Lactose Intolerance

Updated: Dec 04, 2019

Author: Praveen K Roy, MD, MSc; Chief Editor: Burt Cagir, MD, FACS

Overview

Background

Lactose intolerance is a common disorder and is due to the inability to digest lactose into its constituents, glucose and galactose, secondary to low levels of lactase enzyme in the brush border of the duodenum.[1] Lactase deficiency is the most common form of disaccharidase deficiency. Enzyme levels are the highest shortly after birth and decline with aging, despite continued intake of lactose. Within the animal world, nonhuman mammals usually lose the ability to digest lactose as they reach adulthood. Some populations of the human species, including those of Asian, South American, and African descent, have a propensity for developing lactase deficiency. By contrast, races descended from northern Europe or from the northwestern Indian subcontinent are likely to retain the ability to absorb lactose into adulthood.[2]

Symptoms of lactose intolerance include loose stools, abdominal bloating and pain, flatulence, nausea, and borborygmi.[3, 4, 5] A diagnosis or even the suggestion of lactose intolerance leads many people to avoid milk and/or to consume specially prepared food with digestive aids, adding to health care costs.

Pathophysiology

Lactose, a disaccharide, is present in milk and processed foods. Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa. A deficiency of intestinal lactase prevents hydrolysis of ingested lactose. The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached. Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit, which increases the degree of maldigestion. Within the large intestine, free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas.[6] The combined increase in fecal water, intestinal transit, and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms.

An association between certain single nucleotide polymorphisms (C>T-13910 and G>A-22018) with lactose tolerance in a northeaster Brazilian population has been reported.[7] In Indo-Europe, lactase deficiency is associated with rs4982235 SNP (or -13910C>T), which may predispose affected individuals to lactose intolerance.[8]

Etiology

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare.[9, 10]

Primary lactose intolerance is due to low levels of lactase, which develop after childhood.

Secondary, or acquired, lactase deficiency may develop in a person with a healthy small intestine during episodes of acute illness. This occurs because of mucosal damage or from medications. Some causes of secondary lactase deficiency are as follows:

Acute gastroenteritis
Giardiasis
Ascariasis
Crohn disease
Celiac sprue
Tropical sprue
Gastrinoma
Radiation enteritis
Diabetic gastropathy
Carcinoid syndrome
Whipple syndrome
HIV enteropathy
Kwashiorkor
Chemotherapy

Epidemiology

United States statistics

The prevalence of primary lactose intolerance varies according to race. As many as 25% of the white population (prevalence in those from southern European roots) is estimated to have lactose intolerance, while among black, Native American, and Asian American populations, the prevalence of lactose intolerance is estimated at 75-90%.[2]

International statistics

An estimated 70-75% off the world's population is lactose-deficient.[8, 11] Lactose intolerance is very common among Asian, South American, and African persons.

Lactose intolerance also appears to have a higher prevalence in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) than healthy individuals.[12]

Race-, sex-, and age-related demographics

Persons of all races are affected by lactose intolerance, with a higher prevalence among Asian, African, and South American persons.

Males and females are equally affected by lactose intolerance. However, of adult women who are lactose intolerant, 44% regain the ability to digest lactose during pregnancy. This is probably due to slow intestinal transit and bacterial adaptation during pregnancy.

Few data are available regarding the prevalence of lactose intolerance in children aged 1-5 years; however, primary lactose intolerance in this group is estimated to be 0-17.9%, whereas it is a reported 0-19% for secondary lactose intolerance.[13]

Among adults, the age of presentation of lactose intolerance is 20-40 years.[9, 14]

Prognosis

The prognosis of patients with lactose intolerance is excellent with dietary restrictions. Morbidity/mortality include the following:

Lactose intolerance is not lethal.
Morbidity is low from lactose intolerance.
Osteopenia can be a complication of lactose intolerance.[15, 16, 17] Vitamin D deficiency appears to be associated with the LCT-13910C>T gene variant of lactose intolerance in white populations.[17]

Presentation

History and Physical Examination

History

Patients with lactose intolerance may include history of abdominal fullness/bloating, nausea, abdominal pain, diarrhea, and flatulence.[18, 19] Symptomatic variability is dependent on the amount of ingested lactose, the residual lactose activity, and the small bowel transit time.[11] It appears that 12 g of lactose in one intake, with about 18 g of lactose over the course of a day, is tolerable for most lactose-intolerant individuals.[11]

The symptoms of irritable bowel syndrome (IBS) resemble those of lactose intolerance and can easily be confused. Some patients with IBS can also have lactose intolerance. Restriction of milk products in these patients may relieve the symptoms of IBS.[20, 21]

Physical examination

Physical examination findings very often are normal. Borborygmi may be present.

