but, because of an anatomic or cofac- tor deficiency, the disaccharides are not absorbed. Although this disorder may Lactose intolerance have a presentation similar to that of lactose intolerance, it does not necessar- ily parallel it8 (Table 1). R. ALEXANDER RUSYNYK, DO There appears to be an equal preva- CHRISTOPHER D. STILL, DO lence of lactose intolerance among males and females. Interestingly, up to 45% of women who are lactose intolerant will regain the ability to digest lactose during pregnancy. Primary lactose intolerance has a high Lactose intolerance affects more than 50 million Americans. It is one of the most degree of race dependence. The preva- common gastrointestinal disorders seen by primary care physicians. When this dis- lence of primary lactose intolerance in order is properly diagnosed, the patient is easily treated with education and the United States is as follows: 95% to dietary modifications. Lactose intolerance is commonly misdiagnosed because of 100% of American Indians; 80% to its overlapping symptoms of diarrhea and abdominal bloating. This article reviews 90% of blacks, Asians, Mediterraneans, the etiology, diagnosis, and treatment of lactose intolerance. and Jews; and 50% of individuals of (Key words: lactose intolerance, lactase, abdominal bloating, diarrhea, Northern and Central European hydrogen breath test) descent3,8,9 (Table 2). Incidence of sec- ondary lactose intolerance is variable, depending on its underlying etiology. Up t is estimated that 50 million Ameri- a physiologic decline in lactase activity to 50% of infants with acute diarrhea Icans have trouble digesting lactose. coincident with weaning.4,5 This decline have transient lactose intolerance during Although this disorder is usually not in lactase activity in the intestinal mucosa acute viral syndromes. Most commonly dangerous, it can lead to distressing is genetically controlled and follows a implicated are rotavirus and giardiasis. symptoms and multiple office visits to permanent course. Primary lactose intol- the primary care physician.1 Lactose erance may not become clinically evi- Signs and symptoms intolerance is the inability to digest lac- dent until puberty or late adolescence.6,7 The diagnosis may be suspected when a tose into its constituents, glucose and Secondary lactose intolerance is the history of gastrointestinal symptoms fol- galactose, owing to low levels of lactase inability to digest lactose caused by any lows milk ingestion. Symptoms tend to enzyme in the brush border of the duo- condition that leads to injury of the occur about 30 minutes to 2 hours after denum.2 Galactose is then converted to intestinal mucosa or to reductions of the consumption of foods that contain lac- glucose in the liver by a series of reactions functional mucosal surface area. This tose. Symptoms such as bloating, cramp- leading to uridine diphospho (UDP)-glu- form of lactose intolerance tends to be ing, diarrhea, flatulence, and borboryg- cose.2 transient, depending on the nature of mi will develop in one third to one fifth Multiple etiologies of lactose intoler- the primary disorder. Causes include of individuals with lactose intolerance.10 ance exist, the most common being that diarrhea, inflammatory bowel disease, Undigested lactose becomes thick as it of primary lactose intolerance, a com- and the human immunodeficiency virus. passes through the small intestines. This mon disorder in which a low level of Multiple other viral syndromes may lead thickened lactose combines with colonic lactase develops after weaning.3 The con- to secondary lactose intolerance. bacteria to produce excess hydrogen gas. dition appears to parallel the situation in Congenital lactose intolerance is an Lactose that is not absorbed also causes all other land mammals in which there is extremely rare disorder in which the an intraluminal osmotic effect resulting small intestines produce no lactase.3,8 in flatulence, bloating, and loose stools. Consumption of any amount of lactose Another significant change with lactose From Geisinger Medical Center, Danville, Pa, where Dr Rusynyk is a Gastroenterology and is intolerable and even dangerous for intolerance is the decrease in stool pH nutrition fellow, and Dr Dr Still is section head of infants whose diarrhea quickly leads to secondary to production of lactic acid nutrition and associate physician, Department of dehydration. This type of lactose intol- and short-chain fatty acids from the fer- Gastroenterology and Nutrition. Correspondence to Christopher D. Still, DO, erance is usually apparent in the first mentation of lactose by colonic bacte- FACN, FACP, Section Head of Nutrition, Depart- week of life. The infant must be fed a lac- ria. It should be emphasized that varying ment of Gastroenterology and Nutrition, tose-free diet.8 degrees of symptoms occur in patients, Geisinger Medical Center, 100 N Academy Ave, Danville, PA 17822-2111. Lactose “malabsorption” is a disorder depending on the severity of their lac- E-mail: [email protected] in which lactose can be broken down, tose intolerance and on the lactose load

