Evidence supports an important contribution of abdominal obesity and inflammation to the development of insulin resistance (IR) and CVD. Weight loss in obese individuals can reduce inflammation and, consequently, IR, but the role of training remains unclear. The aim of this study was to evaluate the effects of body weight reduction with and without exercise over abdominal fat tissue (primary outcome) and IR. In this randomised clinical trial, forty-eight obese individuals (age 31·8 (sd 6·0) years, BMI 34·8 (sd 2·7) kg/m2) were randomised to either a diet-only group (DI) or a diet and exercise group (DI+EXE). Treatment was maintained until 5 % of the initial body weight was lost. At baseline and upon completion, the following parameters were analysed: biochemical parameters such as glycaemia and insulin for the determination of homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP) and abdominal computed tomography for the determination of visceral and subcutaneous adipose tissue. A total of thirteen individuals dropped out before completing the weight-loss intervention and did not repeat the tests. In both the DI (n 18) and DI+EXE (n 17) groups, we observed significant and similar decreases of visceral adipose tissue (difference between means: 7·9 (95 % CI − 9·5, 25·2) cm2, P= 0·36), hs-CRP (difference between means: − 0·06 (95 % CI − 0·19, 0·03) mg/l, P= 0·39) and HOMA (difference between means: − 0·04 (95 % CI − 0·17, 0·08), P= 0·53). In the present study, 5 % weight loss reduced abdominal fat and IR in obese individuals and exercise did not add to the effect of weight loss on the outcome variables.

Changes in paraoxonase 1 (PON1) activities have been observed in a variety of diseases involving oxidative stress, such as CVD. However, its role in obesity has not been fully established. In the present study, we aimed (1) to genotype sixteen PON1 SNP, (2) to measure serum PON1 activities and (3) to correlate these findings with the incidence of childhood obesity and related traits. We conducted a case–control study of 189 normal-weight and 179 obese prepubertal children, and we measured four different PON1 activities: lactonase; paraoxonase; arylesterase; diazoxonase. Although none of these activities was significantly different between the obese and normal-weight children, lactonase activity was found to be positively correlated with HDL-cholesterol and ApoA1 levels and negatively correlated with myeloperoxidase and fatty acid-binding protein 4 levels. Among the sixteen genotyped PON1 SNP, only the intronic SNP rs854566 exhibited a significant association with obesity (OR 0·61, 95 % CI 0·41, 0·91; P= 0·016). This genetic variant was also associated with increased diazoxonase, lactonase and arylesterase activities and decreased paraoxonase activity. Other genetic variants exhibited different association patterns with serum activities based on their location within the PON1 gene, and SNP that were located within the promoter were strongly associated with lactonase, arylesterase and diazoxonase activities. The functional variant Q192R exhibited the greatest effect on paraoxonase activity (P= 5·88 × 10− 42). In conclusion, SNP rs854566 was negatively associated with childhood obesity and with increased serum PON1 activities in prepubertal children. We determined that lactonase is a reliable indicator of PON1 activities and should be included in future studies of PON1 function.

The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl2; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P= 0·003), serum testosterone levels (P= 0·001), the relative weight of epididymis (P= 0·013) and ventral prostate (P= 0·052), the percentage of normal sperm (P= 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P= 0·001) and of testicular levels of glutathione (P= 0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms.

Initial neonatal gut colonisation is a crucial stage for developing a healthy physiology, beneficially influenced by breast-feeding. Breast milk has been shown not only to provide nutrients and bioactive/immunological compounds, but also commensal bacteria, including gut-associated anaerobic Bifidobacterium spp. The aim of the present study was to investigate bacterial diversity in breast milk, with emphasis on identifying gut-associated obligate anaerobes. Breast milk collected from seven mothers at three sampling points (days 3–6, 9–14 and 25–30 postpartum) was analysed by combined culture-dependent and state-of-the-art, culture-independent methods (Sanger sequencing and 454-pyrosequencing). In addition to the predominance of facultative anaerobes such as Staphylococcus, Streptococcus and Propionibacterium (>90 % of isolated strains and 23·7 % relative abundance using pyrosequencing), significant populations of obligate anaerobes, including Bifidobacterium and Veillonella, were detected using pyrosequencing and confirmed by the isolation of viable strains (3·4 % of isolates and 1·4 % relative abundance). Pyrosequencing also revealed the presence of DNA of multiple major gut-associated obligate anaerobes (6·2 % relative abundance) such as Bacteroides and, for the first time, several members of the Clostridia, including butyrate producers, such as Faecalibacterium and Roseburia, which are important for colonic health. The present study suggests that breast milk may be a major source of bacterial diversity to the neonatal gut, including gut-associated obligate anaerobes, and may thus significantly influence gut colonisation and maturation of the immune system.

