Understanding Lactose Intolerance

Lactose intolerance (LI), a term closely associated with hypolactasia (lactase deficiency) and lactose malabsorption,¹ is a common syndrome composed of diarrhea, abdominal pain, flatulence and/or bloating, and sometimes nausea and vomiting in severe cases, after ingestion of dairy products.² This common disorder results from a deficiency in the enzyme lactase, which makes affected patients unable to digest lactose, a sugar found in milk and other dairy products.³ Malabsorption of lactose produces the symptoms associated with LI.

The level of LI varies among affected individuals, depending on many nutritional and genetic factors, the amount of lactose consumed, the patient’s degree of lactase deficiency, and the substance in which the lactose is ingested.⁴

Epidemiology
LI prevalence is difficult to ascertain because the symptoms are vague and can be attributed to a number of conditions; additionally, there is no gold standard for diagnosis of LI. It is estimated that about 70% of the world population is affected by LI—with great variation among ethnicities and races.^5,6 Some degree of LI is reported in up to 80% of African-Americans and Latinos, and almost 100% of Native Americans and Asian Americans. LI is least common in people of northern European descent (and is unlikely to develop before adulthood⁷), although it has been suggested that 30 million American adults experienced lactose malabsorption to some degree by age 20.^3,8 Heyman⁴ estimates that approximately 2% of people of northern European descent have LI.

Regardless of ethnicity or race, older patients are more susceptible to LI than are younger adults, largely as a result of the normal processes of aging.²

Pathophysiology and Patient Presentation
Cells of the inner lumen of the small intestines, enterocytes, are covered with a membrane that has a brush border composed of microvilli.⁹ The microvilli produce lactase, the enzyme necessary to split and hydrolyze dietary lactose into glucose and galactose for transport across the cell membrane^.6 Unfortunately, lactase is produced in the upper, most shallow section of the villi, which is exceedingly prone to damage by secondary insult.

If the lactase enzymes are absent or deficient, unabsorbed sugars osmotically attract fluid into the bowel lumen. The amount of fluid influx into the bowel is approximately triple the normal amount, based on the osmolality of sugar alone. In addition, the unabsorbed lactose entering the colon is fermented by bacteria, producing gas and resulting in the cleavage of lactose into monosaccharides. Monosaccharides cannot be absorbed by the colonic mucosa; as a result, osmotic pressure increases, and fluid levels rise in the bowel. This process explains the most common symptoms of flatulence, diarrhea, abdominal pain, and bloating.⁶

Most mammalian babies, including human infants, produce enough lactase to digest milk, including breast milk. This ability persists until the child is weaned. In humans, lactase activity drops at age 2 to 3 years and may cease altogether by age 5 to 10.⁹ Worldwide, most humans lose 90% to 95% of birth lactase levels by early childhood, followed by a continuing decline during the course of a lifetime.6 This may help explain why many elderly people are affected by LI.

Typically, development of LI progresses subtly over many years, but onset can also be relatively acute.⁴

Lactose Malabsorption
The three main types of lactose malabsorption are primary, secondary, and congenital. The latter is a rare, genetic form of LI in which the lactase enzyme is entirely absent; for the purposes of this article, congenital lactose malabsorption will not be discussed.

Primary lactase deficiency is the most common form and the focus of this article. It is the normal, gradual reduction in lactase enzyme that a maturing individual experiences through adulthood, and the rate of reduction is genetically determined. Secondary lactose malabsorption occurs following an insult to the small bowel, as in severe diarrhea, infection (eg, rotavirus), chemotherapy, or acute gastroenteritis.⁴ In these situations, lactase is the first enzyme to be negatively affected and the last to return as the insult resolves.¹⁰ Secondary hypolactasia is transient and reversible.^11,12

LI is not to be confused with cow’s milk allergy—an immune response to the protein in cow’s milk, which can be a life-threatening event. A true milk allergy most commonly appears within the first year of life, whereas LI occurs more often in adulthood.^5,8

LI is not considered life threatening, but its symptoms can severely affect a person’s quality of life and productivity. In addition to ethnicity and age, the type and amount of lactose ingested and the amount that the patient is unable to digest all affect the severity of LI symptoms.¹³

Lactose makes up between 2% and 8% of the solids in milk; 1 mL of milk (0.03 fl oz) contains 47.2 mg of lactose. No amount of lactose has been specified to produce symptoms, but most adults can tolerate as much as 8 fl oz of milk without problems,¹ and patients can tolerate more lactose if the food containing it is consumed with a meal.¹¹ Some adults may be able to ingest only 2 to 4 fl oz before symptoms appear⁴; in highly sensitive adults, as little as 200 mg of lactose (0.13 fl oz of milk) can produce symptoms.⁵

Also playing a role are the patient’s gastric emptying time and intestinal transit time.¹² Symptoms of LI can be produced between 30 minutes and two hours after ingestion of milk or a milk product.⁹

Diagnosis
Most patients do not require specialized, sophisticated testing for a diagnosis of LI. A thorough medical history and physical examination are needed to rule out other conditions in the differential diagnosis (see Table 1^6,14). For the primary care provider, a basic workup should include a complete blood count, a comprehensive metabolic panel, erythrocyte sedimentation rate, a thyroid-stimulating hormone level, a stool culture, and if symptoms are severe, abdominal/pelvic radiography and CT.

