Role of juice carbohydrate malabsorption in chronic nonspecific diarrhea in children

CURRENT LITERATURE AND CLINICAL ISSUES

Role of juice carbohydrate malabsorption in chronic nonspecific diarrhea in children Prompted by a historical relationship between clear fluids and chronic diarrhea in children, the American Academy of Pediatrics Committee on Nutrition issued a statement recently on the use of fruit juice in the diets of young children.1 The statement served as a cautionary note to pediatricians on the potential problems associated with the ingestion of excessive amounts of apple and pear juices by young children, particularly because of the amounts of sorbitol contained in these juices. The statement advised that pediatricians should obtain a dietary history for any child with symptoms such as chronic diarrhea, abdominal pain, or bloating, as a means of establishing a link between symptoms and excessive intake of juices that contain sorbitol. The statement did not attribute the symptoms of chronic nonspecific diarrhea to any other carbohydrate found in juices. However, it is possible that sorbitol may not be the only constituent on which to focus attention. Other malabsorbed carbohydrates, such as fructose, also should be considered in a patient with CNSD. Here we review current concepts of juice carbohydrate malabsorption to better serve pediatricians who encounter CNSD in their daily clinical practices. CHRONIC NONSPECIFIC CHILDREN

DIARRHEA IN

Definition. Chronic nonspecific diarrhea, also known as irritable colon of childhood2 and toddlers' diarrhea, 3 is one of the most common problems encountered in pediatric medicine.31~ Typically, onset of the disorder occurs between 6 and 36 months of age, but it can be as late as 54 months. Family members of children with CNSD often report nonspecific gastrointestinal complaints I~ or functional bowel disorders, 2; 3, 11, 12 but the children themselves have normal patterns of growth and development (although a small percentage fail to gain weight because of inadequate Supported by an educational grant from Welch's, Concord, Mass. Reprint requests: Fima Lifshitz, MD, Chairman, Department of Pediatrics, Maimonides Medical Center, Brooklyn, NY 11219. 9/34/35937

caloric intake9). Signs of infection are not evident during the course of CNSD, but some children have gastroenteritis or acute illness before the onset of CNSD. 2, 3, 8, 9 More than 90% of cases of CNSD spontaneously resolve by the time the patient is 39 months of age. 9' 11 Generally, children with CNSD have three or more loose stools per day for at least 3 weeks. Early in the day, stools are large and either formed or partially formed in consistency.2, 3, lO Those produced later in the day are smaller, looser, and may contain undigested food particles 2, 3, 5,10, 13 evidence of the decreased mouth-to-anus transit time and, possibly, of disordered small-intestine motility.5 The stools also have a higher percentage of extractable water, with increased bile acid concentrations.7, 14 CNSD

Chronic nonspecificdiarrhea

I

Cause of CNSD and role of carbohydrate malabsorption. Disordered small-intestine motility,2, 5 dietary fat restriction,8, 9, 15 and excessive fluid intake6, 13 have been cited as possible contributory factors in the pathogenesis of CNSD. However, carbohydrate malabsorption resulting from the ingestion of fluids containing carbohydrates or sugar alcohols in varying concentrations also may cause gastrointestinal complaints, including diarrhea.1623 Malabsorption of the carbohydrates found in fruit juices has been implicated as a cause of CNSD in children. 22, 23 Malabsorption of carbohydrates contained in fruit juices may be fairly common. For example, one of three healthy adults 16 and two of three children 17 incompletely absorb orally administered fructose (0.7 to 2.0 kg/dose). The hexatols, a group of sugar alcohols, also are capable of producing osmotic diarrhea. 13,24-27 Sorbitol, a Well-known hexatol, is contained in apple and pear juice (Table). Malabsorption of sorbitol and fructose has been studied in both adults and children. 16-28 It was found that the capacity of the small intestine to absorb fructose was more limited than was previously thought. 16 The frequency of fructose realabsorption was related to both concentration and dose (Fig.

825

826

Lifshitz et al.