Suboptimal maternal dietary intake during pregnancy might lead to fetal cardiovascular adaptations and higher blood pressure in the offspring. The aim of the present study was to investigate the associations of maternal first-trimester dietary intake with blood pressure in children at the age of 6 years. We assessed first-trimester maternal daily dietary intake by a FFQ and measured folate, homocysteine and vitamin B12 concentrations in the blood, in a population-based prospective cohort study among 2863 mothers and children. Childhood systolic and diastolic blood pressure was measured using a validated automatic sphygmomanometer. First-trimester maternal daily intake of energy, fat, protein and carbohydrate was not associated with childhood blood pressure. Furthermore, maternal intake of micronutrients was not associated with childhood blood pressure. Also, higher maternal vitamin B12 concentrations were associated with a higher diastolic blood pressure (0·31 mmHg per standard deviation increase in vitamin B12 (95 % CI 0·06, 0·56)). After taking into account multiple testing, none of the associations was statistically significant. Maternal first-trimester folate and homocysteine concentrations were not associated with childhood blood pressure. The results from the present study suggest that maternal Fe intake and vitamin B12 concentrations during the first trimester of pregnancy might affect childhood blood pressure, although the effect estimates were small and were not significant after correction for multiple testing. Further studies are needed to replicate these findings, to elucidate the underlying mechanisms and to assess whether these differences in blood pressure persist in later life.

Fibre has been shown to exert a number of benefits on gastrointestinal (GI) health, yet its intake is low. Addition of novel fibres to food products may increase fibre intake and improve gut health. The objective of the present study was to evaluate the influence of three novel fibres on GI outcomes in healthy human subjects. A total of twenty healthy participants (ten men and ten women) with normal BMI (23 (sem 2) kg/m2) participated in the present randomised, double-blind, cross-over study with five treatment periods. Participants consumed a maltodextrin control or 20–25 g/d fibre from soluble maize fibre (SCF) or resistant starch (RS), alone or in combination with pullulan (SCF+P and RS+P). The treatment periods were 7 d with a 3-week washout between the periods. Stool samples were collected on day 7 of each period, and GI tolerance was assessed via a questionnaire on days 1 and 6. There were no treatment differences in stool weight or consistency. SCF significantly reduced stool pH and increased total SCFA production compared with RS and control. RS+P significantly increased the percentage of butyrate compared with all the other treatments. Overall, GI symptoms were minimal. SCF+P led to the highest GI score on day 1, while RS+P had the highest score on day 6. Both SCF treatments caused a significant shift in the gut microbial community. These functional fibres are generally well tolerated, have minimal effects on laxation and may lead to beneficial changes in SCFA production in healthy adults.

The study evaluated whether feeding diosmectite–ZnO composite (DS-ZnO) at 500 mg Zn/kg to early weaned pigs would alleviate the weaning-related intestinal disorders as a substitute for high concentration of ZnO (2250 mg Zn/kg). The pigs weaned at an age of 21 ± 1 d were allotted to four treatments groups as follows: (1) control; (2) DS-ZnO, 500 mg Zn/kg diet; (3) ZnO, 2250 mg Zn/kg diet; and (4) mixture of 2·0 g DS/kg and 500 mg Zn/kg from ZnO (equal amount of DS and ZnO in the DS-ZnO treatment group). The results showed that, compared with the control on days 7 and 14 post-weaning, addition of DS-ZnO at 500 mg Zn/kg improved (P< 0·05) daily gain and feed intake, decreased (P< 0·05) post-weaning scour scores, increased (P< 0·05) jejunal villus height and the ratio of villus height and crypt depth, decreased (P< 0·05) jejunal paracellular permeability of fluorescein isothiocyanate dextran 4 kDa and up-regulated (P< 0·05) tight junction protein expression of occludin, claudin-1 and zonula occludens-1 in jejunal mucosa. The mRNA levels of TNF-α, IL-6 and interferon-γ (IFN-γ) on day 7 post-weaning were also decreased (P< 0·05). The piglets fed DS-ZnO at 500 mg Zn/kg did not differ in the above parameters from those fed ZnO at 2250 mg Zn/kg, while they had better performance than those fed the mixture of DS and ZnO. Supplementation with DS-ZnO at 500 mg Zn/kg was effective in alleviating diarrhoea, barrier dysfunction and inflammatory cytokine expression and up-regulating tight junction protein expression.

Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTX-induced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

Epidemiological studies have indicated that dietary flavonoids generally, and flavonols specifically, may contribute to cardiovascular health. Tea consumption, which is often the main dietary source of flavonoids and flavonols, is associated with a reduced risk of cardiovascular outcomes. The primary objective of the present study was to explore the association of the habitual intake of flavonols from tea and non-tea sources with the risk of atherosclerotic vascular disease mortality in a population of elderly women. A total of 1063 women, aged over 75 years, were randomly selected from ambulant Caucasian women living in Perth, Western Australia. Flavonoid consumption was assessed using the US Department of Agriculture Flavonoid, Flavone and Proanthocyanidin databases. Atherosclerotic vascular disease mortality was assessed over 5 years of follow-up through the Western Australian Data Linkage System. During the follow-up, sixty-four women died from atherosclerotic vascular disease. Women in the highest compared with the lowest tertile of flavonol intake had a lower risk of atherosclerotic vascular disease death (OR 0·27, 95 % CI 0·13, 0·59; P≤ 0·01 for trend in multivariate-adjusted models). Similar relationships were observed for flavonol intake derived from both tea (OR 0·38, 95 % CI 0·18, 0·79; P< 0·01) and non-tea (OR 0·41, 95 % CI 0·20, 0·85; P= 0·05) sources. Tea was the main contributor to flavonol intake (65 %), and the intakes of flavonols from tea and non-tea sources were not significantly correlated. In conclusion, increased consumption of flavonols was independently associated with a lower risk of atherosclerotic vascular disease mortality. Both tea and non-tea sources of flavonols were independently associated with this benefit.

Human milk proteins provide term and preterm infants with both nutrition and protection. The objective of the present study was to examine longitudinal changes in the protein composition of term and preterm milk during the first 2 months of lactation, focusing on protein phosphorylation and glycosylation. Using gel electrophoresis, the relative concentration and glycosylation status of lactoferrin, secretory Ig A, β-casein, α-lactalbumin, serum albumin, bile salt-stimulated lipase, xanthine oxidoreductase, tenascin and macrophage mannose receptor 1 were measured in milk collected on days 7, 10, 14, 18, 21, 28 and 60 postpartum from preterm mothers (28–32 weeks gestation, n 17). The phosphorylation status of β-casein was also investigated. To determine if these variables differ in term and preterm milk, samples from term mothers (38–41 weeks gestation, n 8) collected on days 7, 14 and 30 of lactation were also analysed. The concentration of the abundant milk proteins decreased during lactation in term and preterm milk (P <0·05). No difference in protein glycosylation was observed, except for the glycoproteins serum albumin and tenascin. The phosphorylation of β-casein varied significantly between term and preterm milk. Further investigation is required to determine whether these modifications affect protein function and are clinically important to preterm infants.

Biofortification of cassava with the provitamin A carotenoid β-carotene is a potential mechanism for alleviating vitamin A deficiency. Cassava is a staple food in the African diet, but data regarding the human bioavailability of β-carotene from this food are scarce. The objective of the present study was to evaluate provitamin A-enhanced cassava as a source of β-carotene and vitamin A for healthy adult women. The study was a randomised, cross-over trial of ten American women. The subjects consumed three different porridges separated by 2 week washout periods. Treatment meals (containing 100 g cassava) included: biofortified cassava (2 mg β-carotene) porridge with added oil (15 ml peanut or rapeseed oil, 20 g total fat); biofortified cassava porridge without added oil (6 g total fat); unfortified white cassava porridge with a 0·3 mg retinyl palmitate reference dose and added oil (20 g total fat). Blood was collected six times from − 0·5 to 9·5 h post-feeding. TAG-rich lipoprotein (TRL) plasma was separated by ultracentrifugation and analysed using HPLC with coulometric array electrochemical detection. The AUC for retinyl palmitate increased after the biofortified cassava meals were fed (P< 0·05). Vitamin A conversion was 4·2 (sd 3·1) and 4·5 (sd 3·1) μg β-carotene:1 μg retinol, with and without added oil, respectively. These results show that biofortified cassava increases β-carotene and retinyl palmitate TRL plasma concentrations in healthy well-nourished adult women, suggesting that it is a viable intervention food for preventing vitamin A deficiency.

