Lactose Intolerance Breath Test

Transcription

1 G A S T R O / I M M U N E A S S E S S M E N T S Lactose Intolerance Breath Test What this test does: Precisely diagnoses the most common form of carbohydrate malabsorption. Avoids the misdiagnosis of milk allergy. Turn-around Time 10 days A P P L I C A T I O N G U I D E L I N E S A P P L I C A T I O N G U I D E L I N E S Overview More than 50 million Americans can t digest lactose (milk sugar) or other sugars because they lack the appropriate enzyme in their digestive systems. 1 They may suffer from bloating, diarrhea, flatulence, abdominal cramps and discomfort and may never realize the cause of their symptoms. The almost identical symptom picture between self-reported milk intolerance and irritable bowel syndrome (IBS) suggests that fermentation of malabsorbed lactose is likely reponsible for many cases of IBS. 2 The digestive system uses specific enzymes to break down sugars into smaller components. Disaccharidases are enzymes with the ability to hydrolyze disaccharides into monosaccharides, smaller molecules that the body absorbs more easily. 3 When an individual doesn t produce enough of a particular enzyme to break down a carbohydrate into simpler sugars, the carbohydrate travels into the colon. There, the bacteria fermenting the carbohydrate produce gas. Osmotic imbalances create diarrhea, and the gases cause the bloating seen in individuals with carbohydrate intolerances. Over time, the intestinal mucosal lining becomes irritated. There are degrees of carbohydrate intolerance. Some individuals manufacture a small amount of the enzyme, while others lack the enzyme completely. Any degree will result in malabsorption. 4 Unfortunately, many people never relate their symptoms to their diet and continue to eat foods they cannot digest properly. Studies indicate that as many as 70% of lactose intolerant patients do not relate their symptoms to lactose ingestion. At times, individuals may even mislead their physicians by denying a connection to their symptoms and their diet. 5 Recent studies point out that ongoing carbohydrate malabsorption keeps the digestive system constantly weakened, leading to systemic disorders. The body cannot obtain needed nutrients if other intestinal symptoms disrupt absorption. The weakened digestive system is also more susceptible to attack by parasites, yeast and bacterial overgrowth, which further tip the scales of healthy intestinal balance. Imbalanced gut flora, irritated mucosa, malabsorption, altered permeability, food allergies and chronic illness can result from these intestinal irritations. Therefore, suspected sugar malabsorption should be investigated and treated to ward off further damage to the body s digestive system. Types of sugar intolerance Lactose intolerance is the most common type of malabsorption because milk sugar is common in a typical diet. Without the lactase enzyme, the intestine can t break down lactose into glucose and galactose (Figure 1). Lactase retention is genetically determined as a dominant trait. Lactase reaches its maximum levels in the human intestine shortly after birth and declines after the age of 3 1/2. 3 Lactose malabsorption often is recognized for the first time in older patients, possibly because they are more sensitive to intestinal problems. They may have endured gas and other symptoms for years without connecting the symptoms to their diet. 6 Conditions that damage the intestinal lining can create lactose malabsorption, such as infectious diarrhea, intestinal parasites or inflammatory bowel disease. Alcoholism, malnutrition, pelvic radiation therapy and drugs such as antibiotics can also trigger lactose malabsorption. 7

2 Lactose Digestion Normal Lactose is ingested and travels to the small intestine... Lactase enzymes break down lactose into glucose and galactose... Glucose and galactose are absorbed into the small intestine... Normal digestion is completed. Abnormal Lactose is ingested and travels to the small intestine; there is insufficient lactase enzyme to break it down... Undigested lactose travels to the large intestine. Bacteria ferment lactose... Fermentation produces hydrogen and methane and produces bloating, gas and diarrhea... Some hydrogen and methane are absorbed through the mucosa and are carried by the circulatory system to the lungs. Figure 1 Lactose Lactose intolerance is very different from milk allergy, and individuals who don t produce sufficient quantities of the lactase enzyme aren t necessarily allergic to milk proteins. Fructose Fructose is used as a sweetener in many soft drinks and is present in a number of fruits. Individuals may be fructose malabsorbers and suffer symptoms similar to lactose intolerance. Sucrose Sucrose is common table sugar. The sucrase enzyme is needed to break down sucrose into glucose and fructose. If malabsorption symptoms exist but the lactose test is negative, sucrose intolerance should be considered. Maltose Maltose is contained in some foods, particularly grains. The maltase enzyme is needed to break down maltose into two molecules of glucose. If malabsorption symptoms exist but the lactose test is negative, maltose intolerance should be considered. Why test for lactose intolerance? A reliable test for lactose intolerance can differentiate this disorder from other digestive problems such as milk allergy. While some individuals have genetic deficiencies of lactase that causes permanent lactose intolerance, other individuals have an acquired lactose intolerance that may disappear when intestinal health is restored. An accurate diagnosis is important because: 2

