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Physicochemical characteristics of commercial lactases relevant to their application in the alleviation of lactose intolerance.

Selected microbial lactases are used to treat lactose intolerance. A series of experiments were carried out in vitro in order to determine the likely relative suitability of four major commercial lactase products used in this regard. The lactases displayed between 55 and 61% of maximum activity at 37 degrees C and significant activity between pH 3.0 and 6.5. They retained between 0 and 65% of original activities after exposure to full simulated digestive tract conditions for 6 h. All four enzymes proved to be particularly acid sensitive and only two products were enteric coated. The products demonstrated varying ability to hydrolyze lactose under simulated digestive tract conditions. The most effective product hydrolyzed 2.7 g lactose per capsule, suggesting that consumption of several capsules, as opposed to the usually recommended one or two, would be required to hydrolyze the entire 12 g lactose load characteristic of a dairy-based meal. All enzymes were substantially pure and displayed similar kinetic properties and molecular weights. None appeared ideally suited for use in the alleviation of lactose intolerance. The findings may in part explain the variability and often disappointing results previously reported for lactase-based clinical trials and will provide comparative baseline data against which candidate second-generation lactases may be assessed.

Animals↗

Nursing caries and lactose intolerance.

Caries is associated with fermentable carbohydrates in the diet. Dietary content can be related to personal and cultural preferences, availability of food, or physiologic tolerances. Twenty-seven percent of black children ages 12 to 24 months, in the Baltimore area were reported with symptoms of lactose intolerance. The incidence of lactose intolerance increased to 33 percent by age six years. At the same time, clinical observations of this same population suggested a high prevalence of nursing caries. One purpose of this study was to determine whether parents of black children with nursing caries perceived in their children more severe symptoms of lactose intolerance, which they related to milk products, than did parents of caries-free black children. A second purpose was to determine whether there were differences in feeding habits and types of fluids given children with nursing caries compared with caries-free children. A questionnaire concerning symptoms consistent with lactose intolerance, feeding habits, and fluid-selection was administered to the following groups: parents of 30 black children, ages 18 to 54 months, who were caries-free and parents of 30 black children, ages 18 to 54 months, diagnosed with nursing caries. Chi-square analysis or t-test analysis were performed on results accepting p < 0.05 as significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Lactose intolerance in chronic inflammatory bowel diseases].

In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66] years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74] years) the incidence of lactose intolerance, as measured by the H2 breath test and blood sugar concentration, was determined prospectively. To exclude abnormal bacterial colonization of the small intestine or rapid small-intestine transit after partial resection of the small intestine as a cause of lactose intolerance, the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21 of 124 patients with Crohn's disease (16.9%) had the expected incidence of lactose intolerance, this was present in only 2 of 53 patients with ulcerative colitis (3.8%; P < 0.05). The lactose intolerance was independent of the site of any inflammatory changes, disease activity and extent of small-intestine resection. Oro-caecal transit time for lactose was similar for all patients. There was no lactose intolerance in two patients with abnormal small-intestinal bacterial colonization.--Because of their considerable diagnostic and prognostic significance, tests for lactose intolerance should be performed routinely in all cases of Crohn's disease or ulcerative colitis.

Adolescent↗

Familial aquagenic urticaria associated with familial lactose intolerance.

Aquagenic urticaria is a rare disorder characterized by the occurrence of pruritus and wheals after temporary contact with water. The familial occurrence of aquagenic urticaria over 3 generations is reported here in association with familial lactose intolerance, a condition in which the enzyme lactase encoded on chromosome 2, is deficient. In two patients, a young man and his mother, we verified the appearance of pruritic hives 5 to 10 minutes after contact with water of any temperature. Other types of physical urticaria were absent, and mastocytosis was excluded by extensive laboratory investigations; lactose intolerance was confirmed in both patients by H(2)-exhalation test. In these patients the clinical symptoms did not respond to antihistamines or UV-radiation therapy. Four other members of the family had wheals from water contact, two of whom had lactose intolerance. Two other members had lactose intolerance only. Although the association of aquagenic urticaria with lactose intolerance may be coincidental, attention is drawn to the fact that the 2 conditions, known to be familial, may coexist in the same family, possibly based on an association of gene loci.

