Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.

BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. METHODS: The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. RESULTS: Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. CONCLUSION: We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow.

School Lunch Programs and Nutritional Education Improve Knowledge, Attitudes, and Practices and Reduce the Prevalence of Anemia: A Pre-Post Intervention Study in an Indonesian Islamic Boarding School.

Indonesians face serious health issues that arise from malnutrition, particularly in children who are under unfavorable dietary environments. The present study established a school meal program consisting of dietary and educational interventions and evaluated its impact on promoting continuous improvement in dietary behavior among junior and senior high school students in Indonesia. A total of 319 students belonging to an Islamic Boarding School participated in the pre-post intervention study for 9 months. All participants were assessed based on their Knowledge, Attitude, and Practice (KAP). A subgroup of 115 participants who were anemic and underweight was examined for dietary intake, nutrition status, and hemoglobin level. The KAP test scores for both nutrition and hygiene showed a significant increase for all students and the undernutrition group post-intervention. Protein, iron, and vitamin C intake significantly improved. Although there were no significant improvements in nutrition status, there was a significant increase in the hemoglobin level and a reduction in the prevalence of anemia from 42.6% to 21.7%. Thus, school meal program that combines dietary and educational interventions may effectively improve anemia in undernourished students as well as enhance the knowledge, attitudes, and practices related to health, nutrition, and hygiene in junior and senior high school students.

Validation of Energy and Nutrition Intake in Japanese Elderly Individuals Estimated Based on a Short Food Frequency Questionnaire Compared against a 7-day Dietary Record: The Kyoto-Kameoka Study.

To determine the association between geriatric disorders and dietary intake, validation of a food frequency questionnaire (FFQ) for elderly individuals is needed. We compared energy and nutrient intakes derived from dietary records (DR) and FFQ in an elderly population and compared the data against results from middle-aged individuals (30⁻68 years) from a previous study. Current participants included 65 women and 78 men (65⁻88 years) who completed FFQ and 7-day DR in a subpopulation of the Kyoto-Kameoka study. Our FFQ was created for middle-aged individuals. To validate the FFQ, we investigated equivalent precision by comparing the correlation coefficients between the present and previous study. Median correlations for energy and nutrient intake between the DR and FFQ in the current and previous studies were 0.24 and 0.30 (p = 0.329) in women and 0.24 and 0.28 (p = 0.399) in men, respectively. The median ratio of FFQ to DR for these intakes were also similar. The accuracy and precision of the FFQ for energy and nutrient intake in elderly individuals did not differ compared with previous findings in a middle-aged population. A validation study evaluating energy and nutrient intake using recovery biomarkers is further needed.

Effect of dried-bonito broth intake on peripheral blood flow, mood, and oxidative stress marker in humans.

Dried-bonito broth (DBB) has been confirmed to improve various symptoms related to fatigue, but the reasons for this have remained unclear. Hypothesizing that DBB improves peripheral circulation together with mood states, we performed a randomized, double-blind, placebo-controlled crossover study in thirty-one healthy females. The subjects ingested DBB or a placebo for two weeks and changes in mood states after ingestion were investigated using the profile of mood states (POMS) questionnaire. The peripheral blood flow was also measured before and after ingestion of the test diet using a laser Doppler blood flow meter. The six mood factors and total mood disturbance score which reflect the mental states significantly improved, and a significant increase in peripheral blood flow was also found during DBB ingestion. As a result of correlation analysis between changes in each POMS score and changes in blood flow, it was suggested that a change in blood flow correlated with a change in some POMS factors and total mood disturbance. Based on these findings, we considered that blood flow may have increased in subjects whose mood states were markedly improved, suggesting that the improvement in mood states, including fatigue, was related to the increase in blood flow due to the improvement of peripheral circulation. To clarify whether DBB ingestion exhibits antioxidative activity, we investigated the urinary amounts of 8-hydroxy-2'-deoxyguanosine (8-OHdG) known as an oxidative stress marker and found that urinary excretion of the 8-OHdG for 24 h was significantly decreased during DBB ingestion. This study clarified that DBB ingestion improved mood states, increased peripheral blood flow, and decreased the oxidative stress marker.

Association between the Frequency of Protein-Rich Food Intakes and Kihon-Checklist Frailty Indices in Older Japanese Adults: The Kyoto-Kameoka Study.

We aimed to investigate whether frequencies of protein-rich food intake were associated with frailty among older Japanese adults. A cross-sectional study was conducted in 2011 among 3843 men and 4331 women in a population-based cohort of Kameoka city, Kyoto Prefecture, Japan. Frailty was assessed by the weighted score based on the 25-item Kihon-Checklist. The frequency of protein-rich food intake was examined as "seafood", "meat", "dairy products", "eggs", and "soy products". The outcome of frailty was analyzed with a multiple logistic regression model using the frequency of protein-rich food intake. When compared to the first quartile, it was observed that there was a significant association between the lower adjusted prevalence ratio (PR) for frailty and the frequency of seafood intake in the fourth quartile among men (PR 0.64, 95% confidence interval (CI), 0.42, 0.99) and from the second quartile to the third quartile among women (PR 0.61, 95% CI, 0.43, 0.85; PR 0.64, 95% CI, 0.46, 0.91). The frequency of dairy products intake in the third quartile among women was significantly associated with a lower PR for frailty (p-value = 0.013). Our findings suggest that the consumption of seafood and dairy products may help older adults in maintaining their independence.

