E‐SAR‐94010 (LipoEsar®): A Pleiotropic Lipoprotein Compound with Powerful Anti‐atheromatous and Lipid Lowering Effects

E-SAR-94010 (LipoEsar) is a natural product extracted from the marine species S. pilchardus, by means of non-denaturing biotechnological procedures. The main chemical ingredient of LipoEsar is a lipoprotein (60–80%) whose micelle structure probably mimics that of physiological lipoproteins involved in lipid metabolism. In preclinical studies LipoEsar has shown to be effective in (a) reducing blood cholesterol (Cho), triglyceride (TG), uric acid (UA), and glucose (Glu) levels, as well as liver alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity; (b) enhancing immunological function by regulating both lymphocyte and microglia activity; (c) inducing antioxidant effects mediated by superoxide dismutase activity; and (d) improving cognitive function. Clinical studies have revealed that LipoEsar reduces blood total cholesterol (T-Cho) (20–30%), Glu (5–10%), UA (10–15%), TG (30–50%), ALT and AST, after 1–3 months of treatment at a daily dose of 250–500 mg (t.i.d.). The effect on T-Cho is the result of decreasing LDL-Cho levels and increasing HDL-Cho levels in parallel with an improvement in hepatic protection reflected by reduction in ALT, AST, and GGT activity. Most of these therapeutic effects on the regulation of lipid metabolism tend to show an age-dependent pattern and are also associated with specific genomic profiles in the population. In addition, LipoEsar diminishes the size of xanthelasma plaques by 30–60% after 6–9 months of treatment. Similar effects can be observed on atheromatous plaques on the aortic wall of patients with familial and sporadic hypercholesterolemia. LipoEsar is the first marine biotechnological product with lipoprotein structure displaying hypolipemic activity in blood and tissues acting as a potential neuroprotectant in cerebrovascular disorders and arteriosclerosis. Preliminary studies indicate that the biological activity of LipoEsar is genotype-dependent. Since genetic defects in the APOE gene result in familial dysbetalipoproteinemia or type III hyperlipoproteinemia (HLP-III) with increased plasma Cho and TG as a consequence of impaired clearance of chylomicron and VLDL remnants, in the present paper we have investigated the influence of different APOE genotypes on the therapeutic response of LipoEsar in patients with chronic dyslipemia. The study has been performed in 419 patients (age: 55.24 ± 17.71 years; range: 9–96 years) of both sexes (females: N = 212; age: 57.04 ± 17.68 years; range: 15–96 years; males: N = 207; age: 53.38 ± 17.58