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Medium Chain Triglycerides
GASTROENTEflOLOOY
Vol. 53, No. 6 Printed in U.S.A.
Copyright © 1967 by The Williams & Wilkins Co.
CURRENT CLINICAL CONCEPTS Thomas R. Hendrix, M.D. Current Clinical Concepts Editor The Johns Hopkins University School of Medicine Baltimore, Maryland
MEDIUM CHAIN TRIGLYCERIDES A useful adjunct in nutritional therapy PE ~l'ER
R.
HOLT,
M.D.
Gast1·ointestinal Unit, Department of Medicine, St. Luke' s Hospital Center, New York, New Yor/c
The term medium chain triglycerides (MCT) refers to mixed triglycerides of fatty acids with a chain length of six to 10 carbons. This is in distinction to the fats in the usual American diet which contain principally long chain triglycerides (LCT), mixed triglycerides of fatty acids of over 14 carbon chain lengths. Since the demonstration in 1960 by Hashim et aJ.l that MCT were well tolerated and could maintain weight in man, these synthetic fats have shown promise in the management of two major clinical problems that are encountered by gastroenterologists. 1. In patients with malabsorption MCT provide an easily ingested, rapidly absorbed, and readily metabolized source of calories. MCT have been particularly useful in severely malnourished individuals, in patients during periods of rapid body growth, and in malabsorptive disorders for which no specific therapy is available. , 2. MCT have been valuable in patients having obstruction or other functional abAddress requests for reprints to: Peter R. Holt, M.D., Gastrointestinal Unit, Department of Medicine, St. Luke's Hospital Center, New York, New York 10025. This investigation was supported in part by Grant HE 10055 from the United States Public Health Service and by National Institutes of Health Grant AM-08107.
961
normalities of intestinal lymphatics in whom a diet containing regular fat (LCT) results in significant intestinal protein loss with symptoms of hypoproteinemia. Before describing details of the management of patients with these disorders with MCT, some aspects of the absorption and metabolism of medium chain lipids and of the preparations of MCT that are presently available may be considered briefly. The intestinal absorption and the metabolism of MGT and LCT differ markedly. The important features may be briefly summarized as follows. 1. MCT are more rapidly and completely hydrolyzed in the intestinal lumen by pancreatic enzymes. 2. The presence of bile in the lumen is not necessary for normal absorption of MCT. 3. MCT may be absorbed intact by the small intestine and are completely hydrolyzed in intestinal mucosal cells. 4. The small intestine has a greater capacity to absorb MGT than LCT. 5. Fatty acids derived from MGT are transported principally by the portal vein and not by the intestinal lymphatics. 6. MCT absorption does not involve chylomicron formation. 7. Medium chain fatty acids are more rapidly oxidized than those of long chain
962
CURRENT CLINICAL CONCEPTS
length by many tissues, including the liver, small intestine, and striated muscle. Medium chain triglycerides provide a highly concentrated source of calories in the diet although the caloric value (8.4 kcal per g) is somewhat less than that of LCT. The preparations of MCT that have been used in patient studies since 1958 were synthesized from a distillate of coconut oil (up to 65% of the fatty acids of coconut oil have a chain length less than 14). Following esterification of the distillate with glycerol and purification, a bland oil containing 75 to 80% caprylic acid and 20% capric acid with traces of caproic and lauric acids as a mixed triglyceride is obtained. This oil is liquid at room temperature and has been incorporated into a homogenized formula with carbohydrate and protein in most studies to date. Recently, a powdered commerical product (Portagen, Meade Johnson Laboratories) containing MCT has been marketed which may be made up as a bland formula mixture. When prepared according to the manufacturer's instructions, this formula provides 30 cal per fluid ounce and contains 45 g of fat per quart. Ten per cent carbohydrate is present, about one-half of which is in the form of lactose. Formulas used in studies from this institution have generally been prepared with dextrose as the carbohydrate source. A typical dextrose-containing formula might contain, per liter: sodium or potassium caseinate, 60 g (15% of calories) ; dextrose, 160 g (45% of calories); MCT oil, 75 ml ( 40% of calories). These ingredients are homogenized with water in a MantonGaulin dairy homogenizer and the product is kept frozen until used. We have found that the formula can be kept at -20 C for at least 1 year without spoiling. Enough formula for 1 day's use is defrosted every morning and flavoring is added. The introduction of MCT therapy for malabsorption has demonstrated an unusual union of physiological and clinical observations.2· 3 It could have been predicted from the results of animal studies that MCT might be absorbed better than LCT in malabsorption of any cause. The sub-
