We previously found that thiamine mitigates metabolic disorders in spontaneously hypertensive rats, harboring defects in glucose and fatty acid metabolism. Mutation of thiamine transporter gene SLC19A2 is linked to type 2 diabetes mellitus. The current study extends our hypothesis that thiamine intervention may impact metabolic abnormalities in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, exhibiting obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4 wk old) were given free access to water containing either 0.2% or 0% of thiamine for 21 and 51 wk. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, organs weights, histological findings, and hepatic pyruvate dehydrogenase (PDH) activity in the liver were evaluated. Thiamine intervention averted obesity and prevented metabolic disorders in OLETF rats which accompanied mitigation of reduced lipid oxidation and increased hepatic PDH activity. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, sinusoidal fibrosis with formation of basement membranes (called pseudocapillarization) which accompanied significantly reduced expression of laminin β1 and nidogen-1 mRNA, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of the vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats.

View full abstract

Administration of imatinib is the therapy of choice in patients with advanced (inoperable) or metastatic gastrointestinal stromal tumors (GIST). Gastrointestinal toxicity is one of the most common side effects of anticancer therapy, including imatinib. Measurement of intestinal permeability represents a method of noninvasive laboratory assessment of gastrointestinal toxicity. We have measured intestinal permeability (by determining absorption of lactulose, mannitol and xylose), vitamin A absorption and serum alpha-tocopherol in 16 patients with advanced/metastatic GIST treated with imatinib. Lactulose/mannitol and lactulose/xylose ratios as well as parameters of vitamin A absorption did not change significantly during the treatment, but a significant decrease of alpha-tocopherol was observed. We conclude that, in contrast to most other anticancer agents studied so far, imatinib does not have an effect on intestinal permeability. No effect on vitamin A absorption was observed, but serum alpha-tocopherol decreased significantly during the treatment.

View full abstract

Vitamin E supplement and pseudorabies virus (PRV) infection have a reciprocal role in influencing the maternal immune response, a key determinant of the success or failure of pregnancy. However, it remains unknown whether vitamin E supplement provides protection against PRV-induced failure of pregnancy. This study was therefore conducted to investigate the effect of dietary vitamin E level (0, 75, 375, 750 and 1,500 mg/kg) on the reproduction performance, immunity and expression of Toll-like receptors (TLRs) of PRV-challenged mice. The mortality and abortion rate of PRV-challenged mice decreased with the increase in vitamin E consumption. Overall, PBS-injected mice had a higher live embryo number and live litter size than PRV-challenged mice. Both live embryo number and live litter size of PRV-challenged mice increased with increasing vitamin E levels. Vitamin E supplement resulted in decreased concentration of serum IL-2 and IFN-γ, but increased concentration of serum IL-10. The concentration of serum IgG, IgA and IgM increased with increasing vitamin E levels. In the uterine and embryo mRNA abundance of TLR3, TLR7 and TLR9 was higher in PRV-challenged mice than that in PBS-injected mice fed on the same dosage of vitamin E. The mRNA abundance of embryonic TLR3, TLR7 and TLR9 in PRV-challenged mice decreased with increasing vitamin E levels. Collectively, vitamin E supplement may improve reproductive performance of PRV-challenged mice by attenuating PRV-induced negative effects on the cytokine profile, immunoglobulin synthesis and TLR expression.

