Lactose intolerance

Lactose intolerance is a clinical syndrome resulting from the inability to absorb lactose due to lactase deficiency. Lactase deficiency is caused by a genetic variant resulting in decreased lactase production or by disruption of the epithelium of the small intestine resulting in loss of lactase. After consuming food or beverages containing large quantities of lactose, individuals with lactose intolerance develop abdominal symptoms, such as pain, diarrhea, and bloating. Lactose intolerance is usually diagnosed if there is symptom resolution after a 2-week trial of a strict lactose-free diet. If symptoms persist, a confirmatory test is required (e.g., hydrogen breath test, lactose intolerance test). The condition is managed by adherence to a lactose-restricted diet and the use of oral lactase supplements.

• Lactase deficiency: low levels of lactase in the small intestine due to a genetic variant resulting in decreased lactase production, or disruption to the epithelium of the small intestine resulting in loss of lactase
• Lactose malabsorption
  • Lactase deficiency prevents the digestion of lactose in the small intestine, leading to passage of lactose into the large intestine.
  • Can be asymptomatic or cause gastrointestinal symptoms
• Lactose intolerance: gastrointestinal symptoms resulting from lactose malabsorption

• Approximately 70% of the world's population have a lactase deficiency; the proportion who develop lactose intolerance is unknown.
• Lactase deficiency commonly occurs in people of African, Asian, or Native American ancestry (prevalence is up to 100%).
• The prevalence of lactose intolerance increases with age.

Epidemiological data refers to the US, unless otherwise specified.

• Primary lactase deficiency (lactase nonpersistence)
  • Most common cause of lactose intolerance
  • Genetic polymorphism in the lactase‑coding gene with subsequent downregulation (absence of lactase-persistence allele)
  • Symptoms occur after lactase activity starts to decrease during childhood; the rate of decline is influenced by genetic factors. ^[2]
• Secondary lactase deficiency (acquired)
  • Due to underlying disorders of the small intestine that result in mucosal damage, e.g.:
    • Autoimmune disorders (e.g., gluten-sensitive enteropathy)
    • Viral gastroenteritis (e.g., due to rotavirus)
  • Can occur at any age but most commonly affects infants ^[2]
• Congenital lactase deficiency
  • An autosomal recessive condition (extremely rare)
  • Clinical features develop in the first few days of life.
• Developmental lactase deficiency: transient lactase deficiency that occurs in premature infants, as lactase activity develops late during pregnancy

Not all individuals with lactase deficiency develop lactose intolerance; lactose malabsorption may be asymptomatic. ^[1]

• Lactase is a brush‑border enzyme that cleaves lactose, a disaccharide, into absorbable monosaccharides (galactose and glucose).
• In the case of lactase deficiency, an almost complete absence of lactose digestion is observed, resulting in decreased absorption in the small intestine (particularly the jejunum). ^[3]
  • The transfer of osmotically active amounts of lactose into the large intestine leads to the osmotic binding of water → diarrhea with a high osmotic gap
  • ↓ Stool pH (< 6): due to lactose fermentation by colonic bacterial flora
  • Increased peristalsis due to increased intestinal filling → abdominal pain
  • Metabolism of lactose via the physiological bacterial flora of the colon
    • Formation of short‑chain fatty acids that exacerbate diarrhea
    • Increased gas formation and flatulence

Lactase deficiency is a malabsorption disorder.

Symptoms occur about an hour to several hours following consumption of milk products; the intensity of symptoms correlates with the amount of lactose consumed. ^[2]

• Diarrhea (often watery, bulky, and frothy)
• Cramping abdominal pain (often periumbilical or in the lower abdomen)
• Abdominal bloating, flatulence
• Nausea

Symptoms vary widely as most patients have residual amounts of lactase.

There is no standardized approach to diagnostic evaluation. ^[4]

Approach ^[4][5]

• Rule out differential diagnoses and underlying pathology.
  • Assess for features of underlying causes of secondary lactase deficiency and workup accordingly. ^[6]
  • Consider differential diagnoses of lactose intolerance, e.g., irritable bowel syndrome (IBS).
  • Rule out red flags for colorectal cancer and red flags in diarrhea.
• Trial a 2-week strict lactose-free diet, taking care to exclude hidden sources of lactose. ^[2]
  • If symptoms resolve, then recur with reintroduction of lactose: Diagnose lactose intolerance.
  • If symptoms persist: Refer to gastroenterology to test for lactose malabsorption.