The JournalofPediatrics May 1992

lOO I 80 % subjects with incomplete absorption

T a b l e . Carbohydrate content of fruit juices

71.4%

60 i 50 40

37.5%

Glucose

Sucrose

Sorbitol

Apple Pear White grape Orange

6.2 6.4 7.5 2.4

2.7 2.3 7.1 2.4

1.2 0.9 0.0 4.7

0.5 2.0 0.0 0.0

14.3%

10 0

Fructose

Modifiedfrom HyamsJS, EtienneNL, LeicbtnerAM, TheuerRC (Pediatrics 1988;82:64-8)and HardingeMG, SwarnerJB, CrooksH (J AmDiet Assoc 1965;46:197-204).

30 20"

Juice

0% n=14 50 g 20%

n=16 n=14 50 g 37.5 g 10% 10% Fructose test solutions

n=3 25 g 10%

Fig. I. Frequency of incomplete absorption of fructose in normal subjects, For fructose test solutions,the number of grams dissolved in water for each solution strength (20% or 10%) is shown, n, Number of subjects. (From Ravich WJ, Bayless TM, Thomas M. Gastroenterology 1983;84:26-9.)

1). Of the two mechanisms involved in fructose absorption-~glucose-independent facilitated transport and glucose-dependent fructose cotransport--the latter mechanism was additive to the absorption of fructose. 1s In fact, the presence of glucose in a solution enhanced the absorption of fructose, especially when the concentrations of both sugars were equal (Fig. 2, a). 18 Malabsorption of fructose in the fructose-glucose mixtures was measurable only if fructose was present in excess of glucose (Fig. 2, b and c). Because fructose and sorbitol occur together in significant quantities in common foods, the absorptive capacity of this mixture has been evaluated. Malabsorption was evident when sorbitol was given alone, but when the fructose-sorbitol mixture was given, malabsorption was even more pronounced. 19 Although the mechanisms by which this occurs require additional investigation, the combination of fructose and sorbitol in foods and its gastrointestinal effect were considered to be important. Fructose malabsorption also has been evaluated in subjects with gastrointestinal disease. 2~ 2~ Adults with functional bowel disease were given fructose, sorbitol, a fructose-sorbitol mixture, and sucrose. 2~ As shown in other studies, fructose given as sucrose was well absorbed and well tolerated. When sorbitol alone was given, a rise in breath hydrogen excretion occurred, and some subjects noted mild to moderate gastrointestinal symptoms. The fructose-sorbitol mixture, however, resulted in a more-than-additive effect on breath hydrogen excretion and on the severity of symptoms (Fig. 3). It has been hypothesized that more than

one mechanism for fructose absorption exists, each with varying transport capacities. One of these low-capacity mechanisms may be inhibited by sorbitol, thereby causing the more-than-additive response when subjects receive the fructose-sorbitol mixture. Although threshold absorption levels of sorbitol have been described for adults, children may not be able to tolerate the same amounts. Chronic abdominal pain from chewing sugarless gum that contained only 1.3 to 2.2 gm of sorbito! per stick was reported in a 3-year-old girl. 2s Sorbitol malabsorption was demonstrated in healthy children and in children with CNSD who were challenged with various fruit juices. 22 Breath hydrogen responses in the control children were greater after ingestion of pear juice, apple juice, and the 2% sorbitol solution than with white grape juice. Breath hydrogen responses in the children with CNSD were also greater after ingestion of pear juice and 2% sorbitol solution than with juices not containing this sugar. Breath hydrogen responses were greater after ingestion of apple juice (0.5% sorbitol) than with white grape juice (no sorbitol). In this study, gastrointestinal symptoms, including diarrhea, developed in approximately 40% of children who had increased breath hydrogen responses after drinking pear juice, apple juice, or the sorbitol solution. Eliminating fruit juice from the diets of the children with CNSD often resulted in cessation of diarrhea. Significant increases in breath hydrogen also occurred after children with CNSD ingested nonexcessive quantities of apple juice. 23 After accounting for all other factors that may have contributed to CNSD in these children, tbe investigators concluded that the ingestion of apple juice, even in nonexcessive amounts, may have been a factor in the pathogenesis of CNSD. Children with abdominal symptoms or functional bowel disorders were evaluated after ingesting a fructose solution. 17 Malabsorption of this carbohydrate was noted in 71% of the group. Seven children were rechallenged with a fructose solution to which equal amounts of glucose or galactose had been added. Breath hydrogen increases were 5 ppm after ingestirrg the solution of fructose plus glucose and

