653
pared with bipolar postmenopausal women. Premenopausal bipolar women had a higher peak G.H. than did unipolar premenopausal women but the difference was not significant. The apparent discrepancy between our findings and those of Gold et al. might be due to the fact that they studied bipolar premenopausal females and bipolar males only, while we investigated both premenopausal (N=3) and postmenopausal bipolar women (N=15). G.H. response in the unipolar group is not significantly influenced by the menopausal status. Furthermore, confirm Gold’s observation of a greater prolactin suppression after levodopa in the bipolar patients. In fact, the opposite seems to be true. There is a paradoxical rise in prolactin secretion 30-90 min after levodopa administration followed by a subsequent suppression in the bipolar patients. This peak is not present in the unipolar group. This paradoxical response to levodopa is more apparent in bipolar premenopausal women than in bipolar postmenopausal patients. Baseline prolactin levels were not significantly different in bipolar and unipolar patients. Our results on G.H. response in affective illness accord with the work of Sachar et awl. who found a reduction in G.H. response to levodopa in postmenopausal women, an observation consistent with the fact that G.H. stimutauon is related to circulating aestrogens.4 Bipolar and unipolar premenopausal women cannot be differentiated on the basis of their G.H. response to levodopa, although there is a trend toward a bigger G.H. response and less prolactin suppression in the bipolar group. The results on prolactin response to levodopa in affective illness are conflicting and more difficult to interpret. On our data, the influence of stress-related factors and oestrogen levels on prolactin response to levodopa cannot be excluded. In future studies in affective illness larger and more clinically homogeneous samples of patients must be investigated and the importance of the menopause in neuroendocrine and neurotransmitter research must be allowed for. we were
unable
J. MENDLEWICZ P. LINKOWSKI H. BRAUMAN
CLINICAL SIGN OF UNILATERAL PNEUMOTHORAX
SIR,-Commonly described signs of thorax include diminution of breath
hyperresonance
on
unilateral pneumo-
sounds, diminution of
percussion,
diminished vocal
resonance, tracheal displacement, or apex-beat displacement. The coin test is of little value in tension pneumothorax.5 A
time with clicking sound may occasionally be heard in heart beat, a sign first described by Hamman.b
the
1 would like to describe an additional neglected sign which I have found useful in the diagnosis of a unilateral pneumothorax. The patient with a suspected pneumothorax is sat upright and a stethoscope is applied in the midline at the upper end of the sternum. Percussion at the midpoint of each clavicle in turn with equal impact will then cause the auscultator to hear an obvious relative hyperresonance over the side of the pneumothorax. Also, the pitch and timbre of the sounds produced is very asymmetrical. A useful adjunct to this technique is to reduce progressively the impact of percussion at the midpoint of one clavicle until virtually no sound is audible. Similar percussion of the other clavicle then causes an easily audible sound if there is an underlying pneumothorax. It is important to sit the patient upright to assist the rise of intrapleural air to the lung apex of the affected side. Some sound heard via the stethoscope will have been transmitted by the bony structures, but this component will be symmetrical and any discrepancy Sachar, D. J., and others, ibid. 1975, 32, 502. Merimee, T. J., Fineberg, S. E. J. clin Endocr. Metab. 1965, 25, 1470. 5 Crofton, J., Douglas, A. Respiratory Diseases. Oxford, 1975. 6 Hamman, L. Ann. intern. Med. 1939, 13, 923. Lawson, J. D. New Engl. J Med. 1961, 264, 88. 3 4
7
metrical scratching of the chest wall results in tatory findings at the midline. Royal Northern London N1
unequal
auscul-
Hospital,
PHILIP D. WELSBY
to
Department of Clinical Biochemistry, Institute of Psychiatry, Brugmann University Hospital, 1020 Brussels, Belgium
movement or
be caused by asymmetry of underlying tissue. Use of the stethoscope also eliminates background ward noise which often interferes with the interpretation of unassisted percussion. The demonstration of this sign relies upon the same principle as the "scratch sign" described by Lawson’in which symmust
GENETIC COMPONENT OF OBESITY
