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Is cow's milk suitable for the dietary supplementation of rural Gambian children? 1. Prevalence of lactose maldigestion.

To define the age-related prevalence of lactose maldigestion (LM), 218 children aged 13-72 months from a rural Gambian village were studied using a lactose breath hydrogen test. There was a significant rise in LM from 21% to 76% between the 2nd and 3rd-5th years of life (p < 0.001). Only eight children had diarrhoea within 2 weeks before the test. Diarrhoea and abdominal discomfort followed in only seven children (3%). There was no difference in mean time of introduction of supplementary diet or cessation of breastfeeding between children aged 12-36 months with lactose digestion and LM. There was a greater proportion of children with normal lactose digestion than with LM in those still receiving breast milk (85% vs 15%), and a greater proportion of LM in the fully weaned group (63% vs 37%) (p < 0.001). There was no relation between weight-for-age or weight-for-height and the ability to digest lactose. The ability to digest lactose is lost in the majority of children during the 2nd year, coincident with the cessation of breastfeeding, but is not a major factor associated with growth failure thereafter.

Age Factors↗

Determination of amorphous content of lactose samples by solution calorimetry.

Earlies studies suggest that solution calorimetry can be used to determine the extent of amorphous content of drug and excipient, when the solubility and dissolution rate of the compound in the chosen solvent are reasonably high. In the present study, the use of solution calorimetry for assessment of amorphous content of a sample that is not completely dissolved in a solvent was evaluated. Physical mixtures of lactose and spray-dried lactose samples were analysed. The amorphous content of the physical mixtures and the spray-dried samples varied from 0% to 100% determined by isothermal microcalorimetry. The enthalpy of solution (delta(sol)H) was determined in water. The lactose samples were dissolved quickly in water. In addition, the enthalpy accompanied with an addition of a lactose sample in an over saturated aqueous solution (delta(sat)H) (prepared from the corresponding lactose sample) was determined. The lactose sample did not completely dissolve in the over saturated aqueous solution. An excellent correlation was observed between delta(sol)H and the amorphous content of the samples. Interestingly, there was a linear correlation also between delta(sat)H and the amorphous content of the samples. Further, a linear relationship was observed between the delta(sat)H and the delta(sol)H of the samples. Therefore, solution calorimetry may represent a rapid and simple method for determining the amorphous content also in samples that are not completely dissolved in the solvent.

Calorimetry↗

Rapid and portable methods of lactose tolerance test administration.

Abbreviated, portable methods of lactose tolerance test administration were investigated. Results obtained with the Ames Reflectance Meter/Dextrostix system for blood glucose determination during lactose tolerance testing were compared with those obtained from a standard method, the AutoAnalyzer. Subjects who had maximum blood glucose rises below 20 mg/100 ml were considered to have a flat lactose tolerance curve and were designated lactose nondigesters. Results of the two methods were very similar for determination of maximum rise in blood sugar over fasting level, for obtaining values of individual blood sugar determinations, and for diagnosis of lactose nondigesters. The effect of omission of the final blood sample on tolerance test results was examined. It was found that maximum rises in blood glucose occurred before the final sample in 31 of 35 cases on the AutoAnalyzer and in 26 of 27 cases on the Reflectance Meter. In no case did omission of the final sample change the results of the lactose tolerance test.

Adult↗

Serum lipids and proteins in lactose malabsorption.

It has been suggested that dietary lactose may reduce the intestinal absorption of fat and protein in individuals with lactase deficiency. On the other hand, it is known that a high carbohydrate diet increases serum lipids. The purpose of this study was to examine whether there are differences in the fasting serum lipid and protein concentrations between people with lactose malabsorption and people with normal lactose absorption. Therefore in the connection of a family study serum lipids and proteins were measured in 409 subjects belonging to 11 families. Of these 288 were relatives of the 11 index persons and 121 were spouses or relatives of the spouses. The weight, height, and milk consumption of each person were recorded. When the age, sex, relative weight and milk consumption effects were taken into account there was a statistical difference between the lactose malabsorption and lactose absorption groups for the concentration of serum triglycerides, but not for the other variables. Besides, serum triglyceride values of over 200 mg/100 ml were significantly fewer in people with lactose malabsorption. It was hypothesized that increased intestinal motility may disturb the absorption of fats and cause the observed difference at least in the Finnish population.

Adolescent↗

Effectiveness of milk products in dietary management of lactose malabsorption.

