Effective reduction of lactose maldigestion in preschool children by direct addition of beta-galactosidases to milk at mealtime

We examined the efficiency of two beta-galactosidase preparations--one derived from the yeast, Kluyveromyces lactis (Lactaid), the other derived from the fungus, Aspergillus oryzae (Takamine)--to assist the in vivo digestion of lactose consumed by healthy Guatemalan preschool children. Milk prehydrolyzed by in vitro incubation with enzymes was used as the standard of reference, and the degree of incomplete digestion of lactose from 240 mL of milk was determined using the hydrogen breath test. In in vivo dose-response studies, both 3,250 neutral lactose units of Lactaid and 6,635 food and chemical codex lactose units of Takamine completely eliminated excess H2 excretion in a small sample of lactose-maldigesting subjects. When evaluated in a controlled, clinical trial setting, the same dose of Lactaid added directly to the milk at consumption produced an 82% relative reduction in H2 excretion, whereas Takamine was equally as effective as the prehydrolyzed milk. Thus, intraluminal conditions and gastrointestinal transit in the preschool child support the effective assisted digestion of milk lactose in an efficient manner and with the same enzyme to milk ratios as observed previously in adults.     

Lactose malabsorption in children with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation

An investigation was carried out on 61 children suffering from symptomatic giardiasis with the object of verifying the incidence and entity of lactose malabsorption. Furthermore, the possibility of a substitutive yogurt diet was verified in the lactose malabsorbers. The subjects, all children older than 1 year, were studied according to a schedule that included a lactose hydrogen breath test (BT) performed prior to therapy and a further BT 60 days following therapy. The subjects were divided in two groups: group A, 40 children, received a dose of 250 ml of cow's milk; group B, 21 children, received a stress dose of 2 g/kg lactose (max 50 g). Those subjects who were lactose malabsorbers at the 60 day follow-up were also given a BT at 75 days, and in the case of persistent malabsorption, a further BT was performed after 24 h with the administration of yogurt (450 g containing 12.1 g of lactose). Furthermore, 40 subjects matched for age and sex but without any GI complaints served as controls. The results showed lactose malabsorption to be frequent in children with Giardia lamblia symptomatic infection. According to the BT with a standard lactose load, all patients were malabsorbers; when testing lactose absorption with 250 ml of cow's milk, 45% of patients were found to be malabsorbers. In the latter subjects, the oral load of yogurt was uniformly well tolerated and gave rise to no H2 increment on the BT. We conclude that the occurrence of lactose malabsorption of nutritional relevance is common in children suffering or having suffered from giardiasis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Test-retest reproducibility of hydrogen breath test for lactose maldigestion in preschool children

The test-retest reproducibility of the H2 breath test within the same individual has not been rigorously evaluated in preschool children. In the present study, 10 children--5 of whom were diagnosed as lactose-digesters on their first testing, and 5 of whom were diagnosed as lactose-maldigesters at first screening--were retested under identical conditions of a second opportunity. In each case, the same diagnostic classification was provided, for a reproducibility of 100%. Regression of the area under the curve of the change in breath H2 concentration during the 3 h of the test had a Pearson's correlation coefficient of 0.59 (p = 0.05). The time-course of 3-h H2 breath tests in 43 children with lactose maldigestion revealed a peaking of the concentration of H2 most commonly 120 min following the oral dose of 240 ml whole milk. Seventy-seven percent of the children who eventually proved to be lactose maldigesters were so diagnosed by the end of the second hour of the breath test. Thus, even the abbreviated breath sampling schedule used in children is sensitive, and few maldigesters would go undetected because of a late rise in breath H2 concentration.     

Feeding lactose-intolerant children with a powdered fermented milk

Fresh yogurt has been proposed as a milk substitute for lactase-deficient patients. We investigated the possibility that a dried, low-fat milk fermented by yogurt microorganisms would be effective. Processing of a fermented milk by spray-drying led to a powder with persistence of lactase activity (11.7 units/g) without storage at 4 degrees C and stable at room temperature (20-23 degrees C). The tolerance and absorption of 10.5 g of lactose in a volume of 150 ml was studied in 25 Gabonese lactase-deficient children aged 5-14 years in the form of a standard humanized milk formula followed 1 week later by the powdered fermented milk formula. Results of the breath hydrogen test showed that in 24 of 25 cases, lactose absorption was normal with a maximal rise of hydrogen over baseline of under 13 ppm after ingestion of the powdered fermented milk. The rise was above 20 ppm in the 25 children with the same load of lactose in the form of the standard formula and one-third had symptoms of lactose intolerance. This powdered fermented milk preparation should be considered as a valid approach in programs of nutritional support targeted to countries with a high prevalence of lactase deficiency.     