View full abstract

Quality of life (QOL) encompasses a broad notion of health and is increasingly used to evaluate the effectiveness of health care services. The purpose of this cross-sectional study was to assess health-related quality of life (HR-QOL) in the community-dwelling elderly (mean age, 72.7±0.3 y; female 46.4%, n=179) in Japan and to explore diminished factors. We assessed HR-QOL by the 36-Item Short-Form Health Survey (SF-36), maximum walking speed, step counts, Tokyo Metropolitan Institute of Gerontology (TMIG) index, dietary intake and blood biochemistry. Two summary scores of the SF-36 were calculated (physical component score: PCS, mental component score: MCS). We divided participants into two groups based on the standard values of PCS and MCS classified by age (high and low group), which was further stratified into a high PCS and high MCS (BH) group and a low PCS and low MCS (BL) group. Mean maximum walking speed and daily step counts were 207.7±2.8 cm/s and 7,008±289. Eighty-one percent of the participants had full scores in the TMIG index. Daily intake of energy and protein were 2,081±33 kcal and 74.5±0.9 g. The maximum walking speed, TMIG index, alcohol consumption and chewing ability were significantly higher in the BH group than those in the BL group, but not dietary intake. Stepwise logistic regression analysis indicated that maintaining maximum walking speed might be associated with sustaining HR-QOL in the healthy elderly.

View full abstract

Energy malnutrition worsens survival in patients with liver cirrhosis, and is currently defined as non-protein respiratory quotient (npRQ) <0.85, as measured by indirect calorimetry. However, measurement of this npRQ is limited because of the high cost of indirect calorimetry. Therefore, we sought an alternative marker that can be used in the routine clinical setting. Forty-four inpatients with cirrhosis were recruited in this study. The last meal was served at 18:00 h on the previous day, and indirect calorimetry was performed between 07:00 and 09:00 h while the patients were still in bed. Fasting blood samples were collected in the early morning on the day of the test. Anthropometry was performed by an expert dietician. The correlations among npRQ, Child-Pugh score of disease severity, laboratory parameters, %AC (arm circumference), %TSF (triceps skinfold thickness), and %AMC (arm muscle circumference) were studied using simple linear regression analysis. ROC (Receviver operating characteristic) analysis was used to identify the cut-off values that would best predict npRQ=0.85. npRQ correlated significantly with %AC (r²=0.204, p=0.0021) and %AMC (r²=0.178, p=0.0043) but not with %TSF. npRQ was not significantly correlated with other laboratory or anthropometric measurements. The cut-off value for %AC that showed the largest AUC (area under the curve) by ROC analysis was 95, while that for %AMC was 92. Multiple regression analysis yielded an equation; npRQ=0.0019×(%AC)20.0134×(Child-Pugh score)+0.7791. Patient stratification by %AC=95 or by regression equation-based npRQ=0.85, but not by %AMC=92, produced significant difference in survival curves. %AC and regression equation could represent npRQ to some extent as parameters of energy nutrition in cirrhosis.

View full abstract

To investigate whether preferential fat intake by adult rats could be linked to fat-feeding of rats during the growth period, this paper describes the next two studies. Three groups of 4-wk-old male rats in study 1 received one of three diets: control diet (CTD), low-fat high-carbohydrate diet (LFD), and high-fat low-carbohydrate diet (HFD). After 6 wk (dietary treatment period), 6 rats in each of the groups were sacrificed and the remaining rats were placed on a self-selection regimen of fat-protein diet (FPD) and carbohydrate-protein diet (CPD) for 3 wk (self-selection period). After the dietary treatment period, liver weight and plasma insulin concentration of the LFD group and perirenal fat tissue weight and plasma triacylglycerol and leptin concentrations of the HFD group were higher than those of the CTD group. Although no significant difference in fat energy ratio (F ratio) of combination diets self-selected by the three groups was observed, the F ratios of the combination diets were higher than that of the CTD. After the self-selection period, liver weight and plasma insulin concentration of the LFD group and plasma triacylglycerol concentrations of the HFD group decreased. These data suggested that the dietary selection pattern of the rats was associated with a reduced basal plasma insulin concentration. Three groups of rats in study 2 were placed on a self-selection regimen of the LFD and the HFD after being fed one of three diets (LFD, CTD and HFD) for 6 wk. Although the F ratio of the combination diet consumed by the CTD and the LFD groups was similar to that of the combination diet consumed by rats in study 1, the F ratio of the combination diet consumed by the HFD group was higher than that of other groups. These findings suggest that consumption of the fatty food during the growth period predisposed them to favorably respond to the diet that had become familiar to them in later life.

