Suppressive effect of partially hydrolyzed guar gum on transitory diarrhea induced by ingestion of maltitol and lactitol in healthy humans

OBJECTIVES: To estimate the suppressive effect of partially hydrolyzed guar gum (PHGG) on transitory diarrhea induced by ingestion of a sufficient amount of maltitol or lactitol in female subjects. DESIGN: The first, the minimal dose level of maltitol and lactitol that would induce transitory diarrhea was estimated separately for each subject. Individual subject was administered a dose that increased by 5 g stepwise from 10 to 45 g until diarrhea was experienced. Thereafter, the suppressive effect on diarrhea was observed after each subject ingested a mixture of 5 g of PHGG and the minimal dose level of maltitol or lactitol. SETTING: Laboratory of Public Health Nutrition, Department of Nutrition and Health Sciences, Siebold University of Nagasaki. SUBJECTS: Thirty-four normal female subjects (21.3+/-0.9 years; 49.5+/-5.3 kg). MAIN OUTCOME MEASUREMENT: Incidence of diarrhea caused by the ingestion of maltitol or lactitol and the ratio of suppression achieved by adding PHGG for diarrhea. RESULTS: The ingestion of amounts up to 45 g of maltitol, diarrhea caused in 29 of 34 subjects (85.3%), whereas the ingestion of lactitol caused diarrhea in 100%. The diarrhea owing to maltitol was improved in 10 of 28 subjects by the addition of 5 g of PHGG to minimal dose-induced diarrhea, and that owing to lactitol was in seven of 19 subjects. Adding 10 g of PHGG strongly suppressed the diarrhea caused by maltitol, and the cumulative ratio was 82.1% (23/28). CONCLUSION: The transitory diarrhea caused by the ingestion of maltitol or lactitol was clearly suppressed by the addition of PHGG. These results strongly suggest that diarrhea caused by the ingestion of a sufficient amount of non-digestible sugar substitute can be suppressed by the addition of dietary fiber.     

The effects of maltitol on rat intestinal disaccharidases.

1. The highese disaccharidase activity for sucrose maltose and maltitol was found in the jejunum, followed by the ileum and duodenum. However, the disaccharidase activity for maltitol was extremely low compared with that for sucrose and maltose. 2. For maltitol, the Km value was very large and the Vmax value was very low compared compared with the values for sucrose and maltose. 3. The initial velocity (v) in the presence of the sucrose and maltitol, was equal to the sum of the rates for individual substrates sucrose ann maltitol (v1, v2) respectively (v=v1+v2). Thus, no competition between these substrates was observed. In the case of maltose and maltitol, the initial velocity (v) in the presence of both substrates was less than the sum of the individual rates for maltose and maltitol (v1, v2) in the absence of the other substrate (v is less than v1 + v2). This finding demonstrates that there is competition between these two substrates for the same enzyme. Furthermore, the apparent Michaelis constant (Km) and the apparent maximal velocity (Vmax) for pure and mixed substrates, i.e., maltose and maltitol, at various mole fractions of maltose showed dependence on the mole fraction of maltose. The obtained kinetic data provide strong evidence that both maltose and maltitol react at the single active center of maltase.     

Metabolism of maltitol by conventional rats and mice and germ-free mice, and comparative digestibility between maltitol and sorbitol in germ-free mice

