Abstract
Squalene, a key intermediate of cholesterol synthesis, is present especially in olive oil. Regulation of cholesterol metabolism by dietary squalene in man is unknown, even though olive oil users in Mediterranean areas have low serum cholesterol levels. We have investigated absorption and serum levels of squalene and cholesterol and cholesterol synthesis with the sterol balance technique and serum levels of cholesterol precursors in humans during squalene feeding (900 mg/d for 7-30 days). The results were compared with those during cholestyramine treatment. Fecal analysis suggested that about 60% of dietary squalene was absorbed. Serum squalene levels were increased 17 times, but serum triglyceride and cholesterol contents were unchanged. The squalene feeding significantly (P less than 0.05) increased serum levels of free (1.7-2.3 times) and esterified (1.9-2.4 times) methyl sterol contents, while elevations of free and esterified delta 8-cholesterol and lathosterol levels were inconsistent. Cholestyramine treatment modestly augmented free methyl sterol levels (1.3-1.7 times), less consistently than those of esterified ones, while, in contrast to the squalene feeding, serum contents of free and esterified delta 8-cholesterol and lathosterol were dramatically increased (3.3-8 times). Neither of the treatments significantly affected serum plant sterol and cholestanol levels. The squalene feeding had no consistent effect on absorption efficiency of cholesterol, but significantly increased (paired t-test, P less than 0.05) the fecal excretions of cholesterol and its nonpolar derivatives coprostanol, epicoprostanol, and coprostanone (655 +/- 83 SE to 856 +/- 146 mg/d) and bile acids (212 +/- 24 to 255 +/- 24 mg/d), indicating an increase of cholesterol synthesis by about 50%. We suggest that a substantial amount of dietary squalene is absorbed and converted to cholesterol in humans, but this squalene-induced increase in synthesis is not associated with consistent increases of serum cholesterol levels. The clearly increased serum contents of esterified methyl sterols may reflect stimulated tissue acyl CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity during squalene feeding as these sterols are not esterified in serum.
Highlights
Squalene, a key intermediate of cholesterol synthesis, is present especially in olive oil
We suggest that a substantial amount of dietary squalene is absorbed and converted to cholesterol in humans, but this squalene-induced increase in synthesis is not associated with consistent increases of serum cholesterol levels
Earlier studies have &own that dietary squalene is converted to cholesterol in experimental animals [3,4,5] and that it inhibited the activity of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (EC.1.1.1.34) [6]
Summary
As there are few previous data on the effects of squalene feeding in humans [2, 7, 8], we designed the present experiments to explore short-term effects of dietary squaleneon cholesterol metabolism in humans. The effects of squalene were compared with those of cholestyramine, which is known to increase the activity of HMG-CoA reductase and cholesterol production by a different mechanism, i.e., by bile acid malabsorption-induced depletion of hepatic cholesterol. We could detect possible differences between excess exogenous (dietary) squalene causing suppression of HMG-CoA reductase activity but stimulation of overall synthesis of cholesterol, and excess endogenous squalene formed through the stimulation of HMG-CoA reductase activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