In the absence of accepted guidelines, a common therapeutic approach is to exclude milk and dairy products from the patient’s diet.¹¹ Generally, a two-week trial of a strict lactose-free diet leading to resolution of symptoms, followed by reintroduction of dairy foods and recurrence of symptoms, can be considered diagnostic.⁴

It is important to instruct the patient that while he or she follows this diagnostic diet, all sources of lactose must be eliminated; food labels must be read carefully to identify “hidden” lactose sources (see Table 2⁸). Additionally, many patients (and even clinicians) may not realize that many commonly used prescription and OTC medications contain lactose, including certain agents indicated for gastrointestinal problems⁵ (see Table 3⁵).

During the diagnostic diet, patients may find it helpful to keep a diary of food choices and note any symptoms that may occur. This helps empower them to be an active participant in food choices, using self-experimentation to identify which foods they can and cannot tolerate.

Gastroenterology Consult
Referral to a gastroenterologist is needed if the diagnosis is unclear or if other illnesses are suspected. Tests the specialist may perform include the hydrogen breath test, a small-­intestine biopsy, the lactose tolerance test, and/or the stool acidity test for infants and children,⁴ although these tests vary in sensitivity and specificity.¹³

The hydrogen breath test, by which enzymatic activity is confirmed after the patient consumes 25 to 50 g of lactose,⁶ is the most widely used formal test for confirming a diagnosis of LI because it is relatively inexpensive and is the most sensitive and the most specific for LI, according to Hovde and Farup¹³ and Eadala et al.⁵ The test has been shown to yield positive results in 90% of patients with lactose malabsorption.^6,15 False-negative results may signify absence of bacterial flora, as in the case of recent antibiotic use or a recent high-colonic enema. Previous aspirin use, sleep, exercise, and smoking may increase breath hydrogen secretion unrelated to lactose consumption.⁶

Management of Lactose Intolerance
Although the body’s ability (or inability) to produce lactase cannot be changed, the symptoms of LI can be managed with dietary restrictions. The extent of change needed depends on how much lactose the patient is able to consume before experiencing symptoms.⁸

In patients with secondary LI, a complete lactose-free diet is recommended until the causative pathologic condition has resolved. Patients with primary LI can opt to exclude all milk and dairy products, at least initially, until symptoms have resolved; they can then reintroduce certain milk and dairy products gradually and in small amounts, according to their ­individual tolerance threshold. Certain lactose-containing foods may be easier to digest than others (see Table 4²).

Ingesting lactose-containing foods with a meal helps decrease gastric transit time and can lessen the symptoms of LI.¹¹ Additionally, people who cannot drink milk may find they can eat yogurt because it contains lactase-producing bacteria,⁹ although clinical trials examining consumption of yogurt or probiotics in patients with LI had inconclusive results.¹

Lactose-free milk or soy milk is available at most major grocery stores. These products tend to be more expensive and taste somewhat sweeter than regular milk but can be used as a reasonable substitute.⁹

Some patients may benefit from taking lactase enzyme supplements,^1,16 which are taken with any ingestion of lactose. The enzymes may not completely prevent symptoms because the lactose is not completely digested or because it is difficult to determine an effective dose of the enzyme. Therefore, enzyme supplementation should be an adjunct to, not a substitute for, dietary restrictions.⁶ This may help patients when they eat at restaurants, where they do not know how food is prepared and which are unlikely to offer lactose-free food selections.

Instead of taking lactase enzyme supplements in tablet form, patients may prefer to mix lactase liquid with regular milk, producing lactose-free milk. A waiting period of 24 hours is needed before the mixture can be considered lactose-free. A trial-and-error period should be expected when enzyme supplementation or any dietary approach is tried.¹¹

The theory of adaptative phenomena suggests that most people with LI can teach themselves to ingest more lactose gradually, leading over time to beneficial changes in the microflora of the gut and in improved colonic function.^11,17 The ultimate result, whether the explanation is reduced hydrogen excretion or increased gas absorption, is less severe gastrointestinal symptoms. This strategy is not a cure for LI, nor has it been found effective for all patients with LI,¹ but it can help manage symptoms to some extent.

