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.     

Breath hydrogen and methane excretion produced by commercial beverages containing dietary fiber

Soft drinks containing dietary fiber are popular in Japan. There seem to be two types, one containing polydextrose and the other, oligosaccharide. These beverages are claimed to be useful for constipation or obesity, but data are scanty. We examined four such fiber-containing beverages [Fibe-mini Otsuka Pharmaceuticals (Tokyo, Japan), Seni and Oligo Takeda Food Engineering (Osaka, Japan), Oligo CC (Calpis Food Engineering, Tokyo, Japan), and Sapitus 5289 Nakakita Pharmaceuticals (Nagoga, Japan)] for large intestine fermentability by measuring breath hydrogen (H₂) and methane (CH₄). Five healthy subjects (two men, three women, 22–48 years old) participated in the study. Breath H₂ and CH₄ were measured with a MicroLyzer (Quintron Instruments, Milwaukee, Wis.). Breath H₂ increased within 2h of beverage consumption, but CH₄ excretion was observed in only two subjects. Orocecal transit time was constant for all beverages. Total H₂ plus CH₄ excretion (AUC; area under the curve) after lactulose was 1294±250ppm × min/g fiber. AUC for Oligo CC was significantly greater than that for Fibe-mini or Sapitus 5289 (P<0.05). The AUCs of Fibe-mini, Seni and Oligo, Oligo CC, and Sapitus 5289 were 41%, 129%, 174%, and 40%, respectively, that of lactulose. It is concluded that commercial fiber-containing drinks produce H₂, and CH₄ in some people. Oligosaccharide produces more H₂ and CH₄ than polydextrose.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

Impact of age,sex, race,and functional complaints on hydrogen (H2) production

In order to evaluate factors that may influence H₂ generation, the effects of age, sex, race, and functional complaints on breath H₂ were studied in 62 subjects. These included 34 young hospital employees, 17 healthy ambulatory elderly subjects, and 11 patients with functional bowel disease. The ability to produce H₂ was defined by an increase in breath H₂ to greater than 20 parts per million within 4 hr of ingesting 10 g of the nonabsorbable sugar lactulose. Overall, 21% of subjects were nonproducers, and the incidence of nonproduction did not vary among the groups. The elderly subjects had significantly greater breath H₂ concentrations than the younger subjects at 150 minutes (P<0.05). Sex, race, and functional complaints did not influence H₂ production. These findings indicate that patient's age and potential inability to make H₂ need to be considered in the routine interpretation of H₂ breath tests.     

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.     

The Colon in Carbohydrate Malabsorption: Short-Chain Fatty Acids,pH, and Osmotic Diarrhoea

Holtug K, Clausen MR, Hove H, Christiansen J, Mortensen PB. The colon in carbohydrate malabsorption: short-chain fatty acids, pH, and osmotic diarrhoea. Scand J Gastroenterol 1992;27:545-552.

Short-chain (C₂-C₆) fatty acids (SCFA) are the major anions in colonic contents and the result of anaerobic fermentation of mainly saccharides. The effects and regulation of saccharide fermentation were studied in vitro and in vivo. In vitro faecal incubation was used to study the effects of lactose, glucose, and galactose and of pH on SCFA formation. Changing the pH to below 5 or above 11 abolished SCFA formation in the faecal incubates; in the pH 5-9 interval SCFA production was high, with only minor pH dependence. Adding glucose, galactose, or lactose to the incubation system increased SCFA production, but at high saccharide concentrations (100-300 mmol/1) SCFA formation was inhibited by the pH change. In vivo disaccharide malabsorption with increasing doses of lactulose caused a decrease in faecal pH to < 5, values inhibitory to fermentation, before the appearance of carbohydrate in faeces. In 6 of 12 volunteers diarrhoea occurred suddenly and was caused by malabsorbed non-fermented carbohydrate. The six other volunteers had a gradual increase in faecal output with lactulose dose and developed diarrhoea before the appearance of saccharide in faeces. The intake of lactulose tolerated before diarrhoea ensued varied between individuals, with the majority having diarrhoea of more than 1 1/day at 160 g lactulose per day. At this dose SCFA absorption was estimated to be in the range 550 to 1150mmol/day.     