SIR,-Boggl has criticis.ed our suggestionz that individuals become obese within a population as a result of metabolic factors which are genetically determined. We would stress that our views do not relate merely to the "hard-core of idiopathic obese". We would not, however, deny that cultural factors are important in determining the prevalence of obesity within a community-the changing incidence of obesity in the U.S.A. over the past 20 years is not likely to be due to a change in the genetic pool of the population. But whether an individual becomes obese as the population’s overall physical activity diminishes is, in our view, determined by metabolic differences between subjects. Garn et al. have reported that environmental factors are important in determining the clustering of obesity within families in the U.S.A., but metabolic efficiency in obese and lean families has not been studied in detail. Certainly stability of genetic pools and the dominance of cultural factors may not be observed in developing countries where genetic patterns and metabolic efficiency are continuing to shift, particularly where the mortality-rate among the under-5s remains as high as 10-50%. The idea of the selective advantage of a high metabolic efficiency is not new, and the concept of the "thrifty genotype" has been used by Neel4 to explain the continuing incidence of diabetes, associated with obesity. It should not be assumed that, although we emphasised the metabolic aspects of obesity, we neglect the problem of appetite control, for clearly obesity can only develop when food is not limiting. Indeed an important consequence of our views is that an obese person in energy balance continues to consume too much for his energy needs even though his intake may be within the "normal range". A reduction in weight reduces his energy requirements so that once slimmed he needs to control his food intake permanently at a level below the average. This low energy requirement may account for the frequent relapse in the treatment of obesity and the tendency to regain the lost weight-the "set-point" of body-weight merely reflecting the continuing adjustment of weight and energy expenditure until they match the energy ingested. There is also excellent evidence which shows the variable susceptibility to weight gain on increasing food intake,5 and our argument on the defective thermic responses in obese individuals, also noted by Quaade6 and others, led us to favour reduced catecholamine/ free-fatty-acid responsiveness in the characterisation of the obese and pre-obese subjects. This reduced catecholamine "drive" may be evident not only in the reduced thermogenic response to cooling but also in the differences of muscle tone and small physical movements which are not included in the usual definition of physical activity.7 1. 2.
Bogg, R. A. Lancet, 1976, ii, 1205. James, W. P. T., Trayhurn, P. ibid. p. 770. 3. Garn, S. M., Bailey, S. M., Higgins, I. T. T. Am. J. clin.
Nutr.
1976, 29,
1067. 4. 5. 6. 7.
Neel, J. V. Am. J. hum. Genet. 1962, 14, 353. Sims, E. A. H., Danforth, E., Horton, E. S., Bray, G. A., Glennon, J. A., Salans, L. B Rec Progr. Horm. Res. 1973, 29, 457. Quaade, F. in Energy Balance in Man (edited by M. Apfelbaum); p. 135. Paris, 1973. Research on Obesity: a report of the D.H.S.S./M.R.C. group. (compiled by W. P. T. James). H M. Stationery Office, 1976.
654 NUTRITIONAL HAZARDS OF HIGH-FIBRE DIET SIR,-Rab and Baseerl attribute adult osteomalacia to the phytate present in the chupattis which form the staple diet (with beans) of rural communities, not only in Pakistan but also in India, Iran, Iraq, and other parts of the Middle East where unleavened bread is consumed. Phytate will chelate iron and zinc as well as calcium, and this was thought to lead to the anaemia (iron), retarded growth (zinc and calcium), as well as delayed puberty (zinc) and definitive short stature (zinc and calcium) displayed in its extreme form in the male dwarfs with hypogonadism reported from Iran and Egypt.J-4 Paradoxically, in urban districts where the bread is baked with yeast, loss of stature is far less marked, especially when high-extraction white flour is used in baking. Indeed, the greater the extraction-rate, the better the mineral status of the individual, despite the loss of some of these elements in the extraction pro-
Cultural factors are indeed important in the aetiology of but the very variable nature of man’s susceptibility to the condition must also be recognised.
obesity,
Dunn Nutrition Unit,
University of Cambridge and Medical Research Council, Cambridge CB4 1XJ
W. P. T. JAMES P. TRAYHURN
MECHANISM FOR STARVATION SUPPRESSION AND REFEEDING ACTIVATION OF INFECTION
SIR,-Murray and Murray’ suggested that starvation suprefeeding activates certain infections,’ but they pointed out that the mechanism is unknown. One explanation could lie in the immunosuppressive properties of dietary polyunsaturated fatty acids (P.U.F.A.). presses and
P.U.F.A.