Information for the Patient
Patients often need instruction in reading food labels to identify foods that contain milk, milk products, lactose, whey, curds, milk byproducts, dry milk solids, or even nonfat dry milk powder.⁸ Follow-up with the primary care provider should be arranged on an as-needed basis.

Simply excluding all dairy products from the diet does raise some health concerns. Milk and other dairy products are important sources of calcium and vitamin D, which are needed for growth and bone health in patients of all ages. A decrease in calcium consumption is one of the primary risk factors for osteoporosis, although research examining a possible association between LI and osteoporosis has yielded conflicting results. According to Kudlacek et al,¹⁸ even individuals with severe LI do not appear to be at risk for accelerated bone loss. By contrast, other research groups^7,19 studied patients with LI from various age-groups and concluded that low calcium intake and impaired vitamin D status could lead to increased bone turnover and decreased bone mass, especially in men and postmenopausal women. No guidelines have been published regarding screening for osteoporosis in patients with LI.

According to a consensus statement from the NIH,³ both men and women younger than 50 should consume 1,000 mg/d of calcium, and older persons, 1,500 mg/d. In addition to calcium supplements, patients can obtain the necessary calcium through certain foods, including leafy green vegetables (spinach, kale, broccoli), sardines, calcium-fortified cereal bars, calcium-enriched soy or lactose-free milk and other soy products, fruit juices, dried beans, and tuna.

Calcium is absorbed only when enough vitamin D is present; vitamin D intake should be 400 to 600 IU/d for both women and men.³ Foods that contain vitamin D include eggs, liver, vitamin D–enriched soy or lactose-free milk, and vitamin D–fortified cereals and other processed foods. Regular exposure to sunlight helps the body synthesize vitamin D naturally.³

For optimal bone health, the NIH³ continues to recommend a combination of cardiovascular exercise, weight-bearing exercise, smoking cessation, and a well-balanced diet (including foods that are rich in calcium and vitamin D).

In addition to its role in bone health, calcium has been suggested to improve cardiac and vascular smooth muscle contractility,²⁰ and clinical research is under way to investigate the role of calcium in reducing the risk for adenomatous colon polyps.²¹

Conclusion
Primary LI is a common disorder resulting from a deficiency in the enzyme lactase, making affected patients unable to digest lactose. LI is widespread in varying degrees across all races and ethnicities, affecting people of all ages; however, it is more common among older adults due to natural pathophysiologic processes.

In LI-affected patients, consuming lactose leads to troublesome symptoms of diarrhea, abdominal pain, flatulence, and/or bloating, and sometimes nausea and vomiting.

No tool is considered a “gold standard” for making a diagnosis of LI, so it is important to rule out other gastrointestinal conditions first. Oftentimes a diagnosis of LI is confirmed by the effectiveness of a lactose-free trial diet. When diagnosis is uncertain, referral to a gastroenterologist is required.

Without formal treatment guidelines, the primary form of therapy for LI is to adjust the amount of ingested lactose, with careful attention to adequate calcium and vitamin D intake. Patient education is crucial for management of LI and improvement in the patient’s quality of life.

Lactose intolerance (LI), a term closely associated with hypolactasia (lactase deficiency) and lactose malabsorption,¹ is a common syndrome composed of diarrhea, abdominal pain, flatulence and/or bloating, and sometimes nausea and vomiting in severe cases, after ingestion of dairy products.² This common disorder results from a deficiency in the enzyme lactase, which makes affected patients unable to digest lactose, a sugar found in milk and other dairy products.³ Malabsorption of lactose produces the symptoms associated with LI.

The level of LI varies among affected individuals, depending on many nutritional and genetic factors, the amount of lactose consumed, the patient’s degree of lactase deficiency, and the substance in which the lactose is ingested.⁴

Epidemiology
LI prevalence is difficult to ascertain because the symptoms are vague and can be attributed to a number of conditions; additionally, there is no gold standard for diagnosis of LI. It is estimated that about 70% of the world population is affected by LI—with great variation among ethnicities and races.^5,6 Some degree of LI is reported in up to 80% of African-Americans and Latinos, and almost 100% of Native Americans and Asian Americans. LI is least common in people of northern European descent (and is unlikely to develop before adulthood⁷), although it has been suggested that 30 million American adults experienced lactose malabsorption to some degree by age 20.^3,8 Heyman⁴ estimates that approximately 2% of people of northern European descent have LI.

