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DEFICIENCY OF ESSENTIAL FATTY ACIDS
576
Letters to the Editor DEFICIENCY OF ESSENTIAL FATTY ACIDS
SIR,—Dr. H. M. Sinclair’s engaging essay in your issue merits more detailed comment that I can this distance from my home laboratory. However, some notes may help your readers appraise the situation in a field unduly beset with conflicting claims and feverish competition. Besides solving the coronary heart-disease problem, Sinclair disposes of lung cancer and leukaemia for good measure; but these latter minor problems I shall leave to others. The central issue of Sinclair’s speculations is atherogenesis and the regulation of the concentration of cholesterol in the blood. His thesis is that our present plight in Britain, the United States, and other countries where coronary heart-disease is so alarmingly frequent, is due to dietary deficiency of the " essential " fatty acids-linoleic and arachidonic-largely ascribable to the evils of hydrogenation and deficiencies of vitamin E and pyridoxine. While I join in deploring the increasing use of hydrogenation and many other methods of improving" our natural foods, I think it can be shown that even in the United States hydrogenated fats are only a small fraction of the total fat consumption, which provides, moreover, a per-capita intake of linoleic acid at least as high as that of many populations, as in Japan, who suffer relatively little coronary heart-disease. The idea that a deficiency of essential fatty acids (E.F.A.) in the diet may be related to atherogenesis is not new ; it was suggested a dozen years ago by Dr. George Burr, then at the University of Minnesota, and it has been discussed in the United States for several years, notably by another Minnesotan, Dr. Ralph Holman of our Hormel Institute. Last year Dr. B. Bronte-Stewart developed this thesis in South Africa and recently he discussed the question in England. It is well known that animals fed diets extremely deficient in E.F.A.—and such diets are not easy to prepare-often have increased amounts of cholesterol in the liver, but I know of no demonstration of the production of atheroma in these experiments. Moreover, I am unaware of any evidence that a low intake of E.F.A. in the human diet will, by itself, produce either hypercholesteræmia or atherosclerosis. Indeed, even the possibility of E.F.A. deficiency in adults is debated vigorously, and there is not unanimity of opinion about the situation among infants, where the best case for the essentiality of E.F.A. has been made-by another former Minnesotan, Dr. Arild Hansen. It is easy to show, as we have been doing for half a dozen years in controlled experiments on man, that merely changing the proportion of calories supplied by ordinary food fats (not hydrogenated) in modern Westerntype diets promptly results in corresponding changes in the serum-cholesterol concentration, even when the intake of calories, cholesterol, proteins, and vitamins is constant. In such experiments, each lasting from four to six months and involving twenty or more men, isoca,loric substitution of carbohydrates (sugar, potatoes, and bread) for a large part of the dietary fats involves a sharp reduction in the intake of E.F.A.—and the serum-cholesterol falls and stays down so long as the low-fat diet is continued. But when the reverse substitution is made, using lard, butterfat, cottonseed oil, olive oil, coconut oil, or mixed food fats, the serumcholesterol concentration rises. Supplements of vitamin E or of protein (casein) do not alter the result. These several food fats do not produce quantitatively the same -degree of elevation of the serum-cholesterol, and a few fats, which do not bulk large in our diets, may have no cholesterogenic effect. We have observed this as well as others, including Kinsell in California, of
April 7 supply at
"
yet
Ahrens in New York, and, recently, Bronte-Stewart in South Africa. But the point for the present discussion is that with most of the common food fats an increase in the fat consumption produces an elevation of the serum-cholesterol at the same time the intake of E.F.A. is being increased. Now it is conceivable that E.F.A. may have no cholesterogenic effect and that large amounts of E.F.A. may counter some of the cholesterogenic tendency of fats containing no E.F.A. But even if this were true it seems unreasonable to ascribe to a, deficiency " of E.F.A. the result of increasing the total intake of fats and of E.F.A. (for none of our ordinary food fats are devoid of E.F.A.). I believe it is difficult to ignore the impressive body of evidence leading to the conclusion that our present prevalence of hypercholesteraemia and coronary heart-disease would be much altered if we simply reduced the general level of fat in the diet, and that we got into our present plight, at least in part, because we have adopted an increasingly fat-rich diet. We are rapidly approaching the time when we must ask seriously what is to be done about it. Dr. Sinclair’s argument obviously suggests that we solve the coronary problem, without retreating from our high-fat diet, by taking a daily swig of linoleic acid and a few vitamin pills. I wonder whether this is a responsible answer to a serious question. There are other difficulties with