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MILK FAT, DIARRHOEA, AND THE ILEAL BRAKE
658
MILK FAT, DIARRHOEA, AND THE ILEAL BRAKE ANIMAL fat is prominent in the current list of undesirable food components, and the time may have come for a few words in its defence. In an American paediatric practice numbering 1197 children aged between 1 and 16 years, Koopman and his colleagues found a five-fold higher risk of acute gastrointestinal illness among children taking low fat milk as their only milk source than in children taking whole milk. Interestingly, the ratio was the same for rotavirusinduced infections as for illnesses in which no pathogens were identified. Statistical analysis revealed no alternative explanation, so the authors concluded that there may be a factor in cow’s milk fat that prevents diarrhoeal illness. Although all ages were affected, the risk seemed greatest in children aged 1-2 years of age (children-in the first year of life being excluded from the study).’ A hint of this relation had been given earlier by data from the United States First National Health and Nutrition Examination Survey conducted from 1970 to 1974. At that time, only a small proportion (185 out of2652) of children drank skimmed milk, but among these 6 had diarrhoea at the time of the interview and the diarrhoea prevalence in children aged 1 year who drank predominantly skimmed milk was 3’4 times the prevalence in those drinking predominantly whole milk.2 Although there is very good evidence that whole cow’s milk, whether raw or pasteurised, contains anti-rotavirus properties which are mainly accounted for by its content of specific IgGl,3 laboratory studies have not ruled out the possibility of other non-immunoglobulin factors capable of inhibiting viral replication in tissue culture.4 It is also quite possible that dietary fat could act in other, non-specific ways to abolish the diarrhoeal response to gastrointestinal infection, just as opiates may control diarrhoeal illness without removing the infective agent. Fat affects fluid and electrolyte exchange and motility. For instance, altering the fat composition of the diet in rabbits has a striking effect on the absorption of glucoseS and hence, perhaps, electrolytes. In rats quite small changes in the proportions of saturated to unsaturated fatty acids in the diet influence active and passive intestinal transport.6 Dietary fat delays gastric emptying, and unabsorbed fat further down the alimentary tract will also prolong smallbowel transit time. Infusion of partly hydrolysed triglyceride into the ileum inhibits jejunal motility and delays jejunal transit.’ Long-chain fatty acids, such as oleic acid, are more effective motility inhibitors; the triglyceride triolein elicits a slower response with a slower recovery; and medium-chain triglycerides have an intermediate inhibitory effect, while glycerol does not produce a response.8 It seems, therefore, that the receptors for this "ileal brake" mechanism are more
1.
Koopman JS, Turkish VJ, Monto AS, Thompson FE, Isaacson gastrointestinal illness. Am J Publ Health 1984; 74: 1371-73.
RE. Milk fat and
2. National Center for Health Statistics: Plan and operation of the Health and Nutrition Examination Survey, United States 1971-1973. Vital and health statistics, series 1, numbers 10a and 10b, DHEW Lib No (HSM) 73-1310, Washington DC: Health Services and Mental Health Administration, Government Printing Office, 1973. 3. Yolken RH, Losonksy GA, Vonderfecht S, Leister F, Wee S-B. Antibody to human rotavirus in cow’s milk. N Engl J Med 1985; 312: 605-10. 4. Butler JE. Bovine immunoglobulins: an augmented review. Vet Immunol Immunopathol 1983; 4: 43-152. 5. Thomson ABR. Influence of dietary modifications on uptake of cholesterol, glucose, fatty acids and alcohols into rabbit intestine. Am J Clin Nutr 1982, 35: 556-65. 6. Thomson ABR, Keelan M, Clandinin MT, Walker K. Dietary fat selectively alters transport properties of rat jejunum. J Clin Invest 1986; 77: 279-88. 7. Spiller RC, Trotman IF, Higgins BE, et al. The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984; 25: 365-74. 8. Spiller RC, Trotman IF, Lee YC, et al. Characterisation of the stimulus initiating the ileal brake in man. Gut 1984; 25: A545 (abstr T15).
