Oxidation, lipoproteins, and atherosclerosis: which is wrong, the antioxidants or the theory?
OBJECTIVE
Paradoxically, many well-established components of the heart-healthy lifestyle are pro-oxidant, including polyunsaturated fat and moderate alcohol consumption. Moreover, antioxidant supplements have failed to decrease cardiovascular risk in extensive human clinical trials to date. Recent progress in understanding the roles of oxidants in regulating VLDL secretion and as essential signaling molecules supports the concept that oxidation may be beneficial in certain circumstances but damaging in others. We summarize recent data on the roles played by oxidative metabolism in different tissues and pathways, and address whether it is currently advisable to use antioxidant supplements to reduce cardiovascular risk.


RESULTS
Our recent study reported that in liver cells, polyunsaturated fatty acids increased reactive oxygen species, which in turn lowered the secretion of the atherogenic lipoprotein, VLDL, in vitro and in vivo. Antioxidant treatments prevented VLDL-lowering effects of polyunsaturated fatty acids in vitro, suggesting that supplemental antioxidants could either raise apolipoprotein-B-lipoprotein plasma levels in vivo, or impair the response to lipid-lowering therapies. The failure of antioxidants to decrease cardiovascular disease risk in many trials is also discussed in the context of current models for atherosclerosis progression and regression.


CONCLUSIONS
Oxidation includes distinct biochemical reactions, and it is overly simplistic to lump them into a unitary process that affects all cell types and metabolic pathways adversely. Guidelines for diet should adhere closely to what has been clinically proved, and by this standard there is no basis to recommend antioxidant use, beyond what is inherent to the 'heart healthy' diet in order to benefit cardiovascular health.
Williams
Kevin Jon
KJ
Division of Endocrinology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Fisher
Edward A
EA
D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000378:metabolism* / Q000517:prevention & control; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species
D000975:Antioxidants; D008079:Lipoproteins, VLDL; D017382:Reactive Oxygen Species