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Lactose Intolerance
Introduction
Lactose intolerance is a clinical syndrome that manifests with characteristic signs and symptoms upon consuming food substances containing lactose, a disaccharide. Normally upon lactose consumption, it is hydrolyzed into glucose and galactose by the lactase enzyme, which is found in the small intestinal brush border.[1] Deficiency of lactase due to primary or secondary causes results in clinical symptoms. Disease severity varies among individuals. Lactose is present in dairy, milk products, and mammalian milk.[2] It is also sometimes referred to as lactose malabsorption.
Lactase deficiency is the commonest type of disaccharidase deficiency. Enzyme levels are at the peak shortly after birth and decline after that, despite continued lactose intake. Among the animal world, nonhuman mammals generally lose their ability to digest lactose into its components as they reach adulthood. Certain populations of the human species, such as those of South American, Asian, and African descent, tend to develop lactase deficiency. On the contrary, people of northern Europe origin or northwestern India usually retain the ability to digest lactose into adulthood.[3]
Lactose intolerance presents with abdominal bloating and pain, loose stools, nausea, flatulence, and borborygmi.[4][5] Many people start avoiding milk as soon as a diagnosis is made, or even the suggestion of lactose intolerance is put forward. This leads to consuming specially prepared products with digestive aids, adding to the health care burden.
Etiology
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Etiology
Lactase enzyme deficiency can occur in individuals with lower levels of this enzyme, resulting in failure to hydrolyze lactose into absorbable glucose and galactose components. There are four leading causes of lactase deficiency.
Primary Lactase Deficiency
It is the most common cause of lactase deficiency, also known as lactase non-persistence. There is a gradual decline in lactase enzyme activity with increasing age. Enzyme activity begins to decline in infancy, and symptoms manifest in adolescence or early adulthood. More recently, it has been observed that lactase non-persistence is of the ancestral form (normal Mendelian inheritance), and lactase persistence is secondary to mutation.[6][7][8]
Secondary Lactase Deficiency
Due to several infectious, inflammatory, or other diseases, injury to intestinal mucosa can cause secondary lactase deficiency.[9] Common causes include:
- Gastroenteritis
- Celiac disease
- Crohn disease
- Ulcerative colitis
- Chemotherapy
- Antibiotics
Congenital Lactase Deficiency
There is a decrease or absence of lactase enzyme activity since birth due to autosomal recessive inheritance.[10][11] It manifests in the newborn after ingestion of milk. It is a rare cause of the deficiency, and its genetics are not very well known.[12]
Developmental Lactase Deficiency
It is seen in premature infants born at 28 to 37 weeks of gestation.[13] The infant's intestine is underdeveloped, resulting in an inability to hydrolyze lactose. This condition improves with increasing age due to the maturation of the intestine, which results in adequate lactase activity.
Epidemiology
Lactose intolerance is a common disease; however, it is rare in children younger than 5. It is most often seen in adolescents and young adults. On average, 65% of the world's population is lactose intolerant.[14] The prevalence of lactose intolerance is variable among different ethnicities. It is most common in African Americans, Hispanics/Latinos, and Asians and least prevalent in people of European descent.[15] Ethnic groups with a higher prevalence of lactose intolerance also are more likely to have lactose non-persistence.[16][17]
The primary form is the commonest (found in up to 70% of the world's population, but not all of them are symptomatic).[18][19][20] On the contrary, the congenital type is extremely rare (with around 40 cases reported worldwide to date).[6]
In the US, the primary disease is much more common in certain ethnicities, such as African-Americans, American Indians, Hispanics or Latinos, and Asian-Americans, than in White Americans.[21][22][23][24][21] North Americans, Australians, and White Northern Europeans have the lowest rates, ranging between 2% and 15%.[21][22] On the contrary, the prevalence of lactose intolerance is 50% to 80% in South Americans, around 100% in American Indians and some East Asians, and around 60% to 80% in Ashkenazi Jews and Africans.[21][23][24]
The age-related decline in lactase activity is generally complete during childhood; however, the decline has also been seen to occur later, in adolescence, particularly in Whites.[25] The eventual level and the duration of loss of lactase expression vary considerably per ethnicity. Chinese and Japanese people lose between 80% and 90% of activity within three to four years after weaning. Jews and Asians lose 60% to 70% over many years after weaning, and for White Northern Europeans and North Americans, it could take between 18 and 20 years for lactase expression to reach its lowest levels.[18] A low prevalence of lactase non-persistence is noted in patients of mixed ethnicity, whereas an increased prevalence is observed in the native ethnic group.
