eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Lactose Intolerance

Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston; Delia M Rivera, MD, Assistant Professor, Department of Pediatrics, Division of Infectious Disease and Immunology, University of Miami Leonard M Miller School of Medicine; Stephen Borowitz, MD, Professor of Pediatrics and Public Health Sciences, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Virginia

Updated: Nov 13, 2008

Introduction

Background

Lactose intolerance in adulthood is very common and is the result of a genetically programmed progressive loss of the activity of the small intestinal enzyme lactase. Some scientists believe that human adult lactase polymorphism evolved in the Neolithic period, after animal milk became available for the nutrition of older children and adults. Expression of the lactase enzyme starts to decline in most persons at age 2 years; however, symptoms of lactose intolerance rarely develop in people younger than 6 years.

Milk intolerance is more frequently due to milk-protein allergy than primary lactase deficiency. Although transient lactose intolerance may occur during acute gastroenteritis and as part of any process that leads to reduction of the small intestinal absorptive surface (such as untreated celiac disease), it is rarely clinically significant and, when present, can be easily treated with a short course of a lactose-free diet. Diagnosing lactose intolerance based on symptoms is fairly inaccurate; however, self-reported symptoms of lactose intolerance correlate with low calcium intake. Calcium supplementation should accompany any restriction of milk products.

Pathophysiology

Lactose, a disaccharide unique to mammalian milk, is hydrolyzed into the monosaccharides glucose and galactose at the brush border of enterocytes on the villous tip by the enzyme lactase (a beta-D-galactosidase known as lactase phlorizin hydrolase).

Lactose appears to enhance the absorption of several minerals, including calcium, magnesium, and zinc. It also promotes the colonic growth of Bifidobacterium and is the source of galactose, which is an essential nutrient for the formation of cerebral galactolipids. The gene for lactase is located on chromosome 2. Hypolactasia seems to be strongly correlated with genotype C/C of the genetic variant C-->T(-13910) upstream of the lactase phlorizin hydrolase gene.

Human and animal studies suggest that numerous modulators result in variable expression of lactase at different ages. Thyroxine may promote the decline in lactase enzyme expression that appears in childhood, whereas hydrocortisone appears to increase lactase levels. Although premature infants have partial lactase deficiency because of intestinal immaturity, enzyme expression can be induced by lactose ingestion. Improvement of lactose digestion in a previously intolerant child or adult is caused by growth of lactose-digesting bacteria rather than an induction in activity of the lactase enzyme because lactase is a noninducible enzyme.

Congenital lactase deficiency is an extremely rare autosomal recessive disorder associated with a complete absence of lactase expression. Childhood-onset and adult-onset lactase deficiency are extremely common and are inherited in an autosomal recessive manner. The CC genotype of the 13910 C/T polymorphism of the LCT gene is linked to such late-onset primary hypolactasia. Persistent lactase activity into adulthood is inherited in an autosomal dominant manner. Acquired lactase deficiency, which is a transient phenomenon by definition, is due to damage of the intestinal mucosa by an infectious, allergic, or inflammatory process and resolves once the disease process is corrected and healing of the intestinal mucosa restores the brush border enzymes.

Frequency

United States

As many as 22% of adult white Americans are lactase deficient. The prevalence in other racial groups parallels the country of racial origin. Symptomatic individuals represent only about 50% of lactase deficiency cases.

International

Adult-onset lactase deficiency varies widely among countries. Northern Europeans have the lowest prevalence at approximately 5%. Central Europeans have a higher prevalence at approximately 30%, and Southern Europeans have a much higher prevalence at approximately 70%. Hispanic and Jewish populations also have a high prevalence at approximately 70%, while Northern Indians have a much lower prevalence than Southern Indians, at approximately 25% and 65%, respectively. Almost all (90%) Asians and Africans are affected.

Mortality/Morbidity

Usually, very little morbidity is associated with lactase deficiency. Transient lactase deficiency affects a significant number of infants with severe gastroenteritis and diarrhea. Symptoms generally resolve within 5-7 days.

