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, 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.     

Efficacy of Addition of Exogenous Lactase to Milk in Adult Lactase Deficiency

The efficacy of lactase by Kluyveromyces lactis in hydrolyzing milk lactose and reducing milk intolerance symptoms was tested in 52 proved lactose malabsorbers. The enzyme was added to milk administered to the patients, and H2 breath excretion (as an index of carbohydrate malabsorption), was determined by gas chromatograph technique, and milk intolerance symptoms were recorded. H2 mean excretion was 78.3 +/- 5.49 ppm after administration of intact whole milk 500 ml (test A), 43.5 +/- 4.99 ppm when lactase 2000 U was added to milk 500 ml immediately before administration (test B); 36.7 +/- 5.01 ppm when milk 500 ml was incubated for 12 h with lactase 1000 U (test C), and 29.7 +/- 4.35 ppm when the incubation was prolonged for 24 h (test D). Symptoms score was: test A = 5.85 +/- 0.56, test B = 3.71 +/- 0.45, test C = 2.77 +/- 0.63, test D = 1.7 +/- 0.68. A correlation index of r = 0.44 (p less than 0.01) was obtained between reduction in H2 mean excretion and reduction in symptoms score of a single individual. The addition of this lactase to milk seems to be effective in correcting lactose malabsorption, thus representing a convenient approach in milk intolerance.     

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.     

A standardized milk tolerance test

Inability to hydrolyze lactose does not always cause symptoms. The lactose tolerance test commonly used in diagnosis pinpoints the biochemical anomaly but does not establish whether it causes a functional disability. I therefore compared a milk tolerance test (500 ml milk) with the standard lactose tolerance test in 40 healthy adult volunteers for rise in blood sugar. A maximum glucose rise of 9 mg/100 ml or less indicated lactose malabsorption. Only one subject was misclassified by the milk tolerance test when compared with the lactose tolerance test (specificity 91.7%; sensitivity 100%). The test not only reproduces the worst symptoms that the subject is likely to suffer due to usual milk intake, but also accurately identifies the lactose malabsorber, thus yielding more information than the standard lactose tolerance test.     

Lactose malabsorption in adult patients with Crohn's disease

In order to evaluate, in adult patients with Crohn's disease (CD), the prevalence of lactose malabsorption and intolerance, and the percentage who can tolerate a physiologic amount of milk in their diet, we tested 37 patients with CD (19 with intestinal resection, and 18 without) and 67 healthy controls (C) with the H2-breath test after they had ingested increasing loads of lactose as 10% solution (12.5 g, 25 g, and 50 g). Patients with malabsorption after the 12.5-g dose were tested further with 250 ml of milk. In the total group of patients and in the subgroup of those with resection, the prevalence of malabsorption was higher than in controls at all lactose loads; in patients who had not undergone resection, no significant difference was observed with the 12.5-g dose. Eleven of 18 patients who were malabsorbers with the 12.5-g dose had malabsorption also with 250 ml milk; however, only three of them (8% of the total group) experienced symptoms of intolerance. We conclude that, in adult patients with CD, 1) the prevalence of lactose malabsorption is increased, 2) in patients who have undergone intestinal resection, malabsorption occurs at a lower dose of the sugar than in patients who did not, and 3) since only 8% of patients experienced symptoms of intolerance after the ingestion of milk 250 ml, this amount can be empirically inserted in the daily diet of an adult with CD.     

Double blind study of milk lactose intolerance.

One hundred and fifty subjects were studied in a double blind fashion to determine the relationship between lactose malabsorption and milk lactose intolerance. Each participant received 250 ml of a different type of milk on 3 consecutive days. Milk A contained no lactose, milk B had 12.5 g, and milk C contained 37.5 g of lactose. After the experiment was completed each subject was classified with a lactose tolerance test as having "sufficient" or "insufficient" lactase activity. Milk A produced no gastrointestinal symptoms in either sufficient or in insufficient persons. Milk B produced symptoms in 3.8% of sufficient and 37.1% of insufficient individuals, and Milk C induced symptoms in 7.6% of sufficient and 83.5% of insufficient subjects. These differences are very highly significant (P less than 0.0001). It is concluded that lactose-intolerant subjects are indeed milk-intolerant and that the frequency with which symptoms occur in persons with lactose malabsorption increases in direct relation to the lactose content of the milk.     

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.     

