AuoG r3, 19211 THE PHARMACOLOGICAL VALUE OF COD-LIVER OIL. r Tax Dam - 245' and from those wljich lhad remained neutral. She Yolung animals die fairly rapidly on a diet deprived-of looked to chlild welfare. work to raise a bulwark of vitamins, and tlie addition of vitamins in small quantities goocl feeling wlhich slhould be sufficient to resist national to suclh a diet enables the animals to grow normally, and animosities. MIle. FERRIERE, of tile Union Internationale in this way the existence of vitamins can be demonstrated de Secours aux Eufants, whvlichl is the central organiza- as certainly as can the existence of an antitoxin. 'tion in Geneva of all the " Save the clhildren" funds The demonstration of a vitamin involves, hlowever, pro- in 'tle different counitries, said tlhat this body was longed feeding experiments with very careful controls. now sliaping for its6lf a more permanent structure, Such experiments are very difficult to perform; it is withi the object of maintaining interest in child welfare difficult to obtain a diet which is free from vitamins and in every country. Mme. DUCHtNE, of the French Com- is non-toxic and adequate in all other respects. Moreover, mittee of tllis organization, spoke on similar lines, and tlle experiments are always liable to be upset by epidemics. nobly said tlhat if there was (langer of pauperism in the Finally, the reaction of different animals to vitamin-lack countries which received assistance, tllis was more tllan varies enormously; animals of different species react in counterbalanced bv the gain in education to the countries very different manners; young animals are far more whichi gave it. Fraulein HEYMANN, of Germany, saidl that affected by vitamin-lack than adults; and, finally, animals relief work in lher country also had assisted the inter- of the same species and age fed upon the same diet often national ideal, and slhe thought that the clhildren who had show considerable individual differences. Work upon benefited from tlhis real Samaritanism would later on vitamins is therefore bound to be extremely slow and become apostles of humanity and peace. Frau HERZFELDER, laborious; the number of possible errors is extremely large, of Austria., said that the children's protection societies in and it is therefore not surprising that many questions that country lhad always had an international standpoint, concerning vitamins are still matters of controversy. wllich the war lhad not entirely effaced. Miss JANE Three vitamins are known, namely: (1) the fat-soluble ADDAMS, President of the Women's Inteinational League vitamin A, (2) the antineuritic water-soluble vitamin B, of Peace and Freed6m, urged tlle setting up of an inter- and (3) the antiscorbutic vitamin C. These three vitamins national standard of cllild welfare wlichl should ma.ke it have different distributions, different chemical properties, impossible for childreni to starve on one side of a frontier and different plhysiological actions. It is possible, and wlhen there was bread to spare on the other. Other even probable, that other similar factors exist, which also speakers to the same, effect were Danish and Swedish have the two important characteristics of being necessary ladies. Miss ALICE FITZGERALD, head of the department in minutc amounts for animal nutrition, and of being of nursing of the Leaaue of Red Cross Societies, made the easily destroyed. interesting statement that under the auspices of the None of the vitamins have been isolated, and tlherefore League eighlteen nurses from as miiany different countries it is not possible to say for certain that any two deficiency had been sent to London for post-graduate public health diseases are produced by the lack of the same substance; training. Tlhe lhonorary president of this successful con- all that it is possible to prove is tllat two diseases are ference was Frau Marianne Hainisch, a famous Austrian caused by the lack of factors wlhich have an identical social worker, and mother of the President of the Austrian distribution. The statement that any disease is caused republic. by the lack of any particular vitamin only means, there- fore, that it is caused by the lack of a factor whic'h has the THE PHARMACOLOGICAL VALUE OF same distribution as that vitamin. Animals are unable to synthesize the vitamin A con- COD-LIVER OIL. tained in their fats; they obtain supplies from vegetable CLINNICAL observers have always been positive of the foods and store tlle vitamin in their fat. Adult animals tlherapeutic value of cod-liver oil, but have been