Adult↗

Possible therapeutic use of loperamide for symptoms of lactose intolerance.

OBJECTIVES: To examine a potential practical therapeutic use of loperamide (Lo) to decrease the symptoms of lactose intolerance. SUBJECTS AND METHODS: Nineteen (eight men, 11 women) healthy lactose maldigesters (18 of 19 with symptoms) underwent a 25 g lactose challenge on five separate days. Breath hydrogen was measured, areas under the curve (AUC) were calculated for 4 h, and 4 and 12 h symptom scores were recorded. After establishing baseline measurements, test doses of 4 mg, 8 mg and 12 mg Lo were randomly administered without placebo in a double-blind manner. As well, each subject received seven lactase tablets, in a random, unblinded manner. RESULTS: The median AUC and mean oral cecal transit time followed dose response expectations; however, only lactase treatment achieved significance. Nevertheless, 8 mg Lo significantly improved symptom scores, which were statistically indistinguishable from those of lactase. Four subjects complained of delayed constipation and cramps with various doses of Lo. CONCLUSIONS: Lo monotherapy for lactose intolerance is not economical and may have some side effects. However, Lo may be studied further as an adjunctive treatment of lactose intolerance in an effort to reduce the need for complete lactose digestion. Such a manoeuvre may allow rapid colonic adaptation, which in turn may be beneficial for prophylaxis for a number of colonic diseases.

Adolescent↗

Effect of a single dose of lactase on symptoms and expired hydrogen after lactose challenge in lactose-intolerant subjects.

The effect of a single dose or oral lactase on symptoms, breath hydrogen concentration, and glucose absorption in lactose-intolerant subjects challenged with lactose was studied. Volunteers underwent a lactose challenge test; those whose breath hydrogen concentrations increased 20 ppm or more and who met other criteria were admitted as subjects. After fasting, the subjects were given three chewable lactase tablets (total lactase dose, 9900 FCC units) or placebo tablets in a randomized, double-blind, crossover manner. The subjects also consumed 8 oz of whole milk in which 37.5 g of lactose powder was dissolved (total lactose content, 50 g). The washout period between lactose challenges was at least one week. Breath hydrogen and plasma glucose concentrations were measured before and at intervals after the challenges, and the subjects completed symptom-evaluation questionnaires every eight hours for four days. Twenty-four subjects completed the study. The maximum mean breath hydrogen concentration was significantly lower after lactase treatment than after placebo treatment. In 21 subjects, the area under the hydrogen concentration-time curve (AUC) was lower after lactase than after placebo; three subjects had hydrogen AUCs more than 300 ppm.hr lower. There were no significant differences in plasma glucose levels. Subjective ratings of the severity of abdominal cramping, belching, flatulence, and diarrhea were lower during the first eight hours after challenge in lactase-treated subjects; ratings for bloating were lower during the next eight hours. Single doses of a chewable lactase tablet reduced the concentration of expired hydrogen and symptoms of lactose intolerance after a lactose challenge.

Abdominal Muscles↗

Lactose intolerance in infants, children, and adolescents.

The American Academy of Pediatrics Committee on Nutrition presents an updated review of lactose intolerance in infants, children, and adolescents. Differences between primary, secondary, congenital, and developmental lactase deficiency that may result in lactose intolerance are discussed. Children with suspected lactose intolerance can be assessed clinically by dietary lactose elimination or by tests including noninvasive hydrogen breath testing or invasive intestinal biopsy determination of lactase (and other disaccharidase) concentrations. Treatment consists of use of lactase-treated dairy products or oral lactase supplementation, limitation of lactose-containing foods, or dairy elimination. The American Academy of Pediatrics supports use of dairy foods as an important source of calcium for bone mineral health and of other nutrients that facilitate growth in children and adolescents. If dairy products are eliminated, other dietary sources of calcium or calcium supplements need to be provided.