to free fatty acids than to intact triglyceride, so intraluminal lipolysis may be an important contributory factor. The ileal brake concept helps to explain clinical observations in malabsorption states. The best predictor of delayed transit in patients with coeliac disease in one study was the 24-hour faecal fat, and the degree of delay in smallbowel transit in coeliac patients with steatorrhoea was correlated with various indices of the extent of the jejunal lesion, such as impairment of release of insulin, cholecystokinin, and gastrointestinal polypeptide.9 Smallbowel transit time measured by breath hydrogen studies was increased in 7 out of 10 patients with cystic fibrosis.’" Paradoxically, increasing the intake of pancreatin in cystic fibrosis patients with distal intestinal obstruction syndrome ("meconium ileus equivalent") sometimes worsens their symptoms, but this would be expected if the extra pancreatin serves only to increase the amount of free fatty acid in the ileum without improving its absorption. In the functional disorder known as toddler diarrhoea (which is not accompanied by malabsorption), dietary fat intake in a group of American children was found to be low, and in some cases the onset followed dietary attempts to prevent coronary artery disease."Adding fat to the diet of these children cured the diarrhoea in all cases where original intake was low.l2 Diminished dietary fat was also found to prolong postinfectious diarrhoea."1 If low fat intakes really do cause, prolong, or enhance diarrhoea, and if anti-infective factors are present in milk fat, then as Koopman and his colleagues point out we should consider whether it is appropriate to send skimmed milk from developed to developing countries where diarrhoea is rife.’ Perhaps the milk of human kindness should include the
responsive
cream.
THE DIAGNOSIS OF MYASTHENIA GRAVIS LIKE many other rare conditions, myasthenia gravis has to be thought of or the diagnosis will be missed. It is still all too usual to encounter an aggrieved, or even moribund, patient in whom the intermittent or fluctuating symptoms were initially dismissed as unimportant or "psychogenic". The possibility should be considered in almost any patient with ptosis, diplopia, or painless external ophthalmoplegia (including apparent internuclear ophthalmoplegia), especially if there is diurnal fluctuation. Other patients present with bulbar symptoms such as alteration in voice, nasal regurgitation, choking, or dysphagia. Although some complain of frank limb weakness, others mention only fatigue which, unlike psychogenic fatigue, is usually relieved by rest. Further presenting features are respiratory difficulty in association with an apparently trivial chest infection and prolonged ventilatory failure after general anaesthesia. The cardinal diagnostic feature is weakness or exaggerated
9. 10. 11.
Spiller RC, Lee YC, Edge C, et al. Functional significance of the ileal brake in coeliac disease. Gut 1984; 25: A545 (abstr T16). Bali A, Stableforth DE, Asquith P. Prolonged small-intestinal transit time in cystic fibrosis. Br Med J 1983; 287: 1011-14. Cohen SA, Hendricks KM, Eastham EJ, Mathis RK, Walker WA. Chronic nonspecific diarrhea. A complication of dietary fat restriction. Am J Dis Child 1979, 133: 490-92.
12 Cohen
SA, Hendricks KM, Mathis RK, Laramee S, Walker WA. Chronic nonspecific diarrhea: dietary relationships. Pediatrics 1979; 64: 402-07.
MILK FAT, DIARRHOEA, AND THE ILEAL BRAKE ANIMAL fat is prominent in the current list of undesirable food components, and the time may have come for a few words in its defence. In an American paediatric practice numbering 1197 children aged between 1 and 16 years, Koopman and his colleagues found a five-fold higher risk of acute gastrointestinal illness among children taking low fat milk as their only milk source than in children taking whole milk. Interestingly, the ratio was the same for rotavirusinduced infections as for illnesses in which no pathogens were identified. Statistical analysis revealed no alternative explanation, so the authors concluded that there may be a factor in cow’s milk fat that prevents diarrhoeal illness. Although all ages were affected, the risk seemed greatest in children aged 1-2 years of age (children-in the first year of life being excluded from the study).’ A hint of this relation had been given earlier by data from the United States First National Health and Nutrition Examination Survey conducted from 1970 to 1974. At that time, only a small proportion (185 out of2652) of children drank skimmed milk, but among these 6 had diarrhoea at the time of the interview and the diarrhoea prevalence in children aged 1 year who drank predominantly skimmed milk was 3’4 times the prevalence in those drinking predominantly whole milk.2 Although there is very good evidence that whole cow’s milk, whether raw or pasteurised, contains anti-rotavirus properties which are mainly accounted for by its content of specific IgGl,3 laboratory studies have not ruled out the possibility of other non-immunoglobulin factors capable of inhibiting viral replication in tissue culture.4 It is also quite possible that dietary fat could act in other, non-specific ways to abolish the diarrhoeal response to gastrointestinal infection, just as opiates may control diarrhoeal illness without removing the infective agent. Fat affects fluid and electrolyte exchange and motility. For instance, altering the fat composition of the diet in rabbits has a striking effect on the absorption of glucoseS and hence, perhaps, electrolytes. In rats quite small changes in the proportions of saturated to unsaturated fatty acids in the diet influence active and passive intestinal transport.6 Dietary fat delays gastric emptying, and unabsorbed fat further down the alimentary tract will also prolong smallbowel transit time. Infusion of partly hydrolysed triglyceride into the ileum inhibits jejunal motility and delays jejunal transit.’ Long-chain fatty acids, such as oleic acid, are more effective motility inhibitors; the triglyceride triolein elicits a slower response with a slower recovery; and medium-chain triglycerides have an intermediate inhibitory effect, while glycerol does not produce a response.8 It seems, therefore, that the receptors for this "ileal brake" mechanism are more
1.