The onset of the disease is generally subtle and progressive in primary illness, and many patients first experience symptoms of intolerance in late adolescence and adulthood.[2][3] As opposed to White Northern Europeans, Australians, and North Americans, earlier presentation is noted in Native Americans, Asian-Americans, African-Americans, and Hispanics/Latinos.[21] The secondary disease is commoner in children, particularly in developing countries where infections are a common cause.[9]
The sexes are affected equally.
Pathophysiology
The lactase enzyme is located in the brush border of the small intestinal mucosa. Deficiency of lactase results in the presence of unabsorbed lactose within the bowel. This results in an influx of fluid into the bowel lumen resulting in osmotic diarrhea. Colonic bacteria ferment the unabsorbed lactose-producing gas (hydrogen, carbon dioxide, and methane), which hydrolyzes lactose into monosaccharides.[26] This results in an additional influx of fluid within the lumen. The overall effect of these mechanisms results in various abdominal signs and symptoms.
An association has been reported between certain single nucleotide polymorphisms with lactose tolerance in a northeastern Brazilian population. In Indo-Europe, lactose intolerance is linked with rs4982235 SNP (or -13910C>T).[27]
Histopathology
In lactose intolerance, microscopic findings of the small intestine vary depending on the cause of lactase deficiency. In primary lactase deficiency, the mucosa appears normal. Lactase activity can be measured to assess the severity of the disease. The mucosa may be abnormal in secondary lactase deficiency, depending upon the underlying cause. It helps determine the secondary causes of the disease, such as celiac disease. Biopsy results may be normal if the mucosal abnormality is focal or patchy.[28]
History and Physical
Signs and symptoms of lactose intolerance manifest 30 minutes to 1 to 2 hours after ingesting milk (dairy) products. The severity of symptoms depends upon the amount of lactose consumed, the residual lactase function, and the small bowel transit time.[29] Common signs and symptoms may include the following:
Less commonly, it can present with headache, muscle pain, joint pain, mouth ulcers, urinary symptoms, and loss of concentration.[32][33]
Evaluation
Lactose intolerance is evaluated by getting a careful history, performing a physical exam, and medical tests.
History
It is essential to take a past medical, family, and dietary history to determine the cause of lactose intolerance and exclude secondary causes.
Physical Exam
Assess for the presence of abdominal bloating, tenderness, and pain.
Medical Tests
- Hydrogen breath test: This test measures the hydrogen content of breath after lactose ingestion. The test is positive for lactose malabsorption if the post-lactose breath hydrogen value rises >20 ppm compared with the baseline.[34]
- Stool acidity test: Unabsorbed lactose is fermented by colonic bacteria into lactic acid, which lowers the stool pH.
- Dietary elimination: One way to assess the underlying illness is to eliminate lactose-containing food products, which would result in the resolution of symptoms. Resumption of symptoms with the reintroduction of these products will indicate lactose intolerance.[35]
- Milk tolerance test: Administer 500 mL of milk and obtain the blood glucose level. A rise in blood sugar of less than 9 mg/dL shows lactose malabsorption.[36]
- Lactose tolerance test: This test determines lactose absorption after ingestion of a lactose-containing liquid. Measure serial blood glucose levels after giving an oral lactose load. After obtaining a fasting serum glucose level, 50 g of lactose is administered.[34] Serum glucose level is then measured at 0, 60, and 120 minutes. Failure of blood glucose levels to rise by 20 g may indicate lactose intolerance. This test has a specificity of 96% and a sensitivity of 75%. False-negative results may occur in patients with diabetes or small bowel bacterial overgrowth. The results are also affected by abnormal gastrointestinal emptying.[37]
- Small bowel biopsy: This test is rarely performed as it is invasive. It is only indicated to rule out secondary causes of lactose intolerance.
- Genotyping: It is an emerging test with higher sensitivity and specificity. It has been used in Germany and the Nordic states, but it is yet not widely available or practiced elsewhere.[38]
Treatment / Management
Management of lactose intolerance consists of dietary modification, lactase supplementation, and treating an underlying condition in people with secondary lactase deficiency.