The present study was undertaken to elucidate the effect of ascorbic acid on alcohol-induced reproductive toxicity and also to compare it with that of abstention. A total of thirty-six male guinea pigs were divided into two groups and were maintained for 90 d as control and ethanol-treated groups (4 g/kg body weight (b.wt.)). After 90 d, ethanol administration was stopped and animals in the control group were divided into two groups and then maintained for 30 d as the control and control+ascorbic acid groups and those in the ethanol-treated group as ethanol abstention and ethanol+ascorbic acid (25 mg/100 g b. wt.) groups. Animals treated with ethanol showed a significant decline in sperm quality (P< 0·001), decreased activity of steroidogenic enzymes (P< 0·05) and reduced serum testosterone (P< 0·05), luteinising hormone and follicle-stimulating hormone levels, decrease in the activity of testicular succinate dehydrogenase, adenosine triphosphatase, sorbitol dehydrogenase and reduction in fructose content (P< 0·05). It also caused an increase in testicular malondialdehyde levels (P< 0·05) and decrease in the levels of glutathione content (P< 0·001) of testes. Ascorbic acid levels in testes and plasma were also reduced (P< 0·001) in ethanol-fed animals. Ascorbic acid supplementation altered all these parameters and produced a better and faster recovery from alcohol-induced reproductive toxicity than abstention. The mechanism of action of ascorbic acid may be by reducing the oxidative stress and improving antioxidant status, which eventually changed the microenvironment of testes and enhanced the energy needed for motility of sperms, improved the sperm morphology and elevated the testosterone and gonadotropin levels.

Creatine is essential for normal neural development; children with inborn errors of creatine synthesis or transport exhibit neurological symptoms such as mental retardation, speech delay and epilepsy. Creatine accretion may occur through dietary intake or de novo creatine synthesis. The objective of the present study was to determine how much creatine an infant must synthesise de novo. We have calculated how much creatine an infant needs to account for urinary creatinine excretion (creatine's breakdown product) and new muscle lay-down. To measure an infant's dietary creatine intake, we measured creatine in mother's milk and in various commercially available infant formulas. Knowing the amount of milk/formula ingested, we calculated the amount of creatine ingested. We have found that a breast-fed infant receives about 9 % of the creatine needed in the diet and that infants fed cows' milk-based formula receive up to 36 % of the creatine needed. However, infants fed a soya-based infant formula receive negligible dietary creatine and must rely solely on de novo creatine synthesis. This is the first time that it has been shown that neonatal creatine accretion is largely due to de novo synthesis and not through dietary intake of creatine. This has important implications both for infants suffering from creatine deficiency syndromes and for neonatal amino acid metabolism.

The microbial colonisation of the infant gut begins immediately after birth and is essential for the development of the intestine, the immune system and later well-being. Important differences have been reported in the characteristics of such microbiota in different infant population groups. In the present study, we employed an in vitro faecal batch culture model using faeces from different human population groups (adults and full-term breast-fed, full-term formula-fed and preterm infants) to determine the influence that the addition of four bifidobacterial strains and fructo-oligosaccharides (FOS) exerts on the profile of SCFA measured by GC as well as on the levels of some relevant intestinal microbial groups by quantitative PCR during incubation. Differences were found in the levels of SCFA and intestinal microbial groups in the faecal cultures depending on the human group origin of the faecal samples (P< 0·05), this being a predominant factor, compared with bifidobacteria or FOS added, in determining microbiota dynamics. These results exhibit the importance of the initial characteristics of the basal intestinal microbiota in the effect exerted by bifidobacteria or FOS that are added and highlight the need to design probiotics targeting specific human population groups.

