Tolerance to lactose among lactase-deficient American Indians.

To determine the amount of lactose that could be tolerated in a meal, 59 lactase-deficient American Indians, ranging in age from 5 to 62, were given graded doses of lactose. The diagnosis of lactase deficiency had beeen documented previously by showing increased breath hydrogen after an oral lactose load (2 g per kg, maximum 50 g). With this load, 88% of the subjects had symptoms. On 6 consecutive mornings, each subject was given a breakfast that contained graded doses of lactose ranging from 0 to 18 g. The order of the breakfasts was randomized and the contents were double-blinded. Symptoms, which were assessed by a "blinded" observer, were present after 9% of the breakfasts at all dosage levels, including the lactose-free breakfast. Thus, under the conditions of this study, a modest amount of lactose, equivalent to that present in 1 to 1 1/2 glasses of milk, when taken with a meal, is well tolerated by the lactase-deficient American Indian.     

Absorption of nutrients in lactase deficiency

The influence of malabsorption of lactose, as a result of primary lactase deficiency, on the absorption of the nutrients in milk was tested in four healthy controls and four subjects with lactase deficiency. An ileal perfusion technique was used to quantify arrival in the ileum of nutrients and a nonabsorbable marker (polyethylene glycol, PEG 4000) ingested as a test meal of milk. The meal was 250 ml of whole milk or milk in which the lactose had been hydrolyzed to glucose and galactose. In the fasting state, ileal flow of volume, protein, carbohydrate, and electrolytes was small and not different in controls and lactase-deficient subjects. Ileal flow increased in all subjects after the test meal of milk; more fluid and nutrient was recovered from the ileum in lactase-deficient subjects after whole milk than in control subjects or in lactase deficiency after hydrolyzed milk. Two deficient subjects showed marked malabsorption of lactose (35 and 50%); two did not. Protein, calcium, magnesium, and phosphorus were also recovered from the ileum in greater quantities in lactase deficients after whole milk. However, apart from decreased absorption of lactose, the nutritional consequences of malabsorption in association with primary lactase deficiency in adults are probably minimal.Supported in part by a Grant-in-Aid from the National Dairy Council, and by Research Grants AM-6908 and RR-585 from the National Institutes of Health, Bethesda, Maryland.     

Lactose and calcium absorption in postmenopausal osteoporosis

The prevalence of lactase deficiency and the relationship between lactose and calcium malabsorption in postmenopausal osteoporosis has been assessed in 46 subjects. Malabsorption of lactose occurred in 25 (54%) of the subjects and was associated with a significantly lower milk intake. Malabsorption of calcium occurred in 11 (44%) of the lactase-deficient subjects and in 11 (52%) of normal lactose absorbers. There was no relationship between lactose and calcium malabsorption. Vertebral and forearm mineral densities were not significantly different between normal lactose absorbers and lactase-deficient subjects.     

Calcium absorption from milk in lactase-deficient and lactase-sufficient adults

To determine whether lactose influences the absorption of calcium, the uptake of calcium from lactose-hydrolyzed milk and from unhydrolyzed milk was measured in 20 adults: 10 were lactase-deficient and 10 were lactase-sufficient as defined by breath hydrogen test, plasma glucose determination after oral lactose dose, and presence or absence of symptoms after lactose ingestion. On different days, each subject received either lactose-hydrolyzed or unhydrolyzed milk. Calcium absorption was measured by a double-isotope technique. In the lactase-deficient group, the mean absorptions were 33.5% from hydrolyzed milk and 36.2% from the same volume of unhydrolyzed milk (P greater than 0.30). In the lactase-sufficient group, mean absorptions were 24.2% from hydrolyzed milk and 25.7% from unhydrolyzed milk. The mean calcium absorption from both lactose-hydrolyzed milk and unhydrolyzed milk was significantly greater (P less than 0.01) in the lactase-deficient group compared to the lactase-sufficient group, presumably reflecting lower dietary calcium intake in the former. These data indicate that, in lactase-deficient subjects, malabsorption of lactose does not affect calcium absorption.     

