Lactose malabsorption and diarrhea

EDITORIAL

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Lactose Malabsorption and Diarrhea Lactose malabsorption is a common occurrence in many diarrheal conditions. This malabsorption may be secondary to the condition or result from an unrelated, primary acquired loss of lactase synthesis.’ Since it is commonly believed that lactose malabsorption aggravates diarrhea, milk and milk products are often eliminated from the diet of patients with d&heal disorders. It is of some importance to know if such a dietary manipulation truly is beneficial, since milk is the major natural dietary source of calcium and an inexpensive source of protein. In this issue of Nutrition, Marteau and co-workers* report that contrary to conventional dogma, moderate doses of lactose (20 g/d) did not significantly influence the fecal output of subjects with diarrhea secondary to short-bowel syndrome. Insight into the relationship between lactose malabsorption and fecal water is facilitated by an understanding of the fate of lactose in the colon. Since fecal water is isotonic, the increase in fecal volume expected with lactose malabsorption should be a function of the quantity of lactose-derived osmoles that reach the anus (or the ileostomy in colectomized patients) .3 For a given quantity of malabsorbed lactose, this anal osmolar “load” will be determined by the relation between the ability of the fecal flora to ferment lactose and the efficiency with which the colonic mucosa absorbs these fermentation products.4 Malabsorbed carbohydrate is rapidly fermented by the colonic bacteria to acetate, propionate, and butyrate. In the process, 1 mol of lactose is converted to about 3.7 mol of organic acids5 Since the pKa of these acids is about 4.8, in the physiologic situation in the colon a variable fraction of these organic acids are present in the ionized form associated with osmotically active cations such as sodium and potassium. At fecal pH levels of 4.8, 5.8, and 6.8, these cations will increase the osmotic load resulting from organic acid production by 50%, 90%, and 99%, respectively. Thus, fermentation has the potential to increase the osmotic load of malabsorbed lactose by almost eightfold. An eight-fold increase converts the 171 mOsm represented by 50 g of lactose to about 1368 mOsm, an osmotic load that would result in a “cholera-like” 4,560 mL of fecal water. However, the colon mucosa avidly absorbs organic acids and associated cations, thus markedly reducing the osmotic load and the resultant diarrhea.6 When fermentation and organic acid absorption are extremely efficient, virtually all lactose and lactose fermentation products can be removed from the colon. In this situation, bacterial metabolism eliminates the diarrhea that otherwise would result from lactose malabsorption. However, if organic acid production far exceeds the absorption rate, the colonic bacterial metabolism aggravates the severity of the diarrhea.4 An excellent article by Hammer and co-workers’ sheds light on the role of the colonic bacteria in the diarrhea of lactose malabsorption. Fecal output was carefully monitored as increasing doses of lactulose (45 g/d, 90 g/d, or 125 g/d) were added to the usual diet of healthy subjects. Lactulose is an indigestible disaccharide (galacto-fructose) that is virtually totally nonabsorbable in the small bowel8 However, this sugar is fermented by the colonic bacteria via a pathway similar to that of lactose.’ Some of the results of this study are summarized in Table I. With a daily dose of lactulose of 45 g, colonic fermentation of the disaccharide was virtually complete as evidenced by the minimal fecal carbohydrate. The increase in fecal water of only 98 mL with this lactulose dosage indicates that the overall effect

of bacterial fermentation was to reduce the osmotic load since the 45 g of lactulose (154 mOsm) would have been expected to increase fecal water by at least 515 mL. However, as the lactulose dosage was increased to 90 g/d and then to 125 g/d, the increment in fecal water per gram of lactulose increased, indicating progressively less effective removal of osmoles. This lack of effectiveness reflected both the inability of the bacteria to completely ferment lactulose and the inability of the colon to absorb the fermentation products, as evidenced, respectively, by the increasing quantities of fecal carbohydrate and organic acids. When the lactulose dosage was increased from 90 to 125 g, fermentation markedly increased the osmoles reaching the anus since the osmotic load of this 35-g increment (103 mOsm) would have been expected to increase fecal water by only about 343 mL, whereas fecal water increased by 700 mL. It is apparent from the above data that the efficiency with which the colonic bacteria ferment carbohydrate and the coionic mucosae absorbs fermentation products is dose-dependent and diminishes with increasing dosage. It seems likely that there may be wide individual variability in the efficiency of these processes, thus rendering some individuals more susceptible to diarrhea from lactose malabsorption. The ability of fermentation to bring about nearly complete removal of the osmolar load of 45 g of lactulose/d explains why virtually no diarrhea was reported when we fed 25 g of lactose (240 ml milk/d) to lactase-deficient subjects.” Given the above physiologic scenario for the fate of lactose in the colon, what sort of changes in fecal water might have been expected in the study of Marteau et al., 2 assuming negligible small-bowel absorption of the 20-g dose of lactose? Presumably minimal bacterial fermentation would have taken place in the colectomized subjects, thus the osmolar load resulting from lactose would have been 68 mOsm, which would “hold” about 230 mL of water in the lumen. (Luminal water would be further increased slightly as a result of the inability of the mucosae to maintain zero electrolyte concentration in lumina.) Given that the ileostomy output of the colectomized subjects was 4100 mL in the basal state, it is not surprising that the additional fluid (approximately 230 mL) resulting from lactose malabsorption failed to significantly increase this output. The increase in fecal water predicted for the patients with their colon in continuity ranges from zero (if all lactose were removed from the fecal stream) to 230 mL (if the lactose remained intact in the colon) to 1.35 L (if fermentation were complete, absorption of organic anions negligible, and the pH of luminal contents 7.0). The finding that fecal weight did not significantly increase from the baseline mean of 1534 mL/d suggests that either malabsorbed lactose was not appreciably fermented in the colon or that the absorption of fermentation products was relatively efficient in these subjects. The bottom line take-away message of the article by Marteau et al. is that severe restriction of lactose intake is not necessary in patients with short-bowel syndrome since the ingestion of 20 g of lactose/d produced no increase in diarrhea or in abdominal symptoms. While the authors supplied the lactose primarily as cheese and yogurt, it seems likely that similar results would have been obtained with milk. It should be noted, however, in the base line state, the patients in Marteau’s study had severe

