The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 12 No. 5 • October 2009

Factors Influencing Cholesterol Homeostasis in Subjects at High Risk of Developing Cardiovascular Disease

A new study published in the Journal of Lipid Research1 has examined the relative importance in cholesterol homeostasis of cholesterol synthesis and cholesterol absorption from the gastrointestinal tract in a sample of 3,532 men and women who were offspring of the original participants in the Framingham Heart Study and their spouses. The results are somewhat different than we would have expected.

Of the 3,532 participants, the researchers identified 155 cases (51 female, 104 male) who had documented cardiovascular disease (n=117) and/or ≥50% carotid stenosis (blockage)(n=38) who were not taking lipid lowering medications. They then compared cholesterol homeostastis factors between the cases and 414 control subjects. (Mean age of cases was 67.5 ±0.7 years and of controls was 66.4 ±0.4 years.)

The authors note that “data from several clinical trials suggest that although LDL cholesterol lowering was highly efficacious, the reduction in the relative risk of major coronary events was poorly associated with baseline serum lipid concentrations.” They thus compared cholesterol absorption (using plant sterols and stanols as proxy indicators: campesterol, sitosterol, and cholestanol) in cases compared to controls. After controlling for standard risk factors, they found cholestanol, sitosterol, desmosterol, and lathosterol to be significantly associated with CVD (cardiovascular disease) risk. Thus, the effectiveness of cholesterol absorption by the GI tract is, based on these data, an important risk factor for cardiovascular disease. Of course, this varies from person to person.

The researchers also examined cholesterol synthesis. Surprisingly, markers of cholesterol synthesis (using cholesterol precursors as surrogate markers of cholesterol synthesis) were significantly lower for cases as compared to controls. Thus, this study reports lower synthesis of cholesterol and higher absorption marker concentrations for cholesterol “are highly significant independent predictors of prevalent CVD in this study population.” Interestingly, the authors report that studies by different researchers (see, for example, 2,3) found that, in the absence of CHD (coronary heart disease), diabetics or those with metabolic syndrome had a low cholesterol absorption and high cholesterol synthesis profile, suggesting (the authors1 propose) that “shifts in the balance of whole-body cholesterol homeostasis may predispose individuals to the development of CVD.”

“Specifically, the cholesterol absorption markers campesterol, sitosterol, and cholestanol were associated with a 5.98-, 3.16-, and 2.57-fold increase in CVD risk (highest vs. lowest tertile), respectively. In contrast, the cholesterol synthesis marker lathosterol was associated with a 0.29-fold decrease in CVD risk, respectively highest vs. lowest tertile (all P-values <0.05).” “Additionally, the cholesterol homeostasis markers appear to be better predictors of disease than traditional lipid risk factors in this study population.”


  1. Matthan et al. Alterations in cholesterol absorption/synthesis markers characterize Framingham Offspring Study participants with CHD. J Lipid Res 50:1927-35 (2009).
  2. Gylling and Miettinen. Cholesterol absorption, synthesis and LDL metabolism in NIDDM. Diabetes Care 20:90-5 (1997).
  3. Simonen et al. Introducing a new component of the metabolic syndrome: low cholesterol absorption. Am J Clin Nutr 72:82-8 (2000).

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