Preventive Effects of Green Tea Extract against Obesity Development in Zebrafish.

Various natural products (NPs) have been used to treat obesity and related diseases. However, the best way to fight obesity is preventive, with accurate body weight management through exercise, diet, or bioactive NPs to avoid obesity development. We demonstrated that green tea extract (GTE) is an anti-obesity NP using a zebrafish obesity model. Based on a hypothesis that GTE can prevent obesity, the objective of this study was to assess GTE's ability to attenuate obesity development. Juvenile zebrafish were pretreated with GTE for seven days before obesity induction via a high-fat diet; adult zebrafish were pretreated with GTE for two weeks before obesity induction by overfeeding. As a preventive intervention, GTE significantly decreased visceral adipose tissue accumulation in juveniles and ameliorated visceral adiposity and plasma triglyceride levels in adult zebrafish obesity models. RNA sequencing analysis was performed using liver tissues from adult obese zebrafish, with or without GTE administration, to investigate the underlying molecular mechanism. Transcriptome analysis revealed that preventive GTE treatment affects several pathways associated with anti-obesity regulation, including activation of STAT and downregulation of CEBP signaling pathways. In conclusion, GTE could be used as a preventive agent against obesity.

Anti-Obesity Natural Products Tested in Juvenile Zebrafish Obesogenic Tests and Mouse 3T3-L1 Adipogenesis Assays.

(1) Background: The obesity epidemic has been drastically progressing in both children and adults worldwide. Pharmacotherapy is considered necessary for its treatment. However, many anti-obesity drugs have been withdrawn from the market due to their adverse effects. Instead, natural products (NPs) have been studied as a source for drug discovery for obesity, with the goal of limiting the adverse effects. Zebrafish are ideal model animals for in vivo testing of anti-obesity NPs, and disease models of several types of obesity have been developed. However, the evidence for zebrafish as an anti-obesity drug screening model are still limited. (2) Methods: We performed anti-adipogenic testing using the juvenile zebrafish obesogenic test (ZOT) and mouse 3T3-L1 preadipocytes using the focused NP library containing 38 NPs and compared their results. (3) Results: Seven and eleven NPs reduced lipid accumulation in zebrafish visceral fat tissues and mouse adipocytes, respectively. Of these, five NPs suppressed lipid accumulation in both zebrafish and 3T3-L1 adipocytes. We confirmed that these five NPs (globin-digested peptides, green tea extract, red pepper extract, nobiletin, and Moringa leaf powder) exerted anti-obesity effects in diet-induced obese adult zebrafish. (4) Conclusions: ZOT using juvenile fish can be a high-throughput alternative to ZOT using adult zebrafish and can be applied for in vivo screening to discover novel therapeutics for visceral obesity and potentially also other disorders.

RNA-seq Based Transcriptome Analysis of the Anti-Obesity Effect of Green Tea Extract Using Zebrafish Obesity Models.

Green tea is a popular beverage that is rich in polyphenolic compounds such as catechins. Its major content, (-)-epigallocatechin-3-gallate, has been shown to have beneficial effects on several diseases including cancer, metabolic syndrome, cardiovascular diseases, and neurodegenerative diseases. The aim of this study was to assess the anti-obesity effects and the underlying molecular mechanisms of green tea extract (GTE) using zebrafish larva and adult obesity models. We administered 100 µg/mL GTE to zebrafish larvae and performed a short-term obesogenic test. GTE significantly decreased the visceral adipose tissue volume induced by a high-fat diet. Oral administration (250 µg/g body weight/day) of GTE to adult diet-induced obese zebrafish also significantly reduced their visceral adipose tissue volume, with a reduction of plasma triglyceride and total cholesterol levels. To investigate the molecular mechanism underlying the GTE effects, we conducted RNA sequencing using liver tissues of adult zebrafish and found that GTE may ameliorate the obese phenotypes via the activation of Wnt/ß-catenin and adenosine monophosphate-activated protein kinase (AMPK) pathway signaling. In addition, the comparative transcriptome analysis revealed that zebrafish and mammals may share a common molecular response to GTE. Our findings suggest that daily consumption of green tea may be beneficial for the prevention and treatment of obesity.

