Lactose Intolerance

Lactose intolerance is caused by a deficiency of the intestinal enzyme lactase.

Lactose intolerance is the inability to digest and absorb lactose (the sugar in milk) that results in gastrointestinal symptoms when milk or food products containing milk are consumed. It is due either to a genetically programmed loss of lactase, the intestinal enzyme responsible for the digestion of lactose, or diseases affecting the small intestine that destroy lactase. Genetically programmed loss of lactase occurs between early childhood and age 21. The timing of this loss is determined primarily by ethnicity.

Because diseases of the intestine can occur at any age, lactose intolerance can begin at any age; however, that does not mean that an individual has become genetically lactase deficient.

Lactose is a sugar molecule that is made up of two smaller sugars, glucose and galactose. For lactose to be absorbed from the intestine and into the body, it must first be split into glucose and galactose. The glucose and galactose are then absorbed by the cells lining the small intestine. The enzyme that splits lactose into glucose and galactose is called lactase, and it is located on the surface of the cells lining the small intestine.

Lactose intolerance is caused by the reduced or absent activity of lactase that prevents the splitting of lactose (lactase deficiency). Lactase deficiency may occur for one of three reasons, congenital, secondary, or developmental.

Congenital causes of lactose intolerance

Lactase deficiency may occur because of a congenital absence (absent from birth) of lactase due to a mutation in the gene that is responsible for producing lactase. This is a very rare cause of lactase deficiency, and the symptoms of this type of lactase deficiency begin shortly after birth.

Secondary causes of lactose intolerance

Another cause of lactase deficiency is secondary lactase deficiency. This type of deficiency is due to diseases that destroy the lining of the small intestine along with lactase. An example of such a disease is celiac disease (sprue).

Genetically programmed causes of lactose intolerance

The most common cause of lactase deficiency is a decrease in the amount of lactase that occurs after childhood and persists into adulthood, referred to as adult-type hypolactasia. This decrease in lactase is genetically programmed. Lactase deficiency (and lactose intolerance) is most common among Asians, affecting more than 90% of adults in some communities. People with ancestry from Northern Europe, on the other hand, have a 5% rate of lactase deficiency. In addition to variability in the prevalence of lactase deficiency among ethnic groups, there also is variability in the age at which symptoms of lactase deficiency (and lactose intolerance) appear.

As people age they may develop lactose intolerance; however, the extent of the intolerance appears to be mild and not associated with clinical symptoms.  Therefore, the development of lactose intolerance in the elderly should not be made lightly.

The common primary symptoms of lactose intolerance are gastrointestinal and include:

• Abdominal pain
• Diarrhea
• Flatulence (passing gas)

Less common symptoms of lactose intolerance include:

• Abdominal bloating
• Abdominal distension
• Nausea

Constipation is not a sign of lactose intolerance.

Unfortunately, these symptoms can be caused by several gastrointestinal conditions or diseases, so the presence of these symptoms is not very good at predicting whether a person has lactase deficiency or lactose intolerance.

Symptoms occur because the unabsorbed lactose passes through the small intestine and into the colon. In the colon, one type of normal bacterium contains lactase and can split the lactose and use the resulting glucose and galactose for its purposes. Unfortunately, when they use glucose and galactose, these bacteria also release hydrogen gas. Some of the gas is absorbed from the colon and into the body and is then expelled by the lungs in the breath. Most of the hydrogen, however, is used up in the colon by other bacteria. A small proportion of the hydrogen gas is expelled and is responsible for increased flatulence (passing gas). Some people have an additional type of bacterium in their colons that changes the hydrogen gas into methane gas, and these people will excrete only methane or both hydrogen and methane gas in their breath and flatus.

Not all of the lactose that reaches the colon is split and used by colonic bacteria. The unsplit lactose in the colon draws water into the colon (by osmosis). This leads to loose, diarrheal stools.

Since internists, pediatricians, and family practitioners all see patients with gastrointestinal symptoms, they all are called upon to diagnose and treat lactose intolerance. If their attempts to diagnose and treat do not result in adequate clinical benefit, patients usually will be referred to a gastroenterologist, an internist, or a pediatrician specially trained in diseases of the gastrointestinal tract. These specialists will be able to diagnose and treat causes of symptoms other than lactose intolerance.

Although there are several good ways to diagnose lactose intolerance, most people who consider themselves lactose intolerant have never been formally tested for intolerance; approximately 20% of people who think they are lactose intolerant are not lactose intolerant.

Why do people believe that they are lactose intolerant when they are not? This erroneous belief may be common for several reasons. People with unexplained (undiagnosed) gastrointestinal symptoms are looking for an explanation for their symptoms. Since lactose intolerance is a well-known and common condition, it provides these people with a ready (and welcome) explanation for their symptoms. Confirmation that lactose intolerance is present often is made subjectively and without careful correlation between ingestion of milk or milk products and symptoms. Also, there are placebo responses, that is, people think they are better when they are not.

