> Table of Contents > Lactose Intolerance
Lactose Intolerance
Nihal K. Patel, MD
image BASICS
DESCRIPTION
  • Inability to digest lactose into constituent components (glucose and galactose) due to low levels of lactase in the brush border of the small intestinal mucosa, causing bloating, borborygmi (audible stomach “rumblings”), abdominal pain, and diarrhea
    • Congenital lactose intolerance: very rare
    • Primary lactose intolerance: common in adults who develop low lactase levels after childhood
    • Secondary lactose intolerance: inability to digest lactose caused by any condition injuring the intestinal mucosa (e.g., infectious enteritis, celiac disease, eosinophilic gastroenteritis, or inflammatory bowel disease) or a reduction of available mucosal surface (e.g., resection)
  • Lactase activity peaks at birth then decreases after the first few months of life, declining continuously during lifetime. 75% of adults' worldwide exhibit decline in lactase activity. However, only 50% of lactase activity is needed to digest lactose without causing symptoms of lactose intolerance.
  • Lactose malabsorption also results from reduction of lactase activity. It is asymptomatic, and is as common in healthy patients as in those with functional bowel disorders.
  • System(s) affected: endocrine/metabolic, gastrointestinal
Pediatric Considerations
  • Primary lactose intolerance usually begins in late childhood.
  • No consensus exists on whether young children (<5 years of age) should avoid lactose following diarrheal illness.
  • Lactose-free formulas are available.
  • Exclude milk protein allergy.
EPIDEMIOLOGY
Incidence
  • ≥50% of infants with acute or chronic diarrheal disease have lactose intolerance. Particularly common with rotavirus infection.
  • Lactose intolerance is common with giardiasis, ascariasis, irritable bowel syndrome (IBS), tropical and nontropical sprue, and the AIDS malabsorptive syndrome.
Prevalence
  • In South America, Africa, and Asia, rates of lactose intolerance are >50%.
  • In the United States, the prevalence is 15% among whites, 53% among Hispanic Americans, and 80% among African Americans.
  • In Europe, lactose intolerance varies from 15% in Scandinavian countries to 70% in Italy.
  • Predominant age:
    • Primary: teenage and adult
    • Secondary: depends on underlying condition
  • Predominant sex: male = female
ETIOLOGY AND PATHOPHYSIOLOGY
  • Primary lactose intolerance: Normal decline in the lactase activity in the intestinal mucosa is genetically controlled and permanent after weaning from breastmilk.
  • Secondary lactose intolerance: associated with gastroenteritis in children and with nontropical and tropical sprue, regional enteritis, abetalipoproteinemia, cystic fibrosis, inflammatory bowel disease, celiac disease, and immunoglobulin deficiencies in both adults and children
Genetics
  • In Caucasians, lactase deficiency has been associated with a single nucleotide polymorphism (SNP) consisting of a nucleotide switch of T for C 13.910. bp on chromosome 2. This results in variants of CC-13910 (lactase nonpersistence) OR CT-13910/TT-13910 (lactase persistence) (1).
  • SNP (C/T-13910) is associated with lactase persistence in northern Europeans.
  • Other SNPs (G/C-14010, T/G-13915, and C/G-13907) have been linked to lactase persistence in Africans.
RISK FACTORS
  • Adult-onset lactase deficiency has wide geographic variation.
  • Age:
    • Signs and symptoms usually do not become apparent until after age 6 to 7 years.
    • Symptoms may not be apparent until adulthood, depending on dietary lactose intake and rate of decline of intestinal lactase activity.
    • Lactase activity correlates with age, regardless of symptoms.
GENERAL PREVENTION
Lactose avoidance relieves symptoms. Patients can learn what level of lactose is tolerable in their diet.
