Development of a method for preparing cyclic nigerosylnigerose syrup and investigation of its value as a dietary fiber.

Cyclic nigerosylnigerose (CNN) syrup, containing 76% water-soluble dietary fiber, was prepared from starch on an industrial scale, using isoamylase, 6-α-glucosyltransferase, 3-α-isomaltosyltransferase, and cyclodextrin glucanotransferase. CNN syrup has a unique linkage pattern, consisting mainly of α-1,3 and α-1,6 glucoside linkages, and is characterized by its low weight average molecular weight (807) and moderate sweetness (relative sweetness = 25), unlike in well-known dietary fiber materials. The glass transition temperature of CNN is higher than that of the straight chain structures, maltotetraose and maltosyltrehalose. Even when 40% of normally added sucrose was replaced with CNN syrup, sponge cake puffed up sufficiently. The no observed adverse effect level for a single dose of CNN syrup was 0.88 and 0.89 g dry solid/kg body weight for men and women, respectively. The increase in blood glucose and insulin concentrations during consumption of CNN syrup was lower than that of glucose.

Evaluation of the relative available energy of cyclic nigerosylnigerose using breath hydrogen excretion in healthy humans.

Cyclic nigerosylnigerose (CNN) is a cyclic tetrasaccharide with properties distinct from those of other conventional cyclodextrins. We investigated the relative available energy of CNN in healthy humans. CNN digestibility was determined using brush border membrane vesicles from the small intestines of rats. CNN was not hydrolyzed by rat intestinal enzymes. To investigate breath hydrogen excretion, 13 human subjects were included in a double-blind cross-over, randomized, placebo-controlled study. The effects of CNN on hydrogen excretion were compared with those of a typical nondigestible, fermentable fructooligosaccharide (FOS). In the study participants, hydrogen excretion hardly increased upon CNN and was remarkably lower than for FOS. The available energy value was determined using the fermentability based on breath hydrogen excretion and was evaluated as 0 kcal/g for CNN. CNN was hardly metabolized and hence may be used as a low-energy dietary fiber.

A novel dextrin produced by the enzymatic reaction of 6-α-glucosyltransferase. â ¡. Practical advantages of the novel dextrin as a food modifier.

High-molecular-weight dextrin (WS-1000) was produced from waxy corn starch and enzymatically modified to link glucose by α-1,6 glycosidic bond at the terminal point of the glucose chain, forming MWS-1000. In this study, the physical properties of MWS-1000 were characterized, and the advantages of its use as a food modifier were described. From rheological and calorimetric studies, it was found that MWS-1000 does not undergo retrogradation, but it does not prevent the retrogradation of WS-1000, suggesting that they have no intermolecular interaction in solution. Investigation of the effect of MWS-1000 on the viscoelasticity of gelatinized wheat starch showed that in the linear viscoelastic region, storage modulus decreased and tan δ increased with increase in replaced MWS-1000 content. In addition, it was confirmed that gelatinized starch containing MWS-1000 showed viscoelastic behavior similar to that of commercially available custard cream.

Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers.

BACKGROUND: Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. METHODS: This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. RESULTS: There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. CONCLUSIONS: Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. TRIAL REGISTRATION: UMIN, UMIN000033536 . Registered 27 July 2018.

Inhibitory effect of isomaltodextrin on tyrosine metabolite production in rat gut microbiota.

We examined the effect of isomaltodextrin (IMD), a soluble dietary fiber, on production of putrefactive products by intestinal bacteria using a tyrosine load test to measure phenol production in IMD-treated rats. We observed a significant increase in phenol and p-cresol concentrations in rats administered with only tyrosine, but not for rats co-administered tyrosine and IMD. To elucidate the mechanism of this effect, we analyzed the intestinal microbiota in each group and found that although IMD had no direct effect on the proportion of bacteria known to produce phenols, it did alter the balance of intestinal microbiota. The results suggested that changes in the intestinal microbiota composition reduced the metabolic capacity for tyrosine and in turn suppressed production of phenol or p-cresol, putrefactive products in the intestine.

Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects.