Vol. 53, No. (j
stitution of normal dietary fat by MCT therefore would be expected to reduce fecal fat losses. The potential benefits that a patient with malabsorption gains from this substitution are: 1. MCT provides a concentrated source of calories that is readily absorbed. This simplifies balancing the caloric requirements of grossly malnourished and growing individuals. 2. Substitution of MCT for LCT lessens the passage of unabsorbed fat into the large intestine and results in a reduction in the number, size, and offensive odor of the stools. Gaseous distension, passage of excessive flatus, and urgency will usually be alleviated as less fat is available for bacterial degradation in the colon. 3. MCT therapy usually decreases the fecal losses of water, electrolytes, and minerals (particularly calcium) that accompany the excretion of steatorrhea! stools. Although few balance studies have been performed to demonstrate such changes directly, it has been our impression that as the bulk of the stool lessens the regulation of fluid and electrolyte balance is simplified. MCT should be considered a nutritional adjunct in management and not a substitute for established specific treatment, i.e., gluten elimination in gluten-induced sprue (celiac disease) ; antibiotic therapy in tropical sprue, blind loop syndrome, and Whipple's disease; or pancreatic enzyme replacement in pancreatic insufficiency. In practice, situations in which MCT have been most effective include the following. 1. Malabsorption of any canse in children with growth retardation. In undernourished children with cystic fibrosis, chronic liver disease, or celiac disease (who are also treated with gluten restriction), growth spurts have been observed with MCT treatment. Frequently the precise cause of steatorrhea in children is not clear and MCT therapy has proven useful in this situation. 2. Severe steatorrhea due to small intestinal resection. Gradually increasing
December 1967
963
CURRENT CLINICAL CONCEL'1'S
quantities of MCT have been administered to such patients with considerable success in alleviating symptoms or inducing weight gain. Care must be exercised in the administration of MCT to these patients, as MCT therapy rarely may induce increased diarrhea with concomitant. fecal electrolyte and fluid losses. Although failures of treatment have been reported by others, we have found that patients with steatorrhea following bowel resection uniformly benefit during either temporary or prolonged MCT therapy. 3. Other forms of malabsorption in adults for which there is no specific therapy. Examples of patients who benefit greatly include those with severe postgastrectomy malnutrition in whom increasing LCT intake results in unpleasant steatorrhea ; patients with extensive regional enteritis; and patients with rare forms of steatorrhea due to sarcoidosis, abetalipoproteinemia, etc. (table 1). 4. Exudative e.nteropathy with hypoproteinemia, steatorrhea, or chyluria due to lymphatic abnormalities. Since, following intestinal absorption, MCT are not transported in lymph, they have been used in the treatment of diseases of lymphatics. Chyluria has been eliminated in some patients with relief of associated renal and urethral colic, hematuria, and proteinuria.4 The rate of fluid collection in the chest of patients with chylothorax 4 and in the abdomen of those with chylous ascites may be reduced by the substitution of dietary LCT by MCT. 5 In intestinal lymphangiectasia, relief of the peripheral edema, ascites, symptoms of steatorrhea, and hypoproteinemia has been brought about by elimination of dietary long chain lipids with 6 • 7 or without 8 addition of MCT. A strict low fat diet appears quite effective in this condition but it is dry and unpalatable and it is much better tolerated with supplements of MCT formula or oil. Presumably, the absence of lymphatic transport of dietary lipids results in an alteration in the dynamics of intestinal lymph flow and a resultant reduction of the loss into the intestine of protein-rich lymph. The exudative enteropathy secondary to intestinal
TADLE
1. Use of MC'l' therapy in malabs01·ptivc disordm·s Disorder
Pancreatic insuffic ie ncy Chron ic pancreatitis Cyslic fibrosis
Result of usc of MCT
Useful as addition to enzyme supplements Excellen t growth spu r ts reported in ch ildren
