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The Western diet, comprised of highly refined carbohydrates and fat but reduced complex plant polysaccharides, has been attributed to the prevalence of obesity. A concomitant rise in the consumption of fructose and sugar substitutes such as sugar alcohols, artificial sweeteners, even rare sugars, has mirrored this trend, as both probable contributor and solution to the epidemic. Acknowledgement of the gut microbiota as a factor involved in obesity has sparked much controversy as to the cause and consequence of this relationship. Dietary intakes are a known modulator of gut microbial phylogeny and metabolic activity, frequently exploited to stimulate beneficial bacteria, promoting health benefits. Comparably little research exists on the impact of 'unconscious' dietary modulation on the resident commensal community mediated by increased fructose and sugar substitute consumption. This review highlights mechanisms of potential host and gut microbial fructose and sugar substitute metabolism. Evidence is presented suggesting these sugar compounds, particularly fructose, condition the microbiota, resulting in acquisition of a westernized microbiome with altered metabolic capacity. Disturbances in host-microbe interactions resulting from fructose consumption are also explored., (© 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.)

It is the position of the Academy of Nutrition and Dietetics that consumers can safely enjoy a range of nutritive sweeteners and nonnutritive sweeteners (NNS) when consumed within an eating plan that is guided by current federal nutrition recommendations, such as the Dietary Guidelines for Americans and the Dietary Reference Intakes, as well as individual health goals and personal preference. A preference for sweet taste is innate and sweeteners can increase the pleasure of eating. Nutritive sweeteners contain carbohydrate and provide energy. They occur naturally in foods or may be added in food processing or by consumers before consumption. Higher intake of added sugars is associated with higher energy intake and lower diet quality, which can increase the risk for obesity, prediabetes, type 2 diabetes, and cardiovascular disease. On average, adults in the United States consume 14.6% of energy from added sugars. Polyols (also referred to as sugar alcohols) add sweetness with less energy and may reduce risk for dental caries. Foods containing polyols and/or no added sugars can, within food labeling guidelines, be labeled as sugar-free. NNS are those that sweeten with minimal or no carbohydrate or energy. They are regulated by the Food and Drug Administration as food additives or generally recognized as safe. The Food and Drug Administration approval process includes determination of probable intake, cumulative effect from all uses, and toxicology studies in animals. Seven NNS are approved for use in the United States: acesulfame K, aspartame, luo han guo fruit extract, neotame, saccharin, stevia, and sucralose. They have different functional properties that may affect perceived taste or use in different food applications. All NNS approved for use in the United States are determined to be safe., (Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

D-psicose, a new alternative sweetener, was produced from allitol by microbial oxidation of the newly isolated strain Enterobacter aerogenes IK7. Cells grown in tryptic soy broth medium (TSB) supplemented with D-mannitol at 37 degrees C were found to have the best oxidation potential. The cells, owing to broad substrate specificity, oxidized various polyols (tetritol, pentitol, and hexitol) to corresponding rare ketoses. By a resting cell reaction, 10% of allitol was completely transformed to the product D-psicose, which thus becomes economically feasible for the mass production of D-psicose. Finally, the product was crystallized and confirmed to be D-psicose by analytical methods.

The aim of this study was to determine the postprandial glucose (GR), insulin (IR), and triglyceride response as well as the satiety response (SR) to low-calorie muffins (LCMs) and to compare them to those of conventional plain muffins (PMs) and bread. The LCMs had a lower fat content, their sugar was replaced by maltitol, and wheat flour was partially replaced by high-amylose corn starch. We used bread as a reference to calculate glycemic (GI), insulinemic (II), and satiety indices (SI). Seven men and 7 women (33 +/- 7.8 y; body mass index = 25.8 +/- 2.9) were studied in a randomized crossover design and were given either bread, an LCM, or a PM during 3 different occasions. Plasma glucose, insulin, and triglyceride concentrations were periodically measured for 2 h after consumption. We used the same design in a separate assay to evaluate SR by means a subjective questionnaire. The results show that LCMs reduced the IR by 30% (P= 0.03) and lipemic response by 50% (P < 0.001) compared to PMs. GR was only found to be significantly different between bread and LCMs (52% lower in LCM; P= 0.03), with PMs in an intermediate position. The SR of LCMs is similar to bread and higher than PMs (191%; P= 0.02). We concluded that LCMs are a product with a very low GI with better postprandial and SRs than PMs. These metabolic properties are useful in normal and overweight persons. However, further research is needed on the effects of this type of products in individuals with impaired glucose tolerance.

