Studies of the chemical exchanges in scurvy have been surprisingly few. It is a field that should repay investigation, promising to afford a clearer insight into the intermediary metabolism in this disorder. One of the first to touch upon this question was Garrod, who in 1848 reported that there was a diminution of potassium salts in the urine and in the blood of scurvy patients. In 1877 Ralfe confirmed the potassium deficiency in the urine, but denied its importance from an etiologic standpoint, as he was unable to benefit scurvy patients by administering potassium nitrate. He reported an increase of uric acid in the urine, a diminution of the total acidity, and a reduction of the alkaline phosphates. Litten found the analyses of the urine very contradictory in respect to potassium, but stated that beyond a doubt its uric acid content is increased at the height of the disease, although this diminishes rapidly with convalescence. These few and scattered articles comprise the sum of metabolic studies up to the last decade, and even during the succeeding period they have been very few—so few, indeed, that they furnish insufficient data from which to draw conclusions.

The first careful study of the mineral metabolism in a case of scurvy is that of Baumann and Howard, published in 1912. Its conclusions are not very definite. They may be summed up by their statement that “chlorin and sodium were retained during the fruit-juice period, but excreted in excess of the intake during the preliminary period,” and that “more potassium, calcium and magnesium were retained during the fruit-juice period.”

This same year Lust and Klocman published the first metabolism study of a case of infantile scurvy. The baby was 18 months old and the metabolic changes were investigated during the active, convalescent, and “the healing stage” of the disorder. This study seems to have been carefully carried out. The fact, however, that the infant received 800 c.c. daily of slightly-boiled milk during the active stage, and was improving at this time, may also have had a beneficial effect on the metabolism in respect to scurvy. The results of these writers are surprising—quite different from what they expected or what we should have expected. They write: “The balance of the mineral metabolism, including the total ash, the calcium, phosphorus and chlorin during the florid stage of the disease must be regarded not only as not damaged, compared to that of the healthy child, but indeed as somewhat increased.” “All the more striking, on the contrary, are the results found during the stage of convalescence. Here the balances were all markedly negative, and only after a lapse of weeks was the tendency manifested to a return to normal conditions.” The authors regard these results as indicating a sort of washing out of “dead material” during convalescence—of material which had gathered during the florid stage of the disease. According to their interpretation the disease is due, not to a primary or secondary salt deficiency, but to a disturbance in salt elimination, and in the first place, of a calcium excretion. This is shown by the fact that even in the “stage of healing,” when the total ash and the phosphorus balance once more had become positive, the calcium balance nevertheless remained somewhat negative. The metabolism of infantile scurvy, they believe, far from showing a resemblance to rickets, manifests quite the contrary tendency. The study of this case of infantile scurvy and that of Baumann and Howard of a case of adult scurvy, comprise the total investigation of the metabolism in human scurvy.

In the course of a recent discussion on rickets before the Medical Society of Vienna, Moll states briefly that in a case of infantile scurvy, at the height of the disease, he found a positive calcium balance, which became poor and later negative on giving fruit juice; in other words, a partial confirmation of the work which has just been cited.

In 1913 Bahrdt and Edelstein reported the analyses of the organs of an infant almost nine months old who died of scurvy; an examination of the tissues, especially of the bones, should be most valuable in checking up determinations of the metabolism during life. This investigation runs absolutely contrary to that of Lust and Klocman. The bones showed a decrease of ash, especially of calcium and of phosphorus, and also a lack of calcium in the muscles, but normal amounts in the liver and in the kidneys. These conditions resemble the deficiency of ash and of lime commonly associated with rickets, and it seems quite possible that this infant had rickets as well as scurvy, and that in this way the discrepancy between the two reports is to be explained. The fact that the water content of the bones was two to three times the normal, also lends emphasis to this interpretation. In any metabolism study of infantile scurvy, great care will have to be exercised that the disorder is not complicated by rickets, and the issue thereby confused. It will be very difficult to avoid this pitfall, for there is no test by which early rickets can be diagnosed. The danger of this complication may be realized when we bear in mind that the majority of infants have rickets to some degree. An investigation of the chemistry of adult scurvy has an advantage from this point of view.