Exclusive breast-feeding until 6 months is advised by the WHO as the best practice to feed infants. Yet, some studies have suggested a gap between energy requirements and the energy provided by human milk for many infants at 6 months. In order to assess the adequacy of WHO recommendations in 6-month-old Senegalese lactating infants, a comprehensive study was designed to measure human milk intake by the dose-to-the mother 2H2O turnover method. Infants' energy intakes were calculated using daily breast milk intake and the energy content of milk was estimated on the basis of creamatocrit. Of the fifty-nine mother–infant pairs enrolled, fifteen infants were exclusively breast-fed (Ex) while forty-four were partially breast-fed (Part). Infants' breast milk intake was significantly higher in the Ex group (993 (sd 135) g/d, n 15) compared with the Part group (828 (sd 222) g/d, n 44, P= 0·009). Breast milk energy content as well as infants' growth was comparable in both groups. However, infants' energy intake from human milk was significantly higher (364 (sd 50) kJ/kg per d (2586 (sd 448) kJ/d)) in the Ex group than in the Part group (289 (sd 66) kJ/kg per d (2150 (sd 552) kJ/d), P< 0·01). Compared with WHO recommendations, the results demonstrate that energy intake from breast milk was low in partially breast-fed infants while exclusively breast-fed 6-month-old Senegalese infants received adequate energy from human milk alone, the most complete food for infants. Therefore, advocacy of exclusive breast-feeding until 6 months should be strengthened.

While the need for colostrum in neonates is well established, the systemic effect of feeding bovine colostrum (BC) to adult humans is gaining increasing attention. However, no systematic studies evaluating the immunomodulatory effect of BC in dogs have been reported. The aim of the present study was to evaluate the immunomodulatory effect of dietary supplementation of BC in dogs. The study was conducted in two phases: pre-test (8 weeks) and test (40 weeks), with twenty-four dogs (mean age 2·5 years) randomised into two groups. In the ‘pre-test’ phase, both groups were fed a nutritionally complete diet. At the end of the ‘pre-test’ phase, all dogs received a canine distemper virus (CDV) vaccine, and dogs in the ‘test group’ were switched to a diet supplemented with 0·1 % spray-dried BC. Response to the CDV vaccine was evaluated by measuring vaccine-specific plasma IgG levels. Gut-associated lymphoid tissue response was assessed by measuring faecal IgA levels. Gut microbiota were evaluated by the temporal temperature gel electrophoresis methodology. Dogs fed the BC-supplemented diet demonstrated a significantly higher vaccine response and higher levels of faecal IgA when compared with the control group. Supplementing diets with BC also resulted in significantly increased gut microbiota diversity and stability in the test group. In conclusion, diets supplemented with BC significantly influence immune response in dogs.

The soluble fibre (1 → 3)(1 → 4)-β-d-glucan attenuates postprandial glycaemic responses when administered in solution. This attenuating effect is strengthened when solution viscosity is increased by increasing the β-glucan dose or molecular weight (MW). The effect of varying solution viscosity by changing solution volume, without changing the β-glucan dose or MW, on glycaemic responses was determined. A total of fifteen healthy subjects received six 50 g oral glucose beverages prepared with or without 4 g of high-MW (HMW, 580 000 g/mol) or low-MW (LMW, 145 000 g/mol) β-glucan, with a beverage volume of 250 or 600 ml. Postprandial plasma glucose concentration was measured over 2 h, and the peak blood glucose rise (PBGR) and the incremental area under the glycaemic response curve (AUC) were calculated. Subjects served as their own controls. The physico-chemical properties of the beverages were measured to examine their relationship with glycaemic response results. The HMW β-glucan beverage was more viscous and achieved greater reductions in PBGR than the glucose beverage with LMW β-glucan (P< 0·05). At the same MW, the 250 and 600 ml β-glucan beverages differed in viscosity (>9-fold difference) but not in PBGR (P>0·05). No differences in AUC were detected among the beverages (P= 0·147). The effects of β-glucan on glycaemic response were altered by changes in beverage viscosity achieved through changes in MW but not in volume. Therefore, β-glucan dose and MW are the most vital characteristics for optimising the bioactivity of β-glucan solutions with respect to glycaemic response.