in vitro
can
inhibit
a
number of functions of the
litis in animals maintained on a P.U.F.A.-deficient diet, whereas supplementation of the diet with P.U.F.A. results in striking protective effects.5 In man, P.U.F.A. have been used with beneficial results in multiple sclerosis6 and in the treatment of
kidney-transplant patients.7 be synthesised in the body, they must in the diet. In a normal diet most of the P.U.F.A. comes from cooking oil, cereals, nuts, and so on. The fatty acids are absorbed into the epithelial cells of the small intestine, esterified to triglyceride, and secreted as chylomicrons into the lymph. The chylomicrons enter the bloodstream via the thoracic lymph duct. This duct collects lymph from the abdominal area which contains many lymph-nodes. Consequently, during passage through the thoracic duct, lymphocytes will be challenged with a very high concentration of fat in the form of chylomicrons. If esterified as well as non-esteritied P.U.F.A. can exert an immunosuppressive effect on the lymphocytes (this does not seem to have been tested in vitro), then entry of P.U.F.A. into the lymphatic system may be seen as a natural immunosuppressive mechanism. However, an important symptom of infection is anorexia. The resultant starvation should lead to removal of this natural restriction of lymphocytic activity, so that the full immunological response to the infection could proceed unhindered. This modification of the immunological response by feeding or starvation is, then, a natural mechanism of control of immunological activity and would explain the Murrays’ hypothesis. Ingestion of an abnormally large amount of polyunsaturated fat should reduce the immunological activity of lymphocytes, and this could be important in the treatment of autoimmune diseases and in the prevention of transplant rejection. Thus preliminary successes in the treatment of patients with kidney transplants7 or multiple sclerosis patients6 with sunflower seed oil, which contains a high proportion of P.U.F.A., are consistent with this mechanism to explain starvation suppression and refeeding activation of infection. Since
P.U.F.A. cannot
provided
Department of Biochemistry, University of Oxford, 3QU
Oxford OX1
E. A. NEWSHOLME
1. Murray, M. J., Murray, A. B. Lancet, 1977, i, 123. 2. Weyman, C., Belin, J., Smith, A. D., Thompson, R. H. S. ibid. 1975, i, 33. 3. Mertin, J., Shenton, B. K., Field, E. J. Br. med. J. 1973, ii, 777. 4. Mertin, J. Transplantation, 1976, 21, 1. 5. Mertin, J., Meade, C. J. Br. med. Bull. 1977, 33, 67. 6. Millar, J. H. D. and others, Br. med. J. 1973, i, 765. 7. Uldall, P. R. and others, Lancet, 1974, ii, 514. 8. Geddes, A. M. in Davidson’s Principles and Practice of Medicine (edited by J. Macleod); p. 51. Edinburgh, 1974.
