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PubMed1996

Influence of loperamide on lactose handling and oral-caecal transit time.

BACKGROUND: The influence of pharmacologically prolonged oral caecal transit time on lactose handling is examined in the wake of finding improved lactose handling during naturally occurring prolonged oral-caecal transit time. METHODS: Sixteen normal male volunteers with lactose maldigestion were pretreated with 8 and 12 mg loperamide on different days and lactose handling was compared by measuring areas under the curve during lactose breath H2 testing (3 h). The oral-caecal transit time was similarly measured using lactulose and exhaled breath H2. Symptom scores were recorded and, in three subjects, blood sugar was simultaneously measured. RESULTS: The mean +/-S.E.M. baseline oral-caecal transit time was 56.9 +/- 5.9 min. Loperamide significantly prolonged oral-caecal transit time (90.3 +/- 11.1 and 82.1 +/- 13.9 min for 12 and 8 mg loperamide, respectively; P < 0.05). The lactose breath H2 area under the curve with 12 mg loperamide was significantly less than at baseline (7685 +/- 985.6 vs. 10243.1 +/- 1607, respectively; P < 0.05). Significantly fewer symptoms were recorded with both doses of loperamide during the 3 h test but with 12 mg loperamide only on follow-up. There was no significant rise in blood sugar at any time in the three subjects studied. CONCLUSIONS: Loperamide-induced graded prolongation of oral-caecal transit time is associated with significantly improved lactose handling as measured by a reduction of the area under the curve. Symptoms of lactose intolerance may also be improved with loperamide. Prolongation of oral-caecal transit time with loperamide may be useful as adjunctive or primary therapy of carbohydrate intolerance in patients with rapid transit.

Administration, Oral↗
PubMed1999

Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms.

BACKGROUND: In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose. AIM: To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms. METHODS: After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded. RESULTS: The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0-12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopramide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found. CONCLUSIONS: In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.

Adult↗
PubMed2003

Lactose intolerance: analysis of underlying factors.

BACKGROUND: We studied the degree of lactose digestion and orocecal transit time (OCTT) as possible causes for the variability of symptoms of lactose intolerance (LI) in a sample of a population with genetically determined low lactase activity. METHODS: Lactose digestion index (LDI) was measured by the recently developed 13C-lactose/2H-glucose test. The OCTT was determined using the breath hydrogen test. Based on a 6-h symptom score (SSC) after a challenge dose of 25 g of lactose the subjects were divided into a tolerant group (T: n= 15; SSC = 0) and an intolerant group (IT: n= 28; SSC 1-40). The intolerant group was subdivided according to the severity of symptoms: group ITa (n = 17; mild symptoms without diarrhoea) and group ITb (n = 11; with diarrhoea). RESULTS: The LDI was lower in the intolerant group (0.34 +/- 0.14) (mean +/- SD) than in the tolerant group (0.47 +/- 0.14) (P = 0.008). The OCTT of group IT (60, 30-90 min) (median, quartiles) was significantly shorter than that of group T (105, 60-120 min) (P = 0.003) and was positively correlated with the LDI (P = 0.050). In groups ITa and ITb the OCTT (60, 30-90 min; 60, 26-83 min) and LDI (0.30 +/- 0.14; 0.39 +/- 0.14) were similar. CONCLUSIONS: Lactose digestion capacity, which is determined by small intestinal lactase activity as well as by OCTT, affects the occurrence of lactose intolerance. However, the major difference in intolerance symptoms is caused by differences in the colonic processing of maldigested lactose.

Adult↗
PubMed1984

Yogurt--an autodigesting source of lactose.

Large quantities of yogurt are consumed by some lactase-deficient population groups. We used breath hydrogen measurements to determine whether lactase-deficient subjects absorbed lactose in yogurt better than lactose in milk. Ingestion of 18 g of lactose in yogurt resulted in only about one third as much hydrogen excretion as a similar load of lactose in milk or water, indicating a much better absorption of lactose in yogurt. Ingestion of yogurt also resulted in fewer reports of diarrhea or flatulence than did a similar quantity of lactose ingested in milk or a water solution. The enhanced absorption of lactose in yogurt appeared to result from the intraintestinal digestion of lactose by lactase released from the yogurt organisms. This autodigesting feature makes yogurt a well-tolerated source of milk for lactase-deficient persons and may explain the widespread consumption of yogurt by lactase-deficient population groups.

