Lactose Intolerance

Epidemiology

• In children: low prevalence at < 6 years of age → genetically regulated reductions of lactase activity begin after weaning off breast milk
• In adults:
  • > 70% of adults worldwide have primary lactose deficiency (LD), but less than half of all adults have lactose intolerance (LI).
  • Lowest prevalence of LD: Northern Europeans
  • Highest prevalence of LD: Africans, African Americans, Asians, Asian Americans, Hispanics, and Native Americans

Etiology

Primary LD

• Also called acquired primary lactase deficiency, lactase non-persistence, and primary adult hypolactasia
• Most common type of LD (> 70% adults); a genetically determined epigenetic regulation of the lactase gene that decreases, either partially or completely, lactase activity after weaning 
• More than half of people with primary LD do not have LI.

Secondary LD

• A decrease in lactase and other brush border enzymes as well as abnormalities in transport processes
• Due to small intestine infection or a primary mucosal disease such as celiac disease

Less common types of LD

• Congenital (e.g., rare deficiency of lactase)
• Developmental: in premature infants, since lactase activity develops late in gestation

Pathophysiology

General consideration

• Adults: Most have primary LD, but the majority do not develop LI.
• Infants: all infants have lactase, which digests lactose → the most abundant carbohydrate in breast milk (accounts for 40% of calories in the milk).
• Carbohydrates are only absorbed in the small bowel and only as monosaccharides.

Lactase

• One of the enzymes in the brush border of the small intestine
• Digests lactose into glucose and galactose, which are actively transported into the enterocytes by the sodium/glucose (galactose) co-transporter (SGLT1)
• Lactase activity falls during weaning and does not persist after 6 years of age in > 70% of people, causing primary LD but not necessarily LI.
• In secondary LD, the activity levels of other enzymes and transport processes also fall, secondary to infections or inflammation of the small bowel.

Effects of undigested lactose

• Undigested lactose causes an osmotic load that pulls water and electrolytes into the bowel → watery diarrhea
• Gas is produced by bacterial fermentation of lactose in the colon (hydrogen, carbon dioxide, and methane):
  • Results in excessive bloating, flatulence, and abdominal pain
  • Colonic adaptation or “enhanced colonic lactose processing”: a reduction of intolerance symptoms, likely related to a change in microbiome → reduction of symptoms
• The likelihood of developing symptoms after lactose ingestion depends on a number of factors.

Clinical Presentation

Children and adolescents

• Uncommon to show signs of LI under 6 years of age
• Diarrhea, with bulky, frothy, and watery stools
• Inability to gain weight
• Abdominal pain
• Bloating
• Flatulence
• Nausea
• Vomiting

Adults

• Symptoms depend on multiple factors, including lactose load: usually requires ingestion of > 480 mL (2 cups) of milk
• Abdominal pain 
• Bloating
• Flatulence
• Nausea
• Vomiting
• Diarrhea is rare in adults.

Diagnosis

Consider a diagnosis of LI if typical symptoms occur within a few hours after ingestion of a lactose-containing meal and resolve after 5–7 days.

Testing for LD

Note: Tests for LD alone do not confirm LI unless symptoms are also provoked by lactose loading.

• Validated questionnaire
• Lactose hydrogen breath test:
  • Measures lactose malabsorption
  • Testing method in adults: 
    • Give 50 g of lactose orally and sample breath hydrogen at baseline and every 30 minutes for 3–4 hours. 
    • A rise in hydrogen concentration of 20 parts per million (ppm) over baseline is diagnostic of lactose malabsorption.
    • Sensitivity: 78%; specificity: 98%
• Small bowel biopsy: 
  • The diagnostic gold standard but rarely performed because it is invasive 
  • Can help distinguish between primary and secondary LD

Secondary causes of LD

Always consider potential secondary causes of LD when making the diagnosis:

• Infectious enteritis, including giardiasis
• Celiac disease
• Inflammatory bowel disease (especially Crohn’s disease)
• Drug- or radiation-induced enteritis
• Secondary intestinal bacterial overgrowth

Management

Primary lactose intolerance

• Lactose restriction:
  • Reduce load to ≤ 480 mL (2 cups) of milk or equivalent per day. 
  • Should be consumed with other food to delay gastric emptying
  • Routine daily consumption of lactose is better than intermittent intake due to colonic adaptation. 
  • Milk and ice cream deliver the highest lactose loads: High-fat content can mitigate symptoms as it decreases gastric emptying rate.
  • Cheeses: usually contain lower amounts of lactose
  • Live-culture yogurt contains endogenous lactase → breaks down lactose into galactose and glucose
• Substitute regular dairy products with predigested ones, or vegan products.
• Lactase enzyme preparations: do not completely hydrolyze ingested lactose; efficacy highly variable
• Increase consumption of calcium and vitamin D, with supplements if necessary, if patient avoids all dairy products → monitor blood levels

Secondary lactose intolerance

Treat the primary disorder. It may take months for normal lactase activity to return to normal.

Differential Diagnosis

• Cow’s milk allergy: the most common food allergy in young children but uncommon in adults. Cow’s milk proteins can provoke IgE-mediated and/or non-IgE-mediated immune response. Diagnosis is made by testing for specific IgE antibodies and/or by elimination diet.
• Food protein intolerance: can present with similar symptoms as LI due to unabsorbed substrate in the intestine. Although the temporal association of the symptoms with the type of food ingested can point toward the responsible food product, the best way to differentiate between the 2 conditions is via hydrogen breath test or trial of a lactose-free diet.
• Irritable bowel syndrome: can present with similar symptoms (abdominal pain, bloating, and diarrhea) and may worsen coexisting LI, but the temporal association of the symptoms only with the ingestion of lactose products points toward lactose intolerance. The best way to differentiate between the 2 conditions is by a hydrogen breath test or trial of a lactose-free diet.
• Pediatric diarrhea: has many potential causes, including secretory and osmotic diarrhea, motility disorders, and diarrhea due to decreased surface area. Multiple diagnostic tools are available.
• Incomplete absorption of orally ingested simple carbohydrates: these carbohydrates include sorbitol, mannitol, xylitol, fructose, and FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols). Sorbitol, mannitol, and xylitol are used as artificial sweeteners, and mannitol is used as a laxative. Diagnosis is usually straightforward based on the dietary history or a breath test for fructose.