Breath hydrogen excretion in infants with colic.

Breath hydrogen excretion as an index of incomplete lactose absorption was measured in 118 healthy infants who were either breast fed or given a formula feed containing lactose, some of whom had colic. Infants with colic (n = 65) were selected on the basis of the mother''s report of a history of inconsolable crying lasting several hours each day. Infants in the control group (n = 53) were not reported to cry excessively by their mothers. Breath samples were collected using a face mask sampling device preprandially, and 90 and 150 minutes after the start of a feed. Normalised breath hydrogen concentrations were higher in the group with colic than in the control group at each time point. The median maximum breath hydrogen concentration in the colic group was 29 ppm, and in the control group 11 ppm. The percentage of infants with incomplete lactose absorption (breath hydrogen concentration more than 20 ppm) in the colic group was 62% compared with 32% in the control group. The clinical importance of the observed association between increased breath hydrogen excretion and infantile colic remains to be determined. Increased breath hydrogen excretion indicative of incomplete lactose absorption may be either a cause or an effect of colic in infants.     

Breath hydrogen response to milk containing lactose in colicky and noncolicky infants

In 122 healthy newborn infants, we studied the relationship between breath hydrogen (H2) production after feedings containing lactose (human milk or commercial formula) in colicky and noncolicky infants at 6 weeks and 3 months. Eighty-three infants (68%) developed colic (mild, moderate, or severe) by 2.6 +/- 1.8 weeks of age (mean +/- SD). Zero time (baseline) breath H2 values were significantly higher in colicky compared with noncolicky infants at both 6 weeks (40.6 +/- 41.4 vs 14.8 +/- 32.9 ppm) and 3 months (27.7 +/- 38.1 vs 8.5 +/- 18.2 ppm). There were significantly more positive breath H2 tests in colicky compared with noncolicky infants at 6 weeks (78% vs 36%) and 3 months (89% vs 45%). Failure to produce H2 throughout the breath H2 test was significantly more frequent in noncolicky compared with colicky infants at 6 weeks (50% vs 18%) and 3 months (43% vs 4%). These findings remained significant even when infants with mild colic (at 6 weeks and 3 months) were included in the noncolicky group. We conclude that colicky infants produce more breath H2 in the fasting state and in response to feedings containing lactose than noncolicky infants produce. This may represent increased lactose malabsorption, differences in colonic bacterial fermentation conditions, or differences in the handling of colonic gas produced.     

Lactose maldigestion: increased age-related prevalence in institutionalized children

A study was performed to determine whether the age-related prevalence of lactose maldigestion is increased in healthy institutionalized children. Previous malnutrition did not exclude children from study. The control children had no prior history of malnutrition or hospital admissions for diarrhea. The anthropometric comparison showed the institutionalized children to be shorter and lighter than the controls, but they were of normal weight by stature, suggesting a normal recent nutritional state. Fasting breath hydrogen tests were performed following an oral dose of lactose 1 g/kg, given as a 10% solution. A rise of breath hydrogen of greater than or equal to 20 ppm was considered to indicate lactose maldigestion. Twenty-two of 44 controls and 39 of 49 study children were lactose maldigesters (p less than 0.01). The control children showed an age-related increase in the prevalence of lactose maldigestion, from 31.6% at age less than 5 years to 75% at age greater than 9 years. The institutionalized children, by comparison had an increased prevalence of 78.8% in the group under 5 years of age (p = 0.002). Equally high prevalence rates were found at all ages tested. At follow-up, lactose maldigestion was persistent in the majority of the study children. This had no nutritional impact despite a regular milk intake. The distinction between acquired and primary lactose maldigestion is of no practical significance in these children.     

Clinical and nutritional consequences of lactose feeding during persistent postenteritis diarrhea

In a double-blind prospective trial, 64 children, 3 to 36 months of age, who had diarrhea for at least 14 days were randomly assigned to receive either a milk-based diet containing 6 g/kg of body weight per day of lactose or the same diet in which the lactose was greater than 95% prehydrolyzed with beta-galactosidase. Clinical and nutritional outcomes were compared. The groups were similar at the start of the study. Four of 33 patients (12.1%) in the lactose group were considered to have treatment failure because of excessive purging with or without refusal to accept the diet, compared with 1 of 31 patients (3.2%) in the hydrolyzed lactose group (P = .20). Among successfully treated boys, fecal excretion was initially similar, but on days 3 to 5 of the trial the lactose group purged a mean 74.4 g/kg per day (95% confidence limits 17.8, 131.0) compared with 42.0 g/kg per day (95% confidence limits 11.4, 72.6) in the hydrolyzed lactose group (P less than .01). Diarrhea stopped within 30 hours of hospital admission in 11 children in the hydrolyzed lactose group (35.5%) compared with 1 child in the lactose group (3.3%) (P less than .001). Fecal excretion of carbohydrate, nitrogen, and energy was significantly greater in lactose group (P less than .01), but there were no significant differences in fat excretion or in incremental weight change during hospitalization. Feeding lactose-containing nonhuman milk as the sole nutrient source to children with persistent diarrhea resulted in substantially greater purging which was sufficiently severe to increase the risk of dehydration in these children.     