Adult↗
PubMed1977

Lactose malabsorption in Mexican-American adults.

Lactose malabsorption was determined in 277 Mexican-American (MA) and 142 Anglo-American (AA) adults aged 18 to 94 years old, and correlated with nutrient intake assessed from 24-hr dietary recalls, as well as with milk and dairy product consumption. Lactose malabsorption occurred in 144 of 277 (53%) MA and 21 of 142 (15%) AA. Analysis of dietary questionnaires revealed no differences between lactose absorbers and malabsorbers within each ethnic group in their consumption of protein, calories, riboflavin, vitamin A, or calcium. Vitamin A, calcium, and riboflavin intake was greater in AA than in MA subjects. Milk and dairy product consumption was the same in lactose absorbers and malabsorbers in both ethnic groups. Nearly 60% of MA malabsorbers and 24% of AA malabsorbers recognized experiencing symptoms after milk ingestion. Although group differences in milk consumption on the basis of lactose absorption status are not apparent, individual lactose malabsorbers may alter milk ingestion in response to lactose-induced symptoms. Lactose malabsorption occurs in over half of MA adults and may in some individuals present a clinically relevant problem.

Adolescent↗
PubMed1997

Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance.

We reported previously that consumption of one cup of milk (240 mL) per day produced negligible symptoms in lactase-nonpersistent (LNP) individuals self-described as being severely lactose intolerant. We hypothesized that such LNP individuals could also tolerate two cups of milk per day if taken in two widely divided doses with food, and that psychologic factors play a role in perceptions of lactose intolerance. The Minnesota Multiphasic Personality Inventory 2 (MMPI-2) was administered to 19 LNP subjects self-described as markedly lactose intolerant (S-LNP), 13 LNP subjects who denied lactose intolerance (A-LNP), and 10 lactase-persistent individuals who believed they were lactose intolerant (S-LP). Symptoms were recorded when LNP subjects ingested 240 mL regular or lactose-hydrolyzed milk twice daily for 7 d in a double-blind crossover study. The results showed that neither LNP group had a significant increase in symptoms (P < 0.05) during the regular compared with the lactose-hydrolyzed milk periods. However, S-LNP subjects reported significantly greater gaseous symptoms than did the A-LNP subjects during both treatment periods. The MMPI-2 showed a high score on the "lie" validity scale for S-LNP subjects. We conclude that LNP subjects tolerate two cups of milk per day without appreciable symptoms. S-LNP subjects have underlying flatulence that is misattributed to lactose intolerance. MMPI-2 results were of questionable validity because of the high rate of dissimulation by LNP subjects.

Abdominal Pain↗
PubMed1999

Irritable bowel syndrome and lactose maldigestion in recurrent abdominal pain in childhood.

BACKGROUND: The aim of this study was to evaluate the impact of irritable bowel syndrome (IBS) and lactose maldigestion in children with recurrent abdominal pain. METHODS: Children who had abdominal pain associated with defecation or change in bowel habit, disordered defecation, and distension were diagnosed with IBS, and lactose maldigestion was defined by lactose breath hydrogen testing. Children with IBS were managed with increased fiber intake, while those with lactose maldigestion restricted dietary lactose. A telephone survey was conducted to determine the response to treatment. RESULTS: The mean age of the 59 boys and 87 girls was 9.5 +/- 3.0 years. Children with IBS and lactose maldigestion had more frequent abdominal pain than children without these conditions, but they required less medication for relief of symptoms. CONCLUSIONS. Lactose maldigestion may be a contributory factor in children with IBS, and lactose avoidance in these patients may reduce medication use to relieve symptoms.

Abdominal Pain↗
PubMed1979

Influence of the lactose plasmid on the metabolism of galactose by Streptococcus lactis.

Streptococcus lactis strain DR1251 was capable of growth on lactose and galactose with generation times, at 30 degrees C, of 42 and 52 min, respectively. Phosphoenolpyruvate-dependent phosphotransferase activity for lactose and galactose was induced during growth on either substrate. This activity had an apparent K(m) of 5 x 10(-5) M for lactose and 2 x 10(-2) M for galactose. beta-d-Phosphogalactoside galactohydrolase activity was synthesized constitutively by these cells. Strain DR1251 lost the ability to grow on lactose at a high frequency when incubated at 37 degrees C with glucose as the growth substrate. Loss of ability to metabolize lactose was accompanied by the loss of a 32-megadalton plasmid, pDR(1), and Lac(-) isolates did not revert to a Lac(+) phenotype. Lac(-) strains were able to grow on galactose but with a longer generation time. Galactose-grown Lac(-) strains were deficient in beta-d-phosphogalactoside galactohydrolase activity and phosphoenolpyruvate phosphotransferase activity for both lactose and galactose. There was also a shift from a predominantly homolactic to a heterolactic fermentation and a fivefold increase in galactokinase activity, relative to the Lac(+) parent strain grown on galactose. These results suggest that S. lactis strain DR1251 metabolizes galactose primarily via the tagatose-6-phosphate pathway, using a lactose phosphoenolpyruvate phosphotransferase activity to transport this substrate into the cell. Lac(-) derivatives of strain DR1251, deficient in the lactose phosphoenolpyruvate phosphotransferase activity, appeared to utilize galactose via the Leloir pathway.

Fermentation↗
PubMed1964

BETA-GALACTOSIDASE AND LACTOSE FERMENTATION IN THE IDENTIFICATION OF ENTEROBACTERIA INCLUDING SALMONELLAE.

One hundred and fourteen strains of non-lactose fermenters and 127 lactose fermenters on MacConkey's agar have been compared in the 5% and 1% lactose tests and in beta-galactosidase production, using ortho-nitro-phenyl-beta-D-galactopyranoside (O.N.P.G.) as a test substance. The superiority of the O.N.P.G. test in the number of positive results and its rapidity is shown. In general, late or non-lactose fermenting strains of genera, usually lactose-positive, yield a rapidly positive O.N.P.G. reaction. Forty-one wild strains of Salmonella, Proteus, Providencia, and Pseudomonas aeruginosa were found negative in all three tests. Of 1,075 stock strains of Salmonella examined in the O.N.P.G. test, all were negative except nine; four of these were lactose-positive strains. For practical purposes, Salmonella strains in Great Britain may be regarded as O.N.P.G. negative. Among 100 stock strains of Arizona there was considerable variation of behaviour in the O.N.P.G. test and in the 5% and 1% lactose tests. Most strains of Arizona can be considered to yield a positive O.N.P.G. test but a minority give a negative result. The test is recommended for routine use in the differentiation of Salmonella from other enterobacteria and for use in bacterial identification. The 5% lactose fermentation test in parallel is suggested when the O.N.P.G. test is used for isolating routine pathogens, because organisms such as Shigella sonnei, Shigella dysenteriae 1, and Pasteurella pseudotuberculosis are O.N.P.G. positive.

Bacteriological Techniques↗
PubMed2002

[Study on the expired gas of subjects with lactose intolerance by using H2/13CO2 breath test].

