Safety evaluation and maximum use level for transient ingestion in humans of allitol.

Allitol is a hexitol produced by reducing the rare sugar D-allulose with a metal catalyst under hydrogen gas. To confirm the safe level of allitol, we conducted a series of safety assessments. From the results of Ames mutagenicity assay using Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, Escherichia coli strain WP2uvrA, and an in vitro chromosomal aberration test on cultured Chinese hamster cells, allitol did not show any significant genotoxic effect. No significant effects on general condition, urinalysis, hematology, physiology, histopathology, or at necropsy were observed at a dose of 1500 mg/kg body weight of allitol in the acute and 90-day subchronic oral-toxicity assessments for rats. A further study performed on healthy adult humans showed that the acute use level of allitol for diarrhea was 0.2 g/kg body weight for both men and women. The results of current safety assessment studies suggest that allitol is safe for human consumption.

[Toxicity of d-Arabinose in Male and Female Rats].

In order to investigate the feasibility of using the rare sugar d-arabinose as a functional food material, we examined its toxicity in rats. In an acute toxicity study, the lethal dose (LD50) was calculated to be 12.1 g/kg in males and 11.6 g/kg in females. On the other hand, in a short-term toxicity test, rats developed diarrhea when given feed containing 5% d-arabinose, which was the minimum amount added, so the maximum nontoxic amount was estimated to be less than 5%. Thus, the toxicity of d-arabinose is stronger than that of another rare sugar, d-psicose, which was reported to show no toxicity when added at 10% in the diet. Further studies are needed to establish whether d-arabinose would be safe for use as a functional ingredient.

Effect of egg white and its hydrolysate on stearoyl-CoA desaturase index and fat accumulation in rat tissues.

We investigated the dietary effects of egg white (EW) and its hydrolysate (EWH) on fat metabolism in rats. Wistar rats were divided into casein, EW and EWH dietary groups, and fed their respective diet for 8 weeks. Dietary EW and EWH decreased food intake, body weight gain and fat accumulation in the carcass, liver, muscles and adipose tissues, but muscle weight was increased. In addition, dietary EW and EWH decreased stearoyl-CoA desaturase (SCD) indices and glucose-6-phosphate dehydrogenase activity of the liver and gastrocnemius muscle. Dietary EW also increased the fecal excretion of triacylglycerol, cholesterol and total bile acids, and decreased the serum levels of triacylglycerol and leptin. The suppressive effects of dietary EW on food intake and body fat accumulation were weakened by dietary EWH. These findings indicate that EW and EWH, especially EW, are effective in reducing body fat accumulation by regulating hepatic and muscular SCD indices.

Increased muscular triglyceride content and hyperglycemia in Goto-Kakizaki rat are decreased by egg white hydrolysate.

We investigated the fat metabolic characteristics in non-obese and diabetic Goto-Kakizaki (GK) rat and the effects of dietary egg white hydrolysate (EWH) on glucose and fat metabolism. Wistar (W) and GK (G) rats were placed into dietary casein (WC and GC) or EWH (WE and GE) group, and fed their respective diet for six weeks. Triglyceride (TG) content and stearoyl-CoA desaturase (SCD) indices in the soleus muscle were higher in the GC group than WC group in parallel with worsening serum glucose metabolic parameters. The glucose metabolic parameters were significantly improved in the GE group. The TG accumulation and SCD indices in the soleus muscle were also significantly lower in the GE group than in the GC group. In conclusion, dietary EWH not only improved glucose metabolism but also reduced both TG accumulation and SCD indices in the soleus muscle of GK rat.

D-psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet.

We investigated the anti-obesity effects of D-psicose by increasing energy expenditure in rats pair-fed the high-sucrose diet (HSD). Wistar rats were divided into two dietary groups: HSD containing 5% cellulose (C) and 5% d-psicose (P). The C dietary group was further subdivided into two groups: rats fed the C diet ad libitum (C-AD) and pair-fed the C diet along with those in the P group (C-PF). Resting energy expenditure during darkness and lipoprotein lipase activity in the soleus muscle were significantly higher in the P group than in the C-PF group. Serum levels of glucose, leptin and adiponectin; glucose-6-phosphate dehydrogenase activities in the liver and perirenal adipose tissue; and body fat accumulation were all significantly lower in the P group than in the C-PF group. The anti-obesity effects of D-psicose could be induced not only by suppressing lipogenic enzyme activity but also by increasing EE in rats.

