**4. Future Considerations**

Previous studies focusing brown seaweed-fortified products have demonstrated that in general, macroalgae can improve the nutritional value of the food products, either by incrementing levels of dietary fibres and/or minerals or their lipidic profiles. Thus, fortified foods with seaweed and/or seaweed extracts come out as possible nutritional alternatives to the original formulations. Moreover, the reported information seems to be solid regarding the fact that the fortification of foods with brown seaweeds and/or their extracts in general have positive impacts on both their oxidative stability and microbial inhibition effects. However, discrepant results are reported regarding the technological properties of the fortified products, namely on the stability of the food's structure. Hence, there is the need to guarantee the compatibility of seaweeds and the overall food matrix, which is not only a result of the seaweed itself, but of the combination of the seaweed with the proper ingredients. In addition, the incorporation of seaweeds in foods frequently comprises their sensorial attributes due to colour changes and the appearance of off-flavours. Nevertheless, some strategies such as fermentation, enzymatic processing or encapsulation of seaweeds or their extracts have already shown interesting effects at cloaking seaweeds' negative sensorial characteristics while maintaining their nutritional properties and stability of bioactive components [122–124]. Nevertheless, further research in this field is necessary to understand if the cost-benefit of the application of such techniques is viable on a larger scale.

Being a crucial factor in nutrition, the bioavailability of relevant nutrients and/or phytochemicals is another critical issue that will require much attention in the following years. This is highly dependent on food components and on individual gastrointestinal conditions. Alginic acid, fucoidans and laminarans are considered dietary fibres, meaning that they may be fermented by colon microflora, therefore surviving the majority of the digestion [125]. The rest of the compounds seem, however, to be absorbed at earlier stages. For instance, in vitro studies suggested that dietary fucoxanthin is metabolized to fucoxanthinol and amarouciaxanthin A [126,127]. In fact, daily administered dietary fucoxanthin (*L. japonica* and *U. pinnatifida* origin) was shown to accumulate as amarouciaxanthin A and fucoxanthinol in several mice tissues [128,129]. In humans, however, the plasma concentrations of fucoxanthin metabolites before and after 1-week dietary interventions with *U. pinnatifida* were shown to be either low (fucoxanthinol) or non-existent (fucoxanthin and amarouciaxanthin A), although a higher subject group would be required in order to confirm these results [130].

As for phlorotannins, to the authors knowledge, only one bioavailability study was made using this particular compound from any of the seaweeds of interest to this review. Recently, in a work developed by Corona et al. (2016), a food-grade phlorotannin extract from *A. nodosum* was submitted to in vitro and in vivo assays, the latter involving the oral administration of a 100 mg capsule with the same extract [57]. The in vitro digestion and fermentation allowed for the identification of 11 compounds including hydroxytrifuhalol A, a C-O-C dimer of phloroglucinol, diphlorethol/difucol and 7-hydroxyeckol, some of which were also detected in the urine and plasma of human participants, thus confirming their absorption into the blood circulation. Moreover, although brown seaweeds are considered a great source of iodine, there is limited information regarding its bioavailability. Domínguez-Gonzaléz et al. [131] found out that despite the high in vitro bioaccessibility of iodine from *U. pinnatifida* and *S. japonica*, only a small percentage was bioavailable using dialysis membranes and an even lower in a biological system model consisting of two major cell types present in the intestine. Nevertheless, more favourable results were demonstrated when iodine-insufficient women were supplemented with encapsulated *A. nodosum*, since one third of the ingested iodine was found to be bioavailable [132].

Hence, it is clear that, not only is there a lack of information regarding the bioavailability of nutrients/phycochemicals in seaweeds and seaweeds-fortified foods in general, but also the relationship between seaweed-fortified products and their potential functionality remains almost unexploited. Indeed, evidences of biological effects of seaweeds-fortified products were barely proven in cellular models and even more rarely in in vivo trials and hence, must still be made to assure the conformity of the results. According to Plaza et al. [133], the principal guideline to follow in the design of a new functional food is to increase as much as possible the benefit/risk ratio, by increasing the benefit to the maximum and reducing the risk to the minimum, considering toxicity studies, for example. Increasing the benefit implies looking for a physiological wide effect, assuring the existing bioavailability and that the mentioned bioavailability is going to be kept along all the useful life of the food. Therefore, since the in vivo biological activity of phycochemicals depends on their bioavailability, in the future, it would be interesting to further access how important properties claimed for brown algae can transpose to human beings through seaweed fortified products. In order to reduce the risk, it is necessary to carry out toxicity studies, to use the functional ingredient in minimal effective doses and to use as functional ingredients, the products naturally found in foods or natural sources.
