Lathosterol in plasma measures cholesterol synthesis and identifies the efficiency of dietary phytosterols in reducing the plasma cholesterol concentration

Background Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol measured by the gold standard isotopic procedure we investigated whether the intestinal absorption of phytosterols (PS) depends on the body's cholesterol synthesis rate. Methods 38 volunteers (58 ± 12 years; low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and markers of phytosterol (PS) absorption and non-cholesterol sterol synthesis precursors measured. Results PS treatment reduced plasma total cholesterol concentration (-5,5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration). The lathosterol-to-cholesterol ratio in serum predicted the serum cholesterol response to PS feeding where high basal cholesterol synthesis was associated with lack of response of plasma cholesterol to PS in the diet. Cholesterol synthesis being elevated in the placebo phase in non-responders to dietary PS indicated they were resistant to further synthesis rise, whereas responders, because they have lower synthesis rate than non-responders in the placebo phase, are capable expanding synthesis under the effect of alimentary PS. Conclusions responders absorbed more PS than non-responders likely resulting from responders delivering less endogenous cholesterol than non-responders into the intestinal lumen that facilitates greater absorption of PS by the intestine.