Effect of a fermented brown rice extract on the gastrointestinal function in methotrexate-treated rats.

We investigated the protective effect of a hydrous ethanol extract of brown rice fermented with Aspergillus oryzae (ERF) which contained nucleobases and low fiber on the methotrexate (MTX)-induced gastrointestinal damage in rats. The rats were assigned to three groups: control (CON), MTX, and MTX-ERF. The rats in the CON and MTX groups were fed for 4 weeks on a basal diet, and those in the MTX-ERF group were fed on a 9.16% ERF-containing basal diet. The rats in the MTX and MTX-ERF groups were administered with MTX after 3 weeks. The survival rate and incidence rate of diarrhea were monitored over 1 week. On day 4 after the administration, half of the rats in each group were killed, and gastrointestinal samples were collected. Feeding with ERF improved the incidence rate of diarrhea, increased the protein content in small intestinal mucosa, and also apparently improved the survival rate. These results indicate that dietary ERF could protect against MTX-induced gastrointestinal damage.

Inhibition by dietary D-psicose of body fat accumulation in adult rats fed a high-sucrose diet.

We investigated the anti-obesity effects of dietary D-psicose on adult rats fed a high-sucrose diet. Wistar rats (16 weeks old) that had previously been fed a high-sucrose diet (HSD) were fed HSD or a high-starch diet (HTD) with or without 5% D-psicose for 8 weeks. The food efficiency, carcass fat percentage, abdominal fat accumulation, and body weight gain were all significantly suppressed by dietary D-psicose.

Long-Term Whole-Body Vibration Stimulus Decreases Body Fat Accumulation in Rats Fed a High-Fat Diet.

Whole-body vibration (WBV) is a type of light-resistance exercise that involves exposing the body to rapid and repeated oscillations of a vibrating platform. It has been suggested that long-term WBV can improve bone mass and muscle strength. However, little is known about its effects on body composition, and the safety and efficacy of WBV have not been established. In this study, we investigated the effects of WBV on body fat loss and muscle mass maintenance or improvement in male Wistar rats fed standard or high-fat diets. We also aimed to establish a rat model for future nutritional and physiological studies. We conducted two experiments using male Wistar rats that were 3 weeks old. The rats were randomly divided into two groups: the control group and the vibration group. The rats were fed either a commercial standard diet (Experiment 1) or a high-fat diet (Experiment 2) ad libitum for 8-12 weeks. Our results showed that WBV stimulus dramatically reduced body fat accumulation in rats fed a high-fat diet but not in those fed a standard diet. This suggests that WBV may be particularly effective under dietary conditions that promote obesity. Moreover, WBV increased the mass of several skeletal muscles, which are known to have resistance exercise effects. Our findings indicate that long-term WBV is safe, with no inhibition of growth or feeding. Taken together, our results suggest that WBV may be a promising approach for preventing and treating obesity. Further research is needed to investigate the underlying mechanisms and to determine the optimal WBV for maximum benefits.

Increased stearoyl-CoA desaturase index and triglyceride content in the liver of rats after a single bout of swimming exercise.

Up-regulation of stearoyl-CoA desaturase (SCD) is closely related to improved insulin resistance. We investigated whether the SCD indices in tissues were influenced by a single-endurance exercise and low content of dietary medium-chain fatty acid (FA). Wistar rats were fed a long-chain (S) or medium- and long-chain FA (M) diet for 2 weeks. At the end of the experiment, the rats were further assigned to two sub-groups (sedentary, Sed; exercise, Ex). These groups were defined as S-Sed, S-Ex, M-Sed, and M-Ex. The rats in the exercise groups were subjected to swimming exercise for 4 h, and tissue samples were obtained. The exercise significantly increased the triglyceride (TG) content and SCD index only in the liver. In contrast, no such changes were apparent by intake of the M diet. A single bout of endurance exercise increased the hepatic TG content and SCD index which might be effective in protecting against insulin resistance.

Soy germ protein concentrate diet decreased body fat weight and increased hindlimb muscle weight in rats.

