Hyperhomocysteinemia causes various diseases including cardiovascular disease, osteoporotic fracture and dementia. Although there have been reports that hyperhomocysteinemia decreases physical performance, findings are inconsistent on the association of homocysteine, folate, vitamin B₁₂ and physical performance. Considering that lower physical performance increases the risk of fall and fracture in the elderly, the effect of nutritional status on physical function must be clarified. This is a cross-sectional study conducted from April 2015 to November 2016. Eighty-six residents and users in five care facilities were evaluated for their blood homocysteine, folate and vitamin B₁₂ concentrations and indices for physical performance; lower limb muscle strength, handgrip strength and gait speed. Analyses of physical performance were done in women only, considering the high proportion of women in the study population and the muscular gender difference. In the third tertile of plasma homocysteine concentration, handgrip strength was significantly lower than in the first tertile (p=0.027). In the first tertile of serum folate concentration, handgrip strength was significantly lower than in the third tertile (p=0.002). Although not statistically significant, lower limb muscle strength in the third tertile of folate was higher than in the first (p=0.061) and second (p=0.057) tertile. In the multiple regression analysis, however, only serum folate concentration was a significant contributor except for age. In subjects with their serum folate and vitamin B₁₂ concentrations both exceeding the median, lower limb muscle strength was higher. Low serum folate concentration is a risk factor for lower physical performance independent of homocysteine in elderly women.

The present study was conducted to assess the effect of all-trans retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were excised from the knees of healthy adult Wistar female rats under sterile conditions. We first investigated the synoviums incubated in a control medium or in a medium containing 10 μg/mL LPS, each for 24, 48, and 72 h (LPS-experiment). The changes in inflammatory response from the synoviums were observed at different culture times. Then, we assessed the synoviums exposed to different ATRA concentrations for 24 h (ATRA-experiment). The controls (blank, model group, and solvent groups) were set up. The effects of ATRA on synovitis were evaluated by measuring the production of cytokines, and nitric oxide (NO) and the expression of cartilage damage related proteases. In the LPS-experiment, LPS contributed to the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) in synovial explants. Importantly, LPS did not cause a significant pathological damage. The inflammatory response observed in this model was significant for 24 h, suggesting that LPS-induced synovial explants were successfully established. In the ATRA-experiment, ATRA suppressed the expression of IL-6, TNF-α, NO, a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4), MMP-3, and MMP-9. Taken together, ATRA exhibited inhibitory effects on LPS-induced synovial immune inflammatory response stimulated by the regulation of inflammatory mediators and cartilage damage related proteases in synovial explants, demonstrating a potential protective effect on synovitis and joint destruction in the patients with RA.

Citrus fruits have several potential benefits for maintaining our health. In this study, we investigated the anti-obesity effects of immature Citrus tumida hort. ex Tanaka (C. tumida) peels using an acute obesity mice model. C57BL/6J male mice were divided into 2 groups; HFD-LL subjected to a high fat diet (HFD) and constant light exposure (LL), and HFDC-LL subjected to a HFD containing immature peel powder of C. tumida (5% w/w) and LL. Dietary ingestion of immature C. tumida peels significantly suppressed body weight gain following decreased epidydimal, perirenal, and subcutaneous fat weights. Blood levels of triglyceride and total cholesterol in the HFDC-LL were significantly lower than those in the HFD-LL group; however, there was no significant difference in food or calorie intake between the 2 groups. These results suggested that immature C. tumida peels have a beneficial effect on the prevention of obesity and metabolic syndrome via its biochemical activities of lipid metabolism.

Parenteral nutrition-associated liver disease, a common and life-threating complication among people who require long-term parenteral nutrition, has been associated with abnormal liver function, cholestasis, steatosis and fibrosis. Intravenous soybean lipids may be associated with the development of liver disease. We therefore examined whether different doses of parenteral lipids would affect the development of liver disease, and further investigated the possible pathogenesis of it. C57BL/6J mice with a central catheter placed in the right jugular vein were divided into three groups. The control group received normal mouse chow with intravenous normal saline; The lipids group received parenteral nutrition solution (0.14 g lipids per day); the H-lipids group received parenteral nutrition solution with twice the amount of lipids (0.3 g lipids per day). Changes in body weight, serum biochemical parameters, liver histology and farnesoid X receptor gene expression in the liver were assessed. The values of serum direct bilirubin, total bilirubin and cholesterol were markedly increased in the H-lipids group at day 7. The predominant histologic finding in the H-lipids group was steatosis, and the steatosis score in the H-lipids group was much higher than in the other two groups at either day 5 or day 7. Hepatic expression of farnesoid X receptor mRNA decreased after 7 d of parenteral nutrition. High doses of parenteral lipids are more likely to develop liver disease in a mouse model of parenteral nutrition. Farnesoid X receptor may play a key role in the development of parenteral nutrition-associated liver disease.

