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.

The composition of polyphenols in ileal fluid samples obtained from an ileostomy subject after lingonberry intake was compared with lingonberry extracts obtained after simulated in vitro digestion (IVDL) and subsequent faecal fermentation (IVFL). HPLC-PDA-MS/MS analysis confirmed similar patterns of lingonberry (poly)phenolic metabolism after the in vivo and in vitro digestion, with reduced recovery of anthocyanins and a similar pattern of recovery for proanthocyanidins observed for both methods of digestion. On the other hand, the IVFL sample contained none of the original (poly)phenolic components but was enriched in simple aromatic components. Digested and fermented extracts exhibited significant (P < 0.05) anti-genotoxic (Comet assay), anti-mutagenic (Mutation Frequency assay), and anti-invasive (Matrigel Invasion assay) effects in human cell culture models of colorectal cancer at physiologically-relevant doses (0-50 μg/mL gallic acid equivalents). The ileal fluid induced significant anti-genotoxic activity (P < 0.05), but at a higher concentration (200 μg/mL gallic acid equivalents) than the IVDL. Despite extensive structural modification following digestion and fermentation, lingonberry extracts retained their bioactivity in vitro. This reinforces the need for studies to consider the impact of digestion when investigating bioactivity of dietary phytochemicals.

Evidence from epidemiological studies suggests that diets rich in fruit and vegetables may contribute to a reduced risk of colorectal cancer (CRC). A recent meta-analysis of risk factors associated with colorectal cancer reported a decreased risk associated with fruit consumption (RR = 0·85, 95% CI = 0·75-0·96 for 3 servings/day) and also emphasized that low fruit and vegetable consumption was associated with a moderately increased risk of CRC (1) . Lingonberry (Vaccinium vitis-idaea L) is a popular edible berry in Scandinavian countries and is increasing in popularity across Europe. Lingonberry possesses a complex (poly)phenolic profile, which may contribute to its putative anticancer activity. Following consumption and digestion, limited uptake from the small intestine results in berry (poly)phenolic compounds entering the colon, where they are subject to microbiota-mediated metabolism (2) . Therefore, it is likely that the colonic epithelium is exposed to phenolic metabolites as well as the original parent compounds.The aim of this study was to evaluate the impact of in vivo and in vitro digestion on phenolic composition and bioactivity of lingon berries. Lingonberry extracts obtained after simulated in vitro digestion (IVDL) and subsequent faecal fermentation (IVFL) were compared to samples of ileal fluid (IF) obtained from an ileostomist (3) pre & post lingonberry consumption 150 g (ID 12/WS/0192). Bioactivity of the extracts was tested using a physiologically-relevant dose range (0-50 μg/ml gallic acid equivalents) over a 24 hour exposure period using in vitro colonocyte models of colorectal carcinogenesis (Comet assay HT29, mutagenicity assay HT29G 17 neo, Matrigel invasion assay HT115) (4) . LC-MS analysis confirmed that in vitro digestion altered the (poly)phenol composition relative to the original lingonberry and similar patterns were observed for the ileal fluid. On the other hand, the IVFL sample had high levels of simple aromatic components. Digested and fermented extracts exhibited significant (p < 0·05) anti-genotoxic, antimutagenic and anti-invasive effects compared to the appropriate controls (ANOVA, Post Hoc Dunnett T test) in all in vitro models. The ileal fluid demonstrated a significant reduction in DNA damage (p < 0·05), but at a higher total polyphenol concentration (μg/ml GAE/ml) than the IVDL. Despite extensive structural modification following digestion and fermentation, lingonberry extracts retained their bioactivity. These data reinforce the need for screening studies to consider the impact of digestion when investigating bioactivity of dietary phytochemicals.

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