Luminal bile salt deficiency Biliary atresia, cirTherapy successful but rhos is , extrahepatic IISIIally unnecessary bili ary obstruction, blind loop syndrome Neonatal hepatitis, Excellent resnl ts re childhood chronic ported in child ren active hepatitis Small bowel resection Usually excellent in reducing symptoms and maintaining nutrition. Occasiormlly e nhanced diarrhea necessitates discontinuation Useful but dumping Postgastrectomy sympLoms may be accentuated. Special formulas or MCT oil mny be necessary Small intestinal diseases Sprue Thempy successful but Whipple's disease llllllecessnry Region al enteritis Excellent improveme11 L in nutrit.ion possible Miscellaneous Scleroderma U11successful in a si11gle pa tic11L 10 AbeLalipoproSuccessfu l but; usually Lcinemin llllllcceHsnry lntest.inallymphangi- Successfu l and reduces ectnsia ex uda t.ive e n teropnthy Sarcoidosis Success reported in s inGastrointestin a l masglc patient.s to cytosis
diseases such as celiac sprue has also been rapidly ameliorated with MCT 7 (and our unpublished observations). MCT also has a potential use m the management of disorders of lipid metabolism. As chylomicron formation is unnecessary for medium chain lipid transport
964
CURRENT CLINICAL CONCEPTS
from the intestine following absorption, MCT therapy has been tried experimentally in patients with fat-induced hypertriglyceridemia. At present these patients are usually treated with a low fat diet. The addition of MCT to this diet has not resulted in a rise in serum triglycerides and has improved the palatability of the diet. 9 Recently, experimental alcohol-induced fatty liver in rats has been ameliorated by the provision of isocaloric quantities of MCT for LCT in the diet. 10 These results probably reflect differences in hepatic metabolic pathways for medium and long chain lipids. The author has not read of the application of these interesting experimental results to the management of human liver disease. It has been our experience that MCT formula prepar·ations and diets containing MCT oil have been tolerated very well. Less than 10% of our patients have discontinued using MCT preparations because of unpleasant side effects. Minor symptoms do occur, however, and these have included nausea, occasional vomiting, abdominal discomfort, borborygmi, and diarrhea. The mechanism of such intolerance to MCT preparations is unclear but it may be related to the rapid hydrolysis of this fat and the resultant high concentrations of free fatty acids in the stomach or intestinal lumen. In postgastrectomy patients dumping symptoms have frequently been induced when the formula has been rapidly ingested. We have come to a number of practical conclusions about these side effects of MCT therapy. MCT preparations should initially be introduced in small amounts and the quantity increased gradually. Usually we give the patient a taste of the formula in different flavors (e.g., vanilla, strawberry, lemon, or coffee). The preparation which is best tolerated by taste is then given as a supplement of 3 ounces at regular meal times. After 1 or 2 days, the formula is also given between meals as a full glass of about 6 ounces (with crackers or cookies) and then further increased according to individual patient tolerance.
Vol. 53, No.6
Most patients with fat malabsorption will tolerate a diet containing limited amounts of regular dietary fat (usually about 30 g) without symptoms. In such patients, the aim of therapy is to replace by MCT the calories that have been eliminated by removal of fat from the diet, and this is frequently achieved by the provision of as little as 16 ounces of MCT formula (about 500 cal) daily. For patients allowed 30 g of long chain fat daily, fish, chicken, and lean meat have been included several times weekly to make the dietary regimen much more acceptable. Symptoms may occur only during the first few days of administration and then disappear, so that the patient should be encouraged to persist with at least ·the smallest dose. The formula should not be cold and should be taken quite slowly, a point that is particularly important in postgastrectomy patients. Occasionally, therapy with anticholinergics alleviates symptoms dramatically. Intolerance to the formula may result from lactose intolerance, and the MCT oil or a specially prepared dextrose containing formula may be well accepted. The MCT oil has been used in the preparation and cooking of food for some patients with much success.U Up to 40 or 50 ml of the oil itself (providing 320 to 400 cal) have been taken as "medicine" by some patients who do not tolerate the formula preparations. As an example, for 2 years following Billroth II gastrectomy a 34-year-old woman had severe symptoms of dumping induced by even small quantities of carbohydrate. She weighed only 39 kg and had lost 25% of her preoperative body weight. The addition of MCT formula to a high fat, high protein, low carbohydrate diet increased her dumping symptoms markedly. She was able, however, to take 15 ml of MCT oil at the time of her three main meals, thus increasing her caloric intake by about 380 cal per day, and she slowly gained weight thereafter. In general, children appear to tolerate the formula preparations much better than adults, who tend to have psychologic objections to the ingestion of a bland liquid