DDx

Diagnostic Considerations

Other conditions to consider in the differential diagnosis of lactose intolerance include the following:

Sucrase deficiency
Diabetic diarrhea
Disorders associated with secondary lactose intolerance (see Etiology)

Differential Diagnoses

Workup

Laboratory Studies

Lactose tolerance test

This test is rarely done in clinical practice.

Measure serial blood glucose levels after an oral lactose load. A fasting serum glucose level is obtained, after which 50 g of lactose is administered.[22] Measure the serum glucose level at 0, 60, and 120 minutes.

The lactose tolerance test has a sensitivity of 75% and a specificity of 96%.

False-negative results occur in the presence of diabetes and small bowel bacterial overgrowth. Abnormal gastrointestinal emptying can also affect the results of the lactose tolerance test.[23]

The diagnosis is confirmed if the serum glucose level fails to increase by 20 g/dL above the baseline.

Milk tolerance test

Administer 500 mL of milk and measure the blood glucose level.

An increase of less than 9 mg/dL indicates lactose malabsorption.[24]

Other Tests

Imaging studies

Imaging tests are not helpful in the diagnosis of primary lactose intolerance, but they may be helpful for excluding secondary causes.

Breath hydrogen test

This is the diagnostic test of choice.

Subjects are administered lactose after an overnight fast, after which expired air samples are collected before and at 30-minute intervals for 3 hours to assess hydrogen gas concentrations.

A rise in breath hydrogen concentration greater than 20 parts per million over the baseline after lactose ingestion suggests lactase deficiency.[22]

Dietary elimination

Resolution of symptoms with the elimination of lactose-containing food products and resumption of symptoms with their reintroduction are findings suggestive of lactose intolerance.[25, 26]

Procedures

Small bowel biopsy

This is the criterion standard; however, it is invasive and rarely performed. A major advantage is that it provides definitive information.

Biopsy samples from the small bowel are assayed for lactase activity. The biopsy results may be normal if the deficiency is focal or patchy.

This is not readily available and is not usually necessary.

Treatment

Medical Care

Dietary adjustment is the primary form of therapy for patients with lactose intolerance.[27, 28] Advise patients to reduce or restrict products containing lactose. Prehydrolyzed milk (LACTAID) is available and is effective. Yogurt and fermented products, such as cheeses, are better tolerated than regular milk. Soy-based milk or food products are well tolerated.

Commercially available lactase enzyme preparations (eg, LACTAID, Lactrase) are effective in reducing symptoms; however, they may not be effective in some patients, partially due to insufficient dosing.

Plant-based milk alternatives are emerging; however, although these products show some potential, technologic, palatability, and/or nutritional balance issues remain a concern.[29, 30]

Probiotics (DDS-1 strain of Lactobacillus) have been shown to improve symptoms.[31, 32]

Supplemental calcium and vitamin D should also be recommended.[15]

In secondary lactase deficiency, treatment is directed at the underlying cause.[33]

Consultations

Consider consulting with a gastroenterologist and a nutritionist in the management of patients with suspected lactose intolerance.

Diet

Note the following dietary considerations in patients with lactose intolerance:

Patients should read labels on commercial products.
Patients should avoid or reduce intake of lactose-containing foods.
Most patients who are lactose intolerant can ingest as much as 240 mL of milk without an exacerbation of their symptoms.[34]
Whole milk and chocolate milk may be better tolerated than skim milk.[35]
Certain medications and foods contain hidden lactose, such as breads, margarine, salad dressings, and candies.

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Digestive enzymes

Class Summary

Provide necessary enzymes for lactose digestion.

Lactase enzymes (LACTAID, Dairy Ease, Lactrase)

For patients with lactase enzymatic deficiency. Prevent osmotic diarrhea in patients deficient in lactase enzyme who consume milk.

Questions & Answers

Overview

What is lactose intolerance?

What is the pathophysiology of lactose intolerance?

What causes lactose intolerance?

What causes secondary lactase deficiency?

What is the prevalence of lactose intolerance in the US?

