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A retrospective assessment of the clinical value of jejunal disaccharidase analysis.

BACKGROUND: The measurement of jejunal disaccharidases is used by several gastroenterologists when investigating suspected small-bowel disease. The clinical value of this analysis is assessed. METHOD: The histology and disaccharidase results in 1585 jejunal biopsy specimens were reviewed retrospectively. RESULTS: Disaccharidase and histology results concurred in most cases (72%). However, disaccharidases were an insensitive indicator of small-bowel disease: low levels were found in only 65% of coeliac patients with villous atrophy, 15% of patients with giardiasis, and 6% of patients with villous atrophy associated with non-coeliac histology. Low disaccharidase levels were sometimes found in patients with normal histology (1.6%) and when biopsy specimens were unwittingly taken from non-jejunal sites (1.4%). Isolated low lactase activities were found in 3.2%. Usually this finding was not clinically relevant because patients had no symptoms of lactose intolerance (38%), had another diagnosis that responded to appropriate treatment (8%), or had no response to a low-lactose diet (14%). In 16 patients sucrase activities were markedly low, and this investigation proved central to the diagnosis of sucrase-alpha-dextrinase deficiency, which was subsequently confirmed in 9. CONCLUSION: Jejunal disaccharidases are clinically useful only in the diagnosis of sucrase-alpha-dextrinase deficiency. We recommend that their measurement be reserved for the investigation of patients suspected of having this condition.

Adult↗

Assessment of optimal dose of lactose for lactose hydrogen breath test in Indian adults.

To evaluate the possibility of using a 12.5 g or 25 g oral dose of lactose for hydrogen breath test for diagnosis of lactose intolerance instead of the usual 50 g dose. 35 patients with non-ulcer dyspepsia and an abnormal 50 g lactose breath hydrogen of more than 20 ppm over the base line were retested using 12.5 g and 25 g lactose. 32 (91.4%) and 15 (42.8%) of these 35 patients had an abnormal hydrogen breath test using 25 g (p = ns compared to 50 g dose) and 12.5 g (p < 0.001) lactose doses respectively. This study reveals that it may be possible to use a 25 g lactose dose instead of a 50 g dose for the lactose hydrogen breath test.

Breath Tests↗

Disaccharide consumption and malabsorption in Canadian Indians.

Twenty-eight Sioux and 29 Saluteaux Indians from a southern and an isolated northern Manitoban community were screened for lactose malabsorption; 55 were also screened for sucrose tolerance. Sixty percent of the subjects were lactose malabsorbers; the incidence increased with age. Lactase deficiency appeared, on the average, between 8 and 15 years of age. About 45% of the subjects were lactose intolerant. Malabsorbers who did not regularly drink milk had the highest symptom scores. The northern subjects consumed significantly more lactose and sucrose than the southern subjects. Two Sioux children were sucrose malabsorbers. It was hypothesized that the significantly greater sucrose consumption by the Saulteaux subjects were responsible for their markedly higher blood glucose curve following the sucrose tolerance tests. Dietary sucrose increases jejunal sucrase activity and the intestinal transport of glucose and fructose. Three of eight children less than 4 years were lactose malabsorbers; hence, medical personnel treating noninjective diarrhea in Indian children should examine for lactase deficiency. It was recommended that vitamin D fortified milk supplements to Indian school children be continued and that the milk be treated so as to reduce abdominal symptoms in the intolerant individuals.

Adolescent↗

A possible explanation of the effects of dietary lactose concentration during recovery of protein depletion in growing rats.