December 1967
965
CURRENT CLINICAL CONCEPTS
food. Adults who derive a significant reduction in their symptoms during therapy accept MCT more readily than patients who do not note a relatively rapid response of their complaints. If complete substitution of MCT for LCT is required, the patient is best treated in the hospital, as the persuasive powers of interested physicians and dieticians are required. To improve the palatability of such a strict diet these patients should be allowed other low fat foods such as apples, bananas, lettuce, celery, and rice. Recently Miss R. Reilly, our research dietician, recognized that some patients will not tolerate the taste of caseinate in the regular formula and found that a mixture of skim milk (35 g), dextrose (7 g) and MCT oil (10 ml) made up to 240 ml with water met with considerable acceptance. This formula may be readily prepared in a household blender. It is theoretically possible that absorbed MCT could lead to systemic side effects which have neither been reported nor fully investigated to date. Fatty acids of medium chain length have been shown to produce narcosis in rats, 12 and electroencephalographic changes including slowing of a waves can occur during infusion of fatty acids of 2 to 6 carbon lengths.13 Because of these experimental observations some caution in the administration of large quantities of MCT to patients with severe liver disease and extensive portosystemic shunting seems warranted at present. Although ketone bodies are important products of medium chain lipid metabolism, hyperketonemia does not readily occur in normal or diabetic subjects 14 except in the absence of carbohydrates. 1" Despite these encouraging experimental observations careful monitoring of diabetic control is indicated when such patients are receiving MCT therapy. In summary, medium chain triglycerides have now found a place in the nutritional therapy of selected patients with disorders of abdominal lymphatic drainage and in malabsorptive diseases. Although no major toxic reactions have been described, minor side effects are common, but they may be
overcome when care is taken with the administration and dosage of MCT. REFERENCES 1. Hashim, S. A., A Arteaga, and T. B. Van Itallie. HJ60. Effect of a saturated medium-
chain tryglyceride on serum-lipids in man. Lancet 1: 1105-1108. 2. Holt, P. R., S. A. Hashim, and T. B. Van Itallie. 1965. Treatment of malabsorption syndrome and exudative enteropathy with synthetic medium chain triglycerides. Amer. J. Gastroent. 43: 549-559. 3. Greenberger, N. J., R. D. Ruppert, and M. Tzagournis. 1967. Use of medium chain triglycerides in malabsorption. Ann. Intern. Med. 66: 727-734. 4. Hashim, S. A., H. B. Roholt, V. K. Babayan, and T. B. Van Itallie. 1964. Treatment of chyluria and chylothorax with medium chain triglycerides. New Eng. J. Med . 270: 756-761. 5. Porter, M. G., and W. R. Richardson. 1965.
Effect of medium chain triglyceride diet on gastrointestinal protein loss and ascites formation in an infant with multiple congenital lymphatic anomalies (abstract). Southern Mecl. J. 58: 1590. 6. Holt, P. R. HJ64. Dietary treatment of protein loss in intestinal lymphangiectasia . The effect of eliminating dietary long chain tryglycerides on albumin metabolism in this condition. Pediatrics 31,: 629-635. 7. Jarnum, S., and H. Jensen. 1966. Medium chain triglycerides (MCT) in the treatment of protein-losing enteropathy and malabsorption syndromes. Scancl. J. Gastroent. 1: 306-313.
8. Jeffries, G. H., A. Chapman, Sleisenger. 1964. Low-fat diet lymphangiectasia. Its effect metabolism. New Eng. J.
and M . H. in intestinal on albumin Mecl. 270:
761-766.
9. Furman, R. H., R. P. Howard, 0. J. Brusco, and P. Alaupovic. 1965. Effects of medium chain length triglyceride (MCT) on serum lipids and lipoproteins in familial hyperchylomicronemia (dietary fat-induced lipemia) and dietary carbohydrate-accentuated lipemia. J. Lab. Clin. Med. 66: 912-926. 10. Lieber, C. S., and L . M. DeCarli. 1966. Study of agents for the prevention of the fatty liver produced by prolonged alcohol intake. Gastroenterology 50: 316-322.
966
CURRENT CLINICAL CONCEPTS
11. Scheizas, A., J. A. Cremen, R. O'Brien, and E. Larson. 1967. M edium chain triglycerides-use in food preparation. J . Amer. Diabetic Assn. 51: 228-232 . 12. Samson, F. E., N. Dahl, and D. R. Dahl. 1956. A study on the narcotic action of the short chain fatty acids. J . Clin. Invest. 35 : 12911298. 13. White, R. P ., and F. E . Samson. 1956. Effects
of fatty acid anions on the electroencephalo-
Vol. 53, No .6
gram of unanesthetized rabbits. Amer. J. Physiol.186: 271-274. 14. Bergen, S. S., Jr., S. A. Hashim, and T. B. Van Hallie. 1966. Hyperketonemia induced in man by medium chain triglyceride. Diabetes 15: 723-725. 15. Freund, G., and R. L. Weinsier. 1966. Standardized ketosis in man following medium chain triglyceride ingestion. Metabolism 15: 980-991.
