Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

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 Meta-analysis 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 non-enzymic 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 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/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 overar...

A Rethinking on the Benefits and Drawbacks of Common Antioxidants and a Proposal to Look for the Antioxidants in Allium Products as Ideal Agents: A Review

“…as described earlier in our papers [4-6, 19-21, 34-37]. These results answers the doubts raised by Singh et al [1] as to the effects of AOs on endogenous enzymes.…”

“…Pills or any other purified forms of AO may be a failure as they are devoid of several other protective ingredients present along with the AOs in the plants or their extracts. The purified AOs become over active as reported by Singh et al [1]. This may be due to lop sided disturbances in AO network or deregulating other metabolic activities.…”

“…If we moderately use them every week by turn we get a cock tail of AOs and other nutrients in sufficient but not in excess forms. But out of fear of ROS & RNS if we over load our body with the above items, we shall be destroying all oxidants and producing harmful metabolites of AOs as argued by Singh et al [1,2] This situation also curtails the chances of ROS and RNS to play their role in destroying microbes and also in inducing certain genes [8] responsible for the production of AO enzymes. However the use of plant extracts or their raw forms may do less harm than the pure forms of pills of each e.g.…”

“…However vitamin C & E or EC could not give any protective effect to DNA. The reason may be that their antioxidant actions might have been nullified by the action of their metabolites on reduced thiols like GSH which are endogenous AOs for vitamin regeneration, and accompanied inhibition of gene induction due to sweeping away of ROS and RNS [1,17]. This type of GSH exhaustion can be avoided with such AOs which trap electrons, regenerate themselves and enhance GSH production.…”

“…In two recent articles by Singh et al [1,2] they raised some thought provoking arguments against the time old claims that antioxidants (AOs) are miraculous molecules that can prevent or cure many serious diseases such as cancer, heart problems, aging etc. At the very appearance of the title of Singh's second article [2], the senior author of this paper (KTA) was taken aback and thought that all his seventy and old papers (during 1960-2010) were simply a waste.…”