Sex Difference in the Association Between Protein Intake and Frailty: Assessed Using the Kihon Checklist Indexes Among Older Adults.

BACKGROUND: Dietary protein intake is inversely associated with physical frailty risk. However, it is unknown whether an association exists between dietary protein intake and comprehensive frailty. OBJECTIVE: To evaluate the association between protein intake and comprehensive frailty in older Japanese adults. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study included 5638 Japanese participants (2707 men and 2931 women) aged ≥65 years from Kameoka City, Kyoto, Japan. MEASUREMENTS: Dietary intake was estimated using a validated self-administered food frequency questionnaire. Comprehensive frailty was assessed using a 25-item Kihon Checklist (KCL), which comprised instrumental activities of daily living, mobility disability, malnutrition, oral or eating function, socialization and housebound, cognitive function, and depression domains. A KCL score of 4 to 6 was defined as prefrailty, and ≥7 as frailty. RESULTS: In women, but not in men, protein intake showed a lower prevalence for prefrailty (Q1-Q4, 40.2%, 34.3%, 34.3%, and 36.0%). Higher protein intake was associated with lower prevalence of frailty both in men (32.5%, 28.4%, 28.3%, and 27.3%) and women (35.7%, 31.4%, 27.6%, and 28.2%). Moreover, higher dietary protein intake decreased the odds ratio (OR) for frailty after adjustment for potential confounding factors in both men (OR for highest vs lowest quartile, 0.62; 95% CI, 0.43-0.89; P for trend = 0.016) and women (OR 0.64; 95% CI, 0.45-0.91; P for trend = 0.017). CONCLUSIONS/IMPLICATIONS: The higher dietary protein intake may be inversely associated with the prevalence of comprehensive frailty in Japanese men and women. Future studies are needed to examine associations of dietary protein intake within KCL domains.

Effective prevention of sorafenib-induced hand-foot syndrome by dried-bonito broth.

BACKGROUND: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. MATERIALS AND METHODS: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. RESULTS: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). CONCLUSION: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.

The effect of histidine on mental fatigue and cognitive performance in subjects with high fatigue and sleep disruption scores.

Our previous study reported that a dried bonito broth known in Japan as 'dashi' improved or ameliorated mood states, including fatigue, during the daily lives of human subjects. Histidine is an amino acid that is present in dried bonito broth, and we sought to evaluate whether histidine would affect feelings of fatigue in humans. We investigated the effects of histidine intake on the feeling of fatigue, mood states and mental task performance by performing a placebo-controlled, double-blind crossover trial. Twenty subjects with high fatigue and sleep disruption scores were asked to ingest histidine or a placebo every day for two weeks. The subjects' mood states were evaluated using the Profile of Mood States (POMS) scale and a visual analog scale (VAS) for eight feelings (fatigue, depression, carelessness, drowsiness, clear thinking, motivation, attentiveness and concentration). We also measured subjects' cognitive performance using the CogHealth test battery. The fatigue T-scores on the POMS test decreased significantly following histidine ingestion compared to placebo ingestion (p<0.05). After two weeks of histidine ingestion, the reaction time for the working memory task in the CogHealth test battery was significantly shorten compared to placebo ingestion. The VAS scores for clear thinking and for attentiveness were increased significantly following histidine ingestion compared to placebo ingestion (p<0.05). These results suggest that daily ingestion of histidine may ameliorate feelings of fatigue, increase performance during working memory tasks, and improve the clear thinking and attentiveness.

Dried bonito broth improves cognitive function via the histaminergic system in mice.

Bonito extract, i.e., dried bonito broth (DBB), has been reported to counteract mental fatigue and to increase performance in a simple calculation task, but the mechanism by which DBB increases task performance is not known. The brain neurotransmitter histamine is biosynthesized only from histidine in the tuberomammillary nucleus. Histamine neurons are projected to almost all areas of the cerebral cortex, and histamine has various behavioral and neurobiological functions, particularly in recognition memory. Here we used a mouse model to investigate the effects of the oral ingestion of DBB, which contains abundant histidine, as well as the ingestion of histidine on cognitive function. In a retention trial of novel object recognition test, the administration of 1.6 g/kg of DBB and 500 mg/kg of histidine significantly increased the animals' exploratory behavior toward a novel object, and that these agents significantly increased the spontaneous alternation behavior ratio in a Y-maze under conditions of scopolamine-induced amnesia, which induced learning and memory impairment. These results suggested the improvement of spatial short-term working memory in a scopolamine amnesia model, as well as the strengthening of visual cognitive function by a single ingestion of DBB and histidine. Interestingly, the administration of αFMH, which is an inhibitor of histamine biosynthesis, eliminated the increase in the spontaneous alternation behavior ratio by DBB ingestion in the scopolamine-induced amnesia model, suggesting that DBB may improve working memory impairment via activation of the histaminergic neuron system.