Chemical examination of the blood has yielded such valuable information regarding metabolic diseases, that it might be expected to shed light on the disturbances of scurvy. The only investigation from this standpoint is that of Hess and Killian, who have reported estimations of the urea, creatinine, sugar, CO₂ combining power, diastase, cholesterol, chlorine and calcium.57 The urea content was normal, varying between 12 and 14 mg. per 100 c.c. of blood; this is the average of twenty-one tests on ten cases of infantile scurvy. (In severe cases of beriberi Yano and Nemoti have recently reported that the blood contains an increase of urea, and that its excretion is frequently disturbed.) The creatinine was estimated in two cases and was found to be 2.0 mg. and 1.7 mg. per cent., respectively,—also normal figures. The blood sugar varied from 0.12 to 0.14 per cent. and was examined in almost all the cases in which urea was estimated; these figures are at the upper level of normality (no attention was paid to the interval elapsing between the feeding and the withdrawal of the blood). The diastatic activity was likewise normal. The CO₂ combining power showed figures under 40 to 45, according to the Van Slyke method, and indicated therefore a mild degree of acidosis. In six cases the chlorides were estimated, the figures being remarkably constant at about 0.42 or 0.43. Cholesterol was a little below normal in the four cases examined. Contradictory results were obtained in regard to calcium. Earlier tests showed a definite deficiency of this salt, but those carried out more recently have generally yielded normal results. Further studies of the blood calcium are highly desirable to ascertain whether it varies in amount in the circulation, and especially in different stages of the disease. This aspect is worthy of particular attention in view of the positive calcium balance noted by Lust and Klocman during the active stage of scurvy, and the negative balance during the period of convalescence.

It is evident from the limited data concerning the blood chemistry of scurvy that it is a field which has been inadequately explored and will repay more intensive study. Investigations of this kind have recently been made possible by the introduction of accurate methods requiring only small quantities of blood.

Studies of the metabolism of animals suffering from scurvy are almost as few as those on man. The work of Morgan and Beger, which is frequently quoted in this connection, is not applicable, as it concerns rabbits, which do not develop scurvy. They found that rabbits fed solely on oats and water suffered in their nutrition (loss of appetite, emaciation, paralysis of hind legs), and could be cured by the addition of sodium bicarbonate to the dietary. In 1916 Lewis and Karr published a paper on the constituents of the blood and the tissues of guinea-pigs fed on an exclusive oat diet. They found the urea content several times greater than normal, but that it fell to normal once more if cabbage or orange juice was given. From the standpoint of scurvy, this investigation is open to the criticism that the diet was too incomplete, and also, as the authors suggest, that the animals suffered from partial starvation and a lack of water.

In the following year Karr and Lewis published a paper on a different phase of this subject, and came to the following conclusions: “No changes in urinary elimination of phenols, nor in the degree of conjugation of the phenols, were observed, provided the factor of partial starvation was ruled out. This is believed to indicate that no increased bacterial action occurs in the intestine of scorbutic guinea-pigs despite the difficulty of evacuation of the fÆces.” These results are in harmony with the bacteriological study of Torrey and Hess, who found that there was no increase in the proteolytic flora of the intestine in infants or in guinea-pigs suffering from scurvy.

In 1917 Baumann and Howard published the only metabolism study which has been carried out on guinea-pigs suffering from scurvy, and they are of the opinion that this disorder has a profound effect on the mineral metabolism of this animal. The calcium was excreted in notably large amount; potassium was also lost, and to a greater extent than sodium; the only element which was consistently retained during the active stage as well as during the period of recovery, was magnesium. This study was followed shortly by one from the same laboratory, by Howard and Ingvaldsen, carried out on a monkey suffering from scurvy. It was inconclusive, not conforming to the experiments on the guinea-pigs; the authors state that the “changes in the mineral excretion of the monkey during the scorbutic period were not sufficiently significant to admit of easy interpretation.” “The marked loss of the various mineral substances encountered in experiments with man and guinea-pig was not observed in the present series.” It should be remembered, however, that the diets of the guinea-pigs and the monkeys were quite different, the former consisting mainly of oats, and the latter of condensed milk. It is quite possible that the basic diet may play a rÔle in the metabolism of this disease, although, as stated elsewhere, its effect cannot be noted clinically. Special attention should be paid to this factor in metabolic studies, in view of the widely-held opinion that the carbohydrates exert a potent influence in the development of beriberi.

The investigations of the nitrogen metabolism in man and in animals have been most unsatisfactory. The two on human beings—an infant and an adult—were negative; that on guinea-pig scurvy cannot be utilized on account of the restricted diet of oats, which contained insufficient nitrogen, whereas the one on the monkey showed some loss of nitrogen, which led the authors to suggest an increased nitrogenous catabolism in scurvy. This comprises the total data on this subject.

Summarizing the results of these few metabolic studies, it may be stated that they harmonize on one point only—the positive balance of calcium during the active stage of the disease. The investigation of Baumann and Howard on adult scurvy, of Lust and Klocman and of Moll on infantile scurvy, and of Howard and Ingvaldsen on the monkey, are all in agreement in this important conclusion.