It is generally accepted that lactose intolerance is a cause of delayed recovery from malnutrition. To discriminate the true importance of this factor, the effect of dietary lactose concentration on "catch up" growth was studied on rats fed a protein free diet from weaning to 34 days of age and then refed "ad libitum" with diets providing different levels of Protein Calories (P%: 5, 11, 17 and 25%) and Lactose (L%: 0, 1, 15, 27 and 37%) for 4 days. Weight changes, daily dietary intakes and gastrointestinal disorders (GID) were recorded. The growth rate (GR) -g/100g rat/day- showed a direct correlation with P% whereas a decrease in (GR) as well as in Protein Utilization (PU) was associated with increasing L%, the higher the P%, the greater the effect of L%. The observed effect of lactose on (PU) does not correlate with (GID). Analysis of intake data -expressed as calories/day/W0.73- showed that animals ate less diet when lactose was present resulting in energy restriction (ER) from 12 to 62%. A primary effect of food intake might be proposed as a limiting factor for (GR) and (PU) in rats recovering from depletion. The influence of P% on improved lactose tolerance must also be stressed.

Animals↗

Influence of intestinal parasitism on lactose absorption in well-nourished African children.

Hydrogen breath tests were performed in Gabon (Central Africa) after a loading dose of lactose in 67 well-nourished African children (50 with intestinal parasites and 17 unparasitized) and in 18 unparasitized young adults. All had normal nutritional status, and none had diarrhea or digestive symptoms. Parasites that were found included Ascaris lumbricoides in 76% of the parasitized children, Trichuris trichiura in 58%, Giardia in 24%, Entamoeba histolytica in 20%, Schistosoma intercalatum in 16%, and Necator Americanus in 14%. A similar proportion of parasitized (64%) or unparasitized (62.8%) subjects were lactose malabsorbers. Giardia infection was associated with a higher, but not significantly different, proportion of lactose intolerance (10 of 12, 83.3%). The presence of infection with A. lumbricoides or T. trichiura did not increase the percentage of lactose malabsorption. These data indicate that a decrease of lactase activity in well-nourished African children is not related to the presence or the importance of Ascaris or other intestinal parasites if the nutritional status is normal.

Animals↗

[Breath analysis tests in gastrointestinal disorders (author's transl)].

From various breath tests up to now mainly measurement of respiratory 14CO2 and hydrogen have attained clinical application. Breath tests are easily performable, without discomfort for patient or in investigator and do hardly require active support of the patient. On the other hand absorption tests, as 14C-tripalmitate- and 14C-lactose-breath test, are influenced by alterations of the metabolism in a considerable degree, and clinical significance and specificity of the 14C-cholylcycline-breath test remains questionable hitherto. Nevertheless, obtained values which are independent from metabolism, high sensitivity and lack of competitive methods are arguments for the 14C-cholylglycinebreth test for the diagnosis of bacterial overgrowth in the small bowel. Breath analysis of hydrogen seems to be a very sensitive and reliable method for detecting carbohydrate malabsorption, as lactose intolerance.

Breath Tests↗

Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever.

Abdominal pain and diarrhea are frequent side effects of chronic colchicine therapy. Drug-induced lactose deficiency has been demonstrated in the experimental animal. Lactose malabsorption was assessed by the lactose breath test in 23 patients with familial Mediterranean fever (FMF) receiving colchicine for 0.25-15 years (mean 3.16). Twenty FMF patients not receiving colchicine and 38 non-FMF lactose malabsorbers served as controls. Patients receiving colchicine had a significantly higher percentage of lactose malabsorption (20/23, 87%) versus nontreated FMF patients (13/20, 65%; P < 0.05). Lactose intolerance was also more prevalent in colchicine-treated patients (17/23, 74%) versus nontreated FMF (5/20, 25%; P < 0.0005) and control lactose malabsorbers (16/38, 42%; P < 0.01). Of the 12 patients investigated before and 3 months after colchicine administration, 7 showed induction or aggravation of lactose malabsorption. The lactose-free diet resulted in partial improvement of symptoms. Colchicine induces significant lactose malabsorption in FMF patients and this is partially responsible for the gastrointestinal side effects of the drug.

Abdominal Pain↗

In vitro and in vivo lactose and lactulose effects on colonic fermentation and portal-systemic encephalopathy parameters.