Formal testing for lactose intolerance is valuable. Not only can testing confirm lactose intolerance and prompt the institution of a reduced or lactose-free diet, but it also can exclude lactose intolerance and direct attention to diagnosing other conditions and diseases that are responsible for the symptoms.

Probably the most common way that people self-diagnose lactose intolerance is by an elimination diet, a diet that eliminates milk and milk products.

There are several problems with this type of "testing," such as the following:

1. Milk products are so common in prepared foods from supermarkets or restaurants that, likely, an elimination diet that is not rigorous (i.e., does not eliminate all milk-containing products) will still include substantial amounts of milk. Thus, persons with severe lactase deficiency attempting an elimination diet may be ingesting enough lactose to have symptoms and erroneously conclude that lactose intolerance is not responsible for the symptoms.
2. People often assume that they are lactose intolerant based on a short trial of elimination. A short trial may be adequate if symptoms are severe and occur daily, but not if the symptoms are subtle and/or variable. In the latter case, an elimination diet may need to be continued for several weeks.
3. Because symptoms of lactose intolerance are subjective and variable, there always is the possibility of a "placebo effect" in which people think they feel better eliminating milk when, in fact, they are no better.

If an elimination diet is to be used for diagnosing lactose intolerance, it should be a rigorous diet. A rigorous diet requires counseling by a dietician or reading a guide to a lactose-elimination diet. The diet also needs to be continued long enough to evaluate whether or not symptoms are better. If there is doubt about the improvement in the diet, particularly if symptoms normally fluctuate in intensity over weeks or months, repeated periods of lactose elimination should be tried until a firm conclusion can be drawn. Elimination of all milk products should eliminate symptoms if lactose intolerance alone is the cause of the symptoms.

A milk challenge is a simpler way of diagnosing lactose intolerance than an elimination diet. A person fasts overnight and then drinks a glass of milk in the morning. Nothing further is eaten or drunk for 3-5 hours. If a person is lactose intolerant, the milk should produce symptoms within several hours of ingestion. If there are no symptoms or symptoms are substantially milder than the usual symptoms, it is unlikely that lactose intolerance is the cause of the symptoms. The milk that is used must be fat-free to eliminate the possibility that fat in the milk is the cause of symptoms. It is not possible to eliminate the possibility that symptoms are due to milk allergy, a very different condition from lactose intolerance; however, this usually is not confusing since milk allergy is rare and primarily occurs in infants and young children. (If milk allergy is a consideration, pure lactose can be used instead of milk for the challenge.)

An important issue is the amount of milk required for the milk challenge.

• If a person drinks several glasses of milk or ingests large amounts of milk-containing products in their normal diet, then a larger amount of milk should be used in the challenge, 8-16 ounces in an adult, equivalent to one or two large glasses of milk.
• If the person being tested usually does not drink several glasses of milk or ingest larger quantities of milk-containing products, there may be a problem with using 8-16 ounces of milk for testing. These larger quantities of milk used for testing may cause symptoms, but the smaller amounts of milk or milk products that these persons ingest in their normal diet may not be enough to cause symptoms. Technically, they may be lactose intolerant when they are tested with larger amounts of milk, but lactose in their normal diet cannot be responsible for their usual symptoms.

Recognition of this issue is important in interpreting the results of a milk challenge. Also, it is important to remember that lactose intolerance does not mean that there is a genetic lactase deficiency.

The hydrogen breath test is the most convenient and reliable test for lactose intolerance. For the breath test, pure lactose, usually 25 grams (the equivalent of 16 oz. of milk), is ingested with water after an overnight fast. In persons who are lactose intolerant, the lactose that is not digested and absorbed in the small intestine reaches the colon where the bacteria split the lactose into glucose and galactose and produce hydrogen (and/or methane) gas. Small amounts of hydrogen and methane are absorbed from the colon into the blood and then travel to the lungs where they are excreted in the breath.

• Samples of breath are collected every 10 or 15 minutes for 3-5 hours after ingestion of the lactose, and the samples are analyzed for hydrogen and/or methane.
• If hydrogen and/or methane are found in the breath, it means that the small intestine of the person is unable to digest and absorb all of the lactose. He or she is lactose intolerant.
• The amount of hydrogen or methane excreted in the breath is roughly proportional to the degree of lactose intolerance (and potential lactase deficiency), that is, the larger the amount of hydrogen and/or methane produced, the greater the intolerance or deficiency.
• The amount of hydrogen and/or methane in the breath, however, is not proportional to the severity of the symptoms. In other words, a person who produces little hydrogen and/or methane may have more severe symptoms than a person who produces large amounts of hydrogen and/or methane.