Purpose: The aims were to evaluate a simple method to disclose a microbial shift in saliva and to investigate the short- and long-term effects of daily use of xylitol-containing chewing gums on mutans streptococci (MS) and [14C]-xylitol uptake in saliva., Materials and Methods: In a pilot set-up, saliva samples were collected from 15 healthy adults and the uptake of xylitol was compared with a specific assay determining xylitol-sensitive MS. The main study consisted of 109 schoolchildren (mean age 9.9 years) who volunteered after informed consent. The children were randomly allocated to a test or control group. The control group was given two pellets containing sorbitol and maltitol 3 times daily for 4 weeks and the test group received identical pellets with xylitol as single sweetener (total dose 6.2 g/day). Saliva samples were collected at baseline, after 4 weeks and 6 months after the intervention. The outcome measures were MS and total viable counts, proportion of MS and salivary uptake of [14C]-xylitol., Results: The pilot study disclosed a fair positive correlation (p < 0.05) between the assays. The proportions of MS and salivary xylitol uptake decreased significantly in the xylitol group by 60% and 30% respectively after 4 weeks compared to baseline which was in contrast to the sorbitol/maltitol group (p < 0.05). Six months after the intervention, the outcome measures did not differ significantly from baseline in any of the groups., Conclusion: A relatively high daily dose of xylitol could alter salivary microbial composition during the intervention period but no long-term impact was observed.

Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.

Objective: The carbonyl group of glucose reacts non-enzymatically with the amino group of protein to form advanced glycosylation end-products (AGEs). AGEs are found in the peritoneum of continuous ambulatory peritoneal dialysis patients, and this AGE formation is suspected to be one of the causes of impaired peritoneal function. In order to control AGE formation in the peritoneum, AGE formation and ultrafiltration in rats were examined with peritoneal dialysates using as osmotic agents saccharides that lack a carbonyl group, the saccharic acid lactobionate [molecular weight (MW) 358.30], the sugar alcohol maltitol (MW 344.32), and the nonreducing sugar nistose (MW 666.58)., Design: Bovine serum albumin (BSA) (25 mg/mL) was incubated with 18, 36, and 72 mg/mL maltitol, lactobionate, nistose, and glucose at 37 degrees C. After 3 or 6 weeks, amounts of furosine and N-(carboxymethyl) lysine were measured. A 20-mL intraperitoneal injection of a lactate-based dialysate (osmotic pressure 388 mOsm/kg) containing 4.34% maltitol, 4.52% lactobionate, or 8.4% nistose was given to Sprague-Dawley rats and, after 2, 4, or 6 hours, the quantity of effluent and levels of urea nitrogen and creatinine in the effluent and in serum were measured., Results: No increases in furosine or N-(carboxymethyl) lysine were seen with maltitol, lactobionate, or nistose after 3 and 6 weeks of incubation with BSA; AGE formation was not observed. In the study in rats, the quantity of abdominal fluid after a 6-hour dwell was nistose > lactobionate > maltitol > glucose. No differences in dialysate-to-plasma ratios for urea nitrogen or creatinine were seen in any group., Conclusions: AGE formation in peritoneal tissue might be controlled by using saccharides with a modified carbonyl group as osmotic agents for peritoneal dialysates. Nistose is considered to yield the most efficient dialysis.

There is increased interest in the use of sugar alcohols as substitutes for sucrose in various food products. Part of this interest is derived from studies suggesting that sugar alcohols may have lower energy values because of the way they are metabolized. Contributing to the complexity is the fact that not all sugar alcohols are similarly metabolized. Indirect and direct methods used to assess the energy value of sugar alcohols have often yielded conflicting data. Energy values obtained using mathematical models have been adopted by some countries to account for metabolic processes associated with sugar alcohol digestion and absorption. I focus on two sugar alcohols, sorbitol and maltitol, and describe various methods that have been used to assess their energy value.

In a study with ten pigs of 60-70 kg live weight, provided with a re-entrant cannula at the end of the ileum, and sixteen intact, non-cannulated pigs, the digestion and absorption of a dietary dose of 100 g isomalt/kg, and isomalt given between the meals as a 'sweet' on the basis of 50 and 100 g/kg feed consumption, were examined. In all three isomalt treatments slightly less than 0.40 of the isomalt consumed was digested in the small intestine when the calculations were based on ileal sugar passage. However, when basing the calculations on energy contents of ileal chyme, only approximately 0.10 was digested in the small intestine. The bacterial fermentation of the isomalt flowing into the large intestine was indicated by a decreased faecal energy digestibility and a slight reduction in faecal dry matter and nitrogen digestibility. The retention of the minerals sodium, potassium, magnesium, calcium and phosphorus was not influenced to any measurable extent when isomalt was fed.