Sinclair’s thesis and the facts he adduces in its support. He indicates that Eskimos and ’’ some Norwegians " consume high-fat diets but escape atherosclerosis because they eat marine foods in a diet unsullied by the chemist. He forgets that recently1 he argued persuasively that Eskimos have long since ceased to eat high-fat diets. And he seems to be unaware that large amounts of hydrogenated whale oil are eaten in Norway, which is, nevertheless, not among the countries eating the largest amount of fats. (The latter are, more or less in order of decreasing fat as a percentage of total calories : U.S.A., Finland, Australia, New Zealand, Denmark, Canada.) In any case no-one knows what may be the freedom, if any, of the Eskimo from atherosclerosis ; it is known that coronary-heart disease is a serious problem in Norway. Sinclair makes a good deal of cholesterol esters as the villain in the piece. Two facts should give pause here. In the first place, pathologists tell us that the cholesterol esters, as a fraction of the total, are relatively low in newly formed atheroma and that the percentage of esters rises with the age of the lesion. And in the second place, the proportion of ester to free cholesterol in the serum is substantially the same in hypercholesteræmia as in normal or in coronary patients and in their clinically healthy controls. Further, the amount of cholesterol esters in the liver and in the skin may be interesting, but I do not know that anyone has suggested this as a measure of atherosclerosis. I feel strongly that a most important clue to the solution of the coronary problem is in the differing frequency of the disease in populations that differ in their modes of life. And I am pleased to learn that Dr. Sinclair is agreeing with me that the diet plays a most significant role in this. Consideration of the dietary fat and the role of cholesterol in the blood transport of this (as lipoprotein) seems to resolve the striking contrasts in the burden of coronary heart-disease we have observed in comparing Americans and some Europeans with southern Italians, Sardinians, African Bantu, and Japanese on their native diets. Climate is not the answer, and no more than a minor role can be given to the frequency of obesity in the several populations. If serum-cholesterol is the criterion, dietary fat far outweighs differences in physical activity as a causative factor, and we observe that there are plentv of physically inactive men in Italy and here in Japan but "
hypocholesteræmia,
1. Proc. nutr. Soc. 1953, 12, 69.
577
still coronary disease is relatively
uncommon in these there is no evidence that race is involved and a good deal of evidence that it is not, notably in comparisons between Negroes in Africa and in Chicago, in comparisons between people in the same region who differ in their economic circumstances (as found in our studies in Spain and in Italy), and in our current comparisons between Japanese in Hawaii and here in Kyushu. But in all of these situations attention to the total fat in the diet seems to bring an orderly relationship into focus.
populations. Finally,
such clear and simple relationship would Probably be found if the dietary predilections of the world’s populations for quantities and kinds of fats varied independently. I should not expect to find the same serum-cholesterol levels and frequencies of coronary heart-disease in two populations both getting 40% of their calories from fats but the one deriving this from corn oil and sesame-seed oil while the other got all their fats from coconut oil and lard. But this does not happen to be the way people consume fats. In a desperately poor land the people get very few fats of any kind. As their lot improves economically they increase their total fat consumption, and the fats they eat tend to be more and more the more expensive kinds-the fats that, incidentally, are associated with the foods most highly prized for their nutritional as well as their gustatory value. no
To
some
of us, at
least, it appears that this
response
prosperity can go too far. The problem has been complicated by the enterprise and ingenuity of food producers and technologists who provide a superabundance of all kinds of fats and then persuade *us to eat them. Are we now going to ask them, please, to put some more E.F.A. in their wares Perhaps with a modest increase in cost ?’?, This could be the shape of things to come. Continue, or increase, your high fat consumption to
but be sure you get a lot of corn oil, sesame-seed oil, fish oil, and the like and be careful to swallow it fresh and in the virgin liquid state ! Such considerations may seem inappropriate in a discussion of a problem that is basically chemical and pathological. But the coronary problem has already reached dimensions that cannot be confined in the otherworldly atmosphere of some academic retreats. In the meantime, it is clear that a great deal more research is needed on all aspects of the problem, including food economics and the psychology of food preferences. While this is in course it may be well to ponder whether a diet containing 40%of its calories as fats is really essential for human happiness and, if not, how may it best
be reduced. First Medical Clinic, Kyushu University Medical School, Fukuoka-shi, Japan.
