Background Epidemiologic evidence suggests that a diet rich in (poly)phenols has beneficial effects on many chronic diseases. Brown seaweed is a rich source of (poly)phenols. Objective The aim of this study was to investigate the bioavailability and effect of a brown seaweed (Ascophyllum nodosum) (poly)phenol extract on DNA damage, oxidative stress, and inflammation in vivo. Design A randomized, double-blind, placebo-controlled crossover trial was conducted in 80 participants aged 30–65 y with a body mass index (in kg/m2) ≥25. The participants consumed either a 400-mg capsule containing 100 mg seaweed (poly)phenol and 300 mg maltodextrin or a 400-mg maltodextrin placebo control capsule daily for an 8-wk period. Bioactivity was assessed with a panel of blood-based markers including lymphocyte DNA damage, plasma oxidant capacity, C-reactive protein (CRP), and inflammatory cytokines. To explore the bioavailability of seaweed phenolics, an untargeted metabolomics analysis of urine and plasma samples after seaweed consumption was determined by ultra-high-performance liquid chromatography–high-resolution mass spectrometry. Results Consumption of the seaweed (poly)phenols resulted in a modest decrease in DNA damage but only in a subset of the total population who were obese. There were no significant changes in CRP, antioxidant status, or inflammatory cytokines. We identified phlorotannin metabolites that are considered potential biomarkers of seaweed consumption including pyrogallol/phloroglucinol-sulfate, hydroxytrifurahol A-glucuronide, dioxinodehydroeckol-glucuronide, diphlorethol sulfates, C-O-C dimer of phloroglucinol sulfate, and C-O-C dimer of phloroglucinol. Conclusions To the best of our knowledge, this work represents the first comprehensive study investigating the bioactivity and bioavailability of seaweed (poly)phenolics in human participants. We identified several potential biomarkers of seaweed consumption. Intriguingly, the modest improvements in DNA damage were observed only in the obese subset of the total population. The subgroup analysis should be considered exploratory because it was not preplanned; therefore, it was not powered adequately. Elucidation of the biology underpinning this observation will require participant stratification according to weight in future studies. This trial was registered at clinicaltrials.gov as NCT02295878.

Cardiovascular disease (CVD) is currently the leading cause of death worldwide (1) . Epidemiological evidence has shown a positive effect of polyphenol intake on CVD risk (2) . Seaweed is a rich source of polyphenolic compounds, which can comprise 5 to 15% of the dried weight (3) . Some studies suggest that the potential antioxidant and anti-inflammatory benefits of seaweed-derived polyphenols may yield highly bioactive components with commercial potential for food and pharma applications (4) . The aim of this randomised, double-blind, placebo controlled, crossover design study was to investigate the biological activity of a food grade seaweed polyphenol extract (CEVA, France) in terms of reducing oxidative damage to DNA, modulation of inflammatory responses and reduction on chronic, low level inflammation in vivo.Volunteers were randomised to receive either a capsule containing 100 mg seaweed extract or a matched placebo daily for an 8 week period, with an 8 week washout period between each treatment. Fasting blood and urine samples were taken from each volunteer at 4 time-points during the study, at baseline and completion of the 2 treatment phases.80 apparently healthy volunteers (42·7 (SD 7·1) years, BMI 30·2(SD 3·9) kg/m 2 ) were recruited onto the study for 24 weeks; n = 78 completed both treatment periods. Blood and urine samples were analysed for an array of outcome measures including DNA damage to lymphocytes (Comet assay), intracellular cytokine activity (flow cytometer) (in preparation), C-reactive protein (CRP), triglycerides and isoprostane levels.There were no significant changes in either the placebo or seaweed treatment group for any of the parameters measured. However, there was a 31% decrease in CRP, although this did not reach statistical significance. The inflammatory markers are yet to be analysed but may provide additional information on the anti-inflammatory potential of a range of novel seaweed extracts that could be further exploited.