Lactose malabsorption in a population with irritable bowel syndrome: prevalence and symptoms. A case‐control study

Background: Symptoms after intake of milk are common in persons with irritable bowel syndrome (IBS). The aims of this study were to compare the prevalence of lactose malabsorption (LM) and symptoms related to intake of milk and lactose in subjects with IBS with that of healthy volunteers, and to search for symptoms that are characteristic of LM. Methods: A case‐control study in a Norwegian population was initiated. Subjects with IBS were asked for symptoms related to intake of milk and lactose, tested for LM, and compared with a group of healthy volunteers. Results: The study comprised a total of 187 persons (82 with IBS and 105 volunteers), females/males: 138/49, mean age 47 years. In subjects with IBS and in healthy volunteers, LM was present in 3/74 (4.1%) and 4/105 (3.8%), respectively (ns), milk‐related symptoms in 32/79 (40%) and 13/105 (12%), respectively (P?P?=?0.01). Borborygmi starting within 5?h after intake of lactose and lasting for more than 2?h indicated LM (OR 61 (95% CI:­8–475), P?Conclusions: IBS and LM are unrelated disorders in a Norwegian population. Milk‐related symptoms and symptoms after intake of lactose are unreliable predictors for LM. Precise symptom‐based criteria might enhance the diagnostic accuracy for LM.     

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.     

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.     

Lactose malabsorption in a population with irritable bowel syndrome: prevalence and symptoms. A case-control study

BACKGROUND: Symptoms after intake of milk are common in persons with irritable bowel syndrome (IBS). The aims of this study were to compare the prevalence of lactose malabsorption (LM) and symptoms related to intake of milk and lactose in subjects with IBS with that of healthy volunteers, and to search for symptoms that are characteristic of LM. METHODS: A case-control study in a Norwegian population was initiated. Subjects with IBS were asked for symptoms related to intake of milk and lactose, tested for LM, and compared with a group of healthy volunteers. RESULTS: The study comprised a total of 187 persons (82 with IBS and 105 volunteers), females/males: 138/49, mean age 47 years. In subjects with IBS and in healthy volunteers, LM was present in 3/74 (4.1%) and 4/105 (3.8%), respectively (ns), milk-related symptoms in 32/79 (40%) and 13/105 (12%), respectively (P < 0.001) and symptoms after intake of lactose in 28/74 (38%) and 21/104 (20%), respectively (P=0.01). Borborygmi starting within 5 h after intake of lactose and lasting for more than 2 h indicated LM (OR 61 (95% CI: 8-475), P < 0.001). CONCLUSIONS: IBS and LM are unrelated disorders in a Norwegian population. Milk-related symptoms and symptoms after intake of lactose are unreliable predictors for LM. Precise symptom-based criteria might enhance the diagnostic accuracy for LM.     

Manifestation and occurrence of selective adult-type lactose malabsorption in Finnish teenagers

In 1969–1970, a simple random sample of 129 Finnish school-aged children was examined to study selective adult-type lactose malabsorption (SLM) in this age category. SLM was found in 8 children. All subjects were reexamined 5 years later. SLM was reconfirmed in these 8 persons and found in 3 additional subjects who had normal lactose absorption in the first examination. The prevalence of SLM was 9.3%, being 8.5% in the age category 12–15 years and 9.9% in that 16–20 years. Low rise of blood glucose in the lactose tolerance test of the first examination, very low milk consumption, milk intolerance, and history of gastrointestinal symptoms were found to be of low predictive value as indicators of SLM. It was also concluded that information about dietetic sources of lactose is important to persons with SLM, but categorical exclusion of lactose from the diet is not necessary, at least in the Finnish population.The study was supported by the Finnish Cultural Foundation and the Foundation for Pediatric Research in Finland.     

Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis

Lactose malabsorption was studied, by hydrogen breath test, in 72 adults suffering from irritable bowel syndrome, in 20 ulcerative colitis patients, and in 69 healthy subjects. The minimum dose of lactose required to cause a positive breath test was determined, and the symptoms caused and the resulting hydrogen eliminated quantified. A high incidence of lactose malabsorption was shown at standard doses (up to 50 g) in both the healthy subjects (70%) and the patients (86% and 85%, respectively). In the irritable bowel syndrome and the ulcerative colitis groups, symptoms occurred with a smaller quantity of breath hydrogen, presumably in association with a greater individual sensitivity of the colon to distension. The threshold lactose dose was notably lower in the diseased subjects who registered as evidence a prevalence of malabsorption at a 20-g lactose load. The pathogenetic role of lactose malabsorption in the irritable bowel syndrome is emphasized, as is the importance of the personal lactose tolerance.     

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.     

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.     

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.     

