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Molecularly-defined lactose malabsorption, milk consumption and anthropometric differences in adult males.

BACKGROUND: Lactose malabsorption (LM) may be associated with reduced skeletal calcium content. Diagnosis to date has been based on indirect methods, with a high false-negative rate. Identification of the LCT polymorphism led to development of a PCR-based test. AIM: To evaluate the PCR-based test compared to a combination the hydrogen breath test and the lactose tolerance test, and investigate anthropometrical differences, changes in bone mineral density and oral calcium intake according to LCT polymorphism and milk-drinking habits. METHODS: All participants (n = 278) underwent clinical examination, with measurement of height, weight and bone density (DXA), and were genotyped for LCT polymorphism (LCT CC or LCT TT: CC is associated with LM). A subgroup (n = 51) had a hydrogen breath test and a lactose tolerance test, in addition to genotyping. RESULTS: Detection of LM by LCT polymorphism was highly significant (p = 0.001). The correlation between LCT genotype and self-reported milk-intolerance or dislike of milk with was slight, but the correlation with functional tests was highly significant. Non-milk-drinkers were lighter (-5 kg) and significantly shorter (-4 cm) than milk-drinkers (p = 0.07 and 0.04, respectively). Total calcium consumption was lower among non-milk-drinkers by about 18% (p = 0.03). DISCUSSION: Genotyping is an economic, quick and convenient method for diagnosing lactose malabsorption, with results comparable to existing tests. Sufficient calcium consumption may be relevant to body growth, as milk-drinkers were taller. Negative calcium bone balance may be prevented when provision is made for adequate calcium intake.

Adult↗

Correlation of lactase activity, lactose tolerance and milk consumption in different age groups.

Small intestinal lactase activity in the health adult is either the same as in early infancy or may drop to very low levels. The behavior of the enzymatic state varies with the ethnic group studied. In those adults with low lactase activity little information is availalbe as to the age at which the lactase decreases. We attempted to determine a) the frequency of low intestinal lactase activity and b) the age at which the change occurs. For this purpose we reviewed in a large number of intestinal biopsies both histologically as well as for disaccharidase activities. The biopsies were obtained from a heterogeneous group of Caucasians, including patients, their siblings and parents. The patients were those with failure to thrive in whom no organic cause could be elicited, and those with the irritable colon syndrome. Patients ranged in age from 6 weeks to 50 years and out of a total of 1, 077 jejunal biopsies, 172 morphologically normal biopsies were selected. The milk drinking habits of 118 subjects and their families were elicited and 31 oral lactose tolerance tests performed. The mucosal lactase activity and sucrase-to-lactase ratio in those 172 individuals were plotted against age. In the first 3 years the mean lactase activity was 32.1 plus or minus 10.1 mumoles/g protein per min and the sucrase-to-lactase ratio was 1.7 plus or minus 0.5 with no change from year to year. However, after age 5 two separate groups emerge. A small group (24.6% of the population) with low lactase activity, and a second group possessing the same mean value for lactase activity as noted in the first 3 years. The low lactase activity group included children and adults with clinical lactose intolerance. These individuals consumed relatively small amounts of milk and when 12 of them were tested with an oral lactose tolerance test the result was a "flat" curve with a maximum rise in blood glucose of 9 plus or minus 3.2 mg/100 ml. The second group consumed more milk averaging 1 quart/day with no discomfort and when 19 were tested with oral lactose tolerance tests the values were normal. This study indicates that low lactase activity in the Caucasian population may make its appearance at the age of 5 years.

Adolescent↗

A boy with severe infantile gastrogen lactose intolerance and acquired lactase deficiency.

A 10-year-old boy with severe familial lactose intolerance in infancy (vomiting, failure to thrive, lactosuria (5.25 g/l), sucrosuria (12 g/l), and aminoaciduria. Intestinal disaccharidases (including lactase and sucrase) normal at age 6 and 20 weeks. Oral lactose tolerance test at this age resulted in lactosuria (4.6 g/l); sucrose tolerance test, in sucrosuria (18.5 g/l). In contrast, intraduodenal lactose tolerance test gave only low lactose excretion in urine (0.28 g/l). He improved rapidly and had no lactosuria on intraduodenal feeding with citric acid milk. The lactosuria diminished as age increased, but was still higher at age 6 years than that of controls. He tolerated normal disaccharide containing food after 1.5 years of age. At 5.5 to 6 years, he had symptoms of lactose malabsorption, and an isolated lactase deficiency was proved. At 10 years, he still tolerates only limited amounts of milk. The defect in severe familial infantile lactose intolerance seems to be localized in the gastric mucosa. Acquired lactase deficiency can appear later in childhood in this syndrome.

