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.     

Hydrogen breath test for the diagnosis of lactose intolerance, is the routine sugar load the best one？

AIM： To evaluate the prevalence of lactose intolerance （LI） following a load of 12.5 g in patients diagnosed as high-grade malabsorbers using the hydrogen breath test （HBT）-25. METHODS： Ninety patients showing high-grade malabsorption at HBT-25 were submitted to a second HBT with a lactose load of 12.5 g. Peak hydrogen production, area under the curve of hydrogen excretion and occurrence of symptoms were recorded. RESULTS： Only 16 patients （17.77%） with positive HBT-25 proved positive at HBT-12.5. Hydrogen production was lower as compared to HBT-25 （peak value 21.55 parts per million （ppm） ± 29.54 SD vs 99.43 ppm ± 40.01 SD; P 〈 0.001）. Symptoms were present in only 13 patients. The absence of symptoms during the high-dose test has a high negative predictive value （0.84） for a negative low-dose test. The presence of symptoms during the first test was not useful for predicting a positive low-dose test （positive predictive value 0.06-0.31）. CONCLUSION： Most patients with a positive HBT-25 normally absorb a lower dose of lactose and a strict lactose restriction on the basis of a ＂standard＂ HBT is, in most instances, unnecessary. Thus, the 25 g lactose tolerance test should probably be substituted by the 12.5 g test in the diagnosis of LI, and in providing dietary guidelines to patients with suspected lactose malabsorption/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.     

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.     

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 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.     

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 intolerance in adults with chronic unspecific abdominal complaints

77 hospitalized patients with chronic unspecific abdominal complaints, in whom any other organic disease had been previously excluded, were investigated for lactose malabsorption; they were subdivided into two groups: 46 patients complaining primarily of colicky abdominal pain and/or intermittent diarrhoea (group 1) and 31 patients presenting with dyspepsia as the predominant symptom (group 2). To establish the exact prevalence of isolated lactase deficiency in the healthy adult population served by our hospital, 40 Italian adult healthy subjects were also studied. The prevalence of lactose malabsorption was significantly higher (p less than 0.005) in patients of the 1st group than in patients of the 2nd group, and in the healthy adult population seen at our hospital (74% vs 35.5% and 37.5%, respectively). Furthermore a high prevalence of lactose intolerance, determined by means of a three-week diet trial (lactose free-diet versus normal diet), was documented among lactose malabsorbers of the 1st group. We concluded therefore that lactose intolerance is a factor in some Italian adult patients who suffer from long-standing aspecific abdominal discomfort, and it should be always considered in these patients, especially when colicky abdominal pain and diarrhoea are present, before the diagnosis of irritable bowel syndrome is made.     

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.     

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.     

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.     

Incidence and clinical significance of lactose malabsorption in ulcerative colitis and Crohn's disease

The incidence of lactose malabsorption was investigated in 85 patients with ulcerative colitis and 71 patients with Crohn's disease by means of lactose tolerance tests and disaccharidase determinations in small intestinal mucosa. Eight patients with ulcerative colitis (9%) and four with Crohn's disease (6%) had lactose malabsorption. A control group displayed a similar incidence. It is concluded that lactose malabsorption is not particularly common in ulcerative colitis and Crohn's disease. If it is present, its aetiology seems to be unrelated to the intestinal disease.Transitional lactose malabsorption was detected in two cases during a relapse of ulcerative colitis.Institution of a lactose-free (or lactose-poor) diet was an important supporting measure in seven patients who were unaware of their milk intolerance, in particular in two with ileostomy. Therefore, it is recommended that a lactose tolerance test should always be performed in patients with ulcerative colitis or Crohn's disease.Twenty-one patients with ulcerative colitis and nine with Crohn's disease, none of whom had lactose malabsorption, were placed on milk-free diets. A beneficial effect was noticed in five of the patients with ulcerative colitis, and in three of those with Crohn's disease. The mechanism is unknown.Evidence is presented that milk allergy is not responsible for the beneficial effect of a lactosefree diet in patients with associated lactose malabsorption.     

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.     