In a study with twelve pigs of 60-70 kg live weight provided with a re-entrant cannula at the end of the ileum, and twelve intact, non-cannulated pigs, the fate of dietary doses of 100 and 200 g isomalt/kg during gastrointestinal passage was examined. From sugar analyses in ileal chyme it was calculated that 0.43 and 0.30 of the isomalt consumed was digested in the small intestine with the 100 and 200 g/kg doses of isomalt respectively. From findings on ileal energy digestibility it was calculated that, because of a secondary effect of isomalt on the digestion of the basal diet, isomalt digestibility in the small intestine was distinctly lower. In faeces no sugars were found, so faecal digestibility of isomalt was 1.00 for both doses. The bacterial fermentation in the large intestine of the isomalt not digested in the small intestine caused an increase in the faecal excretion of nitrogen and energy. This increased faecal excretion was hardly (nitrogen) or not (energy) compensated by a decreased urinary excretion.

The effect of maltitol on caries development was examined in an experimental caries system employing specific pathogen-free (SPF) Sprague-Dawley rats. Fourteen strains of oral streptococci, including mutans streptococci, did not utilize the maltitol nor produce sufficient acid to demineralize tooth enamel. Furthermore, maltitol did not serve as a substrate for glucosyltransferases of either Streptococcus mutans MT8148R or Streptococcus sobrinus 6715 to synthesize water-insoluble glucan. Maltitol induced no significant dental caries in SPF rats infected with these mutans streptococci, and replacement of the dietary sucrose content with maltitol resulted in a trend towards caries reduction in SPF rats.

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.

When adapting young rats to different sugar substitutes (sorbitol, PolydextroseR and PalatinitR), effects were seen in the caecal morphology and caecal content e.g. bacterial concentration, which did not occur when adapting rats to sugars (glucose, sucrose). For in vitro studies, anaerobic growth of caecal flora in thioglycollate medium with and without the respective substances was monitored by continuous measurement of heat production, optical density and pH. Additionally, biochemical analyses and light microscopic observations were performed in order to detect differences between adapted and non-adapted flora. In particular the microcalorimetric data furnished valuable information about alterations in bacterial metabolic activity after adaptation to sugars and sugar substitutes, and clearly indicated that all the substances tested influenced the metabolism of caecal flora.

Maltitol is found to be enzymatically hydrolyzed by the small intestinal mucosa of man, rat, and rabbit and metabolized by everted sacs of rabbit intestine at a moderate rate. On in vivo perfusion of maltitol (15.3 mumol/min) through the small intestine, 19% of the sugar alcohol is digested by gnotobiotic rats. 120 min after stomach intubation of gnotobiotic rats, only 31% of the ingested maltitol is found in the ileum. A daily application of 35 g maltitol to 4 human beings does not influence the parameters of well-being, compatibility and fecal state. It is concluded that maltitol will be digested and utilized by man, rat, and rabbit.

For the sake of metabolic insight into the fate of the sugar substitute Palatinit, its two components D-glucosyl-alpha (1 leads to 1)-D-mannitol and D-glucosyl-alpha (1 leads to 6)-D-glucitol [D-glucosyl-alpha-(1 leads to 6)-D-sorbitol] were assayed for glucose bioavailability by the procedure of Karimzadegan et al. using ketotic rats. With conversion rates into glucose of 6 and 20%, respectively, for free mannitol and glucitol (sorbitol), 39% for glucosylmannitol and 42% for glucosylglucitol, the metabolic glucose pool of the rat does not receive the full carbohydrate complement of these compounds. The preformed glucose moiety of the glucosylhexitols is bioavailable by 36 and 32%, respectively, from glucosylmannitol and glucosylglucitol, with 50% as theoretical maximum. Less than theoretical bioavailability of glucose from Palatinit is ascribed to microbial attack in the hindgut. The data on rats are held valid also for other species demonstrating carbohydrate fermentation in the caecum and/or colon. Differences between D-glucosyl-alpha (1 leads to 1)-D-mannitol and D-glucosyl-alpha (1 leads to 6)-D-glucitol are caused by a differential delay of glucose absorption in the small intestine, also exerted by D-glucitol. The deep metabolic insight offered by the glucose bioavailability assay into the fate of carbohydrates includes the mammal-microbial symbiosis in the large bowel. Since a rather complete survey of the metabolic consequences after their intake can be obtained, the assay system should be generally applied in assessments of food safety also of other sugar substitutes.

