eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Lactose Intolerance

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
Coauthor(s): 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
Contributor Information and Disclosures

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.

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