The breath test is the best test for determining lactose intolerance and potentially lactase deficiency, but it has several weaknesses.

• The first is that it is a long, boring test.
• The second is that it suffers from the same issue as the milk challenge test concerning the quantity of lactose that should be used. (See the previous discussion.)
• Lastly, the breath test can be falsely abnormal when there is a spread of bacteria from the colon into the small intestine, a condition called bacterial overgrowth of the small bowel. When overgrowth occurs, the bacteria that have moved up into the small intestine get to the lactose in the intestine before there has been enough time for the lactose to be digested and absorbed normally, and these bacteria produce hydrogen and/or methane. This may lead erroneously to a diagnosis of genetic lactase deficiency; the abnormal test is due to an intestinal condition.
• Other conditions also interfere with the breath test. Thus, diseases that markedly speed up the transit of lactose through the small intestine prevent lactose from being fully digested and absorbed, leading to a misdiagnosis of lactose intolerance.
• Recent treatment with antibiotics can suppress colonic bacteria and their production of hydrogen or methane and lead to a misdiagnosis of lactose tolerance. Fortunately, these latter conditions are uncommon and usually can be anticipated based on a person's history or symptoms.

Genetic testing

The appearance and disappearance of lactase in the intestinal lining are controlled by genes. It is possible to analyze DNA, the substance of genes, from cells in the blood to determine if an individual has the genes that program the disappearance of lactase. If they do, then they are very likely to be lactose intolerant. Genetic testing is the most direct way of diagnosing congenital or developmental lactase deficiency. Unfortunately, the test is relatively complex, expensive, and often not easily available. Moreover, it usually is not necessary to know an individual’s lactase genetics to diagnose and treat.

Intestinal biopsy

The most direct test for lactase deficiency is a biopsy of the intestinal lining with measurement of lactase levels in the lining. The biopsy can be obtained by endoscopy or by special capsules that are passed through the mouth or nose and into the small intestine. The analysis of lactase levels in the biopsy requires specialized procedures that are not often available, and, as a result, lactase levels are not often measured except for research purposes.

Blood glucose test

The blood glucose test is an older test for lactase deficiency and lactose intolerance. For the blood glucose test, lactose is ingested (usually 0.75 to 1.5 gm. of lactose per kg of body weight) after an overnight fast, and serial blood samples are drawn and analyzed for glucose. If the level of blood glucose rises more than 25 mg/100ml, it means that the lactose has been split in the intestine and the resulting glucose has been absorbed into the blood. This implies that lactase levels are normal. Unfortunately, the blood glucose test, though simple in principle, requires the collection of multiple samples of blood. Moreover, the test has many real and potential problems, the most common of which are false positive tests, that is, abnormal tests in people who have normal lactase levels and no lactose intolerance. For these reasons, the blood glucose test is not often used.

The stool acidity test is a test for lactase deficiency in infants and young children. For the stool acidity test, the infant or child is given a small amount of lactose orally. Several consecutive stool samples then are tested for acidity. With a deficiency of lactase, unabsorbed lactose enters the colon and is split into glucose and galactose. Some of the glucose and galactose are broken down by the bacteria into acids, for example, lactic acid. Lactic acid turns the stool acidic. Therefore, a lactase-deficient infant or child will develop an acidic stool following the test dose of lactose.

Despite the availability of the stool acidity test, the superiority of breath testing has led to modifications in the equipment for collecting breath samples that make it easier to do breath testing in young children and even infants. As a result, the stool acidity test is not done frequently.

Dietary changes

The most obvious means of treating lactose intolerance is by reducing the amount of lactose in the diet. Fortunately, most people who are lactose intolerant can tolerate small or even moderate amounts of lactose. It often takes only the elimination of the major milk-containing products to obtain sufficient relief from their symptoms. Thus, it may be necessary to eliminate only milk, yogurt, cottage cheese, and ice cream. Though yogurt contains large amounts of lactose, it often is well-tolerated by lactose-intolerant people. This may be so because the bacteria used to make yogurt contain lactase, and the lactase can split some of the lactose during storage of the yogurt as well as after the yogurt is eaten (in the stomach and intestine). Yogurt also has been shown to empty more slowly from the stomach than an equivalent amount of milk. This allows more time for intestinal lactase to split the lactose in yogurt, and, at least theoretically, would result in less lactose reaching the colon.

Most supermarkets carry milk that has had the lactose already split by the addition of lactase. Milk substitutes also are available, including soy and rice milk. Acidophilus-containing milk is not beneficial since it contains as much lactose as regular milk, and acidophilus bacteria do not split lactose.

For individuals who are intolerant to even small amounts of lactose, the dietary restrictions become more severe. Any purchased product containing milk must be avoided. It is especially important to eliminate prepared foods containing milk purchased from the supermarket and dishes from restaurants that have sauces.