Dietary Modification
Lactase-containing milk products and calcium supplements are recommended. Limiting the dietary intake of lactose by avoiding the intake of lactose-containing products improves the symptoms of the disease. The following products contain lactose and, therefore, must be avoided:
- Soft and processed cheese
- Buttermilk
- Cream
- Milk
- Ice cream
- Sour cream
- Whey
- Pancakes and waffles
- Mashed potatoes
- Butter
- Margarine
- Custard and pudding
Yogurt contains varying amounts of lactose and may cause symptoms in some patients. Greek yogurt has the least. Yogurt culture microorganisms can produce β-galactosidase as part of their lactose utilization pathway. This may promote lactose digestion in vivo.[39] Plant-based milk alternatives are becoming more available; however, technological issues, palatability, and nutritional balance remain concerns.[40][41] Probiotics have been observed to improve symptoms, such as the DDS-1 strain of Lactobacillus acidophilus.[42][43] Calcium and vitamin D supplements should also be recommended. In patients with secondary lactase deficiency, treatment should be directed at the underlying cause.[44](A1)
Lactase Supplements
Lactase enzyme supplements contain lactase which breaks down lactose in milk and milk-containing products. They are available as lactase enzyme tablets or drops.
Differential Diagnosis
Other conditions to be considered in the list of differential diagnoses of lactose intolerance include:
- Irritable bowel syndrome
- Celiac disease
- Tropical sprue
- Cystic fibrosis
- Inflammatory bowel disease
- Diverticular disease
- Intestinal Neoplasm or polyp
- Excessive ingestion of laxatives
- Viral gastroenteritis
- Bacterial infection
- Giardiasis
- Gastrinoma
Pertinent Studies and Ongoing Trials
Emerging treatments include the following:
Fungal Beta-galactosidases
Two fungal beta-galactosidases from Aspergillus carbonarius ATCC6276 are beta-gal 1 and beta-gal 2. They can be given alone or in combination and may be used as an enzyme supplement for lactose intolerance.[45] Unlike current commercialized supplemental lactases, these purified enzymes demonstrate significant stability on exposure to simulated gastric conditions.
Nutrigenomics
Nutrigenomics may be used in the future management of hypolactasia through prompt identification of specific mutations or haplotype patterns that modulate dietary responses in affected individuals.[46]
Prognosis
Lactose intolerance has an excellent prognosis. Most patients have a considerable improvement in signs and symptoms with dietary modification alone. Lactose intolerant may lead to osteopenia.[47][48][49] Vitamin D deficiency is linked to the LCT-13910C>T gene variant of lactose intolerance among Whites.[49]
Complications
Following are some common complications:
- Osteopenia
- Osteoporosis[15]
- Malnutrition
- Weight loss
- Rickets
- Growth failure
Consultations
Once a diagnosis of lactose intolerance is made, consultation should be made with a gastroenterologist and dietician.
Deterrence and Patient Education
Lactose-intolerant patients and their families should be advised that ingestion of lactose-containing products generally only leads to reversible symptoms without causing permanent damage to the gastrointestinal tract (unlike celiac disease). Also, there are no long-term complications if an adequate intake of proteins, calories, calcium, and vitamin D is ensured.[21]
Primary and congenital lactase deficiency can not be prevented. However, secondary lactase deficiency could be prevented if underlying secondary causes are diagnosed early and promptly instituted appropriate treatment to preserve intestinal mucosal integrity. In addition, avoiding lactose-containing foods helps limit long-term disease severity.
Pearls and Other Issues
To avoid their use, people with lactose intolerance can check the ingredients on food labels for lactose on food products.
Some people with lactose intolerance can tolerate some milk and milk-containing products and may not need to avoid them completely.
Lactose intolerance is commonly confused with milk allergy. Lactose intolerance is a gastrointestinal disorder, while milk allergy is an autoimmune reaction against specific milk proteins. Milk allergy is life-threatening and presents early in infancy, while Lactose intolerance usually presents in adolescence or early adulthood.
Milk is rich in calcium and vitamin D. Prolong avoidance of milk in people with lactose intolerance can result in calcium and vitamin D deficiency.
Enhancing Healthcare Team Outcomes
The diagnosis and management of lactose intolerance are with an interprofessional team that includes a nurse practitioner, primary care provider, pediatrician, gastroenterologist, and an allergist. Lactose intolerance is commonly confused with milk allergy. Lactose intolerance is a gastrointestinal disorder, while milk allergy is an autoimmune reaction against certain milk proteins. Milk allergy is life-threatening and presents early in infancy, while Lactose intolerance usually presents in adolescence or early adulthood. It is important to educate the patient that they should always check the ingredients on food labels for lactose on food products to avoid their use when they have lactose intolerance. However, some people with lactose intolerance can tolerate some milk and milk-containing products and may not need to avoid them completely. Prolonged avoidance of milk in people with lactose intolerance can result in calcium and vitamin D deficiency.[50] [level 5]
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