Animal studies on the long-term toxicity of oral isomalt have revealed it to be a safe drug. There is no proof that it is carcinogenic, has a deleterious effect on fertility, reproductive performance, or development, and has no effect on animal mortality [1].

Absorption, Distribution and Excretion
This study used in vitro fermentation experiments to simulate the in vivo metabolism of isomaltitol in the large intestine, using pig digesta as the substrate and inoculating feces to study its degradation. In the first week, the fermentation of isomaltitol (3.65%) by unadapted gut microbiota was studied. In the second week, the fermentation of isomaltitol by adapted gut microbiota isolated from pigs fed a diet supplemented with isomaltitol was studied. In the third week, the fermentation of both unadapted and adapted gut microbiota was studied under a higher isomaltitol concentration (7.30%). Isomaltitol was degraded into lactic acid, volatile fatty acids, and gases (CO2, CH4, and hydrogen). ... Fistula-treated pigs and normal pigs were fed 10% sucrose, 5% or 10% isomaltitol between meals, or 10% isomaltitol during meals. The passage and absorption rates of these substances were determined in the terminal ileum (10 pigs per group) or the entire digestive tract (4 pigs per group), respectively. 10% of the sucrose was completely digested and absorbed in the small intestine. In the three isomaltitol treatment groups, 61-64% of the ingested compounds passed through the terminal ileum as intact isomaltitol, as well as free sorbitol, free mannitol, and free glucose. None of these sugars were excreted in feces, indicating that isomaltitol and its components were completely broken down in the large intestine after passing through the terminal ileum. Renal clearance studies were conducted in adult female rats (250 g weight), who were infused with 1.8 g of isomaltitol, α-OD-glucopyranosyl-1,6-D-sorbitol, or α-OD-glucopyranosyl-1,6-D-mannitol over 3 hours. The highest plasma concentration of these compounds reached 25 mM. These substances are readily eliminated, with urinary concentrations reaching up to 100 mg/mL, compared to a maximum urinary concentration of only 0.6 mg/mL after daily oral administration of 5 g isomaltitol to rats. Following infusion of isomaltitol or α-OD-glucopyranosyl-1,6-D-sorbitol, no free sorbitol was detected in blood or urine, and blood glucose levels remained unchanged, indicating the metabolic inertness of these disaccharides. Based on infusion and excretion rates and observed plasma concentrations, the authors concluded that α-OD-glucopyranosyl-1,6-D-sorbitol is distributed in the extracellular fluid but does not enter the cells. After feeding rats isomaltitol for several weeks, a gradual decrease in fecal excretion and cecal enlargement were observed. The authors concluded that this was a result of gut microbiota adaptation and metabolism. Similarly, during a 17-day feeding period, six female rats ingested 3.5 g of isomaltitol daily, and the fecal isomaltitol content decreased from 25% at the beginning to 1% at the end. For more complete data on the absorption, distribution, and excretion of isomaltitols (9 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Rat intestinal maltase is active for isomaltitol, α-OD-glucopyranosyl-1,6-D-sorbitol, and α-OD-glucopyranosyl-1,6-D-mannitol, but at a slow rate. The ratio of the hydrolysis rates of sucrose, isomaltulose, and isomaltulose by rat intestinal α-glucosidase is 100:30:12. Similarly, porcine intestinal disaccharidase hydrolyzes sucrose approximately 20 times faster than α-OD-glucopyranosyl-1,6-D-sorbitol or α-OD-glucopyranosyl-1,6-D-mannitol, while the relative hydrolysis rates of maltose, sucrose, isomaltulose, and isomaltulose by human intestinal α-glucosidase are 100:25:11:2. The metabolism of isomaltulose in the gastrointestinal tract of female rats adapted to this compound was investigated by increasing the dietary concentration of isomaltulose from 10% to 34.5% over 3–4 weeks. After adding 1.7 g of isomaltulose (dissolved in 5 g of feed) to the diet, the contents of the stomach, small intestine, cecum, and large intestine were examined at intervals (up to 6 hours). Based on the contents of α-OD-glucopyranosyl-1,6-D-sorbitol, α-OD-glucopyranosyl-1,6-D-mannitol, sorbitol, mannitol, and sucrose in these organs, the authors concluded that α-OD-glucopyranosyl-1,6-D-sorbitol and α-OD-glucopyranosyl-1,6-D-mannitol are only partially hydrolyzed by carbohydrate enzymes in the small intestine, while a significant portion of the compounds reaches the cecum, where further hydrolysis of glycosidic bonds occurs. The released hexitol ferments in the cecum, leading to cecal enlargement, and only small amounts of α-OD-glucopyranosyl-1,6-D-sorbitol, α-OD-glucopyranosyl-1,6-D-mannitol, and hexitol reach the large intestine.

[1]. Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried lactate dehydrogenase. Int J Pharm. 2018 Mar 1;538(1-2):287-295.

(2xi)-6-O-α-D-glucopyranosyl-D-arabinohexol is a glycosyl aldose alcohol composed of α-D-glucopyranosyl and (2xi)-D-arabinohexol residues linked sequentially by a (1→1) glycosidic bond. Its function is related to α-D-glucose.

