What makes good antioxidants in lipid-based systems? The next theories beyond the polar paradox

The polar paradox states that polar antioxidants are more active in bulk lipids than their nonpolar counterparts, whereas nonpolar antioxidants are more effective in oil-in-water emulsion than their polar homologs. However, recent results, showing that not all antioxidants behave in a manner proposed by this hypothesis in oil and emulsion, lead us to revisit the polar paradox and to put forward new concepts, hypotheses, and theories. In bulk oil, new evidences have been brought to demonstrate that the crucial site of oxidation is not the air-oil interface, as postulated by the polar paradox, but association colloids formed with traces of water and surface active molecules such as phospholipids. The role of these association colloids on lipid oxidation and its inhibition by antioxidant is also addressed as well as the complex influence of the hydrophobicity on the ability of antioxidants to protect lipids from oxidation. In oil-in water emulsion, we have covered the recently discovered non linear (or cut-off) influence of the hydrophobicity on antioxidant capacity. For the first time, different mechanisms of action are formulated in details to try to account for this nonlinear effect. As suggested by the great amount of biological studies showing a cut-off effect, this phenomenon could be widespread in dispersed lipid systems including emulsions and liposomes as well as in living systems such as cultured cells. Works on the cut-off effect paves the way for the determination of the critical chain length which corresponds to the threshold beyond which antioxidant capacity suddenly collapses. The systematic search for this new physico-chemical parameter will allow designing novel phenolipids and other amphiphilic antioxidants in a rational fashion. Finally, in both bulk oils and emulsions, we feel that it is now time for a paradigm shift from the polar paradox to the next theories.