This
was
of
lymphocyte that are related to the immune response (e.g., phytohaemagglutinin stimulation of transformation and lymphocyte-antigen interactionz 3). In animal experiments, P.U.F.A. decrease the cytotoxic allograft response,4 and there is increased susceptibility to experimental allergic encephalomye-
be
thought to be due entirely to the degradation the phytate by enzymes present in the yeast, but it now seems that the improved absorption of these elements is due more to removal of the fibre than to reduction of phytate, although this is of course nutritionally beneficial.s-’ Cellulose forms the bulk of fibre in cereals and indeed in most plant foodstuffs,7 but no vertebrate can digest it without the aid of bacteria. Ruminants among the herbivores accomplish this most thoroughly by modifying the foregut to accommodate the appropriate flora, well demonstrated by their soft stools which contain little or no undigested residue. Other herbivores modify and lengthen the distal portion of the gut for this purpose, but bacterial digestion of fibre is less complete so that the stools, although well-formed, contain undigested vegetable matter. Man’s ancestors forsook the fringe of the rain forests, where his nearest primate relatives still dwell, for the open savannah to join the large carnivorous predators (lions, leopards, and cheetahs) preying on the deer and other herbivores of the savannah and other grasslands. Conservation of water and salt is essential for survival in this habitat and his colon is adapted for this purpose. It is not designed to scavenge calcium, trace metals, or any other micronutrient that may be bound to the undigested cellulose. Furthermore, 10 000 years is insufficient time for adaptation of his gut to successful diges: tion of fibre-indeed, the trend of human evolution has been away from that of his near relative, the gorilla, who passes five or more motions daily on a vegetable diet but is not far from a rich supply of water in the tropical rain forest. It is perhaps surprising that the role of cellulose was not suspected earlier, especially since its binding capacity has been exploited for many years in paper chromatography. Understanding of the role of zinc in retarding growth and delaying puberty had to await technical developments for efficient assay of the metal. Working with infants and young children with acrodermatitis enteropathica, I found that lower doses of diiodohydroxyquin were needed when the cereal source was rice (with a lower fibre content) rather than wheat. Studies in the United States? indicate not only that children in the lower income group are zinc deficient but that the children of middleclass families do not obtain adequate amounts of this trace metal unless they consume at least 1 oz (30 g) of meat a day. It is significant that the acceleration of the onset of puberty as well as the increase in definitive stature in all classes in the industrial nations began in 1870, precisely the time when roller milling of wheaten flour was introduced. Since then there has been a progressive decrease in the fibre content of the diet concomitant with the improvement in stature and earlier puberty. Since it seems clear that increased availability of zinc and calcium has played a major role in this striking phenomcess.
,
1. 2. 3. 4. 5. 6. 7.
Rab, S. M., Baseer, A. Lancet, 1976, ii, 1211. Prasad, A., et al. Am. J. clin. Nutr. 1963, 12, 437. Sandstead, et al. ibid. 1967, 20, 422. Coble, Y. D., et al. ibid. 1966, 18, 471. Schaller, G. B. The Mountain Gorilla. Chicago, 1965. Hambridge, K. M., et al. Pediat. Res. 1972, 6, 868. Reinhold, J. G., et al. in Trace Metals in Human Health and Disease (edited by A Prasad) New York, 1976.
pared with bipolar postmenopausal women. Premenopausal bipolar women had a higher peak G.H. than did unipolar premenopausal women but the difference was not significant. The apparent discrepancy between our findings and those of Gold et al. might be due to the fact that they studied bipolar premenopausal females and bipolar males only, while we investigated both premenopausal (N=3) and postmenopausal bipolar women (N=15). G.H. response in the unipolar group is not significantly influenced by the menopausal status. Furthermore, confirm Gold’s observation of a greater prolactin suppression after levodopa in the bipolar patients. In fact, the opposite seems to be true. There is a paradoxical rise in prolactin secretion 30-90 min after levodopa administration followed by a subsequent suppression in the bipolar patients. This peak is not present in the unipolar group. This paradoxical response to levodopa is more apparent in bipolar premenopausal women than in bipolar postmenopausal patients. Baseline prolactin levels were not significantly different in bipolar and unipolar patients. Our results on G.H. response in affective illness accord with the work of Sachar et awl. who found a reduction in G.H. response to levodopa in postmenopausal women, an observation consistent with the fact that G.H. stimutauon is related to circulating aestrogens.4 Bipolar and unipolar premenopausal women cannot be differentiated on the basis of their G.H. response to levodopa, although there is a trend toward a bigger G.H. response and less prolactin suppression in the bipolar group. The results on prolactin response to levodopa in affective illness are conflicting and more difficult to interpret. On our data, the influence of stress-related factors and oestrogen levels on prolactin response to levodopa cannot be excluded. In future studies in affective illness larger and more clinically homogeneous samples of patients must be investigated and the importance of the menopause in neuroendocrine and neurotransmitter research must be allowed for. we were