3 1. Many patients don t relate intestinal troubles to what they eat. A lactose intolerance test can dramatically demonstrate to patients the connection between symptoms and diet and the importance of following diet restrictions. Studies show that some patients with lactose intolerance are not observant about food-related symptoms. In one study, 70% of lactose intolerant patients did not associate their symptoms with lactose ingestion Patients may be unnecessarily avoiding dairy products. Some health experts consider milk and dairy products to be important sources of nutrients for children, pregnant women, nursing mothers and older adults, and thus feel that they should not be eliminated from the diet without good reason. 8,9 Treatment options, such as lactase replacement therapy, may help individuals with lactose intolerance enjoy dairy products without experiencing symptoms of maldigestion. Lactase enzyme supplements will not benefit individuals who are allergic to milk proteins or who cannot tolerate some other type of sugar. Obvious Sources All cheeses Butter, many margarines Goat s milk Half-and-half cream Ice cream and many sherbets Milk (whole, skim, dry powdered, evaporated) Yogurt Hidden Sources Artificial sweeteners containing lactose Breads, biscuits and crackers, doughnuts made with milk Breading on fried foods Breakfast and baby cereals containing milk solids Buttered or creamed foods (soups and vegetables) Cake and pudding mixes, many frostings Candies with milk chocolate Cookies made with milk Hot dogs, luncheon meats, sausage, hash, processed and canned meats Mayonnaise and salad dressings made with milk Nondairy creamers (except for Coffee Rich) Pancakes, waffles, toaster tarts Pizza Weight-reduction formulas Many prescription drugs: birth control pills, thyroid medication and medications for gastrointestinal disorders (such as Reglan and Xanax) Many types of vitamins Foods containing whey, casein, caseinate, sodium caseinate and lactose Table 1 Sources of Lactose Lactose intolerance tests Eliminating milk from the diet Excluding milk products from the diet will not be a conclusive test if the patient is unknowingly ingesting foods that contain hidden sources of lactose. Many foods and drugs use lactose as a filler(table 1). Patients who continue eating these foods may experience ongoing symptoms, leading to a false negative diagnosis. 9 Histology This test is rarely used for disaccharide intolerance due to its expense and discomfort for patients. It requires an endoscopic biopsy of the small intestine, which is tested for its ability to generate glucose and galactose from lactose applied in vitro. Blood and urine tests After ingestion of large amounts of lactose (about 2 gm/kilo of body weight), serial blood samples are drawn or serial urine samples collected to measure galactose change. If no change occurs over time, the test suggests lactose malabsorption. Because glucose is rapidly metabolized, a large dose of lactose is necessary, typically producing symptoms in lactase-deficient individuals. The galactose serum and urine tests require prior oral ingestion of alcohol to suppress rapid galactose turnover by the liver, in addition to the large amount of lactose needed to produce measurable results. The alcohol can impair patients physically and mentally, making it impractical. 10 Breath hydrogen/methane test The breath hydrogen/methane test is the standard for testing lactose intolerance because of its many benefits: Breath sampling is simple, noninvasive, inexpensive and well-tolerated by patients. It can be done at home by the patient or in the physician s office. 9,11 A breath test is highly sensitive and specific for lactose malabsorption. It is able to quantify incomplete absorption of even small amounts of lactose, leading to a more precise estimate as to the degree of malabsorption compared to other methods. This enables patients to moderate their diets and enjoy more foods. 5,6,12-15 The lower challenge dose of lactose causes significantly fewer side effects than the dose used in blood tests and does not require blood samples. 16 False positive results are rare and almost always due to improperly taking the test. 3,17 False negative results are fewer than with the blood test, typically only 5%. These results can be reduced by testing suspected false-negative patients with another disaccharide carried to the colon. 5,12,13,18 The breath hydrogen/methane test is the standard in pediatric cases where other tests would be difficult to perform. 3,