Volume 120 Number 5

Juice malabsorption and chronic diarrhea

8 27

loo,I

r

z"

20 0

2o

50 gF

50 gF

50 gF+50 gG

50 gF+25 gG

2~ CO C3_

20 0

50 gF

50gF+12.5 gG

Fig. 2. Effect of glucose (G) on absorption capacity of fructose (F). Absorption capacity of fructose was enhanced by glucose, especially when fructose and glucose concentrations were equal (a). Malabsorption of fructose in the fructose-glucose mixtures was measurable only if fructose was present in excess of glucose (b and c). He-peak, Breath hydrogen production; g, grams of sugar in test solution. (From Rumessen J J, Gudmand-Hoyer E. Gut 1986;27:1161-8.)

A Appm 90

~176

Appm 9

70 50 30

F

20

10 60

120 180 240 minutes

0

0

60

:-

120 180 240 minutes

Fig. 3. Two examples (A and B) of additive effect of fructose-sorbitol (F + S) mixture on breath hydrogen response with time. Malabsorption of fructose-sorbitol mixture exceeded the sum of malabsorbed amounts of individual challenges with fructose (F) and sorbitol (S). Appm, Increase in breath hydrogen. (From Rumessen J J, Gudmand-Hoyer E. Gastroenterology 1988;95:694-700.)

10 ppm after ingesting the solution of fructose plus galactose; but 103 ppm after ingesting the fructose solution alone. Several points emerged from the studies of carbohydrate absorption of sugars contained in fruit juices: 1. The capacity of the small intestine to absorb fructose is more limited than was previously thought. 16 2. When fructose is not combined with any other carbohydrate, its absorptive capacity is concentration and dose dependent. 16' 18 3. Foods that contain equivalent amounts of fructose and glucose are more readily absorbed because of the additive effect of a glucose-dependent fructose cotransport mechanism. 18 4. Foods that contain both fructose and sorbitol intensify

malabsorption and gastrointestinal distress because of an inhibitory effect by sorbitol on the already reduced capacity of the fructose absorption mechanism. 1921 5. The absorptive capacity and symptoms of carbohydrate malabsorption vary within individuals. Peak rises in breath hydrogen excretion may occur; whether or not symptoms develop may be influenced by an individual's ability to handle the colonic fermentation products. 22 6. Fructose and sorbitol malabsorption can occur as frequently in normal, healthy children and adults as in those with functional bowel disease. 21 7. Young children are not able to tolerate and absorb tqae same quantities of sorbitol that adults do. 28

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Lifshitz et al.

8. Juices that contain fructose in excess of glucose and that contain sorbitol may cause gastrointestinal problems in healthy children 22'23 or may exacerbate symptoms in children with functional bowel disorders and CNSD. 22, 23 DISCUSSION

AND CONCLUSIONS

When the capacity for carbohydrate absorption in the small intestine is exceeded, a substantial amount of malabsorbed sugar enters the large intestine, acting as an osmotic laxative. Typical symptoms of carbohydrate malabsorption are diarrhea, flatulence, borborygmus, abdominal distention, and crampy abdominal pain. Malabsorption of the carbohydrates contained in juices has been noted to be a contributory factor in the onset of gastrointestinal symlStoms and CNSD in children) v, 22, 23 Multiple therapeutic interventions for managing CNSD have been tried without consistent results, 3, 9-~2 and some dietary modifications have proved futile. 2, i I For example, altering the total amount of fluids consumed has been evaluated. Children with CNSD were grouped into those who ingested more than 150 ml of fluid per kilogram per day and those who ingested less than 150 ml/kg per day. 6 When the children who consumed the larger quantities of fluid were instructed to decrease their fluid intake to approximately 90 ml/kg per day, a significant decrease in the number of stools and an increase in stool consistency were noted. However, no such change occurred in the group whose intake was unchanged or who did not ingest large quantities of fluid. Other dietary modifications have been tried in children with CNSD. Although fat inhibits gastric emptying, 29 altering levels of dietary fat has shown equivocal results. A prospective study of children with CNSD who were less than 4 years of age showed no improvement in diarrhea with an increased-fat dietlS; yet, another study showed a significant decrease in stool frequency when dietary fat was increased.8 It is apparent, however, that specific dietary factors may play a significant role in the prevention and control of CNSD. One such factor is fruit juice, a fluid staple for children. Fruit juice is appropriately considered a nutritious snack and is an important part of a child's diet. Marketing surveys show that about 90% of infants consume fruit juice by 1 year of age; the average infant consumes 150 ml (5 oz) of juice per day, but approximately 1% consume more than 600 ml (21 oz) per day. Children up to 5 years of age consume 9 gallons of juice per year, of which approximately 50% is apple juice. Children not only accept but at times depend on fruit juice; therefore it is important for the pediatrician to ascertain a child's dietary intake of fruit juice and to understand

