Are fucoidan and alginate active substances affecting CYP7A1 and HMG CoA reductase in dyslipidemia condition?

Context: Dyslipidemia, characterized by abnormal plasma lipid levels, is commonly treated with statins, which may induce adverse effects. Fucoidan and alginate, bioactive marine polysaccharides, have emerged as potential natural modulators of lipid metabolism via cholesterol 7 alpha-hydroxylase 1 (CYP7A1) and HMG-CoA reductase (HMGCR). Aims: To evaluate systematically the efficacy of fucoidan and alginate as adjunctive therapies for dyslipidemia, with a specific focus on lipid profiles mediated through the regulation of CYP7A1 and HMGCR. Methods: This systematic review was conducted according to PRISMA guidelines. Literature was searched across Scopus, PubMed, Cochrane, ScienceDirect, and ProQuest. Research that examined human and mammalian models of dyslipidemia treated with fucoidan or alginate was included; however, no studies specifically addressing human dyslipidemia were found. This review was conducted according to the PRISMA guidelines and follows the PICO format. Risk of bias was assessed using the SYRCLE tool and implemented by the GRADE tools to assess study quality. Results: Nineteen preclinical studies met the inclusion criteria. Fucoidan and alginate interventions consistently improved lipid profiles, with reductions in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides observed in over 85% of studies, and increases in high-density lipoprotein cholesterol (HDL-C) noted in nearly half. Eight studies demonstrated a significant upregulation of CYP7A1 expression, indicating enhanced bile acid synthesis, while eight studies reported significant downregulation of HMGCR, suggesting inhibition of cholesterol biosynthesis. These changes were dose-dependent in several cases, highlighting their regulatory effects on lipid metabolism pathways. Conclusions: Fucoidan and alginate show promise as adjunct therapies for dyslipidemia by modulating lipid metabolism through CYP7A1 and HMGCR. While preclinical findings are encouraging, heterogeneity among studies and the lack of clinical data limit the strength of current evidence. Further mechanistic studies and well-designed clinical trials are warranted to confirm translational relevance.