4 Lactase Deficiency - or other disaccharaidase deficiency Asthma Eczema Headaches Fatigue Joint Pain Lactase deficiency Impaired pancreatic function Decreased stomach activity Bacterial overgrowth Yeast overgrowth Parasite infection Dysbiosis Diarrhea Cramping Gas Bloating Enhanced autoimmune phenomena Food allergies Disaccharidase deficiencies Irritated mucosal epithelial cells Increased antigens into body Altered gut permeability Malabsorption of nutrients "Leaky Gut" Interpreting the results In the breath hydrogen/methane test, a patient fasts overnight and then collects a breath sample. The patient then ingests a challenge dose of lactose (up to a maximum of 25 gm) and collects breath samples at one, two and three-hour intervals. 17,23-25 Longer sample collection periods are optional. If the lactose is not broken down by the lactase enzyme in the small intestine, it travels to the colon and undergoes bacterial fermentation. Due to fermentation, hydrogen and/or methane levels in breath will rise within one to two hours. As little as 2 gm of carbohydrate reaching the colon will produce a detectable increase in breath hydrogen. 26 Testing for both breath hydrogen and methane provides a more comprehensive picture than testing for hydrogen alone since a minority of individuals harbor intestinal bacteria that convert hydrogen to methane. Using the total hydrogen and methane gas response increases the test s accuracy by reducing the number of false negative responses. Hydrogen and methane responses The normal breath hydrogen level in a healthy, fasting patient is less than 10 ppm. 26 Lactose malabsorbers will show an increase in breath hydrogen concentration of 20 ppm or more during the test period. 1,14,27 Lactose absorbers may show a small variation in breath hydrogen of a few ppm during the test period. The normal breath methane level in a fasting patient is 0-7 ppm. An increase of at least 12 ppm of methane alone during the test is considered positive for lactose malabsorption, regardless of the hydrogen response. 3,29,30 4

5 If both breath hydrogen and methane rise after a lactose challenge, the two responses are added to estimate the degree of malabsorption. An increase in methane will decrease the hydrogen response because methane is generated from the same substrate hydrolyzed by hydrogen-producing bacteria or produced by converting hydrogen to methane. When breath hydrogen and methane are summed, the test interpretation requires a rise of 20 ppm or more to suggest lactose malabsorption. 3 Rise of ppm: mild absorption Rise of ppm: moderate absorption Rise of 80+ ppm: severe malabsorption False positive results False positive results are infrequent compared to other types of lactose intolerance testing. The majority of false positives reported in the breath hydrogen/methane test can be eliminated if patients follow proper procedures and preparation instructions. Typical interferences include: Eating high-fiber foods prior to the test, which elevate fiber in the colon at the beginning of the test and increase hydrogen production. Fiber supplements should be discontinued 24 hours prior to the test. Smoking in the area of the test produces elevated hydrogen levels and unstable baseline results. Breath samples should not be collected where patients are exposed to tobacco smoke. Sleeping during the test increases both hydrogen and methane levels. False negative results Approximately 5% of patients tested for lactose intolerance with the breath hydrogen/ methane test produce a false negative result, compared to 8% to 12% if only hydrogen is measured. The majority of malabsorbers who do not produce hydrogen after ingesting lactose will generate methane instead. Therefore, the combined breath hydrogen/methane test identifies most malabsorbers. False negative results can be caused by the use of lactase supplements or antibiotics prior to the test;the use of laxatives or enemas, which decrease hydrogen and methane response in malabsorbers and reduce fermentation in the colon; 32 and severe diarrhea or hyperacidic colon contents. Hyperacidity inhibits the generation of hydrogen and causes generation of methane in addition to, or instead of, hydrogen by colonic bacteria. 33,34 To reduce false negative results, patients should wait at least one week after antibiotic treatment or recovery from severe diarrhea to reestablish colonic flora. Lactase enzyme supplements should be discontinued 24 hours prior to the test. Suspected false negative patients also can be tested with lactulose, another disaccharide carried to the colon and used to test for bacterial overgrowth. Lactulose determines whether patients produce hydrogen or do not react to lactose. A retest on another day with a 10 gm dose of lactulose as the challenge dose will produce positive breath hydrogen tests in patients capable of producing hydrogen High baseline levels Above 10 ppm: a baseline level of hydrogen above 10 ppm indicates the patient may have fasted improperly, eaten high-fiber foods the day before the breath test, or performed the test immediately after awakening. 3 Above 20 ppm: a baseline level above 20 ppm suggests patients have bacterial overgrowth of the small intestine. Levels typically rise during the first hour after lactose is ingested and fall to near-control levels during the test. Elevated methane levels are also seen with bacterial overgrowth. 3,38,39 5

6 Clinical therapeutics One advantage of the Lactose Intolerance Breath Test is its greater specificity, compared to other tests. By determining a patient s degree of malabsorption, physicians can tailor therapeutic recommendations more accurately, rather than removing all milk products from the diet. While the guidelines are somewhat subjective, patients may be able to limit their avoidance of dairy products, depending upon the severity of their malabsorption. For mild to moderate malabsorbers, it may be enough to limit the intake of dairy products at any one time to avoid symptoms drinking one glass of milk a day instead of two, for example. Studies also indicate milk is tolerated better if accompanied by food. 3 Decreasing the rate of gastric emptying by increasing the fat content and/or total caloric density of the lactose-containing meal may reduce symptoms drinking whole rather than skim milk, for example. 9 For severe malabsorbers, lactose-containing foods should be avoided, or lactase enyme preparations may be added to these foods to prevent symptoms. Such preparations often hydrolyze 70% to 99% of the lactose after 24 hours of refrigeration. 9,40,41 How do I order this test? For Lactose Intolerance Breath Test kits or information, please call a Client Services representative at or order online at Genova Diagnostics 6