The relationship between breath gas and lactose intolerance symptoms is studied in the subjects with lactose intolerance and lactose mal-absorption. The breath gas samples are collected for 6 hours after consumption of 25 g 13C-lactose. Expired H2 concentration and 13CO2 abundance at each detecting time point is measured by gas chromatography and continuous flow Gas Isotope Mass Spectrometry respectively. The cumulative amount of breath H2 and 13CO2 for 6 hours are calculated, and the abdominal symptoms are recorded by the questionnaire for 12 hours. The results show that the H2 peak is significantly higher in the intolerance group than that in the mal-absorption group(P < 0.01). The cumulative amount of breath H2 during 6 hours is significantly higher in the intolerance group than that in the mal-absorption group (P < 0.01). The oral-colon transit time (OCTT) is negatively related to the lactose intolerance symptom scores (r = -0.705). There are no significant differences for the amount of 13CO2 excretion at each detecting time point and cumulative percentage of the expired 13CO2 between the intolerance and the mal-absorption groups. It is suggested that the cumulative breath H2 amount is associated with the severity of lactose intolerance, which can reflect the degree of lactose hydrolysis in the small intestine, while there is no such relationship between the amount of expired 13CO2 and the severity of lactose intolerance.

Adult↗
PubMed1976

Quantitative measurement of lactose absorption.

The quantity of lactose not absorbed by 4 normal and 6 lactase-deficient subjects was determined by three indirect methods which involved: (1) measurement of pulmonary hydrogen (H2) excretion, (2) pulmonary (14)CO2 excretion, and (3) stool (14)C excretion, after ingestion of 12.5 g of 1-(14)C-lactose and 4 g of polyethylene glycol (PEG). Results were compared with absorption determined directly from the (14)C:PEG ratio of multiple terminal ileal aspirates. The fraction of lactose not absorbed determined by ileal aspiration ranged from 0 to 8% in normals and 42 to 75% in mild-intolerant subjects. Whereas all three indirect methods were useful in qualitatively separating normal from deficient subjects, the quantity of lactose absorbed as determined by H2 excretion correlated most closely with ileal measurements (r = 0.94). Pulmonary (14)CO2 excretion for 24 hr after (14)C-lactose ingestion did not distinguish normal (17 +/- 4% (SEM) of ingested (14)C per 24 hr) from lactase-deficient subjects (21.1 +/- 3%). Likewise, stool (14)C:PEG ratios grossly underestimated malabsorption with less than one-quarter of the nonabsorbed (14)C appearing in the stool. This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon. Analysis of ileal fluid collected during passage of the lactose meal indicated that about two-thirds of the osmotic load delivered to the colon consists of endogenous electrolytes. Thus the water load delivered to the colon is about 3 times that calculated to be osmotically held by the nonabsorbed sugar.

Carbon Dioxide↗
PubMed1991

The practical significance of lactose maldigestion in institutionalised black children.

A study was carried out to determine the practical significance of a high prevalence of lactose maldigestion in institutionalised children whose diet included 500 ml milk daily. Thirty of 34 children at a child welfare home were found to be lactose maldigesters as judged by a 2-hour rise in breath hydrogen of 20 parts per million or more after an oral load of lactose. Breath hydrogen tests were also performed on the same group of children, before and up to 150 minutes after the routine mid-morning cup of milk. Sixteen of the 30 lactose-maldigesting children did not show increased breath hydrogen up to 2.5 hours after milk. No children were clinically intolerant of either the lactose or the milk. In these children the degree of lactose digestion was much improved in the non-fasting state when measured by the breath hydrogen response to milk lactose. Lactose maldigestion per se is not a contraindication to institutional feeding routines, including regular moderate milk intake.

Animals↗
PubMed2006

Formation of galacto-oligosaccharides during lactose hydrolysis by a novel beta-galactosidase from the moderately thermophilic fungus Talaromyces thermophilus.

Discontinuous and continuous processes of lactose hydrolysis and concomitant galacto-oligosaccharide (GalOS) formation were studied. To this end a wide experimental range of the main variables was evaluated, including the initial lactose concentration, the degree of lactose conversion, the pH value and the temperature for discontinuous transformations, while the initial lactose concentration and the feed rate were varied for the continuous process. For both processes a high-initial lactose concentration proved to be advantageous for the formation of GalOS. The maximum amount of GalOS (100 g/L, corresponding to a yield of approximately 50% based on the initially employed lactose) was obtained after 8 h of incubation when using 200 g/L lactose as substrate and 90% lactose hydrolysis was observed. GalOS productivity in the continuous process (g/L.h) was enhanced by an increase of the flow rate. The maximum GalOS productivity of 70 g/L.h was obtained at a flow rate of 24 mL/h when using a reactor with a total working volume of 21 mL. As was evident from these experiments, this beta-galactosidase from a moderately thermophilic fungus showed a strong transgalactosylation activity and can be used for the formation of GalOS, sugars that are of considerable interest for functional food applications because of their presumed healthpromoting effects.

