Lactose intolerance

Lactose intolerance is caused by the malabsorption of lactose. It may be genetically determined or due to a functional deficiency of the lactase enzyme in the epithelium of the small intestine. After consuming food or beverages containing lactose, affected individuals develop abdominal symptoms, such as pain, diarrhea, and bloating. Lactose intolerance is diagnosed with a hydrogen breath test or lactose intolerance test. The condition may be managed well with lactase supplements or by avoiding lactose altogether.

Lactose intolerance is the inability to absorb lactose, caused by lactase deficiency.

• Approximately 70% of the world's population is lactose intolerant.
• Lactose intolerance is more common in certain regions, particularly Asia, parts of Africa, and South America, where up to 90% of the population is affected.
• Prevalence increases with age.

References:^[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

• Primary (lactase nonpersistence)
  • Most common type of lactose intolerance
  • A decrease in lactase activity is primarily observed during childhood or adolescence.
  • Genetic polymorphism of the lactase‑coding gene with subsequent down‑regulation (absence of lactase-persisting allele)
  • Lactase levels decline with age and are further influenced by genetic factors.
• Secondary (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., rotavirus)
• Developmental: occurs in children born prematurely, as lactase activity develops late during pregnancy
• Congenital: autosomal recessive gene defect (extremely rare)

References:^[4]

• 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). ^[5]
  • The transfer of osmotically active amounts of lactose into the large intestine leads to the osmotic binding of water → diarrhea
  • 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. ^[4]

• 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.

• Trial lactose‑free diet: to see if symptoms resolve
• Hydrogen breath test
  • The amount of hydrogen in the expired air increases after administering lactose in the fasting state.
  • Procedure
    • Fasting for 8–12 hours
    • Ingestion of lactose
    • Measurement of breath hydrogen levels at baseline and at 30‑minute intervals over 3 hours
    • Breath hydrogen levels > 20 ppm are considered diagnostic of lactose intolerance.
• Lactose tolerance test: Following the administration of lactose, the normal rise in blood glucose levels is pathologically reduced (< 20 mg/dL over 2 hours) and symptoms appear (rarely used, as the test has low sensitivity and specificity)
• Stool analysis
  • ↑ Stool osmotic gap
  • ↓ Stool pH (< 6): due to lactose fermentation by colonic bacterial flora
• Biopsy of the small intestine: qualitative and quantitative assessment of lactase via endoscopic tissue biopsy (conclusive, but rarely used, as the test is more invasive than other tests).
  • Primary lactose intolerance: normal intestinal architecture
  • Secondary lactose intolerance
    • Mucosal damage (especially injured tips of intestinal villi)
    • Specific histopathological findings corresponding to the underlying condition (see “Etiology”)
• Genetic test (if primary lactose malabsorption is suspected)

References:^[4]

• Food allergy ^[6]
  • IgE-mediated: cow's milk allergy, peanut allergy
  • Non-IgE-mediated ^[7]
    • 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
• Irritable bowel syndrome
• Inflammatory bowel disease
• Gastrointestinal infections (e.g., giardiasis, bacterial GE, viral GE)
• Small bowel bacterial overgrowth
• Cystic fibrosis
• Bowel malignancy

The differential diagnoses listed here are not exhaustive.

• Avoid or reduce intake of milk products: lactose‑free or lactose‑reduced products have become more readily available
  • Many patients tolerate small amounts of milk (∼ 240 mL per day).
  • Use of alternative foods, such as soy‑based products
  • Awareness of lactose in processed foods or foods other than dairy products (e.g., bread, salad dressings)
• Oral lactase supplements
  • Recommended when traveling or before consuming food or milk products containing lactose
  • A wide variety of nonstandardized over‑the‑counter lactase supplements are available
• Treatment of the underlying condition in patients with secondary lactose intolerance

References:^[4][5]