View full abstract

To investigate the available energy of orally administered [¹⁴C]mannitol via intestinal microbes, [¹⁴C]mannitol (222 kBq, 105 mg) or [¹⁴C]glucose (222 kBq, 105 mg) was administered to conventional rats and antibiotics-treated rats whose intestinal microbes were depleted by drinking water containing antibiotics, respectively. The exhausted CO₂, feces and urine were then separately collected at 2, 4, 6, 8, 10, 12 and 24 h after administration of the test solution. In the conventional rats, 45% of administered radioactivity was recovered as ¹⁴CO₂ in the administration of [¹⁴C]mannitol, while 57% of administered radioactivity was recovered as ¹⁴CO₂ following the administration of [¹⁴C]glucose for 24 h. The time sequence for the ¹⁴CO₂ excretion from [¹⁴C]mannitol was delayed as compared to [¹⁴C]glucose by about 4-6 h (p<0.05). However, when [¹⁴C]mannitol was orally administered to antibiotics-treated rats, only 3% of administered radioactivity was excreted as ¹⁴CO₂ for 24 h. The total radioactivity of the gastrointestinal contents and feces for 24 h after administration was over 70%, much higher than those of the conventional rats (p<0.05). When a half dose (222 kBq, 52.5 mg) of [¹⁴C]mannitol was administered to conventional rats, the recovery as ¹⁴CO₂ for 24 h (%) was significantly higher than that of a regular dose of [¹⁴C]mannitol (105 mg). When cold mannitol (105 mg) was orally administered to the antibiotics-treated rats, about 9% of intact mannitol was excreted in feces within 48 h after administration. However, no intact mannitol was detected in the conventional rats. These results demonstrate that more than 95% of mannitol administered orally is utilized via fermentation by intestinal microbes.

View full abstract

In order to develop a new model of diet research, blood was drawn from 12 adult volunteers for 3 wk on regular diets as controls, and for a subsequent 3 wk supplemented with 18.5 g of freeze-dried tofu (Koya tofu) every day. Triplicate aliquots of 0.06 mL each of whole blood were stimulated ex vivo with phytohemagglutinin (PHA)-P, heat aggregated human IgG (HAG), lipopolysaccharide (LPS), zymosan A, and anti-T cell receptor (TCR) monoclonal antibody to activate specific subsets of leukocytes, then the levels of various inflammatory cytokine mRNA were quantified by real time PCR. Koya tofu significantly (p<0.05) augmented the fold increase of PHA-induced tumor necrosis factor superfamily (TNFSF) 15, IL6, and IL8, HAG-induced TNFSF15 and IL8, LPS-induced IL6 and IL8, zymosan-induced TNFSF15, IL6 and IL8, and TCR-induced TNFSF2 in comparison to the regular diet. Such increase was due to the reduction of baseline mRNA expression, not the enhancement of mRNA induction after specific stimulations. Six (TNFSF15), 4 (IL6), and 3 (IL10) subjects showed significant reduction of baseline mRNA during the Koya tofu diet compared to that of the control diet. Despite large individual-to-individual and day-to-day variation of mRNA, the method employed in this study was sensitive enough to identify statistically significant results as a group as well as on an individual basis, which will be a foundation for tailored diet in the future. The results also indicated that Koya tofu had a power to alter mRNA expression in leukocytes, and TNFSF15, IL6, and IL10 would be biomarkers for soy.