Another means to reduce symptoms of lactose intolerance is to ingest any milk-containing foods during meals. Meals (particularly meals containing fat) reduce the rate at which the stomach empties into the small intestine. This reduces the rate at which lactose enters the small intestine and allows more time for the limited amount of lactase to split the lactose without being overwhelmed by a full load of lactose at once. Studies have shown that the absorption of lactose from whole milk, which contains fat, is greater than from non-fat milk, perhaps for this very reason. Nevertheless, the substitution of whole milk or yogurt for non-fat milk or yogurt does not seem to reduce the symptoms of lactose intolerance.

Lactase enzyme

Caplets or tablets of lactase are available to take with milk-containing foods.

Adaptation

Some people find that by slowly increasing the amount of milk or milk-containing products in their diets they can tolerate larger amounts of lactose without developing symptoms. This adaptation to increasing amounts of milk is not due to increases in lactase in the intestine. Adaptation probably results from alterations in the bacteria in the colon. Increasing amounts of lactose entering the colon change the colonic environment, for example, by increasing the acidity of the colon. These changes may alter how the colonic bacteria handle lactose. For example, bacteria may produce less gas. There also may be a reduction in the secretion of water and, therefore, less diarrhea. Nevertheless, it is not clear how frequently or how many progressive increases in milk intake increase the quantities of milk that can be ingested.

Calcium and vitamin D supplements

Milk and milk-containing products are the best sources of dietary calcium, so it is no wonder that calcium deficiency is common among lactose-intolerant persons. This increases the risk and severity of osteoporosis and the resulting bone fractures. It is important, therefore, for lactose-intolerant persons to supplement their diets with calcium. A deficiency of vitamin D also causes disease of the bones and fractures. Milk is fortified with vitamin D and is a major source of vitamin D for many people. Although other sources of vitamin D can substitute for milk, it is a good idea for lactose-intolerant persons to take supplemental vitamin D to prevent vitamin D deficiency.

The severity of the symptoms of lactose intolerance varies greatly from person to person. One reason for this variability is that people have different amounts of lactose in their diet; the more lactose in the diet, the more likely and severe the symptoms. Another reason for the variability is that people have different severities of lactase deficiency, that is, they may have a mild, moderate, or severe reduction in the amounts of lactase in their intestines. Thus, small amounts of lactose will cause major symptoms in severely lactase-deficient people but only mild or no symptoms in mildly lactase-deficient people. Finally, people may have different responses to the same amount of lactose reaching the colon. Whereas some may have mild or no symptoms, others may have moderate symptoms. The reason for this is not clear but may relate to differences in their intestinal bacteria.

Lactose intolerance is rarely due to milk allergy in adults. Children with milk allergy, where it is more common, usually outgrow the allergy by adulthood.

The important long-term health consequence of lactose intolerance is calcium deficiency which leads to osteoporosis. Less commonly, vitamin D deficiency may occur and compound the bone disease. Both of these health issues can be prevented easily by calcium and vitamin D supplements. The real problem is that many lactose-intolerant people who consciously or unconsciously avoid milk do not realize that they need supplements.

Although milk and foods made from milk are the only natural sources of lactose, lactose often is "hidden" in prepared foods to which it has been added. People with a very low lactose tolerance should know about the many food products that may contain lactose, even in small amounts.

Food products that may contain lactose include:

• Bread
• Baked goods
• Processed breakfast cereals
• Instant potatoes, soups, and breakfast drinks
• Margarine
• Lunch meats (except those that are kosher)
• Salad dressings
• Candies
• Chips and other processed snacks
• Mixes for pancakes, biscuits, and cookies
• Soft cheeses
• Milk
• Nondairy whipped toppings
• Nondairy liquid and powdered coffee creamers

Smart shoppers learn to read food labels with care, looking not only for milk and lactose in the contents but also for such words as whey, curds, milk by-products, dry milk solids, and nonfat dry milk powder. If any of these are listed on a label, the item contains lactose.

In addition to food sources, lactose can be "hidden" in medicines. Lactose is used as the base for many prescription and over-the-counter medications. Many types of birth control pills, for example, contain lactose, as do some tablets used for stomach acid and gas. However, these products typically affect only people with severe lactose intolerance because they contain such small amounts of lactose.

Genetic testing of the DNA of individuals to make a diagnosis of lactase deficiency has already been discussed. This is likely to be an important research tool for studying lactase deficiency. It is still too early to know how helpful this sophisticated test will be in the clinical evaluation and treatment of patients. It is an expensive test. The most important question to answer usually is, does lactose causes symptoms, and not, whether an individual is lactase deficient.

In 1998, scientists were able to make lactose intolerant rats tolerant to lactose by transferring the gene for lactase production to their intestinal lining cells. It is unlikely that this type of gene therapy will find much application in people. Nevertheless, it is a fascinating example of what science can accomplish.