S10 • JAOA • Vol 101 • No 4 • Supplement to April 2001 Rusynyk and Still • Lactose intolerance ingested. Ingestion of only moderate amounts of lactose, 5 g to 12 g or the Table 1 amount in 90 mL to 240 mL (3 to 8 Lactase Deficiency ounces) of milk, may result in gastroin- Type Pathogenesis testinal symptoms. Patients should be educated that symptoms are not caused Congenital Enzyme activity absent from birth by allergic reactions to milk proteins, Primary Genetically predetermined reduction but rather by an inability to break down of enzyme activity during childhood and absorb milk sugars. or adolescence Secondary Reduced to enzyme activity in response Diagnosis to diffuse intestinal insult—giardiasis, A thorough history and physical exam- rotavirus, topical sprue, celiac disease, bacterial overgrowth, Crohn’s disease, ination will yield evidence to point the intestinal resection clinician in the right direction. If defini- tive tests are required to diagnose lac- tose intolerance, the most practical is Table 2 the hydrogen breath test (Table 3). This Ethnic Distribution of Lactase Deficiency test is noninvasive, relatively inexpen- sive, and not labor intensive. Breath Population Prevalence (%) hydrogen levels are measured before and American Indians 95 to 100 after oral administration of a 50-g bolus of lactose. The hydrogen level will rise Mediterranean 80 to 85 secondarily to hydrogen release from the African black 85 to 90 combination of unabsorbed lactose and colonic bacteria.11 Measurement of stool Asian 90 to 100 pH will also lead to evidence of lactose Jewish descent 80 to 95 intolerance. Another definitive test is through a small-bowel biopsy for assay Northern European 40 to 55 of lactase activity. The drawbacks to the Mexican American 50 to 75 latter test include invasiveness and accu- racy. Accuracy may be questionable if the lactase deficiency is focal or patchy; there- lactose-reduced diet. The gastrointesti- By eliminating milk products, many fore, small-bowel biopsy is rarely per- nal symptoms of patients who consume patients require calcium supplementa- formed in clinical practice. Another alter- milk products can be reduced with the tion to prevent the effects of osteoporo- native is the lactose absorption test. This use of commercially available prepara- sis. This supplementation can be accom- test quantifies the amount of lactose tions such as Lactaid or Lactrase. These plished using calcium carbonate. digested after a specific amount of lactose preparations contain the enzyme lactase, Substitution should be emphasized. is ingested. Assays to rule out secondary which is necessary for the hydrolysis of Yogurt and fermented products such as causes of lactose intolerance should be lactose. Lactose intake limited to less cheese are better tolerated than milk considered as the history dictates. If a than 240 mL (8 ounces) of milk per day products.10 The recommended daily child or infant is having lactose intoler- usually causes negligible gastrointestinal allowance for calcium is 800 mg, which ance, many pediatricians simply recom- symptoms. Individuals with severe lactose many experts in bone disease believe is mend changing from cow’s milk to a intolerance should also watch for hid- too low. Postmenopausal women may soy formula and observing for a decrease den lactose, which is often added to pre- require as much as 1500 mg of calcium in symptoms to ensue. pared foods. Moreover, lactose is used as per day, roughly the amount in a quart the base for more than 20% of pre- and a half of milk. Many foods that are Treatment scription drugs and 6% of over-the- rich in calcium and low in lactose include Approximately 70% of patients with counter medications.12 green vegetables, oysters, sardines, primary lactose intolerance will respond Secondary lactose intolerance is gen- molasses, and tofu (Table 4). to a lactose-restricted diet.3 The remain- erally a self-limiting condition that The cornerstone to successful treat- ing 30% are believed to have an under- resolves with treatment of the primary ment is patient education. Reading of lying irritable bowel syndrome. Primary disorder. Patients should be advised to food product labels is necessary to pre- lactose intolerance can be controlled limit consumpation of dairy products vent unintentional ingestion of lactose- with strict adherence to a lactose-free or until the primary disorder is resolved. containing products.