The purpose of this study was to investigate the effects of soy germ protein intake on body composition. Wistar rats were fed experimental diets for 16 weeks. These consisted of soy germ protein, soy protein, or casein. Abdominal adipose tissue weights significantly lower and hindlimb muscle weights were significantly higher in the soy germ protein group than in the casein group.

Effects of Dietary Allitol on Body Fat Accumulation in Rats.

Allitol is a rare sugar alcohol obtained by reducing d-allulose (d-psicose). However, information on the effects of long-term dietary allitol intake is limited. This study aimed to investigate the effect of allitol supplementation, as a sugar substitute, on body fat accumulation in rats compared with sucrose, rare sugar d-allulose, or erythritol. Thirty-two male Wistar rats (3 wk old) were fed experimental diets including 5% sucrose, allitol, erythritol, or d-allulose for 8 wk ad libitum. Weight gain, food intake, and food efficiency did not differ among the groups. The total body fat mass and percentage, and intra-abdominal adipose tissue weights were significantly lower in rats fed with the allitol diet than in those fed with the sucrose diet. These body fat indicators tended to be lower in rats fed with the erythritol and d-allulose diets than in those fed with the sucrose diet, but there was no significant difference. The serum glucose-lowering effect obtained in rats fed with the d-allulose diet did not appear in rats fed with the allitol diet. These results suggest that the anti-obesity effect of allitol may be equal to or greater than that of d-allulose.

Dietary Dried Sweetspire (Itea) Powder Reduces Body Fat Accumulation in Rats Fed with a High-fat Diet.

Sweetspire (Itea) is the only plant that accumulates rare sugars d-allulose and allitol. However, no reports have indicated that sweetspire has a beneficial physiological activity in mammalians. We have examined the effect of dietary dried sweetspire powder (SP) on body fat accumulation in rats fed with a high-fat diet. Twenty-four male Wistar rats were randomized into three groups, the control (C), SP, and rare sugar (RS) groups. The SP diet contained 5% SP (contained 0.4% d-allulose and 0.6% allitol in the diet), and the RS diet contained the same amount of rare sugars as the SP diet. All rats were given free access to the experimental diets for 8 weeks. The percentages of intra-abdominal adipose tissue and total body fat were significantly lower in the SP group than in the C group, suggesting that SP has an anti-obesity effect. Furthermore, this anti-obesity effect may be attributed to the rare sugars in SP.

Dietary D-Allulose Reduces Body Fat Accumulation in Rats with and without Medium-Chain Triacylglycerol Supplementation.

d-Allulose (d-psicose) is a rare sugar, that contains no calories and exhibits 70% relative sweetness when compared with sucrose. Recently, several studies have demonstrated the anti-obesity effect of d-allulose, mediated by suppressing lipogenesis and increasing energy expenditure. Medium-chain triacylglycerols (MCTs) are lipids formed by 3 medium-chain fatty acids (MCFAs) with 6-12 carbon atoms attached to glycerol. MCTs have been expensively studied to reduce body fat accumulation in rats and humans. The anti-obesity effect of MCTs was not confirmed depending on the nutritional conditions because MCT might promote lipogenesis. In the present study, we examined the effects of simultaneous intake of diets containing low (5%) or high (13%) MCTs, with or without 5% d-allulose, on body fat accumulation in rats (Experiment 1). Furthermore, we assessed the interaction between 5% MCT and 5% d-allulose in the diet (Experiment 2). In Experiment 1, intra-abdominal adipose tissue weight was significantly greater in the high MCT diet groups than in the commercial diet (control) group. d-Allulose significantly decreased weights of intra-abdominal adipose tissue, carcass fat, and total body fat, however, these weights increased as the amount of MCT added increased. In Experiment 2, d-allulose significantly decreased almost all body fat indicators, and these values were not influenced by the presence or absence of MCT addition. The anti-obesity effect of d-allulose was observed with or without dietary MCT, and no synergistic effect was detected between d-allulose and MCT. These results suggest that d-allulose is a beneficial food ingredient in diets aimed at reducing body fat accumulation. However, further research is required on the synergistic effects between d-allulose and MCTs.

