The conversion of HMG-CoA to mevalonate by HMG-CoA reductase is the rate-limiting step of cholesterol biosynthesis and is under strict regulatory control (see Figure 1 ). HMGR is the target of compounds that are effective in lowering serum cholesterol levels. Human HMG-CoA reductase consists of a single polypeptide chain of 888 amino acids. The amino-terminal residues are membrane bound and reside in the endoplasmic reticulum membrane, while the catalytic site of the protein resides in its cytoplasmic, soluble carboxy-terminal portion. A linker region connects the two portions of the protein.
From a dietary perspective, plant cells do not manufacture cholesterol, and it is not found in plant foods.   Some plant foods, such as avocado , flax seeds and peanuts , contain phytosterols , which compete with cholesterol for absorption in the intestines, reducing the absorption of both dietary and bile cholesterol.  However, a typical diet contributes on the order of grams of phytosterols, which is not enough to have a significant impact on blocking cholesterol absorption. Phytosterols intake can be supplemented through the use of phytosterol-containing functional foods or dietary supplements that are recognized as having potential to reduce levels of LDL -cholesterol.  Some supplemental guidelines have recommended doses of phytosterols in the – grams per day range (Health Canada, EFSA, ATP III, FDA). A recent meta-analysis demonstrating a 12% reduction in LDL-cholesterol at a mean dose of grams per day.  However, the benefits of a diet supplemented with phytosterols have been questioned.