Galactose↗
PubMed1982

Distribution of physiological adult lactase phenotypes, lactose absorber and malabsorber, in Germany.

A total of 1805 apparently healthy, adult and adolescent Germans (1572 males and 233 females with a mean age of 20.3 years) were examined for lactose absorption capacity employing a field version of the breath hydrogen (H2) test. The diagnostic parameter, maximal change of breath hydrogen concentration 120 or 150 min after a load of 50 g lactose, showed a bimodal distribution, separating lactose absorbers (n = 1537, 85.2%) and lactose malabsorbers (n = 268, 14.8%). The distribution of the adult lactase phenotypes was independent of age, sex, and educational status. The incidence of gastrointestinal symptoms after lactose administration demonstrated the incongruity of lactose malabsorption and lactose intolerance. In addition to grouping by residence, the probands were classified according to the birthplaces of their grandparents in order to reconstruct the distribution pattern of the lactase phenotypes prior to World War I, a period of relative population stability. Considerable differences in the frequency of lactose malabsorption were found in regions corresponding to traditional ethnic groups within the German population: northwest Germany 6-9%, west and south 13-14%, southwest 23%, east (including formerly German territories east of rivers Oder and Neisse) 22%. These differences are discussed with reference to population history. The present fairly even distribution of the lactase phenotypes in West Germany is the result of internal migrations at the end of World War II.

Adolescent↗
PubMed1977

Effects of age on lactose malabsorption in Oklahoma Native Americans as determined by breath H2 analysis.

Breath H2 excretion was used to determine lactose malabsorption in 30 health females and 30 healthy males between the ages of 3 and 64 yr who were at least 7/8 Native American. The test meal consisted of 5 ml reconstituted nonfat dry milk (0.25 g lactose) per kg of body weight. On the basis of breath H2 tests in 15 control subjects with normal oral lactose tolerance tests, a response factor of 20 ppm was selected as the upper limit for lactose absorbers. Of the 60 subjects in the study group, 36 (60%) were classified as lactose malabsorbers since they had a response factor of 20 ppm or greater of breath H2. Only 3 of 20 children (15%) who were under the age of 12 yr were nondigesters of the small lactose dose used in this study. Approximately 82 percent (82.5%) of subjects who were 13 yr and older were lactose malabsorbers. Adolescence appears to be the period in which malabsorption of lactose becomes evident in Native North Americans.

Adolescent↗
PubMed1989

Nipple aspirate fluids in adult nonlactating women--lactose content, cationic Na+, K+, Na+/K+ ratio, and coloration.

The presence of lactose in nipple secretions is considered biochemical evidence of breast secretory activity, and has been reported to occur more frequently in white compared to brownish or green colored breast fluid. We studied lactose, Na+, and K+ concentrations, the Na+/K+ ratio, and the coloration of nipple aspirate fluid (NAF) from 49 nonpregnant women. A significant relationship was found between the concentrations of lactose, Na+, and K+, and age and the coloration of NAF. Lactose was present in 22/49 (44.8%) of the NAF samples and declined with age from 100% positivity in women less than or equal to 29 years to 29% in those less than or equal to 35 years. In NAF of deep yellow, brown and green colorations, only traces of lactose were found. Na+ and K+ increased with age and with darker colorations compared to white, pale yellow, or colorless NAF. Lactose was present in NAF samples from both parous and nulliparous younger women, indicating that the breasts of many nonpregnant women respond to prolactin stimulation; hence, lactose may provide a simple marker indicating active physiologic secretory activity of the breast. As reported previously, NAF of darker coloration, containing elevated levels of cholesterol, cholesterol oxidation products, and other substances, suggests retention and impaired reabsorption of these and other products of secretion. Because of the secretion and temporary retention by the breast glands of chemical substances of exogenous and endogenous origin, including mutagens and carcinogens, lactose concentration and coloration of NAF may be useful as markers of secretion and reabsorption in future physiologically based clinical and epidemiologic studies of the pathogenesis of breast disease.