In Search of a Safe Natural Sleep Aid.

Sleep deprivation is associated with an elevated risk of various diseases and leads to a poor quality of life and negative socioeconomic consequences. Sleep inducers such as drugs and herbal medicines may often lead to dependence and other side effects. L-Theanine (γ-glutamylethylamide), an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of α brain waves without additive and other side effects associated with conventional sleep inducers. Anxiolysis is required for the initiation of high-quality sleep. In this study, we review the mechanism(s), safety, and efficacy of L-theanine. Collectively, sleep studies based on an actigraph, the obstructive sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO) and automatic nervous system (ANS) assessment, sympathetic and parasympathetic nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the administration of 200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis. Because L-theanine does not induce daytime drowsiness, it may be useful at any time of the day. The no observable adverse effect level (NOAEL) for the oral administration of L-theanine was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS: Sleep deprivation-associated morbidity is an increasing public health concern posing a substantial socioeconomic burden. Chronic sleep disorders may seriously affect quality of life and may be etiological factors in a number of chronic diseases such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep inducers are sedatives and are often associated with addiction and other side effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis. This review suggests that L-theanine is a safe natural sleep aid.

Post-meal perceivable satiety and subsequent energy intake with intake of partially hydrolysed guar gum.

Partially hydrolysed guar gum (PHGG), a soluble dietary fibre, has been shown to provide many health benefits. Previous studies had suggested that the combination of PHGG with protein provided a significant satiation effect on visual analogue scales (VAS). What was lacking was only the effect of administration of small doses of PHGG on post-meal satiation and subsequent energy intake. The objectives of the present investigations were to find the subjective perception of post-meal satiety with acute and long term administration of small amounts of PHGG alone with food, its effects on subsequent energy intake and the comparative effects among different types of soluble fibres. The following three separate studies were conducted: in study 1, healthy subjects (n 12) consumed PHGG along with breakfast, lunch and an evening snack; in study 2, healthy subjects (n 24) consumed 2 g of PHGG or dextrin along with yogurt as breakfast for 2 weeks; in study 3, healthy subjects (n 6) took 6 g each of either PHGG or indigestible dextrin or inulin along with lunch. In all the studies, various satiety parameters were measured on VAS before and after consumption of PHGG. The addition of PHGG showed significant (P < 0.05) acute (studies 1 and 3) and long-term (studies 1 and 2) satiety effects compared to the control and/or an equal amount of carbohydrate or other types of soluble fibre. Study 2 also indicated that the prolonged consumption of PHGG may significantly (P < 0.05) reduce energy intake from whole-day snacking. PHGG could be an ideal natural soluble fibre for delivering acute and long term satiety effects for comfortable appetite control.

Engineered Nanoscale Food Ingredients: Evaluation of Current Knowledge on Material Characteristics Relevant to Uptake from the Gastrointestinal Tract.

The NanoRelease Food Additive project developed a catalog to identify potential engineered nanomaterials (ENMs) used as ingredients, using various food-related databases. To avoid ongoing debate on defining the term nanomaterial, NanoRelease did not use any specific definition other than the ingredient is not naturally part of the food chain, and its dimensions are measured in the nanoscale. Potential nanomaterials were categorized based on physical similarity; analysis indicated that the range of ENMs declared as being in the food chain was limited. Much of the catalog's information was obtained from product labeling, likely resulting in both underreporting (inconsistent or absent requirements for labeling) and/or overreporting (inability to validate entries, or the term nano was used, although no ENM material was present). Three categories of ingredients were identified: emulsions, dispersions, and their water-soluble powdered preparations (including lipid-based structures); solid encapsulates (solid structures containing an active material); and metallic or other inorganic particles. Although much is known regarding the physical/chemical properties for these ingredient categories, it is critical to understand whether these properties undergo changes following their interaction with food matrices during preparation and storage. It is also important to determine whether free ENMs are likely to be present within the gastrointestinal tract and whether uptake of ENMs may occur in their nanoform physical state. A practical decision-making scheme was developed to help manage testing requirements.