Race

See Frequency.

Sex

No sex differences in the prevalence of adult-type hypolactasia are known.

Age

Lactase activity in the fetal intestine progressively increases through the third trimester and approaches maximum expression at term. Preterm infants have diminished levels of lactase. Few infants born at 28 weeks' gestation have significant intestinal lactase activity, whereas approximately 40% of infants born at 34 weeks' gestation demonstrate significant intestinal lactase activity. The premature neonatal period is the only time in which lactase enzyme production and expression can be induced. Because congenital lactase deficiency is exceedingly rare, diagnoses such as glucose-galactose malabsorption or the much more common milk-protein allergy should be considered in an infant with symptoms of milk or milk-based formula intolerance.

Lactase activity is genetically programmed to decline, beginning after age 2 years. Signs and symptoms usually do not become apparent until after age 6-7 years, and recent studies have actually shown that hypolactasia may begin even after age 20.¹ Symptoms, therefore, may not be apparent until adulthood, depending on dietary lactose intake and rate of decline of intestinal lactase activity. Lactase enzyme activity is highly correlated with age, regardless of symptoms.

Secondary lactase deficiency due to intestinal mucosal injury can appear at any age; however, children younger than 2 years are very susceptible because of many factors, including a high sensitivity of the gut to infectious agents, low reserve because of the small intestinal surface area, and high reliance on milk-based products for nutrition.

Clinical

History

Symptoms of lactose intolerance include the following:

• GI symptoms
  • Bloating, abdominal discomfort, meteorism, and flatulence that occur from 1 hour to a few hours after ingestion of milk or dairy products may signify lactose intolerance; however, other disorders such as milk-protein sensitivity, allergic-type reactions to other substances in the meal, or other saccharide intolerance may cause similar symptoms.
  • Many individuals with lactose intolerance are concerned about the presence of lactose in many orally administered drugs; however, one investigation concluded that no side effects are experienced by adults with hypolactasia upon ingestion of lactose-containing drugs.²
  • Estimates suggest that more than 240 mL of milk per day (12 g lactose) are necessary to cause symptoms in individuals with lactase deficiency.
  • Although lactose intolerance is often suspected in children with functional recurrent abdominal pain, strong evidence suggests that lactose intolerance plays no role in such condition.
• Associated food
  • The rate of gastric emptying is important in the development of symptoms, which may develop if lactose moves quickly to an intestine that is low in lactase. Fats decrease the rate of gastric emptying, whereas carbohydrates increase the rate of gastric emptying. Thus, if dairy products that contain lactose are ingested with carbohydrates, especially simple carbohydrates, symptoms are more likely.
  • Allergies to food proteins, particularly milk and grain proteins, can mimic lactose intolerance in part.
  • Inflammation of the intestinal mucosa due to infection or protein-sensitive enteritis causes secondary lactose intolerance.
• Stool characteristics: Loose, watery, acidic stool often with excessive flatus and associated with urgency that occurs a few hours after the ingestion of lactose-containing substances is typical.
• Gastroenteritis: Infectious diarrhea, particularly viral gastroenteritis in younger children, may damage the intestinal mucosa enough to reduce the quantity of the lactase enzyme. This does not result in any significant problem and does not require any changes in formula. However, intolerance is rarely more evident, especially in malnourished infants, and requires a few days of lactose-free feedings. Abundant literature conclusively shows that breastfeeding can and should always be continued throughout an episode of gastroenteritis, despite the high content of lactose in breast milk.
• Food avoidance: Many people with lactose intolerance instinctively avoid products that contain lactose.

Physical

• Abdominal pain: Nonspecific, nonfocal abdominal pain and cramping are common and are sometimes associated with bloating and flatus. This pain may mildly increase with palpation. Focal abdominal pain significantly worsened by palpation, the presence of rebound tenderness, or guarding should alert the clinician to a more serious and possibly surgical GI diagnosis.
• Borborygmi: A significant increase in peristaltic activity in the small bowel can cause an audible or palpable increase in bowel activity.