There is a lack of recognised markers for measuring gastrointestinal (GI) well-being and digestive symptoms in the general population. The aim of the present study was to demonstrate construct validity of a global assessment tool of GI well-being. In this randomised double-blind study, 197 adult women consumed either a probiotic fermented milk or a control dairy product daily during 4 weeks. GI well-being was assessed weekly using a single question and subjects indicated whether their GI well-being remained the same, improved or worsened compared with the baseline period. Responders for GI well-being were subjects reporting improvement for at least 2 weeks of the 4 weeks of intervention. Frequency of individual digestive symptoms was assessed weekly. Health-related quality of life (HRQoL) was measured at baseline and at the end of the study. Subjects reporting improvement of their GI well-being had a significantly (P< 0·05) lower frequency of combined digestive symptoms than individuals with no change, whereas subjects with worsened GI well-being had a significantly (P< 0·05) higher digestive symptom frequency. Number of weeks with reported GI well-being improvement was significantly (P< 0·05) correlated with the decrease in digestive symptoms (r 0·58) and the HRQoL digestive comfort dimension (r 0·47). When compared with non-responders, responders had significantly (P< 0·0001) fewer average digestive symptoms and higher scores on digestive comfort of the HRQoL questionnaire. The data provide construct validity for a single-item questionnaire as a measure of GI well-being improvement. These data support the use of this questionnaire as an end point for nutritional intervention in the general population.

Laminaria japonica is traditionally eaten in Japan as a beneficial food for thrombosis. The alga contains two specific ingredients, a xanthophyll fucoxanthin (FX) and a polysaccharide, F-fucoidan (FD). The aim of the present study was to investigate whether FX or FD exhibited anti-thrombotic effects. For this purpose, three types of capsules, containing 1 mg FX, 400 mg fucoidan, and both, were prepared from the alga and administered to volunteers for 5 weeks. The dose of FD or FD+FX significantly shortened lysis time (LT) of the thrombus measured by a global thrombosis test in the blood, but FX did not. Examining the mechanism, dietary FD increased H2O2 and the secretion of prostacyclin (PGI2), a potent inhibitor of platelet aggregation, in the blood, although FD was under the detection limit in the blood, determining with its monoclonal antibody. Furthermore, in mouse experiments, dietary FD was totally excreted into the faeces and was not incorporated into the blood. We then employed a co-culture system of a Caco-2 cell monolayer with fresh human blood. The addition of FD to Caco-2 cells stimulated the expression of NADPH oxidase 1 (NOX1) and dual oxidase 2 (DUOX2) mRNA and secreted H2O2 onto the blood side accompanied by a significant increase in serum PGI2 production. These effects were invalidated by the combined addition of FD with its monoclonal antibody. The results suggested that dietary FD stimulated the expression of H2O2-producing enzymes in intestinal epithelial cells and released H2O2 into the blood, which played a signalling role to increase PGI2 production and then shortened LT for thrombi.

Green tea catechins (GTC) reduce UV radiation (UVR)-induced inflammation in experimental models, but human studies are scarce and their cutaneous bioavailability and mechanism of photoprotection are unknown. We aimed to examine oral GTC cutaneous uptake, ability to protect human skin against erythema induced by a UVR dose range and impact on potent cyclo-oxygenase- and lipoxygenase-produced mediators of UVR inflammation, PGE2 and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively. In an open oral intervention study, sixteen healthy human subjects (phototype I/II) were given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks. Pre- and post-supplementation, the buttock skin was exposed to UVR and the resultant erythema quantified. Skin blister fluid and biopsies were taken from the unexposed and the UVR-exposed skin 24 h after a pro-inflammatory UVR challenge (three minimal erythema doses). Urine, skin tissue and fluid were analysed for catechin content and skin fluid for PGE2 and 12-HETE by liquid chromatography coupled to tandem MS. A total of fourteen completing subjects were supplement compliant (twelve female, median 42·5 years, range 29–59 years). Benzoic acid levels were increased in skin fluid post-supplementation (P= 0·03), and methylated gallic acid and several intact catechins and hydroxyphenyl-valerolactones were detected in the skin tissue and fluid. AUC analysis for UVR erythema revealed reduced response post-GTC (P= 0·037). Pre-supplementation, PGE2 and 12-HETE were UVR induced (P= 0·003, 0·0001). After GTC, UVR-induced 12-HETE reduced from mean 64 (sd 42) to 41 (sd 32) pg/μl (P= 0·01), while PGE2 was unaltered. Thus, GTC intake results in the incorporation of catechin metabolites into human skin associated with abrogated UVR-induced 12-HETE; this may contribute to protection against sunburn inflammation and potentially longer-term UVR-mediated damage.