The Journal of Pediatrics May 1992 that its consumption may be associated with carbohydrate malabsorption. Pediatricians also should be aware of the carbohydrate content of fruit juices (Table) and realize that juices without sorbitol and with equal concentrations of fructose and glucose are less likely to be malabsorbed or to produce gastrointestinal symptoms. Occasionally, intake of excessive quantities of fruit juice may be associated with failure to thrive. 3~ Excessive fruit juice intake may result in inappropriate dietary consumption, which could, in turn, lead to interference with normal growth, with or without symptoms and gastrointestinal complaints. The pursuit of healthful diets, the avoidance of "junk food," and the trend toward natural foods, with selection of juices as important components of the diet, have also been linked with failure to thrive) ~ 9Parents and pediatricians alike worry about what to feed children and what diet constitutes optimal nutrition. Babies need to be introduced gradually to a variety of foods. Children need a diet high in calories and essential nutrients to grow and develop normally; snacks are an important part of this diet. Eating a large variety from all the major food groups ensures the intake of the essential nutrients. However, any food ingested in excess--including fruit juices-can disrupt the balance that is necessary for healthful nutrition and may be associated with gastrointestinal symptoms and CNSD. In summary, fruit juice is considered a nutritious snack, and consumption data prove that it is somewhat of a fluid staple for children. However, fruit juices ingested in excess, particularly those which contain fructose in higher concentrations than glucose, with or without sorbitol, may cause gastrointestinal discomfort in children. Malabsorption of the carbohydrate in the juice can exacerbate gastrointestinal symptoms in children who already have CNSD or could lead to the onset of symptoms in otherwise healthy children. Pediatricians should be aware of the quantities of juice consumed and of the carbohydrate concentrations found in fruit juices (Table). Juices with equivalent fructose-glucose concentrations and low sorbitol concentrations or no sorbitol may be less likely to be associated with carbohydrate malabsorption and therefore may be a good substitute for juices containing sorbitol, together with high concentrations of fructose and low concentrations of glucose. Fima Lifshitz, AID Department of Pediatrics Maimonides Medical Center Brooklyn, N Y 11219

Marvin E. Ament, AID Department of Pediatrics University of California at Los Angeles Los Angeles, CA 90024

Volume 120 Number 5

Juice malabsorption and chronic diarrhea

Ronald E. Kleinman, MD Pediatric Gastroenterology and Nutrition Massachusetts General Hospital Boston, MA 02114 William Klish, MD Pediatric Gastroenterology Texas Children's Hospital Houston, TX 77030 Emanuel Lebenthal, MD Department of Pediatrics Hahnemann University Philadelphia, PA 19102 Jay Perman, MD Pediatric Gastroenterology and Nutrition Johns Hopkins University Baltimore, MD 21205 John N. Udall, Jr., MD, PhD Pediatric Gastroenterology Department of Pediatrics University of Arizona Health Science Tucson, A Z 85724 REFERENCES