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TABLE I. FECAL OUTPUT WITH INGESTION OF INCREASING DOSES OF LACTULOSE Fecal Output Lactulose dosage (g/d)

Fecal Hz0 (mL/d)

0

110

45 90 125

202 483 1184

Incremental fecal HZ0 per increment in lactulose (mL/g lactulose/d)

diarrhea and probably appreciable symptoms. As a result, it might have been particularly difficult to demonstrate a significant increase in diarrhea or symptoms with lactose administration. Similar types of studies will be required to determine if the findings of this article can be extrapolated to less severe diarrhea1 conditions.

FABRIZIS SUAREZ, MD, PHD, RESEARCH ASSOCIATE AND MICHAEL LEVITT, MD ACOS FOR RESEARCH Veterans Affairs Medical Center Minneapolis, Minnesota, USA

REFERENCES 1. Sterchi EE, Mills PR, Franson JAM, et al. Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance: evidence for reduced biosynthesis and slowed-down maturation in enterocytes. J Clin Invest 1990; 86:1329

Carbohydrate (g/d)

Organic acids (mEq/d)

1 12 45

61 98 151

2.0 6.2 16.0

2. Marteau P, Messing B, Arrigoni E, et al. Do patients with shortbowel syndrome need a lactose free diet? Nutrition 1997; 13:13 Christopher NL, Bayless TM. Role of the small bowel and colon in lactose-induced diarrhea. Gastroenterology 197 1;60~845 Saunders DR, Wiggins HS. Conservation of mannitol, lactulose and raffinose by the human colon. Am J Physiol 1981;241:G397 Miller TL, Wolin MJ. Fermentation by saccharolytic intestinal bacteria. Am J Clin Nutr 1979;32:164 Ruppin H, Bar-Meir S, Soergel KH, Wood CM, Schmitt Jr MG. Absorption of short chain fatty acids by the colon. Gastroenterology 1980;78:1500 I. Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS. Studies of osmotic diarrhea in normal subjects by ingestion of polyethylene glycol and lactulose. J Clin Invest 1989;84:1056 8. Menzies IS, Laker MF, Pounder R, et al. Abnormal intestinal permeability to sugars in villous atrophy. Lancet 1979;ii:1107 9. Florent C, Flourie B, Leblond A, Rauturreau M, Bemier JJ, Rambaud JC. Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study). J Clin Invest 1985;75:608 10. Suarez FL, Levitt MD, Savaiano DA. Lactose intolerance: how significant is the problem? (abstract) FASEB 1996; lO:A796

PII: SO899-9007 (96)00294-8

Salt and Water in Nutritional Support The paper by Gil and colleagues’ in this issue of the journal, entitled “Response of Severely Malnourished Patients to Preoperative Parenteral Nutrition,” is a reminder that the intake of salt and water is inseparable from the process of eating food or the administration of nutritional support by artificial means. This group from Barcelona has made several important contributions to the subject in studies on both experimental animals and patients. The response to starvation and also to injury and acute illness involves an expansion of the extracellular fluid volume and an incapacity to excrete an excess salt and water load. In their classical studies of semistarvation in normal volunteers, Keys and colleagues’ showed that, although the fat and lean compartments of body tissues shrink, the extracellular fluid volume remains either at its prestarvation level or decreases very slightly. In relative terms, therefore, the extracellu-

lar fluid volume occupies an increasing proportion of the body mass as starvation progresses. The degree of edema is related to the ingestion of salt and water, and may be exacerbated by refeeding. In a series of studies, Sitges-Serra and colleagues3 showed that starved rabbits tend to retain salt and water when refed intravenously, and that this may lead to increased lung water. This overload was not seen when a low-volume, lowsodium feed was given. They also showed, in the same studies, that a regimen whose sole nonprotein energy source was glucose caused greater fluid retention than one in which half the energy was supplied as fat. Although water is normally retained intracellularly as glycogen is reformed, there was also, in these studies, an increase in extracellular water and a dilution of serum albumin concentration. As these authors point out, Gamble4 had shown in 1946 the sodium-retaining effects of glucose,