Lactose intolerance: lactose tolerance test versus genotyping

OBJECTIVE: Adult lactose intolerance, which affects the majority of the population in the world, has been associated with a single nucleotide polymorphism, C-13910T, located upstream of the lactase gene. MATERIAL AND METHODS: Adult patients undergoing lactose tolerance tests with lactose challenge and plasma glucose measurements were included in the study comprising 44 Swedes and 7 non-Swedish individuals. A real-time PCR method was established for the genotyping. RESULTS: Out of 51 patients 48 had concordant results on genotyping and lactose tolerance tests, e.g. -13910T/T and -13910C/T genotypes had high glucose elevations. All patients with the heterozygous genotype, -13910C/T, had high glucose elevations, and no gene-dose relationship was observed when comparing maximal glucose increases for cases with -13910C/T and -13910T/T genotypes. CONCLUSIONS: Genotyping could replace lactose challenge as a first-stage screening test in adults of European descent, but should be used together with tolerance tests in children and patients where secondary lactose intolerance is suspected.     

Sedation-associated complications in endoscopy are not reduced significantly by implementation of the German S-3-guideline and occur in a severe manner only in patients with ASA class III and higher

Objective. The age at manifestation of primary hypolactasia varies between ethnic groups. Many people report experiencing the first symptoms of lactose intolerance at adult age. The purpose of this study was to investigate whether primary hypolactasia can appear after the age of 20 among the Finnish population and to investigate the outcome of different diagnostic methods of lactose maldigestion. Material and methods. Lactose digestion status was assessed by the lactose tolerance test with ethanol (LTTE) in 42 subjects (38–71 years) who reported having gastrointestinal symptoms after the ingestion of 20 g or less of lactose and who were diagnosed as lactose digesters in earlier studies. Thirteen of the study subjects underwent upper gastrointestinal endoscopy, and 35 gave a blood sample for DNA analysis. Results. Only one of the 42 subjects studied had the genotype C/C_?13910 indicating hypolactasia. Lactase activity was higher in those with the genotype T/T (69.2 U/g protein) than in those with the heterozygous genotype C/T (36.3 U/g protein) (p=0.017). Conclusions. Although primary hypolactasia normally appears before the age of 20 years, the decline in lactase activity may on rare occasions continue after that age. Genotyping of the C/T_?13910 variant was found to be a reliable diagnostic approach in defining the lactase persistence/non-persistence status of the study subjects.     

Lactose intolerance in Jewish patients with ulcerative colitis

Seventy patients with ulcerative colitis had lactose tolerance tests. Of 51 non-Jewish patients, 12 (23.5%) had lactose intolerance, whereas of 19 Jewish patients, 16 (84.2%) had lactose intolerance. This difference is significant (P<0.001). The control group of 41 Jews without ulcerative colitis had a 71% incidence of lactose intolerance, whereas of 53 non-Jewish controls, only 20.7% had such intolerance. These results are also statistically valid (P<0.001). This suggested that segregation of the genes for ulcerative colitis as well as for lactase deficiency in Jews is a possible reason for the high incidence of lactase deficiency found in patients with ulcerative colitis.Supported by a grant from The Hartford Foundation.     

The C/C(-13910) and G/G(-22018) genotypes for adult-type hypolactasia are not associated with inflammatory bowel disease

BACKGROUND: Lactose intolerance with adult-onset is due to the inadequate enzymatic activity of lactasephlorizin hydrolase (LPH). It is frequently seen in patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA genotypes, C/C(-13910) and G/G(-22018), located upstream from the LCT locus, the gene encoding for LPH, were recently identified as representing genetic markers for lactose intolerance. We utilized these two DNA genotypes to study their role in inflammatory bowel disease. METHODS: We investigated the prevalence of these two DNA variants using specific restriction enzyme digest assays in 166 patients with Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients, in 63 patients with ulcerative colitis and in 187 healthy individuals. RESULTS: The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type hypolactasia in our studied German cohort of healthy individuals, which is higher than previously reported (15%) based on the hydrogen (H2) breath test. This might indicate a higher sensitivity of genotyping, but it has to be confirmed in larger cohorts. No significant difference was detectable in the frequency of the C/C(-13910) and G/G(-22018) genotypes in patients with Crohn disease (C/C(-13910): 21.7%; G/G(-22018): 22.3%) compared to first-degree relatives (C/C(-13910): 21.7%; G/G(-22018): 20.8%), patients with ulcerative colitis (C/C(-13910): 20.3%; G/G(-22018): 20.3%) and healthy individuals (C/C(-13910): 21.4%; G/G(-22018): 21.4%). CONCLUSION: The C/C(-13910) and G/G(-22018) genotype of adult-type hypolactasia is not associated with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.     