Causes

• Lactose intolerance: This is caused by a low or absent activity of the enzyme lactase.
• Adult-onset lactose intolerance
  • This deficiency results from an unusual mechanism that involves a developmentally regulated change of the lactase gene product, resulting in a reduced synthesis of the precursor protein.
  • Differences in the rate of gene transcription account for much of the differences in lactose intolerance observed among racial groups.
• Low lactase activity in the small intestine: This allows undigested lactose to pass into the colon. In the colon, bacteria ferment the sugar to hydrogen gas and organic acids. The gas produces distention of the bowel, creating the sensation of bloating, cramping, and abdominal pain. Organic acids can be absorbed, but the quantity produced is rarely large enough to cause systemic symptoms or metabolic acidosis.

Differential Diagnoses

Diarrhea
Malabsorption Syndromes
Protein Intolerance

Workup

Laboratory Studies

The following laboratory studies are indicated in patients with lactose intolerance:

• Blood testing
  • The adult-type hypolactasia (most commonly caused by the CC genotype of the 13910 C/T polymorphism of the LCT gene) can now be easily diagnosed by a genetic analysis.
  • Studies have determined that genetic test results and breath test results are well-correlated, thereby eliminating the need for such testing.³  
• Stool analysis
  • Reducing substances in the stool indicate that carbohydrates are not being absorbed. One common mistake, especially with super-absorbent diapers, is to test the solid portion of the stool instead of the liquid portion.
  • Acidic stool is defined by a pH level of less than 5.5. This is an indication of likely carbohydrate malabsorption, even in the absence of reducing substances.

Other Tests

• Dietary elimination
  • Resolution of diarrhea and symptoms when a suspected substance is removed from the diet, as well as resumption of the diarrhea and symptoms when the substance is reintroduced, are very suggestive signs of intolerance.
  • Lack of diarrhea resolution when a substance is removed from the diet does not necessarily indicate tolerance. Malabsorption of one dietary component can result in diarrhea and subsequent malabsorption of other dietary components; thus, the sensitivity of this procedure can be low.
  • Conversely, resolution of symptoms upon withdrawal of lactose-containing foods from the diet may not confirm lactose intolerance. For instance, in the case of milk products, a patient can be sensitive to the milk proteins, and symptoms of such an allergy resolve once the milk or milk product is withdrawn from the diet.
• Hydrogen breath test
  • Carbohydrate malabsorption results in bacterial fermentation of the unabsorbed sugar. This biochemical process releases hydrogen gas that is absorbed into the blood and excreted by the lungs. In the absence of hydrolysis of lactose into its component monosaccharide sugars, galactose and glucose, lactose cannot be absorbed and passes into the large intestine. Thus, carbohydrate malabsorption can be determined by measuring the exhaled hydrogen concentration after a carbohydrate load is administered.
  • Under normal conditions, the fermenting bacteria reside only in the large intestine. When bacterial overgrowth in the small intestine occurs, upper small bowel fermentation of ingested but nonhydrolyzed lactose occurs and causes an early rise in the exhaled hydrogen concentration (>20 ppm). Under such conditions, an additional later rise in exhaled hydrogen occurs during large bowel fermentation.
  • Antibiotic administration may cause false-negative results. For diagnosis of lactose intolerance, 0.5-1 g/kg to 12-25 g of lactose is administered.

Procedures

• Mucosal biopsy is almost never needed to diagnose lactose intolerance. However, it may prove useful as a part of the workup in patients with malabsorption of obscure cause. A small intestinal mucosal biopsy sample is obtained via endoscopy for direct assay of lactase activity and other brush border disaccharidases.
• The presence of small intestinal mucosal injury can also be assessed as a possible cause of secondary lactase deficiency.