Crohn’s disease is a type of inflammatory bowel disease of unknown etiology. Administration of indomethacin (Indo) to rats induces acute mucosal lesions similar to those observed in Crohn’s disease patients, but the damage can be prevented by feeding the animals an elemental diet (ED). In this study, we examined changes in intestinal macroscopic appearance, permeability, and immunoglobulin production after administration of Indo to male Sprague-Dawley rats fed normal lab chow or an ED. Intestinal damage was induced by subcutaneous injection of Indo on two successive days. Mucosal permeability, as measured by urinary excretion of phenolsulfonphthalein, peaked on day 2 after Indo injection, whereas the most severe intestinal damage, as scored by macroscopic inflammatory changes, was observed on day 3. Flow cytometric analysis of mesenteric lymph node cells revealed that the proportion of CD45RA⁺ cells was increased after Indo treatment. Furthermore, in vitro-cultured mesenteric lymph node and spleen lymphocytes from Indo-treated rats produced higher levels of IgA and IgG than did cells from vehicle-treated rats. In contrast, IgG and albumin concentrations in plasma were significantly decreased by Indo administration. Notably, none of the Indo-induced changes was observed in ED-fed rats. These findings suggest that an ED may prevent the appearance of Indo-induced mucosal lesions, at least in part, by modulating intestinal permeability and antibody production.

Functional constipation negatively affects school-related quality of life for children and adolescents. We investigated the association between functional constipation, defined according to the Rome criteria version III, and dietary habits. The subjects of this cross-sectional study were 1,140 5th graders and 1,054 8th graders attending schools in Shunan City, Japan in 2012. Functional constipation was defined as having two or more symptoms of constipation. Dietary habits were assessed using a brief questionnaire. Self-reported biological, demographic and lifestyle information was obtained. Using multiple logistic models, dose-dependent associations among subgroups stratified with quintiles of nutrient and food intake were examined. The prevalence of functional constipation ranged from 3.7% to 8.3% across the grades. The most prevalent symptom was pain or hard stools. There was a link between higher rates of functional constipation and lower levels of dietary fiber intake, vegetables, and fruits (p_trend=0.010-0.030). Associations with vegetables and fruits attenuated when controlling for dietary fiber intake (p_trend=0.074-0.150). When 5th and 8th graders were separately analyzed, intake of dietary fiber, water from foods, and vegetables had beneficial effects on functional constipation in 8th graders (p_trend=0.005-0.038), and fruit intake had a beneficial effect in 5th graders (p_trend=0.012). Modification of dietary habits may have a positive effect in reducing functional constipation in school-age children. Diets rich in fiber, vegetables, and fruits, have the potential to improve functional constipation in Japanese children and adolescents.

Ingestion of a high-fat (HF) diet is known to enhance bile acid (BA) secretion, but precise information about the BA molecular species is lacking, especially information on the conjugated BAs in enterohepatic circulation. As cholesterol is the precursor of BAs, we analyzed alterations of the entire BA metabolic pathway in response to a HF diet without the addition of cholesterol and BA in the diet. Additionally, we evaluated the relationships between BA metabolism and some disorders, such as plasma transaminase activities and glucose intolerance induced by the HF diet. Acclimated WKAH/HkmSlc male rats (3 wk old) were divided into two groups fed a control or the HF diet for 22 wk. Fasting blood glucose was measured during the experimental period, and an intraperitoneal glucose tolerance test was performed at week 21. As a result, ingestion of the HF diet selectively increased the concentration of taurocholic acid in the bile and small intestinal contents as well as deoxycholic acid in the large intestinal contents and feces. These results indicated a selective increase of 12α-hydroxylated BA concentrations in response to the HF diet. Moreover, fecal 12α-hydroxylated BA concentration was positively correlated with cumulative energy intake, visceral adipose tissue weight, and glucose intolerance. The present study suggests that fecal 12α-hydroxylated BA is a non-invasive marker that can detect the early phase of glucose intolerance.

