d-Allulose enhances postprandial fat oxidation in healthy humans.

OBJECTIVE: d-Allulose, a C-3 epimer of d-fructose, has been reported to decrease body weight and adipose tissue weight in animal studies and is expected to be a potent antiobese sweetener. Our animal study suggested that one of the mechanisms of d-allulose's antiobesity function is an increase in energy expenditure. However, a few studies have thus far explored the underlying mechanism in humans. The aim of this study was to examine the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy participants. METHODS: Thirteen healthy men and women (mean age of 35.7 ± 2.1 y and body mass index 20.9 ± 0.7 kg/m2) were studied. The study was a randomized, single-blind crossover design with a 1-wk washout period. At 30 min after taking 5 g of d-allulose or 10 mg of aspartame without any sugar as a control, overnight-fasted participants ingested a standardized meal, and energy metabolism was evaluated by a breath-by-breath method. During the experiment, blood was collected and biochemical parameters such as plasma glucose were analyzed. RESULTS: In the d-allulose-treated group, the area under the curve of fat oxidation was significantly higher than in the control group (10.5 ± 0.4 versus 9.6 ± 0.3 kJ·4 h·kg-1 body weight [BW]; P < 0.05), whereas that of carbohydrate oxidation was significantly lower (8.1 ± 0.5 versus 9.2 ± 0.5 kJ·4 h·kg-1 BW; P < 0.05). Furthermore, plasma glucose levels were significantly lower, and free fatty acid levels were significantly higher in the d-allulose group than in the control group. No other parameters such as insulin, total cholesterol, or triacylglycerol were modified. CONCLUSION: d-Allulose enhances postprandial fat oxidation in healthy humans, indicating that it could be a novel sweetener to control and maintain healthy body weight, probably through enhanced energy metabolism.

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.

Growth inhibitory effect of D-arabinose against the nematode Caenorhabditis elegans: Discovery of a novel bioactive monosaccharide.

Biological activities of unusual monosaccharides (rare sugars) have largely remained unstudied until recently. We compared the growth inhibitory effects of aldohexose stereoisomers against the animal model Caenorhabditis elegans cultured in monoxenic conditions with Escherichia coli as food. Among these stereoisomers, the rare sugar D-arabinose (D-Ara) showed particularly strong growth inhibition. The IC50 value for D-Ara was estimated to be 7.5 mM, which surpassed that of the potent glycolytic inhibitor 2-deoxy-D-glucose (19.5 mM) used as a positive control. The inhibitory effect of D-Ara was also observed in animals cultured in axenic conditions using a chemically defined medium; this excluded the possible influence of E. coli. To our knowledge, this is the first report of biological activity of D-Ara. The D-Ara-induced inhibition was recovered by adding either D-ribose or D-fructose, but not D-glucose. These findings suggest that the inhibition could be induced by multiple mechanisms, for example, disturbance of D-ribose and D-fructose metabolism.

[Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females.

Dietary D-sorbose decreases serum insulin levels in growing Sprague-Dawley rats.

D-Sorbose is naturally occurring rare sugar. In this study, we examined the effects of dietary D-sorbose in rats. Four-week-old male Sprague-Dawley rats were fed either an AIN-93G-based control diet or a 3% D-sorbose diet for 28 d. Body weight and body fat accumulation were not different between the two diet groups. Dietary supplementation of D-sorbose lowered the serum insulin level (*p<0.05) significantly compared to the control, although the glucose was not changed. In addition, the relative weight of the cecum increased significantly in the D-sorbose group (**p<0.01). These findings suggest that intake of D-sorbose may improve the glucose metabolism by reducing insulin secretion, and D-sorbose can be used as a food ingredient.

The metabolizable energy of dietary resistant maltodextrin is variable and alters fecal microbiota composition in adult men.

