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Efficacy testing of beta-galactosidase with H2 breath test in patients with carbohydrate malabsorption.

The clinical efficacy and the potential side-effects of beta-galactosidase were studied in adult lactose intolerance. Various randomized oral tolerance tests were performed using lactose solution (35 g), glucose + galactose solution (17.5 + 17.5 g), native, skimmed milk and milk pretreated with beta-galactosidase. In each case, simultaneous examinations were made of the glucose concentration of capillary blood by an instrument constructed by the authors, of the H2 content of expired air as also of the subjective complaints and of the number of stools and their pH. It was established that pretreatment of milk with beta-galactosidase has a beneficial effect in adult lactose maldigestion, since it stops dyspeptic complaints and diarrhoea due to milk, it reduces the H2 content of expired air increases blood glucose concentration. Measuring the H2 content of the breath by using and instrument constructed by the authors, exact data can be obtained noninvasively, and rapidly on the degree of carbohydrate malabsorption in patients with lactose-intolerance.

Adult↗

[Lactase deficiency in the intestinal mucosa. Demonstration by hydrogen detection in the expired air after lactose loading (author's transl)].

Lactose malabsorption can be demonstrated by detecting hydrogen (H2) in the expired air after oral loading with lactose. A comparative study was carried out on 24 subjects. Following an oral loading dose of lactose, the H2 eliminated during expiration was assayed by gas chromatography, and blood galactose levels were measured. The results showed that the test was reliable, well tolerated and reproductible. However, the method does not measure the amounts of lactase present in the intestinal mucosa. The lactose loading test seems to be valuable for studies on lactose and carbohydrate malabsorption.

Adult↗

Lactose malabsorption. Optimalization of investigational methods.

Although the prevalence of lactose malabsorption is high and the importance of this diagnosis is established in gastroenterological practice, still a variety of poorly standardized tests is used to investigate the ability of the small bowel to digest lactose. In this report the various most commonly used lactose malabsorption tests are described and compared with each other knowing that a 'gold standard' does not exist. The hydrogen breath test is the test most used in clinical practice. On the basis of recent investigations the recommendation is made to improve the accuracy of this test by prolonging it to 4 hours and by simultaneous measuring of the oro-coecal transit time.

Blood Glucose↗

[Lactose malabsorption diagnosis with H2 breath test].

One hundred and five healthy subjects under investigation for lactose malabsorption were enrolled in this prospective study. After an overnight fast, breath was collected immediately before and every 15 minutes for three hours after an oral administration of 50 g lactose dissolved in 200 mL of water (lactose overload). Blood samples were also collected before and 20, 40 and 60 minutes after the lactose overload for blood glucose determination. Expired H2 was measured by gas chromatography using a Quintron Microlyser and the maximum increase in H2 (delta-H2) was calculated. The area under the curve (ASC-H2) was also calculated using the trapezoid model. Lactose malabsorption was defined as a maximum increase in blood glucose (delta-G) under 18 mg%. The sensibility (S), specificity (E) and accuracy (A) of the H2 determination was analyzed using (a) linear regression [log (ASC-H2) = 4.034-0.029. delta-G], (b) receiver operating curve (ROC) and by (c) Q-Q plot of the cubit root transformation of the ASC-H2 values. Our results demonstrate that ASC-H2, but not delta-H2, correlates with delta-G, suggesting that the measurement of maximum increase in H2 expired following a lactose overload is not reliable for the diagnosis of lactose malabsorption. The cutoff value for the ASC-H2 using linear regression was 3260 (S = 89.3%, E = 80% and A = 86.7%), while using ROC it was 3353 (S = 88.0%, E = 80.0% and A = 85.7%) and while using Q-Q plot method it was 2936 (S = 92.0%, E = 80.0% and A = 88.6%). When the cutoff value was set to 3000, the sensibility, specificity and accuracy were 90.7%, 80.0% and 88.6%, respectively. We conclude that the calculation of the ASC-H2, but not delta-H2, following a lactose overload is reliable in detecting lactose malabsorption and can be used in the clinical practice.

Blood Glucose↗

Comparative tolerance of adolescents of differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks. II. Improvement of a double-blind test.