BACKGROUND: Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers. METHODS: In a crossover study, 20 fasted healthy volunteers consumed 25 g trehalose or glucose in 100 mL water. Blood samples were taken frequently over the following 3 h, and blood glucose, insulin, active gastric inhibitory polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) levels were measured. RESULTS: Trehalose ingestion did not evoke rapid increases in blood glucose levels, and had a lower stimulatory potency of insulin and active GIP secretion compared with glucose ingestion. Conversely, active GLP-1 showed higher levels from 45 to 180 min after trehalose ingestion as compared with glucose ingestion. Specifically, active GIP secretion, which induces fat accumulation, was markedly lower after trehalose ingestion. CONCLUSIONS: Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

Erratum: Attenuation of postprandial blood glucose in humans consuming isomaltodextrin: carbohydrate loading studies.

[This corrects the article DOI: 10.1080/16546628.2017.1325306.].

Biochemical characterization of L-carnitine dehydrogenases from Rhizobium sp. and Xanthomonas translucens.

Recently, we obtained two L-carnitine dehydrogenases (CDHs) from soil isolates, Rhizobium sp. (Rs-CDH) and Xanthomonas translucens (Xt-CDH). The respective molecular masses of Rs-CDH and Xt-CDH were approximately 50 kDa and 37 kDa. In this study, the genes encoding both enzymes were cloned. Their primary structures exhibited high identities with those of 3-hydroxyacyl-CoA dehydrogenases. In addition, Rs-CDH had a 180-residue long extra sequence in its C-terminal region. Except for the initial 20 residues, the extra sequence exhibited similarity to thioesterase. The activity of Rs-CDH was affected only slightly by deletion of thioesterase domain, but it was eliminated by the deletion of the whole C-terminal extra sequence. A further deletion experiment indicated that the region of Ala330-Pro335 of Rs-CDH has important functions in catalytic activity. Moreover, based on the deletion experiment on Xt-CDH, the five-residue tail is considered to have a function similar to Ala330-Pro335 of Rs-CDH.

Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice.

BACKGROUND: Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. METHODS: Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis. RESULTS: Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cells in vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce adipocyte hypertrophy. CONCLUSIONS: The suppression of adipocyte hypertrophy in the presence and absence of trehalase indicates that trehalose mediates effects prior to being hydrolyzed into glucose. In both trehalase KO and WT mice, trehalose treatment increased the rate of CLDs in jejunal epithelium, reduced chylomicron migration from the intestinal epithelium to the periphery, and suppressed adipocyte hypertrophy. Thus, trehalose ingestion could prevent metabolic syndrome by trapping fat droplets in the intestinal epithelium and suppressing rapid increases in chylomicrons.

Anti-Inflammatory Activity of Isomaltodextrin in a C57BL/6NCrl Mouse Model with Lipopolysaccharide-Induced Low-Grade Chronic Inflammation.

：The purpose of this study was to identify the anti-inflammatory activity and mechanism of isomaltodextrin (IMD) in a C57BL/6NCrl mouse model with lipopolysaccharide (LPS)-induced systemic low-grade chronic inflammation and the effect on inflammation-induced potential risk of metabolic disorders. Pre-treatment of IMD decreased the production of pro-inflammatory mediators, TNF-α and MCP-1, and stimulated the production of the anti-inflammatory mediator, adiponectin by increasing the protein expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in the white adipose tissues. IMD administration reduced plasma concentrations of endotoxin, decreased macrophage infiltration into adipocytes, and increased expression of mucin 2, mucin 4, and the tight junction protein claudin 4. These results suggest that IMD administration exerted an anti-inflammatory effect on mice with LPS-induced inflammation, potentially by decreasing circulating endotoxin, suppressing pro-inflammatory mediators and macrophage infiltration, or by improving mucus or tight junction integrity. IMD exerted protein expression of insulin receptor subset-1 (IRS-1). IMD alleviated the disturbance of gut microflora in LPS-treated mice, as the number of B. bifidum, L. casei, and B. fragilis increased, and E. coli and C. difficile decreased, when compared to LPS-treated mice. The analysis of short chain fatty acids (SCFAs) further supported that the concentrations of acetic and butyric acids were positively correlated with IMD, as well as the number of beneficial bacteria. This study provides evidence that IMD possesses anti-inflammatory properties and exerts beneficial functions to prevent systemic low-grade chronic inflammation and reduces the risk of developing insulin resistance and associated metabolic diseases.

Prophylactic effects of isomaltodextrin in a Balb/c mouse model of egg allergy.