unable
J. MENDLEWICZ P. LINKOWSKI H. BRAUMAN
CLINICAL SIGN OF UNILATERAL PNEUMOTHORAX
SIR,-Commonly described signs of thorax include diminution of breath
hyperresonance
on
unilateral pneumo-
sounds, diminution of
percussion,
diminished vocal
resonance, tracheal displacement, or apex-beat displacement. The coin test is of little value in tension pneumothorax.5 A
time with clicking sound may occasionally be heard in heart beat, a sign first described by Hamman.b
the
1 would like to describe an additional neglected sign which I have found useful in the diagnosis of a unilateral pneumothorax. The patient with a suspected pneumothorax is sat upright and a stethoscope is applied in the midline at the upper end of the sternum. Percussion at the midpoint of each clavicle in turn with equal impact will then cause the auscultator to hear an obvious relative hyperresonance over the side of the pneumothorax. Also, the pitch and timbre of the sounds produced is very asymmetrical. A useful adjunct to this technique is to reduce progressively the impact of percussion at the midpoint of one clavicle until virtually no sound is audible. Similar percussion of the other clavicle then causes an easily audible sound if there is an underlying pneumothorax. It is important to sit the patient upright to assist the rise of intrapleural air to the lung apex of the affected side. Some sound heard via the stethoscope will have been transmitted by the bony structures, but this component will be symmetrical and any discrepancy Sachar, D. J., and others, ibid. 1975, 32, 502. Merimee, T. J., Fineberg, S. E. J. clin Endocr. Metab. 1965, 25, 1470. 5 Crofton, J., Douglas, A. Respiratory Diseases. Oxford, 1975. 6 Hamman, L. Ann. intern. Med. 1939, 13, 923. Lawson, J. D. New Engl. J Med. 1961, 264, 88. 3 4
7
metrical scratching of the chest wall results in tatory findings at the midline. Royal Northern London N1
unequal
auscul-
Hospital,
PHILIP D. WELSBY
to
Department of Clinical Biochemistry, Institute of Psychiatry, Brugmann University Hospital, 1020 Brussels, Belgium
movement or
be caused by asymmetry of underlying tissue. Use of the stethoscope also eliminates background ward noise which often interferes with the interpretation of unassisted percussion. The demonstration of this sign relies upon the same principle as the "scratch sign" described by Lawson’in which symmust
GENETIC COMPONENT OF OBESITY
SIR,-Boggl has criticis.ed our suggestionz that individuals become obese within a population as a result of metabolic factors which are genetically determined. We would stress that our views do not relate merely to the "hard-core of idiopathic obese". We would not, however, deny that cultural factors are important in determining the prevalence of obesity within a community-the changing incidence of obesity in the U.S.A. over the past 20 years is not likely to be due to a change in the genetic pool of the population. But whether an individual becomes obese as the population’s overall physical activity diminishes is, in our view, determined by metabolic differences between subjects. Garn et al. have reported that environmental factors are important in determining the clustering of obesity within families in the U.S.A., but metabolic efficiency in obese and lean families has not been studied in detail. Certainly stability of genetic pools and the dominance of cultural factors may not be observed in developing countries where genetic patterns and metabolic efficiency are continuing to shift, particularly where the mortality-rate among the under-5s remains as high as 10-50%. The idea of the selective advantage of a high metabolic efficiency is not new, and the concept of the "thrifty genotype" has been used by Neel4 to explain the continuing incidence of diabetes, associated with obesity. It should not be assumed that, although we emphasised the metabolic aspects of obesity, we neglect the problem of appetite control, for clearly obesity can only develop when food is not limiting. Indeed an important consequence of our views is that an obese person in energy balance continues to consume too much for his energy needs even though his intake may be within the "normal range". A reduction in weight reduces his energy requirements so that once slimmed he needs to control his food intake permanently at a level below the average. This low energy requirement may account for the frequent relapse in the treatment of obesity and the tendency to regain the lost weight-the "set-point" of body-weight merely reflecting the continuing adjustment of weight and energy expenditure until they match the energy ingested. There is also excellent evidence which shows the variable susceptibility to weight gain on increasing food intake,5 and our argument on the defective thermic responses in obese individuals, also noted by Quaade6 and others, led us to favour reduced catecholamine/ free-fatty-acid responsiveness in the characterisation of the obese and pre-obese subjects. This reduced catecholamine "drive" may be evident not only in the reduced thermogenic response to cooling but also in the differences of muscle tone and small physical movements which are not included in the usual definition of physical activity.7 1. 2.