What is the global prevalence of lactose intolerance?

Which patient groups have the highest prevalence of lactose intolerance?

What is the prognosis of lactose intolerance?

Presentation

Which clinical history findings are characteristic of lactose intolerance?

Which physical findings are characteristic of lactose intolerance?

DDX

Which conditions should be considered in the differential diagnoses of lactose intolerance?

What are the differential diagnoses for Lactose Intolerance?

Workup

What is the role of a lactose tolerance test in the workup of lactose intolerance?

What is the role of milk tolerance test in the workup of lactose intolerance?

What is the role of imaging studies in the workup of lactose intolerance?

What is the role of a breath hydrogen test in the workup of lactose intolerance?

What is the role of dietary elimination in the workup of lactose intolerance?

What is the role of biopsy in the workup of lactose intolerance?

Treatment

How is lactose intolerance treated?

Which specialist consultations are beneficial to patients with lactose intolerance?

Which dietary modifications are used in the treatment of lactose intolerance?

Medications

Which medications in the drug class Digestive enzymes are used in the treatment of Lactose Intolerance?

Author

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah D Komanapalli, MBBS Resident Physician in Internal Medicine, Marshfield Clinic

Sarah D Komanapalli, MBBS is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Homayoun Shojamanesh, MD Former Fellow, Digestive Diseases Branch, National Institutes of Health

Homayoun Shojamanesh, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Showkat Bashir, MD Assistant Professor, Department of Medicine, Division of Gastroenterology, George Washington University, Washington, DC

Showkat Bashir, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Burt Cagir, MD, FACS Associate Regional Dean and Professor of Surgery, Geisinger Commonwealth School of Medicine; Director, General Surgery Residency Program, Executive Director, Donald Guthrie Foundation for Research and Education, Guthrie Robert Packer Hospital; Medical Director, Guthrie/RPH Skills and Simulation Lab; Associate in Surgery, Guthrie Robert Packer Hospital and Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, Association of Program Directors in Surgery, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Additional Contributors

Ronnie Fass, MD, FACP, FACG Chief of Gastroenterology, Head of Neuroenteric Clinical Research Group, Southern Arizona Veterans Affairs Health Care System; Professor of Medicine, Division of Gastroenterology, University of Arizona School of Medicine

Ronnie Fass, MD, FACP, FACG is a member of the following medical societies: American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, American Neurogastroenterology and Motility Society, American Society for Gastrointestinal Endoscopy, Israeli Medical Association

Disclosure: Received grant/research funds from Takeda Pharmaceuticals for conducting research; Received consulting fee from Takeda Pharmaceuticals for consulting; Received honoraria from Takeda Pharmaceuticals for speaking and teaching; Received consulting fee from Vecta for consulting; Received consulting fee from XenoPort for consulting; Received honoraria from Eisai for speaking and teaching; Received grant/research funds from Wyeth Pharmaceuticals for conducting research; Received grant/research funds f.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, American Gastroenterological Association

Disclosure: Received grant/research funds from Novartis for other; Received grant/research funds from Bayer for other; Received grant/research funds from Otsuka for none; Received grant/research funds from Bristol Myers Squibb for other; Received none from Scynexis for none; Received grant/research funds from Salix for other; Received grant/research funds from MannKind for other.

Abhishek Choudhary, MD Resident Physician, Department of Internal Medicine, University Hospital of Missouri-Columbia

