Lactose malabsorption

Opinion statement Lactose malabsorption is a syndrome producing constellation of symptoms, including abdominal pain, bloating, flatulence, diarrhea, and sometimes nausea and/or vomiting. Primary causes of lactose malabsorption due to loss of intestinal lactase activity include genetic/racial lactase nonpersistence, congenital lactase deficiency, and developmental lactase deficiency. Secondary lactose malabsorption can be caused by any disorder that injures the small intestinal mucosa, such as viral gastroenteritis, celiac disease, allergic (eosinophilic) gastroenteritis, and radiation enteritis. The diagnosis depends on careful clinical evaluation and is customarily confirmed with a lactose breath hydrogen test. As the symptoms are nonspecific, many adults diagnosed with lactose malabsorption actually have irritable bowel syndrome. Treatment consists of a trial of eliminating lactose-containing dairy foods, with supplementation of alternative calcium and protein sources. Commercial enzyme products containing β-galactosidases can be prescribed to help patients digest dietary lactose. Long-term lactose restriction usually is not necessary and can lead to reduced bone mineral density.     

Lactose malabsorption and intolerance: What should be the best clinical management?

Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a wellknown cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake. Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.     

Incidence and Clinical Significance of Lactose Malabsorption in Adult Coeliac Disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day—statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Incidence and clinical significance of lactose malabsorption in adult coeliac disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day--statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Possible therapeutic use of loperamide for symptoms of lactose intolerance.

OBJECTIVES: To examine a potential practical therapeutic use of loperamide (Lo) to decrease the symptoms of lactose intolerance. SUBJECTS AND METHODS: Nineteen (eight men, 11 women) healthy lactose maldigesters (18 of 19 with symptoms) underwent a 25 g lactose challenge on five separate days. Breath hydrogen was measured, areas under the curve (AUC) were calculated for 4 h, and 4 and 12 h symptom scores were recorded. After establishing baseline measurements, test doses of 4 mg, 8 mg and 12 mg Lo were randomly administered without placebo in a double-blind manner. As well, each subject received seven lactase tablets, in a random, unblinded manner. RESULTS: The median AUC and mean oral cecal transit time followed dose response expectations; however, only lactase treatment achieved significance. Nevertheless, 8 mg Lo significantly improved symptom scores, which were statistically indistinguishable from those of lactase. Four subjects complained of delayed constipation and cramps with various doses of Lo. CONCLUSIONS: Lo monotherapy for lactose intolerance is not economical and may have some side effects. However, Lo may be studied further as an adjunctive treatment of lactose intolerance in an effort to reduce the need for complete lactose digestion. Such a manoeuvre may allow rapid colonic adaptation, which in turn may be beneficial for prophylaxis for a number of colonic diseases.     

More evidence for the recessive inheritance of selective adult type lactose malabsorption

Selective adult type lactose malabsorption appears in childhood or adolescence because of the great decline in jejunal lactase activity. There is strong evidence that this is a genetically determined disorder. Specifically, selective adult type lactose malabsorptions seem to be inherited by a single autosomal recessive gene. In the present prospective study the transition from the state of lactose absorption to that of lactose malabsorption was documented for the first time in two Finnish boys who were at risk for selective adult type lactose malabsorption because the parents of both boys had the disorder. At the age of 14 and 9 years, respectively, the boys had normal lactose absorption. Three years and 7 months and 4 years and 5 months later, respectively, the boys were shown to have lactose malabsorption. The period of documented transition averaged less than 4 years. These manifestations clearly strengthen the genetic model proposed.     

A geographic approach to senile cataracts

Examined in this article is presently available evidence for the hypothesis that some types of senile cataracts may be brought on by decades-long consumption of milk and milk products. The author approaches the question from a background of research in the geography and history of dairying as these relate to present-day differences among the world's peoples in prevalence of primary adult lactose malabsorption, which is based on a deficiency of the enzyme lactase in adulthood. Among peoples who have consumed milk in lactose-rich forms over a long historical period, there seems to have been a mutation for persistence of high lactase activity throughout life (PHLA), which distinguishes them from human populations of nonmilking tradition and from most land mammals. PHLA permits greater intestinal hydrolysis of lactose and absorption of galactose by adults. The mutation for PHLA, however, was not accompanied by a second one raising galactokinase activity to high levels through life. The result may be that adults who consume large quantities of milk, who have high lactase activity, lactose hydrolysis, and galactose absorption, suffer repeated small galactose challenges, accumulation of galactitol in the lens, and a greater likelihood of developing senile cataracts.     

Genetic test for lactase non-persistence and hydrogen breath test: Is genotype better than phenotype to diagnose lactose malabsorption?