unable to contain a large reserve of the vitamin in their fat, and can give any explanation of its superiority to other oils. live on these supplies for prolonged periods; and therefore It was believed formerly that the special value of cod- it is not easy to produce any very obvious effects upon liver oil depended upon its high content of unsaturated fatty adult animals by deprivation of vitamin A. Young growing acids, and on this assuLiption substitutes for cod-liver oil animals require much larger amounts of this vitamin and have-been prepared from vegetable oils, such as.poppy seed have smaller reserves, and in these deficiency of vitamin A oil or soya oil, wlhich contained a large amount of un- produces effects in a few weeks or months. saturated fatty acids.- Substitutes for cod-liver oil have Vitamin A is contained in the green leaves and tlhe even been prepared from olive oil. growing parts of plants, and it is from tlhese that the Cod-liver oil suffers from the disadvantages of lhaving animal world ultimately obtains its supply of vitamins. an unpleasant taste, and of readily becoming rancid, and Vitamin A is stored by animals in their fats, and occurs manufacturers have devoted their energies to producing in large quantities in milk fat and in egg yolk. The fats highly refined preparations of the oil so as to eliminate aind 'oils of fisshes and of whales also contain an exception- these unpleasant qualities. Doubt has frequently been ex- ally' large amount of this vitamin. pressed, however, whether the purified forms of the oil All of the vitamin A present in milk is contained in the were as efficacious in therapeutics as the older and cruder milk fat; there is therefore very little in skimmed milk; preparations. the vitamin A content of milk depends entirely upon the Recent research upon vitamins has thrown an entirely diet of the animal, and vitamin A may be almost com- new light upon the action of cod-liver oil, for it has been pletely absent from the milk of stall-fed cows. Similarly, shown tllat crude cod-liver oil is peculiar in containing a it may be absent from the milk of women fed on a diet free far larger amount of the fat-soluble vitamin A than any from vitamins. Vitamin A is a more stable substance than otlher foodstuff. At the present time it is difficult to form- the antiscorbutic vitamin C, but it is fairly readily destroyed a correct estimate of tlle importance of vitamin deficiency by heating in the presence of oxygen. Hopkins' and in the production of disease; there' is fairlv conclusive others have shiown tlhat butter can be rendered vitamin- evidence that such deficiency causes scurvy, infantile free by heating to 1200 C. for four hours, provided that a scurvy and beri-beri, and there is a very strong probability current of air is passed through it. that it is tlle cllief cause of rickets; and, finally, thoere The vitamin content of milk is reduced by pasteurization is the possibility that vitamiin deficiency may produce a- or by boiling, and both condensed and dried milk contain host of otber chronic disorders ranging from dental caries smaller amounts of the vitamin than does fresh milk. to amer4orrhoea anmd reduced resistance to infections. Lard as. ordinarily manufactured contains no vitamin, and ThJ degree to which vitamin deficiency affects the all of the vitamins of wlhale oil are destroyed by hydro- health of the community is at present uncertain, and it is genation; vegetable oils and fats contain little or none of very necessary to steer a course between the two extremes the vitamin. of an uncritikal enthusiasm which attributes every dis- The absence of vitamin A from' the diet can be slhown to order to lack of vitamins, and an equally irrational pioduce in animals the following effects:2 scepticism -which denies any importance to vitamins 1. Lack of growth in young rats (Hopkins, Drummond, and because they are a new discovery, and because their others). importance is exaggerated by others. Vitamins are not 2. Rickets in puppies (Mellanby). exceptionally mysterious substances; it is true that they '3; Disorders of de'ntitio'n. in pnuppies (MI. Mellanby). have not been isolated, and that are readily destroyed 4. Diminished resistance to infections. they 5. Failure of the nutrition of the cornea resultingin xeroph- by chemical treatment, but these properties they share .thalmia"..-.' with bicterial toxins and' a titoxin'. 6. Tenldencyo to ocdema. 246 AUG. T3, 192I TIHE PHARMACOLOGICAL VALUE OF COD-LIVER OIL.