The metabolism of maltitol (4-alpha-D-glucosylsorbitol) was assessed in fasting conventional (C) rats, C mice and germ-free (GF) mice, using [U-14C]maltitol. The radiorespirometric patterns of 14CO2 collected for 48 h after the administration of labelled maltitol were characterized by a constant rate of 14CO2 production lasting 4 h for both C rats and mice. The pattern for the GF mice showed a peak at the second hour followed immediately by a slow decrease. The percentage recovery of 14CO2 was significantly lower for the GF mice (59%) compared with C animals (72-74%). Urine, faeces and intestinal contents after 48 h totalled 19% of the administered radioactivity in the C rats and mice and 39% in the GF mice. The digestibility of maltitol and the absorption of sorbitol in GF mice was also assessed. The caecum and small intestine of GF mice, 3 h after administration of equimolar quantities of maltitol (140 mg/kg body-weight) or sorbitol (70 mg/kg body-weight), contained 39 and 51% of the ingested dose respectively, present mostly in the caecum as sorbitol. The alpha-glucosidase (maltase) (EC3.2.1.20) activity of the small intestine was appreciably higher (1.5-1.7 times) in the GF mice than in the C mice. These results suggest that the enzymic activities in the small intestine of mice and rats are sufficient to hydrolyse maltitol extensively. Consequently, the slow absorption of sorbitol seems to be an important factor limiting the overall assimilation of maltitol in the small intestine.     

Effect of maltitol intake on intestinal calcium absorption in the rat.

To examine whether sugar alcohol affects intestinal calcium absorption, 5-week-old male Wistar rats were fed a basal diet (66% starch) or the diets containing either 10% maltitol, 10% sorbitol or 10% lactose. At 2 and 6 weeks after the start of feeding, the animals were subjected to 5-day-period calcium balance study. Feeding maltitol diets as well as sorbitol diet led to a significantly elevated intestinal calcium absorption and calcium retention. Lactose diet did not produce an increased intestinal calcium absorption in the condition used in the present study. To explore whether maltitol can exert its effect in a short period of time, the rats were starved for 16h and were fed by a polyethylene tube the diet containing 0.44% calcium together with either 10% maltitol or 10% glucose. The total calcium remaining in the gastrointestinal tract at 6h after feeding was significantly decreased in the rats given maltitol diet as compared to the rats given glucose diet. When 10 microCi of 45CaCl2 was given orally with the diets containing maltitol or glucose, the amount of 45Ca remaining in the gastrointestinal tract at 6h after its administration was smaller in the rats fed maltitol diet than in the rats fed glucose diet. These results suggest that both di- and monosaccharide alcohols might affect intestinal epithelium, resulting in an enhanced intestinal calcium absorption.     

Influence of the disaccharide lactitol on intestinal absorption and body retention of calcium in rats

Various sugars are known to stimulate intestinal calcium absorption by a mechanism that is still poorly understood. One of those, the disaccharide 4-gal-actosyl-sorbitol (lactitol), is only metabolized in the large intestine, where it is converted into acidic residues. We investigated the effect of this compound on net intestinal absorption and body retention of calcium in rats. Because dietary calcium is in a poorly absorbable form when it reaches the large intestine, attempts were made to modify the absorption of calcium present in the large intestine contents by administering lactitol. Net intestinal absorption and body retention of calcium were significantly increased by 2.5 g lactitol/(kg b.w.d) given by a gavage over a 7-d period. This was associated with a lower pH and a better availability to absorptive systems of calcium present in the large intestine contents. The results indicate that in rats lactitol given chronically increases net intestinal absorption of calcium with a subsequently more positive calcium balance.     

Hydrolysis of alpha-D-glucopyranosyl-1,6-sorbitol and alpha-D-glucopyranosyl-1,6-mannitol by rat intestinal disaccharidases