Bogg, R. A. Lancet, 1976, ii, 1205. James, W. P. T., Trayhurn, P. ibid. p. 770. 3. Garn, S. M., Bailey, S. M., Higgins, I. T. T. Am. J. clin.
Nutr.
1976, 29,
1067. 4. 5. 6. 7.
Neel, J. V. Am. J. hum. Genet. 1962, 14, 353. Sims, E. A. H., Danforth, E., Horton, E. S., Bray, G. A., Glennon, J. A., Salans, L. B Rec Progr. Horm. Res. 1973, 29, 457. Quaade, F. in Energy Balance in Man (edited by M. Apfelbaum); p. 135. Paris, 1973. Research on Obesity: a report of the D.H.S.S./M.R.C. group. (compiled by W. P. T. James). H M. Stationery Office, 1976.
654 NUTRITIONAL HAZARDS OF HIGH-FIBRE DIET SIR,-Rab and Baseerl attribute adult osteomalacia to the phytate present in the chupattis which form the staple diet (with beans) of rural communities, not only in Pakistan but also in India, Iran, Iraq, and other parts of the Middle East where unleavened bread is consumed. Phytate will chelate iron and zinc as well as calcium, and this was thought to lead to the anaemia (iron), retarded growth (zinc and calcium), as well as delayed puberty (zinc) and definitive short stature (zinc and calcium) displayed in its extreme form in the male dwarfs with hypogonadism reported from Iran and Egypt.J-4 Paradoxically, in urban districts where the bread is baked with yeast, loss of stature is far less marked, especially when high-extraction white flour is used in baking. Indeed, the greater the extraction-rate, the better the mineral status of the individual, despite the loss of some of these elements in the extraction pro-
Cultural factors are indeed important in the aetiology of but the very variable nature of man’s susceptibility to the condition must also be recognised.
obesity,
Dunn Nutrition Unit,
University of Cambridge and Medical Research Council, Cambridge CB4 1XJ
W. P. T. JAMES P. TRAYHURN
MECHANISM FOR STARVATION SUPPRESSION AND REFEEDING ACTIVATION OF INFECTION
SIR,-Murray and Murray’ suggested that starvation suprefeeding activates certain infections,’ but they pointed out that the mechanism is unknown. One explanation could lie in the immunosuppressive properties of dietary polyunsaturated fatty acids (P.U.F.A.). presses and
P.U.F.A.
in vitro
can
inhibit
a
number of functions of the
litis in animals maintained on a P.U.F.A.-deficient diet, whereas supplementation of the diet with P.U.F.A. results in striking protective effects.5 In man, P.U.F.A. have been used with beneficial results in multiple sclerosis6 and in the treatment of
kidney-transplant patients.7 be synthesised in the body, they must in the diet. In a normal diet most of the P.U.F.A. comes from cooking oil, cereals, nuts, and so on. The fatty acids are absorbed into the epithelial cells of the small intestine, esterified to triglyceride, and secreted as chylomicrons into the lymph. The chylomicrons enter the bloodstream via the thoracic lymph duct. This duct collects lymph from the abdominal area which contains many lymph-nodes. Consequently, during passage through the thoracic duct, lymphocytes will be challenged with a very high concentration of fat in the form of chylomicrons. If esterified as well as non-esteritied P.U.F.A. can exert an immunosuppressive effect on the lymphocytes (this does not seem to have been tested in vitro), then entry of P.U.F.A. into the lymphatic system may be seen as a natural immunosuppressive mechanism. However, an important symptom of infection is anorexia. The resultant starvation should lead to removal of this natural restriction of lymphocytic activity, so that the full immunological response to the infection could proceed unhindered. This modification of the immunological response by feeding or starvation is, then, a natural mechanism of control of immunological activity and would explain the Murrays’ hypothesis. Ingestion of an abnormally large amount of polyunsaturated fat should reduce the immunological activity of lymphocytes, and this could be important in the treatment of autoimmune diseases and in the prevention of transplant rejection. Thus preliminary successes in the treatment of patients with kidney transplants7 or multiple sclerosis patients6 with sunflower seed oil, which contains a high proportion of P.U.F.A., are consistent with this mechanism to explain starvation suppression and refeeding activation of infection. Since
P.U.F.A. cannot
provided
Department of Biochemistry, University of Oxford, 3QU
Oxford OX1
E. A. NEWSHOLME
1. Murray, M. J., Murray, A. B. Lancet, 1977, i, 123. 2. Weyman, C., Belin, J., Smith, A. D., Thompson, R. H. S. ibid. 1975, i, 33. 3. Mertin, J., Shenton, B. K., Field, E. J. Br. med. J. 1973, ii, 777. 4. Mertin, J. Transplantation, 1976, 21, 1. 5. Mertin, J., Meade, C. J. Br. med. Bull. 1977, 33, 67. 6. Millar, J. H. D. and others, Br. med. J. 1973, i, 765. 7. Uldall, P. R. and others, Lancet, 1974, ii, 514. 8. Geddes, A. M. in Davidson’s Principles and Practice of Medicine (edited by J. Macleod); p. 51. Edinburgh, 1974.