Regardless of ethnicity or race, older patients are more susceptible to LI than are younger adults, largely as a result of the normal processes of aging.²

Pathophysiology and Patient Presentation
Cells of the inner lumen of the small intestines, enterocytes, are covered with a membrane that has a brush border composed of microvilli.⁹ The microvilli produce lactase, the enzyme necessary to split and hydrolyze dietary lactose into glucose and galactose for transport across the cell membrane^.6 Unfortunately, lactase is produced in the upper, most shallow section of the villi, which is exceedingly prone to damage by secondary insult.

If the lactase enzymes are absent or deficient, unabsorbed sugars osmotically attract fluid into the bowel lumen. The amount of fluid influx into the bowel is approximately triple the normal amount, based on the osmolality of sugar alone. In addition, the unabsorbed lactose entering the colon is fermented by bacteria, producing gas and resulting in the cleavage of lactose into monosaccharides. Monosaccharides cannot be absorbed by the colonic mucosa; as a result, osmotic pressure increases, and fluid levels rise in the bowel. This process explains the most common symptoms of flatulence, diarrhea, abdominal pain, and bloating.⁶

Most mammalian babies, including human infants, produce enough lactase to digest milk, including breast milk. This ability persists until the child is weaned. In humans, lactase activity drops at age 2 to 3 years and may cease altogether by age 5 to 10.⁹ Worldwide, most humans lose 90% to 95% of birth lactase levels by early childhood, followed by a continuing decline during the course of a lifetime.6 This may help explain why many elderly people are affected by LI.

Typically, development of LI progresses subtly over many years, but onset can also be relatively acute.⁴

Lactose Malabsorption
The three main types of lactose malabsorption are primary, secondary, and congenital. The latter is a rare, genetic form of LI in which the lactase enzyme is entirely absent; for the purposes of this article, congenital lactose malabsorption will not be discussed.

Primary lactase deficiency is the most common form and the focus of this article. It is the normal, gradual reduction in lactase enzyme that a maturing individual experiences through adulthood, and the rate of reduction is genetically determined. Secondary lactose malabsorption occurs following an insult to the small bowel, as in severe diarrhea, infection (eg, rotavirus), chemotherapy, or acute gastroenteritis.⁴ In these situations, lactase is the first enzyme to be negatively affected and the last to return as the insult resolves.¹⁰ Secondary hypolactasia is transient and reversible.^11,12

LI is not to be confused with cow’s milk allergy—an immune response to the protein in cow’s milk, which can be a life-threatening event. A true milk allergy most commonly appears within the first year of life, whereas LI occurs more often in adulthood.^5,8

LI is not considered life threatening, but its symptoms can severely affect a person’s quality of life and productivity. In addition to ethnicity and age, the type and amount of lactose ingested and the amount that the patient is unable to digest all affect the severity of LI symptoms.¹³

Lactose makes up between 2% and 8% of the solids in milk; 1 mL of milk (0.03 fl oz) contains 47.2 mg of lactose. No amount of lactose has been specified to produce symptoms, but most adults can tolerate as much as 8 fl oz of milk without problems,¹ and patients can tolerate more lactose if the food containing it is consumed with a meal.¹¹ Some adults may be able to ingest only 2 to 4 fl oz before symptoms appear⁴; in highly sensitive adults, as little as 200 mg of lactose (0.13 fl oz of milk) can produce symptoms.⁵

Also playing a role are the patient’s gastric emptying time and intestinal transit time.¹² Symptoms of LI can be produced between 30 minutes and two hours after ingestion of milk or a milk product.⁹

Diagnosis
Most patients do not require specialized, sophisticated testing for a diagnosis of LI. A thorough medical history and physical examination are needed to rule out other conditions in the differential diagnosis (see Table 1^6,14). For the primary care provider, a basic workup should include a complete blood count, a comprehensive metabolic panel, erythrocyte sedimentation rate, a thyroid-stimulating hormone level, a stool culture, and if symptoms are severe, abdominal/pelvic radiography and CT.

In the absence of accepted guidelines, a common therapeutic approach is to exclude milk and dairy products from the patient’s diet.¹¹ Generally, a two-week trial of a strict lactose-free diet leading to resolution of symptoms, followed by reintroduction of dairy foods and recurrence of symptoms, can be considered diagnostic.⁴

It is important to instruct the patient that while he or she follows this diagnostic diet, all sources of lactose must be eliminated; food labels must be read carefully to identify “hidden” lactose sources (see Table 2⁸). Additionally, many patients (and even clinicians) may not realize that many commonly used prescription and OTC medications contain lactose, including certain agents indicated for gastrointestinal problems⁵ (see Table 3⁵).

During the diagnostic diet, patients may find it helpful to keep a diary of food choices and note any symptoms that may occur. This helps empower them to be an active participant in food choices, using self-experimentation to identify which foods they can and cannot tolerate.