Koopman JS, Turkish VJ, Monto AS, Thompson FE, Isaacson gastrointestinal illness. Am J Publ Health 1984; 74: 1371-73.
RE. Milk fat and
2. National Center for Health Statistics: Plan and operation of the Health and Nutrition Examination Survey, United States 1971-1973. Vital and health statistics, series 1, numbers 10a and 10b, DHEW Lib No (HSM) 73-1310, Washington DC: Health Services and Mental Health Administration, Government Printing Office, 1973. 3. Yolken RH, Losonksy GA, Vonderfecht S, Leister F, Wee S-B. Antibody to human rotavirus in cow’s milk. N Engl J Med 1985; 312: 605-10. 4. Butler JE. Bovine immunoglobulins: an augmented review. Vet Immunol Immunopathol 1983; 4: 43-152. 5. Thomson ABR. Influence of dietary modifications on uptake of cholesterol, glucose, fatty acids and alcohols into rabbit intestine. Am J Clin Nutr 1982, 35: 556-65. 6. Thomson ABR, Keelan M, Clandinin MT, Walker K. Dietary fat selectively alters transport properties of rat jejunum. J Clin Invest 1986; 77: 279-88. 7. Spiller RC, Trotman IF, Higgins BE, et al. The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984; 25: 365-74. 8. Spiller RC, Trotman IF, Lee YC, et al. Characterisation of the stimulus initiating the ileal brake in man. Gut 1984; 25: A545 (abstr T15).
to free fatty acids than to intact triglyceride, so intraluminal lipolysis may be an important contributory factor. The ileal brake concept helps to explain clinical observations in malabsorption states. The best predictor of delayed transit in patients with coeliac disease in one study was the 24-hour faecal fat, and the degree of delay in smallbowel transit in coeliac patients with steatorrhoea was correlated with various indices of the extent of the jejunal lesion, such as impairment of release of insulin, cholecystokinin, and gastrointestinal polypeptide.9 Smallbowel transit time measured by breath hydrogen studies was increased in 7 out of 10 patients with cystic fibrosis.’" Paradoxically, increasing the intake of pancreatin in cystic fibrosis patients with distal intestinal obstruction syndrome ("meconium ileus equivalent") sometimes worsens their symptoms, but this would be expected if the extra pancreatin serves only to increase the amount of free fatty acid in the ileum without improving its absorption. In the functional disorder known as toddler diarrhoea (which is not accompanied by malabsorption), dietary fat intake in a group of American children was found to be low, and in some cases the onset followed dietary attempts to prevent coronary artery disease."Adding fat to the diet of these children cured the diarrhoea in all cases where original intake was low.l2 Diminished dietary fat was also found to prolong postinfectious diarrhoea."1 If low fat intakes really do cause, prolong, or enhance diarrhoea, and if anti-infective factors are present in milk fat, then as Koopman and his colleagues point out we should consider whether it is appropriate to send skimmed milk from developed to developing countries where diarrhoea is rife.’ Perhaps the milk of human kindness should include the
responsive
cream.
THE DIAGNOSIS OF MYASTHENIA GRAVIS LIKE many other rare conditions, myasthenia gravis has to be thought of or the diagnosis will be missed. It is still all too usual to encounter an aggrieved, or even moribund, patient in whom the intermittent or fluctuating symptoms were initially dismissed as unimportant or "psychogenic". The possibility should be considered in almost any patient with ptosis, diplopia, or painless external ophthalmoplegia (including apparent internuclear ophthalmoplegia), especially if there is diurnal fluctuation. Other patients present with bulbar symptoms such as alteration in voice, nasal regurgitation, choking, or dysphagia. Although some complain of frank limb weakness, others mention only fatigue which, unlike psychogenic fatigue, is usually relieved by rest. Further presenting features are respiratory difficulty in association with an apparently trivial chest infection and prolonged ventilatory failure after general anaesthesia. The cardinal diagnostic feature is weakness or exaggerated
9. 10. 11.
Spiller RC, Lee YC, Edge C, et al. Functional significance of the ileal brake in coeliac disease. Gut 1984; 25: A545 (abstr T16). Bali A, Stableforth DE, Asquith P. Prolonged small-intestinal transit time in cystic fibrosis. Br Med J 1983; 287: 1011-14. Cohen SA, Hendricks KM, Eastham EJ, Mathis RK, Walker WA. Chronic nonspecific diarrhea. A complication of dietary fat restriction. Am J Dis Child 1979, 133: 490-92.
12 Cohen
SA, Hendricks KM, Mathis RK, Laramee S, Walker WA. Chronic nonspecific diarrhea: dietary relationships. Pediatrics 1979; 64: 402-07.