Four-sample lactose hydrogen breath test for diagnosis of lactose malabsorption in irritable bowel syndrome patients with diarrhea

AIM: To validate 4-sample lactose hydrogen breath testing (4SLHBT) compared to standard 13-sample LHBT in the clinical setting.METHODS: Irritable bowel syndrome patients with diarrhea (IBS-D) and healthy volunteers (HVs) were enrolled and received a 10 g, 20 g, or 40 g dose lactose hydrogen breath test (LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h (13 measurements). The detection rates of lactose malabsorption (LM) and lactose intolerance (LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT.RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups (P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT (97%-100%, Kappa​​ 0.815-0.942) with high sensitivity (90%-100%) and specificity (100%) at all three lactose doses in both groups.CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.     

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.     

Prevalence and consistency of low breath H2 excretion following lactulose ingestion

The clinical use of the H₂ breath test is limited by the finding that a variable fraction of the population fails to excrete appreciable H₂ during colonic carbohydrate fermentation. Therefore, we assessed the ability to increase breath H₂ excretion in 371 patients (224 female, 147 male) by administering the nonabsorbable sugar lactulose. Following 12 g of lactulose, 27% of 94 patients did not increase their breath H₂ concentration over 20 ppm and were considered low H₂ excretors. Ingestion of 20 g of lactulose in 277 patients yielded a frequency of low H₂ excretors of 14%. Six of 10 patients that were low H₂ excretors after 12 g of lactulose increased their breath H₂ levels over 20 ppm when tested with 20 g. In 35 patients tested with the same amount of lactulose on two separate occasions, the subject frequently altered his or her H₂ producing status over a period of a few weeks. Low H₂ excretors had a significantly higher breath CH₄ concentration, both fasting (22 ± 34 ppm) and after lactulose (51 ± 58 ppm) compared to the remaining patients (5 ± 13 ppm and 16 ± 40 ppm, respectively). While the mean age of low excretors (54 ± 17 years) was significantly higher than the others (44 ± 17 years), no difference was found for sex prevalence and stool pH. This study demonstrates that respiratory H₂ excretion following lactulose ingestion is not consistent and suggests that the application of too restrictive criteria could lead to improper interpretation of the H₂ breath test.     

Breath hydrogen determination in patients following partial gastrectomy

ＩＮＴＲＯＤＵＣＴＩＯＮＭａｌｎｕｔｒｉｔｉｏｎｗｉｔｈｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌｓｙｍｐｔｏｍｓｉｎｃｌｕｄｉｎｇｃｈｒｏｎｉｃｄｉａｒｒｈｅａｈａｓｂｅｅｎｃｏｍｍｏｎｌｙｏｂｓｅｒｖｅｄｉｎｐａｔｉｅｎｔｓｆｏｌｏｗｉｎｇｐａｒｔｉａｌｇ...     

D-Xylose hydrogen breath tests compared to absorption kinetics in human patients with and without malabsorption