Lactose intolerance occurs in the majority of human groups, excluding people from Northern Europe. Because its effect is similar to that of lactulose, lactose seems to be an alternative treatment for patients with portal-systemic encephalopathy (PSE) and lactase deficiency. The mechanism of action of lactose is similar to that of lactulose. In vivo, lactose improves PSE parameters and causes acidic diarrhea. We performed in vitro studies in a fecal incubation system to investigate the biochemical and bacteriological effects induced by different substances customarily used for the treatment of patients with PSE (lactose, lactulose and Neomycin). In vitro experiments showed that lactose and lactulose decreased aerobic flora counts and reduced the pH of fecal incubation. Both disaccharides reduced the ammonia concentration in the incubation system.

Anti-Bacterial Agents↗

Lactose digestion and clinical tolerance to milk, lactose-prehydrolyzed milk and enzyme-added milk: a study in undernourished continuously enteral-fed patients.

We investigated: (1) the capacity to digest and tolerate the lactose administered by continuous infusion of intact milk to undernourished tube-fed patients, and (2) the effectiveness of lactose-prehydrolyzed milk, and of the addition of exogenous lactase to milk at infusion time, to reduce lactose maldigestion and increase clinical tolerance. Carbohydrate digestion was evaluated in 10 subjects with the hydrogen breath analysis test during 8 hr of observation. Lactose intolerance was determined by evaluation of subject's symptoms. With the infusion of intact milk (IM), none of the subjects were able to efficiently digest the lactose infused (5.6 +/- 0.35 g/hr, mean +/- SEM) and 86% of them experienced major symptoms of intolerance. With the infusion of lactose-prehydrolyzed milk (HM) and enzyme-added milk (EM) there was a highly significant reduction in lactose maldigestion. More importantly, major symptoms were present in only 10% of subjects with EM, and were completely eliminated with HM. Lactose maldigestion and intolerance represent a major limitation for the application of milk-based polymeric formula for liquid diets in undernourished subjects. The use of exogenous beta-galactosidases represents an alternative to avoid such reactions.

Adult↗

PCR-RFLP genotyping assay for a lactase persistence polymorphism upstream of the lactase-phlorizin hydrolase gene.

The majority of the world's human population experiences a decline of lactase gene expression during maturation, so-called lactase nonpersistence. Thus, adults with lactase nonpersistence are susceptible to developing symptoms of lactose intolerance. By contrast, lactase persistence is an autosomal dominant heritable condition that results in a high level of lactase gene expression throughout adulthood and sustained lactose tolerance. Lactase persistence has recently been correlated with a single nucleotide genetic variant (a C --> T mutation) located 13,910 bases upstream from the lactase structural gene. We aimed to develop a restriction fragment length polymorphism (RFLP) method of detecting the C/T variants as a means of identifying individuals genetically inclined toward lactase persistence or nonpersistence. Genomic DNA in a 210-bp region surrounding the -13,910-bp variant site was PCR amplified with unique primers designed to avoid or mutate adjacent restriction sites. The amplified DNA was digested with a restriction enzyme, CviJI, that recognizes the base pair sequence generated by the lactase nonpersistence variant. Restriction digest gel analysis yielded DNA fragments of the expected diagnostic molecular weight sizes for individuals that were homozygote or heterozygote for the lactase persistence and nonpersistence variants. The genotypes predicted by the RFLP-based method were confirmed by DNA sequence analysis. The RFLP-based method provides a quick and noninvasive means of molecular detection of the presence or absence of the lactase persistence variant.

Adult↗

Carbohydrate digestion and absorption studies in the horse.

The ability of the horse to digest and absorb soluble carbohydrates was assessed using a series of oral disaccharide tolerance tests followed in the same animals by tolerance tests with the constituent monosaccharides. In horses older than three years, lactose did not produce an increase in the plasma glucose levels but induced the passing of soft faeces, indicating that adult horses are lactose intolerant. Horses of all ages could absorb the glucose: galactose mixture without any change in the faeces. The tolerance is due to a failure to hydrolyse lactose and does not involve the monosaccharide transport systems. These findings correspond to the known development pattern of brush border lactase activity in the equine small intestine. Both sucrose and maltose were rapidly hydrolysed, the resulting tolerance curves closely approximating to those for the constituent monosaccharides. Galactose was absorbed at a similar rate to glucose, although a dose of 1g/kg was necessary to produce galactosaemia. An oral lactose tolerance test (1 g/kg as a 20 per cent solution) could be of clinical value to determine small intestinal mucosal damage in diarrhoeic foals when the continued ingestion of lactose might be detrimental.