McCarrison, has carried out extensive observations on Vitamin A is widely distributed in nature and can be the effects of lack of vitamins in pigeons and in monkevys; easily preserved in fats, but various causes have led to its most of tl]ese experiments were conducted witlh diets gradual elimination from the food of the people. deficient in more tllan one vitanmin; tlhev provcd that Tllis vitamin is contained in wlhole-meal bread and in vitamin lack induces a wlhole series of gastro-intestinal buitter, btut is absent from wlhite bread and margarine. disorders, includina diarrhoea, dysentery, an(d gastric ulcer. Thie whole milli of grass-fed cows contains large amounts, Vitam-in lacli also caused profound derangemnent of the but less is contailned in the i-ilk of stall-fed cows. '1'lio functions of tlle endocrine organs. McCarrison's resulis quantity is dimiiinislhed by boiling; it occurs in diminislhed slhowed that lack of vitamin A was responsible in monkeys quantities in condenised and dried milk, and slimmed muill anid pigeons for excessive production of adrenaline, and that contains very little. Vitam:in A occurs in freslh meat, hut in pigeons lack of this vitamin produced oedema. tinned meat contains little or none. The following diseases are all believed to be related to A diet of white bread, marwgaline, jam, and salt fislh or lack of vitamin A in rnan: rick-ets, osteonmalacia, kerato- tinned meat is tlherefore almLost free fromvitamin. The mnalacia, and war oedemDa. chief sources of vitamin A in a normlal diet are green The etiology of rickets is a question of enormous socio- veaetables, eggs, butter, millk, and mleat fat. logical inmportance, and controversy lhas arisen concerning The effects produced upon adults by deprivation of Mellanby's conclusion that rickets is a deficiency disease vitamin A are unicertain; the clhief effects or deficiency of caused by deficiency in a factor wlhichl lhas the same this vitanin are observed in babies and children, but they distribution as vitamin A. can be noted also in women during pregnancy and lactation, MIellanby2 found that young puppies fed on a diet which Deficiency of vitamin A is the probable cause of ricklets contained no vitamin A but was sufficient in every otlher and osteomalacia, and is very possibly an important catIse respect developed typical rickets after about six weeks. of dental caries and of impaired growtlh. The recruitiDg The bones slhowed typical signs of rickets on inspectioni, results in the war suggested that the urban population of and also on radiological and histological examination. The England is undergoing physical deaeneration, and if tlhis addition of 10 c.cru. of cod-liver oil to the above diet view is accepted, an inmportant contributory cause may be prevented the occurrence of rickets, and cured rickets in found in vitamin deficienicy. cases in which it lbad already been establislhed. The cliniical results recorded witlh cod-liver oil slhow that Thle results of Mellanby were very definite and positive, it must be regarded as an extremely inlportant druLa, but but lhe noted many possible sources of error. Rickets sinice the wlhole importance of the oil is due to its vitamin could be produced only in puLppies under four nmontlhs, and content, only those preparations of the oil wlhiclh contain could be produced muclh more rapidly in rapidly growing large quantities of vitamin can be considered as tllera- tlhan in slowly growing animals; the addition of large peutically active. amouints of carbohydrates to the diet increased tlle liability Hitlherto the efforts of the manufacturers of cod-liver oil to rickets, and the addition of large amounts of meat seem to have been directed to tlle preparation of as decreased the tendency to rickets. purified anid tasteless a product as possible, and no regard Paton3 denies that rickets is a deficiency disease and lhas been paid to the vitamin content. attributes it to bad lhousing, and lhas obtained negative Zilwa and AIiura found that crude cod-liver oil con. results with feeding experiments. tained no less than 250 times as muclh vitamiiin A as butter, The possible sources of error in experiments upon buit that the refined oil contained mluclh less vitamin, deficient diets are so numuerous that it would appear proper althouhll its activity was superior to that of butter. Tlhc to attaclh more wveiglht to positive than to negative results. vitamin of cod-liver oil is fortunately fairly resistant to Tle tragic -experience of' Central Europe furnislhes a clhem-ical treatmnent, alnd a degree of lheatilng anid oxidatioll strikinig proof that rickets