Adult↗
PubMed2002

Altered sugar selection and transport conferred by spontaneous point and deletion mutations in the lactose carrier of Escherichia coli.

Spontaneous mutants harboring the lacY gene on an F'-factor were isolated. Those mutants that failed to grow on 5 mM lactose minimal media plates were chosen for further study. The mutants showed striking mutations in the lactose carrier as well as in sugar selection properties during transport assays. DNA sequencing of the lacY gene of the mutants revealed the following mutations: M-1-I, R-144-W, G-370-C and a deletion of residues 387-392, located in helix 12 of the carrier. Transport studies indicated that ONPG transport ranged between 8 and 25% of normal for the M-1-I, G-370-C and D387-392 mutants and 51% of normal for the R-144-W mutant. The downhill transport of lactose was 2-fold greater than for melibiose in cells harboring the M-1-I mutation and 3-fold higher for cells with the G-370-C mutation. On the other hand, cells with the D387-392-deletion mutation showed no lactose downhill transport, but 47% melibiose transport. Accumulation of TMG, a lactose analog, was 3-fold higher than the accumulation of melibiose in cells with the G-370-C mutation. On the other hand, in cells with the D387-392 mutation, TMG accumulation was completely defective, whereas melibiose accumulation was 50-fold higher than that of TMG, indicating that one or more of these residues in helix 12 of the carrier play a role in the active transport of b-galactoside, but not a-galactoside sugars. Initial lactose downhill transport rates were too unreliable to obtain trustworthy kinetic data. TMG and melibiose accumulation activities were present, but severely reduced in the mutant containing the R144W mutation, confirming that Arg-144 is important for active transport. All transport data were normalized for expression levels. The results indicate that the affected residues play a role in dictating sugar specificity and transport in the lactose carrier. The results here are novel in that they represent mutations in unique locations along the lactose carrier protein. For example, the M-1-I mutation was located at the N-terminal cytoplasmic tail of the carrier. Furthermore, G-370-C was located in the periplasmic loop between helices 11 and 12, suggesting a role for residues in this loop in mediating sugar selection.

Amino Acid Sequence↗
PubMed2004

Control of H+/lactose coupling by ionic interactions in the lactose permease of Escherichia coli.

A combinatorial approach was used to study putative interactions among six ionizable residues (Asp-240, Glu-269, Arg-302, Lys-319, His-322, and Glu-325) in the lactose permease. Neutral mutations were made involving five ion pairs that had not been previously studied. Double mutants, R302L/E325Q and D240N/H322Q, had moderate levels of downhill [(14)C]-lactose transport. Mutants in which only one of these six residues was left unchanged (pentuple mutants) were also made. A Pent269(-) mutant (in which only Glu-269 remains) catalyzed a moderate level of downhill lactose transport. Pent240(-) and Pent 322(+) also showed low levels of downhill lactose transport. Additionally, a Pent240(-) mutant exhibited proton transport upon addition of melibiose, but not lactose. This striking result demonstrates that neutralization of up to five residues of the lactose permease does not abolish proton transport. A mutant with neutral replacements at six ionic residues (hextuple mutant) had low levels of downhill lactose transport, but no uphill accumulation or proton transport. Since none of the mutants in this study catalyzes active accumulation of lactose, this is consistent with other reports that have shown that each residue is essential for proper coupling. Nevertheless, none of the six ionizable residues is individually required for substrate-induced proton cotransport. These results suggest that the H(+) binding domain may be elsewhere in the permease or that cation binding may involve a flexible network of charged residues.

Biological Transport, Active↗