This review focuses on several key aspects related to the main group of phenolic metabolites in circulation.

Seaweeds may have an important role in modulating chronic disease. Rich in unique bioactive compounds not present in terrestrial food sources, including different proteins (lectins, phycobiliproteins, peptides, and amino acids), polyphenols, and polysaccharides, seaweeds are a novel source of compounds with potential to be exploited in human health applications. Purported benefits include antiviral, anticancer, and anticoagulant properties as well as the ability to modulate gut health and risk factors for obesity and diabetes. Though the majority of studies have been performed in cell and animal models, there is evidence of the beneficial effect of seaweed and seaweed components on markers of human health and disease status. This review is the first to critically evaluate these human studies, aiming to draw attention to gaps in current knowledge, which will aid the planning and implementation of future studies.

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The traditional Mediterranean diet is thought to represent a healthy lifestyle; especially given the incidence of several cancers including colorectal cancer is lower in Mediterranean countries compared to Northern Europe. Olive oil, a central component of the Mediterranean diet, is believed to beneficially affect numerous biological processes. We used phenols extracted from virgin olive oil on a series of in vitro systems that model important stages of colon carcinogenesis. The effect the extract on DNA damage induced by hydrogen peroxide was measured in HT29 cells using single cell microgel-electrophoresis. A significant anti-genotoxic linear trend (p 5 0.011) was observed when HT29 cells were preincubated with olive oil phenols (0,5,10,25,50, 75, 100 lg/ml) for 24 hr, then challenged with hydrogen peroxide. The olive oil phenols (50, 100 lg/ml) significantly (p 5 0.004, p 5 0.002) improved barrier function of CACO2 cells after 48 hr as measured by transepithelial resistance. Significant inhibition of HT115 invasion (p < 0.01) was observed at olive oil phenols concentrations of 25, 50, 75, 100 lg/ml using the matrigel invasion assay. No effect was observed on HT115 viability over the concentration range 0, 25, 50 75, 100 lg/ml after 24 hr, although 75 and 100 lg/ml olive oil phenols significantly inhibited HT115 cell attachment (p 5 0.011, p 5 0.006). Olive oil phenols had no significant effect on metastasis-related gene expression in HT115 cells. We have demonstrated that phenols extracted from virgin olive oil are capable of inhibiting several stages in colon carcinogenesis in vitro. ' 2005 Wiley-Liss, Inc.

Brown seaweeds such as Ascophyllum nodosum are a rich source of phlorotannins (oligomers and polymers of phloroglucinol units), a class of polyphenols that are unique to Phaeophyceae. At present, there is no information on the bioavailability of seaweed polyphenols and limited evidence on their bioactivity in vivo. Consequently, we investigated the gastrointestinal modifications in vitro of seaweed phlorotannins from A. nodosum and their bioavailability and effect on inflammatory markers in healthy participants. In vitro, some phlorotannin oligomers were identified after digestion and colonic fermentation. In addition, seven metabolites corresponding to in vitro-absorbed metabolites were identified. Urine and plasma samples contained a variety of metabolites attributed to both unconjugated and conjugated metabolites (glucuronides and/or sulphates). In both urine and plasma, the majority of the metabolites were found in samples collected at late time points (6-24 h), suggesting colonic metabolism of high-molecular-weight phlorotannins, with three phlorotannin oligomers (hydroxytrifuhalol A, 7-hydroxyeckol, C-O-C dimer of phloroglucinol) identified in urine samples. A significant increase of the cytokine IL-8 was also observed. Our study shows for the first time that seaweed phlorotannins are metabolised and absorbed, predominantly in the large intestine, and there is a large inter-individual variation in their metabolic profile. Three phlorotannin oligomers present in the capsule are excreted in urine. Our study is the first investigation of the metabolism and bioavailability of seaweed phlorotannins and the role of colonic biotransformation. In addition, IL-8 is a possible target for phlorotannin bioactivity.Key words: Polyphenols: Phlorotannins: Brown seaweed: Bioavailability: Metabolism: Human subjects There has been increasing interest in the past few years on the bioactive compounds present in seaweeds (1)(2)(3) . Traditionally, seaweeds are consumed as a food product in Asian countries and are increasingly used worldwide as ingredients for industrial applications. In Japan, over twenty species of red, green and brown algae (seaweed) are included in meals (4) , and daily seaweed consumption per person has remained relatively consistent over the past 40 years, in the range of 1·50-3·65 kg/ person per year, as reported by a range of studies (5)(6)(7) . Seaweeds are a rich source of polyphenolic compounds (8) , and polyphenols extracted from algae (9,10) show some similarities to those found in land plants (9)(10)(11) . Thus, the main polyphenols found in brown seaweeds are phlorotannins (12)(13)(14)(15) , a type of phenolic compound only found in brown seaweeds (16) . Brown seaweed phlorotannins are oligomers and polymers of phloroglucinol units, and their oligomer and polymer molecular weights can greatly vary, from 126 Da to 650 kDa (3) , comprising up to 15 % of the plant dried weight (11) . It has been reported that the consumption of brown algae is on average 1·342 kg/ person per year, containing ...

Globally, colorectal cancer (CRC) is a leading cause of mortality from malignant disease. Case–control and cohort studies provide strong support for a role of diet in the aetiology of CRC. However to establish causal relationships and to identify more precisely the dietary components involved, intervention studies in human subjects are required. Cancer is an impractical endpoint in terms of numbers, cost, study duration and ethical considerations. Consequently, intermediate biomarkers of the disease are required. This review aims to provide an overview of the intermediate endpoints available for the study of CRC, particularly non-invasive faecal biomarkers. Examples of their use in dietary intervention studies are given.

BackgroundThere is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins.MethodsA "colon-available" raspberry extract (CARE) was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion.ResultsThe phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G1 phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function) assessed by recording the trans-epithelial resistance (TER) of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay.ConclusionThe results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro.