A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control.

Diabetes mellitus is the most common metabolic disorder contributing to significant morbidity and mortality in humans. Different preventive and therapeutic agents, as well as various pharmacological strategies or non-pharmacological tools, improve the glycemic profile of diabetic patients. Isomaltulose, d-tagatose, and trehalose are naturally occurring, low glycemic sugars that are not synthesized by humans but widely used in food industries. Various studies have shown that these carbohydrates can regulate glucose metabolism and provide support in maintaining glucose homeostasis in patients with diabetes, but also can improve insulin response, subsequently leading to better control of hyperglycemia. In this review, we discussed the anti-hyperglycemic effects of isomaltulose, D-tagatose, and trehalose, comparing their properties with other known sweeteners, and highlighting their importance for the development of the pharmaceutical and food industries.

Oral administration of palatinose vs sucrose improves hyperglycemia in normal C57BL/6J mice.

Palatinose is a sucrose analog with a slower digestion rate than that of sucrose. For this reason, palatinose shows better effects on hepatic lipogenesis and cholesterol homeostasis compared with sucrose. We hypothesized that supplementation with palatinose instead of sucrose improves postprandial hyperglycemia and hyperinsulinemia in mice. Herein, we compared the digestion rates in vitro and observed physiological changes in vivo between sucrose- and palatinose-containing diets given to mice. Palatinose was hydrolyzed only by enzymes of the small intestine and was digested more slowly compared with sucrose in vitro. In mice, a diet containing palatinose resulted in significantly lower body weight gain and food efficiency rate values than those given a diet with sucrose. In this study, changes in serum biochemistry; hepatic fatty acid synthesis; cholesterol homeostasis; glucogenic, proinflammatory cytokines; and oxidative stress-related genes and proteins in the palatinose- and sucrose-fed mice were measured. Compared with the mice fed the sucrose diet, the palatinose diet resulted in lower serum glucose, insulin, and total cholesterol levels, as well as lower expression of several lipogenesis-related genes and proteins. Histological analysis of hepatic cells of palatinose-fed mice showed normal morphology. In conclusion, palatinose intake results in lower hepatic lipogenesis and better cholesterol homeostasis than the effects from sucrose.

Ethnic Variability in Glycemic Response to Sucrose and Isomaltulose.

The aim of this study was to compare the glycemic response of Caucasians and Asians to two disaccharides of different glycemic index (GI), and to examine if ethnic groups that showed the largest glycemic response to sucrose would benefit the most when it is replaced with isomaltulose. Forty healthy participants (10 Chinese; 10 Malays; 10 Caucasians; and 10 Indians) consumed beverages containing 50 g of sucrose or isomaltulose on two separate occasions using a randomized crossover design. Capillary blood glucose was measured in a fasted state and at 15, 30, 45, 60, 90, and 120 min after beverage ingestion. Glycemic response to sucrose was significantly higher in Malays compared to Caucasians (p = 0.041), but did not differ between Caucasians vs. Chinese (p = 0.145) or vs. Indians (p = 0.661). When sucrose was replaced with isomaltulose, glycemic responses were significantly reduced in all ethnic groups, with the largest reduction in glycemic response being observed in Malays. Malays, who had the greatest glycemic response to sucrose, also showed the greatest improvement in glycemic response when sucrose was replaced with isomaltulose. This implies that Malays who are more susceptible to type 2 diabetes mellitus may benefit from strategies that replace high GI carbohydrate with lower GI alternatives to assist in glycemic control.

Low Glycemic Index Prototype Isomaltulose-Update of Clinical Trials.

Low glycemic index diets are supposed to achieve a more beneficial effect on blood glucose control in people with diabetes mellitus and may also provide metabolic benefits for the general population. A prototype of a low-glycemic index carbohydrate is the natural occurring disaccharide isomaltulose that can be commercially produced from sucrose (beet sugar) to industrial scale. It is currently used in various food and drink applications as well as special and clinical nutrition feeds and formula diet as a food ingredient and alternative sugar. Here we provide an overview on clinical trials with isomaltulose including an analysis of its effects on glycemia and fat oxidation as compared to high glycemic index sugars and carbohydrates. In addition, we discuss recent reports on beneficial effects in weight-loss maintenance and pregnancy.

Effects of Low versus High Glycemic Index Sugar-Sweetened Beverages on Postprandial Vasodilatation and Inactivity-Induced Impairment of Glucose Metabolism in Healthy Men.

Intake of sugar-sweetened beverages (SSB) may contribute to cardiovascular risk. The aim of this study was to investigate whether functional sugars with low compared to high glycemic index (GI) have beneficial effects on arterial stiffness during a period of low-physical activity. In a controlled cross-over dietary intervention (55% CHO, 30% fat, 15% protein), 13 healthy men (age: 23.7 ± 2.2 years, body mass index: 23.6 ± 1.9 kg/m²) completed 2 × 1 week of low physical activity following 1 week of normal physical activity (2363 ± 900 vs. 11,375 ± 3124 steps/day). During inactive phases participants consumed either low-GI (isomaltulose) or high-GI SSB (maltodextrin-sucrose), providing 20% of energy requirements. Postprandial vasodilatation (augmentation index, AIx), insulin sensitivity (IS) and Glucagon-like-peptide 1 (GLP-1) responses were measured during a meal test before and after SSB-intervention. Compared to maltodextrin-sucrose-SSB, postprandial vasodilatation was prolonged (AIx after 120 min: 9.9% ± 4.3% vs. 11.4% ± 3.7%, p < 0.05) and GLP-1 secretion was higher with isomaltulose-SSB (total area under the GLP-1 curve (tAUCGLP)-1: 8.0 ± 4.4 vs. 5.4 ± 3.4 pM × 3 h; p < 0.05). One week of low-physical activity led to impaired IS that was attenuated with low-GI SSB consumption, but did not affect arterial stiffness (p > 0.05). Higher postprandial GLP-1 secretion after intake of low compared to high-GI beverages may contribute to improved postprandial vasodilatation. Although one week of low-physical activity led to marked impairment in IS, it had no effect on arterial stiffness in healthy men.

The addition of beta-hydroxy-beta-methylbutyrate and isomaltulose to whey protein improves recovery from highly demanding resistance exercise.

OBJECTIVE: This study evaluated whether a combination of whey protein (WP), calcium beta-hydroxy-beta-methylbutyrate (HMB), and carbohydrate exert additive effects on recovery from highly demanding resistance exercise. METHODS: Thirteen resistance-trained men (age: 22.6 ± 3.9 years; height: 175.3 ± 12.2 cm; weight: 86.2 ± 9.8 kg) completed a double-blinded, counterbalanced, within-group study. Subjects ingested EAS Recovery Protein (RP; EAS Sports Nutrition/Abbott Laboratories, Columbus, OH) or WP twice daily for 2 weeks prior to, during, and for 2 days following 3 consecutive days of intense resistance exercise. The workout sequence included heavy resistance exercise (day 1) and metabolic resistance exercise (days 2 and 3). The subjects performed no physical activity during day 4 (+24 hours) and day 5 (+48 hours), where recovery testing was performed. Before, during, and following the 3 workouts, treatment outcomes were evaluated using blood-based muscle damage markers and hormones, perceptual measures of muscle soreness, and countermovement jump performance. RESULTS: Creatine kinase was lower for the RP treatment on day 2 (RP: 166.9 ± 56.4 vs WP: 307.1 ± 125.2 IU · L(-1), p ≤ 0.05), day 4 (RP: 232.5 ± 67.4 vs WP: 432.6 ± 223.3 IU · L(-1), p ≤ 0.05), and day 5 (RP: 176.1 ± 38.7 vs 264.5 ± 120.9 IU · L(-1), p ≤ 0.05). Interleukin-6 was lower for the RP treatment on day 4 (RP: 1.2 ± 0.2 vs WP: 1.6 ± 0.6 pg · ml(-1), p ≤ 0.05) and day 5 (RP: 1.1 ± 0.2 vs WP: 1.6 ± 0.4 pg · ml(-1), p ≤ 0.05). Muscle soreness was lower for RP treatment on day 4 (RP: 2.0 ± 0.7 vs WP: 2.8 ± 1.1 cm, p ≤ 0.05). Vertical jump power was higher for the RP treatment on day 4 (RP: 5983.2 ± 624 vs WP 5303.9 ± 641.7 W, p ≤ 0.05) and day 5 (RP: 5792.5 ± 595.4 vs WP: 5200.4 ± 501 W, p ≤ 0.05). CONCLUSIONS: Our findings suggest that during times of intense conditioning, the recovery benefits of WP are enhanced with the addition of HMB and a slow-release carbohydrate. We observed reductions in markers of muscle damage and improved athletic performance.