Amino Acids↗

[Chronic diarrhea--value of function tests in diagnosis].

The D-xylose-adsorption test yields information about small intestinal absorptive function. To investigate ileal absorptive function the Schilling test is performed. The standard diagnostic test for hypolactasia is the oral lactose tolerance test with lactose breath hydrogen testing. Various radioactive and nonradioactive breath tests have been proposed as noninvasive tests for small intestinal bacterial overgrowth. Intubation tests for pancreatic function testing are time-honored and direct, but limited by several technical difficulties. Measurement of pancreatic enzymes in stool has received a high degree of acceptance.

Breath Tests↗

Recurrent abdominal pain in children: lactose and sucrose intolerance, a prospective study.

Thirty-eight consecutive children with recurrent abdominal pain underwent lactose tolerance tests; 28 of these were also given sucrose tolerance tests. Abdominal pain and abnormal lactose tolerance tests were noted in 11 of 38, while none of the 28 had an abnormal sucrose tolerance test; however, 1 had abdominal pain. Elimination diet for 4 weeks produced significant or total pain relief in 10 of 11 (lactose free) and 0 of 1 children (sucrose free). Lactose intolerance seems to play a contributory role in recurrent abdominal pain in children, while sucrose intolerance does not.

Abdomen↗

[The application of a combined Xylose-lactose tolerance-test in children with suspected malabsorption (author's transl)].

A combined xylose-lactose tolerance-test and a duodenal biopsy were performed in 68 children with suspected malabsorption-syndrome. The purpose of the present work was to assess the diagnostic value of xylose concentrations in blood at different times and to determine the additional discriminatory value to glucose levels. The contribution of the glucose rise to a calculated discriminant function is statistically significant but practically negligible and therefore does not justify its determination. A small-bowel biopsy is recommended if the concentration of xylose after 60 min is less than 26 mg/100 ml or the increment of xylose concentration above fasting level is 18 mg/100 ml or less.

Biopsy↗

Lactase deficiency--a comparative study of diagnostic methods.

The diagnostic value of 1-14C-lactose breath test was compared with the standard lactose tolerance test and lactase assay in jejunal biopsies in 16 control subjects, 14 patients with lactase deficiency (LD) proven by lactase assay and 20 patients with irritable bowel syndrome (IBS). 14CO2 specific activity in the 2-hr breath collection after administration of 1-14C-lactose (5 muCi) provided a satisfactory separation between the control and LD group. Values were 7.0 +/- 2.0% dose administered/mmoles 14CO2 X 10(-3) (mean +/- SD) in the control group versus 2.1 +/- 1.5 in LD (P less than 0.001) versus 4.9 +/- 2.3 in IBS (P less than 0.01). 1-14C-lactose breath test was superior to standard lactose tolerance test in specificity (P less than 0.05) and provided a satisfactory correlation between 14C-lactose absorption and lactase assay (r = 0.77). The prevalence of LD in IBS was 40% by the breath test and 35% by lactase assay, suggesting that lactose malabsorption may play a role in the symptoms in the population of some patients with IBS. It appears that 1-14C-lactose breath test is a sensitive, specific and accurate method for the diagnosis of LD in clinical practice and suitable for large scale epidemiological surveys.

Breath Tests↗

Relative lactose intolerance. A clinical study of tube-fed patients.

A relative intolerance of lactose was demonstrated in 14 of 16 patients receiving nasogastric tube feedings following surgery for head or neck carcinoma. Two liquid diets differing only in the presence or absence of lactose, were administered for eight to 20 days per patient in a double-blind crossover study. Increased stool frequency, decreased stool consistency, and more frequent flatulence, borborygmi, and distention were found with the lactose diet, although classic lactose intolerance (plasma glucose rise of less than 26 mg/dl) was indicated in only two patients. Differences between amounts and times of peak rise following the glucose tolerance test and lactose tolerance test for each patient indicated the advisability of locating patients on a continuum of ability to hydrolyze lactose. The results indicate that lactose should be reduced or eliminated from tube-feeding diets to improve patient tolerance and comfort and to reduce diarrhea.

Aged↗

Adequacy of endoscopic biopsy specimens for disaccharidase assays.