Enzyme replacement therapy for primary adult lactase deficiency. Effective reduction of lactose malabsorption and milk intolerance by direct addition of beta-galactosidase to milk at mealtime

The addition of microbial beta-galactosidases directly to milk at mealtime represents a potential "enzyme replacement therapy" for primary lactase deficiency. We used the hydrogen breath test as the index of incomplete carbohydrate absorption to assess the efficacy of two enzymes--one from yeast, Kluyveromyces lactis (LactAid), and the other from the fungus Aspergillus niger (Lactase N)--to assist in the hydrolysis of 18 g of lactose in 360 ml (12 oz) of whole milk when consumed by an adult lactose malabsorber. Graded amounts of Lactase N produced, at best, a 53% relative reduction in breath hydrogen excretion, whereas quantitative elimination of excess hydrogen excretion was produced by 1 and 1.5 g of LactAid. A double-blind, controlled, crossover trial was subsequently performed in 50 healthy, unselected Mexican adults, to whom 360 ml of cow's milk was presented in the three forms in a randomized order: intact milk, prehydrolyzed milk, and milk to which 1 g of LactAid was added immediately before consumption. Among the 25 subjects with incomplete carbohydrate absorption with intact milk, adding enzyme 5-min before consumption produced a 62% reduction in breath hydrogen excretion, and symptoms of intolerance were significantly reduced. The feasibility of effective enzyme replacement therapy with a beta-galactosidase from K. lactis is demonstrated.     

Lactase deficiency in Singapore-born and Canadian-born Chinese

Seventy-three of 77 adult Singapore-born Chinese (95%) and 48 of 49 Canadian-born adult Chinese (98%) were demonstrated to be lactase deficient using the lactose breath hydrogen test. The similar prevalence of lactase deficiency in the Singapore- and the Canadian-born Chinese despite a larger estimated amount of daily milk ingestion in the Canadian-born Chinese (430 ml vs 157 ml) supports the concept that lactase deficiency, which is transmitted genetically, does not have an adaptable component related to the quantity of lactose ingested. When the lactose breath hydrogen test performed with a dose of 0.5 g/kg of lactose was compared with the test using a standard dose of 50 g of lactose, there was very little loss of sensitivity. In spite of the presence of lactase deficiency, only 32% of the Singapore subjects and 23% of the Canadian subjects had gastrointestinal symptoms when milk was ingested in the daily diet. Peak breath H₂ was higher in females than males, but the difference was more significant in the Canadian cohort.     

All Lactase Preparations Are Not the Same: Results of a Prospective, Randomized, Placebo-Controlled Trial

Objective: To compare the efficacy of three commercially available oral lactase preparations in adults with lactose intolerance. Methods: Design—Prospective, randomized, placebo-controlled trial. Setting—Outpatient study in a General Clinical Research Center. Subjects—Ten lactose-intolerant healthy volunteers were challenged with ice cream containing 18 g of lactose. Lactase or placebo was given immediately prior to challenge. Measurements—Symptoms and breath hydrogen excretion were recorded for 3 h following lactose challenge. Results: The three products differed in their abilities to influence symptoms and breath hydrogen excretion. Only Lactaid reduced the breath hydrogen excretion with lactose (mean peak, area under the curve and cumulative breath hydrogen excretion) ( P < 0.05). Lactrase and Dairy Ease influenced symptoms: Lactrase reduced pain, bloating and total symptomatic scores ( P < 0.05), whereas Dairy Ease only reduced pain ( P < 0.05). Lactaid administration did not reduce symptoms. Conclusion: In lactose-intolerant subjects, the available lactase preparations differ in their ability to improve both breath hydrogen excretion and symptoms. Lactrase may be the product of choice for achieving symptomatic improvement.     

Studies on the etiology of milk intolerance in Japanese adults.

1. The incidence of milk intolerance is approximately 19% in Japanese adults when 200 ml of milk is given. However, a much greater incidence was assumed when considered under the criteria of Western standard. 2. The lactase activity was significantly greater in milk drinkers than non-drinkers. And, internationally, the active is higher in those nationalities whose milk consumption is greater. 3. Lactase is an adaptive enzyme and rather easily induced by lactose load feeding in animals. From the data of our own and of the literature, it was further confirmed that environmental factors play a more important role than genetic factors in the etio-pathogenesis of milk intolerance.     