Histologic Findings

• No abnormal histologic findings in the small intestinal mucosa are present in adult-type lactose intolerance and the exceedingly rare primary lactase deficiency.
• Villous blunting and lamina propria inflammatory changes are seen in cases of secondary lactase deficiency.

Treatment

Medical Care

Treatment of lactose intolerance may include the following:

• Lactase deficiency: This can be induced by lactose only during the newborn period. Studies demonstrate the use of inducing lactase activity by tube feedings with milk-containing lactose in premature infants. Early initiation of half-strength lactose-containing formula or breast milk results in rapid induction of lactase activity in the brush border and less feeding intolerance. One study suggested that full-strength lactose formula resulted in more feeding intolerance than low-lactose formula in premature infants;⁴ thus, the precise lactose concentration of lactose for inducing lactase activity is still undetermined.
• Lactose intolerance: This can be improved by dietary manipulation. If the quantity of lactose is increased slowly over time, lactobacilli are stimulated to grow in the colon. A greater number of lactobacilli allow the lactose to break down into monosaccharides. Although this allows much of the sugar to be absorbed, some of the resulting monosaccharides are still fermented by colonic bacteria; however, the relative amount of colonic fermentation is decreased.
• Dietary aids
  • Lactase derived from yeast can be added to milk products as drops or ingested as chewable tablets prior to ingestion of lactose-containing substances. Studies demonstrate varying success. Digestive supplementations are apparently limited in their ability to digest large quantities of lactose.
  • Yogurt with live cultures is generally well tolerated by individuals with lactose intolerance. Dairy products with reduced or no lactose are widely available.

Consultations

Consultation with a pediatric gastroenterologist is suggested if the patient has symptoms that do not resolve after dietary elimination of lactose or if the patient has severe symptoms.

Diet

Lactose is believed to enhance the absorption of several minerals, including calcium, magnesium, and zinc. In addition, milk products that contain a large amount of lactose also contain a high amount of calcium. Because calcium is extremely important in bone growth, children can quickly become deficient if adequate calcium intake is not maintained; thus, calcium supplementation is required in anyone restricted from dairy products. In fact, primary adult hypolactasia has been associated with decreased serum calcium level and lower bone mineral density in postmenopausal women.⁵

Medication

Medication is not currently a component of care in this condition. See Treatment.

Follow-up

Complications

• Milk is the primary source of calcium for children. Children who are lactose intolerant and do not ingest proper quantities of dairy products quickly become depleted of calcium, which places them at risk for rickets and osteomalacia.
• Calcium supplementation through the administration of dietary or pharmacological supplements is suggested for any child who does not receive adequate calcium.

Patient Education

• Lower calcium levels are found in individuals with lactose intolerance; thus, emphasizing the importance of calcium supplementation is important.
• Although the symptoms are directly related to the quantity of lactose ingested, the patient should be educated about the fact that lactose may be hidden, in low amounts, in the following foods:
  • Breads
  • Baked goods
  • Cereals
  • Instant mixes
  • Margarine
  • Dressings
  • Candies
  • Snacks
• Some over-the-counter drugs can reduce symptoms (eg, simethicone for relief of flatulence, exogenous lactase drops or tablets derived from yeast).

Miscellaneous

Medicolegal Pitfalls

No medical or legal pitfalls are associated with the diagnosis of lactose intolerance.

References

1. Seppo L, Tuure T, Korpela R, et al. Can primary hypolactasia manifest itself after the age of 20 years? A two-decade follow-up study. Scand J Gastro. 2008;43:1082-1087. [Medline].

2. Montalto M, Gallo A, Santoro L, et al. Low-dose lactose in drugs neither increases breath hydrogen excretion nor causes gastrointestinal symptoms. Aliment Pharmacol Ther. Oct 15 2008;28(8):1003-12. [Medline].

3. Krawczyk M, Wolska M, Schwartz S, et al. Concordance of genetic and breath tests for lactose intolerance in a tertiary referral centre. J Gastrointestin Liver Dis. Jun 2008;17(2):135-9. [Medline].

