Pro-Oxidant Effect of Vitamin E in Cigarette Smokers Consuming a High Polyunsaturated Fat Diet

Abstract

Abstract-Dietary polyunsaturated fats and vitamin E are associated with reduced risk for atherosclerosis, but in smokers, they could promote lipid oxidation. Therefore, we examined the effects of a high polyunsaturated fat diet and vitamin E supplementation on measures of lipid oxidation in cigarette smokers. Ten subjects who smoked Ͼ1 pack of cigarettes per day were sequentially fed the following: a baseline diet in which the major fat source was olive oil, a diet in which the major fat source was high-linoleic safflower oil, and finally, the safflower oil diet plus 800 IU vitamin E per day. LDL oxidation lag time and rate and plasma total F 2 -isoprostanes and prostaglandin F 2␣ (PGF 2␣ ) were determined after 3 weeks on each diet. is the leading cause of morbidity and mortality in the developed world. Peroxidation of plasma LDLs by oxygen-derived free radicals has been ascribed a central role in the etiology of ASCVD. 1 The corollary to this theory is that agents that can protect LDL from peroxidation should decrease the risk of developing ASCVD, attenuate its progression, or even reverse established disease. 2 Indeed, epidemiological studies have suggested that antioxidants, such as ␣-tocopherol, confer dose-dependant protection against ASCVD, 3-5 yet prospective intervention trials 6 -8 have failed to observe a protective effect.Tobacco use is one of the most potent risk factors for ASCVD. The high concentration of free radical oxidants in tobacco smoke 9 and the fact that the impact of smoking on the incidence ASCVD correlates with plasma LDL levels 10,11 are consistent with the concept that LDL peroxidation by cigarette smoke promotes atherogenesis. 12 Indeed, measures of lipid oxidation, such as thiobarbituric acid-reactive substances (TBARS) in plasma, 13 LDL, 14 -16 and red blood cells 17 ; breath alkane excretion 18 -20 ; and F 2 -isoprostanes in urine 21 and plasma, 22 are increased in cigarette smokers. Conversely, plasma levels of antioxidant vitamins in smokers, which could protect LDL against the damaging effects of free radicals, are depressed. 23 Cigarette smokers thus constitute a high-risk population in which intervention could reduce the risk of ASCVD. Diets high in monounsaturated fatty acid (MUFA) or polyunsaturated fatty acid (PUFA) effectively lower plasma LDL, 24 but high PUFA diets constitute a theoretical risk, because PUFAs are excellent substrates for lipid peroxidation. 25 Indeed, studies in cigarette smokers 15 and in nonsmokers 26,27 have found that PUFAs increase LDL oxidation rate and also breath pentane excretion. 28 The deleterious impact of dietary PUFA on lipid oxidation, in theory, could be mitigated by concomitant supplementation with antioxidant vitamins. However, although antioxidant vitamins are generally considered to be nontoxic, 29 vitamin E is a redox reagent that can function as a pro-oxidant under certain conditions. 30 -32 This has led some to voice concerns that antioxidant vitamins could function as pro-oxidants in vivo. 33,34 The fact that prospective studi...

Effects of vitamin E on the toxicity of oxidized LDL on endothelial cells in vitro in smokers vs nonsmokers on diets rich in fish

“…Our results on vascular endothelial cell culture are contradictory to the present hypothesis postulating that antioxidants reduce cell damage (Estrada-García et al, 2002). In a study by Weinberg et al (2001), in accord to our study, smokers consumed a high polyunsaturated fat diet. Addition of vitamin E (800 IU/day) to the diet prolonged the mean LDL oxidation lag time, but further increased F 2 -isoprostanes, which are used as indicator of global in vivo oxygenderived free radical stress.…”

Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression

“…6,7,14 When vitamin E works as an antioxidant, it is oxidized to harmful radical, which needs to be reduced back to ␣-tocopherol, eg, by vitamin C. 15 Recently, supplementing smokers with high polyunsaturated fatty acid diet with high doses of vitamin E alone promoted rather than reduced lipid peroxidation. 16 In our prospective population study, vitamin C deficiency was associated with coronary events. 17 Thus, it is conceivable that in most completed and ongoing antioxidant supplementation trials, a wrong kind of supplement is given.…”

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

“…A further complication is that all antioxidants can become oxidants in certain environments and at particular doses. For example, VitC in high doses increases DNA damage in healthy volunteers (Podmore et al 1998), and VitE may act as a pro-oxidant in cigarette smokers (Weinberg et al 2001). …”