Chinese diet pattern known as plant-based is more linked with seasonal supply, but it is lack of study on seasonal difference in dietary intakes in China. Our study was to assess seasonal variation in the absolute dietary intake among general population in a metropolis, Shanghai, China. A representative sample of general population aged 15 and older (n=1,704) were randomly stratified-sampled from communities in Shanghai. Dietary survey included consecutive 3-day-24-hour diet record recall and household condiments weighing. Data was collected across four seasons during 2012-2014. Most of food and condiments consumption differed across seasons in Shanghai. Intakes of grains, legumes and cooking oil were highest in spring; vegetables, fruit and non-alcoholic beverage highest, but cooking oil and cooking salt lowest in summer; red meat, nuts and cooking salt highest in winter. Seasonality existed in the intakes of energy and energy contributed from macronutrients that fat contributed more in winter but less in summer. Seasonal variations were also found in beta-carotene, vitamin E, vitamin K, thiamin, folate and sodium intakes. Seasonal changes of dietary intake were extensively observed in Shanghai, a highly-developed metropolis in China. Given the seasonal differences and their features described in current article, the estimation methods of the average dietary intake across whole year by just conducting dietary survey in one single season warrants further study.

Diabetes mellitus (DM) has been increasing rapidly in Vietnam. We hypothesized that the main reason may be low fiber intake. Regarding sources, fiber comes mainly from vegetables. However, vegetables popular in Vietnam have low fiber (<2 g fiber/100 g vegetable), so it is difficult to supply sufficient fiber only from vegetables. Therefore, in this study we tried to increase fiber intake a day by using 60 g of Okara foods, containing about 6 g of fiber per day, and assess the effects on the blood glucose levels of DM patients. We contacted 300 type 2 DM outpatients at a hospital and selected 60 of them. We formed 30 pairs matched by gender, age, BMI and years with DM and divided them randomly into an intervention group and a control group. The intervention group consumed about 6 g of fiber from Okara per day for 2 wk. At the baseline and final periods, anthropometric measurements, blood withdrawal and a 3-d weighing method nutrition survey were conducted. Dietary fiber intake increased from 6.9 to 12.6 g (p<0.01) in the intervention group, but there was no change in the control group. Fasting blood glucose and fructosamine in the intervention group dropped from 6.3 to 5.4 mmol/L (p<0.05) and from 319 to 301 μmol/L (p<0.05), respectively but they remained unchanged in the control group. Vietnamese people consumed about 60 g of Okara per day from various menus and increased fiber intake to 6 g/d in 2 wk, which improved blood glucose in DM patients.

Cerebral ischemia/reperfusion leads to delayed neuronal cell death, resulting in brain damage. Auraptene (AUR) and naringin (NGIN), which exert neuroprotective effects in ischemic brain, are abundant in the peel of Citrus kawachiensis. Although parts of AUR/NGIN are transited from the peel to the juice during the squeezing of this fruit, these amounts in juice might be too low to exert effects. We thus prepared the AUR/NGIN-rich fruit juice of C. kawachiensis by addition of peel paste to the raw juice. The present study revealed that orally administration of the dried powder of this AUR/NGIN-rich fruit juice (2.5 g/kg/d) for 7 d to ischemic mice significantly suppressed the ischemia-induced neuronal cell death in the hippocampus, which was coincidently with the reduction of hyperactivation of microglia and astrocytes. These results suggest that AUR/NGIN-rich juice of C. kawachiensis may possess therapeutic potential for the prevention of neurodegenerative diseases via inhibition of inflammatory processes.

This meta-analysis aimed to explore the association between anthocyanins intake and the risk of gastric cancer. All the relative articles have been searched in the online databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library until June 11th, 2018. Risk ratios (RRs) or odds ratio (ORs) and their 95% confidence intervals were calculated and pooled through the STATA 12.0. A total of 6 studies were finally selected in the meta-analysis. No significant association was found between total anthocyanins consumption and gastric cancer risk (RR=0.92, 95%CI: 0.81-1.04). Likewise, there was also no significant evidence of the relationship between anthocyanins intake and gastric cancer in tumor site (cardia: RR=0.90, 95%CI: 0.62-1.31; noncardia: RR=0.86, 95%CI: 0.69-1.07) and gender (men: RR=1.02, 95%CI: 0.73-1.40; women: RR=0.80, 95%CI: 0.52-1.23). The dose-response relationship was also not found in this meta-analysis. The Grades of Recommendations Assessment, Development and Evaluation (GRADE) quality in our study was very low. The results of our meta-analysis suggested the intake of anthocyanins had no association with the risk of gastric cancer and further studies are needed.