7 References 1 Hamilton LH. Breath tests and gastroenterology. Milwaukee, Wis.: QuinTron Instruments Company, Keusch, Solomons. Nutritional consequences of bacterial overgrowth syndromes. Effects of microorganisms on GI tract Salemans JM, Nagengast FM, Jansen JBMJ. The c-xylose breath test in chronic pancreatitis:evidence for small intestinal bacterial overgrowth. Gastroenterol 1994;106(4):A Riordan SM, McIver CJ, Duncombe VM, Bolin TD. The association between small intestinal bacterial overgrowth and ageing. Gastroenterol 1994;106(4):A Toskes PP. Bacterial overgrowth of the gastrointestinal tract. Adv Int Med 1993;38: Bjorneklett A, Jenssen E. Relationships between hydrogen (H2) and methane (CH4) production in man. Scand J Gastroenterol 1982;17(8): Strocchi A, Furne J, Ellis C, Levitt MD. Methanogens outcompete sulphate reducing bacteria for H2 in the human colon. Gut 1994;35(8): Florin TH, Jabbar IA. A possible role for bile acid in the control of methanogenesis and the accumulation of hydrogen gas in the human colon. J Gastroenterol Hepatol1994;9: El Oufir L, Flourie B, Bruley des Varannes S, Barry JL, Cloarec D, Bornet F, Galmiche JP. Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans. Gut 1996;38(6): Le Marchand L, Wilkens LR, Harwood P, Cooney RV. Breath hydrogen and methane in populations at different risk for colon cancer. Int J Cancer 1993;55: Pique JM, Pallares M, Cuso E, Vilar-Bonet J, Gassull MA. Methane production and colon cancer. Gastroenterol 1984;87: Kajs TM, Fitzgerald JA, Buckner RY, Coyle GA, Stinson BS, Morel JG, Levitt MD. Influence of a methanogenic flora on the breath H2 and symptom response to ingestion of sorbitol or oat fiber. Am J Gastroenterol 1997;92(1): King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet 1998;352(9135): McKay LF, Eastwood MA, Brydon WG. Methane excretion in man a study of breath, flatus, and faeces. Gut 1985;26(1): Christl SU, Gibson GR, Cummings JH. Role of dietary sulphate in the regulation of methanogenesis in the human large intestine. Gut 1992;33(9): Christl SU, Sisner HD, Dusel G, Kasper H, Scheppach W. Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerative colitis. Dig Dis Sci 1996;41(12): Magee EA. Richardson CJ, Hughes, R, Cummings JH. Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans. Am J Clin Nutr 2000;72(6): Thompson DG, O Brien JD, Hardie JM. Influence of the oropharyngeal microflora on the measurement of exhaled breath hydrogen. Gastroenterol 1986;91: Rhodes JM, Middleton P, Jewell DP. The lactulose hydrogen breath test as a diagnostic test for small-bowel bacterial overgrowth. Scand J Gastroenterol 1979;14(3): Rhodes JM, Jewell DP. Lactulose hydrogen breath test in the diagnosis of bacterial overgrowth. Gastroenterol 1990;99(5): Lerch MM, Rieband HC, Feldberg W, Matern S. Concordance of indirect methods for the detection of lactose malabsorption in diabetic and nondiabetic subjects. Digestion 1991;48(2): Gilat T, Ben Hur H, Gelman-Malachi E, Terdiman R, Peled Y. Alterations of the colonic flora and their effect on the hydrogen breath test. Gut 1978;19(7): Solomons NW, Garcia R, Schneider R, Viteri FE, von Kaenel VA. H2 breath tests during diarrhea Acta Paediatr Scand 1979;68(2): Vogelsang H, Ferenci P, Frotz S, Meryn S, Gangl A. Acidic colonic microclimate--possible reason for false negative hydrogen breath tests. Gut 1988;29(1): Perman JA, Modler S, Olson AC. Role of ph in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J Clin Invest. 1981;67(3): Corazza GR, Ventrucci M, Strocchi A, Sorge M, Pranzo L, Pezzilli R, Gasbarrini G. Treatment of small intestine bacterial overgrowth with rifaximin, a non-absorbable rifamycin. J Int Med Res 1988;16(4): Gottschall E. Breaking the vicious cycle. Baltimore:Kirkton Press, Genova Diagnostics 7

8 63 Zillicoa Street Asheville, NC This information is for the sole use of a licensed health care practitioner and is for educational purposes only. It is not meant for use as diagnostic information. All claims submitted to Medicare/Medicaid for Genova Diagnostics laboratory services must be for tests that are medically necessary. Medically necessary is defined as a test or procedure that is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. Consequently, tests performed for screening purposes will not be reimbursed by the Medicare program. g,ag,lactose,