BackgroundAdult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. The lactose breath test is a simple tool for diagnosis but the need for prolonged monitoring of hydrogen excretion has led to a genetic test proposal. The aim of this study was to compare the genetic test with the lactose breath test in order to give some insights into the clinical value of genetic testing.MethodsThirty-two consecutive functional patients underwent lactose breath test and lactase genetic polymorphism analysis (C/T 13910 and G/A 22018). Intolerance symptoms after lactose load were also monitored.ResultsAll patients with positive lactose breath test showed homozygosis for both polymorphisms. Among the nine patients with a negative breath test result, six showed heterozygosis while three showed homozygosis. Intolerance symptoms were present in 16 homozygotic patients but also in one heterozygotic patient. The k value for the agreement between the genetic test and the lactose breath test was 0.74.ConclusionA positive genetic test for lactase non-persistence indicates whether lactase activity decline may represent a clinical problem for the patient, but does not give information on actual patient symptoms. On the contrary, this information is already available by combining the lactose breath test with intolerance symptom evaluation. Lactose absorption phenotype may be not yet evident until young adult age.     

Lactase deficiency and lactose malabsorption. A review

The results of previous investigations of lactase deficiency and lactose malabsorption are reviewed. It showed that lactase activity and its decline in animals and humans is controlled genetically, but also that its phenotypic expression as lactose malabsorption is influenced by nongenetic factors: adaptation, biological (circadian) rhythmicity, hormones, gastrointestinal functions, and nutritional components can alter the response to lactose intake.     

Assessment of lactose absorption by measurement of urinary galactose

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.     

Lactose malabsorption in adult patients at the Hospital das Clínicas de Ribeir?o Preto

A standard oral lactose tolerance test (LTT) was performed in 32 white and 18 non-white hospitalized Brazilian adults. A flat LTT was found in 22 (68,75%) white and in 17 (97,45%) non-white patients indicating a 78% overall rate of lactose malabsorption, Both lactose absorbers and malabsorbers showed a modal milk ingestion of less than a 1 glass/day. Symptoms related to milk consumption or lactose administration were more common among lactose malabsorbers. Estimations of disaccharidase activity in intestinal mucosa specimens obtained by peroral biopsy in 28 patients confirmed a high prevalence of lactose deficiency, and disclosed only one false result, in the patient with a flat LTT and high intestinal lactase levels.     

Lactose malabsorption in adult patients with Crohn's disease

In order to evaluate, in adult patients with Crohn's disease (CD), the prevalence of lactose malabsorption and intolerance, and the percentage who can tolerate a physiologic amount of milk in their diet, we tested 37 patients with CD (19 with intestinal resection, and 18 without) and 67 healthy controls (C) with the H2-breath test after they had ingested increasing loads of lactose as 10% solution (12.5 g, 25 g, and 50 g). Patients with malabsorption after the 12.5-g dose were tested further with 250 ml of milk. In the total group of patients and in the subgroup of those with resection, the prevalence of malabsorption was higher than in controls at all lactose loads; in patients who had not undergone resection, no significant difference was observed with the 12.5-g dose. Eleven of 18 patients who were malabsorbers with the 12.5-g dose had malabsorption also with 250 ml milk; however, only three of them (8% of the total group) experienced symptoms of intolerance. We conclude that, in adult patients with CD, 1) the prevalence of lactose malabsorption is increased, 2) in patients who have undergone intestinal resection, malabsorption occurs at a lower dose of the sugar than in patients who did not, and 3) since only 8% of patients experienced symptoms of intolerance after the ingestion of milk 250 ml, this amount can be empirically inserted in the daily diet of an adult with CD.     

Redefining lactose as a conditional prebiotic.

Lactose in dairy products is maldigested by up to 70% to 75% of the world's population and many people may therefore suffer symptoms reminiscent of irritable bowel syndrome. As a result, most research to date has concentrated on ways of improving lactose tolerance to enhance dairy as a source of nutrition. However, research on other possible benefits of lactose and its maldigestion has lagged. In view of an exponential growth in the understanding of intestinal microfloral host interactions and the expanding therapeutical potential of probiotics, a reassessment of the role of lactose as a potential prebiotic in lactase nonpersistent subjects is required. Gibson and Roberfroid introduced the concept of prebiotics and outlined definitive requirements for such a compound. The present article examines scientific and clinical knowledge about the properties of lactose and argues that in lactase nonpersistent subjects, lactose qualifies as a prebiotic.     

Double blind study of milk lactose intolerance.