COMMONLY ASSOCIATED CONDITIONS
  • Tropical or nontropical sprue
  • Giardiasis
  • Inflammatory bowel disease
  • Immunoglobulin deficiencies
  • Celiac disease
  • Cystic fibrosis
image DIAGNOSIS
  • Lactose intolerance is defined by a positive lactose hydrogen breath test result plus accompanying clinical symptoms.
  • Lactose intolerance can mimic symptoms of functional gastrointestinal disorders. Lactose intolerance can also be a coexisting condition.
PHYSICAL EXAM
Borborygmi may be audible on physical examination and to the patient. The exam is otherwise typically nonspecific.
DIFFERENTIAL DIAGNOSIS
  • Sucrase deficiency
  • Cow's milk protein allergy
  • IBS
  • Bacterial overgrowth
  • Celiac disease
  • Inflammatory bowel disease
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • The lactose breath hydrogen test (LBT) is the best diagnostic test for lactose intolerance. It is noninvasive, easy to perform, and cost effective. It is limited by suboptimal sensitivity (2)[B]. Intestinal bacteria digest carbohydrates and produce hydrogen and methane that are measurable in expired air:
    • Oral lactose is administered in the fasting state, (2 g/kg; max dose 25 g). Breath hydrogen is sampled at baseline and at 30-minute intervals for 3 hours. The postlactose and baseline values are compared. A breath hydrogen value of 10 ppm is normal. Values between 10 and 20 ppm may be indeterminate unless accompanied by symptoms; values >20 ppm are considered diagnostic of lactose malabsorption.
  • The biochemical assay of lactase activity on duodenal sampling is as sensitive as LBT in detecting lactase deficiency. It is more accurate than LBT in predicting the clinical response to a lactose-free diet. Cost and invasiveness limit clinical utility
  • For patients with symptoms of lactose intolerance who are undergoing endoscopy for other reasons, a biochemical assay on duodenal biopsies can rule out lactose malabsorption.
  • A positive LBT confirms lactose malabsorption but does not define the etiology.
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Diagnostic Procedures/Other
Lactose absorption test is an alternative to LBT in adults (more invasive and equivalent in sensitivity and specificity to breath test). Following oral administration of a 50-g test dose in adults (2 g/kg in children), blood glucose levels are monitored at 0, 60, and 120 minutes. An increase in blood glucose of <20 mg/dL (1.1 mmol/L) with the concurrent development of symptoms is diagnostic. False-negative results may occur in patients with diabetes or bacterial overgrowth.
Test Interpretation
Lactase deficiency in intestinal mucosa may be patchy or focal.
image TREATMENT
There is insufficient evidence on treatments (including probiotics, colonic adaptation, and other supplements) to recommend any as definitive first-line.
  • Treatment of lactose malabsorption in the absence of a correctable underlying disease includes four general principles (3)[B].
    • Patients should avoid milk and dairy products in order to improve symptoms.
    • Up to 12 to 15 g of lactose can be tolerated in patients with lactose intolerance without significant symptoms (1 cup of milk).
    • Lactose should be gradually reintroduced along with other nutrients until the patient's threshold for symptoms is reached. Spreading lactose servings throughout the day instead of a single dose has been shown to improve tolerance.
    • If symptoms persist, patients can substitute fermented and matured milk products for lactose.
  • Certain strains, concentrations, and preparations of probiotics may alleviate symptoms.
  • Incrementally increasing doses of lactose to induce colonic adaptation have met with limited success.
  • To date, insufficient scientific evidence exists to strongly recommend lactose-reduced or hydrolyzed milk, lactase supplements taken with milk, probiotics, or colonic adaptation to treat lactose intolerance. Use of these supplements should be considered on a case-by-case fashion.
  • Maintain calcium and vitamin D intake.
MEDICATION
First Line
Lactase (Lactaid, Lactrase):
  • Commercially available “lactase” preparations are bacterial or yeast &bgr;-galactosidases.
  • Take 1 to 2 capsules or tablets prior to ingesting milk products.