The aim of this study was to evaluate the potential effects of isomaltodextrin (IMD), a dietary saccharide polymer derived from enzymatically produced from starch, on the ability to alter immune response (IR) bias to hen egg ovalbumin (Ova) induced allergic inflammation in mice. Groups of Balb/c mice were pre-treated with various doses of IMD in drinking water (1.0, 2.5, and 5.0% w/v) for 6 weeks and subsequently sensitized to the Ova together with continuous administration of IMD. To evaluate changes in immune response bias, immunoglobulin isotype-associated antibody activity, concentrations of type 1 and 2 cytokines and the percentage of T-regulatory cells (T-regs) in blood were measured. Clinical signs of allergy were assessed after oral challenge with Ova. Treatment with IMD did not significantly alter the frequency of clinical signs, however there was a trend in the overall reduction of clinical signs. Effect on IR bias was observed in the treatment groups as reflected by reduction in a type 1-biased phenotype as evident by decrease in isotype-specific IgE, IgG and increase in IL-12 cytokine production and a high proportion of T-regs. This study revealed that IMD could be a useful prophylactic candidate for alteration of allergic IR bias in mice and an immune-stimulator for reducing egg induced allergic reactions.

Continuous intake of Trehalose induces white adipose tissue Browning and Enhances energy metabolism.

BACKGROUND: Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. METHODS: Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. RESULTS: Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. CONCLUSIONS: Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.

Effects of isomaltodextrin in postprandial lipid kinetics: Rat study and human randomized crossover study.

Isomaltodextrin (IMD) is a novel dietary fiber-like polysaccharide: a type of α-glucan produced from starch using enzymes derived from microorganisms. The results of cohort studies show that dietary fiber can prevent cardiovascular disorders caused by lifestyle-related diseases such as metabolic syndrome. Inhibition of excess fat absorption by dietary fiber is known to be one of the mechanisms, and it is also known that the actions of dietary fiber vary depending on factors such as its structure or origin. Thus, we investigated the inhibitory actions of IMD on fat absorption, and analyzed its mechanism of action. In rats, the absorption of fat given by gavage was significantly lower at 1, 2, and 6 hours after IMD administration than after vehicle administration. In humans, IMD was associated with a lesser increase in blood triglycerides in subjects whose blood triglycerides were otherwise apt to rise. We also found by in vitro emulsion studies that IMD, which had no effect on digestive enzyme activity or emulsion formation, stabilized the micro size micelle by inducing enlarged micelle particle size and increased zeta potential. In conclusion, the mechanism of inhibition of fat absorption by IMD may be a delay in micelle particles accessing the intestinal epithelium through changes in the surface structure and the physical properties of the micelle particles.

Intervention of Isomaltodextrin Mitigates Intestinal Inflammation in a Dextran Sodium Sulfate-Induced Mouse Model of Colitis via Inhibition of Toll-like Receptor-4.

Isomaltodextrin (IMD), a highly branched α-glucan, is a type of resistant starch. Earlier studies have indicated that polysaccharides could prevent inflammation and can be effective in reducing the complications of chronic gastrointestinal diseases such as inflammatory bowel disease (IBD). Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of IMD in dextran sodium sulfate (DSS)-induced colitis in a mouse model. IMD (0.5, 1.0, 2.5, and 5.0% (w/v)) was given orally for 23 days to female Balb/c mice, and then 5% DSS was administered to induce colitis (from day 15 onward to the end of the trial). IMD could not prevent DSS-induced weight loss or colon shortening. However, IMD could reduce inflammatory cytokines, TNF-α and IL-6, in the colon. Gene expression indicated the tendency of IMD to suppress pro-inflammatory cytokines IL-1ß, MCP-1, and IL-17 and to increase an anti-inflammatory cytokine, IL-10. Further study revealed that the anti-inflammatory action of IMD mediates through inhibition of the expression of Toll-like receptor-4.

Attenuation of postprandial blood glucose in humans consuming isomaltodextrin: carbohydrate loading studies.

Background: Isomaltodextrin (IMD) is a novel highly branched α-glucan and its function as a soluble dietary fiber is expected. Objective: The goal of this study was to evaluate the effects of IMD on postprandial glucose excursions in healthy people and to make the mechanism clear. Design: Twenty-nine subjects ingested a solution containing maltodextrin (MD) or sucrose with or without IMD. Fourteen subjects ingested a solution containing glucose with or without IMD. Blood glucose concentrations were then compared between the groups. Furthermore, in vitro digestion, inhibition of digestive enzymes, and glucose absorption tests were conducted. Results: IMD attenuated blood glucose elevation in the subjects with blood glucose excursions at the high end of normal following the ingestion of MD or sucrose or glucose alone. This effect of 5 g IMD was most clear. IMD was digested partially only by small intestinal mucosal enzymes, and maltase and isomaltase activities were weakly inhibited. Furthermore, IMD inhibited the transport of glucose from mucosal side to serosal side. Conclusions: IMD attenuated postprandial blood glucose, after the ingestion of MD or sucrose or glucose. As one of the mechanism, it was suggested that IMD inhibited the absorption of glucose on small intestinal mucosal membrane.

Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl hesperidin.

Our previous study has shown that a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), preferentially lowers serum triglyceride (TG) level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein (VLDL) metabolic abnormality. G-Hesperidin has also been found to decrease an elevated serum apolipoprotein B (apo B) level in the hypertriglyceridemic subjects, suggesting a possibility that this compound suppresses excess VLDL secretion in the liver. In the present study, to gain a better understanding of possible mechanisms by which G-hesperidin lowers serum TG, we examined whether this derivative affects apo B secretion from HepG2 human hepatoma cells, a model of hepatic VLDL secretion. As a result, G-hesperidin significantly reduced apo B secretion from the oleate-stimulated HepG2 cells. Furthermore, G-hesperidin significantly suppressed apo B secretion only in the oleate-stimulated cells and failed to act on the cells incubated without oleate. In the oleate-stimulated cells, G-hesperidin significantly decreased cellular cholesteryl ester (CE), although it had no effect on cellular TG or free cholesterol amounts. Moreover, the oleate-stimulated cells had a decrease in cellular apo B amounts by G-hesperidin exposure. These findings indicate that G-hesperidin down-regulates the assembly of apo B-containing lipoproteins via the reduction of CE synthesis augmented with oleate and results in suppressing excess apo B secretion from the cells. This effect is speculated to be associated with the improvement of VLDL metabolic abnormality in hypertriglyceridemic subjects and considered as a mechanism of lowering serum TG.

Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice.

Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation, and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH.

Daily Intake of Trehalose Is Effective in the Prevention of Lifestyle-Related Diseases in Individuals with Risk Factors for Metabolic Syndrome.

We previously performed animal studies that suggested that trehalose potentially prevents the development of metabolic syndrome in humans. To evaluate this possibility, we examined whether trehalose suppressed the progression of insulin resistance in a placebo-controlled, double-blind trial in 34 subjects with a body mass index (BMI) ≥23. The subjects were divided into two groups and were assigned to ingest either 10 g/d of trehalose or sucrose with meals for 12 wk. During the study, body composition and blood biochemical parameters were measured at week 0, 8, and 12. These parameters were also measured 4 wk after the end of intake to confirm the washout of test substances. In the trehalose group, blood glucose concentrations after a 2-h oral glucose tolerance test significantly decreased following 12 wk of intake in comparison with baseline values (0 wk). When a stratified analysis was performed in the subjects whose percentage of truncal fat approached the high end of the normal range, the change in body weight, waist circumference, and systolic blood pressure were significantly lower in the trehalose group than in the sucrose group. Our data indicated that a daily intake of 10 g of trehalose improved glucose tolerance and progress to insulin resistance. Furthermore, these results suggested that trehalose can potentially reduce the development of metabolic syndrome and associated lifestyle-related diseases, such as type 2 diabetes.

Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality.

To examine the serum triglyceride (TG)-lowering effect of a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), and its mechanisms, we carried out a G-hesperidin administration test in hypertriglyceridemic subjects. G-Hesperidin was administered to the subjects at 500 mg/d for 24 wk. In this study, the subjects were classified into high-TG type (TG > 150 mg/dL), borderline-TG type (TG 110-150 mg/dL) and normal-TG type (TG < 110 mg/dL) on the basis of their initial serum TG values. Among these phenotypes, serum TG level significantly decreased in the high-TG type during the G-hesperidin administration period. It was also observed that elevated values of serum remnant-like particle cholesterol (RLP-C), apolipoprotein (apo) B, apo C-II, apo C-III and apo E occurred in the high-TG type and that these serum levels were significantly reduced by G-hesperidin administration. Moreover, polyacrylamide gel electrophoresis analysis of serum lipoproteins revealed that the very low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) ratio and LDL migration index of the high-TG type were remarkably higher than those of the other phenotypes but that their high values were significantly reduced by the administration. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the improvement of VLDL metabolic abnormality, leading to the reduction of small dense LDL.