Vol. 53, No. 6 Printed in U.S.A.
Copyright © 1967 by The Williams & Wilkins Co.
CURRENT CLINICAL CONCEPTS Thomas R. Hendrix, M.D. Current Clinical Concepts Editor The Johns Hopkins University School of Medicine Baltimore, Maryland
MEDIUM CHAIN TRIGLYCERIDES A useful adjunct in nutritional therapy PE ~l'ER
R.
HOLT,
M.D.
Gast1·ointestinal Unit, Department of Medicine, St. Luke' s Hospital Center, New York, New Yor/c
The term medium chain triglycerides (MCT) refers to mixed triglycerides of fatty acids with a chain length of six to 10 carbons. This is in distinction to the fats in the usual American diet which contain principally long chain triglycerides (LCT), mixed triglycerides of fatty acids of over 14 carbon chain lengths. Since the demonstration in 1960 by Hashim et aJ.l that MCT were well tolerated and could maintain weight in man, these synthetic fats have shown promise in the management of two major clinical problems that are encountered by gastroenterologists. 1. In patients with malabsorption MCT provide an easily ingested, rapidly absorbed, and readily metabolized source of calories. MCT have been particularly useful in severely malnourished individuals, in patients during periods of rapid body growth, and in malabsorptive disorders for which no specific therapy is available. , 2. MCT have been valuable in patients having obstruction or other functional abAddress requests for reprints to: Peter R. Holt, M.D., Gastrointestinal Unit, Department of Medicine, St. Luke's Hospital Center, New York, New York 10025. This investigation was supported in part by Grant HE 10055 from the United States Public Health Service and by National Institutes of Health Grant AM-08107.
961
normalities of intestinal lymphatics in whom a diet containing regular fat (LCT) results in significant intestinal protein loss with symptoms of hypoproteinemia. Before describing details of the management of patients with these disorders with MCT, some aspects of the absorption and metabolism of medium chain lipids and of the preparations of MCT that are presently available may be considered briefly. The intestinal absorption and the metabolism of MGT and LCT differ markedly. The important features may be briefly summarized as follows. 1. MCT are more rapidly and completely hydrolyzed in the intestinal lumen by pancreatic enzymes. 2. The presence of bile in the lumen is not necessary for normal absorption of MCT. 3. MCT may be absorbed intact by the small intestine and are completely hydrolyzed in intestinal mucosal cells. 4. The small intestine has a greater capacity to absorb MGT than LCT. 5. Fatty acids derived from MGT are transported principally by the portal vein and not by the intestinal lymphatics. 6. MCT absorption does not involve chylomicron formation. 7. Medium chain fatty acids are more rapidly oxidized than those of long chain
962
CURRENT CLINICAL CONCEPTS
length by many tissues, including the liver, small intestine, and striated muscle. Medium chain triglycerides provide a highly concentrated source of calories in the diet although the caloric value (8.4 kcal per g) is somewhat less than that of LCT. The preparations of MCT that have been used in patient studies since 1958 were synthesized from a distillate of coconut oil (up to 65% of the fatty acids of coconut oil have a chain length less than 14). Following esterification of the distillate with glycerol and purification, a bland oil containing 75 to 80% caprylic acid and 20% capric acid with traces of caproic and lauric acids as a mixed triglyceride is obtained. This oil is liquid at room temperature and has been incorporated into a homogenized formula with carbohydrate and protein in most studies to date. Recently, a powdered commerical product (Portagen, Meade Johnson Laboratories) containing MCT has been marketed which may be made up as a bland formula mixture. When prepared according to the manufacturer's instructions, this formula provides 30 cal per fluid ounce and contains 45 g of fat per quart. Ten per cent carbohydrate is present, about one-half of which is in the form of lactose. Formulas used in studies from this institution have generally been prepared with dextrose as the carbohydrate source. A typical dextrose-containing formula might contain, per liter: sodium or potassium caseinate, 60 g (15% of calories) ; dextrose, 160 g (45% of calories); MCT oil, 75 ml ( 40% of calories). These ingredients are homogenized with water in a MantonGaulin dairy homogenizer and the product is kept frozen until used. We have found that the formula can be kept at -20 C for at least 1 year without spoiling. Enough formula for 1 day's use is defrosted every morning and flavoring is added. The introduction of MCT therapy for malabsorption has demonstrated an unusual union of physiological and clinical observations.2· 3 It could have been predicted from the results of animal studies that MCT might be absorbed better than LCT in malabsorption of any cause. The sub-