Abhishek Choudhary, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Vesa TH, Marteau P, Korpela R. Lactose intolerance. J Am Coll Nutr. 2000 Apr. 19(2 Suppl):165S-175S. [QxMD MEDLINE Link].
Newcomer AD, McGill DB, Thomas PJ, et al. Tolerance to lactose among lactase-deficient American Indians. Gastroenterology. 1978 Jan. 74(1):44-6. [QxMD MEDLINE Link].
Di Stefano M, Miceli E, Mazzocchi S, et al. Visceral hypersensitivity and intolerance symptoms in lactose malabsorption. Neurogastroenterol Motil. 2007 Nov. 19(11):887-95. [QxMD MEDLINE Link].
Micic D, Rao VL, Rubin DT. Clinical approach to lactose intolerance. JAMA. 2019 Sep 26. [QxMD MEDLINE Link].
Malik TF, Panuganti KK. Lactose intolerance. Stat Pearls. 2019 Jan. [QxMD MEDLINE Link]. [Full Text].
Zhong Y, Priebe MG, Vonk RJ, et al. The role of colonic microbiota in lactose intolerance. Dig Dis Sci. 2004 Jan. 49(1):78-83. [QxMD MEDLINE Link].
Ponte PR, de Medeiros PH, Havt A, et al. Clinical evaluation, biochemistry and genetic polymorphism analysis for the diagnosis of lactose intolerance in a population from northeastern Brazil. Clinics (Sao Paulo). 2016 Feb. 71(2):82-9. [QxMD MEDLINE Link]. [Full Text].
Delacour H, Leduc A, Loucano-Perdriat A, Plantamura J, Ceppa F. Diagnosis of genetic predisposition for lactose intolerance by high resolution melting analysis. Ann Biol Clin (Paris). 2017 Feb 1. 75(1):67-74. [QxMD MEDLINE Link].
Auricchio S, Rubino A, Landolt M, Semenza G, Prader A. Isolated intestinal lactase deficiency in the adult. Lancet. 1963 Aug 17. 2(7303):324-6. [QxMD MEDLINE Link].
Upton J, Mackay R, George P. A simple gene test for lactose intolerance/adult hypolactasia. N Z Med J. 2007 Nov 9. 120(1265):U2817. [QxMD MEDLINE Link].
Corgneau M, Scher J, Ritie-Pertusa L, et al. Recent advances on lactose intolerance: tolerance thresholds and currently available answers. Crit Rev Food Sci Nutr. 2017 Oct 13. 57(15):3344-56. [QxMD MEDLINE Link].
Xiong L, Wang Y, Gong X, Chen M. Prevalence of lactose intolerance in patients with diarrhea-predominant irritable bowel syndrome: data from a tertiary center in southern China. J Health Popul Nutr. 2017 Nov 21. 36(1):38. [QxMD MEDLINE Link]. [Full Text].
Harvey L, Ludwig T, Hou AQ, et al. Prevalence, cause and diagnosis of lactose intolerance in children aged 1-5 years: a systematic review of 1995-2015 literature. Asia Pac J Clin Nutr. 2018. 27(1):29-46. [QxMD MEDLINE Link]. [Full Text].
Kern F Jr, Struthers JE Jr. Intestinal lactase deficiency and lactose intolerance in adults. JAMA. 1966 Mar 14. 195(11):927-30. [QxMD MEDLINE Link].
Kudlacek S, Freudenthaler O, Weissboeck H, et al. Lactose intolerance: a risk factor for reduced bone mineral density and vertebral fractures?. J Gastroenterol. 2002. 37(12):1014-9. [QxMD MEDLINE Link].
Di Stefano M, Veneto G, Malservisi S, et al. Lactose malabsorption and intolerance and peak bone mass. Gastroenterology. 2002 Jun. 122(7):1793-9. [QxMD MEDLINE Link].
Alharbi O, El-Sohemy A. Lactose intolerance (LCT-13910C>T) genotype is associated with plasma 25-hydroxyvitamin D concentrations in caucasians: a Mendelian randomization study. J Nutr. 2017 Jun. 147(6):1063-9. [QxMD MEDLINE Link].
Bayless TM, Rothfeld B, Massa C, et al. Lactose and milk intolerance: clinical implications. N Engl J Med. 1975 May 29. 292(22):1156-9. [QxMD MEDLINE Link].
Deng Y, Misselwitz B, Dai N, Fox M. Lactose intolerance in adults: biological mechanism and dietary management. Nutrients. 2015 Sep 18. 7(9):8020-35. [QxMD MEDLINE Link]. [Full Text].
Mishkin S. Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory bowel disease. Am J Clin Nutr. 1997 Feb. 65(2):564-7. [QxMD MEDLINE Link].
Portincasa P, Bonfrate L, de Bari O, Lembo A, Ballou S. Irritable bowel syndrome and diet. Gastroenterol Rep (Oxf). 2017 Feb. 5(1):11-9. [QxMD MEDLINE Link]. [Full Text].