Consumption of bonito extract suppresses the decrease in cerebral blood flow in stroke-prone spontaneously hypertensive rats.

The effect of consuming bonito extract (BE) on cerebral blood flow was evaluated in stroke-prone spontaneously hypertensive rats (SHRSP), a cerebrovascular disease model. BE dissolved in drinking water was given to 5-week-old male SHRSP for 7 weeks. Tap water was given to the control group. At the age of 12 weeks, blood flow and vascular diameter were measured in the middle cerebral artery. Both cerebral blood flow and cerebral vessel width were greater in the BE group than in the control group. Also, stroke occurred in 7 (with death in 2) of the 8 animals in the control group but in none of the 6 animals in the BE group. To clarify its mechanism, the expressions of nitrogen oxide synthase (NOS) and the superoxide dismutase activity (SOD) in the brain were evaluated. NOS mRNA expression and SOD activity in the cerebrum were higher in the BE group. These results suggest that the consumption of BE suppresses the decrease of cerebral blood flow and reduces the risk of stroke to maintain vasorelaxation through the production of nitrogen oxide and suppression of active oxygen generation.

Ingestion of bonito extract ameliorates peripheral blood flow in mice loaded from over crowding stress.

Bonito extract (BE) has been shown to improve various fatigue-related symptoms. The possibility that the improvement of blood flow contributes to the improvement of fatigue-related symptoms has been reported. However, even though BE has been found to increase peripheral blood flow in humans, an understanding of its mechanisms has remained elusive. The purpose of the present study is to construct an animal model system with which the blood flow-increasing effects of BE can be examined. Using mice loaded with crowding stress, an attempt was made to reproduce the increases in peripheral blood flow observed in humans after a single administration of BE. In this study, the crowded-condition mice (20 mice/cage) showed significantly increased catecholamine levels (noradrenaline, adrenaline, and dopamine) in their circulating blood and a decreased rate of skin blood perfusion in comparison with the normal-condition mice (6 mice/cage). The rate of skin blood perfusion was significantly increased by BE in the crowded-condition mice in comparison with the controls, but not influenced by BE in the normal-condition mice. This suggests that BE expands the vascular diameter by affecting the constriction of vessels induced by catecholamines.

The anti-fatigue effects of the low-molecular-weight fraction of bonito extract in mice.

Bonito extract (BE), a hot-water extract of bonito muscle, has traditionally been considered as a folk remedy for fatigue. In this study we investigated the effects of BE on physical fatigue. BE was divided into, high, mid, and low-molecular-weight fractions (LMF), to explore the effectiveness of BE compounds. The swimming times to exhaustion of mice administered 0.86 g/kg BE and those administered 0.86 g/kg LMF were significantly longer than those of the vehicle-treated mice in a forced swimming model, indicating that BE possesses an anti-fatigue effect and that the LMF contributes to this effect. The LMF was also confirmed to aid the recovery of locomotor activity after physical fatigue in a forced walking model. We also examined respiratory gas levels and found that oxygen consumption and lipid oxidation were significantly greater in the group administered LMF than in the vehicle group, indicating that LMF promotes the utilization of fatty acids as an energy source. To elucidate why the mice administered LMF showed an anti-fatigue effect, we evaluated metabolic variables during exercise. The concentrations of nonesterified fatty acids and ketone bodies were higher, whereas serum and muscle lactic acid levels were lower in the mice administered LMF than in those in the vehicle group after the start of swimming. When the results were taken as a group they indicated that the effect of BE administration on improving endurance capacity was mediated, at least partly, by an increased utilization of lipids as a source of energy during exercise.

Effect of dried-bonito broth on mood states: a pooled analysis of four randomized controlled human trials.

Dried-bonito broth is commonly employed as a soup and sauce base in Japanese cuisine and is considered to be a nutritional supplement that promotes recovery from fatigue. Previous human trials have indicated that the ingestion of dried-bonito broth improves several mood states including fatigue, however, the effects in these studies have differed. The aim of this study was to clarify the effects of daily ingestion of dried-bonito broth on mood states by a pooled analysis of the randomized placebo-controlled trials. Five comparisons in four trials were selected for the pooled analysis (n = 159). The ingestion of dried-bonito broth significantly decreased the scores for fatigue (P = 0.032) and increased those for vigor (P = 0.027) compared to the placebo ingestion, suggesting that the dried-bonito broth improved fatigue felt in daily life. Furthermore, the ingestion of dried-bonito broth decreased the scores for tension-anxiety (P = 0.004) and confusion (P = 0.008) compared to the placebo ingestion. The ingestion of dried-bonito broth also significantly decreased the scores for total mood disturbance (P = 0.005). These results suggest that the ingestion of dried-bonito broth improves mood states especially fatigue, vigor, tension-anxiety and confusion.