Postprandial substrate use in overweight subjects with the metabolic syndrome after isomaltulose (Palatinose™) ingestion.

OBJECTIVE: Dietary interventions with a low glycemic index have shown to be successful for the prevention and therapy of the metabolic syndrome. In the present study, we investigated the postprandial metabolic response at rest and during physical activity the low glycemic carbohydrate isomaltulose (Palatinose™) intake compared with a conventional carbohydrate (glucose syrup/sucrose [glc/suc]) with a higher glycemic index. METHODS: Twenty overweight or obese men (32-64 y old) with the metabolic syndrome and insulin resistance were enrolled in this double-blinded, randomized, cross-over study. In the morning, a breakfast consisting of a 250-mL drink and 140 g of cookies containing in a total of 50 g of Palatinose™ or glc/suc was consumed. Two hours after breakfast, subjects exercised at moderate intensity on a treadmill for 30 min. Thereafter, subjects ingested a standardized lunch consisting of a 250-mL drink with 10% Palatinose™ or glc/suc, mini pizzas, and an apple. RESULTS: Blood levels of glucose and insulin were measured and the postprandial substrate metabolism was determined. The glycemic and insulinemic responses were considerably lower after the ingestion of Palatinose™ (incremental area under the curve, P < 0.05). The total fat oxidation was significantly higher with Palatinose™ from breakfast to the beginning of lunch including the exercise and postexercise periods (P < 0.05). Fat oxidation with Palatinose™ was numerically higher throughout the entire examination period (P = 0.09). CONCLUSION: In obese subjects with insulin resistance and the metabolic syndrome, the partial substitution of carbohydrates with a higher glycemic index in foods and drinks by Palatinose™ resulted in greater postprandial fat oxidation at rest and during physical activity. It is hypothesized that this increased fat oxidation may confer further benefits for long-term weight management and for an improvement in metabolic risk factors.

Reduced glycaemic and insulinaemic responses following trehalose and isomaltulose ingestion: implications for postprandial substrate use in impaired glucose-tolerant subjects.

The impact of slowly digestible sugars in reducing the risk of developing obesity and related metabolic disorders remains unclear. We hypothesised that such carbohydrates (CHO), resulting in a lower glycaemic and insulinaemic response, may lead to greater postprandial fat oxidation rates in subjects with impaired glucose tolerance (IGT). The present study intends to compare the postprandial metabolic responses to the ingestion of glucose (GLUC) v. trehalose (TRE) and sucrose (SUC) v. isomaltulose (IMU). In a randomised, single-blind, cross-over design, ten overweight IGT subjects were studied four times, following ingestion of different CHO drinks either at breakfast or in combination with a mixed meal at lunch. Before and 3 h after CHO ingestion, energy expenditure, substrate utilisation and circulating metabolite concentrations were determined. Ingestion of CHO drinks with a meal resulted in an attenuated rise in GLUC (-33 %) and insulin (-14 %) concentrations following TRE when compared with GLUC and following IMU, an attenuation of 43 and 34 % when compared with SUC ingestion, respectively. Additionally, there was less inhibition of the rise in NEFA concentrations and less decline in postprandial fat oxidation (22 %) after IMU when compared with SUC, whereas TRE did not differ from GLUC. The attenuated rise in GLUC and insulin concentrations following IMU ingestion attenuated the postprandial inhibition of fat oxidation compared with SUC when co-ingested with a meal. This suggests that exchange of SUC in the diet for IMU may result in a more favourable metabolic response and may help to reduce the risks associated with obesity and type 2 diabetes.