1. American Academy of Pediatrics Committee on Nutrition. The use of fruit juice in the diets of young children. AAP News 1991;7(2):11. 2. Davidson M, Wasserman R. The irritable colon of childhood (chronic nonspecific diarrhea syndrome). J PEDIATR 1966; 69:1027-38. 3. Walker-Smith JA. Toddler's diarrhoea. Arch Dis Child 1980; 55:329-30. 4. Fitzgerald JF, Clark JH. Chronic diarrhea. Pediatr Clin North Am 1982;29:221-31. 5. Fenton TR, Harries JT, Milla PJ. Disordered small intestinal motility: a rational basis for toddlers' diarrhoea. Gut t983; 24:897-903. 6. Greene HL, Ghishan FK. Excessive fluid intake as a cause of chronic diarrhea in young children. J PEDIATR 1983;102:83640. 7. Jonas A, Diver-Haber A. Stool output and composition in the chronic nonspecific diarrhoea syndrome. Arch Dis Child 1982; 57:35-9. 8. Cohen SA, Hendricks KM, Mathis RK, et al. Chronic nonspecific diarrhea: dietary relationships. Pediatrics 1979;64:402-7. 9. Lloyd-Still JD. Chronic diarrhea of childhood and the misuse of elimination diets. J PEDIATR 1979;95:10-3.

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10. Werlin S. Diseases of the gastrointestinal system. In: Hockelman R, Blatman S, Brunell P, eds. Principles of pediatrics: health careoftheyoung. New York: McGraw-Hill, 1978:842-3. 11. Davidson M. Chronic nonspecific diarrhea syndrome: irritable colon of childhood. In: Gellis SS, Kagen BM, eds. Current pediatric therapy; vol 6. Philadelphia: WB Saunders, 1973:192-3. 12. Silverman A, Roy CC. Diarrheal disorders. In: Silverman A, Roy CC, eds. Pediatric clinical gastroenterology. 3rd ed. St Louis: CV Mosby, 1983:190-236. 13. Baldassano RN, Liacouras CA. Chronic diarrhea: a practical approach for the pediatrician. Pediatr Clin North Am 1991; 38:667-86. 14. Gryboski JD, Kocoshis S. Effect of bismuth subsalicylate on chronic diarrhea in childhood: a preliminary report. Rev Infect Dis 1990;12(suppl 1):$36-40. 15. Boyne L J, Kerzner B, Juhling McClung H. Chronic nonspecific diarrhea: the value of a preliminary observation period to assess diet therapy. Pediatrics 1985;76:557-61. 16. Ravich W J, Bayless TM, Thomas M. Fructose: incomplete intestinal absorption in humans. Gastroenterology 1983;84:26-9. 17. Kneepkens CMF, Vonk R J, Fernandes J. Incomplete intestinal absorption of fructose. Arch Dis Child 1984;59:735-8. 18. Rumessen J J, Gudmand-Hoyer E. Absorption capacity of fructose in healthy adults: comparison with sucrose and its constituent monosaccharides. Gut 1986;27:1161-8. 19. Rumessen JJ, Gudmand-Hoyer E. Malabsorption of fructosesorbitol mixtures: interactions causing abdominal distress. Scand J Gastroenterol 1987;22:431-6. 20. Rumessen J J, Gudmand-Hoyer E. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 1988;95:694-700. 21. Nelis GF, Vermeeren MAP, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology 1990;99:1016-20. 22. Hyams JS, Etienne NL, Leichtner AM, Theuer RC. Carbohydrate malabsorption following fruit juice ingestion in young children. Pediatrics 1988;82:64-8. 23. Hyams JS, Leichtner AM. Apple juice: an unappreciated cause of chronic diarrhea. Am J Dis Child 1985;139:503-5. 24. Wick AN, Almen MC, Joseph L. Metabolism of sorbitol. J Am Pharm Assoc 1951;40:542-4. 25. Gryboski JD. Diarrhea from dietetic candies. N Engl J Med. 1966;275:718. 26. Goldberg LD, Ditchek NT. Chewing gum diarrhea. Am J Dig Dis 1978;23:568. 27. Ravry M JR. Dietetic food diarrhea. JAMA 1980;244:270. 28. Hyams JS. Chronic abdominal pain caused by sorbitol malabsorption. J PED1ATR 1982;100:772-3. 29. Cooke AR. Control of gastric emptying and motility. Gastroenterology 1975;68:804-16. 30. Lifshitz F, Finch NM, Lifshitz JZ. Children's nutrition. Boston: Jones & Bartlett, 199h186-210, 253-70.