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 tolerance in a jewish population

In order to investigate the possible effect of environment on lactose deficiency, lactose tolerance tests were performed on 32 healthy Jewish adults living in Western Canada. The results were compared with those obtained in Jewish communities in Israel. There were 20 males and 12 females, 20–47 years of age, with a mean of 27.2 years. The tests revealed that 22 (68.8%) of the subjects were lactose intolerant on the basis of a maximal blood glucose rise of less than 20 mg/100 ml above the fasting level after the lactose load. The mean maximum blood glucose rise was 4.1 mg/100 ml in the 22 lactose-intolerant subjects and 33.6 mg/100 ml in the 10 lactose-tolerant subjects. Gastrointestinal symptoms during the test were observed in 95.5% of the subjects with a low rise in blood glucose, and in 10% of those with a normal rise in blood glucose. There was no relationship between lactose tolerance and milk intake. The results suggest a high incidence of lactose intolerance among North American Jews, and are similar to findings in Jewish communities in Israel.Supported by Grant A6249, National Research Council of Canada.The author wishes to thank Dr. M. Lee for his helpful comments; and Dr. J. A. Birkbeck and Mrs. Karen M. Ulveteg for their assistance with the lactose tolerance test.     

Lactose Malabsorption in Patients Operated Upon for Peptic Ulcer

A lactose tolerance test was performed and small intestinal mucosal disaccharidase activity was determined in 12 patients operated upon for peptic ulcer who had lactose malabsorption. Most patients were misjudged, since they were considered to suffer from post-operative complaints (vagotomy diarrhoea, afferent loop syndrome, recurrent ulcer and dumping). Three patients did not develop symptoms of milk intolerance until immediately after an operation for peptic ulcer; in 3 other patients this operation exacerbated the existing symptoms after consumption of milk. Two patients had steatorrhoea, which disappeared or diminished when lactose excluded from the diet.     

Inverse Dose Effect of Pretest Dietary Lactose Intake on Breath Hydrogen Results and Symptoms in Lactase Nonpersistent Subjects

The aim of this study was to determine a relationship between pretest intake of lactose and outcome of lactose breath hydrogen test. Patients presented at a testing laboratory participated in the study. A 3-hour breath hydrogen, 50-g lactose challenge was carried out. Results were tabulated and patients completed a 3-day recall diet questionnaire. Daily lactose intake was independently calculated and was associated with breath hydrogen and total symptom score. Statistical analysis used Spearman's correlation, Mann-Whitney U-test and χ² or Fisher exact test. Of 118 patients, 50% were lactose maldigesters. In these patients, measured breath hydrogen and symptom scores were significantly higher in the lowest intake group (< 5 g/d) than in the highest intake group (> 20 g/d) (P < .05). In the presumed lactose digesters, 59% experienced some symptoms during testing for unclear reasons. Pretest dietary intake of lactose inversely affects results of breath hydrogen.     