Gastroenterology Consult
Referral to a gastroenterologist is needed if the diagnosis is unclear or if other illnesses are suspected. Tests the specialist may perform include the hydrogen breath test, a small-­intestine biopsy, the lactose tolerance test, and/or the stool acidity test for infants and children,⁴ although these tests vary in sensitivity and specificity.¹³

The hydrogen breath test, by which enzymatic activity is confirmed after the patient consumes 25 to 50 g of lactose,⁶ is the most widely used formal test for confirming a diagnosis of LI because it is relatively inexpensive and is the most sensitive and the most specific for LI, according to Hovde and Farup¹³ and Eadala et al.⁵ The test has been shown to yield positive results in 90% of patients with lactose malabsorption.^6,15 False-negative results may signify absence of bacterial flora, as in the case of recent antibiotic use or a recent high-colonic enema. Previous aspirin use, sleep, exercise, and smoking may increase breath hydrogen secretion unrelated to lactose consumption.⁶

Management of Lactose Intolerance
Although the body’s ability (or inability) to produce lactase cannot be changed, the symptoms of LI can be managed with dietary restrictions. The extent of change needed depends on how much lactose the patient is able to consume before experiencing symptoms.⁸

In patients with secondary LI, a complete lactose-free diet is recommended until the causative pathologic condition has resolved. Patients with primary LI can opt to exclude all milk and dairy products, at least initially, until symptoms have resolved; they can then reintroduce certain milk and dairy products gradually and in small amounts, according to their ­individual tolerance threshold. Certain lactose-containing foods may be easier to digest than others (see Table 4²).

Ingesting lactose-containing foods with a meal helps decrease gastric transit time and can lessen the symptoms of LI.¹¹ Additionally, people who cannot drink milk may find they can eat yogurt because it contains lactase-producing bacteria,⁹ although clinical trials examining consumption of yogurt or probiotics in patients with LI had inconclusive results.¹

Lactose-free milk or soy milk is available at most major grocery stores. These products tend to be more expensive and taste somewhat sweeter than regular milk but can be used as a reasonable substitute.⁹

Some patients may benefit from taking lactase enzyme supplements,^1,16 which are taken with any ingestion of lactose. The enzymes may not completely prevent symptoms because the lactose is not completely digested or because it is difficult to determine an effective dose of the enzyme. Therefore, enzyme supplementation should be an adjunct to, not a substitute for, dietary restrictions.⁶ This may help patients when they eat at restaurants, where they do not know how food is prepared and which are unlikely to offer lactose-free food selections.

Instead of taking lactase enzyme supplements in tablet form, patients may prefer to mix lactase liquid with regular milk, producing lactose-free milk. A waiting period of 24 hours is needed before the mixture can be considered lactose-free. A trial-and-error period should be expected when enzyme supplementation or any dietary approach is tried.¹¹

The theory of adaptative phenomena suggests that most people with LI can teach themselves to ingest more lactose gradually, leading over time to beneficial changes in the microflora of the gut and in improved colonic function.^11,17 The ultimate result, whether the explanation is reduced hydrogen excretion or increased gas absorption, is less severe gastrointestinal symptoms. This strategy is not a cure for LI, nor has it been found effective for all patients with LI,¹ but it can help manage symptoms to some extent.

Information for the Patient
Patients often need instruction in reading food labels to identify foods that contain milk, milk products, lactose, whey, curds, milk byproducts, dry milk solids, or even nonfat dry milk powder.⁸ Follow-up with the primary care provider should be arranged on an as-needed basis.

Simply excluding all dairy products from the diet does raise some health concerns. Milk and other dairy products are important sources of calcium and vitamin D, which are needed for growth and bone health in patients of all ages. A decrease in calcium consumption is one of the primary risk factors for osteoporosis, although research examining a possible association between LI and osteoporosis has yielded conflicting results. According to Kudlacek et al,¹⁸ even individuals with severe LI do not appear to be at risk for accelerated bone loss. By contrast, other research groups^7,19 studied patients with LI from various age-groups and concluded that low calcium intake and impaired vitamin D status could lead to increased bone turnover and decreased bone mass, especially in men and postmenopausal women. No guidelines have been published regarding screening for osteoporosis in patients with LI.

According to a consensus statement from the NIH,³ both men and women younger than 50 should consume 1,000 mg/d of calcium, and older persons, 1,500 mg/d. In addition to calcium supplements, patients can obtain the necessary calcium through certain foods, including leafy green vegetables (spinach, kale, broccoli), sardines, calcium-fortified cereal bars, calcium-enriched soy or lactose-free milk and other soy products, fruit juices, dried beans, and tuna.