One hundred and fifty subjects were studied in a double blind fashion to determine the relationship between lactose malabsorption and milk lactose intolerance. Each participant received 250 ml of a different type of milk on 3 consecutive days. Milk A contained no lactose, milk B had 12.5 g, and milk C contained 37.5 g of lactose. After the experiment was completed each subject was classified with a lactose tolerance test as having "sufficient" or "insufficient" lactase activity. Milk A produced no gastrointestinal symptoms in either sufficient or in insufficient persons. Milk B produced symptoms in 3.8% of sufficient and 37.1% of insufficient individuals, and Milk C induced symptoms in 7.6% of sufficient and 83.5% of insufficient subjects. These differences are very highly significant (P less than 0.0001). It is concluded that lactose-intolerant subjects are indeed milk-intolerant and that the frequency with which symptoms occur in persons with lactose malabsorption increases in direct relation to the lactose content of the milk.     

Lactose Malabsorption Is Associated with Early Signs of Mental Depression in Females (A Preliminary Report)

Lactose malabsorption is characterized by adeficiency of mucosal lactase. As a consequence, lactosereaches the colon where it is broken down by bacteria toshort-chain fatty acids, CO₂, andH₂. Bloating, cramps, osmotic diarrhea, and other symptoms ofirritable bowel syndrome are the consequence and can beseen in about 50% of lactose malabsorbers. Having madethe observation that females with lactose malabsorption not only showed signs of irritable bowelsyndrome but also signs of premenstrual syndrome andmental depression, it was of interest to establishwhether a statistical correlation existed betweenlactose malabsorption and mental depression. Thirtyfemale volunteers were analyzed by measuring breathH₂ concentrations after an oral dose of 50 glactose and were classified as normals or lactosemalabsorbers according to their breath H₂concentrations. All patients filled out a Beck'sdepression inventory questionnaire. Of the 30 femalevolunteers, six were lactose intolerant (20%) and 24were normal lactose absorbers (80%). Subjects with lactosemalabsorption showed a significantly higher score in theBeck's depression inventory than normal lactoseabsorbers did. The data thus suggest that lactosemalabsorption may play a role in the development of mentaldepression. In lactose malabsorption high intestinallactose concentrations may interfere with L-tryptophanmetabolism and 5-hydroxytryptamine (serotonin)availability. Lactose malabsorption should be considered inpatients with signs of mental depression.     

Efficacy of Addition of Exogenous Lactase to Milk in Adult Lactase Deficiency

The efficacy of lactase by Kluyveromyces lactis in hydrolyzing milk lactose and reducing milk intolerance symptoms was tested in 52 proved lactose malabsorbers. The enzyme was added to milk administered to the patients, and H2 breath excretion (as an index of carbohydrate malabsorption), was determined by gas chromatograph technique, and milk intolerance symptoms were recorded. H2 mean excretion was 78.3 +/- 5.49 ppm after administration of intact whole milk 500 ml (test A), 43.5 +/- 4.99 ppm when lactase 2000 U was added to milk 500 ml immediately before administration (test B); 36.7 +/- 5.01 ppm when milk 500 ml was incubated for 12 h with lactase 1000 U (test C), and 29.7 +/- 4.35 ppm when the incubation was prolonged for 24 h (test D). Symptoms score was: test A = 5.85 +/- 0.56, test B = 3.71 +/- 0.45, test C = 2.77 +/- 0.63, test D = 1.7 +/- 0.68. A correlation index of r = 0.44 (p less than 0.01) was obtained between reduction in H2 mean excretion and reduction in symptoms score of a single individual. The addition of this lactase to milk seems to be effective in correcting lactose malabsorption, thus representing a convenient approach in milk intolerance.     

Incidence and clinical significance of lactose malabsorption in ulcerative colitis and Crohn's disease

The incidence of lactose malabsorption was investigated in 85 patients with ulcerative colitis and 71 patients with Crohn's disease by means of lactose tolerance tests and disaccharidase determinations in small intestinal mucosa. Eight patients with ulcerative colitis (9%) and four with Crohn's disease (6%) had lactose malabsorption. A control group displayed a similar incidence. It is concluded that lactose malabsorption is not particularly common in ulcerative colitis and Crohn's disease. If it is present, its aetiology seems to be unrelated to the intestinal disease.Transitional lactose malabsorption was detected in two cases during a relapse of ulcerative colitis.Institution of a lactose-free (or lactose-poor) diet was an important supporting measure in seven patients who were unaware of their milk intolerance, in particular in two with ileostomy. Therefore, it is recommended that a lactose tolerance test should always be performed in patients with ulcerative colitis or Crohn's disease.Twenty-one patients with ulcerative colitis and nine with Crohn's disease, none of whom had lactose malabsorption, were placed on milk-free diets. A beneficial effect was noticed in five of the patients with ulcerative colitis, and in three of those with Crohn's disease. The mechanism is unknown.Evidence is presented that milk allergy is not responsible for the beneficial effect of a lactosefree diet in patients with associated lactose malabsorption.     

Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance

BACKGROUND: The relationship between lactose malabsorption, irritable bowel syndrome and development of intestinal symptoms is unclear, especially when the ingested dose of milk is small. Thus, the role of hydrogen breath testing in the diagnostic work-up of patients with nonspecific intestinal symptoms is still debated. AIMS: To establish the relationship between lactose malabsorption, severe self-reported milk intolerance, irritable bowel syndrome and related symptoms. METHODS: The prevalence of lactose malabsorption was prospectively assessed by means of a hydrogen breath test in 839 patients (503 with irritable bowel syndrome, based on the Rome criteria, regularly consuming milk, and 336 subjects who identified themself as milk intolerant, after an oral load of 25 g lactose). The test was considered "positive" when a hydrogen peak exceeding 20 ppm over baseline values was observed in two or more samples. Attempts were also made to establish whether the predominant presenting symptom (diarrhoea, constipation, alternating diarrhoea and constipation, pain and gaseousness) might be helpful in predicting the outcome of the breath test. RESULTS: The prevalence of a positive breath test was comparable in the two groups (337 patients with irritable bowel syndrome (66.9%) vs 240 patients with milk intolerance (71.4%)). The same holds true for the first peak of hydrogen excretion, total hydrogen output and prevalence of symptoms during, and in the four hours after, the test. The predominant presenting symptom was not useful for predicting outcome of the test either in regular milk users or in milk intolerant subjects. CONCLUSIONS: The almost identical results of the lactose breath test of patients with irritable bowel syndrome and subjects with self-reported milk intolerance suggests that the two conditions overlap to such an extent that the clinical approach should be the same. A lactose breath test should always be included in the diagnostic work-up for irritable bowel syndrome, as fermentation of malabsorbed lactose is likely responsible for triggering symptoms. Conversely, lactase deficiency is probably irrelevant in most subjects not affected by irritable bowel syndrome, within a moderate milk consumption.     

Intestinal lactase deficiency in an apparently normal Peruvian population

The prevalence of milk and lactose intolerance and intestinal lactase deficiency was studied in 30 apparently healthy Peruvian individuals. At the same time, 20 milk-intolerant persons were included in the study. According to the results of lactose-tolerance tests and intestinal lactase assays, one-third of the 30 were considered normal and were used as controls. The other two-thirds were found to be abnormal and were referred to asasymptomatics; they tolerated well small amounts of milk consumed daily. Upon lactose load, they developed gastro-intestinal symptoms, and maximal rise of blood glucose was below normal limits. Enzymatic assay indicated that they were deficient in intestinal lactase. The remaining 20 were intolerant to milk and the results of their tests were abnormal. Sucrase activity was similar in the 3 groups. This high incidence of lactase deficiency in apparently normal individuals seems to be acquired.     

Evaluation of a new DNA test compared with the lactose hydrogen breath test for the diagnosis of lactase non-persistence

BACKGROUND AND AIMS: Recent publications have found that the CC genotype of the DNA variant -13910 T/C upstream of the LCT gene is associated with lactase non-persistence. We therefore compared the value of DNA testing for this variant (DNA test) with the lactose hydrogen breath test (H2 test), which is the clinical standard for the diagnosis of lactase non-persistence. PATIENTS AND METHODS: One hundred and twenty-three consecutive patients with suspected lactose malabsorption were tested for the presence of the -13910 T/C variant by polymerase chain reaction-restriction fragment length polymorphism analysis. These patients also underwent the H2 test after ingestion of 50 g lactose. RESULTS: Thirty-seven subjects had a CC genotype of the -13910 T>C polymorphism suggesting lactase non-persistence; 36 (97%) had also a positive H2 test. Eighty-six subjects had either a TC or a TT genotype suggestive of lactase persistence. Seventy-four (86%) of these tested negative on the H2 test, while 12 patients had a positive H2 test. In eight of these 12 patients duodenal biopsies showed no evidence of small bowel disease. One patient carrying a CC genotype had a negative H2 test. In this patient the rise in serum glucose after oral lactose was normal, furthermore H2 non-excretion was also excluded. CONCLUSIONS: An excellent correlation is observed between a CC genotype and a positive H2 test, whereas the correlation between a TC or TT genotype and a negative H2 test result is less strong. Analysis of the -13910 T/C variant can be considered a good test for predicting the presence of lactase non-persistence in a patient population with suspected lactose malabsorption.