The C/C_₁₃₉₁₀ and G/G_₂₂₀₁₈ Genotypes for Adult-type Hypolactasia are not Associated with Inflammatory Bowel Disease

Background: Lactose intolerance with adult-onset is due to the inadequate enzymatic activity of lactase-phlorizin hydrolase (LPH). It is frequently seen in patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA genotypes, C/C_????? and G/G_?????, located upstream from the LCT locus, the gene encoding for LPH, were recently identified as representing genetic markers for lactose intolerance. We utilized these two DNA genotypes to study their role in inflammatory bowel disease. Methods: We investigated the prevalence of these two DNA variants using specific restriction enzyme digest assays in 166 patients with Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients, in 63 patients with ulcerative colitis and in 187 healthy individuals. Results: The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type hypolactasia in our studied German cohort of healthy individuals, which is higher than previously reported (15%) based on the hydrogen (H?) breath test. This might indicate a higher sensitivity of genotyping, but it has to be confirmed in larger cohorts. No significant difference was detectable in the frequency of the C/C_????? and G/G_????? genotypes in patients with Crohn Disease (C/C_?????: 21.7%; G/G_?????: 22.3%) compared to first-degree relatives (C/C_?????: 21.7%; G/G_?????: 20.8%), patients with ulcerative colitis (C/C_?????: 20.3%; G/G_?????: 20.3%) and healthy individuals (C/C_?????: 21.4%; G/G_?????: 21.4%). Conclusions: The C/C_????? and G/G_????? genotype of adult-type hypolactasia is not associated with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.     

Lactose malabsorption after bypass operation for obesity.

After bypass operation for obesity the remaining lactose-hydrolyzing capacity of the functioning shunt is very low, especially if the shunt is constructed from a shorter jejunal and a longer ileal segment. In most cases a temporary decrease in the lactase activity of the jejunal part of the shunt occurs during the first postoperative months. In the present study lactose provoked or aggravated diarrhoea and other symptoms in 20 of 33 shunt-operated patients, and 10 patients reported milk intolerance postoperatively. Oral glucose tolerance tests indicated that the lactase activity was rate limiting for lactose absorption postoperatively.     

Prediction of lactose malabsorption in referral patients

Two hundred forty-two patients referred for various gastrointestinal complaints were evaluated for clinical parameters that would predict findings of lactose malabsorption. Breath hydrogen and blood glucose lactose tests were performed after ingestion of 50 g lactose. Presenting complaints, duration of symptoms, and patient demographics such as age, sex, and ethnic heritage were not different between lactose malabsorbers and absorbers as defined by the breath hydrogen lactose test. Foodrelated symptoms in general and after specific foods such as milk, ice cream, cheese, and yogurt were also similar between groups. Prior to testing, 30% of malabsorbers (N=161) and 36% of absorbers (N=81) reported lactoserelated symptoms (P=NS). The blood glucose response to lactose was abnormal in 60% of malabsorbers and 15% of absorbers. This study confirmed our impression that it is difficult to predict lactose absorption status by clinical parameters. The majority of our lactose malabsorber patients were unaware of lactose-associated symptoms. Furthermore, symptom assessment, demographics, food history, and blood glucose testing did not predict abnormal hydrogen responses to lactose.The opinions and assertations expressed herein are those of the authors and are not to be construed as reflecting opinions of the United States Air Force or the Department of Defense.This work has been presented in part at the Annual Scientific Session of the American Gastroenterological Association, San Francisco, California, May 19, 1986, and published as an abstract (Gastroenterology 90:1562, 1986).     

Incidence and Clinical Significance of Lactose Malabsorption in Adult Coeliac Disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day—statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Applicability of short hydrogen breath test for screening of lactose malabsorption

The gold standard for diagnosing lactose malabsorption is the H₂ hydrogen breath test (HBT). Different methods of HBT have been proposed. However, in clinical practice the HBT is often shortened to 1–2 hr without proper validation. Our objective was to establish whether the usefulness of the HBT is influenced by shortening of the test and/or by substrate variations. In 62 patients with clinically suspected lactose intolerance and a positive lactose HBT we calculated the sensitivity of the HBT depending on the duration of the HBT. To determine whether substrate variations influence the sensitivity of the HBT, in another group of 32 patients with clinically suspected lactose intolerance and a positive milk HBT, the sensitivity of the HBT was also calculated depending on the duration of the test after milk ingestion. In other unselected 97 individuals, the result of the HBT with 360 ml of whole milk supplemented with lactose was compared with a symptomatic score for lactose intolerance to evaluate the specificity of the shortened milk HBT. Breath H₂ excretion was significantly higher after lactose than after milk load (P < 0.01), and the increase in H₂ appeared earlier with lactose than with milk (60 vs 90, min respectively). HBT duration influenced the sensitivity of the test that decreased from 95% for the 3-hr HBT to 37% for the 1-hr HBT with lactose and from 80% for 3-hr HBT to 21% for 1-hr HBT with milk. The specificity was similar for the 3-hr milk HBT and the 5-hr test (67 vs 62%). In conclusion, for screening of lactose malabsorption, the HBT can be shortened to 3 hr without loss of sensitivity and specificity, when a high dose of lactose load is used.     

