The new results emerging from these analyses demonstrate that during plant stanol consumption, serum non-cholesterol sterol/cholesterol- ratios reflect the fractional absorption and whole-body synthesis of cholesterol. In addition, serum absorption/synthesis marker ratios were found to be valid markers of cholesterol metabolism during plant stanol intervention. Second, serum levels of plant sterols were dose-dependently reduced by plant stanols. The serum cholestanol level was reduced less frequently than the serum plant sterol levels during consumption of STAEST. The cholesterol precursor sterols, cholestenol, desmosterol and lathosterol, were not increased similarly or were not increased at all in some studies emphasizing the importance of adopting more than one surrogate serum marker. The serum squalene level was not related to cholesterol metabolism.
The study population contained all randomized controlled plant stanol interventions in adults gathered from PubMed, in which at least two serum synthesis markers, two serum plant sterols, and serum cholestanol were analysed. It turned out that the requirement for the non-cholesterol sterols excluded other than our own studies. In fact, 4 more studies could be retrieved from PubMed containing serum lathosterol and plant sterol quantifications, but not the other non-cholesterol sterols.
If one adopts surrogate serum markers, there is always the caveat that their validity should not be considered as self-evident . In situations when there is interference with the homeostasis of cholesterol or the metabolism of an individual marker, the serum value of the marker/s no longer reflects cholesterol metabolism. Accordingly, the metabolism of both cholesterol and the individual marker need to be taken into consideration when interpreting the data. A classic example of potential misinterpretation is the fact that plant sterols cannot be used as cholesterol absorption markers at the same time when the subjects are consuming plant sterol-added products. Similarly, when dietary intake of cholesterol was increased by adding daily egg consumption, there was an elevation in the serum lathosterol concentration, but this no longer reflected cholesterol synthesis but instead the increased intake of lathosterol present in the egg yolk . Even under baseline situations, the relative serum markers may not reflect cholesterol metabolism. In vegetarians, cholesterol synthesis is known to be elevated as compared with control subjects, but there was no increase in the concentrations of the serum cholesterol precursors .
In the present study, all serum cholesterol precursors were unchanged in two studies. The subjects in one of these studies were type 1 diabetics, and the precursor ratios to cholesterol varied from −30% to +2%. Why in type 1 diabetes cholesterol synthesis seems not to be activated remains open and warrants further investigation. Regarding the second study, the cholesterol precursors were increased from 14% to 30%, but the increment did not reach significance.
Cholestanol is a saturated derivative of cholesterol produced by the liver. Its synthesis involves mainly a rate-limiting oxidation pathway, but a smaller fraction is also synthesized as a by-product of bile acid production . The dietary intake of cholestanol is minimal, less than 2 mg/d , but if biliary secretion is impaired such as in cholestasis, then serum cholestanol values rapidly increase and no longer reflect the absorption efficiency of cholesterol . Even though the serum cholestanol concentration and the cholestanol/cholesterol-ratio correlated with fractional cholesterol absorption during STAEST, in the individual studies the cholestanol/cholesterol-ratio was less frequently reduced than the serum plant sterol/cholesterol-ratios.
In the present analysis, the relative LDL cholesterol reduction varied from 6 to 17% depending on the plant stanol dose used in the different studies. Similarly, the relative reduction for campesterol/cholesterol-ratio varied from 35 to 62%. One can calculate that a 2 g plant stanol dose can achieve about a 10% reduction in the LDL cholesterol concentration and a 32% decrease in the serum campesterol/cholesterol-ratio (Figure 2). Accordingly, the change in serum campesterol/cholesterol-ratio can also be utilized as an indicator of the compliance of the STAEST intake. An earlier study demonstrated that when LDL cholesterol was lowered by 10% with plant stanols, fractional cholesterol absorption was reduced by 45% and the serum campesterol/cholesterol-ratio by 34% (p < 0.05 for all) , which is the same magnitude estimated in the present study. These values suggest that approximately a four-fold inhibition in cholesterol absorption efficiency is needed to achieve a unit decrease in the LDL cholesterol concentration.