Eleven lactose malabsorbers were studied to compare the effectiveness of commercially available products recommended for dietary treatment of lactose malabsorption. One product, a commercial lactase preparation, is added to milk for lactose hydrolysis before consumption. The other is a commercial milk product containing lactose-hydrolyzing, nonpathogenic bacteria, Lactobacillus acidophilus. Both of these products are presently recommended for management of lactose malabsorption, although such recommendations have not been validated by controlled studies. Lactose malabsorption was determined by breath H2 analyses after subjects drank four different test doses on 4 different days. The first test dose was 480 ml of low fat milk; the second was 480 ml of milk treated with a commercial lactase preparation; the third was 480 ml of a commercial L. acidophilus-containing milk; and the fourth was 480 ml of the L. acidophilus-containing milk after 1 wk of gastrointestinal exposure to this commercial bacteria-containing milk. The mean breath H2 response to the lactase-treated milk was significantly lower (p less than 0.001) than the mean response to regular milk. However, the mean breath H2 response to either of the test doses of the L. acidophilus-containing milk were not significantly different than responses to regular milk. It is concluded that the lactase-treated milk reduces breath H2 responses and symptomatic discomfort from malabsorption while the L. acidophilus-containing milk does not.

Adult↗

Population dynamics of a Lac- strain of Escherichia coli during selection for lactose utilization.

During selection for lactose utilization, Lac+ revertants of FC40, a Lac- strain of Escherichia coli, appear at a high rate. Yet, no Lac+ revertants appear in the absence of lactose, or in its presence if the cells have another, unfulfilled requirement for growth. This study investigates more fully the population dynamics of FC40 when incubated in the absence of a carbon source or when undergoing selection for lactose utilization. In the absence of a carbon source, the viable cell numbers do not change over 6 days. When incubated in liquid lactose medium, Lac- cells do not undergo any measurable increase in numbers or in turbidity for at least 2 days. When FC40 is plated on lactose minimum medium in the presence of scavenger cells, the upper limit to the amount of growth of Lac- cells during 5 days is one doubling, and there is no evidence for turnover (i.e., a balance between growth and death). The presence of a minority population that could form microcolonies was not detected. The implications of these results, plus the fact that the appearance of Lac+ revertants during lactose selection is nearly constant with time, are discussed in reference to several models that have been postulated to account for adaptive mutations.

Alleles↗

Interactions of lactose with calcium, magnesium and zinc in rats.

The effects of lactose on utilization of calcium, magnesium and zinc were examined in two studies. In study 1, weanling male rats were fed either nonfat dry milk or CaHPO4, dolomite or a calcium chelate with supplemental lactose or sucrose for 27 d. In study 2, weanling male rats were fed diets based on milk or lactose-hydrolyzed milk for 28 d or in one meal labeled with 45Ca. Rats fed the lactose-hydrolyzed milk rather than the untreated milk digested their diet more completely, apparently absorbed total calcium and 45Ca less efficiently, and lost more calcium in urine but retained similar amounts of total calcium and 45Ca in bone. The effect of lactose hydrolysis on the absorption of 45Ca was similar whether rats were fed only one meal of the milk-based diets or were fed the diets chronically. The rats fed supplemental lactose (study 1) or unhydrolyzed milk (study 2) retained more magnesium and zinc in bone.

Absorption↗

Carbohydrate binding specificity of monoclonal antibodies raised against lactose-protein Maillard adducts.

Three hybridoma antibodies (L101, L104, and L117) specific for lactose-protein amino carbonyl products (Maillard adducts) were obtained by immunizing mice with the lactose-ovalbumin Maillard adduct and by screening with the lactose-bovine serum albumin (BSA) adduct. They reacted with the Maillard adducts of lactose with several different proteins, but not with the adducts of several other reducing sugars. L101 reacted well with the lactose-BSA adducts formed by 2- to 16-day incubation, whereas L104 and L117 reacted with the advanced stage reaction products but not with the adducts of 2-day incubation. The competitive inhibition of the antibody binding by several mono- and disaccharides showed that lactulose (4-O-beta-D-galactopylanosyl-D-fructose) was the best inhibitor for all three antibodies, and that L104 and L117 were inhibited by methyl-beta-D-galactoside more effectively than L101. These results suggested that different components produced during the progress of the Maillard reaction could be antigenic determinants, and that the carbohydrate moiety including the terminal galactosyl residue played an important role in the antibody binding to the lactose-protein Maillard adducts.

Animals↗

Characteristics of intact lactose transport in rat jejunum in vitro.

The characteristics and kinetics of intact transmucosal transport of lactose have been studied in the rat jejunum using an everted sac preparation. Lactose transport displayed linear kinetics up to the maximum concentration (150 mM) of lactose studied. Ouabain (1 mM) when placed in the serosal solution, and phlorhizin (0.1 mM) when placed in the mucosal solution, had no significant effect on lactose transport. In contrast to glucose, transport of intact lactose did not occur against a concentration gradient. These results strongly suggest that intact transmucosal transport of lactose occurs by a process of simple passive diffusion, and that it is independent of the sodium-coupled glucose transport system.