Lactose absorption and malabsorption in healthy Italian children: do the quantity of malabsorbed sugar and the small bowel transit time play roles in symptom production?

Using breath hydrogen analysis after an oral lactose load (2 g/kg; maximum 50 g), we investigated the prevalence of lactose malabsorption in 61 healthy Italian children aged 6-13 years. We also examined the relationship between symptoms and small bowel transit time and the degree of sugar malabsorption. Three of 61 subjects produced no H2 after both lactose and lactulose load and thus were eliminated at the outset. Lactose malabsorption was defined as excretion of greater than 20 ppm H2. Lactose intolerance was classified as mild (colicky pain, flatulence, abdominal distension, borborygmi) or severe (diarrhea). The frequency of lactose malabsorption in the children aged 6-8 years (group I) was 25%; in the children aged 8-11 years (group II), it was 35%, and in the children aged 11-13 years (group III) 56%. The differences in frequency between the first and the third groups were significant (p = 0.05). Three of 20 (15%) in group I, two of 20 (10%) in group II, and three of 18 (17%) in group III were classified not only as lactose malabsorbing, but also as lactose intolerant, with symptoms during and after the test. We found no difference in the small bowel transit times or in the quantities of malabsorbed lactose in symptomatic and asymptomatic malabsorbing subjects. Other factors that may play a role in symptom production are discussed.     

Ineffectiveness of breath methane excretion as a diagnostic test for lactose malabsorption

BACKGROUND: In clinical and field conditions, breath gas analysis has been widely used in evaluating carbohydrate digestion. A field study was performed to determine the prevalence of lactose malabsorption in Myanmar children and to evaluate the possibility of using breath methane excretion to indicate lactose malabsorption in a field situation. METHODS: The study population consisted of 118 children aged 1 to 12 years. A hydrogen breath test after a lactose meal (2 g/kg, maximum 50 g) was used as a standard test. RESULTS: Lactose malabsorption was detected in 16.7% of children aged 1 to 2.9 years, with the prevalence increasing with age from 40.5% of those aged 3 to 5.9 years to 88.5% of those aged 6 to 8.9 years and reaching 91.7% in those aged 9 to 11.9 years. Lactose malabsorption was more prevalent when children were weaned before 4 months of age (87.2 vs. 41.1%; p < 0.01). Compared with lactose-tolerant children, those with lactose malabsorption had significantly higher concentrations of breath hydrogen excretion 60 minutes after the lactose test meal. Breath methane excretion was also significantly higher in samples at 120 minutes in children with lactose malabsorption. Breath methane excretion of greater than or equal to 2 parts per million at 180 minutes as a diagnostic test for lactose malabsorption had a sensitivity of 61.5% and a specificity of 84.6%. CONCLUSION: The breath methane test for lactose malabsorption has a lower sensitivity and specificity than the breath hydrogen test and therefore does not replace the lactose breath hydrogen test.     

Extent of lactose absorption in children with active celiac disease

We have estimated lactose absorption indirectly by the breath H test to see if disaccharide exclusion is necessary for untreated celiac children. Lactose at 2 g/kg body weight (maximum 50 g) was administered to 42 infants and children (ranging in age from 9 months to 12 years) with flat small intestinal mucosa. Later, different amounts of lactose were given to determine the quantities tolerated and absorbed. One hundred percent of patients expired hydrogen more than 20 ppm over the baseline after an oral lactose load of 2 g/kg (maximum 50 g). Thirty-eight percent of them did not tolerate this quantity. Thirty-seven subjects aged 0-6 years absorbed and tolerated 0.5-1.5 g/kg (5-12.5 g total), and five patients aged 6-12 years absorbed and tolerated 0.5-0.6 g/kg (12-16.2 g total). We conclude that in many subjects with untreated celiac disease, lactase activity is sufficient for absorption and tolerance of the amount of lactose present in 250-300 ml cow's milk. Because of lactose's nutritional value, it should not be excluded unless necessary.     