L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion.

While the neuroprotective effect of green tea (Camellia sinensis) might be explained by the presence of amino acid L-theanine in the tea leaves, it is not known whether postischemic administration of L-theanine could also provide neuroprotection. In the present study, we investigated the neuroprotective effect of L-theanine (1 and 4 mg/kg) administered at 3, 12, and 24 h after reperfusion in the rat model of stroke. We also studied the effect of L-theanine on brain injury caused by exogenous administration of N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate/kainate receptor agonists during reperfusion. Rats were subjected to 30-min middle cerebral artery occlusion followed by 48-h reperfusion. Neurological deficit and infarct size were determined at the end of reperfusion. At 3 and 12 h, but not at 24 h of reperfusion, L-theanine substantially reduced the size of brain infarct. Neurological status was improved when L-theanine was administered 3, 12, and 24 h after reperfusion. Repeated intrastriatal injections of L-theanine at a total dose of 800 µg/kg during reperfusion prevented brain injury caused by glutamate receptor agonists. In conclusion, L-theanine at reperfusion exerts neuroprotective effect in the in vivo rat model of stroke. Local treatment with L-theanine at reperfusion prevents glutamate receptor agonist-mediated brain injury.

Dietary Approaches to Stop Hypertension via Indo-Mediterranean Foods, May Be Superior to DASH Diet Intervention.

Western-type diet with high salt and sugar, sedentary behavior, obesity, tobacco and alcoholism are important risk factors for hypertension. This review aims to highlight the role of western diet-induced oxidative stress and inflammation in the pathogenesis of hypertension and the role of various types of diets in its prevention with reference to dietary approaches to stop hypertension (DASH) diet. It seems that it is crucial to alter the western type of diet because such diets can also predispose all CVDs. Western diet-induced oxidative stress is characterized by excessive production of reactive oxygen species (ROS) with an altered oxidation-reduction (redox) state, leading to a marked increase in inflammation and vascular dysfunction. Apart from genetic and environmental factors, one important cause for differences in the prevalence of hypertension in various countries may be diet quality, deficiency in functional foods, and salt consumption. The role of the DASH diet has been established. However, there are gaps in knowledge about the role of some Indo-Mediterranean foods and Japanese foods, which have been found to decrease blood pressure (BP) by improving vascular function. The notable Indo-Mediterranean foods are pulses, porridge, spices, and millets; fruits such as guava and blackberry and vegetables, which may also decrease BPs. The Japanese diet consists of soya tofu, whole rice, in particular medical rice, vegetables and plenty of fish rich in fish oil, fish peptides and taurine that are known to decrease BPs. Epidemiological studies and randomized, controlled trials have demonstrated the role of these diets in the prevention of hypertension and metabolic diseases. Such evidence is still meager from Japan, although the prevalence of hypertension is lower (15-21%) compared to other developed countries, which may be due to the high quality of the Japanese diet. Interestingly, some foods, such as berries, guava, pumpkin seeds, carrots, soya beans, and spices, have been found to cause a decrease in BPs. Omega-3 fatty acids, fish peptide, taurine, dietary vitamin D, vitamin C, potassium, magnesium, flavonoids, nitrate and l-arginine are potential nutrients that can also decrease BPs. Larger cohort studies and controlled trials are necessary to confirm our views.

Zebrafish obesogenic test identifies anti-adipogenic fraction in Moringa oreifera leaf extracts.