Vol. 53, No. (j
stitution of normal dietary fat by MCT therefore would be expected to reduce fecal fat losses. The potential benefits that a patient with malabsorption gains from this substitution are: 1. MCT provides a concentrated source of calories that is readily absorbed. This simplifies balancing the caloric requirements of grossly malnourished and growing individuals. 2. Substitution of MCT for LCT lessens the passage of unabsorbed fat into the large intestine and results in a reduction in the number, size, and offensive odor of the stools. Gaseous distension, passage of excessive flatus, and urgency will usually be alleviated as less fat is available for bacterial degradation in the colon. 3. MCT therapy usually decreases the fecal losses of water, electrolytes, and minerals (particularly calcium) that accompany the excretion of steatorrhea! stools. Although few balance studies have been performed to demonstrate such changes directly, it has been our impression that as the bulk of the stool lessens the regulation of fluid and electrolyte balance is simplified. MCT should be considered a nutritional adjunct in management and not a substitute for established specific treatment, i.e., gluten elimination in gluten-induced sprue (celiac disease) ; antibiotic therapy in tropical sprue, blind loop syndrome, and Whipple's disease; or pancreatic enzyme replacement in pancreatic insufficiency. In practice, situations in which MCT have been most effective include the following. 1. Malabsorption of any canse in children with growth retardation. In undernourished children with cystic fibrosis, chronic liver disease, or celiac disease (who are also treated with gluten restriction), growth spurts have been observed with MCT treatment. Frequently the precise cause of steatorrhea in children is not clear and MCT therapy has proven useful in this situation. 2. Severe steatorrhea due to small intestinal resection. Gradually increasing
December 1967
963
CURRENT CLINICAL CONCEL'1'S
quantities of MCT have been administered to such patients with considerable success in alleviating symptoms or inducing weight gain. Care must be exercised in the administration of MCT to these patients, as MCT therapy rarely may induce increased diarrhea with concomitant. fecal electrolyte and fluid losses. Although failures of treatment have been reported by others, we have found that patients with steatorrhea following bowel resection uniformly benefit during either temporary or prolonged MCT therapy. 3. Other forms of malabsorption in adults for which there is no specific therapy. Examples of patients who benefit greatly include those with severe postgastrectomy malnutrition in whom increasing LCT intake results in unpleasant steatorrhea ; patients with extensive regional enteritis; and patients with rare forms of steatorrhea due to sarcoidosis, abetalipoproteinemia, etc. (table 1). 4. Exudative e.nteropathy with hypoproteinemia, steatorrhea, or chyluria due to lymphatic abnormalities. Since, following intestinal absorption, MCT are not transported in lymph, they have been used in the treatment of diseases of lymphatics. Chyluria has been eliminated in some patients with relief of associated renal and urethral colic, hematuria, and proteinuria.4 The rate of fluid collection in the chest of patients with chylothorax 4 and in the abdomen of those with chylous ascites may be reduced by the substitution of dietary LCT by MCT. 5 In intestinal lymphangiectasia, relief of the peripheral edema, ascites, symptoms of steatorrhea, and hypoproteinemia has been brought about by elimination of dietary long chain lipids with 6 • 7 or without 8 addition of MCT. A strict low fat diet appears quite effective in this condition but it is dry and unpalatable and it is much better tolerated with supplements of MCT formula or oil. Presumably, the absence of lymphatic transport of dietary lipids results in an alteration in the dynamics of intestinal lymph flow and a resultant reduction of the loss into the intestine of protein-rich lymph. The exudative enteropathy secondary to intestinal
TADLE
1. Use of MC'l' therapy in malabs01·ptivc disordm·s Disorder
Pancreatic insuffic ie ncy Chron ic pancreatitis Cyslic fibrosis
Result of usc of MCT
Useful as addition to enzyme supplements Excellen t growth spu r ts reported in ch ildren
Luminal bile salt deficiency Biliary atresia, cirTherapy successful but rhos is , extrahepatic IISIIally unnecessary bili ary obstruction, blind loop syndrome Neonatal hepatitis, Excellent resnl ts re childhood chronic ported in child ren active hepatitis Small bowel resection Usually excellent in reducing symptoms and maintaining nutrition. Occasiormlly e nhanced diarrhea necessitates discontinuation Useful but dumping Postgastrectomy sympLoms may be accentuated. Special formulas or MCT oil mny be necessary Small intestinal diseases Sprue Thempy successful but Whipple's disease llllllecessnry Region al enteritis Excellent improveme11 L in nutrit.ion possible Miscellaneous Scleroderma U11successful in a si11gle pa tic11L 10 AbeLalipoproSuccessfu l but; usually Lcinemin llllllcceHsnry lntest.inallymphangi- Successfu l and reduces ectnsia ex uda t.ive e n teropnthy Sarcoidosis Success reported in s inGastrointestin a l masglc patient.s to cytosis