Lactase deficiency and lactose intolerance-related symptoms in adult healthy subjects from western France]

The prevalence of lactase deficiency (LD) and lactose intolerance is not well known in France. Using breath hydrogen and methane analysis after 50 g oral lactose load, we investigated the prevalences of LD, lactose intolerance, and methane producer status in 102 healthy adults born in western France, and we examined the relationships between these parameters and the daily milk consumption. In 10 subjects with LD and lactose intolerance, we studied the reproducibility of the lactose hydrogen breath test results for the diagnosis of LD and lactose intolerance and estimated the quantity of lactose malabsorbed in comparison with the lactulose hydrogen breath test. The prevalence of LD was 23.4 percent and symptoms of lactose intolerance were observed in 50 percent of the 24 subjects with LD. The daily milk consumption was not significantly different in the 24 subjects with LD and in the 78 subjects without LD (281 +/- 197 vs 303 +/- 217 ml/24 h). The prevalence of methane producer status was 42.1 percent. The symptomatic group of lactose malabsorbers (n = 12) was characterized by a shorter lactose mouth to caecum transit time (39 +/- 20 vs 88 +/- 48 min; P less than 0.05), and more marked hydrogen production (6.1 +/- 2.3 vs 3.4 +/- 2.4 10(3) ppm.min; P less than 0.04). In the 10 subjects with LD and lactose intolerance, the hydrogen breath test was reproducible for diagnosis of LD and lactose intolerance, and for hydrogen production. The quantity of lactose malabsorbed was 60 percent. In France, symptoms of lactose intolerance are not severe and do not affect the daily consumption of milk and dairy products.     

Lactose malabsorption in adult patients at the Hospital das Clínicas de Ribeir?o Preto

A standard oral lactose tolerance test (LTT) was performed in 32 white and 18 non-white hospitalized Brazilian adults. A flat LTT was found in 22 (68,75%) white and in 17 (97,45%) non-white patients indicating a 78% overall rate of lactose malabsorption, Both lactose absorbers and malabsorbers showed a modal milk ingestion of less than a 1 glass/day. Symptoms related to milk consumption or lactose administration were more common among lactose malabsorbers. Estimations of disaccharidase activity in intestinal mucosa specimens obtained by peroral biopsy in 28 patients confirmed a high prevalence of lactose deficiency, and disclosed only one false result, in the patient with a flat LTT and high intestinal lactase levels.     

Respiratory methane excretion in children with lactose intolerance

Two evaluate the relationship between colonic methane production and carbohydrate malabsorption, we measured end-expiratory methane levels in 70 normal and 40 lactose-intolerant children. Time-dependent excretion of hydrogen and methane was determined every 30 min for 120 min following a fasting oral lactose challenge (2 g/kg). Mean breath hydrogen levels in normals (lactose-tolerant) equaled 3.7 parts per million (ppm) throughout the study, but increased to >10 ppm by 60 min and remained elevated in lactose-intolerant subjects. Breath methane in normal children averaged 1.6 ppm from 0 to 120 min. In contrast, CH₄ excretion by lactose-intolerant children averaged 5.1 ppm at 90 min; and, by 120 min levels increased significantly compared with control. Breath methane levels in lactose-intolerant subjects following a lactose load continued to increase, however, despite the coingestion of exogenous lactase in amounts calculated to result in complete hydrolysis of the disaccharide. These data demonstrate that lactase-deficient children manifest significant increases in breath methane excretion following lactose ingestion and that enhanced methane production may be a consequence of several factors, including altered fecal pH and increased methanogenic substrates provided by colonic lactose fermentation. Further studies are required to determine the clinical significance of elevated methane production in lactose intolerance.     

Molecularly defined adult-type hypolactasia in school-aged children with a previous history of cow＇s milk allergy

AIM: To assess the role of lactase non-persistence/persistence in school-aged children and their milk-related symptoms. METHODS: The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years (SE = 0.02, 93 boys) participating in a follow-up study for cow's milk allergy. The parents were asked to assess their children's milk consumption and abdominal symptoms. RESULTS: The presence of allergy to cow's milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood (lactase non-persistence). The frequency of the C/C-13910 genotype (16%) was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children (90%) in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping (P< 0.004 when compared to the other genotypes). CONCLUSION: Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow's milk allergy.     

Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance

BACKGROUND: The relationship between lactose malabsorption, irritable bowel syndrome and development of intestinal symptoms is unclear, especially when the ingested dose of milk is small. Thus, the role of hydrogen breath testing in the diagnostic work-up of patients with nonspecific intestinal symptoms is still debated. AIMS: To establish the relationship between lactose malabsorption, severe self-reported milk intolerance, irritable bowel syndrome and related symptoms. METHODS: The prevalence of lactose malabsorption was prospectively assessed by means of a hydrogen breath test in 839 patients (503 with irritable bowel syndrome, based on the Rome criteria, regularly consuming milk, and 336 subjects who identified themself as milk intolerant, after an oral load of 25 g lactose). The test was considered "positive" when a hydrogen peak exceeding 20 ppm over baseline values was observed in two or more samples. Attempts were also made to establish whether the predominant presenting symptom (diarrhoea, constipation, alternating diarrhoea and constipation, pain and gaseousness) might be helpful in predicting the outcome of the breath test. RESULTS: The prevalence of a positive breath test was comparable in the two groups (337 patients with irritable bowel syndrome (66.9%) vs 240 patients with milk intolerance (71.4%)). The same holds true for the first peak of hydrogen excretion, total hydrogen output and prevalence of symptoms during, and in the four hours after, the test. The predominant presenting symptom was not useful for predicting outcome of the test either in regular milk users or in milk intolerant subjects. CONCLUSIONS: The almost identical results of the lactose breath test of patients with irritable bowel syndrome and subjects with self-reported milk intolerance suggests that the two conditions overlap to such an extent that the clinical approach should be the same. A lactose breath test should always be included in the diagnostic work-up for irritable bowel syndrome, as fermentation of malabsorbed lactose is likely responsible for triggering symptoms. Conversely, lactase deficiency is probably irrelevant in most subjects not affected by irritable bowel syndrome, within a moderate milk consumption.     

Lactase deficiency in Jewish communities in Israel

Lactase deficiency and lactose tolerance were studied in several Jewish communities in Israel. Lactase deficiency was found in 60% of biopsied subjects. Forty-one biopsies were peroral and 22, surgical; histologically, the jejunal mucosa of all specimens was normal. Lactose tolerance tests were performed on 217 subjects, 118 patients and 99normals. A low glucose rise was found in 44.4% of Yemenites, 62.5% of North Africans (Sephardi), 72.2% of others (Sephardi), 79.2% of Ashkenazi, 84.2% of Iraqis and 85.0% of others (Oriental); the overall incidence was 71.1%. Statistical analysis confirmed that the population studied was heterogenous. Most subjects with a low glucose rise had symptoms during the test. Milk intake, low in almost all subjects, did not correlate with lactose tolerance. Most lactose intolerant subjects were not aware of milk intolerance; the condition is not usually symptomatic in Israel. Lactase deficiency in various population groups has been reviewed and evidence in favor of a genetic etiology emphasized.The authors wish to thank the staff of the Tel-Aviv Government Municipal Hospitals, in particular, the Department of Pediatrics-B for their help in carrying out this investigation and for permission to study their patients; Dr. A. Adam, Department of Human Genetics, Tel-Aviv University Medical School, for helpful advice and criticism. Blood sugar estimations were performed at the Central Biochemical Laboratory of the Workers Sick Fund, Tel-Aviv.     

Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis.

BACKGROUND: Patients with active Crohn's disease (CD) often report having abdominal symptoms after ingestion of milk products, but the pathomechanism for lactose malabsorption seems to be complex. GOALS: To investigate the prevalence of clinical milk intolerance and to objectify symptoms with hydrogen (H 2 ) breath testing, analysis of lactase protein, and enzyme activity in the duodenal mucosa in patients with CD and in healthy controls. STUDY: In 49 patients with CD and 24 controls, H 2 breath testing was performed. All individuals underwent endoscopy of the upper gastrointestinal tract, in which multiple pinch samples were taken from the distal duodenum. Lactase activity was measured using the method of Dahlquist. The lactase protein expression was analyzed by gel electrophoresis using the monoclonal antibody mlac 10 and by immunochemistry using the monoclonal antibody mlac 4. RESULTS: Prevalence of milk intolerance in healthy controls was 16.6% versus 46.9% in patients with CD, with a high frequency (83.3%) in patients with active disease (CD activity index >150). Milk intolerance was correlated to the duration of inflammatory bowel disease ( p = 0.023) but not to the location or previous bowel resection. Hydrogen breath testing had a moderate sensitivity in detecting lactose maldigestion (70.4%) and a high specificity (95.6%). Duodenal lactase levels were also correlated to disease activity, whereas correlations to clinical symptoms remained poor. Patients with milk intolerance had a significantly reduced bone density at the lumbar spine (z-score, -1.33 +/- 0.92 vs. -0.19 +/- 0.95 [mean +/- SD]; p = 0.002) CONCLUSIONS: Milk intolerance is a frequent problem in active CD, which can be objectified accurately by H 2 lactose breath testing. Decreased lactase levels in the duodenal mucosa may be found during an acute flare but are not the predominant cause of milk intolerance in CD.     

