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Studies in Deficiency Disease
By Sir Robert McCarrison
Oxford Medical Publications, 1921
CUSTOM has sanctioned the application of the term 'deficiency disease' to a group of maladies the chief causal factor of which is deficiency in the food of certain substances, named 'accessory food factors' by Gowland Hopkins, their discoverer. These substances are also spoken of as 'growth determinants', 'food hormones', 'exogenous hormones', 'advitants', or more commonly 'vitamines': the last term was applied to them by Casimir Funk (1910).
Neither the term 'deficiency disease' nor 'vitamine' is free from objection. The former is too restricted in its application, and should embrace disorders due to faulty and ill-balanced food deficient, either in quantity or quality, in any essential food requisite; the term is here used in this sense. 'Vitamine' is a misnomer, since there is no evidence that accessory food factors are amines. Following a suggestion made by Drummond (1920), that 'the final "e" of "vitamine" be dropped, so that the resulting word "Vitamin" may conform with the standard scheme of nomenclature adopted by the Chemical Society, which permits a neutral substance of undefined chemical composition to bear a name ending in "in"', accessory food factors will here be referred to as 'vitamins'; the word meaning 'substances essential to life'.
The object of my studies has been twofold: first, to find out how the animal body goes sick in consequence of deficient and ill-balanced food; and, secondly, to deduce therefrom what forms of sickness in the human subject may reasonably be attributed to, or connected in their origin with, such foods. It was recognized early in the course of these studies that deficient foods are in practice usually ill-balanced foods, and that the effects of avitaminosis are bound up with maladjustments both in quality and quantity of other essential requisites of the food. The method of investigation adopted was, therefore, to study the effects of vitamin-deficiency in association with other food faults which may accompany it.
It is rare that the food of human beings is totally devoid of any one vitamin; it is more usual for the deficiency to be partial, and for more than one vitamin to be partially deficient; it is more usual still for partial deficiency of vitamins to be associated with deficiency of suitable protein and inorganic salts and with an excessive richness of the food in carbohydrates. Consequently, the manifestations of disease resulting from the faulty food are compounded of the several effects of varying degrees of avitaminosis on the one hand, and of ill-balance of the food on the other.
Nor is this all, for pathogenic organisms present in the body, during the period of its subjection to the faulty food, contribute their share to the general morbid result. For instance, a diet deficient in vitamins and disproportionately rich in starch leads to depression of digestive and gastro-intestinal function. If, then, these organs are exposed at the same time to the action of pathogenic micro-organisms, their depression, which is at first functional, may become accentuated or fixed by organic changes due to the pathogenic agent. Further, under conditions of food deficiency, the presence in the bowel -- let us say -- of such agents may determine the character of the morbid states initiated by the food deficiency, and even impart to them endemic or epidemic characters. In these circumstances the etiological significance of the underlying food defects, which have permitted the unhampered action of the pathogenic agent, may be obscured.
Experiences illustrating these points are given in succeeding pages, but it can not be too strongly emphasized that many of the infectious scourges to which human beings are subject -- such, for example, as infantile diarrhoea and tuberculosis -- require consideration as much from this point of view as from that of the pathogenic organism to which they are due.
Other factors also, such as age, sex, individual idiosyncrasy, rate of metabolism, fatigue, cold, insanitary surroundings, overcrowding, the varying susceptibilities of different individuals, of different organs and of the same organs in different individuals, all play a determining part in the production of the morbid result of food deficiency.
So it is that in practice the manifestations of deficiency disease are influenced by a number of factors apart from the actual food-fault. It may be expected, therefore, that wide variations in the incidence, the time of onset, and the character of the symptoms will occur in human beings in whom the dietetic fault has been to all appearances the same.
My investigations have so far been concerned with this wider aspect of food deficiency. For I have thought it well to make a general survey of this largely unexplored territory of disease before attempting more detailed studies. Indeed, however important it is to be in a position to compare the effects of different food deficiencies in order to learn what is peculiar to any one, it is, in the present state of knowledge, of still greater importance to be aware of the extent and variety of the morbid change to which food deficiency in general may give rise, since this knowledge can at once be applied in practice. For whether these changes are the result of a single deficiency or of several, they are amenable to the same remedy: the provision of a well-balanced diet of good biological value and rich in vitamins of every class.