The zebrafish obesogenic test (ZOT) is a powerful tool for identifying anti-adipogenic compounds for in vivo screening. In our previous study, we found that Moringa oleifera (MO) leaf powder suppressed the accumulation of visceral adipose tissue (VAT) in ZOT. MO demonstrates a wide range of pharmacological effects; however, little is known about its functional constituents. To identify the anti-adipogenic components of MO leaves, we prepared extracts using different extraction methods and tested the obtained extracts and fractions using ZOT. We found that the dichloromethane extract and its hexane:EtOAc = 8:2 fraction reduced VAT accumulation in young zebrafish fed a high-fat diet. We also performed gene expression analysis in the zebrafish VAT and found that CCAAT/enhancer-binding protein beta and CCAAT/enhancer-binding protein delta (associated with early stages of adipogenesis) gene expression was downregulated after fraction 2 administration. We identified a new MO fraction that suppressed VAT accumulation by inhibiting early adipogenesis using the ZOT. Phenotype-driven zebrafish screening is a reasonable strategy for identifying bioactive components in natural products.

The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: The purpose of this study was to investigate the efficacy and safety of L-theanine as an aid to the improvement of objectively measured sleep quality in a population of 98 male children formally diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHODS: A randomized, double-blind, placebo-controlled trial was conducted involving boys, ages 8-12 years, who had been previously diagnosed with ADHD. An experienced physician confirmed the diagnosis of ADHD in each subject. Randomization was stratified based upon current use of stimulant medication to ensure an equal distribution of stimulant/non-stimulant treated subjects into active and placebo treated groups. Participants consumed two chewable tablets twice daily (at breakfast and after school), with each tablet containing 100 mg of L-theanine (total 400 mg daily Suntheanine®, Taiyo Kagaku, Yokkaichi, Japan) or identical tasting chewable placebo for six weeks. Subjects were evaluated for five consecutive nights using wrist actigraphy at baseline, and again at the end of the six-week treatment period. The Pediatric Sleep Questionnaire (PSQ) was completed by parents at baseline and at the end of the treatment period. RESULTS: Actigraph watch data findings indicated that boys who consumed L-theanine obtained significantly higher sleep percentage and sleep efficiency scores, along with a non-significant trend for less activity during sleep (defined as less time awake after sleep onset) compared to those in the placebo group. Sleep latency and other sleep parameters were unchanged. The PSQ data did not correlate significantly to the objective data gathered from actigraphy, suggesting that parents were not particularly aware of their children's sleep quality. L-theanine at relatively high doses was well tolerated with no significant adverse events. CONCLUSIONS: This study demonstrates that 400 mg daily of L-theanine is safe and effective in improving some aspects of sleep quality in boys diagnosed with ADHD. Since sleep problems are a common co-morbidity associated with ADHD, and because disturbed sleep may be linked etiologically to this disorder, L-theanine may represent a safe and important adjunctive therapy in childhood ADHD. Larger, long-term studies looking at the wider therapeutic role of this agent in this population are warranted.

Pilot-scale commercialization of iron-fortified rice: effects on anemia status.

BACKGROUND: Rice, the staple food of the Philippines, is an appropriate vehicle for iron fortification to combat the high prevalence of iron-deficiency anemia. A previous study among schoolchildren supplemented with iron-fortified rice showed a significant reduction in the rate of iron-deficiency anemia from 100% to 33%. OBJECTIVE: To document the processes involved in commercializing iron-fortified rice and to determine its effects on anemia prevalence. SUBJECTS AND METHODS: This study was conducted on 766 mothers and their children aged 6 to 9 years in Orion, Bataan. Soliciting political support, networking with local organizations, market surveys, and social marketing activities were conducted. The iron content of iron-fortified rice was tested for each production run. Hemoglobin measurements were performed on the mothers and children at baseline and endline. RESULTS: A municipal ordinance to sell iron-fortified rice was issued, while the local federation provided funds to kick off the sale of iron-fortified rice. Sales of iron-fortified rice were highest when the rice was sold at Php 27 (Php 1 = US$0.025) per kilogram and lowest when the price was Php 37 per kilogram or greater. The municipal ordinance was not strictly enforced because of the global rice crisis. Social marketing activities encouraged families to buy iron-fortified rice. The iron content of the iron-rice premix was within the set specification limits of 600 to 760 mg of iron per 100 g of premix, while the iron-fortified rice was within 3 to 3.8 mg of iron and 1 to 2 mg (BC No. 2009-010) per 100 g of raw and cooked fortified rice, respectively. The decrease in the rate of anemia was significant among children (from 17.5% to 12.8%) but not among mothers (from 13.0% to 12.5%) after 9 months of study implementation. CONCLUSIONS: Strong political support and intensive social marketing activities are crucial inputs in commercializing iron-fortified rice. Keeping the cost affordable and maintaining the commitment of identified partners were the key factors for providing a continuous supply of iron-fortified rice. Commercializing iron-fortified rice can be considered as one of the strategies for decreasing anemia prevalence.