View full abstract

Multiple epidemiological studies have emphasized the intake of dark green leafy vegetables rich in xanthophylls in reducing the risk of developing age-related macular degeneration (AMD). Therefore, the present study was undertaken to quantify the levels of major carotenoids in commonly consumed fruits and vegetables of Indian origin and of xanthophylls in the macula of Indian human donor eyes. Fresh fruits (n=20) and vegetables (n=51) collected from two zones of India were tested for the estimation of xanthophyll, lycopene and β-carotene by using HPLC with Photodiode Array Detection. Lutein and zeaxanthin were quantified from macula and in selected vegetables collected from both southern (SI) and northern (NI) regions of India. Xanthophylls, β-carotene and lycopene were found in many affordable vegetables commonly available for consumption in India. Higher content of lutein and zeaxanthin was confirmed in many economical leafy vegetables and fruits. Surprisingly, the mean macular levels of lutein and zeaxanthin of SI donor eyes (n=13) were found to be significantly (p<0.001) four times less than in NI donor eyes (n=15) and the macular levels of Northern India were comparable with reported levels in western populations. The present study showed considerable levels of xanthophylls in many of the commonly consumed fruit and vegetable sources in both parts of India. However, SI donor eyes showed lower levels as compared to NI donors and this warrants further investigation about the bioavailability of xanthophylls in their blood and food intake. The relevance of these findings with prevalence of AMD in South India needs to be explored.

View full abstract

Oxidized low-density lipoprotein (LDL) is believed to contribute to atherosclerosis in part by being taken up into macrophages via scavenger receptors, thus accounting for foam cells. Balsamic vinegar is made from grapes and generally consumed in the Mediterranean region. In this study, we investigated the preventive effects of balsamic vinegar on LDL oxidation and foam cell formation. Balsamic vinegar had stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging abilities and higher polyphenol concentrations than rice vinegar. Balsamic vinegar dramatically inhibited LDL oxidation by azoradicals and endothelial cell-mediated oxidation in vitro. Further, we assessed the anti-oxidative effect against LDL after balsamic vinegar consumption in human subjects. Balsamic vinegar prolonged the LDL oxidation lag time and decreased lipid peroxide (LPO) and lyso-phosphatidylcholine (LPC) in LDL particles. We next examined the effect of balsamic vinegar on foam cell formation. Oil red O staining showed that balsamic vinegar inhibited oxidized LDL-induced foam cell formation in THP-1 macrophages. The concentrations of intracellular triglycerides and total cholesterols were reduced in the presence of balsamic vinegar. In addition, balsamic vinegar decreased the mRNA and protein expression level of scavenger receptors in THP-1 macrophages. These results showed that balsamic vinegar contained abundant polyphenols and inhibited LDL oxidation and oxidized LDL-induced foam cell formation by decreasing the expression of scavenger receptors.

View full abstract

Free D-amino acids have increasingly attracted attention due to their physiological roles and pathological effects on animals, including humans. In this study, using a chiral high-performance liquid chromatography system, we determined free D-amino acids, particularly D-Ala and D-Glu, in traditional seasonings of four soy sauces, three misos, and four fish sauces that are commonly used in Asian cuisine. Examination of the average contents of the free D-amino acids in all the samples revealed that the content of D-Ala was 3.6 times higher than that of free D-Glu, while the average content of free L-Ala was lower (0.8 times) than that of free L-Glu. The average content of free L-Ala was significantly higher in the soy sauces (53 μmol/g sample) and fish sauces (53 μmol/g sample) than in the misos (14 μmol/g sample), whereas the average content of free D-Ala was almost equal among the soy sauces, misos, and fish sauces (0.25, 0.29, and 0.23 μmol/g sample, respectively). Taken together, neither free D-Ala nor D-Glu content showed a correlation with its free L-form in the samples, suggesting that the D-enantiomers are not necessarily produced by the same factors as those for the L-enantiomers, which originate from raw materials. Thus, factors specific to the production process of the fermented seasonings appear to play a significant role in their enantiomer content.

