Fate of intravenously administered squalene and plant sterols in human subjects

Abstract

We have studied metabolism of plant sterols and squalene administered intravenously in the form of lipid emulsion mimicking chylomicrons (CM). The CM-like lipid emulsion was prepared by dissolving squalene in commercially available Intralipid ® . The emulsion was given as an intravenous bolus injection of 30 ml containing 6.3 mg of cholesterol, 1.9 mg of campesterol, 5.7 mg of sitosterol, 1.6 mg of stigmasterol, 18.1 mg of squalene, and 6 g of triglycerides in six healthy volunteers. Blood samples were drawn from the opposite arm before and serially 2.5-180 min after the injections. The decay of CM squalene, plant sterols, and triglycerides was monoexponential. The half-life of CM squalene was 74 ؎ 8 min, that of campesterol was 37 ؎ 5 min ( P Ͻ 0.01 from squalene), and those of sitosterol, stigmasterol, and triglycerides were 17 ؎ 2, 15 ؎ 1, and 17 ؎ 2 min, respectively ( P Ͻ 0.01 from squalene and campesterol). The CM squalene concentration still exceeded the baseline level 180 min after injection ( P ‫؍‬ 0.02), whereas plant sterols and triglycerides returned to the baseline level between 45 and 120 min after injection. The half-lives of squalene and campesterol were positively correlated with their fasting CM concentrations. In addition, VLDL squalene, campesterol, and triglyceride concentrations, VLDL, LDL, and HDL sitosterol concentrations, as well as VLDL and LDL stigmasterol concentrations were increased significantly. Cholesterol concentrations increased in VLDL ( P Ͻ 0.05), but were unchanged in CM after injection. These data suggest that squalene clearance occurs more slowly than that of plant sterols and triglycerides from CM, and that squalene is more tightly associated with triglyceriderich lipoproteins than are plant sterols in injected CM-like emulsions. -Relas, H., H. Gylling, and T. A. Miettinen. Fate of intravenously administered squalene and plant sterols in human subjects.

Evaluating the efficacy of extracted squalene from seed oil in the form of microemulsion for the treatment of COVID‐19: A clinical study

“…In humans and animal trials, intravenous administration of SQ emulsion is safe and well-tolerated, with a slower clearance from the circulation compared to triglycerides and plant sterols. 38,61 SQ is a safe, effective, and preferred vaccine adjuvant, 37,62 as it improves antigen uptake by immune cells and evokes humoral and cell-mediated immunity. 63 Immune-modulating treatments in severe COVID-19 cases and antioxidant applications are considered as potential treatment strategies.…”

“…Toxicity or hypersensitive reaction was not reported. 38 In addition, in another study, vaccination with a subunit influenza vaccine with the MF59 adjuvant showed no antisqualene antibodies nor enhanced pre‐existing antisqualene antibody titers. It confirmed that antisqualene antibodies are not increased by immunization with vaccines with the MF59 adjuvant.…”

“…The safety and biocompatibility of SQ microemulsions have been shown in various studies. 36 , 37 , 38 , 39 …”

“…Due to the lipophilic structure of SQ, oil‐in‐water microemulsions can offer a suitable form for SQ intravenous injection. The safety and biocompatibility of SQ microemulsions have been shown in various studies 36–39 …”

“…The safety and biocompatibility of SQ microemulsions have been shown in various studies. [36][37][38][39] Developing novel therapeutics is crucial, but formulating new drugs and evaluating their safety and efficacy in a short time seems impractical due to the time-consuming nature of this process. Therefore, it is reasonable to examine substances with confirmed antiviral potentials that are safe and well-tolerated.…”