The hydrolyzing activities in rat small intestine for newly developed sugar substitutes, alpha-D-glucopyranosyl-1,6-sorbitol (GPS) and alpha-D-glucopyranosyl-1,6-mannitol (GPM), both of which are produced by hydrogenation of palatinose, were characterized. GPS and GPM were hydrolyzed in mucosal homogenate as well as in brush border membranes of rat small intestine at a slower rate than the rate of hydrolysis of palatinose (30%) and sucrose (6-7%). Gel filtration column chromatography of disaccharidases solubilized from brush border membranes revealed that GPS and GPM were hydrolyzed mainly by sucrase-isomaltase complex and its degradation product, i.e. isomaltase monomer. The isomaltase monomer, purified from small intestine of rats, possessed similar Km values for GPS (2.47 mM) and GPM (5.38 mM) as compared to those of purified sucrase-isomaltase complex. The Vmax values of isomaltase monomer for GPS and GPM were twice as high as those of sucrase-isomaltase, suggesting that GPS and GPM are hydrolyzed by the active site of isomaltase. On the other hand, a small amount (up to 17%) of GPS- and GPM-hydrolyzing activities was ascribed to glucoamylase, which possessed relatively high Km values for GPS (18.7 mM) and GPM (32.9 mM). To examine a physiological significance of GPS- and GPM-hydrolyzing activities, the transmural potential difference (delta PD) evoked by Na+-dependent active transport of glucose, produced by the hydrolysis of these disaccharide alcohols, was measured in everted segments of rat jejunum. The relative rates of absorption of glucose produced by the hydrolysis of GPS and GPM were 36% and 27% of that of palatinose, directly reflecting the hydrolyzing activities determined in jejunal homogenate. These results suggest that the process of hydrolysis is the rate limiting step in digestion-absorption process of palatinose, GPS and GPM in small intestine.     

Hydrolysis of zeaxanthin esters by carboxyl ester lipase during digestion facilitates micellarization and uptake of the xanthophyll by Caco-2 human intestinal cells

Zeaxanthin (Zea) and lutein are the only dietary carotenoids that accumulate in the macular region of the retina and lens. It was proposed that these carotenoids protect these tissues against photooxidative damage. Few plant foods are enriched in Zea, and information about the bioavailability of Zea from these foods and its accumulation in ocular tissues is limited. The amounts of free Zea and its mono- and diesters were measured for several plant foods that have relatively high concentrations of this xanthophyll. Wolfberry had the greatest concentration of Zea with a diester that accounts for 95% of the total. Free, mono-, and diesters of Zea were present in orange and red peppers, whereas only Zea monoesters were detected in squash. Zea esters were partially hydrolyzed by carboxyl ester lipase (CEL) during simulated digestion. The efficiency of micellarization was dependent on speciation with combined means of free Zea, Zea monoesters, Zea diesters from the digested foods of 81 +/- 8, 44 +/- 5, and 11 +/- 4%, respectively. When exposed to micelles generated during digestion of the test foods, Zea uptake by Caco-2 cells was proportional to the medium content (11-14%). Free Zea was the most abundant form in Caco-2 cells, although Zea monoesters also were detected (<8 +/- 0.7% vs. free Zea). CEL enhanced Zea uptake from micelles (12.3-fold; P < 0.05) by hydrolyzing Zea esters. After cell uptake, concentrations of free and monoesterified Zea remained relatively stable. These data suggest that dietary Zea esters are hydrolyzed by CEL during the small intestinal phase of digestion and that this conversion enhances Zea bioavailability.     

Influence of a combination of Lactobacillus acidophilus NCFM and lactitol on healthy elderly: intestinal and immune parameters

With increasing age, a number of physiological changes take place which are reflected in immune and bowel function. These changes may relate to the commonly assumed age-related changes in intestinal microbiota; most noticeably a reduction in bifidobacteria. The current study aimed at modifying the intestinal microbiota with a potential synbiotic on selected immune and microbiota markers. Healthy elderly subjects were randomised to consume during 2 weeks either a placebo (sucrose) or a combination of lactitol and Lactobacillus acidophilus NCFM twice daily in a double-blind parallel trial. After the intervention, stool frequency was higher in the synbiotic group than in the placebo group and a significant increase in faecal L. acidophilus NCFM levels was observed in the synbiotic group, after baseline correction. In contrast to the generally held opinion, the study subjects had faecal Bifidobacterium levels that were similar to those reported in healthy young adults. These levels were, nevertheless, significantly increased by the intervention. Levels of SCFA were not changed significantly. Of the measured immune markers, PGE2 levels were different between treatments and IgA levels changed over time. These changes were modest which may relate to the fact that the volunteers were healthy. Spermidine levels changed over time which may suggest an improved mucosal integrity and intestinal motility. The results suggest that consumption of lactitol combined with L. acidophilus NCFM twice daily may improve some markers of the intestinal microbiota composition and mucosal functions.     