Using an improved double-blind test procedure, the relationship between lactose malabsorption and lactose intolerance was investigated in 87 healthy teenagers (14--19 years old) of differing ethnic backgrounds. Capillary blood glucose analysis after an oral dose of 50 g of lactose identified 45 lactose malabsorbers. A lactose-free (LF) chocolate dairy drink and one containing 4.5% lactose (LC) were administered under double-blind conditions on 4 consecutive mornings. As in a similar prior study, no statistically significant differences were found in the incidence of symptoms reported by malabsorbers and absorbers after drinking 240 ml of either the LF or the LC preparation. However, 12 lactose absorbers reported symptoms apparently not due to lactose, i.e., after 240 ml of LF, after this amount of both LF and LC, or after 240 ml (but not 480 ml) of LC. Such false-positive results would only be identified by the double-blind approach. It did not appear that any of the malabsorbers had symptoms due to the lactose in 240 ml of LC. However, 16% of the malabsorbers apparently reacted to the lactose in 480 ml of LC. Well designed, double-blind clinical trials are essential for evaluation of gastrointestinal responses to lactose or other ingredients in milk.

Adolescent↗

Diagnostic value of disaccharide tolerance tests in children.

Diagnostic value of disaccharide tolerance tests in children. Acta Paediatr Scand, 64:693, 1975.--The diagnostic value of oral lactose and sucrose tolerance tests was investigated in 61 children. A total of 105 oral disaccharide tests were carried out. When the rise in blood sugar was low, the same disaccharide was, as a control measure, instilled directly into the small intestine through a tube. This was carried out in 40 cases. In 21 patients the rise in blood sugar following the two forms of administration was correlated with the disaccharidase activity in a peroral small-intestine biopsy. The incidence of false-positive oral lactose tests was between 23 and 30%, that of false-positive oral sucrose tests between 24 and 33%. A border value of 20 mg per 100 ml in the rise of blood glucose within the first hour following a direct intra-intestinal administration affords a very satisfactory distinction between patients with and without disaccharide malabsorption. Blood glucose determinations exceeding one hour were found to be without diagnostic value.

Adolescent↗

Breath hydrogen test for lactose absorption capacity: importance of timing of hydrogen excretion and of high fasting hydrogen concentration.

The breath hydrogen (H2) test for lactose absorption capacity is a simple, noninvasive method for the determination of the adult lactase phenotypes, lactose absorber and malabsorber, in healthy subjects. Two breath H2 tests with a load of 50 g lactose monohydrate were performed on 25 healthy adult lactose malabsorbers in order to determine the validity of simplified versions of the test for field studies. A high variability of peak H2 excretion times, rapid changes in breath H2 concentrations and a significant correlation of intraindividual peak H2 excretion times were observed. High fasting excretion of H2 in breath was a frequent cause of misclassification of probands. It is recommended that at least three breath samples per proband should be collected in field studies of lactose absorption and that special diagnostic criteria be applied in classifying subjects with high initial H2 excretion.

Absorption↗

Breath hydrogen excretion after lactose and whole milk ingestion. A prospective comparison in lactase deficiency.

As the 50 g of lactose in the usual clinical test is unphysiologic both because it is equivalent to 1 L milk and because the usual dietary intake is not the purified sugar, but milk, we undertook a prospective comparison of the absorption of lactose after both lactose and milk ingestion with an equivalent lactose content. We studied 51 healthy volunteers, using the hydrogen breath test technique. All patients received 25 g lactose in aqueous solution. Subjects with an abnormal test had the test repeated with 500 ml whole cow's milk, whereas subjects with a normal test repeated the test after ingesting the unabsorbable sugar lactulose to detect the capacity of their colonic flora to produce the gas. Symptoms of gastrointestinal intolerance were also recorded. Compared to an equivalent lactose amount, milk lactose is better absorbed (8% of the entire population malabsorbed 500 ml whole milk, whereas 33.33% malabsorbed 25 g lactose) and induces intolerance in fewer subjects. We conclude that milk rather than pure lactose must be used in clinical evaluation of lactose malabsorption and intolerance.

Adult↗