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Mechanism of Action
Researchers compared the effects of various sugar alcohols on calcium absorption in the rat small and large intestines in vitro. Net calcium transport was determined using a chamber technique from epithelial cells isolated from the rat jejunum, ileum, cecum, and colon. Calcium concentrations in Tris buffer solution on the serosal and mucosal sides were 1.25 mM and 10 mM, respectively. Calcium concentration in the serosal medium was measured after 30 minutes of incubation, and net calcium absorption was assessed. The addition of 0.1–200 mM erythritol, xylitol, sorbitol, maltitol, palatinib, or lactitol to the mucosal medium affected net calcium absorption in intestinal preparations. Differences in calcium transport were observed in different parts of the intestine, but no differences were observed among the tested sugar alcohols. The authors concluded that sugar alcohols directly affect epithelial tissue and promote calcium absorption in the small and large intestines in vitro. Isomaltitol is a non-cariogenic sweetener widely used in sugar-free candies and chewing gum. Little is known about the effects of isomaltitol on demineralization and remineralization. It has been reported that calcium binds to isomaltitol, which may affect mineral balance. This study aimed to investigate the effects of isomaltitol on demineralization and remineralization of bovine dental enamel damage in in vitro and in vivo experiments. In in vitro experiments, subenamel lesions were subjected to a 3-week pH cycling treatment. Treatment included rinsing the mouth daily with a 10% isomaltitol solution for 5 minutes, and adding 10% isomaltitol to the remineralization or demineralization solution. The remineralization phase used standard pH cycling conditions and maintained a 0.2 ppm fluoride background concentration. In in vivo experiments, subenamel lesions were exposed for two months, with patients brushing three times daily with toothpaste containing 10% isomaltitol. Treatment efficacy was assessed through chemical analysis of the solutions (in vitro) and transverse radiographic microscopy (in vitro and in vivo). In vitro studies showed that rinsing with a 10% isomaltitol solution for 5 minutes slightly promoted remineralization, but sustained presence of 10% isomaltitol (in remineralization or demineralization solutions) inhibited demineralization and/or remineralization. This resulted in a significant reduction in overall mineral loss when isomaltitol was added during demineralization. In vivo studies confirmed that short-term isomaltitol treatment promoted remineralization. Under application-relevant conditions, isomaltitol had a positive effect on the demineralization/remineralization balance. Reports and reviews from authoritative institutions indicate that when glycolytic bacteria are exposed to fermentable carbohydrates (i.e., sugars and starches), the resulting metabolic acids lower the pH of dental plaque, which may promote demineralization and inhibit the remineralization of hydroxyapatite crystals. Hydroxyapatite crystals in teeth exhibit strong resistance to dissolution at neutral pH, but their solubility increases dramatically as the pH decreases. Typically, the critical pH for tooth enamel is approximately 5.5. Dietary acids from ingested foods or beverages can also lead to tooth demineralization, and frequent intake can cause tooth erosion. Xylitol, sorbitol, mannitol, maltitol, lactitol, isomaltulose, erythritol, D-tagatose, isomaltulose, sucralose, and polydextrose are slowly metabolized by oral bacteria. The rate and amount of acid produced by these food components are far lower than that produced by sucrose. Xylitol, sorbitol, mannitol, maltitol, lactitol, isomaltulose, erythritol, D-tagatose, isomaltulose, sucralose, and polydextrose do not promote tooth decay because they do not lower the pH of dental plaque to levels associated with enamel demineralization. Studies have shown a causal relationship between consuming sugary foods/beverages four or more times daily and increased tooth demineralization. Furthermore, if sugar in sugary foods/beverages is replaced with xylitol, sorbitol, mannitol, maltitol, lactitol, isomaltulose, erythritol, D-tagatose, isomaltulose, sucralose, or polydextrose, tooth mineralization may be maintained by reducing tooth demineralization, provided these foods/beverages do not cause tooth erosion. Compared to sugars, food ingredients such as xylitol, sorbitol, mannitol, maltitol, lactitol, isomaltulose, erythritol, D-tagatose, isomaltulose, sucralose, or polydextrose, by weight, can reduce postprandial glycemic (or insulin) response. Because of reduced/delayed digestion/absorption and/or lower available carbohydrate content, consuming foods/beverages that use xylitol, sorbitol, mannitol, maltitol, lactitol, isomaltulose, erythritol, D-tagatose, isomaltulose, sucralose, or polydextrose as sugar substitutes can lower postprandial blood glucose and insulin response compared to consuming sugary foods/beverages. …It has been demonstrated that consuming foods/beverages that use xylitol, sorbitol, mannitol, maltitol, lactitol, isomaltulose, erythritol, D-tagatose, isomaltulose, sucralose, or polydextrose as sugar substitutes is causally related to lowering postprandial blood glucose response (without disproportionately increasing postprandial insulin response).

C33H51N9O7

685.827

344.131

64519-82-0

3034828

White to off-white solid powder

1.7±0.1 g/cm3

788.5±60.0 °C at 760 mmHg

215-217°C

430.7±32.9 °C

0.0±6.2 mmHg at 25°C

1.634

-5.72

9

11

8

23

343

8

C([C@@H]1[C@H]([C@@H]([C@H]([C@H](O1)OC[C@H]([C@H]([C@@H](C(CO)O)O)O)O)O)O)O)O

SERLAGPUMNYUCK-BLEZHGCXSA-N

InChI=1S/C12H24O11/c13-1-4(15)7(17)8(18)5(16)3-22-12-11(21)10(20)9(19)6(2-14)23-12/h4-21H,1-3H2/t4?,5-,6-,7-,8-,9-,10+,11-,12+/m1/s1

(3R,4R,5R)-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexane-1,2,3,4,5-pentol

Isomalt; Palatinit

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~250 mg/mL (~726.09 mM)

Solubility in Formulation 1: 100 mg/mL (290.44 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)