Curcumin is known to have potent anti-inflammatory effects. We have reported that acute curcumin ingestion attenuates eccentric exercise-induced muscle damage. This study aimed to examine the effect of curcumin ingestion timing (before or after exercise) on the changes in muscle damage markers after eccentric exercise. In this randomized, single-blind, parallel design study, 24 healthy young men performed 30 maximal isokinetic (120º/s) eccentric contractions of the elbow flexors using an isokinetic dynamometer. Subjects were randomly assigned to ingest 180 mg/d of oral curcumin either 7 d before (PRE) or 4 d after exercise (POST) or 180 mg/d of oral placebo 4 d after exercise (CON). The maximal voluntary contraction (MVC) torque of the elbow flexors, elbow joint range of motion (ROM), muscle soreness, and serum creatine kinase (CK) activity were measured before, immediately after, and 1-4 d after exercise. Changes in these variables were compared over time. In the POST group, ROM were higher at 3-4 d and muscle soreness was lower at 3 d after exercise compared with the CON group (p<0.05). However, in the PRE group, there were no significant differences compared with the CON group in changes in ROM and muscle soreness. Meanwhile, there were no significant differences among the groups in terms of changes in MVC torque and serum CK activity. Our results suggest that curcumin ingestion after exercise had a more beneficial effect in attenuating muscle soreness.

Roasted barley extract (RBE) is a traditional Japanese beverage. Previously, we reported the effects of RBE containing cyclo(d-Phe-l-Pro) on blood flow in animals and humans and investigated rapid skin temperature recovery from cold-water immersion in women. The present randomized, double-blind study investigated the effects of RBE containing cyclo(d-Phe-l-Pro) on men’s and women’s skin temperature in excessively air-cooled conditions. Participants felt cold in the test room (25.5±0.5ºC). They ingested an RBE or placebo beverage and remained in the air-conditioned room for 100 min. Skin temperature of the left foot was measured every 5 min using infrared thermography. We evaluated effect of RBE administration by paired t-test. The skin temperature of the RBE group remained higher than that of the placebo group. The skin temperature changes 100 min after RBE or placebo ingestion were −3.67±1.14ºC and −4.59±0.89ºC, respectively in all participants. We also did subclass analysis focusing on men or women. In a previous study, RBE efficacy for skin temperature in men was not clearly demonstrated. RBE consumption was also effective not only in female participants but also in male participants. The skin temperature changes 100 min after RBE or placebo ingestion were −3.65±0.64ºC and −4.55±0.32ºC, respectively in male participants. Therefore, RBE containing cyclo(d-Phe-l-Pro) prevented skin temperature decreases in excessively air-cooled conditions in both men and women.

Despite previous studies suggesting that choline and betaine ameliorate lipid accumulation in rat livers, the relative effectiveness of the two nutrients is unclear. We examined the efficacy of dietary supplementation with choline or betaine in ameliorating lipid accumulation induced by vitamin B₆ (B₆) deficiency in the rat liver. Male Wistar rats were fed control, B₆-deficient, choline-supplemented B₆-deficient, betaine-supplemented B₆-deficient, or both choline and betaine-supplemented B₆-deficient diets (all containing 9 g of l-methionine (Met)/kg) for 35 d. Two experiments were performed, i.e., one using 17 mmol/kg diet choline bitartrate, betaine anhydrous, and the combination and another using 8.5 mmol/kg diet. Rats fed a B₆-deficient diet developed lipid accumulation in the liver with a reduction of plasma lipids induced by the disruption of Met metabolism. However, the addition of 17 mmol/kg diet choline or betaine was sufficient to ameliorate the disruptions of lipid and Met metabolism. Additionally, 8.5 mmol/kg diet choline ameliorated liver lipid deposition, while the same amount of betaine had no significant effects on liver or plasma lipid profiles. Supplementation with choline resulted in a higher liver betaine than that found using the same amount of betaine alone, although the overall liver betaine content was reduced in B₆-deficient rats. Our findings indicate that choline is more effective than betaine in ameliorating B₆ deficiency-related disruptions in Met metabolism and liver lipid accumulation by increasing liver betaine levels.

To clarify the degree of consistency between the international recommendations and the national Japanese system, the nutrient reference values (NRVs) adopted by the CODEX were compared with current Japanese NRVs 2015, the dietary reference intakes for Japanese (DRIs-J) 2015, and actual nutrient intake levels by the Japanese population. The Japanese NRV for protein was high relative to CODEX NRV-R (i.e., NRV-Requirement). The Japanese NRVs for folate and calcium were low, and vitamin K was high, relative to each CODEX NRV-R. However, it was similar to the DRI-J values, and current intake levels for the Japanese population. For iron, calculation methods were different between the CODEX and Japan. Japanese iron NRV was calculated based on the RDA without menstruatating women, whereas CODEX NRV-R was calculated based on the INL98 of all adult men and women. Actual intake levels of iron for the Japanese population were similarly low. The Japanese NRV for sodium was high and potassium was low based on DRI-J values, relative to the CODEX NRV-NCD. For nutrients that show large discrepancies between the CODEX and Japanese NRVs, the values should be discussed further.