Plasma noncholesterol sterols as indicators of cholesterol absorption

Abstract

A publication by Jakulj et al. ( 1 ) in this issue of the Journal of Lipid Research calls into question the validity of plasma noncholesterol sterols for the evaluation of cholesterol absorption in humans. This method was fi rst proposed by Miettinen and coworkers ( 2 -5 ), who showed that either sitosterol/total cholesterol or campesterol/lathosterol ratios refl ect amounts of cholesterol absorbed by the intestine. Normally only small amounts of plant sterols (sitosterol and campesterol) are absorbed, but Miettinen and associates claimed that quantities absorbed are proportional to amounts of cholesterol absorbed. In turn, the greater the total of plant sterol absorbed, the higher will be the plasma level, normalized for plasma cholesterol levels. These investigators ( 4 , 6 , 7 ) further showed that plasma levels of a cholesterol synthesis precursor, lathosterol, refl ect the body's cholesterol synthesis rate. Because absorbed cholesterol returns to the liver and suppresses cholesterol synthesis, a low level of plasma lathosterol will denote reduced cholesterol synthesis because of more cholesterol absorption. Consequently, the campesterol/ lathosterol ratio should better indicate cholesterol absorption than the sitosterol/cholesterol ratio. Jakulj et al. ( 1 ) attempted to validate plant sterols in plasma as a marker of cholesterol absorption. To do so, they compared plasma campesterol/cholesterol ratios with cholesterol absorption in mildly hypercholesterolemic subjects. Fractional absorption of dietary cholesterol was determined by comparing isotope ratios of plasma cholesterol following oral and intravenous administration. They found no difference in fractional cholesterol absorption in those with the highest and lowest campesterol/ cholesterol ratios. Nor was there a correlation between these ratios and fractional absorption in the total population. The authors concluded that previous studies claiming a relationship between plasma sterol ratios and cholesterol absorption are of questionable validity.It might be noted that Jakulj et al.( 1 ) did not measure a marker of cholesterol synthesis, e.g., lathosterol. Because of the inverse relation between cholesterol absorption and synthesis, the addition of a synthesis precursor could have helped to validate the use of noncholesterol sterols as a marker for cholesterol absorption as well as synthesis.The overall design of the study of Jakulj et al.( 1 ) nonetheless is of interest. Testing whether subgroups with the highest and lowest plant sterol levels have a different fractional absorption of cholesterol is innovative and worthy of further evaluation. On the other hand, methodological issues raised by this study deserve consideration.The method for measuring fractional absorption of cholesterol employed a dual stable-isotope method ( 1 ). ]sitosterol in sunfl ower oil by gentle heating and stirring before adding it to stomach-soluble gelatin capsules. Cholesterol absorption was determined by differences in isotope ratios between oral administration and fecal...

The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition on Sterol Absorption Markers in a Cohort of Real-World Patients

“…[13][14][15] Some have also suggested using ratio of cholesterol absorption to synthesis biomarkers, such as campesterol-lathosterol ratio, to evaluate absorption. 13,[37][38][39] These data were not available for our study due to low levels of synthesis markers that frequently fell below the level of detection and that lathosterol was not measured in our study. Utilization of phytosterol serum values as markers for cholesterol absorption have recently been called into question by Jakulj et al, 40 although the accompanying editorial commentary had concerns for methodologic issues.…”

“…Utilization of phytosterol serum values as markers for cholesterol absorption have recently been called into question by Jakulj et al, 40 although the accompanying editorial commentary had concerns for methodologic issues. 37 It seems that the ideal noninvasive method for accurately measuring cholesterol absorption remains debatable, although various methods have supportive data. Serum sterols and stanols continue to be used because they can be obtained noninvasively through a readily available assay.…”

Cholesterol metabolism in cardiac sarcoidosis

“…Serum cholesterol precursors, plant sterols, and cholestanol are valid biomarkers of whole-body cholesterol metabolism [11e20, 24,25]. To be certain that they operated also in CS as expected, we interrelated the cholesterol precursors with each other in both groups as well as the plant sterols and cholestanol.…”

“…Serum concentrations of non-cholesterol sterols were expressed in mg/dl and also as the ratio to cholesterol (10 2 x mmol/mmol of cholesterol) by adjusting the non-cholesterol sterol concentrations to the cholesterol value of the same GLC run, and multiplying the ratio by 10 2 in order to get rid of the decimals. Because the assessment of absolute whole-body cholesterol metabolism is difficult and laborious, it is generally accepted that the ratios of serum non-cholesterol sterols to cholesterol are valid biomarkers of cholesterol metabolism [24,25]. Accordingly, the ratios of serum cholesterol precursors to cholesterol reflect cholesterol synthesis [11e16], while the ratios of plant sterols and cholestanol reflect cholesterol absorption efficiency [14,16e20].…”

Plant sterols, cholesterol precursors and oxysterols: Minute concentrations—Major physiological effects

“…The results from a number of cross-sectional or prospective studies, meta-analyses and gene polymorphism studies have been controversial, ranging from protective effects of plant sterols to harmful, pro-atherogenic roles of these compounds [9][10][11][12][13][14]. Since the serum plant sterol concentrations in the normal population are suggested by several laboratories to act as biomarkers for cholesterol absorption [15], it is possible that in those studies in which plant sterol concentrations correlate with the prevalence of arterial disease, the actual risk factor is a high efficiency of cholesterol absorption and not the plant sterol itself. To conclude, a possible role of plant sterols in the development of atherosclerotic arterial disease is as yet poorly understood.…”