ANCEL KEYS.
VOMITING SICKNESS IN JAMAICA
SiR,-There are two important points which might be added to your leading article (April 14). As far as I know, chemical analysis has not yet been published to indicate in what part of the ackee fruit the toxins are found. If they are only in the seed, then the population can continue to eat the arillus with impunity. Children who eat the seed in play, or tragically driven by hunger, must be more carefully supervised. The other point is quantitative : not only which part, but how much of which part, of the fruit is likely to produce a toxic effect. The full report of the work done in 1952-53 (excepting the chemical section) was published by the Government Printers, Kingston, Jamaica, in 1954, as a monograph on Vomiting Sickness in Jamaica. London School of Hygiene and Tropical Medicine, W.C.1.
CICELY D. WILLIAMS.
REVISION OF THE CURRICULUM
SIR,—The only positive contribution in the proposals of the Royal College of Physicians anent revision of the medical curriculum is the suggestion that the G.M.C. should cease to issue recommendations-in other words, abrogate its function as guide and supervisor of the training of medical students. Otherwise the report (of which extracts appeared in your issue of April 14) consists in the usual ponderous, pontifical pronouncements that the aim of medical education should be to give " a broad the acquisition of a scientific cultural background," attitude," " principles and outlines without the burden of fact," &c., &c. We have heard most of it before in the perennial bellyache about the medical curriculum which is a perpetual item on the agenda of committees of medical schools and Royal colleges and corporations, in fact of every conceivable body except those best suited to advise-namely, the general practitioner. No other training schemes-for lawyers, engineers, scientists, &c.-a,re subjected to so much interminable research." Quite obviously the present training of the medical student is unsatisfactory, uneconomic, and much of it wholly irrelevant to the work subsequently undertaken by the great proportion of medical graduates. Medicine is not a philosophy, nor is it a science. It is a skill, much of it still empirical; and, like training for any other skilled job, the education of the medical student should include, from an early stage, a concurrent and remunerated apprenticeship. The people want a doctor who knows his job-who can, for example, recognise scabies when he sees it and tell them how to treat it. They are not particularly concerned whether he can discourse on Scabies in Mediaeval Times or The Adaptive Mutations from which Evolved the Behaviour Pattern of Acartts scabiei. Would it be wrong to suspect that given freedom from G.M.C. recommendations a model " curriculum emanate from the would Royal College of Physicians, which even be prepared to send its representatives to the various medical schools to initiate the new era ? "
1,
"
might
Department of Anatomy, University of Glasgow.
GEORGE M. WYBURN.
SIR,—The very interesting report by the Royal College of Physicians, prompts me to ventilate an idea which might possibly be applicable as an experiment at one, say, of our " red brick " universities.
It
is, in effect, the introduction of
a
tutorial
system,
whereby each of the younger clinicians attached to the medical school would act as tutor to some five or six students for the whole of their undergraduate life. They would meet him perhaps for two one-hour sessions each week, on one occasion to discuss an essay he had set, and on the other for a general round-table conference. The value to the students would be obvious in bringing them from the first into personal contact with an active practitioner of their craft and would give them an initiation, particularly when they reached their clinical years, to the real as distinct from the textbook problems of medical work. The value to the tutor would hardly be less, since it would necessarily keep him up to date not only with other branches besides his own specialty but with his anatomical, physiological, and psychological knowledge. One of the dangers of the age of specialism is that, while knowledge in a particular field may become ever more detailed and exact, the specialist is liable to fall behind even the newly qualified graduate where the rest of the subject is concerned ; and my scheme would very effectively prevent this, since it would be useless to try and talk to a critical audience without an adequate familiarity with the matters under discussion. JOSEPH V. WALKER Darlington.