Comparative study of maltitol and sucrose by means of continuous indirect calorimetry

The metabolism of the hydrogenated disaccharide maltitol was compared to that of sucrose in a group of eight normal subjects. On two separate days, with an interval of at least one week each subject ingested a load of 30 g of either substance. The evolution of the levels of plasma glucose, insulin, and free fatty acids was followed during the 6 hr following the oral load. Carbohydrate and lipid oxidation rates were assessed simultaneously by continuous indirect calorimetry during the 6 hr following the oral load. Plasma glucose and insulin peaks occurred 30 min after ingestion of the load for both sugars. The peak of the delta glucose concentration was significantly smaller after maltitol than after sucrose (21 +/- 4 vs 38 +/- 4 mg/100 ml, p less than 0.02), as was the peak of the delta insulin concentration (9.3 +/- 2.7 microU/ml after maltitol vs 25.5 +/- 5.0 microU/ml after sucrose, p less than 0.001). The peak of the stimulation of glucose oxidation occurred 60 min after the load of sucrose and 90 min after the load of maltitol. The delta glucose oxidation was significantly lower with maltitol than with sucrose during the first 90 min after the ingestion of the load. It was slightly higher (although not significantly) with maltitol than with sucrose starting from the 210th min. Maltitol resulted in a cumulated suprabasal glucose oxidation which amounted to 40% that obtained with sucrose after 180 min.     

Comparative digestion of maltitol and maltose in unanesthetized pigs

Four Large White pigs (mean body weight 62.8 +/- 0.6 kg) were fitted with permanent catheters in the portal vein, carotid artery and duodenum, and with an electromagnetic flow probe around the portal vein. Eight days after surgery each animal received at 4-d intervals two duodenal infusions for 1 h each of solutions (1000 mL) containing 110 g of mild enzymic milk protein hydrolysate and 440 g of either a maltose-rich glucose syrup (54.6% maltose, 5.2% free glucose) or a maltitol-rich hydrogenated glucose syrup (54.2% maltitol, 6% free sorbitol). For 8 h after the beginning of each infusion, portal blood flow rate was recorded continuously, and blood samples were collected at various intervals (15 to 30 min) for the analysis of aminonitrogen, glucose and sorbitol. Maltitol was hydrolyzed substantially in the small gut. The absorption coefficient of glucose (percentage of infused glucose appearing in the portal blood) was the same 8 h after infusion of maltitol (78.1%) and maltose (78.8%). Sorbitol was poorly absorbed, with an absorption coefficient of 7.2% after 8 h. Its presence in the gut lumen did not inhibit the absorption of glucose. Aminonitrogen from milk oligopeptides appeared more rapidly in the portal vein during the first 4 h after infusion of maltitol than after that of maltose. This was probably due to a reduced competition between absorption of glucose and oligopeptides because of the smaller amount of glucose in the digestive lumen after maltitol hydrolysis.     

Dose dependence of breath hydrogen and methane in healthy volunteers after ingestion of a commercial disaccharide mixture, Palatinit

Breath hydrogen and methane were determined by gas chromatography in eleven normal individuals given a low-fibre, mixed diet (control) and after ingestion of 20-50 g Palatinit/d, an equimolar mixture of D-glucosyl-alpha(1----1)-D-mannitol and D-glucosyl-alpha(1----6)-D-glucitol (Isomalt). A linear relation was found (r 0.85; P less than 0.001) between the amount of Palatinit ingested and breath H2 per 10 h in subjects who did not exhale methane. If methane was formed in addition to H2, the sum of both gases followed a linear dose-effect relation. The mouth-to-caecum time, indicated by the first increase in breath H2 after ingestion, was shortened by about half, yet no sign of diarrhoea was observed. Stool weight and stool frequency did not change significantly. The linear relation between a dose of 20-50 g Palatinit and exhalation of H2 (eventually plus methane) indicated that a relatively constant fraction of the dose given underwent cleavage and absorption in the small intestine, the remainder being transported into the large bowel. Microbial gas formation in the colon as well as the fractional transfer of these gases into the expiratory air occurred at fixed proportions, thus allowing an insight into colonic microbial contributions to carbohydrate utilization in the human large bowel.     

