Reconvene and Reconnect the Antioxidant Hypothesis

Authors: P P Singh Anu Chandra Farzana Mahdi Ajanta Roy Praveen Sharma

Publish Date: 2010/09/03

Volume: 25, Issue: 3, Pages: 225-243

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Abstract

The antioxidants are essential molecules in human system but are not miracle molecules They are neither performance enhancers nor can prevent or cure diseases when taken in excess Their supplemental value is debateable In fact many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality Several Chochrane Metaanalysis and Markov Model techniques which are presently best available statistical models to derive conclusive answers for comparing large number of trials support these claims Nevertheless none of these statistical techniques are flawless Hence more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind placebo controlled interventional clinical trials which are gold standard should be implicitly conducted to get explicit answers Superoxide dismutase SOD glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide All these three enzymes are inducible enzymes thereby inherently meaning that body increases or decreases their activity as per requirement Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed probably because SOD is a large molecule and can not cross cell membrane The dietary antioxidants including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species ROS and reactive nitrogen species RNS within physiological limits Since body is able to regulate its own requirements of enzyme antioxidants the diet must provide adequate quantity of nonenzymic antioxidants to meet the normal requirements and provide protection in exigent condition So far there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized We are not yet certain about optimal levels of antioxidants in tissues Two ways have been used to assess them first by dietary intake and second by measuring plasma levels Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes The recommended levels for vitamin A E and C and beta carotene are 22–28 μmol/l 275–30 μmol/l 40–50 μmol/l and 04–05 μmol/l respectively The requirement and recommended blood levels of other dietary antioxidants are not established The resolved issues are 1 essential to scavenge excess of radical species 2 participants in redox homeostasis 3 selective antioxidants activity against radical species 4 there is no universal antioxidant and 5 therapeutic value in case of deficiency The overarching issues are 1 therapeutic value as adjuvant therapy in management of diseases 2 supplemental value in developing population 3 selective interactivity of antioxidant in different tissues and on different substrates 4 quantitative contribution in redox balance 5 mechanisms of adverse action on excess supplementation 6 advantages and disadvantages of prooxidant behavior of antioxidants 7 behavior in cohorts with polymorphic differences 8 interaction and intervention in radiotherapy diabetes and diabetic complications and cardiovascular diseases 9 preventive behavior in neurological disorders 10 benefits of nonnutrient dietary antioxidants 11 markers to assess optimized antioxidants status 12 assessment of benefits of supplementation in alcoholics and heavy smokers The unresolved and intriguing issues are 1 many compounds such as vitamin A and many others possessing both antioxidant and nonantioxidant properties contribute to both the activities in vivo or exclusively only to nonantioxidant activity and 2 since human tissues do not experience the surge of FR whether there is any need to develop stronger synthetic antioxidants Theoretically such antioxidants may do more harm than good

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