Animals↗

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.

Breath Tests↗

Efficient assimilation of lactose carbon in premature infants.

Previous studies have shown that there is minimal fecal excretion of carbohydrate energy in premature infants with high breath H2 concentrations, implying that the colon plays an important role in salvaging lactose energy. The present study extends this work by using a stable isotope method for serial assessment of lactose carbon excretion. Thus, in nine premature infants (30-32 weeks of gestation and 11-36 days of age), we conducted 23 longitudinal studies of breath hydrogen concentration and the cumulative fecal excretion of 13C derived from a single dose of [D-1-13C]lactose. The ranges of values (mean +/- SD) for breath hydrogen concentration and lactose absorption were respectively 4-440 ppm/5% CO2 (92 +/- 100) and 82-100% tracer dose (98.4 +/- 3.9). In 21 studies, lactose carbon excretion was less than 2% of the dose. There was a significant correlation between postnatal age and breath hydrogen concentration (R = 0.48; p = 0.02). These studies suggest that colonic fermentation activity is adequate for efficient colonic salvage of lactose even during the second week of life.

Breath Tests↗

Malabsorption of different lactose loads in children with human immunodeficiency virus infection.

Thirty children infected with human immunodeficiency virus (HIV) (18 P1 and 12 P2, according to the classification system of the Centers for Disease Control) and 54 noninfected children were evaluated for lactose malabsorption with use of the hydrogen breath test after different lactose loads. Lactose malabsorption after load of 2 g/kg occurred in 75% of P2, 67% of P1, and in 46% of noninfected children. With a lower lactose load (1 g/kg), the prevalence of malabsorption was significantly higher among P2 children than P1 and noninfected cases. A similar figure was obtained after the lowest load (0.5 g/kg). Infected children with lactose malabsorption were significantly younger than noninfected malabsorbers (mean age +/- SD; 50.3 +/- 22 vs. 63.5 +/- 20.9 months) when the load of 2 g/kg was used. The use of lower lactose loads seems to be helpful in finding the dose that can be tolerated. This finding could have nutritional importance and could lead to better dietary management.

Breath Tests↗

Lactose intolerance and lactase deficiency in children.

The term lactase deficiency is widely used to indicate a low or absent level of lactase enzyme in the small intestine, leading to lactose intolerance. This term is correctly used when the intestinal mucosa is damaged and results in secondary lactase deficiency. In the case of the genetically determined decrease of lactase activity during childhood, however, low lactase levels suggest that the majority of the world's population is "abnormal," whereas individuals from caucasian extraction with high levels of lactase enzyme throughout life are then considered "normal." It would be better to ascribe racial and ethnic lactose malabsorption as the result of genetically determined reduction of lactase activity, rather then implying an "abnormality" by the term, "deficiency." Recent studies reveal that this genetic control is at the transcriptional level. The symptomatology of lactose intolerance varies widely, and the diagnostic method of choice is the lactose breath hydrogen test in combination with clinical findings, although small intestinal biopsies should be performed when mucosal diseases are suspected. Treatment of lactose intolerance depends on the age of the child. In young infants complete restriction of lactose containing foods is rarely necessary.

Adult↗

Regulation of the lactose phosphotransferase system of Streptococcus bovis by glucose: independence of inducer exclusion and expulsion mechanisms.

Streptococcus bovis had a diauxic pattern of glucose and lactose utilization, and both of these sugars were transported by the sugar phosphotransferase system (PTS). Lactose catabolism was inducible, and S. bovis used the tagatose pathway to ferment lactose. Since a mutant that was deficient in glucose PTS activity transported lactose as fast as the wild-type, it appeared that S. bovis has separate enzyme IIs for glucose and lactose. The nonmetabolizable glucose analogue 2-deoxyglucose (2-DG) was a noncompetitive inhibitor of methyl beta-D-thiogalactopyranoside (TMG) transport, and cells that were provided with either glucose or 2-DG were unable to transport TMG or lactose. Because the glucose-PTS-deficient mutant could ferment glucose, but could not exclude TMG, it appeared that enzyme IIGlc rather than glucose catabolism per se was the critical feature of inducer exclusion. Cells that had accumulated TMG as TMG 6-phosphate expelled free TMG when glucose was added, but 2-DG was unable to cause TMG expulsion. The glucose-PTS-deficient mutant could still expel TMG in the presence of exogenous glucose. Membrane vesicles also exhibited glucose-dependent TMG exclusion and TMG expulsion. Membrane vesicles that were electroporated with phosphoenolpyruvate (PEP) and HPr retained TMG for more than 3 min, but vesicles that were electroporated with PEP plus HPr and fructose 1,6-diphosphate (FDP) (or glycerate 2-phosphate) lost their ability to retain TMG. Because FDP was able to trigger the ATP-dependent phosphorylation of HPr, it appeared that inducer expulsion was mediated by an FDP-activated protein kinase.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗

Escherichia coli heat-labile enterotoxin binds to glycosylated proteins with lactose by amino carbonyl reaction.