Medical Officer of Health.
Letters to the Editor DEFICIENCY OF ESSENTIAL FATTY ACIDS
SIR,—Dr. H. M. Sinclair’s engaging essay in your issue merits more detailed comment that I can this distance from my home laboratory. However, some notes may help your readers appraise the situation in a field unduly beset with conflicting claims and feverish competition. Besides solving the coronary heart-disease problem, Sinclair disposes of lung cancer and leukaemia for good measure; but these latter minor problems I shall leave to others. The central issue of Sinclair’s speculations is atherogenesis and the regulation of the concentration of cholesterol in the blood. His thesis is that our present plight in Britain, the United States, and other countries where coronary heart-disease is so alarmingly frequent, is due to dietary deficiency of the " essential " fatty acids-linoleic and arachidonic-largely ascribable to the evils of hydrogenation and deficiencies of vitamin E and pyridoxine. While I join in deploring the increasing use of hydrogenation and many other methods of improving" our natural foods, I think it can be shown that even in the United States hydrogenated fats are only a small fraction of the total fat consumption, which provides, moreover, a per-capita intake of linoleic acid at least as high as that of many populations, as in Japan, who suffer relatively little coronary heart-disease. The idea that a deficiency of essential fatty acids (E.F.A.) in the diet may be related to atherogenesis is not new ; it was suggested a dozen years ago by Dr. George Burr, then at the University of Minnesota, and it has been discussed in the United States for several years, notably by another Minnesotan, Dr. Ralph Holman of our Hormel Institute. Last year Dr. B. Bronte-Stewart developed this thesis in South Africa and recently he discussed the question in England. It is well known that animals fed diets extremely deficient in E.F.A.—and such diets are not easy to prepare-often have increased amounts of cholesterol in the liver, but I know of no demonstration of the production of atheroma in these experiments. Moreover, I am unaware of any evidence that a low intake of E.F.A. in the human diet will, by itself, produce either hypercholesteræmia or atherosclerosis. Indeed, even the possibility of E.F.A. deficiency in adults is debated vigorously, and there is not unanimity of opinion about the situation among infants, where the best case for the essentiality of E.F.A. has been made-by another former Minnesotan, Dr. Arild Hansen. It is easy to show, as we have been doing for half a dozen years in controlled experiments on man, that merely changing the proportion of calories supplied by ordinary food fats (not hydrogenated) in modern Westerntype diets promptly results in corresponding changes in the serum-cholesterol concentration, even when the intake of calories, cholesterol, proteins, and vitamins is constant. In such experiments, each lasting from four to six months and involving twenty or more men, isoca,loric substitution of carbohydrates (sugar, potatoes, and bread) for a large part of the dietary fats involves a sharp reduction in the intake of E.F.A.—and the serum-cholesterol falls and stays down so long as the low-fat diet is continued. But when the reverse substitution is made, using lard, butterfat, cottonseed oil, olive oil, coconut oil, or mixed food fats, the serumcholesterol concentration rises. Supplements of vitamin E or of protein (casein) do not alter the result. These several food fats do not produce quantitatively the same -degree of elevation of the serum-cholesterol, and a few fats, which do not bulk large in our diets, may have no cholesterogenic effect. We have observed this as well as others, including Kinsell in California, of
April 7 supply at
"
yet
Ahrens in New York, and, recently, Bronte-Stewart in South Africa. But the point for the present discussion is that with most of the common food fats an increase in the fat consumption produces an elevation of the serum-cholesterol at the same time the intake of E.F.A. is being increased. Now it is conceivable that E.F.A. may have no cholesterogenic effect and that large amounts of E.F.A. may counter some of the cholesterogenic tendency of fats containing no E.F.A. But even if this were true it seems unreasonable to ascribe to a, deficiency " of E.F.A. the result of increasing the total intake of fats and of E.F.A. (for none of our ordinary food fats are devoid of E.F.A.). I believe it is difficult to ignore the impressive body of evidence leading to the conclusion that our present prevalence of hypercholesteraemia and coronary heart-disease would be much altered if we simply reduced the general level of fat in the diet, and that we got into our present plight, at least in part, because we have adopted an increasingly fat-rich diet. We are rapidly approaching the time when we must ask seriously what is to be done about it. Dr. Sinclair’s argument obviously suggests that we solve the coronary problem, without retreating from our high-fat diet, by taking a daily swig of linoleic acid and a few vitamin pills. I wonder whether this is a responsible answer to a serious question. There are other difficulties with Sinclair’s thesis and the facts