diseases such as celiac sprue has also been rapidly ameliorated with MCT 7 (and our unpublished observations). MCT also has a potential use m the management of disorders of lipid metabolism. As chylomicron formation is unnecessary for medium chain lipid transport
964
CURRENT CLINICAL CONCEPTS
from the intestine following absorption, MCT therapy has been tried experimentally in patients with fat-induced hypertriglyceridemia. At present these patients are usually treated with a low fat diet. The addition of MCT to this diet has not resulted in a rise in serum triglycerides and has improved the palatability of the diet. 9 Recently, experimental alcohol-induced fatty liver in rats has been ameliorated by the provision of isocaloric quantities of MCT for LCT in the diet. 10 These results probably reflect differences in hepatic metabolic pathways for medium and long chain lipids. The author has not read of the application of these interesting experimental results to the management of human liver disease. It has been our experience that MCT formula prepar·ations and diets containing MCT oil have been tolerated very well. Less than 10% of our patients have discontinued using MCT preparations because of unpleasant side effects. Minor symptoms do occur, however, and these have included nausea, occasional vomiting, abdominal discomfort, borborygmi, and diarrhea. The mechanism of such intolerance to MCT preparations is unclear but it may be related to the rapid hydrolysis of this fat and the resultant high concentrations of free fatty acids in the stomach or intestinal lumen. In postgastrectomy patients dumping symptoms have frequently been induced when the formula has been rapidly ingested. We have come to a number of practical conclusions about these side effects of MCT therapy. MCT preparations should initially be introduced in small amounts and the quantity increased gradually. Usually we give the patient a taste of the formula in different flavors (e.g., vanilla, strawberry, lemon, or coffee). The preparation which is best tolerated by taste is then given as a supplement of 3 ounces at regular meal times. After 1 or 2 days, the formula is also given between meals as a full glass of about 6 ounces (with crackers or cookies) and then further increased according to individual patient tolerance.
Vol. 53, No.6
Most patients with fat malabsorption will tolerate a diet containing limited amounts of regular dietary fat (usually about 30 g) without symptoms. In such patients, the aim of therapy is to replace by MCT the calories that have been eliminated by removal of fat from the diet, and this is frequently achieved by the provision of as little as 16 ounces of MCT formula (about 500 cal) daily. For patients allowed 30 g of long chain fat daily, fish, chicken, and lean meat have been included several times weekly to make the dietary regimen much more acceptable. Symptoms may occur only during the first few days of administration and then disappear, so that the patient should be encouraged to persist with at least ·the smallest dose. The formula should not be cold and should be taken quite slowly, a point that is particularly important in postgastrectomy patients. Occasionally, therapy with anticholinergics alleviates symptoms dramatically. Intolerance to the formula may result from lactose intolerance, and the MCT oil or a specially prepared dextrose containing formula may be well accepted. The MCT oil has been used in the preparation and cooking of food for some patients with much success.U Up to 40 or 50 ml of the oil itself (providing 320 to 400 cal) have been taken as "medicine" by some patients who do not tolerate the formula preparations. As an example, for 2 years following Billroth II gastrectomy a 34-year-old woman had severe symptoms of dumping induced by even small quantities of carbohydrate. She weighed only 39 kg and had lost 25% of her preoperative body weight. The addition of MCT formula to a high fat, high protein, low carbohydrate diet increased her dumping symptoms markedly. She was able, however, to take 15 ml of MCT oil at the time of her three main meals, thus increasing her caloric intake by about 380 cal per day, and she slowly gained weight thereafter. In general, children appear to tolerate the formula preparations much better than adults, who tend to have psychologic objections to the ingestion of a bland liquid
December 1967
965
CURRENT CLINICAL CONCEPTS