Hydrogen (H2) breath test following lactose loading in children with recurrent abdominal pain

To define the practical diagnostic value of H2 breath testing after lactose load in children with chronic abdominal pain, we measured end-expiratory H2 every 30 minutes for 2 hours after peroral lactose (2 g/kg body weight, Lactoscreen). H2 testing was done in 62 children (28 female, 32 male), aged between 2 and 16 years. Abdominal pain had been observed in these children for more than 2 months. Causes of abdominal pain other than lactose intolerance had been excluded. In 2 out of 62 children, H2 testing was impossible for lack of cooperation. 17 out of the remaining 60 children showed a positive test result (28.3%). In 15 patients, the rise in H2 exceeded 40 ppm, and was thus easily distinguished from a nonspecific rise (less than 25 ppm). Stool pH and Clini-test results were not correlating well with H2 findings, In 16 out of 17 children with positive H2 tests, abdominal pain had ceased on a diet free of lactose after a month. After 6 months 15 out of 17 children were symptom free. These data confirm early indication of non-invasive H2 testing in children with chronic abdominal pain.     

Incomplete lactose absorption from breast milk during acute gastroenteritis

The incidence and degree of incomplete lactose absorption was investigated in breast fed infants and children up to two years of age during acute gastroenteritis (GE). Lactose absorption was assessed in 50 patients by means of the hydrogen breath test (HBT), approximately 5.5 days after the admission to hospital. HBT detected incomplete lactose absorption of marked (lactose malabsorption) and probably mild degree in 8 and 6 patients respectively. Incomplete lactose absorption appeared to be transient in all 5 patients retested after discharge. HBT failed to identify 8 cases of lactose intolerance which were detected by investigation of the stools. In 31 breast fed controls of a similar age range incomplete lactose absorption of only mild degree was probably present in 2 and lactose intolerance in 1, which too was only detected by investigation of stools. During acute GE the use of HBT is appropriate to detect milder forms of incomplete lactose absorption than lactose intolerance. For the detection of lactose intolerance the measurement of pH and reducing substances in the stools remains the method of choice. The findings are in favour of the continuation of breast feeding during acute GE.     

Two-hour lactose breath hydrogen test

Current requirements for the lactose breath hydrogen test (LBHT) include serial expired air samplings and multiple hydrogen (H2) determinations. One hundred thirty-two consecutive LBHTs were evaluated to determine whether multiple samplings are indeed necessary for detection of lactose malabsorption. Expired air samples were collected at 0, 30, 60, 90, 120, 150, and 180 min following ingestion of lactose. Fifty-five LBHTs were positive for lactose malabsorption. All tests showed abnormally elevated breath H2 concentrations at 120 min. The mean value of the change in parts per million (delta ppm) of H2 at 120 min (51.1 +/- 4.7 SEM) was higher than at any other time point. If only the 120-min samples were examined without subtracting the initial concentrations, four of the 77 negative tests (5.2%) would have been falsely positive. Thus, the values of H2 at 0 and 120 min were sufficient to define lactose malabsorption in all cases. We conclude that just as a single blood sample now suffices for determining xylose malabsorption, so expired air sampling at only 0 and 120 min during the LBHT is a reliable method for detecting lactose malabsorption and diminishes the need for acquiring and analyzing multiple samples.     

Incomplete Lactose Absorption from Breast Milk during Acute Gastroenteritis

ABSTRACT. The incidence and degree of incomplete lactose absorption was investigated in breast fed infants and children up to two years of age during acute gastroenteritis (GE). Lactose absorption was assessed in 50 patients by means of the hydrogen breath test (HBT), approximately 5.5 days after admission to hospital. HBT detected incomplete lactose absorption of marked (lactose malabsorption) and probably mild degree in 8 and 6 patients respectively. Incomplete lactose absorption appeared to be transient in all 5 patients retested after discharge. HBT failed to identify 8 cases of lactose intolerance which were detected by investigation of the stools. In 31 breast fed controls of a similar age range incomplete lactose absorption of only mild degree was probably present in 2 and lactose intolerance in 1, which too was only detected by investigation of stools. During acute GE the use of HBT is appropriate to detect milder forms of incomplete lactose absorption than lactose intolerance. For the detection of lactose intolerance the measurement of pH and reducing substances in the stools remains the method of choice. The findings are in favour of the continuation of breast feeding during acute GE.     

Interpreting the 13C-urea breath test among a large population of young children from a developing country.

The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.     