Globin Digest Improves Visceral Adiposity Through UCP1 Upregulation in Diet-Induced Obese Zebrafish and Mice.

Globin digest (GD), a bioactive oligopeptide derived from porcine hemoglobin proteins, has been demonstrated to have beneficial effects on improving postprandial hyperlipidemia, hyperglycemia, and liver injury. We previously reported the lipid-lowering effects of GD using a zebrafish obesogenic test. Here, we sought to evaluate the effect of GD on visceral adiposity and the underlying molecular mechanisms using zebrafish and mouse obesity models. GD ameliorated dyslipidemia and suppressed the accumulation of visceral adipose tissue (VAT) in adult obese zebrafish. Transcriptomic analysis by RNA sequencing of GD-treated adult zebrafish revealed that GD upregulated UCP1-related pathways. Further, we performed mouse experiments and found that GD intake (2 mg/g body weight/day) was associated with lowered plasma triglyceride and total cholesterol levels, decreased VAT accumulation, and improved adipocyte hypertrophy with the upregulation of Ucp1 expression in white adipose tissue at both the mRNA and protein levels. Taken together, these results indicate that GD improves visceral adiposity by upregulating UCP1 expression, providing a novel perspective on combating obesity.

Attitudes Toward Psychological Disorders and Alternative Medicine in Saudi Participants.

Background: This study was designed to investigate Saudis' attitudes toward mental distress and psychotropic medication, attribution of causes, expected side effects, and to analyze participants' expectations toward alternative or complementary medicine using aromatic and medicinal plants, through a survey. Method: The study included 674 participants (citizens and residents in Saudi Arabia) who were randomly contacted via email and social media and gave their consent to complete a questionnaire dealing with 39 items that can be clustered in six parts. Descriptive statistics and Chi-square for cross-tabulation were generated using SPSS. Results: Among the 664 participants, 73.4% believed that there are some positive and negative outcomes of psychotropic medication. Participants (72.0%) think that the most important reason leading to psychological disorders is mainly due to the loss of a relative or beloved person, and 73.9% considered psychic session as one of the possible treatments of psychological disorders. Surprisingly, only 18.8% of the participants agreed that medicinal and aromatic plants could be a possible treatment of the psychological disorder. Participants (82%) consider that physicians are the most trustful and preferred source of information about alternative and complementary medicine.

The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model.