It is to this variety of morbid change that I desire to draw attention, since it seems to me to impart to the term 'deficiency disease' a wider significance than has been attached to it hitherto. It is a curious fact that the nomenclature of vitamins has been responsible, in considerable measure, for the narrowness of outlook with regard to diseases which are either favoured in their origin or initiated by an insufficient supply of these substances. We speak, for instance, of 'anti-neuritic' or 'anti-beri-beri' vitamin, thus directing attention to one system of the body and to one disease syndrome while ignoring others. The effects on the nervous system of a dietary deficient in anti-neuritic vitamin and disproportionately rich in starch, as observed in animals, have thus often been emphasized to the almost complete exclusion of other equally important, if less prominent, symptoms.
Long before nervous symptoms supervene, others, such as loss of appetite, impaired digestion, diarrhoea, colitis, unhealthy skin, low temperature, slow respiration, cardio-vascular depression, progressive anaemia, and asthenia result from the deficient and ill-balanced food. Do not these form a disease syndrome which is, in children especially, as familiar as its cause is unrecognized? It is to my mind with these earlier evidences of disease -- with these beginnings of morbidity -- that we as physicians are mainly concerned in practice.
It will be shown in the course of this book that such evidences of disease as those I have just recounted manifest themselves as certainly when partial deficiency is protracted over long periods as when more extreme deficiency is experienced over shorter periods. It is no doubt of great importance to be aware that food deficient in certain vitamins will ultimately cause nervous symptoms of a definite order. But since these are end-results, it is of still greater importance to realize that the same faulty food will give rise more early to gastrointestinal disturbance and other forms of vague ill health, and that these, like the nervous symptoms, can be prevented by supplying the necessary vitamins and adjusting the balance of the food.
Another matter of importance concerns us here: it is often stated that vitamins are so widely distributed amongst naturally occurring foodstuffs that the variety of foods consumed by European peoples -- in times of peace -- protects them from risk of any deficiency in these essential substances. If vitamins be considered solely from the point of view of the grosser manifestations of disease -- beri-beri, keratomalacia, scurvy, etc. -- to which their want gives rise, then this statement is to a great extent true.
But is it wholly true? Is not scurvy a common disorder of infants, and is it always recognized as such (Comby, 1918)? Is rickets rare? Are the forms of peripheral neuritis of undetermined cause so uncommon that without their study the food factor can be excluded as a possible cause of some of them? May it not be that, because we do not seek for alimentary neuritis, we do not find it? Pellagra has seemed to spread rapidly in America since 1902 (Roberts, 1920). But is this due to comparatively sudden alterations in the dietetic habits of the people, or to more accurate diagnosis and the recognition of minor manifestations of this malady consequent on increasing knowledge of the nutritional factor in its production? Is this disease, in its varying manifestations, as uncommon in the British Isles as is generally assumed? We know nothing of its true incidence, since the health of the people has not been considered in regard to it. But, apart from the incompleteness of knowledge as to the prevalence of the grosser evidences of deficiency disease in this country, are there no lesser manifestations due to the supply of vitamins and of suitable protein and salts in quantities insufficient for the needs of the body?
The statement above referred to might be true, also, were it a fact that Europeans invariably used naturally occurring foodstuffs in quantities sufficient for their needs. But do they? Is it not common knowledge that, disregarding nature's plan, the modern tendency is to rear infants artificially on boiled or pasteurized milk and proprietary foods, which are all of them inferior to mother's milk in substances essential to the well-being of the child; inferior not only in vitamins, but in thyroid derivatives and other essentials?
Again, is not cow's milk -- an important dietary constituent for young and old alike -- gradually becoming a luxury reserved for the few? Vegetable margarines are replacing butter even among the richer classes. Fresh fruit is a comparative rarity, even on the tables of the rich. Green vegetables are scanty, and such as there are are often cooked to the point of almost complete extraction of their vitamin-content and salts. White bread has largely replaced wholemeal bread, and it is notorious that bread form's a high proportion of the dietaries of persons of limited means.
It is notable that, despite the food restrictions imposed upon the people of Belgium during the late war (1914-18), the infant mortality and infantile diarrhoea decreased greatly -- a circumstance which was due to the organized propaganda encouraging mothers to nurse their infants, and to the establishment of national canteens which provided prospective mothers from the fifth month of pregnancy onwards with eggs, meat, milk, and vegetables (Demoor and Slosse, 1920).
Again, fresh eggs are so expensive as to debar the struggling masses from their use. Meat is at best but poor in vitamins, and its value in these essentials is not enhanced by freezing and thawing. Sugar is consumed in quantities unheard of a century ago, and sugar is devoid of vitamins which the cane juice originally contained (Osborne, 1920). The use of stale foods, involving the introduction of factors incidental to oxidation and putrefaction, is the rule, that of fresh foods the exception.