Isomaltulose Improves Postexercise Glycemia by Reducing CHO Oxidation in T1DM.

PURPOSE: individuals with type 1 diabetes mellitus (T1DM) are encouraged to consume CHO to prevent hypoglycemia during or after exercise. However, the research comparing specific types of CHO is limited. This study compared the alterations in metabolism and fuel oxidation in response to running after preexercise ingestion of isomaltulose or dextrose in T1DM. METHODS: after preliminary testing, on two occasions, eight T1DM individuals consumed 75 g of either dextrose (DEX; GI = 96) or isomaltulose (ISO; GI = 32), 2 h before performing 45 min of treadmill running at 80% ± 1% VO(2peak). Blood glucose (BG) was measured for 2 h before and 3 h after exercise. Cardiorespiratory parameters were collected at rest and during exercise. Data (mean ± SEM) were analyzed using repeated-measures ANOVA. RESULTS: there was a smaller increase in BG in the preexercise period under ISO with peak BG occurring at 120 min after ingestion compared with 90 min under DEX (Δ+4.5 ± 0.4 vs Δ+9.1 ± 0.6 mmol·L, P < 0.01). During the final 10 min of exercise, there were lower CHO (ISO 2.85 ± 0.07 vs DEX 3.18 ± 0.08 g·min, P < 0.05) and greater lipid oxidation rates (ISO 0.33 ± 0.03 vs DEX 0.20 ± 0.03 g·min, P < 0.05) under ISO. After exercise, ISO BG was lower than DEX for the entire 180-min period, with BG area under the curve and mean BG concentrations being 21% ± 3% and 3.0 ± 0.4 mmol·L lower, respectively (P < 0.05). CONCLUSIONS: consumption of ISO improves BG responses during and after exercise through reduced CHO and improved lipid oxidation during the later stages of exercise.

Safer glycemic control using isomaltulose-based enteral formula: a pilot randomized crossover trial.

PURPOSE: Preventing harmful hyperglycemia is important in critical illness. However, insulin therapy increases the risk of hypoglycemia. In patients with diabetes, isomaltulose-based enteral formula (IF) feeding has been shown to reduce glycemia. This randomized controlled crossover study was conducted to determine whether IF feeding improves glycemia in postoperative critically ill patients. MATERIAL AND METHODS: Eight patients who developed hyperglycemia (>150 mg/dL) after esophagectomy were included. Patients were randomized to either the IF or the standard feeding formula (SF) arm. After 16 hours of administration of randomized formula and 8 hours of washout, patients crossed over to the other formula for the next 16 hours. Continuous glucose measurement using STG-22 (Nikkiso, Tokyo, Japan) was performed during the trial. RESULTS: Maximum blood glucose concentration was 181 mg/dL with IF, significantly lower than the 206 mg/dL with SF (P = .001). Mean glycemia during feeding periods was 162 mg/dL with IF, significantly lower than the 176 mg/dL with SF (P = .0001). Seven (87.5%) patients taking SF exceeded 180 mg/dL compared with 3 (37.5%) patients taking IF (P = .005). This effect was seen without any risk of hypoglycemia and complication. CONCLUSIONS: Isomaltulose-based enteral formula might be useful for safer glycemic control in postoperative critically ill patients. Further study to determine clinical benefit of IF feeding is justified.

Effects of a novel palatinose based enteral formula (MHN-01) carbohydrate-adjusted fluid diet in improving the metabolism of carbohydrates and lipids in patients with esophageal cancer complicated by diabetes mellitus.