View full abstract

Oxidative stress plays an important role in the pathogenesis of cardiovascular disease (CVD). Growing evidence suggest that antioxidant vitamins might reduce the risk of disease outcomes by their ability to scavenge free radicals. The aim of the present study was to evaluate the supplementation of vitamins E and C on oxidant and antioxidant status in CVD patients. We conducted a case-control study with vitamin E (400 IU/d) and vitamin C (500 mg/d) supplementation in 40 CVD patients for 2 mo. Antioxidant (enzymatic and non-enzymatic) and oxidant status were analyzed pre and post supplementation. In the initial stage the activity of both enzymatic and non-enzymatic antioxidants were lower, while the malondialdehyde (MDA) level was elevated (p<0.0001). After intervention, a significant increase in superoxide dismutase (SOD) activity (61.7%), glutathione peroxidase (GPx) activity (59.3%), the levels of vitamin E (83.7%), C (145.3%), total antioxidant capacity (TAC) (62.8%) and a significant decrease in MDA (40%) value were observed (p<0.0001). There was a significant negative correlation between MDA and TAC. The results suggest that supplementation with a combination of vitamins E and C reduced lipid peroxidation and strengthened the antioxidant defense system. Hence, there will be beneficial effects on the heart by reducing oxidative stress in CVD patients.

View full abstract

We investigated the effect of Lactobacillus crispatus KT-11 (KT-11) on intestinal immune systems in C3H/HeN mice. The level of intestinal total immunoglobulin (Ig) A was significantly higher in mice given KT-11 than in mice not given KT-11. Gene expression relating to antibody production and innate immune response increased more than 2-fold in the former compared with the later. Moreover, the number of IL-6⁺CD11b⁺ cells was significantly higher in Peyer's patch cells cultured with KT-11 than in those cultured without KT-11, although the number of CD4⁺ cells and the cell ratio of CD4⁺/CD8⁺ were remarkably lower in the culture with KT-11. These results indicate that KT-11 enhances intestinal IgA production and innate immune response in C3H/HeN mice.

View full abstract

This study was performed to evaluate the nutritional value of silkworm pupae (Bombyx mori) and the content of α-glucosidase inhibitor. The percentages of total protein and lipid contents by dry weight were 55.6 and 32.2%, respectively. Silkworm pupae protein had high levels of essential amino acids such as valine, methionine and phenylalanine. The contents of essential amino acids in silkworm pupae protein satisfied the FAO/WHO/UNU suggested requirements (2007). In addition, they also possessed n-3 fatty acids, especially α-linolenic acid (36.3%), as a major component. The 50% ethanol extract of silkworm pupae contained 1-deoxynojirimycin (DNJ), which is a potent α-glucosidase inhibitor. These results suggest that silkworm pupae are a new source of high quality protein, lipid, and α-glucosidase inhibitor.

View full abstract

Biotin is a widely distributed water soluble vitamin. Adequate intake of biotin was set at 50 μg/d in Japan 2010. Recently, the importance of the application of probabilistic techniques to estimate the share of the population at risk of deficient and excessive nutrient intake has been increasingly emphasized for assessing nutrient adequacy. Monte Carlo simulation, a computer-based method of analysis that uses statistical sampling techniques yielding a probabilistic approximation to the solution of a mathematical model, has been used to estimate the probabilistic distribution of the dietary intake of food chemicals. For this study, we used two preliminary models to estimate the dietary biotin intake with food consumption data based on the National Health and Nutrition Survey in Japan. One is evaluated by biotin concentration data from the total diet study; the other is a dataset of biotin concentration in individual foods. After removing outliers from the individual foods dataset, probability density distributions from two models showed analogous mean, median, 5th percentile, and 95th percentile values. The daily biotin intakes from these probabilistic methods showed that more than 80% of the Japanese population had higher than the adequate intake of biotin. However, the contribution of each food group to the total daily biotin intake was somewhat different. Improvement of these methods necessitates the collection of more actual data associated with sample compositional variability and evaluation of uncertainty associated with the food group classification of biotin.

View full abstract