Adolescent↗

Symptom response to lactose-reduced milk in lactose-intolerant adults.

The possible usefulness of low-lactose milk for those lactose-intolerant subjects who develop symptoms from milk consumption was investigated. In the first part of the study, 16 intolerant subjects (blood glucose rise less than 25 mg/100 ml) received low-lactose skim milk containing 15 g lactose (2.5 cups) and 7.5 g lactose (2.5 cups), regular skim milk containing 30 g lactose (2.5 cups), and all three milks plus a small breakfast. The low lactose milks produced significantly fewer symptoms. The food given with the milk had no significant effect on symptomatic response. The second group of 17 subjects received 25 g lactose in water (250 ml), skim milk (500 ml) and whole milk (500 ml); 10 g lactose in lactose-reduced skim (500 ml) and whole milk (500 ml) and whole milk (500 ml); and a placebo (250 ml). There was a significant positive relationship between amount of lactose consumed and symptom response. The form in which the lactose was administered (e.g., whole versus skim milk) was not significantly related to symptoms. It is concluded that in a symptomatic subjects a significantly greater quantity of low-lactose milk than regular milks can be consumed.

Adult↗

Lactose intolerance and intestinal villi morphology in Thai people.

OBJECTIVE: To study the relationship of lactose intolerance and intestinal villi morphology in Thai people. MATERIAL AND METHOD: Subjects for this study were patients with functional dyspepsia who had no history of milk allergy and underwent gastroduodenoscopy. Two mucosal biopsy specimens were taken from beyond the distal end of the second part of the duodenum. The specimens were carefully orientated and were graded according to the following scheme: group I: finger shaped villi; group II: mixed finger and leaf shaped villi; group III: clubbing or blunting shaped villi. All subjects were tested for lactose malabsorption by breath hydrogen analysis after consuming 50 gram lactose. Breath hydrogen concentration was analyzed in samples collected intermittently by end-expiratory technique. A rise in breath hydrogen concentration of 20 PPM over baseline was considered evidence of lactose malabsorption. RESULTS: The twenty-five subjects were twenty females (80.0%) and five males (20.0%) who ranged in age from 18 to 53 years (mean 31 +/- 8.29). Sixteen subjects belonged to the finger shaped villi group (64.0%), five to the mixed finger and leaf shaped villi, group (20.0%) and four to the clubbing or blunting shaped villi group (16.0%). Results of breath hydrogen excretion test identified the prevalence of lactose intolerance in 68 per cent of the subjects: 15/16 (93.75%) of group I; 1/5 (20.0%) of group II and 1/4 (25%) of group III respectively (P<0.001). The symptom of diarrhea after lactose loading was correlated well in patients who had positive breath hydrogen analysis. CONCLUSION: As shown in this study, the lactose intolerance is not related to intestinal villi morphology. It is implied that primary lactase deficiency is more common in Thai people than secondary lactase deficiency.

Adolescent↗

Do probiotics reduce adult lactose intolerance? A systematic review.

PURPOSE: To assess the efficacy of oral probiotics in adults with lactose intolerance through a systematic review of its effects on symptoms and breath hydrogen tests, and whether adding probiotics to nonfermented dairy products decreases lactose intolerance at that meal. METHODS: We searched randomized controlled trials published between 1966 and December 2002. Databases in the search strategy included Medline and AMED. We reviewed references of clinical trials and contacted authors of major articles and manufacturers of probiotic commercial products. Quality assessment was based on the McMaster guides and was performed by 5 independent reviewers. Data extraction was performed by 2 reviewers. RESULTS: A master list of 90 articles was compiled. Ten articles met inclusion and exclusion criteria and were consistent with our clinical question. Of the 9 studies that measured breath hydrogen, 3 were positive, 3 were negative, and 3 had both positive and negative results. Of the 7 studies that measured symptoms, 1 yielded positive results, 5 were negative, and 1 had both positive and negative outcomes. CONCLUSIONS: Probiotic supplementation in general did not alleviate the symptoms and signs of lactose intolerance in adults in this review. Some evidence suggests that specific strains, concentrations, and preparations are effective. Further clinical trials of specific strains and concentrations are necessary to delineate this potential therapeutic relationship.

