The action of peroxyl radicals, powerful deleterious reagents, explains why neither cholesterol nor saturated fatty acids cause atherogenesis and age-related diseases

Chemistry. 2014 Nov 10;20(46):14928-45. doi: 10.1002/chem.201404383. Epub 2014 Oct 15.


Cells respond to alterations in their membrane structure by activating hydrolytic enzymes. Thus, polyunsaturated fatty acids (PUFAs) are liberated. Free PUFAs react with molecular oxygen to give lipid hydroperoxide molecules (LOOHs). In case of severe cell injury, this physiological reaction switches to the generation of lipid peroxide radicals (LOO(·)). These radicals can attack nearly all biomolecules such as lipids, carbohydrates, proteins, nucleic acids and enzymes, impairing their biological functions. Identical cell responses are triggered by manipulation of food, for example, heating/grilling and particularly homogenization, representing cell injury. Cholesterol as well as diets rich in saturated fat have been postulated to accelerate the risk of atherosclerosis while food rich in unsaturated fatty acids has been claimed to lower this risk. However, the fact is that LOO(·) radicals generated from PUFAs can oxidize cholesterol to toxic cholesterol oxides, simulating a reduction in cholesterol level. In this review it is shown how active LOO(·) radicals interact with biomolecules at a speed transcending usual molecule-molecule reactions by several orders of magnitude. Here, it is explained how functional groups are fundamentally transformed by an attack of LOO(·) with an obliteration of essential biomolecules leading to pathological conditions. A serious reconsideration of the health and diet guidelines is required.

Keywords: atherosclerosis; biochemistry; cholesterol; medicinal chemistry; polyunsaturated fatty acids; superoxide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / enzymology
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Cholesterol / analysis
  • Cholesterol / metabolism*
  • Fatty Acids / analysis
  • Fatty Acids / metabolism*
  • Free Radicals / analysis
  • Free Radicals / metabolism*
  • Humans
  • Lipid Peroxidation
  • Peroxides / analysis
  • Peroxides / metabolism*


  • Fatty Acids
  • Free Radicals
  • Peroxides
  • perhydroxyl radical
  • Cholesterol