Beyerlein L, Pohl D, Delco F, et al. Correlation between symptoms developed after the oral ingestion of 50 g lactose and results of hydrogen breath testing for lactose intolerance. Aliment Pharmacol Ther. 2008 Apr. 27(8):659-65. [QxMD MEDLINE Link].
Hermans MM, Brummer RJ, Ruijgers AM, et al. The relationship between lactose tolerance test results and symptoms of lactose intolerance. Am J Gastroenterol. 1997 Jun. 92(6):981-4. [QxMD MEDLINE Link].
Arola H. Diagnosis of hypolactasia and lactose malabsorption. Scand J Gastroenterol Suppl. 1994. 202:26-35. [QxMD MEDLINE Link].
Carroccio A, Montalto G, Cavera G, et al. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998 Dec. 17(6):631-6. [QxMD MEDLINE Link].
Suarez FL, Savaiano DA, Levitt MD. A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. N Engl J Med. 1995 Jul 6. 333(1):1-4. [QxMD MEDLINE Link].
Patel YT, Minocha A. Lactose intolerance: diagnosis and management. Compr Ther. 2000 Winter. 26(4):246-50. [QxMD MEDLINE Link].
Suarez FL, Savaiano DA, Levitt MD. Review article: the treatment of lactose intolerance. Aliment Pharmacol Ther. 1995 Dec. 9(6):589-97. [QxMD MEDLINE Link].
Sethi S, Tyagi SK, Anurag RK. Plant-based milk alternatives an emerging segment of functional beverages: a review. J Food Sci Technol. 2016 Sep. 53(9):3408-23. [QxMD MEDLINE Link]. [Full Text].
Paul AA, Kumar S, Kumar V, Sharma R. Milk analog: plant based alternatives to conventional milk, production, potential and health concerns. Crit Rev Food Sci Nutr. 2019 Oct 16. 1-19. [QxMD MEDLINE Link].
Pakdaman MN, Udani JK, Molina JP, Shahani M. The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial. Nutr J. 2016 May 20. 15(1):56. [QxMD MEDLINE Link]. [Full Text].
Shi LH, Balakrishnan K, Thiagarajah K, Mohd Ismail NI, Yin OS. Beneficial properties of probiotics. Trop Life Sci Res. 2016 Aug. 27(2):73-90. [QxMD MEDLINE Link]. [Full Text].
Vonk RJ, Priebe MG, Koetse HA, et al. Lactose intolerance: analysis of underlying factors. Eur J Clin Invest. 2003 Jan. 33(1):70-5. [QxMD MEDLINE Link].
Suarez FL, Savaiano D, Arbisi P, et al. Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance. Am J Clin Nutr. 1997 May. 65(5):1502-6. [QxMD MEDLINE Link].
Jarvinen RM, Loukaskorpi M, Uusitupa MI. Tolerance of symptomatic lactose malabsorbers to lactose in milk chocolate. Eur J Clin Nutr. 2003 May. 57(5):701-5. [QxMD MEDLINE Link].
Beja-Pereira A, Luikart G, England PR, et al. Gene-culture coevolution between cattle milk protein genes and human lactase genes. Nat Genet. 2003 Dec. 35(4):311-3. [QxMD MEDLINE Link].
Born P, Sekatcheva M, Rosch T, et al. Carbohydrate malabsorption in clinical routine: a prospective observational study. Hepatogastroenterology. 2006 Sep-Oct. 53(71):673-7. [QxMD MEDLINE Link].
Hammer HF, Hammer J. Diarrhea caused by carbohydrate malabsorption. Gastroenterol Clin North Am. 2012 Sep. 41(3):611-27. [QxMD MEDLINE Link].
Lomer MC, Parkes GC, Sanderson JD. Review article: lactose intolerance in clinical practice--myths and realities. Aliment Pharmacol Ther. 2008 Jan 15. 27(2):93-103. [QxMD MEDLINE Link].
Mattar R, de Campos Mazo DF, Carrilho FJ. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol. 2012. 5:113-21. [QxMD MEDLINE Link]. [Full Text].
Bayless TM, Brown E, Paige DM. Lactase non-persistence and lactose intolerance. Curr Gastroenterol Rep. 2017 May. 19(5):23. [QxMD MEDLINE Link].
Szilagyi A, Galiatsatos P, Xue X. Systematic review and meta-analysis of lactose digestion, its impact on intolerance and nutritional effects of dairy food restriction in inflammatory bowel diseases. Nutr J. 2016 Jul 13. 15(1):67. [QxMD MEDLINE Link]. [Full Text].
Szilagyi A. Adult lactose digestion status and effects on disease. Can J Gastroenterol Hepatol. 2015 Apr. 29(3):149-56. [QxMD MEDLINE Link]. [Full Text].