The problems of the biochemical effects of sugar substitutes and bacteriologic response to such substitutes in the oral cavity may fill a whole book. Therefore, considerable restrictions in the presentation are necessary. Noncaloric sweeteners and additives are not utilized by the oral microorganisms for metabolism and acid production and are therefore of minor interest in this connection. This presentation mainly concerns sugar alcohols and related substances, primarily sorbitol, xylitol and Lycasin. Monosaccharides and other saccharides are not dealt with in this presentation even if some of them are of considerable interest; for example fructose, invert sugar and others. Sugar alcohols are used as substitutes because they cannot be utilized by the vast majority of oral organisms for fermentation, acid production or production of polysaccharides. There is a risk that the oral flora will adapt to these products and that such a substitute, which is originally nonacidogenic, may subsequently be utilized for fermentation and may even induce dental caries.

Research on the dental properties of lactitol as a bulk sweetener to replace dietary sugar is reviewed under three headings: microbiological experiments in vitro, investigations in laboratory animals, and studies in man. Lactitol was not easily metabolized by acidogenic and polysaccharide-forming oral micro-organisms, its enamel-demineralizing potential in vitro intra-oral acid development and dental plaque formation from lactitol in man were substantially lower than from sucrose. The indications for dental health benefits are promising.

Several caloric sugar substitutes are available today, e.g. maltitol, Lycasin, sorbitol, xylitol, palatinit, sorbose, coupling sugar, palatinose, fructose and invert sugar. When evaluating the cariogenicity of these sugar substitutes from a bacteriological point of view, different analytical procedures should be considered. In vitro studies on the capacity of pure oral bacterial strains and dental plaque material to decompose the substitute to acid. Studies on the catabolism of the substitute. Possible adaptation of the oral microflora to metabolize the substitute in vivo as well as in vitro. Studies on any inhibitory effect of the substitute on the microbial activities in dental plaque and on the oral microflora. The capacity of oral bacteria, e.g. Streptococcus mutans, to induce caries in animal experiments should also be considered. Results from such microbiological studies make it possible to classify the caloric sugar substitutes into different groups. The first, most suitable, group seems to consist of xylitol and sorbose. These substitutes are fermented by few oral bacteria and no negative adaptation of the oral flora has been observed. A reducing effect upon dental plaque formation and on acid production from glucose has been reported. A second group consists of maltitol, palatinite, palatinose, sorbitol and Lycasin. These substitutes are fermented by certain groups of organisms within the oral genera Actinomyces, Lactobacillus and Streptococcus. Adaptation of oral bacteria to palatinose and to sorbitol, resulting in a more pronounced acid production, has been observed. No inhibitory effects have been reported. The results from experimental studies suggest that these sugar substitutes have no or little cariogenic action in rodents inoculated with S. mutans.(ABSTRACT TRUNCATED AT 250 WORDS)

Five successive experiments, with rats fed ad libitum on diets containing sucrose or Lycasin 80/55, were carried out. In experiment I, the rats were inoculated with Streptococcus mutans alone or with Strep. mutans in combination with Actinomyces viscosus. In three successive transmission experiments (II, III, IV), the rats were inoculated with plaque of the rats of the preceding experiment. The rats of experiment V were inoculated with the original strains or with plaque derived from experiment IV. After five successive transmissions of the plaque flora, no alterations were demonstrated in the numbers and percentages of Strep. mutans and A. viscosus or in the fermentation rate of Lycasin by the plaque flora in vitro. Lycasin 80/55 was virtually non-cariogenic compared with sucrose (p less than 0.001) irrespective of whether the rats were inoculated with Strep. mutans alone or in combination with A. viscosus, with the original strains or with plaque from the preceding experiments with rats on a Lycasin 80/55-containing diet.

By means of programmed feeding experiments on rats, the caries-producing properties of a new sugar substitute Palat-nit were compared with those of other carbohydrates. The cariogenicity of Palatinit was significantly lower than that of sucrose and lactose and roughly comparable to that of L-sorbose. Reference strains of s. mutans are unable to produce extra-cellular polysaccharide or notable amounts of acid from Palatinit. The use of this substance as sugar substitute can be recommended for caries prophylaxis on the basis of these experiments.

