Impact of a (poly)phenol-rich extract from the brown algae Ascophyllum nodosum on DNA damage and antioxidant activity in an overweight or obese population: a randomized controlled trial

Abstract

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.

Fucus vesiculosus and Ascophyllum nodosum Ameliorate Liver Function by Reducing Diet-Induced Steatosis in Rats

“…In this study, we investigated the effects of the five-week administration of the phytocomplex obtained from two brown algae, A. nodosum and F. vesiculosus, on glycemic control and liver function of HFD-treated Wistar rats. Several studies have confirmed the multiple beneficial effects of seaweed products, since their bioactive components have antidiabetic, antiobesity, and antioxidant properties [4,13,[16][17][18][19][20]. A recent study reported that ascophyllan from A. nodosum is able to induce glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells, suggesting that it may represent a useful agent for controlling blood glucose in humans [21,22].…”

Biomarkers of seaweed intake

“…Hydroxytrifuhalol A, 7-hydroxyeckol, C-O-C dimer of phloroglucinol, diphloroethol, fucophloroethol, dioxinodehydroeckol, and/or their glucuronides or sulfate esters (Additional file 1: Figure S1) were selected as candidate BFIs for brown seaweed because of their apparent specificity and their suitable postprandial kinetics [20,21]. Fucoxanthinol, a metabolite of fucoxanthin, has also been found in plasma from a study after only a single oral dose of brown seaweed, making it interesting also as a candidate short-term biomarker [22].…”

“…In the study by Corona et al, there were substantial differences among volunteers in their pattern and extent of phlorotannin metabolism [20]. The total level of phlorotannins and their metabolites ranged from 0.01 to 7.8 μg/ ml and from 0.15 to 33.5 μg/ml quantified as phloroglucinol equivalents in urine and plasma, respectively [20], while the range extended from 0.13 to 522.09 μg/ml quantified as phloroglucinol equivalents in urine in another study [21]. The large inter-individual differences have been attributed to variation in the microbiota composition in the colon and to differences in expression of phase II metabolizing enzymes [46,54], suggesting large inter-individual variation in metabolite kinetics and, consequently, in their potential usefulness as BFIs for quantitative intake assessment.…”

“…Therefore, these two ions can be regarded as clues for further identifications [20]. Another study [21] also reported that the phloroglucinol derivatives, pyrogallol and phloroglucinol sulfates, dioxinodehydroeckol glucuronide, diphlorethol sulfate, and fucophloroethol glucuronide, can be found in human urine after seaweed intake. Pyrogallol and phloroglucinol sulfates would not be considered as plausible biomarkers of seaweed, although they can be measured in urine after seaweed intake.…”

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

“…Higher oxidant status increases the oxidative damage of macromolecules, which, associated with obesity, increases the probability of chronic disease development [167], with obese individuals as a risk group. Baldrick et al [168] investigated the bioavailability and effect of an Ascophyllum nodosum (Linnaeus) Le Jolis polyphenol-rich extract on DNA damage, oxidative stress, and inflammation level. Eighty participants, of which 36 were obese, consumed daily, for eight weeks, a capsule containing 100 mg of Ascophyllum nodosum (Linnaeus) Le Jolis polyphenol-rich extract.…”