Calcium is absorbed only when enough vitamin D is present; vitamin D intake should be 400 to 600 IU/d for both women and men.³ Foods that contain vitamin D include eggs, liver, vitamin D–enriched soy or lactose-free milk, and vitamin D–fortified cereals and other processed foods. Regular exposure to sunlight helps the body synthesize vitamin D naturally.³

For optimal bone health, the NIH³ continues to recommend a combination of cardiovascular exercise, weight-bearing exercise, smoking cessation, and a well-balanced diet (including foods that are rich in calcium and vitamin D).

In addition to its role in bone health, calcium has been suggested to improve cardiac and vascular smooth muscle contractility,²⁰ and clinical research is under way to investigate the role of calcium in reducing the risk for adenomatous colon polyps.²¹

Conclusion
Primary LI is a common disorder resulting from a deficiency in the enzyme lactase, making affected patients unable to digest lactose. LI is widespread in varying degrees across all races and ethnicities, affecting people of all ages; however, it is more common among older adults due to natural pathophysiologic processes.

In LI-affected patients, consuming lactose leads to troublesome symptoms of diarrhea, abdominal pain, flatulence, and/or bloating, and sometimes nausea and vomiting.

No tool is considered a “gold standard” for making a diagnosis of LI, so it is important to rule out other gastrointestinal conditions first. Oftentimes a diagnosis of LI is confirmed by the effectiveness of a lactose-free trial diet. When diagnosis is uncertain, referral to a gastroenterologist is required.

Without formal treatment guidelines, the primary form of therapy for LI is to adjust the amount of ingested lactose, with careful attention to adequate calcium and vitamin D intake. Patient education is crucial for management of LI and improvement in the patient’s quality of life.

Lactose intolerance (LI), a term closely associated with hypolactasia (lactase deficiency) and lactose malabsorption,¹ is a common syndrome composed of diarrhea, abdominal pain, flatulence and/or bloating, and sometimes nausea and vomiting in severe cases, after ingestion of dairy products.² This common disorder results from a deficiency in the enzyme lactase, which makes affected patients unable to digest lactose, a sugar found in milk and other dairy products.³ Malabsorption of lactose produces the symptoms associated with LI.

The level of LI varies among affected individuals, depending on many nutritional and genetic factors, the amount of lactose consumed, the patient’s degree of lactase deficiency, and the substance in which the lactose is ingested.⁴

Epidemiology
LI prevalence is difficult to ascertain because the symptoms are vague and can be attributed to a number of conditions; additionally, there is no gold standard for diagnosis of LI. It is estimated that about 70% of the world population is affected by LI—with great variation among ethnicities and races.^5,6 Some degree of LI is reported in up to 80% of African-Americans and Latinos, and almost 100% of Native Americans and Asian Americans. LI is least common in people of northern European descent (and is unlikely to develop before adulthood⁷), although it has been suggested that 30 million American adults experienced lactose malabsorption to some degree by age 20.^3,8 Heyman⁴ estimates that approximately 2% of people of northern European descent have LI.

Regardless of ethnicity or race, older patients are more susceptible to LI than are younger adults, largely as a result of the normal processes of aging.²

Pathophysiology and Patient Presentation
Cells of the inner lumen of the small intestines, enterocytes, are covered with a membrane that has a brush border composed of microvilli.⁹ The microvilli produce lactase, the enzyme necessary to split and hydrolyze dietary lactose into glucose and galactose for transport across the cell membrane^.6 Unfortunately, lactase is produced in the upper, most shallow section of the villi, which is exceedingly prone to damage by secondary insult.

If the lactase enzymes are absent or deficient, unabsorbed sugars osmotically attract fluid into the bowel lumen. The amount of fluid influx into the bowel is approximately triple the normal amount, based on the osmolality of sugar alone. In addition, the unabsorbed lactose entering the colon is fermented by bacteria, producing gas and resulting in the cleavage of lactose into monosaccharides. Monosaccharides cannot be absorbed by the colonic mucosa; as a result, osmotic pressure increases, and fluid levels rise in the bowel. This process explains the most common symptoms of flatulence, diarrhea, abdominal pain, and bloating.⁶

Most mammalian babies, including human infants, produce enough lactase to digest milk, including breast milk. This ability persists until the child is weaned. In humans, lactase activity drops at age 2 to 3 years and may cease altogether by age 5 to 10.⁹ Worldwide, most humans lose 90% to 95% of birth lactase levels by early childhood, followed by a continuing decline during the course of a lifetime.6 This may help explain why many elderly people are affected by LI.

Typically, development of LI progresses subtly over many years, but onset can also be relatively acute.⁴

Lactose Malabsorption
The three main types of lactose malabsorption are primary, secondary, and congenital. The latter is a rare, genetic form of LI in which the lactase enzyme is entirely absent; for the purposes of this article, congenital lactose malabsorption will not be discussed.