1. The hydrolysis of sugar alcohols of the disaccharide type such as lactitol, maltitol and Palatinit (the latter an equimolar mixture of 6-O-alpha-D-glucopyranoside-D-mannitol and 6-O-alpha-D-glucopyranoside-D-sorbitol) by homogenates of human intestinal biopsies were compared with corresponding natural disaccharides such as lactose, maltose and isomaltose. Seven of the human biopsies were normal with regard to their disaccharidase activities, while twelve biopsies showed decreased levels of disaccharidase activities. 2. All biopsies, normal as well as abnormal, showed essentially the same capacity to hydrolyse the sugar alcohols. Activities towards lactitol (0.34 IE/g protein (where IE = mumol disaccharide hydrolysed/min at 37 degrees)) and Palatinit (2.50 IE/g protein) were only 1.3% of those towards lactose and isomaltose. The activity towards maltitol was much higher (19.1 IE/g protein), approximately 10% of that towards maltose and about as high as the activity towards trehalose. This finding indicates that despite the fact that lactitol and Palatinit were poor substrates, significant amounts of ingested maltitol might be digested and utilized by man. 3. Glucose release was reduced by approximately 25% when maltitol or Palatinit were present at concentrations equal to those of maltose. Palatinit decreased the hydrolysis of sucrose by 12%. Lactitol had no inhibitory effect on the hydrolysis of disaccharides.

Boiled sweets formulated with Lycasin were compared with conventional sugar-base sweets. Incubated in media containing solutions of the sweets, mixed cultures of oral microorganisms produced less polysaccharide and acid, with significantly less demineralizing action on dental enamel and hydroxylapatite, from the Lycasin than from the sugar-base products. In comparison with these differences, the effects of changing the flavouring acid combination in the sweets were minor, but levels of citric and malic acids as high as 1.00% showed some inhibition of the activity of the oral microorganisms.

Lycasin, its parent glucose syrup, maize starch and sorbitol were subjected to the action of a specific amyloglucosidase at 37 degrees C, and samples were analysed at set intervals for D-glucose and total reducing sugars. Glucose syrup was hydrolysed rapidly and completely to D-glucose, but Lycasin produced only 40-50% as much, and D-glucose production ceased after the first 2-4 h. Dimers of linked D-glucose and sorbitol units remaining after degradation of the Lycasin oligosaccharides were cleaved at a much lower rate by the amyloglucosidase.

Standardized mixed cultures of dental plaque microorganisms were incubated for 24 h in media containing six different bulk sweeteners as energy source. The attack of the acid generated on tooth mineral was measured by calcium and phosphorus analyses. Demineralization was most severe with glucose and sucrose. Less acid was generated from sorbitol and mannitol, with much reduced demineralization. Fermentation of lactitol and xylitol was only very slight, leaving the final pH high and leading to extremely low enamel demineralization figures. The amounts of polysaccharide synthesized by the microorganisms in the incubations decreased in the order: glucose greater than sucrose greater than sorbitol greater than mannitol greater than lactitol greater than xylitol.

Conventional (CV) rats were given a single oral dose of 1 or 2 g maltitol. Urine and faeces were collected during the following 24 h and their contents of maltitol and sorbitol were measured. 2. Very little of either substance appeared in the faeces but appreciable amounts of sorbitol found in the urine indicated that the maltitol had been hydrolysed. 3. Excretion of maltitol and sorbitol was compared in germ-free and CV rats given an oral dose of 2 g maltitol. Significantly less of both substances was recovered in the faeces of CV rats, but urinary excretion was similar in both environments. 4. Maltitol injected intravenously gave rise to only traces of sorbitol in the excreta. A dose of 250 mg was cleared almost completely from the circulation within 1 h. 5. It is concluded that maltitol is hydrolysed by animal tissues, either in the gut lumen before absorption or in the gut wall during absorption. Maltitol and sorbitol are also degraded by gut bacteria, mostly in sites distal to the main absorptive area. The contribution to the host's nutrition would depend on the extent to which the end-products of fermentation are absorbed from the colon.

Isomalt (Palatinit) an equimolar mixture of alpha-D-glucopyranosido-1,6-sorbitol and alpha-D-glucopyranosido-1,6-mannitol, was compared to sucrose in a prospective double-blind controlled crossover study. The acute effects of oral ingestion of 30-g loads of isomalt or sucrose on plasma glucose, insulin, free fatty acids (FFA), lactic acid, and carbohydrate (CHO) and lipid oxidation were studied over six hours by means of continuous indirect calorimetry in ten healthy normal-weight subjects. Unlike sucrose, whose ingestion was followed by significant changes in plasma glucose, insulin, and lactic acid during the first 60 minutes of the test, no significant changes in these parameters were observed following the administration of isomalt. The increase in CHO oxidation occurring between 30 and 150 minutes was significantly lower (P less than 0.01) following isomalt than after sucrose. Conversely, the decrease in lipid oxidation was significantly less (P less than 0.01) after isomalt in comparison to sucrose. It is concluded that the rise in CHO oxidation and in plasma glucose and insulin levels is markedly reduced when sucrose is replaced by an equal weight of isomalt. In contrast to other sugar substitutes, no increase in plasma lactic acid was observed after isomalt administration.