Breath hydrogen excretion after lactose and whole milk ingestion. A prospective comparison in lactase deficiency

As the 50 g of lactose in the usual clinical test is unphysiologic both because it is equivalent to 1 L milk and because the usual dietary intake is not the purified sugar, but milk, we undertook a prospective comparison of the absorption of lactose after both lactose and milk ingestion with an equivalent lactose content. We studied 51 healthy volunteers, using the hydrogen breath test technique. All patients received 25 g lactose in aqueous solution. Subjects with an abnormal test had the test repeated with 500 ml whole cow's milk, whereas subjects with a normal test repeated the test after ingesting the unabsorbable sugar lactulose to detect the capacity of their colonic flora to produce the gas. Symptoms of gastrointestinal intolerance were also recorded. Compared to an equivalent lactose amount, milk lactose is better absorbed (8% of the entire population malabsorbed 500 ml whole milk, whereas 33.33% malabsorbed 25 g lactose) and induces intolerance in fewer subjects. We conclude that milk rather than pure lactose must be used in clinical evaluation of lactose malabsorption and intolerance.     

A New Type of Low-Lactose Milk

By ultrafiltration of skim milk a new low-lactose milk powder was developed whose lactose content was reduced by 86%. The lactose was replaced by malto-dextrin. In contrast to lactose-hydrolyzed milk powder, no protein-destroying processes (Mail-lard reactions) could be demonstrated during production or after storage at standard conditions. Tolerance of the new low-lactose milk versus regular skim milk was tested in 35 well-nourished, adult Latin Americans with lactose malabsorption. The ingestion of 500 ml of the low-lactose milk gave rise to significantly (p < 0.05) fewer symptoms than regular skim milk. After the intake of 250 ml there was a tendency to fewer symptoms after the low-lactose milk, although the difference was not significant (0.05 < p < 0.1). The new milk may be of potential usefulness in the treatment of protein calorie malnutrition in the developing countries, where lactose malabsorption is highly prevalent.     

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.     

Comparative tolerance of elderly from differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks: a double-blind study.

Milk intolerance was investigated in 87 healthy elderly individuals with a mean age of 77 years who were given 240 ml of a chocolate dairy drink twice in one week with a light lunch. No significant differences in symptomatic responses distinguished the subjects consuming a lactose-free (LF) drink from those consuming a drink containing 4.5% lactose (LC) under double-blind study conditions. Breath hydrogen analysis during lactose tolerance testing identified 23 malabsorbers, none of whom responded exclusively to the LC drink, although five were symptomatic on both days, and two had symptoms only on the day the LF drink was served. A similar percentage of absorbers (72%) and malabsorbers (70%) were asymptomatic on both days. Factors other than lactose malabsorption appeared to be responsible for the symptoms of intolerance reported, and most may have been psychosomatic in origin.     

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.     

Carbohydrate Malabsorption Syndromes and Early Signs of Mental Depression in Females

Fructose and lactose malabsorption are characterized by impaired duodenal fructose transport or by the deficiency of mucosal lactase, respectively. As a consequence, the nonabsorbed saccharides reach the colon, where they are broken down by bacteria to short fatty acids, CO₂, and H₂. Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of carbohydrate malabsorbers. We have previously shown that fructose as well as lactose malabsorption were associated with signs of mental depression. It was therefore of interest to investigate possible interactions between fructose and lactose malabsorption and their influence on the development of signs of depression. In all, 111 otherwise healthy volunteers (81 females and 30 males) with gastrointestinal complaints were analyzed by measuring breath H₂ concentrations after an oral dose of 50 g lactose and of 50 g fructose one week apart. They were classified as normals, isolated fructose malabsorbers, isolated lactose malabsorbers, and combined fructose/lactose malabsorbers. All patients filled out a Becks depression inventory–questionnaire. Twenty-five individuals (22.5%) were neither fructose nor lactose malabsorbers (group 1), 69 (62.2%) were only fructose malabsorbers (group 2), 4 (3.6%) were only lactose malabsorbers (group 3), and 13 (11.7%) presented with fructose and lactose malabsorption together (group 4). Isolated fructose malabsorption and combined fructose/lactose malabsorption was significantly associated with a higher Becks depression score. Further analysis of the data show that this association was strong in females (P < 0.01), but there was no such association between carbohydrate malabsorption and early signs of depression in males. In conclusion, the data confirm that fructose malabsorption may play a role in the development of mental depression in females and additional lactose malabsorption seems to further increase the risk for development of mental depression.     

Individual sensitivity to lactose in lactose malabsorption

The clinical significance of lactose malabsorption and the individual sensitivity to lactose were investigated in 20 patients with verified lactose malabsorption. Thirteen patients were relieved of all symptoms while seven improved only on a lactose-free diet. The healthy patients did not experience any symptoms following provocation with lactose-free milk but following provocation with increasing amounts of lactose, the tendency to diarrhea and abdominal discomfort increased considerably. Three patients experienced discomfort after provocation with only 5 g lactose. On provocation with increasing amounts of lactose the seven patients who had not recovered also developed increased abdominal discomfort but none of them developed increased tendency to diarrhea. It is concluded that, in addition to lactose malabsorption, these patients must suffer from irritable colon with tendency to constipation.This investigation was supported by The Danish Medical Research Council and The Danish Hospital Foundation for Medical Research, Region of Copenhagen, Faroe Islands and Greenland.     

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 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.     

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.