Resistant maltodextrin (RM) is a novel soluble, nonviscous dietary fiber. Its metabolizable energy (ME) and net energy (NE) values derived from nutrient balance studies are unknown, as is the effect of RM on fecal microbiota. A randomized, placebo-controlled, double-blind crossover study was conducted (n = 14 men) to determine the ME and NE of RM and its influence on fecal excretion of macronutrients and microbiota. Participants were assigned to a sequence consisting of 3 treatment periods [24 d each: 0 g/d RM + 50 g/d maltodextrin and 2 amounts of dietary RM (25 g/d RM + 25 g of maltodextrin/d and 50 g/d RM + 0 g/d maltodextrin)] and were provided all the foods they were to consume to maintain their body weight. After an adaptation period, excreta were collected during a 7-d period. After the collection period, 24-h energy expenditure was measured. Fluorescence in situ hybridization, quantitative polymerase chain reaction, and 454 titanium technology-based 16S rRNA sequencing were used to analyze fecal microbiota composition. Fecal amounts of energy (544, 662, 737 kJ/d), nitrogen (1.5, 1.8, 2.1 g/d), RM (0.3, 0.6, 1.2 g/d), and total carbohydrate (11.1, 14.2, 16.2 g/d) increased with increasing dose (0, 25, 50 g) of RM (P < 0.0001). Fat excretion did not differ among treatments. The ME value of RM was 8.2 and 10.4 kJ/g, and the NE value of RM was -8.2 and 2.0 kJ/g for the 25 and 50 g/d RM doses, respectively. Both doses of RM increased fecal wet weight (118, 148, 161 g/d; P < 0.0001) and fecal dry weight (26.5, 32.0, 35.8 g/d; P < 0.0001) compared with the maltodextrin placebo. Total counts of fecal bacteria increased by 12% for the 25 g/d RM dose (P = 0.17) and 18% for the 50 g/d RM dose (P = 0.019). RM intake was associated with statistically significant increases (P < 0.001) in various operational taxonomic units matching closest to ruminococcus, eubacterium, lachnospiraceae, bacteroides, holdemania, and faecalibacterium, implicating RM in their growth in the gut. Our findings provide empirical data important for food labeling regulations related to the energy value of RM and suggest that RM increases fecal bulk by enhancing the excretion of nitrogen and carbohydrate and the growth of specific microbial populations.

Reduction of abdominal fat accumulation in rats by 8-week ingestion of a newly developed sweetener made from high fructose corn syrup.

Many studies have shown that ingestion of high-fructose corn syrup (HFCS) may cause an increase in body weight and abdominal fat. We recently developed a new sweetener containing rare sugars (rare sugar syrup; RSS) by slight isomerization of HFCS. Here, the functional effects of RSS on body weight and abdominal fat, and biochemical parameters in Wistar rats were examined. Rats (n=30) were randomly divided into three groups and maintained for 8-weeks on starch, starch+HFCS (50:50), and starch+RSS (50:50) diets. Rats in the Starch and HFCS groups gained significantly more body weight and abdominal fat than the RSS group. Fasting serum insulin in the RSS group was significantly lower than in the Starch and HFCS groups, although serum glucose in the HFCS and RSS groups was significantly lower than that in the Starch group. Thus, the substitution of HFCS with RSS prevents obesity induced by the consumption of HFCS.

Determination of insoluble, soluble, and total dietary fiber (CODEX definition) by enzymatic-gravimetric method and liquid chromatography: collaborative study.

A method for the determination of insoluble (IDF), soluble (SDF), and total dietary fiber (TDF), as defined by the CODEX Alimentarius, was validated in foods. Based upon the principles of AOAC Official Methods 985.29, 991.43, 2001.03, and 2002.02, the method quantitates water-insoluble and water-soluble dietary fiber. This method extends the capabilities of the previously adopted AOAC Official Method 2009.01, Total Dietary Fiber in Foods, Enzymatic-Gravimetric-Liquid Chromatographic Method, applicable to plant material, foods, and food ingredients consistent with CODEX Definition 2009, including naturally occurring, isolated, modified, and synthetic polymers meeting that definition. The method was evaluated through an AOAC/AACC collaborative study. Twenty-two laboratories participated, with 19 laboratories returning valid assay data for 16 test portions (eight blind duplicates) consisting of samples with a range of traditional dietary fiber, resistant starch, and nondigestible oligosaccharides. The dietary fiber content of the eight test pairs ranged from 10.45 to 29.90%. Digestion of samples under the conditions of AOAC 2002.02 followed by the isolation, fractionation, and gravimetric procedures of AOAC 985.29 (and its extensions 991.42 and 993.19) and 991.43 results in quantitation of IDF and soluble dietary fiber that precipitates (SDFP). The filtrate from the quantitation of water-alcohol-insoluble dietary fiber is concentrated, deionized, concentrated again, and analyzed by LC to determine the SDF that remains soluble (SDFS), i.e., all dietary fiber polymers of degree of polymerization = 3 and higher, consisting primarily, but not exclusively, of oligosaccharides. SDF is calculated as the sum of SDFP and SDFS. TDF is calculated as the sum of IDF and SDF. The within-laboratory variability, repeatability SD (Sr), for IDF ranged from 0.13 to 0.71, and the between-laboratory variability, reproducibility SD (SR), for IDF ranged from 0.42 to 2.24. The within-laboratory variability Sr for SDF ranged from 0.28 to 1.03, and the between-laboratory variability SR for SDF ranged from 0.85 to 1.66. The within-laboratory variability Sr for TDF ranged from 0.47 to 1.41, and the between-laboratory variability SR for TDF ranged from 0.95 to 3.14. This is comparable to other official and approved dietary fiber methods, and the method is recommended for adoption as Official First Action.

Improvement effect of resistant maltodextrin in humans with metabolic syndrome by continuous administration.

Resistant maltodextrin (RMD) is a soluble dietary fiber ingredient whose physiological functions are well recognized in Foods for Specified Health Use (FOSHU) for maintaining healthy intestinal regularity, blood glucose levels, and serum lipids. However, its efficacy on combined health risks--metabolic syndrome--was not studied yet. In this study the efficacy of RMD on humans with metabolic syndrome was investigated. A randomized double-blind placebo-controlled parallel-group trial was conducted. Thirty subjects with metabolic syndrome were randomly allocated into 2 groups and took either tea containing 9 g of RMD (treatment group) or placebo tea at three mealtimes daily for 12 wk. Blood was collected and body fat was scanned periodically. In the RMD treatment group, waist circumference, visceral fat area, fasting blood glucose, HOMA-R and serum triacylglycerol (TG) were significantly decreased compared to baseline, and significant time-by-treatment interaction was observed for waist circumference, visceral fat area, HOMA-R and serum TG (p=0.044, p=0.012, p=0.032, and p=0.049, respectively). The change ratio of visceral fat area showed negative statistical correlation with the baseline value (p=0.033), suggesting that efficacy of RMD was emphasized in the subjects having a larger visceral fat area. After the 12-wk RMD treatment, the total number of metabolic syndrome risk factors decreased to 20 from 32 with 2 subjects having no risks, while that of the placebo group decreased to 25 from 32. These findings suggest that continuous ingestion of RMD may improve the risk factors of metabolic syndrome by reducing visceral fat and improving glucose and lipid metabolism.

Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects.

This clinical study was conducted to investigate the safety and effect of D-psicose on postprandial blood glucose levels in adult men and women, including borderline diabetes patients. A randomized double-blind placebo-controlled crossover experiment of single ingestion was conducted on 26 subjects who consumed zero or 5 g of D-psicose in tea with a standard meal. The blood glucose levels at fasting and 30, 60, 90, and 120 min after the meal were compared. The blood glucose level was significantly lower 30 and 60 min after the meal with D-psicose (p<0.01, p<0.05), and a significant decrease was also shown in the area under the curve (p<0.01). The results suggest that D-psicose had an effect to suppress the postprandial blood glucose elevation mainly in borderline diabetes cases. A randomized double-blind placebo-controlled parallel-group experiment of long-term ingestion was conducted on 17 normal subjects who took 5 g of D-psicose or D-glucose with meals three times a day for 12 continuous weeks. Neither any abnormal effects nor clinical problems caused by the continuous ingestion of D-psicose were found.