Administration, Oral↗

The response to dietary treatment of patients with chronic post-infectious diarrhea and lactose intolerance.

The response to dietary treatment of patients with chronic post-infectious diarrhea and lactose intolerance was prospectively studied in 29 infants less than 1 year of age. All had gastroenteritis with diarrhea which persisted for more than 3 weeks. In the hospital, diarrhea continued and lactose intolerance was documented while being fed half-strength cow's milk formula. They were given dietary treatment with one of three formulas used for treatment of diarrhea in infancy. Improvement of diarrhea was more frequently achieved with Pregestimil when given as the initial therapy than with the other two formulas. With Pregestimil nine of 10 patients improved whereas only four of nine infants fed Portagen and one of 10 patients initially treated with soy formula improved. Pregestimil was also effective in three of five patients who initially failed to improve with Portagen and in four of eight patients tried with soy formula with or without carbohydrate. Additionally, in the patients who improved, recovery was more rapidly achieved with Pregestimil than with the other two formulas. Formula failures were due to intolerance to glucose polymers in three patients, possibly to protein in seven infants, and an intolerance to all nutrients in five patients. The improvement of the diarrhea was slower in patients who had evidence of colitis in rectal biopsies regardless of the dietary treatment given, but was not correlated with other variables, i.e., etiology of diarrhea, jejunal histology, or duration of diarrhea prior to treatment. However, as a group, the patients who failed to respond to Pregestimil were younger (less than 3 months of age), had more formula changes and associated infections, and were given more antibiotics; they also had more prolonged diarrhea before treatment and more severe jejunal mucosal lesions and jejunal bacterial overgrowth. The data suggests that Pregestimil seems to be the most effective formula for the treatment of infants with chronic post-infectious diarrhea and lactose intolerance.

Age Factors↗

Lactose intolerance: a self-fulfilling prophecy leading to osteoporosis?

Symptoms of lactose intolerance are unlikely to occur under usual dietary conditions. Yet, self-described "lactose-intolerant" individuals often restrict dairy and calcium intake. A new study suggests that such individuals have reduced peak bone mass and increased incidence of osteopenia, and are at greater risk of osteoporosis and bone fractures.

Bone Density↗

Lactose intolerance symptoms assessed by meta-analysis: a grain of truth that leads to exaggeration.

A meta-analysis was conducted to compare the lactose intolerance symptoms of lactose maldigesters after consuming lactose (as milk, lactose dissolved in water, milk products, or commercial product) with responses after a placebo under masked conditions. An English language MEDLINE search was conducted using the medical subject heading of "lactose intolerance" from 1966 to January 2002. From an initial 1,553 citations, 2 independent reviewers selected 21 studies based on study design (randomized, crossover, blind) and use of an amount of lactose likely to be found in a meal (7-25 g) and a placebo among subjects free of gastrointestinal problems and >4 years old. Mean severity of symptom responses were analyzed as standardized differences, and the presence or absence of a symptom was estimated as pooled incidence differences (ID). For severity of flatulence, the standardized difference was 0.18 (95% confidence interval [CI] -0.16 to +0.52). The CIs for abdominal bloating and pain, degree of diarrhea, frequency of bowel movements per day, and frequency of diarrhea per day also included 0. For abdominal bloating, the ID was 5.9 more people per 100 with symptoms after lactose than placebo (CI -0.07 to +0.19). This same nonsignificant relationship was found for abdominal pain. The ID for diarrhea or loose stools was 0.15 (CI 0.03 to 0.28). Although the incidence of diarrhea was significantly higher, the size of the effect was very small. The results indicate that lactose is not a major cause of symptoms for lactose maldigesters following usual intakes of dairy foods, that is, 1 cup.

Abdominal Pain↗

Systemic lactose intolerance: a new perspective on an old problem.