Intestinal mucosa from 40 patients obtained by fiber-endoscopic biopsy was assayed for disaccharidases to determine suitability of this tissue for assay. The combined specimens from each patient provided 4.7-38.7 mg of tissue, adequate in all instances for duplicate determinations of protein, lactase, sucrase, and maltase. Tissue remained for assays of palatinase in 39 instances, trehalase and cellobiase in 37, and alkaline phosphatase in 22 cases. Twenty-four subjects had normal lactose tolerance tests and normal sucrase/lactase ratios. Thirteen patients with abnormal oral lactose tolerance tests were identified as having a primary low lactase activity on the basis of elevated sucrase/lactase ratios. This ratio was most helpful in making the diagnosis of a primary low lactase, since the mucosal specimens were not obtained from comparable areas. Tissue from three subjects with an abnormally low maltase was unsuitable for diagnosis. Endoscopic biopsy of mucosa appears to be satisfactory for disaccharidase assays in most instances.

Adult↗

[Diagnostics of lactose-malabsorption: value of tolerance tests and 14CO2 exhalation test in patients with and without lactase deficiency (author's transl)].

Lactose-tolerance-test (LTT), ethanol-lactose-tolerance-test (ELTT), 14CO2 breath test and 14C-glucose determination were simultaneously performed in 27 healthy subjects, 16 patients with a Billroth II gastrectomy and 6 patients with a malabsorption syndrome. Intestinal mucosal lactase was absent or significant diminished in 5 of the B II cases and in all patients with malabsorption. In the lactase deficient patients a diminished serum glucose rise after ingestion of 50 g lactose was observed in LTT as well as in ELTT. False positive results in LTT could not be prevented by performing the ELTT. Furthermore the ELTT is not suitable for ambulant investigations because of the required high ethanol load of 0.5 g/kg. Most reliable results were obtained by determination of 14C-serum-glucose after oral application of about 15 muCi of 14C lactose. In respect to lactase level neither false positive nor false negative results were observed. For clinical investigations the procedure of isolation and measurement of 14C-glucose is too laborious however. 14CO2-exhalation test cannot be recommended because of many false positive and false negative results. Moreover 14CO2-exhalation seemed to be insensible and predominant depending on factors other than lactose absorption.

Blood Glucose↗

The strip test for hypolactasia also works without ethanol.

Detection of urinary galactose with a special test strip has been shown to work well with the lactose tolerance test with ethanol. In this study the strips were used in combination with a lactose load alone or with another alcohol, beta-pyridylcarbinol, and the results were compared with those of the urinary lactose tolerance test with ethanol (ULTTE) as the reference method. Sixty-nine patients were studied. With lactose alone the specificity was 83%, the sensitivity 88%, and the kappa coefficient 0.61. It is concluded that the strip test for hypolactasia works without ethanol with sufficient reliability for the daily clinical work of a general practitioner. Adding beta-pyridylcarbinol to the test does not markedly increase the validity of the test.

Adult↗

Dysfunction of the continent ileostomy: clinical features and bacteriology.

The pathogenesis and treatment of dysfunction of the continent ileostomy was investigated in 12 patients, five of whom had asymptomatic malabsorption and seven of whom had acute complaints. The number of anaerobic bacteria in jejunal aspirates was increased in patients with pouch malfunction (range 10(3) to 10(8)/g aspirate), but the microbiology of ileal effluent and the morphology of the ileal mucosa could not be correlated with dysfunction. Bile acid breath tests and lactose tolerance tests were not, however, reliable indicators of jejunal bacterial overgrowth. The symptoms, the malabsorption, and the number of jejunal and ileal anaerobic bacteria decreased in patients during treatment with metronidazole, implicating overgrowth of anaerobic bacterial flora in the pathogenesis of the syndrome.

Adolescent↗

Effect of an episode of severe malnutrition and age on lactose absorption by recovered infants and children.

The degree of which the ability to absorb lactose can be regained after recovery from an acute episode of severe malnutrition is in doubt. Lactase activity was indirectly assessed by means of a standard lactose tolerance test (2 g lactose per kilogram of body weight) in 71 Peruvian Mestizo infants and children (age 5 to 55 months) who had suffered such an episode. All were studied just before discharge after several months of hospital rehabilitation, during which linear growth and weight gain had accelerated and signs of significant malabsorption of other nutrients had disappeared. Only 39% of the total group had a positive test (delta blood glucose greater than 25 mg/dl); there was a decreasing proportion of positive responders with increasing age. No difference in response attributable to type or severity of malnutrition was found. Comparison of the present data with previous data from children in the same community who had never been acutely malnourished suggests that acute malnutrition may hasten the permanent decline of lactase activity normally expected later in life.