Primary lactase deficiency is the most common form and the focus of this article. It is the normal, gradual reduction in lactase enzyme that a maturing individual experiences through adulthood, and the rate of reduction is genetically determined. Secondary lactose malabsorption occurs following an insult to the small bowel, as in severe diarrhea, infection (eg, rotavirus), chemotherapy, or acute gastroenteritis.⁴ In these situations, lactase is the first enzyme to be negatively affected and the last to return as the insult resolves.¹⁰ Secondary hypolactasia is transient and reversible.^11,12

LI is not to be confused with cow’s milk allergy—an immune response to the protein in cow’s milk, which can be a life-threatening event. A true milk allergy most commonly appears within the first year of life, whereas LI occurs more often in adulthood.^5,8

LI is not considered life threatening, but its symptoms can severely affect a person’s quality of life and productivity. In addition to ethnicity and age, the type and amount of lactose ingested and the amount that the patient is unable to digest all affect the severity of LI symptoms.¹³

Lactose makes up between 2% and 8% of the solids in milk; 1 mL of milk (0.03 fl oz) contains 47.2 mg of lactose. No amount of lactose has been specified to produce symptoms, but most adults can tolerate as much as 8 fl oz of milk without problems,¹ and patients can tolerate more lactose if the food containing it is consumed with a meal.¹¹ Some adults may be able to ingest only 2 to 4 fl oz before symptoms appear⁴; in highly sensitive adults, as little as 200 mg of lactose (0.13 fl oz of milk) can produce symptoms.⁵

Also playing a role are the patient’s gastric emptying time and intestinal transit time.¹² Symptoms of LI can be produced between 30 minutes and two hours after ingestion of milk or a milk product.⁹

Diagnosis
Most patients do not require specialized, sophisticated testing for a diagnosis of LI. A thorough medical history and physical examination are needed to rule out other conditions in the differential diagnosis (see Table 1^6,14). For the primary care provider, a basic workup should include a complete blood count, a comprehensive metabolic panel, erythrocyte sedimentation rate, a thyroid-stimulating hormone level, a stool culture, and if symptoms are severe, abdominal/pelvic radiography and CT.

In the absence of accepted guidelines, a common therapeutic approach is to exclude milk and dairy products from the patient’s diet.¹¹ Generally, a two-week trial of a strict lactose-free diet leading to resolution of symptoms, followed by reintroduction of dairy foods and recurrence of symptoms, can be considered diagnostic.⁴

It is important to instruct the patient that while he or she follows this diagnostic diet, all sources of lactose must be eliminated; food labels must be read carefully to identify “hidden” lactose sources (see Table 2⁸). Additionally, many patients (and even clinicians) may not realize that many commonly used prescription and OTC medications contain lactose, including certain agents indicated for gastrointestinal problems⁵ (see Table 3⁵).

During the diagnostic diet, patients may find it helpful to keep a diary of food choices and note any symptoms that may occur. This helps empower them to be an active participant in food choices, using self-experimentation to identify which foods they can and cannot tolerate.

Gastroenterology Consult
Referral to a gastroenterologist is needed if the diagnosis is unclear or if other illnesses are suspected. Tests the specialist may perform include the hydrogen breath test, a small-­intestine biopsy, the lactose tolerance test, and/or the stool acidity test for infants and children,⁴ although these tests vary in sensitivity and specificity.¹³

The hydrogen breath test, by which enzymatic activity is confirmed after the patient consumes 25 to 50 g of lactose,⁶ is the most widely used formal test for confirming a diagnosis of LI because it is relatively inexpensive and is the most sensitive and the most specific for LI, according to Hovde and Farup¹³ and Eadala et al.⁵ The test has been shown to yield positive results in 90% of patients with lactose malabsorption.^6,15 False-negative results may signify absence of bacterial flora, as in the case of recent antibiotic use or a recent high-colonic enema. Previous aspirin use, sleep, exercise, and smoking may increase breath hydrogen secretion unrelated to lactose consumption.⁶

Management of Lactose Intolerance
Although the body’s ability (or inability) to produce lactase cannot be changed, the symptoms of LI can be managed with dietary restrictions. The extent of change needed depends on how much lactose the patient is able to consume before experiencing symptoms.⁸

In patients with secondary LI, a complete lactose-free diet is recommended until the causative pathologic condition has resolved. Patients with primary LI can opt to exclude all milk and dairy products, at least initially, until symptoms have resolved; they can then reintroduce certain milk and dairy products gradually and in small amounts, according to their ­individual tolerance threshold. Certain lactose-containing foods may be easier to digest than others (see Table 4²).

