SAFETY AND HEALTH IMPLICATIONS OF OXIDIZED LIPIDS

IV. SAFETY AND HEALTH IMPLICATIONS OF OXIDIZED LIPIDS

ROOH produced in foods are themselves odorless. However, carbonyl compounds formed upon decomposition can impart to the food undesirable off-flavors. These products, includ- ing short chain aldehydes, ketones, and alcohols (Frankel, 1991), as well as radicals, can compromise health in a number of ways. (1) The direct oxidation of susceptible molecules can result in loss of normal biological function. For example, oxidation of membrane lipids alters membrane integrity, promotes red blood cell fragility and membrane leakage. The oxidation of proteins results in loss of enzyme catalytic activity and/or regulation. (2) Reaction of some of these products leads to adduct formation with loss of native functions of specific molecules. The oxidative modification of the apoB molecule on low- density lipoprotein (LDL) prevents uptake by the LDL receptor and stimulates uptake by the scavenger receptor. (3) Oxidation can cleave DNA, and cause point, frame shift, dele- tion, and base damage. This oxidative cleavage impairs or destroys normal functionality. (4) Oxidative reactions can liberate signal molecules or analogs that elicit inappropriate responses such as the activation of platelet aggregation and down-regulation of vascular relaxation by leukotoxin and eicosanoid analogs.

The susceptibility and overall rate of oxidation of a lipid molecule, whether in food or within the body, is related to the number of double bonds on the fatty acids. The rate of oxidation is determined by the ease of hydrogen abstraction. An increase in the num- ber of double bonds increases the oxidation rate. These relative rates of oxidation as a function of number of double bonds may be important to rates of deterioration of various components in foods as well as biological molecules in vivo. Foods high in PUFA require more antioxidants to prevent oxidation and rancidity (Fritsche and Johnston, 1988). Con- sumption by animals, including humans, of foods with high amounts of PUFA appears to increase the antioxidant requirement to prevent tissue damage (Muggli, 1989). The molecular basis for this increased requirement is not known. Frequently, reports of in- creased in vivo oxidative damage are based on crude measures of lipid oxidation such as The susceptibility and overall rate of oxidation of a lipid molecule, whether in food or within the body, is related to the number of double bonds on the fatty acids. The rate of oxidation is determined by the ease of hydrogen abstraction. An increase in the num- ber of double bonds increases the oxidation rate. These relative rates of oxidation as a function of number of double bonds may be important to rates of deterioration of various components in foods as well as biological molecules in vivo. Foods high in PUFA require more antioxidants to prevent oxidation and rancidity (Fritsche and Johnston, 1988). Con- sumption by animals, including humans, of foods with high amounts of PUFA appears to increase the antioxidant requirement to prevent tissue damage (Muggli, 1989). The molecular basis for this increased requirement is not known. Frequently, reports of in- creased in vivo oxidative damage are based on crude measures of lipid oxidation such as

With the increasing interest in the public health implications of edible oils and the possibility that oxidation products of particular lipids may have uniquely detrimental prop- erties, some emphasis has been placed on analyzing fats for the presence of oxidation products. Foremost among these are the oxides of cholesterol (Esterbauer, 1993; Morin and Peng, 1989; Sevanian et al., 1991). How much of the toxicity of cholesterol oxides in vivo is related to cholesterol oxides from ingested food is not known. Overall, the overt toxicity of all oxidized lipids ingested in foods appears to be remarkably low (Esterbauer, 1993). Nevertheless, the long-term influence of lipid peroxides and oxides of cholesterol, etc., may be deleterious, especially toward the development of chronic disease (Halliwell, 1993). In ongoing research attempting to elucidate the basis of LDL modification and the accumulation of atherosclerotic plaque, many studies have measured cholesterol oxides as the index of LDL oxidation. This is a useful but not particularly sensitive barometer of the deterioration of LDL particles; the cholesterol molecule is not readily oxidized, hence the accumulation of the oxidation products of cholesterol readily confirms extensive decomposition of the particle. At the point at which LDL contain oxides of cholesterol, they can be readily shown to be taken up by the so-called scavenger receptor on macro- phage. This then is consistent with the conversion of native LDL to modified and athero- genic LDL (Steinberg et al., 1989). This cholesterol oxide index of oxidation may have been overly interpreted as reflecting the fact that oxides of cholesterol are the most toxic and important components leading to the atherogenicity of LDL, and this has been further translated to foods that contain cholesterol in general. Although cholesterol oxides are toxic to a variety of cells and biochemical processes, it is not yet clear that particular oxides of cholesterol found in foods are uniquely toxic or that their presence in foods contributes inordinately to chronic disease. Nevertheless, research that is beginning to catalog the abundance of oxidized lipids in foods and edible oils has emphasized the need to stabilize oils against oxidation and has increased the rate of disappearance of animal- derived, cholesterol-containing cooking fats (Fontana et al., 1992; Morin and Peng, 1989; Zhang and Addis, 1990), all with arguably highly beneficial results. The potential adverse effect of this research focus on cholesterol oxides as uniquely deleterious agents is that it may shift emphasis away from dietary antioxidants and the broader protection of suscep- tible in vivo targets such as lipoproteins. Ongoing research suggests that such protection is involved in attenuating the risk of atherosclerosis and other degenerative diseases (Ames, 1989; Ames et al., 1993; Esterbauer, 1993; Halliwell, 1993).