Acute Disease↗

The effect of lactose maldigestion on the stools of young Tswana children.

During diarrhoeal disease, stool mass is usually increased. Lactose content of stools and stool pH have been used as tests for secondary lactose maldigestion. The effect of a lactose-free diet and various lactose loads on the stools of 30 children with primary adult-type lactose maldigestion was investigated. Stool mass following the lactose tolerance test was the largest (mean = 80 g/day); that following the milk tolerance test less--62 g (not significantly), that on a milk containing diet significantly less (35 g), while stool mass produced on a lactose-free diet (22 g) was significantly less than that produced on any of the three lactose-containing diets. The stool pH on a milk containing diet (mean = 6.3) was significantly higher than those of the three other diets (after lactose tolerance test, pH = 5.85; after milk tolerance test, pH = 5.86; after lactose-free diet, pH = 5.83). Although stool bulk was greater when these lactose maldigesters were consuming a lactose containing diet, it was still considerably less than the stool mass associated with secondary lactose maldigestion, which is believed to be a cause of diarrhoeal disease. In contrast, the primary adult-type of lactose maldigestion does not commonly cause diarrhoea, as shown in this study.

Africa↗

Antimicrobial alternatives for calf diarrhea: enteric responses to Escherichia coli, deferoxamine, or gallium in neonatal calves.

Intestinal malabsorption or transferable resistance in enteric bacteria are potentially serious complications of routine oral administrations of antibiotics. On the basis of reports on antimicrobial effects of host iron sequestration and on synthetic iron chelators or competitors in vitro, 2 iron antagonists were studied for their potential as alternative antimicrobials for Escherichia coli diarrhea. Deferoxamine, a fungal iron chelator used to treat acute iron intoxication, and elemental gallium, a competitive inhibitor of iron activity in metabolic enzyme systems, were examined for their effects on enteric morphology and function in neonatal calves. Twelve male calves were allotted to 4 groups: (1) given nonpathogenic E coli (control); (2) given enterotoxigenic B44 E coli; (3) given deferoxamine (50 mg/kg, twice a day); and (4) given gallium (4 mg/kg, twice a day). Calves were studied for 8 days, including the conduct of oral glucose and lactose tolerance tests on days 1, 3, and 7. By day 7, according to oral glucose and lactose tolerance tests, peak plasma glucose concentrations in all calves of groups 2, 3, and 4 were lower than those values in controls. The frequency of diarrhea was significant in all treated calves, and disease was most severe in the deferoxamine-treated calves. Quantitative cultural examination on day 8 showed significant numerical increases of jejunal and ileal E coli and ileal lactobacilli in deferoxamine-treated calves (group 3) and of ileal streptococci in gallium-treated calves (group 4) and showed jejunal and ileal overgrowths of Saccharomyces yeast in deferoxamine-treated calves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recurrent abdominal pain and lactose absorption in children.

The association of lactase deficiency with recurrent abdominal pain was investigated. One hundred three white children between the ages of 6 to 14 years with recurrent abdominal pain were evaluated. Sixty-nine underwent lactose tolerance tests and 26 had intestinal biopsies with lactase determinations; 21 of 69 (30.4%) had abnormal lactose tolerance tests and eight of 26 (31%) were lactase deficient. However, 16 of 61 (26.4%) control subjects matched for age and ethnic background exhibited lactase deficiency. Thus, a similar prevalence of lactase deficiency was found in the control and the recurrent abdominal pain groups. Thirty-eight patients with recurrent abdominal pain completed three successive six-week diet trials conducted in a double-blind fashion. An increase above base line value in pain frequency was seen in ten of 21 (48%) lactose malabsorbers and four of 17 (24%) lactose absorbers. After a 12-month milk elimination diet, six of 15 (40%) malabsorbers and five of 13 (38%) absorbers had elimination of their pain. This result compared with improvement occurring in five of 12 (42%) absorbers with recurrent abdominal pain who received a regular diet for one year and suggests that the elimination of lactose will not affect the overall frequency of improvement in recurrent abdominal pain. In addition, the recovery rate from recurrent abdominal pain is similar in both lactose absorbers and nonabsorbers independent of dietary restrictions.

Abdomen↗

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.

Adolescent↗