A genetic test which can be used to diagnose adult-type hypolactasia in children

Background/ AIMS: Adult-type hypolactasia (primary lactose malabsorption) affects most of world's human population and limits the use of fresh milk due to lactose intolerance. The diagnosis of adult-type hypolactasia has been difficult to establish because of unsatisfactory diagnostic methods. C/T(-13910) single nucleotide polymorphism residing 13910 base pairs from the 5' end of the lactase gene has been shown to be associated with lactase persistence. The aim of the study was to assess the applicability of the C/T(-13910) variant as a diagnostic test for adult-type hypolactasia during childhood. METHODS: Intestinal biopsies were obtained from 329 children and adolescents of African, Finnish, and other White origins aged 0.1-20 years undergoing upper gastrointestinal endoscopy because of abdominal complaints. The biopsies were assayed for lactase, sucrase, and maltase activity and genotyped for the C/T(-13910) variant using polymerase chain reaction minisequencing. RESULTS: The frequency of the C/C(-13910) genotype defining lactase non-persistence was well in agreement in this study with published figures for the prevalences of adult-type hypolactasia in Africans and Whites. The C/C(-13910) genotype was associated with very low lactase activity (<10 U/g protein) in the majority of children tested at 8 years of age and in every child older than 12 years of age giving a specificity of 100% and sensitivity of 93% for the genetic test. The decline of lactase activity was somewhat earlier in African compared with Finnish children with C/C(-13910) genotype (p<0.03). CONCLUSIONS: Genetic test of C/T(-13910) polymorphism can be used as a first stage screening test for adult-type hypolactasia.     

Lactose tolerance in a Slavic population

In order to gather data on the frequency of primary lactase deficiency in various population groups, lactose tolerance tests were performed on 38 healthy adults of Slavic origin who had recently left Eastern Europe and are presently living in Western Canada. Twenty-one of the subjects were born in Poland and 17 in Czechoslovakia. There were 16 males and 22 females, aged 17–65 years, with a mean of 29.8 years. The tests revealed that 9 (23.9%) of the 38 subjects were lactose intolerant on the basis of both criteria, showing a maximum rise in blood glucose of less than 20 mg/100 ml above the fasting blood glucose level after ingesting 50 g of lactose, and experiencing gastrointestinal symptoms during the test. The mean maximum rise in blood glucose was 39.1 mg/100 ml in the 29 lactose tolerant subjects and 7.3 mg/100 ml in the 9 lactose intolerant subjects. Gastrointestinal symptoms during the test were observed in all 9 subjects with a low rise in blood glucose, and no symptoms were produced in any of the 29 subjects with a significant rise in blood glucose (> 20 mg/100 ml). Most of the subjects consumed 1 cup of milk per day. In addition, they were irregularly consuming lactose-containing products such as ice cream, chocolate drinks, etc. The results suggest a relatively low frequency of lactose intolerance among Eastern Europeans of Slavic origin, and in this respect, they resemble Northern Europeans.Supported by grants from the National Research Council of Canada (A6249), and from the Committee on Research of The University of British Columbia (26–9682).The author wishes to thank Dr. J. A. Birkbeck for his assistance.     