he adduces in its support. He indicates that Eskimos and ’’ some Norwegians " consume high-fat diets but escape atherosclerosis because they eat marine foods in a diet unsullied by the chemist. He forgets that recently1 he argued persuasively that Eskimos have long since ceased to eat high-fat diets. And he seems to be unaware that large amounts of hydrogenated whale oil are eaten in Norway, which is, nevertheless, not among the countries eating the largest amount of fats. (The latter are, more or less in order of decreasing fat as a percentage of total calories : U.S.A., Finland, Australia, New Zealand, Denmark, Canada.) In any case no-one knows what may be the freedom, if any, of the Eskimo from atherosclerosis ; it is known that coronary-heart disease is a serious problem in Norway. Sinclair makes a good deal of cholesterol esters as the villain in the piece. Two facts should give pause here. In the first place, pathologists tell us that the cholesterol esters, as a fraction of the total, are relatively low in newly formed atheroma and that the percentage of esters rises with the age of the lesion. And in the second place, the proportion of ester to free cholesterol in the serum is substantially the same in hypercholesteræmia as in normal or in coronary patients and in their clinically healthy controls. Further, the amount of cholesterol esters in the liver and in the skin may be interesting, but I do not know that anyone has suggested this as a measure of atherosclerosis. I feel strongly that a most important clue to the solution of the coronary problem is in the differing frequency of the disease in populations that differ in their modes of life. And I am pleased to learn that Dr. Sinclair is agreeing with me that the diet plays a most significant role in this. Consideration of the dietary fat and the role of cholesterol in the blood transport of this (as lipoprotein) seems to resolve the striking contrasts in the burden of coronary heart-disease we have observed in comparing Americans and some Europeans with southern Italians, Sardinians, African Bantu, and Japanese on their native diets. Climate is not the answer, and no more than a minor role can be given to the frequency of obesity in the several populations. If serum-cholesterol is the criterion, dietary fat far outweighs differences in physical activity as a causative factor, and we observe that there are plentv of physically inactive men in Italy and here in Japan but "
hypocholesteræmia,
1. Proc. nutr. Soc. 1953, 12, 69.
577
still coronary disease is relatively
uncommon in these there is no evidence that race is involved and a good deal of evidence that it is not, notably in comparisons between Negroes in Africa and in Chicago, in comparisons between people in the same region who differ in their economic circumstances (as found in our studies in Spain and in Italy), and in our current comparisons between Japanese in Hawaii and here in Kyushu. But in all of these situations attention to the total fat in the diet seems to bring an orderly relationship into focus.
populations. Finally,
such clear and simple relationship would Probably be found if the dietary predilections of the world’s populations for quantities and kinds of fats varied independently. I should not expect to find the same serum-cholesterol levels and frequencies of coronary heart-disease in two populations both getting 40% of their calories from fats but the one deriving this from corn oil and sesame-seed oil while the other got all their fats from coconut oil and lard. But this does not happen to be the way people consume fats. In a desperately poor land the people get very few fats of any kind. As their lot improves economically they increase their total fat consumption, and the fats they eat tend to be more and more the more expensive kinds-the fats that, incidentally, are associated with the foods most highly prized for their nutritional as well as their gustatory value. no
To
some
of us, at
least, it appears that this
response
prosperity can go too far. The problem has been complicated by the enterprise and ingenuity of food producers and technologists who provide a superabundance of all kinds of fats and then persuade *us to eat them. Are we now going to ask them, please, to put some more E.F.A. in their wares Perhaps with a modest increase in cost ?’?, This could be the shape of things to come. Continue, or increase, your high fat consumption to
but be sure you get a lot of corn oil, sesame-seed oil, fish oil, and the like and be careful to swallow it fresh and in the virgin liquid state ! Such considerations may seem inappropriate in a discussion of a problem that is basically chemical and pathological. But the coronary problem has already reached dimensions that cannot be confined in the otherworldly atmosphere of some academic retreats. In the meantime, it is clear that a great deal more research is needed on all aspects of the problem, including food economics and the psychology of food preferences. While this is in course it may be well to ponder whether a diet containing 40%of its calories as fats is really essential for human happiness and, if not, how may it best
be reduced. First Medical Clinic, Kyushu University Medical School, Fukuoka-shi, Japan.