Thed-xylose breath H₂ test may be useful in characterizing intestinal absorptive function. Our aim was to determine whether breath H₂ followingd-xylose administration reflects the extent to which thed-xylose is absorbed by comparing it to a kinetic model ofd-xylose absorption. Twenty-five subjects were studied. They ingested 15 gd-xylose on the first day and 25 gd-xylose on the third day. On the second day they received 10 g intravenousd-xylose along with 15 g oral lactulose. Multiple serum and urine samples were obtained ford-xylose content to calculate its rate constants and extent of absorption by multicompartmental analysis. Breath H₂ determinations were obtained every 15 min for 3 hr following the 15 gd-xylose and lactulose ingestion. Peak breath H₂ concentration correlated with extent of absorption (r=–0.787,P<0.001),K ₀, the rate constant for nonabsorptive loss (r=0.744,P<0.001), and 5-hr urine content (r=–0.705,P<0.001). Area under the breath H₂ curve also correlated with these parameters: extent of absorption (r=–0.770,P<0.001),K ₀ (r=0.662,P<0.001), 5-hr urine content (r=–0.629,P<0.012). Peakd-xylose breath H₂ to peak lactulose breath H₂ showed no correlation with extent of absorption. The extent of absorption was higher with the 15-g dose than the 25-g dose in all patients tested (P<0.01). This was the result of decreased nonabsorptive loss (lowerK ₀), as the rate constant for absorption,K _a , was not statistically different (P>0.05). Peakd-xylose breath H₂ can be used as an inverse estimate ofd-xylose absorption. Lactulose breath H₂ cannot be used as a standard for comparison ford-xylose. The three compartment kinetic model ford-xylose absorption with passive absorption of this carbohydrate is supported by similar rate constants for absorption for the twod-xylose doses used.d-xylose at 15 g may be a more appropriate dose than 25 g for H₂ breath testing as it does not lead to increased nonabsorptive losses.Supported in part by grant RR0048, National Institutes of Health, National Center for Research Resources.     

Carbohydrate Malabsorption: Quantification by Methane and Hydrogen Breath Tests

Rumessen JJ, Nordgaard-Andersen I, Gudmand-Høyer E. Carbohydrate malabsorption: quantification by methane and hydrogen breath tests. Scand J Gastroenterol 1994;29:826-832.

Background: Previous studies in small series of healthy adults have suggested that parallel measurement of hydrogen and methane resulting from gut fermentation may improve the precision of quantitative estimates of carbohydrate malabsorption. Systematic, controlled studies of the role of simultaneous hydrogen and methane measurements using end-expiratory breath test techniques are not available. Methods: We studied seven healthy, adult methane and hydrogen producers and seven methane non-producers by means of end-expiratory breath test techniques. Breath gas concentrations and gastrointestinal symptoms were recorded at intervals for 12 h after ingestion of 10,20, and 30 g lactulose. Results: In the seven methane producers the excretion pattern was highly variable; the integrated methane responses were disproportional and not reliably reproducible. However, quantitative estimates of carbohydrate malabsorption on the basis of individual areas under the methane and hydrogen excretion curves (AUCs) tended to improve in methane producers after ingestion of 20 g lactulose by simple addition of AUCs of methane to the AUCs of the hydrogen curves. Estimates were no more precise in methane producers than similar estimates in non-producers. Gastrointestinal symptoms increased significantly with increasing lactulose dose; correlation with total hydrogen and methane excretion was weak. Conclusions: Our study suggests that in methane producers, simple addition of methane and hydrogen excretion improves the precision of semiquantitative measurements of carbohydrate malabsorption. The status of methane production should, therefore, be known to interpret breath tests semiquantitatively. The weak correlation between hydrogen and methane excretion and gas-related abdominal complaints suggests that other factors than net production of these gases may be responsible for the symptoms.     

Respiratory methane excretion in children with lactose intolerance

Two evaluate the relationship between colonic methane production and carbohydrate malabsorption, we measured end-expiratory methane levels in 70 normal and 40 lactose-intolerant children. Time-dependent excretion of hydrogen and methane was determined every 30 min for 120 min following a fasting oral lactose challenge (2 g/kg). Mean breath hydrogen levels in normals (lactose-tolerant) equaled 3.7 parts per million (ppm) throughout the study, but increased to >10 ppm by 60 min and remained elevated in lactose-intolerant subjects. Breath methane in normal children averaged 1.6 ppm from 0 to 120 min. In contrast, CH₄ excretion by lactose-intolerant children averaged 5.1 ppm at 90 min; and, by 120 min levels increased significantly compared with control. Breath methane levels in lactose-intolerant subjects following a lactose load continued to increase, however, despite the coingestion of exogenous lactase in amounts calculated to result in complete hydrolysis of the disaccharide. These data demonstrate that lactase-deficient children manifest significant increases in breath methane excretion following lactose ingestion and that enhanced methane production may be a consequence of several factors, including altered fecal pH and increased methanogenic substrates provided by colonic lactose fermentation. Further studies are required to determine the clinical significance of elevated methane production in lactose intolerance.     

