Venturi, S. Department of Health, ASL n. 1, Pennabilli (Rimini), Italy. E-mail: dr.venturi.sebastiano@gmail.com Venturi, M. Department of Oral Sciences, Faculty of Medicine, University of Bologna, Italy. Iodine, PUFAs and Iodolipids in Health and Diseases: An Evolutionary Perspective Key words: antioxidants, brain, evolution, iodine, iodolipids, PUFAs. Vol. 29 n. 1-3 (185-205) - 2014 HUMAN EVOLUTION The structural, metabolic and synergic actions of iodine and polyunsaturated fatty acids (PUFAs) in life evolution and in the ‘membrane lipid language’ of cells are reviewed. Iodine is one of the most electron-rich atoms in the diet of marine and terrestrial organisms and, as iodide (I-), acts as an ances- tral electron-donor through peroxidase enzymes. It is the most primitive inorganic antioxidant in all iodide-concentrating cells, from primitive marine algae to more recent vertebrates. About 500 million years ago, the thyroid cells originated from the primitive gut of vertebrates, then migrated and specialized in the uptake and storage of iodocompounds in the thyroid, a new follicular organ. In parallel, ectodermic cells, differenti- ated into neuronal cells, became the primitive nervous system and brain. Both these cells synthesized iodolipids, as novel ‘words’ of the chemical ‘lipid language’ devoloped among cell membranes during the evolution of life, for better adaptation to terrestrial environments. The study of iodolipids is a new area of investigation, which might be useful for research on apop- tosis, carcinogenesis and degenerative diseases, as well as for trying to understand some problems discussed regarding human evolution. Forward Evolution of the hominin lineage was marked by progressive brain expansion and complexity, in concomitance with coordinated changes in other morphological and be- havioral traits that characterized speciation events. In addition to gene variation, changes in climate, habitat, and diet are well-recognized environmental stimuli for evolutionary changes. Iodine is an environmental stimulus to which living organisms react, some- thing particularly evident in amphibian metamorphosis and also in hominin evolution (Venturi & Bégin, 2010). A common biochemical control mechanism could potentially be responsible for coordinating a suite of physiological, morphological and behavioral changes as important as brain evolution. In a process such as this, iodine and polyunsatu- rated fatty acids (PUFAs) are important components, both by themselves and also via iodolipid molecules, as new ‘words’ of the chemical ‘lipid language’ developed among cell membranes during life evolution, for a better adaptation to terrestrial environments (Figures 1 & 2). Iodine is the richest in electrons of the elements presently considered essential in animal and human diets. Inorganic iodide appears to be necessary for all liv- ing animal cells, but only vertebrates have the thyroid gland and its iodinated hormones. Iodine (I) is scarce in the earth’s surface because over hundreds of millions of years it