Dietary squalene increases cholesterol synthesis measured with serum non-cholesterol sterols after a single oral dose in humans

Studies considering long-term squalene consumption have revealed no consistent effects on serum cholesterol levels but the immediate effect of dietary squalene on cholesterol synthesis has not been studied. Thus, the effect of a single dose of dietary squalene on postprandial lipid metabolism was studied in 16 male volunteeers aged 22–79 years. Two oral fat meals a week apart were administered to every subject, one without (control) and the other with 500 mg of squalene. Lipids, retinyl palmitate, squalene and non-cholesterol sterols were measured at baseline and after 3, 4, 6, 9, 12 and 24 h postprandially in plasma, chylomicron, VLDL and VLDL bottom and, in six randomly chosen subjects, also in IDL, LDL and HDL. In the fasting samples, squalene was mainly transported in LDL and HDL, whereas in squalene-supplemented postprandium most of squalene was carried in the triglyceride-rich lipoproteins. Postprandial squalene and retinyl palmitate curves closely resembled each other. After the squalene-enriched dietary fat load, squalene was significantly increased compared to control fat loads in plasma, chylomicrons, VLDL and IDL. Squalene addition increased significantly lathosterol/campesterol ratio in chylomicrons and VLDL at 12 h and in VLDL bottom at 9–12 h, and increased significantly VLDL lanosterol/campesterol ratio at 12 h, indicating enhanced cholesterol synthesis caused by squalene. Plasma plant sterol levels remained unchanged. In conclusion, a single oral dose of squalene representing a potential daily dietary amount increases cholesterol synthesis within 9–12 h detected in chylomicrons, VLDL and VLDL bottom.