is a deficiency disease, for sufficient to destroy all the vitamnin of butter does not Dalyell states that 100 per cent. of infants of nine m-onths deprive c.d-liver oil of all its vitamin. in Vienna have rickets, and since the climate and housing Tlle estimation of the tlherapeutic efficielncy of cod-liver conditions of Vienna are the same as ini 1914 tllis result oil is at present a very difficult matter, for the qualitative must be due to malnutrition; moreover, since a large pro- demoonstration of vitanmin A takes over tlhree weelis, and portion of the Viennese clhildren are breast-fed the rickets the quantitative estimation takes several montlhs. must be due to mDaterlnal malnutrition. Two samiiples of cod-liver oil are now before us. Both Striking beneficial results have been obtained from the. are excellent reparations in that tlhey are of a good colour, administration of cod-liver oil in all of the diseases of pleasant taste, and give all the correct reactions of attributed to lack of vitamin A. cod-liver oil, but unfortunately these facts give no iniforma- 1. Deficienzt Grow&th.-Tle addition of cod-liver oil to the tion about the all-important ouestion of vitanmin content. diet of the mother in breast-fed infants in Vienna produced The mianufacturers of the Gadus cod-liver oil claimitlat- a most striking beneficial effect upon the rate of growtlh the purity of their compound is due to tlhe fact that the. (Dalyell).4 livers are treated on the same dav that the cod is cauglt, 2. Rickets.-Hess and linger2 found that 90 per cent. of. and point Qut that Xas tlle fishing is.conducted in tlle cold tlle negro clhildren in a New York district developed rickets, weatlier any clhance of putrefaction is prevented. Suclir but that ouit of 32 infants given 54 oz. of cod-liver oil in precautions are of obvious advantage, since they tend to six montlhs only 2 developed ricliets. Hess 5 believes that reduce the amount of treatment necessary to produce a rickets is primarily a dietetic disorder, anid admits that a palatable oil. lack of vitamin A plays a part in its pathogenesis, but le M1essrs. Allen and Hanburys have also seint us a believes that otlher factors arc involved and that the salt specimen of cod-liver oil, of. pale colour and very slighlt content of the diet is of importance; lhe is, however, con- odour and taste. It is, they say, prepared from fresh, vinced tllat cod-liver oil given in full doses, and not carefully selected cod livers, witlh tlle minimum of: rendereed impotent by excessive refining, is almnost a exposure to oxidation, whiclh they recognize tends to specific in the treatment of rickets. diminish tlhe amount of vitamin A. 3_ Keratoniialacia.- Blocll slhowed that this disease, Cod-liver oil, may be crude and unpalatable owing to wlhiclh occurred -in Danislh clhildren durina the war, was one of two causes: the oil muay have undergone no refinirng cured by cod-liver oil, and similar results were obtained in process, and therefore contains the full vitamin conitent; Vienna. on the other hand, it may be unpalatable because excessive 4. Oedemma.-Ilenzies 6 observed lhunger oedenla in Poor putrefaction of the livers has been allowed to occur bdf-ore Law institutions in England in the winter of 1917-1918 extraction, so that the resulting oil is so impure that it anid found tllat it was cured by cod-liver oil. cannot be fully purified; suclh an oil will probably contain There.is a great amount of clinical evidence of the very no vitamins at all. This point is of somie importance, valuable action of cod-liver oil in all tlle above cases; in because it must not be assumed that the vitamin content none of them is a similar effect produced by vegetable fats, of an oil is necessarily indicated by its dark colour and and the only probable explanation is that the specific action high flavour. of cod-liver oil is du:e to its hiiglh content of vitamin A. Thle mlost strikiing results withl cod-liver oil hsave been RZFEREl;NCES. 1Hopkiins, BRITISH MIEDICAL. JOURNALX, 1920. ;, 147. 2 AJRC Rerorts, obtained inl thle starving populations of Cenltral Europe, but No. 38. Paton, Brit. JouriaX. of Expel-. Pat/i., ii, 75, 1921. i)lalyeli, thlere is strong evidence that lack of vitamuin A is an B3RITISHI MEDICALj JOURtNAL, 1920, i, 152. 5Hess, Jowin?. A4mter. Mcdz. important factor in producinlg disease in urban populations Assoc., 1921, 76, 693. 6 MTenzies, Lancet. 1920. i. 3t0. 7 Z,ilwva anld MIiura, la.ncet,1921, i,.323. 8McC&rrison: Studies i?l Deficiencyv Disease, under nlormaal conditions. Ljondon. 1921.