Animals↗

Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactose-free diet.

Lactose malabsorption may induce abdominal symptoms indistinguishable from those of the irritable bowel syndrome (IBS), however the exact relationship between the two conditions and the optimal differential diagnostic workup are still to be defined. We prospectively studied the prevalence of lactose malabsorption (by means of a hydrogen breath test) and the clinical effect of a long-term lactose-free diet in 230 consecutive patients with a suggested diagnosis of irritable bowel syndrome, no organic disease of the GI tract, and no history of milk intolerance. Lactose malabsorption was diagnosed in 157 patients (68.2%). In 48 (43.6%) of the 110 patients who complied with the diet symptoms subsided, in 43 they were somewhat reduced and in 17 they remained unchanged. Symptoms never fully subsided in lactose malabsorbers non-compliant with the diet or in normal lactose absorbers who adhered to a lactose-free regimen. Partial improvement was observed in 20% of these subjects. No relation was demonstrated between pre-trial symptoms and the outcome of the diet. The occurrence of symptoms during the lactose breath test strongly suggested a favorable response to diet, but did not help in predicting whether symptoms would subside or be reduced. Conversely, their absence during the test was not associated with an acceptable negative predictive value. The high prevalence of lactose malabsorption in the patients under study suggests that in Italy IBS and lactose malabsorption are frequently associated. A test for diagnosing lactose malabsorption should always be included in the diagnostic workup for IBS and a long-term lactose-free regimen recommended if the test is positive.

Adult↗

Identification of a variant associated with adult-type hypolactasia.

Adult-type hypolactasia, also known as lactase non-persistence (lactose intolerance), is a common autosomal recessive condition resulting from the physiological decline in activity of the lactase-phlorizin hydrolase (LPH) in intestinal cells after weaning. LPH hydrolyzes lactose into glucose and galactose. Sequence analyses of the coding and promoter regions of LCT, the gene encoding LPH, has revealed no DNA variations correlating with lactase non-persistence. An associated haplotype spanning LCT, as well as a distinct difference in the transcript levels of 'non-persistence' and 'persistence' alleles in heterozygotes, suggest that a cis-acting element contributes to the lactase non-persistence phenotype. Using linkage disequilibrium (LD) and haplotype analysis of nine extended Finnish families, we restricted the locus to a 47-kb interval on 2q21. Sequence analysis of the complete region and subsequent association analyses revealed that a DNA variant, C/T-13910, roughly 14 kb upstream from the LCT locus, completely associates with biochemically verified lactase non-persistence in Finnish families and a sample set of 236 individuals from four different populations. A second variant, G/A-22018, 8 kb telomeric to C/T-13910, is also associated with the trait in 229 of 236 cases. Prevalence of the C/T-13910 variant in 1,047 DNA samples is consistent with the reported prevalence of adult-type hypolactasia in four different populations. That the variant (C/T-13910) occurs in distantly related populations indicates that it is very old.

Adult↗

A study of lactose absorption capacity in twins.