Ingesting lactose-containing foods with a meal helps decrease gastric transit time and can lessen the symptoms of LI.¹¹ Additionally, people who cannot drink milk may find they can eat yogurt because it contains lactase-producing bacteria,⁹ although clinical trials examining consumption of yogurt or probiotics in patients with LI had inconclusive results.¹

Lactose-free milk or soy milk is available at most major grocery stores. These products tend to be more expensive and taste somewhat sweeter than regular milk but can be used as a reasonable substitute.⁹

Some patients may benefit from taking lactase enzyme supplements,^1,16 which are taken with any ingestion of lactose. The enzymes may not completely prevent symptoms because the lactose is not completely digested or because it is difficult to determine an effective dose of the enzyme. Therefore, enzyme supplementation should be an adjunct to, not a substitute for, dietary restrictions.⁶ This may help patients when they eat at restaurants, where they do not know how food is prepared and which are unlikely to offer lactose-free food selections.

Instead of taking lactase enzyme supplements in tablet form, patients may prefer to mix lactase liquid with regular milk, producing lactose-free milk. A waiting period of 24 hours is needed before the mixture can be considered lactose-free. A trial-and-error period should be expected when enzyme supplementation or any dietary approach is tried.¹¹

The theory of adaptative phenomena suggests that most people with LI can teach themselves to ingest more lactose gradually, leading over time to beneficial changes in the microflora of the gut and in improved colonic function.^11,17 The ultimate result, whether the explanation is reduced hydrogen excretion or increased gas absorption, is less severe gastrointestinal symptoms. This strategy is not a cure for LI, nor has it been found effective for all patients with LI,¹ but it can help manage symptoms to some extent.

Information for the Patient
Patients often need instruction in reading food labels to identify foods that contain milk, milk products, lactose, whey, curds, milk byproducts, dry milk solids, or even nonfat dry milk powder.⁸ Follow-up with the primary care provider should be arranged on an as-needed basis.

Simply excluding all dairy products from the diet does raise some health concerns. Milk and other dairy products are important sources of calcium and vitamin D, which are needed for growth and bone health in patients of all ages. A decrease in calcium consumption is one of the primary risk factors for osteoporosis, although research examining a possible association between LI and osteoporosis has yielded conflicting results. According to Kudlacek et al,¹⁸ even individuals with severe LI do not appear to be at risk for accelerated bone loss. By contrast, other research groups^7,19 studied patients with LI from various age-groups and concluded that low calcium intake and impaired vitamin D status could lead to increased bone turnover and decreased bone mass, especially in men and postmenopausal women. No guidelines have been published regarding screening for osteoporosis in patients with LI.

According to a consensus statement from the NIH,³ both men and women younger than 50 should consume 1,000 mg/d of calcium, and older persons, 1,500 mg/d. In addition to calcium supplements, patients can obtain the necessary calcium through certain foods, including leafy green vegetables (spinach, kale, broccoli), sardines, calcium-fortified cereal bars, calcium-enriched soy or lactose-free milk and other soy products, fruit juices, dried beans, and tuna.

Calcium is absorbed only when enough vitamin D is present; vitamin D intake should be 400 to 600 IU/d for both women and men.³ Foods that contain vitamin D include eggs, liver, vitamin D–enriched soy or lactose-free milk, and vitamin D–fortified cereals and other processed foods. Regular exposure to sunlight helps the body synthesize vitamin D naturally.³

For optimal bone health, the NIH³ continues to recommend a combination of cardiovascular exercise, weight-bearing exercise, smoking cessation, and a well-balanced diet (including foods that are rich in calcium and vitamin D).

In addition to its role in bone health, calcium has been suggested to improve cardiac and vascular smooth muscle contractility,²⁰ and clinical research is under way to investigate the role of calcium in reducing the risk for adenomatous colon polyps.²¹

Conclusion
Primary LI is a common disorder resulting from a deficiency in the enzyme lactase, making affected patients unable to digest lactose. LI is widespread in varying degrees across all races and ethnicities, affecting people of all ages; however, it is more common among older adults due to natural pathophysiologic processes.

In LI-affected patients, consuming lactose leads to troublesome symptoms of diarrhea, abdominal pain, flatulence, and/or bloating, and sometimes nausea and vomiting.

No tool is considered a “gold standard” for making a diagnosis of LI, so it is important to rule out other gastrointestinal conditions first. Oftentimes a diagnosis of LI is confirmed by the effectiveness of a lactose-free trial diet. When diagnosis is uncertain, referral to a gastroenterologist is required.

Without formal treatment guidelines, the primary form of therapy for LI is to adjust the amount of ingested lactose, with careful attention to adequate calcium and vitamin D intake. Patient education is crucial for management of LI and improvement in the patient’s quality of life.