food. Adults who derive a significant reduction in their symptoms during therapy accept MCT more readily than patients who do not note a relatively rapid response of their complaints. If complete substitution of MCT for LCT is required, the patient is best treated in the hospital, as the persuasive powers of interested physicians and dieticians are required. To improve the palatability of such a strict diet these patients should be allowed other low fat foods such as apples, bananas, lettuce, celery, and rice. Recently Miss R. Reilly, our research dietician, recognized that some patients will not tolerate the taste of caseinate in the regular formula and found that a mixture of skim milk (35 g), dextrose (7 g) and MCT oil (10 ml) made up to 240 ml with water met with considerable acceptance. This formula may be readily prepared in a household blender. It is theoretically possible that absorbed MCT could lead to systemic side effects which have neither been reported nor fully investigated to date. Fatty acids of medium chain length have been shown to produce narcosis in rats, 12 and electroencephalographic changes including slowing of a waves can occur during infusion of fatty acids of 2 to 6 carbon lengths.13 Because of these experimental observations some caution in the administration of large quantities of MCT to patients with severe liver disease and extensive portosystemic shunting seems warranted at present. Although ketone bodies are important products of medium chain lipid metabolism, hyperketonemia does not readily occur in normal or diabetic subjects 14 except in the absence of carbohydrates. 1" Despite these encouraging experimental observations careful monitoring of diabetic control is indicated when such patients are receiving MCT therapy. In summary, medium chain triglycerides have now found a place in the nutritional therapy of selected patients with disorders of abdominal lymphatic drainage and in malabsorptive diseases. Although no major toxic reactions have been described, minor side effects are common, but they may be
overcome when care is taken with the administration and dosage of MCT. REFERENCES 1. Hashim, S. A., A Arteaga, and T. B. Van Itallie. HJ60. Effect of a saturated medium-
chain tryglyceride on serum-lipids in man. Lancet 1: 1105-1108. 2. Holt, P. R., S. A. Hashim, and T. B. Van Itallie. 1965. Treatment of malabsorption syndrome and exudative enteropathy with synthetic medium chain triglycerides. Amer. J. Gastroent. 43: 549-559. 3. Greenberger, N. J., R. D. Ruppert, and M. Tzagournis. 1967. Use of medium chain triglycerides in malabsorption. Ann. Intern. Med. 66: 727-734. 4. Hashim, S. A., H. B. Roholt, V. K. Babayan, and T. B. Van Itallie. 1964. Treatment of chyluria and chylothorax with medium chain triglycerides. New Eng. J. Med . 270: 756-761. 5. Porter, M. G., and W. R. Richardson. 1965.
Effect of medium chain triglyceride diet on gastrointestinal protein loss and ascites formation in an infant with multiple congenital lymphatic anomalies (abstract). Southern Mecl. J. 58: 1590. 6. Holt, P. R. HJ64. Dietary treatment of protein loss in intestinal lymphangiectasia . The effect of eliminating dietary long chain tryglycerides on albumin metabolism in this condition. Pediatrics 31,: 629-635. 7. Jarnum, S., and H. Jensen. 1966. Medium chain triglycerides (MCT) in the treatment of protein-losing enteropathy and malabsorption syndromes. Scancl. J. Gastroent. 1: 306-313.
8. Jeffries, G. H., A. Chapman, Sleisenger. 1964. Low-fat diet lymphangiectasia. Its effect metabolism. New Eng. J.
and M . H. in intestinal on albumin Mecl. 270:
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9. Furman, R. H., R. P. Howard, 0. J. Brusco, and P. Alaupovic. 1965. Effects of medium chain length triglyceride (MCT) on serum lipids and lipoproteins in familial hyperchylomicronemia (dietary fat-induced lipemia) and dietary carbohydrate-accentuated lipemia. J. Lab. Clin. Med. 66: 912-926. 10. Lieber, C. S., and L . M. DeCarli. 1966. Study of agents for the prevention of the fatty liver produced by prolonged alcohol intake. Gastroenterology 50: 316-322.
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11. Scheizas, A., J. A. Cremen, R. O'Brien, and E. Larson. 1967. M edium chain triglycerides-use in food preparation. J . Amer. Diabetic Assn. 51: 228-232 . 12. Samson, F. E., N. Dahl, and D. R. Dahl. 1956. A study on the narcotic action of the short chain fatty acids. J . Clin. Invest. 35 : 12911298. 13. White, R. P ., and F. E . Samson. 1956. Effects
of fatty acid anions on the electroencephalo-
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gram of unanesthetized rabbits. Amer. J. Physiol.186: 271-274. 14. Bergen, S. S., Jr., S. A. Hashim, and T. B. Van Hallie. 1966. Hyperketonemia induced in man by medium chain triglyceride. Diabetes 15: 723-725. 15. Freund, G., and R. L. Weinsier. 1966. Standardized ketosis in man following medium chain triglyceride ingestion. Metabolism 15: 980-991.