Lactose tolerance despite hypolactasia in adult coeliac disease

Although symptoms of milk intolerance are common in primary (genetically determined) hypolactasia it is a clinical impression that such symptoms are infrequent in adult patients with hypolactasia secondary to damage of the mucosa of the small intestine. This study was designed to determine whether a lactose (50 g) challenge is better tolerated by patients with coeliac disease and secondary hypolactasia than patients with primary hypolactasia. Based on intestinal histology and disaccharidase levels, three groups of adults were studied: controls ( n = 20), patients with primary hypolactasia ( n = 20) and patients with hypolactasia secondary to newly diagnosed coeliac disease ( n = 15). The response to a challenge with 50 g lactose was assessed by a score of five symptoms and breath hydrogen production. Despite an equivalent level of hypolactasia, symptoms affected fewer patients with coeliac disease (33%) than subjects with primary hypolactasia (90%). Further, a positive lactose breath hydrogen test was noted in all (100%) patients with primary hypolactasia but in only six (40%) of those patients with newly diagnosed coeliac disease. These results suggest the presence of a considerable absorptive reserve for lactose in the distal small bowel of many patients with coeliac disease.     

Lactose intolerance in Canadian West Coast Indians

Lactose tolerance tests were performed on 30 healthy Canadian West Coast Indians and 16 non-Indians of Northern European extraction. Among the Indians, there were 7 males and 23 females, aged 14–24 years, with only 1 above 20 years of age (mean 15.8 years). The non-Indians consisted of 3 males and 13 females, aged 15–26 years, with only 2 above 18 years of age (mean 17.4 years). The tests revealed that of the 30 Indians, 19 (63.3%) were lactose intolerant on the basis of maximal blood glucose rise of less than 20 mg/100 ml above the fasting level after the lactose load. Gastrointestinal symptoms during or after the test were observed in 68.4% of the subjects with a flat blood glucose curve and in 18.2% of those with normal curves. In contrast, of the 16 non-Indians, only 1 (6.3%) was lactose intolerant, and none experienced abdominal discomfort during or after the test. Milk consumption among most of the Indian subjects seems to be low by North American standards, as judged by their past milk-drinking habits. The results suggest a high incidence of lactose intolerance among West Coast Indians during adolescence.Supported by National Health Grant 609-7-236 and NRC Grant A6249, Canada.The authors wish to thank Father T. Lobsinger and the students at the Cariboo Student Residence, Williams Lake, British Columbia for their cooperation; and Dr. J. A. Birkbeck and Miss Ilse Borgen for their assistance.     

Use of genetic testing for hypolactasia trait in the North Denmark Region

Abstract

Objective

Lactose intolerance (LI) may be considered in patients with unspecific gastrointestinal symptoms, but there is no clear consensus on when and how to diagnose the disorder. The LCT-13910?CC genotype is associated with acquired primary lactase deficiency (adult-type hypolactasia; ATH). We aimed to describe the number of tests and test results in the North Denmark Region considering patient age, geographical origin and repeated testing.     

Lactose tolerance in an Arab population

Lactose tolerance tests were performed on 67 adult Arab villagers. Fifty-four (80.6%) had a low rise in glucose and most had symptoms during the test. Lactose tolerance was not related to age or sex and did not correlate with milk consumption. A high incidence of adult lactose intolerance has been found in all Mediterranean groups studied to date—Greek Cypriots, Jews, and now Arabs.The authors wish to thank O. Mizrahy, PhD, of the Central Biochemical Laboratory of the Workers' Sick Fund, Tel-Aviv, for performing the blood sugar determinations; Mrs. Ora Ronen and Mr. Said Raby for valuable help in carrying out this study.     

Effect of Ulcer Surgery on Disaccharidase Activities of the Small Bowel and on Lactose Absorption

In 14 patients with peptic ulcer, admitted to hospital for surgical treatment, the lactose tolerance test and a small-intestinal biopsy with disaccharidase (maltase, sucrase, lactase) assays were performed before and 1 month and 6 months after operation. In 10 patients without evident organic disease of the gastrointestinum, the small-intestinal biopsy with disaccharidase assays was repeated at an average interval of 1 week, and these form the control group. The mean maltase, sucrase and lactase activities in the 1 and 6-month follow-up studies were increased over the preoperative values. When the changes were compared with the alterations noted in the control group, no statistically significant difference could be noted. In 3 patients with small-intestinal lactase deficiency the symptoms following lactose tolerance test became worse in one and a history of milk intolerance appeared in one after ulcer surgery.