Glutamine transport by human intestinal basolateral membrane vesicle

This study characterizes for the first time, by use of a well-validated technique, glutamine transport across human basolateral membrane vesicles. Glutamine transport represented uptake into an osmotically active intravesicular space without significant metabolism. Glutamine uptake was temperature- and pH-dependent with maximal uptake at pH 7.5, and it was mediated by sodium-dependent and -independent processes. The initial rate of uptake was linear up to 20 s, as depicted by the formula gamma (nmol/mg protein) = 0.0009 X (s) - 0.0011 (r = 0.99). Kinetic analysis of glutamine uptake at concentrations between 0.01 and 0.3 mmol/L at 5 s under sodium and potassium gradients showed a maximal transport capacity (Vmax) of 0.39 +/- 0.04 and 0.21 +/- 0.02 nmol.mg protein-1.5 s-1 for sodium-dependent and -independent processes, respectively (p less than 0.01). Km values were 0.17 +/- 0.04 and 0.06 +/- 0.2 mmol/L, respectively (p less than 0.05). Glutamine uptake under the sodium-gradient condition was electrogenic whereas under the potassium-gradient it was electroneutral. Neutral amino acids inhibited both sodium-dependent and -independent processes. This study confirms and characterizes the presence of carrier-mediated glutamine uptake at the basolateral membranes of human enterocytes.     

Threshold for transitory diarrhea induced by ingestion of xylitol and lactitol in young male and female adults

The ingestion of a sufficiently large amount of non-digestible and/or non-absorbable sugar substitutes causes overt diarrhea. The objective is to estimate the non-effective dosage that does not cause transitory diarrhea for xylitol, lactitol, and erythritol in healthy subjects. Twenty-seven males and 28 females gave informed and written consent to participate, were selected, and participated in the study. The oral dose levels of xylitol were 10, 20, 30, 40 and 50 g, while those of lactitol were 10, 20, 30, and 40 g. Those of erythritol were 20, 30, 40 and 50 g. The test substance was ingested in 150 mL of water 2-3 h after a meal. The ingestion order progressed from the smallest to larger amounts, and stopped at the dose that caused diarrhea, or at the largest dose level to be set up. The non-effective dose level of xylitol was 0.37 g/kg B.W. for males and 0.42 g/kg B.W. for females. That of lactitol was 0.25 g/kg B.W. for males and 0.34 g/kg B.W. for females, and that of erythritol was 0.46 g/kg B.W. for males and 0.68 g/kg B.W. for females. These results appear reasonable, because xylitol is poorly absorbed from the small intestine, and the absorption rate is less than that of erythritol, while lactitol is not hydrolyzed. Non-digestible and/or non-absorbable sugar alcohols and oligosaccharides with beneficial health effects inevitably cause overt diarrhea. The estimation of the non-effective dose level of these sugar substitutes is essential and important to produce processed foods that the consumer can use safely and with confidence.     

