contra-indicated in all renal diseases, in arterio-sclerosis, and in cardiac affections secondary to them. The inaccuracy of these conclusions regarding the non-elimination of caffein and those of Albanese,[274] Bondzynski and Gottlieb[275], Leven[276], Schurtzkwer[277], and Minkowski[278], has been shown by Mendel and Wardell[279], who point out that many of these experimenters worked with dogs, in which the chief end-product of purin metabolism is not uric acid, but allantoin. They observe that the increase in excretion of uric acid after the addition of caffein to the diet seems to be proportional to the quantity of caffein taken, and equivalent to from 10 to 15 percent of the ingested caffein. The remainder of the caffein is probably eliminated as mono-methylpurins. Regarding the alleged cumulative action of caffein, Pletzer[280], Liebreich,[281] Szekacs[282], Pawinski,[283] and Seifert[284] all concluded from their investigations that the action of caffein is usually of brief duration, and does not have a cumulative effect, because of its rapid elimination; so that there is no danger of intoxication. Dr. Oswald Schmiedeberg says: Caffein is a means of refreshing bodily and mental activity, so that this may be prolonged when the condition of fatigue has already begun to produce restraint, and to call for more severe exertion of the will, a state which, as is well known, is painful or disagreeable. This advantageous effect, in conditions of fatigue, of small quantities of caffein, as it is commonly taken in coffee or tea, might, however, by continued use become injurious, if it were in all cases necessarily exerted; that is to say, if by caffein the muscles and nerves were directly spurred on to increased activity. This is not the case, however, and just in this lies the peculiarity of the effect in question. The muscles and the simultaneously-acting nerves only under the influence of caffein respond more easily to the impulse of the will, but do not develop spontaneous activity; that is, without the co-operation of the will. The character of caffein action makes plain that these food materials do not injure the organism by their caffein content, and do not by continued use cause any chronic form of illness. According to Dr. Hollingworth's[285] deductions, caffein is the only known stimulant that quickens the functions of the human body without a subsequent period of depression. His explanation for this behavior is that "caffein acts as a lubricator for the nervous system, having an actual physical action whereby the nerves are enabled to do their work more easily. Other stimulants act on the nerves themselves, causing a waste of energy, and consequently, according to nature's law, a period of depression follows, and the whole process tends to injure the human machine." In not a single instance during his experiments at Columbia University did depression follow the use of caffein. Of course, caffein, like any other alkaloid, if used to excess will prove harmful, due to the over-stimulation induced by it. However, taken in moderate quantities, as in coffee and tea by normal persons, the conclusions of Hirsch[286] may be taken as correct, namely: caffein is a mild stimulant, without direct effect on the muscles, the effect resulting from its own destruction and being temporary and transitory; it is not a depressant either initially or eventually; and is not habit-forming but a true stimulant, as distinguished from sedatives and habit-forming drugs. _Caffein and Mental and Motor Efficiency_ The literature on the influence of caffein on fatigue has been summarized, and the older experiments clearly pointed out, by Rivers[287]. A summary of the most important researches which have had as their object the determination of the influence of caffein on mental and motor processes has been made by Hollingworth[288], from whose monograph much of the following material has been taken. Increase in the force of muscular contractions was demonstrated in 1892 by De Sarlo and Barnardini[289] for caffein and by Kraepelin for tea. These investigators used the dynamometer as a measure of the force of contraction; however, most of the subsequent work on motor processes has been by the ergographic method. Ugolino Mosso[290], Koch[291]. Rossi[292], Sobieranski[293], Hoch and Kraepelin,[294] Destrée,[295] Benedicenti,[296] Schumberg,[297] Hellsten,[298] and Joteyko,[299] have all observed a stimulating effect of caffein on ergographic performance. Only one investigation of those reported by Rivers failed to find an appreciable effect, that of Oseretzkowsky and Kraepelin,[300] while Feré[301] affirms that the effect is only an acceleration of fatigue. In spite of the general agreement as to the presence of stimulation there is some dissension regarding whether only the height of the contractions or their number or both are affected. As might be expected from the great diversity of methods employed, the quantitative results also have varied considerably. Carefully controlled experiments by Rivers and Webber[302] "confirm in general the conclusion reached by all previous workers that caffein stimulates the capacity for muscular work; and it is clear that this increase is not due to the various psychical factors of interest, sensory stimulation, and suggestion, which the experiments were especially designed to exclude. The greatest increase ... falls, however, far short of that described by some previous workers, such as Mosso; and it is probable that part of the effect described by these workers was due to the factors in question." Investigations of mental processes under the influence of caffein have been much less frequent, most notable among which are those of Dietl and Vintschgau,[303] Dehio,[304] Kraepelin and Hoch,[305] Ach,[306] Langfeld,[307] and Rivers.[308] Kraepelin[309] observes: "We know that tea and coffee increase our mental efficiency in a definite way, and we use these as a means of overcoming mental fatigue ... In the morning these drinks remove the last traces of sleepiness and in the evening when we still have intellectual tasks to dispose of they aid in keeping us awake." Their use induces a greater briskness and clearness of thought, after which secondary fatigue is either entirely absent or is very slight. Tendency toward habituation of the pyschic functions to caffein has been studied by Wedemeyer[310], who found that in the regular administration of it in the course of four to five weeks there is a measurable weakening of its action on psychic processes. Rivers[311], who seems to have been the first to appreciate fully the genuine and practical importance of thoroughly controlling the psychological factors that are likely to play a rôle in such experiments, concludes that "caffein increases the capacity for both muscular and mental work, this stimulating action persisting for a considerable time after the substance has been taken without there being any evidence, with moderate doses, of reaction leading to diminished capacity for work, the substance thus really diminishing and not merely obscuring the effects of fatigue." EFFECT OF CAFFEIN ON MENTAL AND MOTOR PROCESSES Schematic Summary of All Results St.=Stimulation. 0=No effect. Ret.=Retardation. PRIMARY EFFECT Small Doses | Medium Doses | | Large Doses | | | Secondary Reaction | | | | Action Time Hrs. | | | | | Duration | | | | | in Hrs. Process Tests | | | | | | Motor speed 1. Tapping St. St. St. None .75-1.5 2-4 Coordination 2. Three-hole St. 0 Ret. None 1-1.5 3-4