Lactose absorption capacity was determined by lactose tolerance tests with breath hydrogen determination in 102 healthy, adult, Hungarian pairs of twins in order to test monogenic Mendelian inheritance of the absorptive lactase phenotypes, lactose absorber and lactose malabsorber. Of the total, 52 pairs were monozygous (MZ) and 50 dizygous (DZ) twins of identical sex. All MZ twins were concordant with respect to lactase phenotype. Among DZ twins, the distribution of lactase phenotypes was in agreement with Hardy-Weinberg expectations derived from the frequencies of the hypolactasia gene in DZ and MZ twins, and in the general Budapest population. In the second part of the study, three commonly used methods of lactose tolerance testing, the blood glucose, the blood galactose, and the breath hydrogen tests, were compared in 49 pairs of twins concordant for lactase phenotype. Blood galactose concentration showed the greatest and only significant difference between the intrapair correlation coefficients of MZ and DZ, and no overlap between lactose absorbers and lactose malabsorbers. The intrapair correlation coefficients of peak breath hydrogen concentration in MZ and DZ twins did not significantly differ from zero, but the resolution of lactase phenotypes was satisfactory. Differences in glucose absorption and concentration in lactose absorbers and malobsorbers overlapped considerably, and among lactose absorbers correlation coefficients in DZ were higher than in MZ twins. In MZ and DZ twins, the difference in concordance and constancy of lactose intolerance symptoms was not significant.

Adolescent↗

Relative efficiency of yogurt, sweet acidophilus milk, hydrolyzed-lactose milk, and a commercial lactase tablet in alleviating lactose maldigestion.

The relative effectiveness of commercially available plain yogurt (Y), sweet acidophilus milk (SAM), hydrolyzed-lactose milk (HLM), a lactase tablet (LT), and whole milk (WM) was evaluated in 10 lactose-intolerant black subjects. In a 5 x 5 Latin square design, hourly breath hydrogen excretion (BHE) was measured for 5 h after the subjects consumed the above products (18 g lactose in each except HLM, which had 5 g). Mean BHE (ppm) for Y, SAM, LT, HLM, and WM were 12, 37, 29, 18, and 33, respectively. There was a significant (p less than 0.05) positive correlation of 0.808 between the symptoms reported and the mean peak BHE. However, the correlation between the symptoms and diagnosis by history was not significant. Although Y was as effective as HLM in minimizing lactose maldigestion, it was the least accepted by the subjects in sensory evaluations. Results of this study also indicate that microbial endogenous lactase in yogurt is superior to exogenous commercial lactase in alleviating lactose maldigestion.

Adult↗

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.

Adolescent↗

[Trial of milk with low-lactose contents in acute diarrhea].

Fifty infants with acute diarrhea (less than or equal to 5 days of duration) were refed with either a low-lactose formula (experimental group, N = 25) or whole powdered cow's milk (control group, N = 25). During a two-month follow up etiology, clinical course, changes of anthropometric parameters and tolerance to the milk products were evaluated. The etiology of diarrhoea, the mean duration of the episodes (3.6 +/- 1.9 and 3.9 +/- 1.9 days in the experimental and control group, respectively) and the clinical course were comparable in both groups. Nutritional parameters remained unchanged during and after the episode. In two children (8.3%) of the control group stools continued to be liquid, fecal pH was 5 and reducing substances were positive. They had to be refed with the low-lactose product to induce remission of the symptoms. Both products were well tolerated. These findings suggest that availability of low-lactose formulae may be advantageous in the clinical management of infants with acute diarrhea and evidence of lactose intolerance.

Acute Disease↗

Lactose: the milk sugar from a biotechnological perspective.

Lactose is a very important sugar because of its abundance in the milk of humans and domestic animals. Lactose is a valuable asset as a basic nutrient and the main substrate in fermentative processes that led to the production of fermented milk products, such as yogurt and kefir. In some instances, lactose also can be a problem as the causative agent of some diseases, such as lactose intolerance and galactosemia, or for being a by-product generated in huge amounts by the cheese industry. The study of the biochemical reactions leading to the synthesis and assimilation of lactose has provided valuable models for the understanding of biosynthetic and catabolic processes. Lactose-hydrolyzing enzymes are structurally and phylogenetically related to different types of beta-galactosidases and bacterial cellobiases involved in the enzymatic degradation of cellulose. Biotransformation of lactose, by either enzymatic or fermentative procedures, is important for different types of industrial applications in dairy and pharmaceutical industries.

Animals↗