**4. Conclusions**

Our review revealed that fucosterols derived from macroalgae can potentially be applied in the nutraceutical and pharmacological industries based on its bioactivities, safety, and toxicity. Fucosterol derived from brown macroalgae exhibits potentially beneficial activities; however, certain research gaps should be addressed. Despite the uncovered biological activities, most studies remain at a preliminary stage, and some of them have not included the study of safety and toxicity to organisms; hence, more in-depth studies are required. The studies of bioactivity, safety, and toxicity of fucosterol have been carried out mostly at the in vitro level (52%), and only 26% have been conducted at the in vivo level using a mouse model. An in vivo experiment can provide fundamental data for understanding the mechanism of nutraceutical and pharmacological properties of sterol before it is used in clinical trials. However, we did not find any clinical studies on fucosterol published between 2002 and 2020. Studies on the safety and toxicity levels of fucosterol at the clinical stage are very important for the development of this sterol for the nutraceuticals and pharmaceutical industry. Brown macroalgae (Phaeophyta) are a major source of fucosterol. A total of 2071 species belonging to the class Phaeophyta have been recorded [68]. However, the study of fucosterol in brown macroalgae continues to be limited to only certain species. *Hizikia fusiformis/Sargassum fusiforme* and *Ecklonia cava* subsp. *stolonifera* are the two species with the highest number of publications. Additional studies on other Phaeophyta species are required to elucidate the fucosterol content in specific algal classes. Future comprehensive research on fucosterol, including the study of macroalgae sources, chemical characterization, pharmacokinetic mechanisms, in vitro, in vivo, and clinical experiments will elucidate the role of fucosterol as a potent bioactive compound derived from marine sources.

**Author Contributions:** Conceptualization, M.D.N.M., J.-S.K. and J.-S.C.; formal analysis, M.D.N.M., D.H., B.F.S.P.N. and G.T.; investigation, M.D.N.M., D.H., J.-S.C., B.F.S.P.N. and G.T.; methodology, M.D.N.M., J.-H.S. and J.-S.C.; software, D.H.; supervision, M.D.N.M., J.-S.K. and J.-S.C.; visualization, M.D.N.M., J.-H.S. and D.H.; writing—original draft, M.D.N.M. and D.H.; writing—review and editing, M.D.N.M. and J.-S.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Ministry of Oceans and Fisheries, Korea, under the Project No. PJT200885 entitled: "Development and commercialization of traditional seafood products based on the Korean coastal marine resources".

**Institutional Review Board Statement:** Not applicable.

**Data Availability Statement:** Data supporting reported results are available upon request.

**Conflicts of Interest:** The authors declare no conflict of interest.