Rusynyk and Still • Lactose intolerance JAOA • Vol 101 • No 4 • Supplement to April 2001 • S11 4. Hammer HF, Fine KD, Santa Ana CA, Porter JL, Table 3 Schiller LR, Fordtran JS. Carbohydrate malabsorption: Diagnostic Tests for Lactose Intolerance Its measurement and its contribution to diarrhea. J Clin Invest 1990;86:1936-1944.

Test Result 5. Dahlqvist A, Hammond JB, Crane RK, Dunphy JV, Littman A. Intestinal lactase deficiency and lactose Breath hydrogen Rise in breath hydrogen intolerance in adults. Preliminary report. Gastroen- 20 ppm terology 1968;54(Suppl):807-810.

Stool pH Acid pH (6.0) 6. Escher JC, de Koning ND, van Engen CG, Arora S, Buller HA, Montgomery RK, et al. Molecular basis of lac- Small-bowel biopsy Disaccharidase assay tose levels in adult humans. J Clin Invest 1992;89:480- (13 IU/g of mucosal protein) 483. 7. Lloyd M, Mevissen G, Fischer M, Olsen W, Good- Lactose absorption to speed D, Genini M, et al. Regulation of intestinal lactase (fecal-reducing substances) in adult hypolactasia. J Clin Invest 1992;89:524-529.

8. Saavedra JM, Perman JA. Current concepts in lac- Key: minimal; significant. tose malabsorption and intolerance. Annu Rev Nutr 1989;9:475-502.

9. Johnson JD, Simoons FJ, Hurwitz R, Grange A, Mitchell CH, Sinatra FR, et al. Lactose malabsorption Table 4 among the Pima indians of Arizona. Gastroenterology Calcium and Lactose Content of Some Common Foods 1977;73:1299-1304. Food product Calcium, mg Lactose, g 10. Hurst JW. Medicine for the Practicing Physicians, 2nd ed. 1988. Vegetables 11. Lewitt MD, Donaldson RM. Use of respiratory hydro- Broccoli (1 cup) 95 to 175 0 gen excretion to detect carbohydrate malabsorption. Collard greens (1 cup) 145 to 350 0 J Lab Clin Med 1970;75:937-945. Spinach (1 cup) 60 to 100 0 Chinese cabbage (1 cup) 160 to 180 0 12. Martens RA, Martens S. The Milk Sugar Dilemma: Living With Lactose Intolerance. Chicago, Ill: Ameri- can Dietetic Association; 1985. Dairy products Ice cream (8 oz) 175 to 200 6 to 8 Milk (8 oz) 280 to 320 12 to 14 Processed cheese (1 oz) 150 to 220 2 to 4 Yogurt (8 oz) 275 to 400 12 to 15

Seafood Shrimp (3 oz) 100 0 Oysters (1 cup) 225 0 Salmon ( 3 oz) 165 0 Sardines (3 oz) 370 0

Other Molasses (2 tbsp) 270 0 Tofu (3 oz) 225 0

Comment References Lactose intolerance is a disorder fre- 1. US Department of Health and Human Services. National Digestive Disease Information. Washington, quently seen by the primary care physi- DC: National Institute of Diabetes and Digestive and Kid- cian. It can be diagnosed by a careful his- ney Diseases; 1998.] tory and physical examination and, 2. Marsh MN, Riley SA. Digestion and absorption of when necessary, using diagnostic pro- nutrients and vitamins. In: In: Feldman M, Sleisenger MH, Scharschmidt BF, Klein S, eds. Sleisenger and cedures. Lactose intolerance is general- Fordtran’s Gastrointestinal and Liver Disease, Volume ly treated with patient education and 2 6th ed. Philadelphia, Pa: WB Saunders Co; 1998; maintenance of a lactose-free diet. A pp 1480, 1495-1496. carefully chosen diet is the key to reduc- 3. Greenberger NJ, Isselbacher KJ. Disorders of absorp- tion. In: Fauci AS, Braunwald E, Isselbacher KJ, et ing symptoms and protecting future al,eds. Harrison’s Principles of Internal Medicine, 14th health. ed. New York, NY: McGraw-Hill; 1998; pp 1630-1631.

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