Can it, then, truly be said that the variety of natural foodstuffs consumed by Europeans protects them from any deficiency of vitamins? My own clinical experience justifies no such belief; rather does it point in the contrary direction. Nor does it appear to be the experience of the compiler of the 38th Report of the Medical Research Council (1919), who writes: 'From a consideration of dietaries consumed by the poorer classes in the towns of this country, one is led to suggest that no inconsiderable proportion of the population is existing on a food supply more or less deficient in fat-soluble factor' -- deficient, that is to say, in a vitamin one of whose cardinal functions is to maintain the natural resistance of the subject against infections. Neither is it the experience of Osborne (1920), who asserts that a large part of the food eaten by civilized people has been deprived of vitamin B by 'improvements' in manufacture; nor of Hess (1920), who emphasizes that latent and sub-acute forms of scurvy are common disorders of infancy.
But the frequency with which deficient and ill-balanced foods are used is most apparent when the dietetic habits of persons in subnormal health are considered. It will surprise those who study them to find how many there are, of capricious appetite, who habitually make use of foods sometimes deficient in calories -- for it is not the food presented to the subject that counts, but the food eaten and assimilated -- and often dangerously deficient in one or more vitamins, in protein of good biological value, and disproportionately rich in starch or sugar or fats, or in all three. Infants fed on many of the proprietary foods in common use come within the category of the deficiently-fed, unless deficiencies are made good. The food of young children is commonly low in vitamin-content, in salts, and suitable protein, while it is frequently disproportionately rich in starch and sugar -- a circumstance which enhances the danger of vitamin-deficiency. It may, indeed, be accepted as an axiom that the vitamin-value of a child's food is reduced in proportion to its excessive richness in carbohydrates.
But the ranks of the deficiently-fed do not include only infants and young children; they include also those whose food is composed mainly of white bread, margarine, tea, sugar and jam, with a minimum of meat, milk, eggs, and fresh vegetables. Even amongst those whose diet is more perfectly balanced, the commoner articles of food, as they are prepared for the table, are so low in vitamin-value that, unless they are enriched with a sufficiency of natural foods in the raw state, they are prone to cause ill health, and especially gastro-intestinal ill health. Such is my experience in India, where this European patient 'cannot digest vegetables or fruit', and never touches them 'as they carry infection', or that one 'suffers so from indigestion' that he or she lives chiefly on custards and milk-puddings; where milk is, of necessity, boiled and reboiled until as a carrier of vitamins it is almost useless; where meat is made tender by the simple device of boiling it first and roasting it afterwards; where every third or fourth European child has mucous disease, the direct outcome of bad feeding. So it is that the forms of food which such as these so commonly adopt are those most calculated to promote the very disorder from which they seek relief.
Access to abundance of food does not necessarily protect from the effect of food deficiency, since a number of factors -- prejudice, penury, ignorance, habit -- often prevent the proper use and choice of health-giving foods. Who in the ranks of practising physicians is not familiar, among the well-to-do classes, with the spoilt child of pale, pasty complexion and unhealthy appetite, of sluggish bowel, and often with mucous stools or enuresis, who, deprived of the wholesome ingredients of a well-balanced natural food, craves for sweetmeats, chocolates, pastries and other dainties as devoid of natural health-giving properties as their excessive use is common? Constantly one encounters the anxious mother of the 'highly-strung', 'nervous' child 'of delicate digestion', whose ignorance of essential principles of feeding is only excelled by her desire to do what is best for her offspring; who, guided by the child's preferences, supplies the means to convert it into a static, constipated, unhealthy-skinned adolescent, equipped with digestive and endocrine systems wholly unfitted to sustain the continued exercise of healthy function. Here it is that overfeeding joins with underfeeding and vitamin-insufficiency in swelling the C3 ranks of the nation.
Or, again, who is not familiar with the overworked anaemic girl, static and with visceroptosis, acne or seborrhoea, and oftentimes with vague psychoses, who ekes out a paltry wage for teaching, sewing, or selling, satisfying the cravings of her tissues principally with white bread, margarine, and tea? Or with the languid lady, devoid of healthful occupation, who, living in the midst of plenty, deprives herself, for some imaginary reason, of substances essential to her well-being? Or with the harassed mother of children, oppressed with the constant struggle to make ends meet, stinting herself that others may not want, exhausted by childbearing and suckling, worry, and too little of the right food? What wonder that such a woman is dyspeptic, and that 'every bite' she eats 'turns on her stomach'. Some there are, living in luxury, whom ignorance or fancy debars from choosing their food aright; others for whom poverty combines with ignorance to place an impassable barrier in the way of discriminating choice. It is for us so to instruct ourselves that we may instruct such as these, and use our newer knowledge to the end that customs and prejudices may be broken and a more adequate dietary secured for those under our care. I do not doubt that, if the practice I now follow of estimating the vitamin-value and qualitative balance of the food in every case that comes before me is followed by others, they will be impressed as I am with the vast importance of the food factor in the causation of disease.