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.     

Hydrogen concentration in expired air analyzed with a new hydrogen sensor, plasma glucose rise, and symptoms of lactose intolerance after oral administration of 100 gram lactose

A rapid breath hydrogen analyzer to detect lactose malabsorption is described. After ingestion of a lactose solution the patient expires into a mouthpiece attached to a hydrogen sensor at 30-min intervals for 3 1/2 h. The hydrogen of the expired air causes a voltage change that can be transformed into ppm from a calibration curve. A tolerance test with a load of 100 g lactose was performed in 43 consecutive patients with various gastrointestinal disturbances, referred to the laboratory for the commonly used lactose tolerance test based on plasma glucose measurements. Eleven patients developed symptoms of lactose intolerance during the test. Biopsy specimens from the distal duodenum or proximal jejunum showed partial villous atrophy in one, in whom celiac disease with lactose intolerance was diagnosed; the other 10 had normal specimens. In nine of them lactose intolerance was diagnosed and confirmed by observation for months on a lactose-poor diet. The 10th patient (H.P.L.) did not improve on such a diet. He also showed pronounced symptoms of intolerance during a test with monosaccharides (glucose + galactose). His intestinal disease remained undiagnosed. The 11 patients with symptoms of intolerance and 3 patients without symptoms during the lactose load showed a flat plasma glucose curve after drinking the lactose solution--that is, a maximum rise of the glucose concentration of 1.5 mmol/l. One of the symptom-free patients dropped out and could not be observed, another did not improve on a lactose-poor diet, and the third noticed a favorable effect of the diet on stool consistency but not on other abdominal symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Lactose malabsorption and intolerance in Italians

Lactose malabsorption was assessed by the hydrogen breath test in 40 Italian patients with irritable bowel syndrome and 42 controls without abdominal disturbances. Sixty-five percent of patients were "low milk consumers" (0-250 ml milk per day) compared with 38% of controls (P less than 0.02). Lactose loads of 25 and 50 g caused malabsorption in 82.5 and 87.5% patients and in 55 and 62% controls, respectively (patients vs controls P less than 0.02). Malabsorption was more frequent in the "low milk consumers" group (P less than 0.05). During a four-month lactose-free diet as the only treatment 7.5% of patients became symptom-free (and remained so for a further eight-month diet), 52.5% improved, and 40% showed no change.     

Irritable bowel syndrome: is the search for lactose intolerance justified?

OBJECTIVES: To determine if confirmation of hypolactasia offers any benefit to the dietary treatment of patients with irritable bowel syndrome (IBS). METHODS: One hundred and twenty-two consecutive IBS patients (37 male, 85 female) were given lactose hydrogen breath tests (LHBT). Those with positive LHBT followed a low lactose diet for 3 weeks. Those improving on the diet were given double-blind, placebo-controlled challenges (DBPCC) with 5 g, 10 g and 15 g of lactose and a placebo, to confirm lactose intolerance. Those who did not respond to the low lactose diet followed either an exclusion or low fibre diet. Symptoms scores were kept prior to the LHBT, 8 h post-LHBT and daily whilst following any dietary change. Patients with negative LHBT returned to clinic and subsequent dietary interventions were recorded. RESULTS: LHBT was positive in 33/122 (27%) IBS patients. Syrr otom scores prior to LHBT were not significantly different between the two groups, but after LHBT the symptoms in the positive group were significantly worse. Twenty-three patients followed a low-lactose diet of which only nine (39%) improved. Six who did not improve followed an exclusion diet, three improved and all were intolerant of milk. Three tried a low fibre diet with two improving. DBPCC were inconclusive. In the negative LHBT group 35 agreed to try a diet and 24 improved (69%). Eight were intolerant of cow's milk. CONCLUSIONS: Use of a low lactose diet was disappointing in IBS patients with lactose malabsorption. Food intolerance was demonstrated in IBS patients with positive or negative LHBT and milk was identified as a problem in both groups. DBPCC were inconclusive. There appears to be little advantage in trying to separate patients who malabsorb lactose from others with IBS.     

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.