Intolerance to certain foods can cause a range of gut and systemic symptoms. The possibility that these can be caused by lactose has been missed because of "hidden" lactose added to many foods and drinks inadequately labelled, confusing diagnosis based on dietary removal of dairy foods. Two polymorphisms, C/T13910 and G/A22018, linked to hypolactasia, correlate with breath hydrogen and symptoms after lactose. This, with a 48 hour record of gut and systemic symptoms and a six hour breath hydrogen test, provides a new approach to the clinical management of lactose intolerance. The key is the prolonged effect of dietary removal of lactose. Patients diagnosed as lactose intolerant must be advised of "risk" foods, inadequately labelled, including processed meats, bread, cake mixes, soft drinks, and lagers. This review highlights the wide range of systemic symptoms caused by lactose intolerance. This has important implications for the management of irritable bowel syndrome, and for doctors of many specialties.

Asthma↗

Lactose intolerance in East Indians of Trinidad.

The incidence of lactose intolerance and by inference intestinal lactase deficiency was investigated by means of the oral lactose tolerance test in 30 East Indians born in Trinidad but of Indian heritage. Twenty showed flat curves (67%) and twenty had cramps and diarrhoea following the lactose load (67%). In India milk consumption is less than in Trinidad. Since all subjects were of the same racial origin the findings are interpreted as suggesting that lactase deficiency among East Indians is inherited on a genetic basis.

Adolescent↗

Comparison of lactose intolerance in healthy Kuwaiti and Asian volunteers.

OBJECTIVE: To study and compare the incidence of lactose intolerance among Kuwaiti and Asian healthy volunteers as measured by breath hydrogen level following challenge with lactose drink. SUBJECTS AND METHODS: The study involved 70 Kuwaiti and 79 Asian healthy volunteers. The volunteers were physicians, medical students and other hospital workers. The study was carried out prospectively at Amiri Hospital, Kuwait. None of the volunteers was sick or had taken antibiotics or any other drug that could influence breath hydrogen level 2 weeks prior to the study. After an overnight fast 20-ml baseline samples of exhaled air were collected from each volunteer prior to oral administration of 40 g of lactose drink. Following this, the same amount of exhaled air was collected at 30-min intervals for 2 h. All samples were analyzed for hydrogen level using a Quintron microlyzer. Hydrogen level of 20 ppm more than baseline value was considered positive. RESULTS: The basal breath hydrogen levels were 12.49 +/- 8.4 and 6.97 +/- 6.9 for Kuwaitis and Asians, respectively. Thirty-three (47%) of the 70 Kuwaitis and 46 (58%) of the 79 Asians were positive for the breath hydrogen test. The clinical symptoms of flatulence, abdominal pain, and diarrhea were associated with high levels of breath hydrogen. CONCLUSION: The findings indicate that the Kuwaiti volunteers had higher breath hydrogen levels than Asians, but the incidence of lactose intolerance was similar in both groups.

Abdominal Pain↗

A boy with severe infantile gastrogen lactose intolerance and acquired lactase deficiency.

A 10-year-old boy with severe familial lactose intolerance in infancy (vomiting, failure to thrive, lactosuria (5.25 g/l), sucrosuria (12 g/l), and aminoaciduria. Intestinal disaccharidases (including lactase and sucrase) normal at age 6 and 20 weeks. Oral lactose tolerance test at this age resulted in lactosuria (4.6 g/l); sucrose tolerance test, in sucrosuria (18.5 g/l). In contrast, intraduodenal lactose tolerance test gave only low lactose excretion in urine (0.28 g/l). He improved rapidly and had no lactosuria on intraduodenal feeding with citric acid milk. The lactosuria diminished as age increased, but was still higher at age 6 years than that of controls. He tolerated normal disaccharide containing food after 1.5 years of age. At 5.5 to 6 years, he had symptoms of lactose malabsorption, and an isolated lactase deficiency was proved. At 10 years, he still tolerates only limited amounts of milk. The defect in severe familial infantile lactose intolerance seems to be localized in the gastric mucosa. Acquired lactase deficiency can appear later in childhood in this syndrome.

Amino Acids↗