In this connection reference may be made to the experiences of the Danes during the late war, as narrated by Hindhede (1920). When, as was the lot of other countries, the food supply of Denmark had to be conserved, and rationing was strict, it was considered that to feed cattle and swine with cereals and potatoes that might be used for human consumption was wasteful, since it meant a loss of approximately 80 per cent in the nutritional value of the foods as compared with the yield in the flesh of animals. For this reason the potatoes and grain were reserved for the use of the people, and the stock of cattle and swine was reduced. The cereals and potatoes were taken 'from the distillers, so that they could not make brandy, and one-half of the cereals from the brewers, so that the beer output was reduced one-half.' The people received a sufficiency of potatoes, whole rye bread -- containing wheat bran and 24 per cent of barleymeal -- barley porridge, grains, milk, abundance of green vegetables, and some butter.
In consequence of this enforced alteration in the dietetic habits of the Danish people, the death-rate dropped as much as 34 per cent, being as low as 10.4 per cent when the regime had been in force for one year. Hindhede, therefore, concludes that 'the principal cause of death lies in food and drink'; and few will be disposed to doubt the justice of his contention in the face of an experiment so unequivocal.
My own experience provides an example of a race, unsurpassed in perfection of physique and in freedom from disease in general, whose sole food consists to this day of grains, vegetables, and fruits, with a certain amount of milk and butter, and meat only on feast days. I refer to the people of the State of Hunza, situated in the extreme northernmost point of India. So limited is the land available for cultivation that they can keep little livestock other than goats, which browse on the hills, while the food supply is so restricted that the people, as a rule, do not keep dogs. They have, in addition to grains -- wheat, barley, and maize -- an abundant crop of apricots. These they dry in the sun and use very largely in their food.
Amongst these people the span of life is extraordinarily long; and such service as I was able to render them during some seven years spent in their midst was confined chiefly to the treatment of accidental lesions, the removal of senile cataract, plastic operations for granular eyelids, or the treatment of maladies wholly unconnected with food supply. Appendicitis, so common in Europe, was unknown. When the severe nature of the winter in that part of the Himalayas is considered, and the fact that their housing accommodation and conservancy arrangements are of the most primitive, it becomes obvious that the enforced restriction to the unsophisticated foodstuffs of nature is compatible with long life, continued vigour, and perfect physique.
Although no statistics are available in this country as to the precise influence of malnutrition in contributing to the low standard of physique revealed during the later years of the war, there can be no doubt that the food factor is connected with it. In America, during the year 1917-18, Manny (1918) estimated that about 30 per cent of the schoolchildren were suffering from malnutrition. This condition was not always limited to the poor, but was found to a certain extent among all classes. Chapin (1920) remarks with regard to it that 'the malnutrition was due to a failure in the proper selection and preparation of food materials in addition to poverty'.
With increasing knowledge of nutritional problems, it has become apparent that our dietetic habits need remodelling, and that education of the people as to what to eat and why they eat it is urgently necessary. It is clear that green vegetables, milk and eggs should form a far higher proportion of the food of the nation than is now customary. So far from curtailing the beneficent scheme whereby portions of land were made available to town-dwellers during the war for cultivation by allotment-holders, this scheme should be extended and facilities given to allotment-holders for the keeping of fowls. Municipalities and other public bodies should concentrate on the provision of an abundance of milk, eggs, and vegetables, for there is no measure that could be devised for improving the health and well-being of the people at the present time that surpasses this either in excellence or in urgency.
The results revealed in the course of these studies provide the pathological basis for attaching to food deficiencies a prominent etiological significance in regard to that great mass of ill-defined gastro-intestinal disorder and vague ill-health which throngs clinics at the present day, and concerning which we have hitherto known little or nothing.
It is necessary to emphasize that the problems of nutrition must not be viewed from a too 'vitaminic' outlook. Vitamins have their place in nutrition; it is that of one link in a chain of essential substances requisite for the harmonious regulation of the chemical processes of healthy cellular action.