The binding of Escherichia coli heat-labile enterotoxin (LT) type I to glycosylated proteins with lactose (Gal beta 1-4Glc) by amino carbonyl reaction was studied by the Western blot assay and by the microtiter well binding assay. LT bound to a lactose-alpha-lactalbumin amino carbonyl product (Lac-LA), whereas cholera toxin did not. The binding ability of Lac-LA was abolished by beta-galactosidase treatment, indicating that the terminal galactose is essential for the binding of LT. The binding of LT to Lac-LA was inhibited by galactose and lactose, and most effectively inhibited by lactulose (Gal beta 1-4Fru), which is a structural analog of the Amadori rearrangement product of the amino carbonyl reaction between lactose and an epsilon-amino group of a lysine residue (lactuloselysine). The results suggest that LT recognizes the portion of lactuloselysine in Lac-LA. LT also bound to a melibiose (Gal alpha 1-6Glc)-alpha-lactalbumin amino carbonyl product (Mel-LA), but the binding ability of Mel-LA was weaker than that of Lac-LA, suggesting that the beta 1-4 linked terminal galactose is dispensable but preferable for the binding. Furthermore, LT bound to the amino carbonyl products of lactose with beta-lactoglobulin, caseins, bovine serum albumin, and ovalbumin. These results indicate that LT binds to the amino carbonyl products between proteins and sugars containing the terminal galactose, such as lactose.

Animals↗

Genetic characterization of a Rhizobium meliloti lactose utilization locus.

We identified several linked genes of a lactose regulon in Rhizobium meliloti. These were lacZ, the structural gene for beta-galactosidase; lacR, the lactose repressor gene; and two genes encoding proteins of unknown function, lacW and lacX. Insertion mutants in lacW and lacZ belonged to a single genetic complementation group, and lacW appeared to lie upstream of lacZ in an operon. Expression of lacZ, lacW and lacX was repressed by lacR, and expression of lacZ and lacW was derepressed by lactose. lacZ was not required for induction of lacW by lactose, suggesting that lactose itself, rather than a processed form of lactose, may be the actual inducer molecule. Expression of all three genes was repressed by succinate, and the lacR independence of this repression showed that inducer exclusion could not be the sole mechanism. This pattern of lac gene organization and regulation differs in several ways from that observed in enteric bacteria.

DNA Transposable Elements↗

The regulation of expression of the Lactococcus lactis lactose operon.

Translational gene fusions between the Escherichia coli beta-galactosidase (lacZ) gene and the Lactococcus lactis lactose operon were constructed such that transcription from the lactose operon promoter could be assessed by measuring beta-galactosidase activity. The level of beta-galactosidase activity was up to 2.5-fold lower when MG5267 cells, which contain a chromosomal copy of the lactose operon, were grown in glucose compared to those grown in lactose. A greater degree of repression was seen in cells containing the multi-copy plasmid-encoded repressor than in those with only the single-copy chromosomal gene, indicating that the repressor protein is at least partly responsible for the reduction in expression when the cells are grown in glucose (i.e. in the absence of inducer). However, the beta-galactosidase activity was found to be 5.5-fold lower in glucose than in lactose in cells which lacked a fully functional lactose operon. The decrease in expression was shown to be due to glucose repression. The levels of expression when the cells were grown in glucose were considerably higher for MG5267 than for MG1363 suggesting perhaps that a product of the chromosomally-encoded operon in MG5267 has a positive effect on transcription.

Cloning, Molecular↗

Lactose and protein absorption from breast milk and cow's milk preparations and its influence on the intestinal flora. Investigations on two infants with an artificial anus.

Lactose and protein absorption from breast milk and a cow's milk preparation enriched up to 7% of lactose were studied in two infants with an artificial anus applied in the ascending colon region. The concentrations of protein, lactose, glucose and galactose were measured in the fistula stools. In addition, the stools were analysed microbiologically. There were relatively high concentrations of lactose and its decomposition products and low concentrations of protein and aminonitrogen in the fistula stools when breast milk was fed. When the cow's milk formula was applied, only traces of lactose but high amounts of protein were measured. The microbiological findings are in agreement with the hypothesis that the bacterial flora of the large intestine is influenced by the lactose and protein concentrations in the intestinal content which reach the large intestine.

Animals↗