Determination of total dietary fiber (CODEX definition) by enzymatic-gravimetric method and liquid chromatography: collaborative study.

A method for the determination of total dietary fiber (TDF), as defined by the CODEX Alimentarius, was validated in foods. Based upon the principles of AOAC Official Methods 985.29, 991.43, 2001.03, and 2002.02, the method quantitates high- and low-molecular-weight dietary fiber (HMWDF and LMWDF, respectively). In 2007, McCleary described a method of extended enzymatic digestion at 37 degrees C to simulate human intestinal digestion followed by gravimetric isolation and quantitation of HMWDF and the use of LC to quantitate low-molecular-weight soluble dietary fiber (LMWSDF). The method thus quantitates the complete range of dietary fiber components from resistant starch (by utilizing the digestion conditions of AOAC Method 2002.02) to digestion resistant oligosaccharides (by incorporating the deionization and LC procedures of AOAC Method 2001.03). The method was evaluated through an AOAC collaborative study. Eighteen laboratories participated with 16 laboratories returning valid assay data for 16 test portions (eight blind duplicates) consisting of samples with a range of traditional dietary fiber, resistant starch, and nondigestible oligosaccharides. The dietary fiber content of the eight test pairs ranged from 11.57 to 47.83%. Digestion of samples under the conditions of AOAC Method 2002.02 followed by the isolation and gravimetric procedures of AOAC Methods 985.29 and 991.43 results in quantitation of HMWDF. The filtrate from the quantitation of HMWDF is concentrated, deionized, concentrated again, and analyzed by LC to determine the LMWSDF, i.e., all nondigestible oligosaccharides of degree of polymerization > or =3. TDF is calculated as the sum of HMWDF and LMWSDF. Repeatability standard deviations (Sr) ranged from 0.41 to 1.43, and reproducibility standard deviations (S(R)) ranged from 1.18 to 5.44. These results are comparable to other official dietary fiber methods, and the method is recommended for adoption as Official First Action.

Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans.

Experiments with rats have produced data on the metabolism and energy value of d-psicose; however, no such data have been obtained in humans. The authors assessed the availability of d-psicose absorbed in the small intestine by measuring carbohydrate energy expenditure (CEE) by indirect calorimetry. They measured the urinary excretion rate by quantifying d-psicose in urine for 48 hours. To examine d-psicose fermentation in the large intestine, the authors measured breath hydrogen gas and fermentability using 35 strains of intestinal bacteria. Six healthy subjects participated in the CEE test, and 14 participated in breath hydrogen gas and urine tests. d-Psicose fermentation subsequent to an 8-week adaptation period was also assessed by measuring hydrogen gas in 8 subjects. d-Psicose absorbed in the small intestine was not metabolized into energy, unlike glucose, because CEE did not increase within 3 hours of d-psicose ingestion (0.35 g/kg body weight [BW]). The accumulated d-psicose urinary excretion rates were around 70% for 0.34, 0.17, and 0.08 g/kg BW of ingested d-psicose. Low d-psicose fermentability was observed in intestinal bacteria and breath hydrogen gas tests, in which fructooligosaccharide (0.34, 0.17, and 0.08 g/kg BW) was used as a positive control because its available energy is known to be 8.4 kJ/g. Based on the results of the plot of breath hydrogen concentration vs calories ingested, the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental d-psicose fermentability subsequent to an adaptation period was not observed.

Comprehensive measurement of total nondigestible carbohydrates in foods by enzymatic-gravimetric method and liquid chromatography.