We investigated the effects of amla (Emblica officinalis Gaertn.) on fructose-induced metabolic syndrome using a rat model. Male Wistar rats were fed a high-fructose (65 %) diet or standard chow for 1 week, and treated with an ethyl acetate (EtOAc) extract of amla, a polyphenol-rich fraction, at 10 or 20 mg/kg body weight per d, or vehicle, for 2 weeks. Serum glucose, TAG, total cholesterol and blood pressure levels of the high-fructose diet-fed rats were increased compared with those of the normal rats (P < 0.001). However, the EtOAc extract of amla ameliorated the high fructose-induced metabolic syndrome, including hypertriacylglycerolaemia and hypercholesterolaemia. Also, the elevated levels of hepatic TAG and total cholesterol in rats given the high-fructose diet were significantly reduced by 33.8 and 24.6 %, respectively (P < 0.001), on the administration of the EtOAc extract of amla at the dose of 20 mg/kg with the regulation of sterol regulatory element-binding protein (SREBP)-1 expression. The protein levels of PPARalpha and SREBP-2 were not affected by the feeding of the high-fructose diet or EtOAc extract of amla. In addition, oral administration of the amla extract at the dose of 20 mg/kg significantly inhibited the increased serum and hepatic mitochondrial thiobarbituric acid-reactive substance levels (21.1 and 43.1 %, respectively; P < 0.001). Furthermore, the amla extract inhibited the increase of cyclo-oxygenase-2 with the regulation of NF-kappaB and bcl-2 proteins in the liver, while the elevated expression level of bax was significantly decreased by 8.5 and 10.2 % at the doses of 10 and 20 mg/kg body weight per d, respectively. These findings suggest that fructose-induced metabolic syndrome is attenuated by the polyphenol-rich fraction of amla.

ORAC and DPPH assay comparison to assess antioxidant capacity of tea infusions: relationship between total polyphenol and individual catechin content.

Commercially available tea infusions are the major source of catechins for preparing bottled tea beverages and tea supplements available in the market today. In the present study, we analyzed five tea infusions to measure the total antioxidant capacity (TAC) by oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity (DRSC) assays, total polyphenol content by the colorimetric method and individual catechin content by high-performance liquid chromatography. Four major tea catechins were also analyzed for their TAC to reveal differential antioxidant behavior of the tea infusions, resulting in the ORAC and DRSC methods. The correlation coefficients between DRSC and the total polyphenol or total catechin content of the tea infusions were 1.0 and 0.99. However, the values fall to 0.73 and 0.69, respectively, while the ORAC activity was correlated with total polyphenol and total catechin content. Determining the TAC of individual tea catechins showed that ORAC of epicatechin was seven-fold higher than that of epigallocatechin gallate; on the contrary, epigallocatechin gallate showed significantly (P < 0.05) stronger DRSC activity than epicatechin. By evaluating the structure-activity relationship, this study further revealed that OH substitution at the 3' position in pyrogallol moieties contributes to the lower ORAC value of epigallocatechin and epigallocatechin gallate comparing with their non-3'-OH counterparts, such as epicatechin and epicatechin gallate, respectively. Also, numbers of OH substitutions were poorly correlated with the observed ORAC value unlike the DRSC. Overall, results of this study enabled us to hypothesize that substances having a lower TAC value in the ORAC assay compared with that in DPPH assays may pertain to a pro-oxidant effect by generating reactive oxygen species in an aqueous buffer, at a physiological pH. We also propose that substances exhibiting lower TAC value in the ORAC assay compared with that in the DPPH assay are powerful pro-oxidants compared with the substances showing a higher TAC value in the ORAC assay than that in the DPPH assay.

Characteristic Analysis of Trigonelline Contained in Raphanus sativus Cv. Sakurajima Daikon and Results from the First Trial Examining Its Vasodilator Properties in Humans.

Vascular disease poses a major public health problem worldwide. Trigonelline isolated from Raphanus sativus cv. Sakurajima Daikon (Sakurajima radish) induces nitric oxide production from vascular endothelial cells and enhances vascular function. Here, we investigated the characteristics of trigonelline and its effects on endothelial function after consumption of Sakurajima radish by humans. Our results show that Sakurajima radish contains approximately 60 times more trigonelline than other radishes and squashes. Additionally, no significant differences were observed between varieties of Sakurajima radish, suggesting that any type of Sakurajima radish can be ingested for trigonelline supplementation. The effects of cooking and processing Sakurajima radish were also evaluated, as were the effects of freezing, and changes in osmotic pressure and pH. A first-in-human trial using Sakurajima radish showed that ingestion of 170 g/day of Sakurajima radish for ten days increased blood trigonelline concentrations and significantly improved flow-mediated dilation, which is a measure of vascular endothelial function. Overall, our findings suggest that the trigonelline contained in Sakurajima radish may contribute to improved human vascular endothelial function. Hence, Sakurajima radish may enhance vascular endothelial function as a functional food.

Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test.

We identified an effect of theanine on memory functions in a novel object test. Rats were fed theanine for 3 weeks ad libitum, and then they performed the object test. The theanine-fed group performed search behavior for the novel object in the test session. The results suggest that theanine-fed rats showed improved recognition, and that theanine affected learning and memory.

Administration of theanine, a unique amino acid in tea leaves, changed feeding-relating components in serum and feeding behavior in rats.

We identified an effect of gamma-glutamylethylamide (theanine) on feeding in a rat study. Oral theanine suppressed the food intake of rats. The serum glucose level did not differ from the control, but the insulin concentration was reduced and the corticosterone concentration was increased by theanine. We suggest that the effect of theanine on feeding involved hormones.

Possible carcinogenic risks of copper gluconate and their prevention by co-administered green tea catechins evaluated by a rat medium-term multi-organ carcinogenicity bioassay protocol.

Carcinogenic risks of copper gluconate, green tea catechins and their combined exposure were evaluated using a rat medium-term multi-organ carcinogenicity bioassay protocol. Male BrlHan:WIST@Jcl (GALAS) rats were given N-nitrosodiethylamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). Rats were then given a diet containing copper gluconate at a concentration of 0, 10, 300, 3000 or 6000 ppm with or without a co-administration of catechins starting 1 week later by admixing in the drinking water at a concentration of 5000 ppm. All survivors were sacrificed at the end of week 29. Number of putatively preneoplastic, glutathione S-transferase placental form-positive, liver lesions significantly increased by copper gluconate of 300 ppm or greater. In addition, both incidence and grade of hyperplasia in the forestomach significantly increased by copper gluconate of 6000 ppm. Catechins, exerting no effects by themselves, inhibited these effects of copper gluconate. The present results indicate that copper gluconate may possess carcinogenic risks for the liver and forestomach at its high dose level, and that co-administered green tea catechins may exert preventive effects.

Zinc bioavailability is improved by the micronised dispersion of zinc oxide with the addition of L-histidine in zinc-deficient rats.

Zinc fortification of milk or soft drinks is usually used to combat zinc deficiencies in developing countries. Water-soluble zinc compounds, such as zinc sulfate or zinc citrate, are better absorbed but have an unacceptable taste. A micronised, dispersible zinc oxide (MDZnO), which does not have such a problem concerning taste, had higher solubility compared to ZnO (zinc oxide) in an artificial gastric solution. MDZnO was tested for its bioavailability using zinc-deficient Wistar rats. Prior to the experiment, rats were fed zinc-deficient diet for 3 wk and were orally administered control (distilled water) or zinc solutions (ZnO, ZnO+L-histidine (His), MDZnO, MDZnO+His, 1 mg zinc/kg or 3.2 mg His/kg body weight). Compared to ZnO, MDZnO showed a lag in peak time and a lengthy period of continued high plasma zinc concentration after the single oral administration of zinc compounds. Addition of His to MDZnO elevated serum zinc concentration. Serum zinc concentration (area under the curve) in rats administered MDZnO with His was significantly higher than in rats administered distilled water (p<0.05). Liver zinc level was significantly higher in rats administered MDZnO with His compared with control rats (p<0.05), although the level was not affected by the administration with ZnO alone, ZnO+His, or MDZnO alone. In conclusion, the solubility of ZnO was elevated by the micronised dispersion tecnique and an in vivo study using zinc-deficient rats confirmed that its bioavailability was significantly improved compared to ZnO and the coadministration of His additively enhanced the bioavailability of MDZnO.