• Clinical science

Lactose intolerance (Lactase deficiency)

Abstract

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.

Definition

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

Epidemiology

  • 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.
  • The prevalence increases with age
  • Prevalence in the United States reflects worldwide figures, with Americans of European descent being least affected by primary lactose intolerance. In Asian, African, Hispanic, and Native American populations, the prevalence is higher.

References:[1][2][3][4]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Primary (lactase non‑persistence): most common type of lactose intolerance; a decrease in lactase activity is primarily observed during childhood or adolescence
  • Secondary (acquired): due to underlying disorders of the small intestine that result in mucosal damage (e.g., gluten‑sensitive enteropathy following gastroenteritis)
  • Developmental: occurs in children born prematurely, as lactase activity develops late during pregnancy
  • Congenital: autosomal recessive gene defect (extremely rare)

References:[5]

Pathophysiology

  • 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).
    • The transfer of osmotically active amounts of lactose into the large intestine leads to the osmotic binding of waterdiarrhea
    • Increased peristalsis due to increased intestinal filling → stomach 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!

References:[6][7]

Clinical features

Symptoms occur about an hour to several hours following consumption of milk products. The intensity of symptoms correlates with the amount of lactose consumed.

  • 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!
References:[6][5]

Diagnostics

  • Stool analysis: ↑ stool osmotic gap , stool pH < 6
  • Hydrogen breath test
    • The amount of hydrogen in the expired air increases after administering lactose in the fasting state.
    • Measurement at baseline and at 30‑minute intervals over 3 hours following the ingestion of 50 g of lactose (children: 2 g/kg lactose (max. amount 25 g)) Breath hydrogen levels > 20 ppm are considered diagnostic.
  • Lactose tolerance test: Following the administration of lactose, the normal rise in blood glucose levels is pathologically reduced (less than 20 mg/dL over two hours) and symptoms appear → rarely used, as the test has low sensitivity and specificity.
  • Trial lactose‑free diet: to see if symptoms resolve
  • Biopsy of the small intestine: : qualitative and quantitative assessment of lactase via an endoscopic tissue biopsy (conclusive, although rarely used). Histologic analysis shows normal intestinal architecture.
  • Genetic test (if primary lactose malabsorption is suspected)

References:[6][5]

Differential diagnoses

  • Food protein intolerance
    • Common antigens: cow milk proteins (lactalbumin or casein, among others); soy protein; egg protein
    • Reactions are either IgE‑mediated (e.g., cow's milk allergy) or non‑IgE‑mediated
    • Clinical findings
      • Abdominal pain, nausea, vomiting, and diarrhea
      • Food protein-induced proctocolitis (e.g., caused by milk or soy protein)
        • Affects primarily young infants; typically manifests at 2–8 weeks of age
        • Stools tinged with blood and mucus in otherwise healthy children
        • A clinical diagnosis
        • Management: continue breastfeeding and advise the mother to avoid dairy and soy products
        • Resolution of symptoms once causative antigen is removed
  • Irritable bowel syndrome
  • Inflammatory bowel disease
  • Gastrointestinal infections (e.g., giardiasis, bacterial, viral)
  • Small bowel bacterial overgrowth
  • Cystic fibrosis
  • Bowel malignancy

References:[8][9][7]

The differential diagnoses listed here are not exhaustive.

Treatment

  • 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 non‑standardized over‑the‑counter lactase supplements are available
  • Treatment of the underlying condition in patients with secondary lactose intolerance
  • Abstaining from milk products may result in relative calcium and/or vitamin D deficiencies, requiring substitution.

References:[7][5]