Total nondigestible carbohydrate (NDC) in foods was determined by combining, not modifications, AOAC Official Methods 991.43, 2001.03, and 2002.02. Total NDC included insoluble dietary fiber (IDF) + high-molecular-weight soluble dietary fiber (HMWSDF), nondigestible oligosaccharides (NDO) not precipitated in ethanol solution, and resistant starch (RS). Eight sources of NDC (cellulose, wheat bran, gum arabic, resistant maltodextrin, polydextrose, fructooligosaccharide, galactooligosaccharides, and RS) were incorporated in different combinations into standard formula bread samples. All of the NDC sources and bread samples were analyzed for their (1) IDF + HMWSDF content with corrections for residual RS amount using AOAC Official Method 991.43, (2) NDO by liquid chromatography (LC) in AOAC Official Method 2001.03, and (3) RS by AOAC Official Method 2002.02. The correlation coefficient (R(2)) comparing calculated amounts versus measured amounts of total NDC in 11 bread samples was 0.92. Analysis of commercial food samples was also well matched with the DF + NDO value on their nutritional label. Consequently, we confirmed a single measurement of LC can determine all NDO in foods, and total NDC in foods can be determined by unifying existing AOAC Official Methods.

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.

Suppressive effect of resistant maltodextrin on postprandial blood triacylglycerol elevation.

BACKGROUND: As the physiological functions of soluble dietary fibre, the favourable efficacy, such as attenuating the absorption of saccharides or lipids, is expected. Resistant maltodextrin, a soluble dietary fibre, was investigated and found that it delays the glucose absorption and attenuates the postprandial rise in the blood glucose levels, however, the efficacy of resistant maltodextrin on lipid metabolism is not yet reported. AIM OF THE STUDY: We conducted an animal experiment and a human experiment to investigate the effect of resistant maltodextrin on postprandial blood triacylglycerol elevation. METHODS: 1. Rats were fed corn oil with or without resistant maltodextrin and the postprandial changes in triacylglycerol were examined. 2. We then conducted a dietary loading experiment on 13 healthy adult male and female subjects using a meal containing approximately 50 g fat. A beverage not containing resistant maltodextrin was used as a placebo; subjects consumed the loading meal and a beverage containing either 5 g or 10 g resistant maltodextrin; blood was periodically collected to see the changes in serum constituents. RESULTS: 1. The corn oil administration experiment using rats showed that resistant maltodextrin dose-dependently suppressed elevation of blood triacylglycerol levels after corn oil administration. 2. The dietary loading experiment on 13 healthy subjects with 5 or 10 g of resistant maltodextrin showed that; in each administration group, resistant maltodextrin significantly suppressed postprandial elevation of blood triacylglycerol, RLP-cholesterol and insulin. CONCLUSION: These results indicate that resistant maltodextrin ingested with fatty meals suppresses the postprandial elevation of blood triacylglycerol levels.

Determination of total dietary fiber in selected foods containing resistant maltodextrin by enzymatic-gravimetric method and liquid chromatography: collaborative study.

A method was developed for determination of total dietary fiber (TDF) in foods containing resistant maltodextrin (RMD) which includes nondigestible carbohydrates that are not fully recovered as dietary fiber by conventional TDF methods such as AOAC 985.29 or 991.43. Because the average molecular weight (MW) of RMD is 2000 daltons, lower MW soluble dietary fiber components do not precipitate in 78% ethanol; therefore, RMD is not completely quantitated as dietary fiber by current AOAC methods. The accuracy and precision of the method was evaluated through an AOAC collaborative study. Ten laboratories participated and assayed 12 test portions (6 blind duplicates) containing RMD. The 6 test pairs ranged from 1.5 to 100% RMD. The method consisted of the following steps: (1) The insoluble dietary fiber (IDF) and high MW soluble dietary fiber (HMWSDF) were determined by AOAC 985.29. (2) Ion exchange resins were used to remove salts and proteins contained in the AOAC 985.29 filtrates (including ethanol and acetone). (3) The amount of low MWRMD (LMWRMD) in the filtrates were determined by liquid chromatography. (4) The TDF was calculated by summation of the IDF, HMWSDF, and LMWRMD fractions having nondigestible carbohydrates with a degree of polymerization of 3 and higher. Repeatability standard deviations (RSDr) were 1.33-7.46%, calculated by including outliers, and 1.33-6.10%, calculated by not including outliers. Reproducibility standard deviations (RSDR) were 2.48-9.39%, calculated by including outliers, and 1.79-9.39%, calculated by not including outliers. This method is recommended for adoption as Official First Action.