Dental and metabolic effects of lactitol in the diet of laboratory rats

1. Because so little is known about the properties of lactitol as a possible alternative bulk sweetener to sucrose, it was tested in two large-scale experiments in laboratory rats. Matched groups of caries-active Osborne-Mendel rats were fed on uniform diets containing lactitol and compared with a sucrose control in both experiments, plus a xylitol control in the first experiment. 2. In the early stages of the experiments weight gains and food utilization were better on the sucrose than on the lactitol regimens. Body-fat storage was higher on the sucrose than on the polyol regimens. 3. At the end of 8 weeks the mandibular molars were examined for dental plaque accumulation and dental caries. The dental caries scores when 160 g sucrose/kg in the diet was replaced by lactitol were lower by a highly significant margin, bringing them down to the same low level as those on a 160 g xylitol/kg regimen. 4. Testing lactitol in a manufactured food product, shortbread biscuits, in comparison with ordinary sucrose biscuits, showed differences in plaque scores (significant) and caries levels (highly significant), with 60% fewer lesions on the lactitol regimen. 5. The results confirm the low cariogenic potential of lactitol, but show metabolic differences compared with sucrose.     

Effects of low doses of lactitol on faecal microflora,pH, short chain fatty acids and gastrointestinal symptomology

BACKGROUND: Lactitol (4-beta-D: -galactopyranosyl-D: -glucitol) is a sugar alcohol used as a sweetener. Previous studies have shown that it has a beneficial effect on intestinal microflora. AIMS OF THE STUDY: To determine whether low doses of lactitol had beneficial effects without eliciting adverse gastrointestinal symptoms. METHODS: Faecal bacterial populations (total anaerobes, total aerobes, enterobacteria, bifidobacteria and lactobacilli), faecal pH and faecal short chain fatty acids (SCFA) were studied in a randomized longitudinal study of 75 non-adapted healthy adults before and after consumption of low doses of lactitol. Subjects consumed 25 g tablets of milk chocolate containing 10 g sweetener as sucrose:lactitol in ratios of 10:0, 5:5 or 0:10 daily for 7 d. RESULTS: No significant changes in faecal bacterial counts occurred in the 10:0 or 5:5 sucrose:lactitol groups. There were no significant changes in faecal anaerobes, aerobes, Enterobacteriaceae or lactobacilli during the study period in subjects consuming 0:10 sucrose:lactitol but there was a significant increase (P = 0.017) in bifidobacteria. There were no significant changes in faecal pH and SCFA for the 10:0 or 5:5 sucrose:lactitol groups but a significant decrease (P = 0.02) in faecal pH and significant increases (P = 0.001) in concentrations of propionic and butyric acids were observed in the 0:10 sucrose:lactitol group. There were few adverse symptoms of gastrointestinal intolerance to the daily consumption of 10 g lactitol. CONCLUSIONS: The results show that low doses of lactitol can beneficially affect the faecal flora without eliciting gross symptoms of intolerance and that lactitol can be classified as a prebiotic.     

Suppressive effect of cellulose on osmotic diarrhea caused by maltitol in healthy female subjects

Using a single-group time-series design, we determined that osmotic diarrhea caused by maltitol ingestion was suppressed by the addition of not only soluble but also insoluble dietary fiber in healthy humans. We then clarified that cellulose delayed gastric emptying in rats. Twenty-seven healthy volunteers ingested maltitol step-wise at doses of 15, 20, 25, 30, 35, 40 and 45 g from small to large amounts. Within that range of ingested amounts, 22 out of 27 subjects experienced osmotic diarrhea from maltitol ingestion, and the minimal dose level of maltitol that induced osmotic diarrhea (MMD) was established for each subject. When 5 g of cellulose was added to the MMD, osmotic diarrhea was suppressed in 13 out of 19 subjects (68.4%), while partially hydrolyzed alginate-Na (PHA-Na), a soluble dietary fiber, suppressed osmotic diarrhea in 10 out of 20 subjects (50.0%). When a mixed solution of cellulose and maltitol was administered to rats, the gastric emptying of maltitol was significantly delayed at 30 and 60 min after administration (p=0.019, p=0.013), respectively. PHA-Na also significantly delayed gastric emptying at 30 min (p=0.013). In conclusion, cellulose can suppress the osmotic diarrhea caused by maltitol ingestion in humans and delay the gastric emptying of maltitol in rats. A new physiological property of cellulose was clarified in this study.