Delayed complete functional lactase sufficiency in breast-fed infants

Colonic fermentation of unabsorbed lactose was evaluated by measuring breath hydrogen (BH2) after a regular feeding in 17 white, normal, exclusively breast-fed infants 4-5 weeks of age. Interval breath samples were collected with a specially modified face mask and analyzed by gas chromatography for H2 and CO2 concentrations. Five infants (29%) produced 20 ppm or more of H2, four of whom underwent repeated testing. Three infants stopped producing over 20 ppm of H2 as they grew older. On a repeat evaluation, one of these three infants had levels over 20 ppm when other foods were introduced into his diet. The other continued to have elevated BH2 when weaned. Stools of infants with elevated BH2 levels had no detectable glucose, and pH was over 5.5. Weight-for-age of infants with elevated BH2 was at or above the 75th percentile. BH2 levels, normalized for the amount of breast milk ingested, fell significantly with age. These results show that complete small bowel absorption of lactose from breast milk does not occur in all white, normal, term, appropriate-for-gestational-age infants in the first months of life. The absence of glucose in the stool and the normal stool pH suggest that the unabsorbed lactose that produced H2 can be degraded in the colon.     

Calcium absorption and acceptance of low-lactose milk among children with primary lactase deficiency

A calcium absorption investigation was carried out with the purpose of determining whether lactose-hydrolyzed milk facilitates calcium absorption in subjects with lactose malabsorption. Nine children participated in the study, which was divided into two investigation periods separated by at least 1 week. During the first period the children were given a lactose-free diet, whereas during the second period their diet contained lactose-hydrolyzed milk. The amount of calcium, number of calories, and rotation of specifically defined meals in the diet during the two periods were identical, and the children functioned as their own controls. We found calcium absorption to be significantly higher with the diet containing hydrolyzed milk than with the lactose-free diet supplemented with extra calcium (p less than 0.05). During the study a double-blind lactose intolerance test was performed. The children had significantly fewer clinical symptoms and signs, such as abdominal pain, borborygmus, meteorism, and defecations, within 24 h after drinking 0.5 L of lactose-hydrolyzed milk as compared with drinking ordinary milk (25 g of lactose). None of the children experienced any unpleasant side effects when consuming the lactose-hydrolyzed milk (approximately 94% degree of hydrolysis) during the study period. All the children liked the hydrolyzed milk because it had a pleasant, sweet flavor as a result of the increased content of glucose.     

Effects in premature infants of normalizing breath H2 concentrations with CO2: increased H2 concentration and reduced interaliquot variation

Interval sampling of expired breath samples from the anterior nares is a feasible and noninvasive method for detecting elevated breath H2 and thus colonic carbohydrate fermentation, especially in nontherapeutic research studies of healthy premature infants. However, there may be a risk of falsely low breath H2 concentration and an unacceptable experimental error due to contamination with room air as well as with dead space air. We studied ten premature infants (28-32 week gestational age and 2-4 weeks postnatal age) who were receiving either a proprietary formula containing equal proportions of lactose and glucose polymer, or a similar formula in which lactose was the sole carbohydrate. In 70 breath samples (obtained 30-180 min after feeding) we assessed the coefficient of variation in breath hydrogen concentration among three aliquots obtained over a 3-5 min interval. Breath was collected from the anterior nares. The interaliquot coefficient of variation averaged 11% when expressed as parts per million per 5% CO2, compared to 19% when expressed as parts per million (Wilcoxon, p less than 0.001). Mean breath hydrogen concentration at each time period using the former method (parts per million per 5% CO2) was about 100% higher than when using the latter method. Although ventilation rate can alter alveolar CO2, normalizing for CO2 concentration reduces a major source of experimental error.     

Lactose Malabsorption and Giardiasis in Basotho School Children

ABSTRACT. The prevalence of primary, adult-type, lactose malabsorption was assessed by means of the hydrogen breath test after intake of 360 ml of full cream milk (∼18 g lactose) in 96 randomly selected Basotho school children, aged 5–15 years. Of 86 children who did not have diarrhoea in the previous week 82 (85 %) were lactose malabsorbers, while 4 (5 %) could not be classified because of undetectable hydrogen excretion. Milk intolerance presenting as diarrhoea was significantly ( p <0.01) more common in children who associated previous abdominal complaints with milk intake and/or did not like milk. A negative hydrogen breath test was significantly ( p <0.05) more often observed in children who had diarrhoea in the previous week. Giardia was present in 18 (19 %) of 93 children. The incidence of giardiasis did not correlate with the presence of lactose malabsorption in children without diarrhoea in the previous week. However, milk intolerance presenting as diarrhoea was significantly ( p <0.05) more common in children with giardiasis. The findings support the use of physiological quantities of milk in Basotho school children.