ANCEL KEYS.
VOMITING SICKNESS IN JAMAICA
SiR,-There are two important points which might be added to your leading article (April 14). As far as I know, chemical analysis has not yet been published to indicate in what part of the ackee fruit the toxins are found. If they are only in the seed, then the population can continue to eat the arillus with impunity. Children who eat the seed in play, or tragically driven by hunger, must be more carefully supervised. The other point is quantitative : not only which part, but how much of which part, of the fruit is likely to produce a toxic effect. The full report of the work done in 1952-53 (excepting the chemical section) was published by the Government Printers, Kingston, Jamaica, in 1954, as a monograph on Vomiting Sickness in Jamaica. London School of Hygiene and Tropical Medicine, W.C.1.
CICELY D. WILLIAMS.
REVISION OF THE CURRICULUM
SIR,—The only positive contribution in the proposals of the Royal College of Physicians anent revision of the medical curriculum is the suggestion that the G.M.C. should cease to issue recommendations-in other words, abrogate its function as guide and supervisor of the training of medical students. Otherwise the report (of which extracts appeared in your issue of April 14) consists in the usual ponderous, pontifical pronouncements that the aim of medical education should be to give " a broad the acquisition of a scientific cultural background," attitude," " principles and outlines without the burden of fact," &c., &c. We have heard most of it before in the perennial bellyache about the medical curriculum which is a perpetual item on the agenda of committees of medical schools and Royal colleges and corporations, in fact of every conceivable body except those best suited to advise-namely, the general practitioner. No other training schemes-for lawyers, engineers, scientists, &c.-a,re subjected to so much interminable research." Quite obviously the present training of the medical student is unsatisfactory, uneconomic, and much of it wholly irrelevant to the work subsequently undertaken by the great proportion of medical graduates. Medicine is not a philosophy, nor is it a science. It is a skill, much of it still empirical; and, like training for any other skilled job, the education of the medical student should include, from an early stage, a concurrent and remunerated apprenticeship. The people want a doctor who knows his job-who can, for example, recognise scabies when he sees it and tell them how to treat it. They are not particularly concerned whether he can discourse on Scabies in Mediaeval Times or The Adaptive Mutations from which Evolved the Behaviour Pattern of Acartts scabiei. Would it be wrong to suspect that given freedom from G.M.C. recommendations a model " curriculum emanate from the would Royal College of Physicians, which even be prepared to send its representatives to the various medical schools to initiate the new era ? "
1,
"
might
Department of Anatomy, University of Glasgow.
GEORGE M. WYBURN.
SIR,—The very interesting report by the Royal College of Physicians, prompts me to ventilate an idea which might possibly be applicable as an experiment at one, say, of our " red brick " universities.
It
is, in effect, the introduction of
a
tutorial
system,
whereby each of the younger clinicians attached to the medical school would act as tutor to some five or six students for the whole of their undergraduate life. They would meet him perhaps for two one-hour sessions each week, on one occasion to discuss an essay he had set, and on the other for a general round-table conference. The value to the students would be obvious in bringing them from the first into personal contact with an active practitioner of their craft and would give them an initiation, particularly when they reached their clinical years, to the real as distinct from the textbook problems of medical work. The value to the tutor would hardly be less, since it would necessarily keep him up to date not only with other branches besides his own specialty but with his anatomical, physiological, and psychological knowledge. One of the dangers of the age of specialism is that, while knowledge in a particular field may become ever more detailed and exact, the specialist is liable to fall behind even the newly qualified graduate where the rest of the subject is concerned ; and my scheme would very effectively prevent this, since it would be useless to try and talk to a critical audience without an adequate familiarity with the matters under discussion. JOSEPH V. WALKER Darlington.
Medical Officer of Health.