This
was
of
lymphocyte that are related to the immune response (e.g., phytohaemagglutinin stimulation of transformation and lymphocyte-antigen interactionz 3). In animal experiments, P.U.F.A. decrease the cytotoxic allograft response,4 and there is increased susceptibility to experimental allergic encephalomye-
be
thought to be due entirely to the degradation the phytate by enzymes present in the yeast, but it now seems that the improved absorption of these elements is due more to removal of the fibre than to reduction of phytate, although this is of course nutritionally beneficial.s-’ Cellulose forms the bulk of fibre in cereals and indeed in most plant foodstuffs,7 but no vertebrate can digest it without the aid of bacteria. Ruminants among the herbivores accomplish this most thoroughly by modifying the foregut to accommodate the appropriate flora, well demonstrated by their soft stools which contain little or no undigested residue. Other herbivores modify and lengthen the distal portion of the gut for this purpose, but bacterial digestion of fibre is less complete so that the stools, although well-formed, contain undigested vegetable matter. Man’s ancestors forsook the fringe of the rain forests, where his nearest primate relatives still dwell, for the open savannah to join the large carnivorous predators (lions, leopards, and cheetahs) preying on the deer and other herbivores of the savannah and other grasslands. Conservation of water and salt is essential for survival in this habitat and his colon is adapted for this purpose. It is not designed to scavenge calcium, trace metals, or any other micronutrient that may be bound to the undigested cellulose. Furthermore, 10 000 years is insufficient time for adaptation of his gut to successful diges: tion of fibre-indeed, the trend of human evolution has been away from that of his near relative, the gorilla, who passes five or more motions daily on a vegetable diet but is not far from a rich supply of water in the tropical rain forest. It is perhaps surprising that the role of cellulose was not suspected earlier, especially since its binding capacity has been exploited for many years in paper chromatography. Understanding of the role of zinc in retarding growth and delaying puberty had to await technical developments for efficient assay of the metal. Working with infants and young children with acrodermatitis enteropathica, I found that lower doses of diiodohydroxyquin were needed when the cereal source was rice (with a lower fibre content) rather than wheat. Studies in the United States? indicate not only that children in the lower income group are zinc deficient but that the children of middleclass families do not obtain adequate amounts of this trace metal unless they consume at least 1 oz (30 g) of meat a day. It is significant that the acceleration of the onset of puberty as well as the increase in definitive stature in all classes in the industrial nations began in 1870, precisely the time when roller milling of wheaten flour was introduced. Since then there has been a progressive decrease in the fibre content of the diet concomitant with the improvement in stature and earlier puberty. Since it seems clear that increased availability of zinc and calcium has played a major role in this striking phenomcess.
,
1. 2. 3. 4. 5. 6. 7.
Rab, S. M., Baseer, A. Lancet, 1976, ii, 1211. Prasad, A., et al. Am. J. clin. Nutr. 1963, 12, 437. Sandstead, et al. ibid. 1967, 20, 422. Coble, Y. D., et al. ibid. 1966, 18, 471. Schaller, G. B. The Mountain Gorilla. Chicago, 1965. Hambridge, K. M., et al. Pediat. Res. 1972, 6, 868. Reinhold, J. G., et al. in Trace Metals in Human Health and Disease (edited by A Prasad) New York, 1976.
