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.     

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

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

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.     

Interval sampling of breath hydrogen (H2) as an index of lactose malabsorption in lactase-deficient subjects

Interval sampling of breath hydrogen content was used in lactose malabsorbers: (1) to compare hydrogen responses following increasing oral doses of lactose in milk and aqueous solutions; (2) to determine the reproducibility of interval breath sampling, and (3) to compare carbohydrate malabsorption following ingestion of either regular milk or milk containingLactobacillus acidophilus. Significant differences in breath hydrogen responses due to increasing amounts of lactose in milk and aqueous solutions were observed. The individual breath hydrogen responses were reproducible using the same lactose dose on different days. There was no significant difference in breath hydrogen responses or symptoms following administration of either regular milk or milk containingLactobacillus acidophilus. Breath hydrogen sampling at intervals, as performed in these studies, provides a sensitive and reproducible index of lactose malabsorption.Supported by the Oklahoma Agricultural Experiment Station, Stillwater, Oklahoma, and the Veterans Administration.     

Does Oral Enzyme Replacement Therapy Reverse Intestinal Lactose Malabsorption?

The effects of oral enzyme replacement therapy on breath hydrogen excretion and symptoms after milk ingestion were studied in lactase-deficient patients. Sixteen symptomatic patients underwent interval hydrogen breath tests using whole milk as substrate. Each study was repeated with the addition of 250 mg of β-D-galactosidase derived from Aspergillus oryzae (Lactrase) given orally with the milk. Subsequently seven of those 11 patients who did not normalize their hydrogen excretion with 250 mg of Lactrase were available to be restudied with a 500-mg dose. Mean cumulative and peak hydrogen excretions were calculated for the baseline (milk alone), 250 mg, and 500 mg Lactrase groups. Significant (p ≤ 0.05) decreases in cumulative and peak hydrogen excretion were noted between the 500 mg Lactrase versus the baseline group, but not between the 250 mg versus baseline group. Five of the 16 (31%) symptomatic lactase-deficient patients normalized their hydrogen excretion after 250 mg of Lactrase; four of seven (57%) who bad not normalized on 250 mg, normalized their hydrogen excretion with 500 mg of Lactrase. A different pattern was observed in the incidence of symptoms. Five of the nine patients (56%) whose hydrogen excretion normalized with the addition of Lactrase at either dosage became asymptomatic after milk ingestion; in addition, three patients who did not normalize their hydrogen also became asymptomatic. We conclude that oral Lactrase in sufficient dosage temporarily reverses lactose malabsorption in some patients.     

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.     

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

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

Studies on the etiology of milk intolerance in Japanese adults.

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

Carbohydrate malabsorption in alcoholic pancreatic insufficiency. The effect of pancreatic enzyme therapy on intestinal transit time

The absorption of rice flour and the mouth-to-cecum transit time of a nonabsorbable carbohydrate were measured by breath hydrogen excretion technique in 10 patients with alcoholic pancreatic insufficiency, to evaluate the underlying mechanisms of carbohydrate malabsorption. Breath hydrogen excretion after ingestion of rice pancakes was significantly higher in patients than in 10 controls, suggesting malabsorption of carbohydrates. Mouth-to-cecum transit time was not significantly different between the two groups. Pancreatic enzyme therapy significantly reduced both fecal fat excretion and the degree of carbohydrate malabsorption, but, in contrast, did not significantly change mouth-to-cecum transit. There was no correlation between the degree of carbohydrate or fat malabsorption and mouth-to-cecum transit time. Carbohydrate malabsorption is common in pancreatic insufficiency and is markedly improved by enzyme supplementation. Mouth-to-cecum transit, however, does not play a major role in carbohydrate or fat malabsorption in these patients.     

Carbohydrate malabsorption following acarbose administration

Carbohydrate absorption was assessed during acarbose administration to investigate the actions of this drug. In 7 healthy volunteers, breath hydrogen concentration was measured at 15-min intervals after administration of 6 g of lactulose, and continued until 4 h after the breath hydrogen level exceeded its pretreatment value by ≥10 ppm, then the amount of undigested carbohydrate was calculated following administration of various doses of acarbose and Ensure Liquid. Breath hydrogen data were also obtained before and after administration of acarbose to 8 patients with Type 2 diabetes mellitus for 2 and 4 months. After administration of 50 mg of acarbose with 250 ml or 500 ml of Ensure, the mean amount of unabsorbed carbohydrate was 5.3 g and 7.7 g, respectively, while unabsorbed carbohydrate increased to 10.8 g after 100 mg of acarbose with 500 ml of Ensure. In the diabetic patients, breath hydrogen excretion decreased to 31.6 % of baseline after 2 months of acarbose administration, indicating decreased carbohydrate malabsorption. Despite this, the haemoglobin A_1c level remained stable after 5 months. In conclusion, the extent of carbohydrate malabsorption depended on the acarbose dose and the carbohydrate load. Although carbohydrate malabsorption decreased with continued acarbose administration, the improvement of glycaemic control was maintained. © 1998 John Wiley & Sons, Ltd.     

Prevalence of lactose maldigestion

Ninety-eight adults ranging from 20 to 89 years in age (52 blacks, 46 whites; 48 males, 50 females) were tested for lactose maldigestion by breath hydrogen analysis after consuming milk containing 16.5 g lactose (360 ml milk). Older adults (50 years) displayed a significantly higher incidence (46%) of lactose maldigestion than younger adults (<50 years, 26%). In younger adults there were 2.4 times more maldigesters in blacks than in whites, while in older groups this ratio was 3.6. Level of breath hydrogen significantly increased with age up to the age group of 60–69 years. The interaction between age groups and race was highly significant. Of the maldigesters, 63% reported symptoms and 3% of the total sample reported severe symptoms. Results of this study indicate that the prevalance of lactose maldigestion significantly increases with age in blacks compared to whites and that the magnitude of the problem may be greater in black maldigesters than in white maldigesters.     