Lactose malabsorption in Greek adults: correlation of small bowel transit time with the severity of lactose intolerance.

Using breath hydrogen analysis after 139 mmol (50 g) oral lactose load, we investigated the prevalence of lactose malabsorption in 200 Greek adults and examined the relationship between symptoms and small bowel transit time. One hundred and fifty subjects had increased breath hydrogen concentrations (greater than 20 ppm) after the lactose load. In these individuals peak breath hydrogen concentration was inversely related to small bowel transit time (r = 0.63, 6 = 6.854, p less than 0.001) and the severity of symptoms decreased with increasing small bowel transit time. Lactose malabsorbers with diarrhoea during the lactose tolerance test had a small bowel transit time of 51 +/- 22 minutes (x +/- SD; n = 90) which was significantly shorter than the small bowel transit time of patients with colicky pain, flatulence, and abdominal distension (74 +/- 30, n = 53; p less than 0.001) and both groups had significantly shorter small bowel transit time than that of asymptomatic malabsorbers (115 +/- 21 n:7; p less than 0.001). When the oral lactose load was reduced to 33 mmol (12 g), the small bowel transit time increased five-fold and the overall incidence of diarrhoea and/or symptoms decreased dramatically. These results indicate that the prevalence of lactase deficiency in Greece may be as high as 75% and suggest that symptom production in lactose malabsorbers is brought about by the rapid passage down the small intestine of the malabsorbed lactose.     

Intestinal lactase deficiency in an apparently normal Peruvian population

The prevalence of milk and lactose intolerance and intestinal lactase deficiency was studied in 30 apparently healthy Peruvian individuals. At the same time, 20 milk-intolerant persons were included in the study. According to the results of lactose-tolerance tests and intestinal lactase assays, one-third of the 30 were considered normal and were used as controls. The other two-thirds were found to be abnormal and were referred to asasymptomatics; they tolerated well small amounts of milk consumed daily. Upon lactose load, they developed gastro-intestinal symptoms, and maximal rise of blood glucose was below normal limits. Enzymatic assay indicated that they were deficient in intestinal lactase. The remaining 20 were intolerant to milk and the results of their tests were abnormal. Sucrase activity was similar in the 3 groups. This high incidence of lactase deficiency in apparently normal individuals seems to be acquired.     

Lactase deficiency in Nigerians

A combination of lactose and glucose-galactose tolerance tests was carried out on 83 patients to determine the prevalence of isolated lactase deficiency in the the various ethnic groups of Nigerians living in Ibadan. Lactase deficiency was found in 81% of all the subjects. This consisted of 40 out of 48 Yorubas (84%), 9 out of 15 Hausa/Fulani (60%), 9 out of 11 Ibos (82%), and all 9 Nigerians belonging to other ethnic groups. The results indicate that lactase deficiency may be widespread throughout Nigeria. It is proposed that the high incidence of lactase deficiency is not caused by an inherited genetic defect of enzyme production in the intestinal mucosa, but might be due to a lack of induction from poor milk intake after weaning.     

Lactase non-persistence and milk consumption in Estonia

INTRODUCTION Lactase enzyme hydrolyses lactose to glucose and galactose facilitating their absorption through the gut wall. Adult- type hypolactasia (lactase non-persistence, primary lactose malabsorption) is the most common enzyme def iciency in the worl…     

Treatment of chronic portal-systemic encephalopathy with lactose in lactase-deficient patients

A controlled cross-over clinical comparison of lactose (50 g twice a day) versus neomycin (3 g/day) plus milk of magnesia, was carried out in ten cirrhotic patients with chronic portal-systemic encephalopathy and documented lactase deficiency. Serial semiquantitative assessments were done including: mental state, asterixis, number connection test, electroencephalogram, and blood ammonia levels. No patient developed deep coma while ingesting either lactose or neomycin plus milk of magnesia. However, a significant improvement of mental state, asterixis, number connection tests, and electroencephalograms was evident during lactose therapy. Apart from mild diarrhea and bloating, no severe side effects were noticeable during lactose treatment. Based on these results, we propose lactose as a valuable alternate treatment of portal-systemic encephalopathy in lactase-deficient populations.With technical assistance of Arabella Briones, BS, and Sofía Gil, BS.