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Non-extractable polyphenols (NEPP) are a fraction of dietary polyphenols that, for a long time, have been omitted from studies in the field. However, they are major contributors, quantitative and qualitatively, to the pool of dietary antioxidants ingested daily. This chapter summarises the story of the discovery of the existence of NEPP, as well as further steps in the chemical analysis, estimation of the dietary intake and evaluation of the biological activities of these compounds. Also, methodological aspects, such as the comparison between chemical and physiological approaches for the analysis of these compounds, are discussed. Finally, the recent concept of macromolecular antioxidants, as an updated definition of NEPP, is presented, together with the biological implications and potential applications of NEPP.

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