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.     

Assessment of lactose absorption by measurement of urinary galactose

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.     

Evaluation of the hydrogen breath test in man: definition and elimination of the early hydrogen peak.

After ingestion of a non-absorbable carbohydrate breath hydrogen excretion increases early at about 10 minutes, and again later when the ingested carbohydrate enters the caecum. The late rise has been used as a marker of mouth to caecum transit time, but the source of the early rise has not been satisfactorily explained. We studied in 60 healthy volunteers the source and frequency of the early rise in breath hydrogen after ingestion of a non-absorbable carbohydrate. After ingestion of either lactulose solution (10 g in 150 ml water), lentil soup (46 g carbohydrate) or solid meal containing baked beans (15 g carbohydrate), breath hydrogen was significantly raised above basal concentrations within 10 minutes (81 +/- 27, 395 +/- 138 and 110 +/- 52% above basal respectively). A significant rise in breath hydrogen (75 +/- 21%) occurred 10 minutes after sham lactulose feeding (lactulose applied to oral cavity but not swallowed), but no early peak occurred after sham saccharin feeding (non-fermentable carbohydrate), intragastric or intraduodenal administration of lactulose. Ten of the 12 subjects given lactulose sham feeding were restudied after oral hygiene with chlorhexidine mouthwash. In these the early hydrogen peak was abolished. Oral hygiene also reduced the occurrence and magnitude of the early hydrogen rise after lactulose ingestion. These findings indicate that the early rise in breath hydrogen observed after ingestion of lactulose is produced by interaction with oral bacteria.     

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.     

Impairment of Starch Absorption by a Potent Amylase Inhibitor

Many previous investigations of available amylase inhibitors have not been able to demonstrate significant carbohydrate malabsorption. This study uses breath hydrogen analysis, a sensitive method for detecting the passage of starch into the colon, to determine if a potent amylase inhibitor is capable of producing carbohydrate malabsorption. Thirteen volunteers underwent three studies, ingesting as a carbohydrate substrate: lactulose 20 g, spaghetti alone, and spaghetti with amylase inhibitor (3.8 g). Samples of breath were collected (at frequent intervals) for 2 h after the lactulose and for 8 h after the spaghetti meal and analyzed for hydrogen concentration. The ingestion of spaghetti alone resulted in significant increases in breath hydrogen concentration at 420-450 min. The mean (+/- SE) hydrogen excretion rate was increased more than 2-fold with the amylase inhibitor, from 0.4 +/- 0.2 to 0.9 +/- 0.3 ml/h (p less than 0.05). Use of the amylase inhibitor in powder form produced a similar increase in the rate of hydrogen excretion to 1.1 +/- 0.4 ml/h. The percentage of carbohydrate malabsorbed was calculated for the spaghetti meal and spaghetti with amylase inhibitor using each individual's observed hydrogen excretion with lactulose. Over the 8-h observation period, 4.7 +/- 1.9% of the spaghetti was malabsorbed and 7.0 +/- 1.4% of the spaghetti with amylase inhibitor was malabsorbed (p less than 0.05). Measurements of the effect of the amylase inhibitor on amylase activity of duodenal juice revealed that the amylase inhibitor at a concentration of more than 5 mg/ml decreased the amylase activity by more than 96%. These results indicate that this potent amylase inhibitor is capable of enhancing malabsorption of wheat starch.     

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.     

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.     

Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate.

The extent to which monitoring breath hydrogen excretion provides information concerning the entry of the residues of a solid test meal into the colon was investigated in 89 normal subjects, and 11 patients with the irritable bowel syndrome. The profile of breath hydrogen concentration showed an early peak, that occurred soon after ingesting the test meal in 89% subjects. This was followed by a later more prolonged rise in breath hydrogen concentration. The early peak occurred well before a radioactive marker, incorporated in the test meal, reached the caecum and the data suggest it was predominantly caused by the emptying of the remnants of the previous meal from the ileum into the colon. This hypothesis was supported by direct measurements of the rate of delivery of ileostomy effluent in 12 subjects with terminal ileostomies. Fermentation of carbohydrate in the mouth may, however, contribute to the initial peak, but this contribution may be avoided by collecting gas samples from the nares. The secondary rise in breath hydrogen excretion was closely correlated with the arrival of the radioactive marker in the caecum (r = 0.91), p less than 0.001), though the time, at which the secondary peak of breath hydrogen excretion occurred was poorly correlated with the time that all the radioactive test meal had entered the colon. When lactulose was infused directly into the colon, as little as 0.5 g produced a discernible hydrogen response, which occurred within two minutes of the infusion. Increasing the rate of colonic infusion of a 50 ml solution of 10% lactulose from 0.02 to 0.15 g/min in five subjects significantly increased the breath hydrogen concentration. At infusion rates below 0.075 g lactulose/minute, the peak breath hydrogen response preceded the end ot the infusion, while at higher rates of infusion, the peak hydrogen response occurred after the end of the infusion. Although these results confirmed that monitoring breath hydrogen concentration usefully signalled the time taken for a meal containing unabsorbed carbohydrate to reach the colon, it did not reliably indicate the time when all of the meal had entered the colon. Finally, the use of the maximum increase in breath hydrogen concentration as an index of the degree of carbohydrate malabsorption assumes uniform rates of entry into the colon.