  • Vary in effectiveness at preventing symptoms
  • Can add tablets or contents of capsules to milk (1 to 2 caps/tabs per quart of milk) before drinking; also available in milk in some areas
  • Not effective for all people with lactose intolerance
  • High-quality, large, randomized controlled trials showing efficacy and safety are lacking.
COMPLEMENTARY & ALTERNATIVE MEDICINE
Certain probiotic formulations taken with meals may alleviate some symptoms of lactose intolerance (4)[B].
image ONGOING CARE
DIET
  • Reduce or restrict dietary lactose to control symptoms. This is patient-specific and done as “trial-and-error.”
  • Yogurt and fermented products such as hard cheese are often better tolerated than milk.
  • Supplement calcium (e.g., calcium carbonate)
  • Prehydrolyzed milk (Lactaid) is available.
PATIENT EDUCATION
  • Patients must learn to read labels on commercial products because milk sugar is used in many products and may cause symptoms.
  • Lactose-intolerant patients may tolerate whole milk or chocolate milk better than skim milk due to slower rate of gastric emptying.
  • Lactose consumed with other food products is better tolerated than when consumed with milk alone.
  • Primary lactase deficiency is permanent; secondary lactose intolerance usually is temporary, although it may persist for months after the inciting event.
  • 20% of prescription drugs and 6% of over-thecounter (OTC) medicines use lactose as a base.
  • Most patients can tolerate 12 to 15 g of lactose, despite lactose intolerance or malabsorption.
PROGNOSIS
  • Normal life expectancy
  • Symptoms can be controlled through diet alone if lactase tablets are ineffective.
REFERENCES
1. Mattar R, de Campos Mazo DF, Carrilho FJ. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol. 2012;5:113-121.
2. Law D, Conklin J, Pimentel M. Lactose intolerance and the role of the lactose breath test. Am J Gastroenterol. 2010;105(8):1726-1728.
3. Shaukat A, Levitt MD, Taylor BC, et al. Systematic review: effective management strategies for lactose intolerance. Ann Intern Med. 2010;152(12):797-803.
4. Levri KM, Ketvertis K, Deramo M, et al. Do probiotics reduce adult lactose intolerance? A systematic review. J Fam Pract. 2005;54(7):613-620.
Additional Reading
&NA;
  • Almeida CC, Lorena SL, Pavan CR, et al. Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients. Nutr Clin Pract. 2012;27(2):247-251.
  • Boettcher E, Crowe SE. Dietary proteins and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108(5):728-736.
  • Fernández-Bañares F. Reliability of symptom analysis during carbohydrate hydrogen-breath tests. Curr Opin Clin Nutr Metab Care. 2012;15(5):494-498.
  • Furnari M, Bonfanti D, Parodi A, et al. A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance. J Clin Gastroenterol. 2013;47(2):148-152.
  • Tan-Dy CR, Ohlsson A. Lactase treated feeds to promote growth and feeding tolerance in preterm infants. Cochrane Database Syst Rev. 2013;(3):CD004591.
Codes
&NA;
ICD10
  • E73.9 Lactose intolerance, unspecified
  • E73.8 Other lactose intolerance
  • E73.1 Secondary lactase deficiency
Clinical Pearls
&NA;
  • The diagnosis of lactose intolerance is based on clinical history and typically confirmed by hydrogen breath testing.
  • Most lactose intolerant patients can tolerate 12 to 15 g of lactose per day.
  • Lactose-intolerant patients may tolerate yogurt and fermented products better than milk and cheese.
  • A food diary helps identify problematic foods.
  • Patients should read ingredient labels to look for milk, lactose, whey, and curd.
  • Lactose-intolerant patients may tolerate whole milk or chocolate milk better than skim milk due to a slower rate of gastric emptying.
  • Many patients with lactose intolerance unnecessarily avoid all dairy products, causing inadequate intake of calcium and vitamin D, which may predispose them to osteoporosis.