Circadian rhythm of breath hydrogen in young women

Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of α-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21–23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, α-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 ± 3.9 ppm (mean ± SE), which did not differ from the value for the previous night. α-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 ± 2.4 ppm (P < 0.05). There was a clear circadian pattern of breath hydrogen, high in the morning and decreasing to the nadir by 16:00. After dinner, the level increased again and stayed high during the night. Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day. (Received Sept. 16, 1997; accepted Jan. 23, 1998)     

Intestinal disaccharidases assessed in congenital asucrasia by differential urinary disaccharide excretion

Summary A patient with congenital asucrasia was investigated usingin vivo differential urinary disaccharide excretion. Impaired hydrolysis of sucrose and isomaltose, but normal lactase activity, were demonstrated and confirmed byin vitro estimation. The technique of differential disaccharide excretion can now be used to assess three disaccharidases simultaneously,in vivo, including isomaltase.     

Small bowel transit time measured by hydrogen breath test in patients with anorexia nervosa

The gastrocecal transit time was measured in 10 patients suffering from anorexia nervosa,using a lactulose hydrogen breath test, and was compared with the orocecal transit time in 11 healthy controls. One of the 10 patients and one of the 11 controls were excluded from this study because of no discernible increase in hydrogen excretion. The transit time was significantly prolonged in patients with anorexia nervosa compared with controls (117 min ±31 sd vs 81 min + 33 SD, P <0.02). In addition to delayed gastric emptying, which has hitherto been well known, the small bowel transit time was considered to be prolonged in patients with anorexia nervosa. Both these abnormalities seem to contribute to the development of various gastrointestinal symptoms in patients with anorexia nervosa.     

Comparison of Inulin and Lactulose as Reference Standards in the Breath Hydrogen Test Assessment of Carbohydrate Malabsorption in Patients with Chronic Pancreatic Exocrine Insufficiency

Although often used as a reference standard in the breath hydrogen test (BHT), lactulose fermentation produces more hydrogen, compared to starch, and may therefore not be ideal. This study compares inulin with lactulose as reference standard in the study of carbohydrate malabsorption. Seventeen patients with malabsorption due to chronic pancreatitis and 15 normal controls were studied. Following overnight fasts, BHTs were performed after ingesting 10 g lactulose, 10 g inulin, and 200 g (16 g highly resistant starch) maize meal. Lactulose fermentation produced significantly more hydrogen than inulin in patients with malabsorption (97± 20 vs 45± 22 ppm ⋅ hr; P < 0.05) and controls (43 ± 18 vs 21 ± 10 ppm ⋅ hr; P < 0.05). Patients produced more hydrogen than controls with both standards (lactulose, 97 ± 20 vs 43 ± 18 ppm ⋅ hr, P < 0.05; inulin 45 ± 22 vs 21 ± 10 ppm ⋅ hrs; P < 0.05), suggesting adaptation of the colonic flora. Calculated CHO malabsorption was 2.5 ± 0.8 vs 5.2 ± 3.8 g with lactulose and 5.2 ± 3.1 vs 11.2 ± 9.6 g with inulin as standards in controls and patients, respectively (P < 0.05). Lactulose produces more breath hydrogen than inulin. Calculation of CHO malabsorption using these standards is therefore not comparable.This work was supported by a grant from the South African Medical Research Council.     

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

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