4. Griffin MP, Hansen JW. Can the elimination of lactose from formula improve feeding tolerance in premature infants?. J Pediatr. Nov 1999;135(5):587-92. [Medline].

5. Bacsi K, Kosa JP, Lazary A, et al. LCT 13910 C/T polymorphism, serum calcium, and bone mineral density in postmenopausal women. Osteoporos Int. Aug 13 2008;[Medline].

6. Bodlaj G, Stocher M, Hufnagl P, et al. Genotyping of the lactase-phlorizin hydrolase -13910 polymorphism by LightCycler PCR and implications for the diagnosis of lactose intolerance. Clin Chem. 2006;52:148-151. [Medline].

7. Guandalini S. Treatment of acute diarrhea in the new millennium. J Pediatr Gastroenterol Nutr. 2000;30:486-9. [Medline].

8. He T, Venema K, Priebe MG, Welling GW, Brummer RJ, Vonk RJ. The role of colonic metabolism in lactose intolerance. Eur J Clin Invest. Aug 2008;38(8):541-7. [Medline].

9. Kuokkanen M, Kokkonen J, Enattah NS. Mutations in the Translated Region of the Lactase Gene (LCT) Underlie Congenital Lactase Deficiency. Am J Hum Genet. 2006;78:339-44. [Medline].

10. Montalto M, Curigliano V, Santoro L. Management and treatment of lactose malabsorption. World J Gastroenterol. 2006;14:187-91. [Medline].

11. Savaiano DA, Boushey CJ, McCabe GP. Lactose intolerance symptoms assessed by meta-analysis: a grain of truth that leads to exaggeration. J Nutr. 2006;136:1107-13. [Medline].

12. Shulman RJ,, Wong WW, Smith EO. Influence of changes in lactase activity and small-intestinal mucosal growth on lactose digestion and absorption in preterm infants. Am J Clin Nutr. 2005;81:472-9. [Medline].

13. Srinivasan R, Minocha A. When to suspect lactose intolerance. Symptomatic, ethnic, and laboratory clues. Postgrad Med. Sep 1998;104(3):109-11, 115-6, 122-3. [Medline].

Keywords

lactose intolerance, hypolactasia, lactase, milk intolerance, milk-protein allergy, milk protein allergy, primary lactase deficiency, congenital lactase deficiency, gastroenteritis, acute gastroenteritis, adult-onset lactase deficiency, glucose-galactose malabsorption, borborygmi, celiac disease, food allergy, diarrhea, infectious diarrhea, viral gastroenteritis

Contributor Information and Disclosures

Author

Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Coauthor(s)

Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and International Neuropsychological Society
Disclosure: Nothing to disclose.

Delia M Rivera, MD, Assistant Professor, Department of Pediatrics, Division of Infectious Disease and Immunology, University of Miami Leonard M Miller School of Medicine
Delia M Rivera, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, and Pediatric Infectious Diseases Society
Disclosure: Abbott Pharmaceuticals Honoraria Consulting; Monogram Biosciences Honoraria Consulting; Sanofi Pasteur: Combination Pediatric Vaccines Honoraria Speaking and teaching

Stephen Borowitz, MD, Professor of Pediatrics and Public Health Sciences, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Virginia
Stephen Borowitz, MD is a member of the following medical societies: American Academy of Pediatrics, American Gastroenterological Association, American Pediatric Society, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Alan D Schmetzer, MD, Professor and Vice-Chair for Education, Director of Residency Training, Department of Psychiatry, Indiana University School of Medicine
Alan D Schmetzer, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Society of Transplant Surgeons, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

B U K Li, MD, Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Director, Pediatric Fellowships and Gastroenterology Fellowship, Medical Director, Functional Gastrointestinal Disorders and Cyclic Vomiting Program, Medical College of Wisconsin; Attending Gastroenterologist, Children's Hospital of Wisconsin
B U K Li, MD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

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