Lactose malabsorption studies ^[4][7]

• The following tests detect lactose malabsorption; care must be taken to ensure symptoms are not attributable to a different cause. ^[1][8]
• For children, the hydrogen breath test is the preferred study.
• For adults, there is no preferred test; choose based on patient characteristics, preference, and local availability. ^[2][5][6]

Options

• Hydrogen breath test (least invasive) ; ^[7]
  • Principle
    • Hydrogen is produced due to bacterial fermentation following the transfer of undigested lactose from the small intestine to the large intestine, which is then reabsorbed into the blood and excreted by the lungs.
    • The excreted hydrogen can then be measured.
  • Method
    • Fast for 8–12 hours.
    • Ingest 25 g lactose with 1 cup of water. ^[2][7]
    • Measure breath hydrogen levels at set intervals for 3 hours.
  • Diagnostic result: increase in breath hydrogen levels of > 20 ppm ^[7]
• Lactose tolerance test ^[6]
  • Method
    • Ingestion of 50 g lactose ^[4]
    • Serial measurements of serum glucose ^[1][4]
  • Diagnostic result: rise in serum glucose of < 20 mg/dL from pretest values ^[4]
• Endoscopy with small intestine biopsy ^[1][2]
  • Primary lactase deficiency: normal intestinal architecture
  • Secondary lactase deficiency: mucosal damage, e.g., injured tips of intestinal villi
  • All patients: low levels of lactase
• Genetic testing: limited use in selected populations ^[4][5]

• Food allergy ^[9]
  • IgE-mediated: cow's milk allergy, peanut allergy
  • Non-IgE-mediated ^[10]
    • Allergy to common antigens, such as cow's milk proteins (e.g., lactalbumin, casein), soy proteins, and egg proteins
    • Food protein-induced allergic proctocolitis
  • Mixed IgE/non-IgE-mediated: eosinophilic gastrointestinal disorder
• Food intolerance: fructose intolerance, intolerance of short-chain fermentable carbohydrates
• Celiac disease ^[6]
• Irritable bowel syndrome
• Inflammatory bowel disease
• Gastrointestinal infections (e.g., giardiasis, bacterial or viral gastroenteritis)
• Small bowel bacterial overgrowth
• Cystic fibrosis
• Bowel malignancy

The differential diagnoses listed here are not exhaustive.

Approach ^[4][5]

• Advise a lactose-restricted diet.
  • Primary lactose intolerance: Dietary changes will be lifelong.
  • Secondary lactose intolerance
    • Treat the underlying condition (e.g., IBD, infectious gastroenteritis).
    • It may be possible to reintroduce lactose once the underlying condition has been managed effectively. ^[1][6][11]
• Recommend ; taking commercially available oral lactase supplements when consuming lactose. ^[2][6]
• Ensure patients receive the recommended daily intake of calcium and vitamin D through diet or supplementation to prevent osteomalacia. ^[2][5]

Although prebiotics and probiotics may reduce symptoms of lactose intolerance, high-quality evidence is lacking and, currently, there are no definitive recommendations. ^[1][5][12]

Lactose-restricted diet

• Reduce lactose intake. ; ^[4]
  • Use lactose‑free or low-lactose products. ^[4]
  • Some lactose (e.g., 8–12 fluid oz of cow's milk per day) is often tolerated. ^[5][6]
  • Advise reading food labels to identify lactose in unexpected items (e.g., bread, certain medications, salad dressing). ^[6]
• When consuming lactose, consume other solid foods to slow gastric emptying. ^[2]

Yogurt is usually well-tolerated because of the bacteria-derived lactase in live cultures. ^[6]

Lactose intolerance in children ^[2]

Clinical features

• Clinical features of lactose intolerance are similar in children and adults.
• The age of onset varies depending on population genetics. ^[2]

Diagnostics ^[2]

• < 3 years of age: Primary lactose intolerance is unlikely.
  • Refer to pediatric gastroenterology to evaluate for secondary lactase deficiency or, rarely, congenital lactase deficiency.
  • Infants: Consider assessing for carbohydrate (including lactose) malabsorption with stool analysis. ^[2]
    • ↑ Stool osmotic gap
    • ↓ Stool pH (< 5) ^[2]
• ≥ 3 years of age
  • Diagnostics for lactose intolerance are the same as for adults.
  • Refractory cases: Refer to gastroenterology for further studies; secondary lactase deficiency is likely. ^[2]

Congenital lactase deficiency can be life-threatening and must be identified immediately. ^[2]

Treatment

• Treatment of lactose intolerance in children is similar to that in adults.
• Children may be able to tolerate a smaller amount of lactose than adults (e.g., 4–8 oz of milk per day). ^[2]
• Infants: Management depends on underlying etiology of lactose intolerance. ^[2]
  • Congenital lactase deficiency: Give lactose-free formula.
  • Secondary lactase deficiency or developmental lactase deficiency
    • Breastfed infants: Continue breastfeeding.
    • Formula fed infants: Give low-lactose or lactose-free formula if symptoms are severe.