Coincidental Malabsorption of Lactose, Fructose, and Sorbitol Ingested at Low Doses Is Not Common in Normal Adults

Normal subjects may incompletely absorb either lactose, fructose, or sorbitol and may therefore have abdominal symptoms. The frequency of coincidental malabsorption of these sugars is not known. This is clinically important, since we often ingest them during the same day and malabsorption may cause abdominal symptoms. To shed light on this issue we studied 32 normal subjects. Volunteers drank in random order the following solutions: 20 g lactulose, 50 g sucrose, 50 and 25 g lactose, 50 and 25 g fructose, 20 and 10 g sorbitol. Semiquantitative carbohydrate malabsorption was estimated with lactulose standards. Frequency of 50-g lactose (69%), 50-g fructose (81%), and 20-g sorbitol (84%) malabsorption was not significantly different (P = 0.3). The estimated median fraction of the ingested high dose malabsorbed was 42, 19, and 68% for lactose, fructose, and sorbitol, respectively. At low challenging doses, 63% of the volunteers absorbed two of three or all three sugars, and 88% were asymptomatic to two or all three sugars. In conclusion, the frequency of coincidental malabsorption of lactose, fructose, and sorbitol and intolerance to these sugars is not common, when normal adults ingest them at low doses.     

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.     

Gastric emptying of sugar solutions and cow's milk with and without carbohydrates in adult rats]

In this study, we determined the gastric retentions in rats of aqueous solutions or cow's milk containing different compositions of sugars. The following meals were tested: 1. aqueous solutions containing one sugar at 10% (lactose, sucrose or maltose), or 2. containing a combinations of two sugars (lactose + sucrose, lactose + maltose, sucrose + maltose), 3. cow's milk alone, or 4. containing one of the above sugar at 5%. Wistar male rats received a test meal (2 mL/100 g weight) with a marker: phenol red (6 mg/dL) in the sugars aqueous solutions ant polyethyleneglycol (PEG) 4000 (2 g/dL) in the cow's milk test meal. The gastric retention was measured by determining the amount of the marker remaining in the stomach by spectrophotometry. The results show larger gastric retention of maltose solutions, alone or in association with other sugar, than the lactose or sucrose ones. There was no difference between gastric retentions of cow's milk without sugar and those with addition of sucrose 5% or maltose 5%, 15 minutes after the administration of test meal. Nevertheless, 30 minutes later the administration, the gastric retention of whole cow's milk plus maltose 5% was larger than that of cow's milk without additional sugar. At the time of 45 minutes, the gastric retention of cow's milk plus sucrose 5% was larger than that of cow's milk without additional sugar. In conclusion the gastric emptying of maltose in aqueous or milk solution is smaller than those of lactose or sucrose in solutions at the same energetic density. Yet, this effect is seen even when the maltose is associated with one of the other two disaccharide in the same solution.     

Lactose malabsorption and intolerance: What should be the best clinical management?

Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a wellknown cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake. Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.     

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.     

Lactase deficiency: a common genetic trait of the American Indian

Intestinal lactase activity was assessed indirectly in 156 American Indians by measuring breath hydrogen after an oral lactose load. Lactase deficiency was present in 66% of subjects and correlated highly with the percentage of Indian blood. Lactase deficiency was present by the age of 5 years and was unrelated to sex. Most lactase-deficient subjects (81%), but only a minority (23%) of lactase-sufficient subjects, developed symptoms after the oral lactose load, and among lactase-deficient subjects, symptoms occurred more frequently in adults than in children (P = 0.05). Indeed, by history, 53% of lactase-deficient adults, but only 10% of lactase-deficient children under 18 years of age, were aware of milk intolerance. Despite these differences, milk consumption was only slightly less (19 g) in the lactase-deficient subjects than in those with normal lactase activity (25 g) (P less than 0.05). The results indicate that lactase deficiency is a common autosomal genetic trait in the American Indian that becomes manifest in early childhood. Tolerance to dietary lactose appears to decline in the American Indian as he reaches adulthood, but in this population the decline in tolerance had only minor influence on lactose intake.     

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 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.     

Changes in plasma free fatty acid concentration following oral lactose tolerance tests as a test for lactose absorption in infants and children

Changes in blood glucose and plasma free fatty acid (FFA) following oral lactose tolerance tests (LTT) were measured in three groups of children. In three out of seventeen infants with secondary lactose intolerance, only a small increase (less than 25 mg/100 ml) in glucose was found, but a normal decline (more than 50% of fasting value) in FFA concentration occurred. Resumption of milk feeding proved that they were not intolerant to lactose. Six infants (37%) without lactose intolerance who were on a normal lactose-containing diet showed only small increases in glucose; five of them showed a normal decline in plasma FFA. Nine out of thirteen children with no symptoms following oral LTT failed to show an increase in blood glucose, while in only one there was a decline of less than 50% in FFA concentration. Our results suggest that measurement of plasma FFA following oral LTT may be a more reliable test for cleavage and absorption of lactose than LTT alone, but for the final evaluation of this test a study of larger groups is obviously needed.     

Management and treatment of lactose malabsorption

Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world's population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenousβ-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.     

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.