Acute and sub-chronic toxicity of D-allose in rats.

We examined the acute and sub-chronic toxicity of D-allose in rats. In the acute toxicity test, the calculated LD(50) value was 20.5 g/kg. In the sub-chronic toxicity test, no difference was found among the four groups in most of the serum chemical and hematological test results. These results suggest that D-allose is not toxic to rats.

Effects of Short-Term Dietary Change from High-Carbohydrate Diet to High-Fat Diet on Storage, Utilization, and Fatty Acid Composition of Rat Muscle Triglyceride during Swimming Exercise.

The purpose was to examine the effects of a 3-day dietary change from a high-carbohydrate (C) to high-fat (F) diet on muscle triglyceride (MTG) storage and utilization during the swimming exercise in rats. Rats were meal-fed on either the F diet or the C diet for 11 days. For an additional 3 days, half of the rats in each group were fed the same diets and the other rats were switched to counterpart diets. On the final day, half of the rats in each group were killed before the exercise and the others were killed after the exercise. Serum concentrations of glucose and free fatty acids (FFA) were higher in the post-exercise groups than in the pre-exercise groups. The tissue glycogen contents were lower in the post-exercise groups. However, the MTG contents and fatty acid (FA) compositions were not influenced by the exercise and dietary change. The F diet increased the FFA concentration and slightly increased the MTG content. Moreover, the dietary FA composition influenced the FA composition of the MTG. These results suggest that the exercise did not affect the contents and FA composition of MTG, but that the F diet had an effect on the MTG contents and FA composition.

d-Psicose Inhibits Intestinal alpha-Glucosidase and Suppresses the Glycemic Response after Ingestion of Carbohydrates in Rats.

d-psicose is one of the rare sugars present in small quantities in commercial carbohydrates and agricultural products. In this study, we investigated the effects of d-psicose on the activities of alpha-amylases and alpha-glucosidases in vitro, and evaluated the effects of d-psicose on the in vivo postprandial glycemic response using rats. In the in vitro study, d-psicose potently inhibited the intestinal sucrase and maltase, however, slightly inhibited the intestinal and salivary alpha-amylase activities. Male Wistar rats (6 months old) were administrated 2 g/kg of sucrose, maltose or soluble starch together with 0.2 g/kg of d-psicose or d-fructose. The d-psicose significantly inhibited the increment of plasma glucose concentration induced by sucrose or maltose. The starch-induced glycemic response tended to be suppressed by d-psicose, however the suppression was not significant. These results suggest that d-psicose inhibits intestinal sucrase and maltase activities and suppresses the plasma glucose increase the normally occurs after sucrose and maltose ingestion. Thus, d-psicose may be useful in preventing postprandial hyperglycemia in diabetic patients when foods containing sucrose and maltose are ingested.

Kaempferia parviflora Ethanol Extract, a Peroxisome Proliferator-Activated Receptor γ Ligand-binding Agonist, Improves Glucose Tolerance and Suppresses Fat Accumulation in Diabetic NSY Mice.

This study assessed the effect of Kaempferia parviflora, also known as black ginger (BG), and its ethanol extract (BGE) on peroxisome proliferator-activated receptor (PPAR) γ agonistic activity, glucose tolerance, fat accumulation, and lipids-induced hypertriglyceridemia in mice. PPARγ ligand-binding capacity in vitro and polymethoxy flavone contents were highly observed in organic solvent extracts. In an animal experiment A, male diabetic Nagoya-Shibata-Yasuda mice were divided into five dietary groups and fed each diet for 8 weeks: AIN-93G diet (low-fat [LF] diet), high-fat (HF) diet, HF diet supplemented with 1% BG, HF diet supplemented with 0.19% BGE, and HF diet supplemented with pioglitazone (PPARγ agonist, 3 mg/kg/day) as a PPARγ agonistic positive control. As determined from glucose and insulin tolerance tests, plasma glucose levels were improved in the BG and BGE groups. The BGE extract suppressed fat accumulation in adipose tissues, liver, and muscles without changing the plasma adiponectin level. In an animal experiment B, in order to investigate the effect of BG and BGE on lipid-induced hypertriglyceridemia, male ddY mice were divided into three test groups: control, BG-administered group (500 mg/kg), and BGE-administered group (100 mg/kg). The plasma triacylglycerol level was not different among the groups during the lipids administration test. These results conclude that the BGE extract containing several kinds of polymethoxy flavones showed PPARγ ligand-binding capacity in vitro and prevented obesity and insulin resistance independent of adiponectin secretion in mice. PRACTICAL APPLICATION: Kaempferia parviflora, also known as black ginger (BG), is often used as a folk medicine and a functional food material to prevent metabolic syndrome mainly in Asian regions. Here, we have clarified that ethanol extract from BG (BGE) contains several kinds of polymethoxy flavones to show PPARγ ligand-binding capacity and is an active extract for the improvement of obesity and insulin resistance. The BGE is expected to be applied for functional food materials in health food markets. Also, polymethoxy flavones to show PPARγ ligand-binding capacity can be generally applied as a physiological active compound of functional food supplements.

Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults.

An examination was conducted to verify D-psicose suppressed the elevation of blood glucose and insulin concentration in a dose-dependent manner under the concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted as a randomized single blind study. The subjects took one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of administration were at least 1 wk. The load test with 75 g maltodextrin showed significant suppressions of the elevation of blood glucose and insulin concentration under the doses of 5 g or more D-psicose with dose dependency. An independent administration of 7.5 g D-psicose had no influence on blood glucose or insulin concentration. D-Psicose is considered efficacious in the suppression of the elevation of blood glucose concentration after eating in humans.

Comparison of Anti-Obesity Effect between Two Types of Syrup Containing Rare Sugars in Wistar Rats.

D-Allulose-containing rare sugar sweeteners have been categorized into two types, rare sugar syrup (RSS), consisting of 4 rare monosaccharides, and modified glucose syrup (MGS), rich in D-allulose, which was previously referred to D-psicose. The anti-obesity effect of RSS and D-allulose has been already clarified, but that of rare monosaccharides other than D-allulose in RSS has not yet been well understood. Here, we investigated and compared the anti-obesity effect of RSS and MGS in rats. Male Wistar rats were divided into 4 dietary groups: a high-sucrose control diet group (S), a high-fructose corn syrup diet group (HFCS), an RSS diet group (RSS), and an MGS diet group (MGS). RSS significantly suppressed abdominal adipose tissue weight and total body fat accumulation in comparison to sucrose. On the other hand, MGS reduced body weight gain, but not abdominal fat accumulation, relative to sucrose. The weight of the liver and kidneys was significantly higher in the RSS and MGS groups than in the S and HFCS groups, but serum biochemical parameters and hepatic lipids contents were not significantly different among the groups. The present study shows that two types of D-allulose-containing rare sugar sweeteners can suppress body fat accumulation or weight gain in a different manner and that RSS could be used as more effective sweeteners in place of sucrose and HFCS to maintain healthy body weight.

Egg White Hydrolysate Can Be a Low-Allergenic Food Material to Suppress Ectopic Fat Accumulation in Rats Fed an Equicaloric Diet.

Egg white (EW) is known as a nutritional protein but can induce allergic reactions in humans. We investigated the dietary effects of EW and its hydrolysate (EWH), which contains less allergen, on body fat accumulation in Wistar rats fed an equicaloric high-fat and high-sucrose diet for 8 wk (Exp A). The pair-feeding of EW and equicaloric-feeding of EWH increased fecal fat excretion and suppressed lipid accumulation in the liver and muscles but not in the abdominal adipose tissues, carcass, or total body. Dietary EWH also suppressed the serum glucose level and alkaline phosphatase activity. Further, we showed a higher dispersibility of EW and EWH in physicochemical assay (Exp B). Next, we investigated the suppressive effects of a single administration of EW and EWH on lipid-induced hypertriglyceridemia and small intestinal meal transit in ddY mice (Exp C). However, a single administration of EW or EWH did not suppress the lipid-induced hypertriglyceridemia nor did it delay the rate of small intestinal transit. These findings indicated that dietary EW and EWH reduce hepatic and muscular (ectopic) fat accumulation mainly by suppressing fat absorption and supplying fat to the liver and muscles. Therefore, the low-allergenic EWH can be effective for the prevention of high-fat-diet-induced obesity.