Toward a new definition of essential nutrients: is it now time for a third 'vitamin' paradigm?

The concepts of vitamin 'deficiency' diseases and the recommended dietary allowances (RDAs) have not kept pace with the growing understanding of the cellular and molecular functions of vitamins and other micronutrients. As a consequence, many researchers and clinicians rely on outdated signs and symptoms in assessing nutritional deficiencies. A new paradigm, presented here, proposes that: (1) deficiencies can be identified on biochemical and molecular levels long before they become clinically visible; (2) the definition of essential micronutrients be broadened to include some carotenoids and flavonoids, as well as various human metabolites, such as coenzyme Q10, carnitine, and alpha-lipoic acid, which are also dietary constituents; (4) individual nutritional requirements are partly fixed by genetics but also dynamically influenced by variations in the body's biochemical milieu and external stresses; and (5) the distinction between nutritional and pharmacological doses of vitamins is meaningless, since high doses of micronutrients may be required to achieve normal metabolic processes in some people.