BACKGROUND: During perioperative management of patients with gastrointestinal cancer complicated by diabetes mellitus, adequate alimentation is required, but we often face difficulties associated with hyperglycemia and other accompanying complications. Recently, we investigated the effects of a novel palatinose based enteral formula (MHN-01) in suppressing post-prandial hyperglycemia and improving lipid metabolism in experimental animals and perioperative management of patients with esophageal cancer complicated by diabetes mellitus. MATERIALS AND METHODS: We gave normal rats and rats with type 2 diabetes mellitus a single oral dose of fluid diet, and analyzed comparatively the time course of blood glucose level in each group until 3 h after the dose. In both the normal rat group and the type 2 diabetes group, peak blood glucose level after the MHN-01 dose was significantly lower than after a dose of ordinary fluid diet and was comparable to the peak level after a dose of a fluid diet rich in MUFA (monounsaturated fatty acid). We allowed normal mice free access to fluid diet for 43 days, and measured their body fat levels. Fat accumulation was significantly lower in mice given MHN-01 than in mice given ordinary fluid diet. We also analyzed the respiratory quotient and resting energy expenditure of normal Sprague-Dawley rats fed by MHN-01 or an ordinary fluid diet. The respiratory quotient of the MHN-01 group was significantly lower than the ordinary fluid group, although the resting energy expenditure of both groups was almost the same level. The effect of MHN-01 was estimated to be based on improvement of lipid metabolism. RESULTS: Between 2003 and 2005, among 164 patients who underwent radical thoracic esophagectomy and/or reconstruction for esophageal carcinoma at Okayama University Hospital, nine patients (5.5%) were diagnosed with diabetes mellitus in pre-operative screening and were treated with MHN-01. Clinical courses of two cases with severe status of diabetes mellitus were presented as successful case reports of MHN-01. CONCLUSION: MHN-01 was very useful in perioperative management of patients complicated by diabetes mellitus, unable to ingest food p.o. such as esophageal cancer or other diseases.

Oral dosing of neonatal mice with sucrose reduces infection with Cryptosporidium parvum.

Cryptosporidium parvum is a significant cause of diarrheal disease in humans and economically important livestock species. There is no effective treatment available for this protozoan parasite. Mechanisms of intestinal colonization by C. parvum are not well understood, but it has been suggested that the parasite may utilize a lectin-like receptor. We used an infant mouse model to test whether high sugar concentrations in the intestine would affect in vivo colonization with C. parvum. We found that a single oral dose of sucrose, administered to mice at the time of, or 24 hr before, challenge with C. parvum significantly reduced infection. Significant reduction of infection was also seen in mice given isomaltose. Histologic examination of intestinal sections of mice treated with sucrose or isomaltose, but not other sugars, showed marked vacuolation of the small intestinal epithelium 1 day after treatment. Three days after treatment, tissue appeared normal. Thus, sucrose and, to a lesser extent, isomaltose reduced in vivo colonization with C. parvum and altered epithelial cell morphology in intestines of mice.

Response in serum ferritin and haemoglobin to iron therapy in blood donors.

Seven hundred seventeen healthy male blood donors regularly donating four or more units a year were surveyed for haemoglobin and serum ferritin levels. One hundred fifty-one (21%) had a haemoglobin less than 13.5 g/dl and were therefore disqualified from further blood donation, having a mean serum ferritin of 28 micrograms/liter. Of the remaining 566 donors with haemoglobin levels equal to or greater than 13.5 g/dl, the mean serum ferritin was 33 micrograms/liter, although in 299 (53%) the value was less than 28 micrograms/liter. To document response to iron therapy 46 donors with haemoglobin levels equal to or greater than 13.5 g/dl were stratified into those with the lowest iron stores (group 1; n = 23), defined as a serum ferritin less than 20 micrograms/liter, and controls (group 2; n = 23), with serum ferritin between 50 and 150 micrograms/liter. Within each stratum donors randomly received ferric polymaltose at a dose of 100 mg elemental iron twice daily for 56 days (groups 1a and 2a) or an identical iron-free placebo tablet administered on the same schedule (groups 1b and 2b). Iron therapy in the iron-deficient group (group 1a:n = 11) resulted in a significant rise in haemoglobin (p = .03) and iron stores reflected in serum ferritin (p = .002) compared to those receiving placebo (group 1b). In the control group iron therapy or placebo was without significant effect. Thus, ferric polymaltose preparation is bioavailable and is notable for the virtual absence of gastrointestinal tract side effects.