Atherosclerotic disease is one of the major causes of mortality in Japan. Modifiable environmental factors, diet and lifestyle, in particular, are largely responsible for the increased risk of atherosclerotic disease. However, the role of specific dietary factors had not been clearly defined until recently. Meta-analysis of prospective epidemiological studies showed that there is no conclusive evidence that dietary saturated fat is associated with an increased risk of coronary heart disease (CHD) or cardiovascular disease (CVD). This means that risks of atherosclerosis are influenced by the specific nutrients used to replace saturated fatty acids (SFAs). Studies showed that consuming polyunsaturated fatty acids (PUFAs) in place of SFAs reduces CHD events, and that replacing SFAs with carbohydrates is modestly associated with a higher risk of CHD. However, a study suggested that replacing SFAs with carbohydrates of low-glycemic index (GI) value is associated with a lower risk of CHD. In addition, not only an increase in serum LDL, but also a decrease in HDL and elevated triglycerides (TG) levels, which are often accompanied by an increase in small dense LDL, are known to accelerate the atherosclerotic process. It is important to understand the effects of SFAs and other nutrients used for replacing SFAs on lipid metabolism. Although no significant relationship has been found to date between egg consumption and CHD or CVD, reducing cholesterol absorption was shown to be effective in lowering CVD risk in clinical studies. Further studies on the appropriate amount of cholesterol intake are necessary.

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It is essential for cholesterol absorption to be solubilized in bile salt micelles in intestinal lumen. It is believed that the bile salt micelles can reach to the surface of intestinal epithelial cells through unstirred water layer covering on the apical side of the cells. Since the bile salt micelles cannot be directly incorporated into the cells, cholesterol is believed to be released as a monomer and then to be incorporated into the cells through brush border membrane. Comparative studies of cholesterol and poorly absorbable plant sterols suggest that both solubility in and affinity for the micelles can be major determinants of sterol absorption. The process mediated by NPC1L1 on the brush border membrane is thought to be the major route of the incorporation of cholesterol and plant sterols into the cells. It is thought that a part of incorporated cholesterol and plant sterols is excreted through ABCG5/ABCG8. Mutation in ABCG5 or ABCG8 causes an increase in sterol absorption and therefore, induces deposition of plant sterols. A large part of cholesterol incorporated into the intestinal cells is esterified by ACAT2 and incorporated into chylomicrons and then they are secreted to the lymph.

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About 3,000 reports on oxidized cholesterols were published until 2011. Oxidized choles terols are related to development of several diseases. Their physiological significance is as following; (1) interference of synthesis and/or action of steroid hormones, (2) intermediates in bile acids synthesis, (3) promotion or suppression of development of atherosclerosis, (4) ligands for LXR, (5) suppression of de novo cholesterol synthesis, (6) intermediates of cholesterol metabolism in the brain, and (7) disrupters of lipid metabolism by dietary oxidized cholesterols. In order to grasp these phenomena, there has to be a better way to analyze oxidized cholesterols in vivo with accuracy.

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