N-3 FATTY-ACIDS INDUCE OXIDATIVE MODIFICATIONS IN HUMAN ERYTHROCYTES DEPENDING ON DOSE AND DURATION OF DIETARY SUPPLEMENTATION

The present work was performed to study an optimal dose and duration o f dietary n-3 polyunsaturated fatty acid (PUFA) supplementation that w ould not result in harmful modifications of oxidative cell metabolism. Forty healthy subjects were divided into four groups that received 2. 5 g/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), 5.1 g EPA + DHA/d, 7.7 g EPA + DHA/d, or placebo. Fatty acid composition, to copherol status, and susceptibility to lipid peroxidation induced in v itro by 2,2'-azobis-(2-amidinopropane) (AAPH) were evaluated in human red blood cell (RBC) membranes on days 30 and 180. n-3 PUFA treatment increased EPA and DHA concentrations in RBC membranes in a time-depend ent manner in all of the n-3 PUFA groups. These modifications occurred with concomitant dose- and time-dependent increases in the membrane u nsaturation index. After 30 d of treatment with n-3 PUFAs, alpha-tocop herol significantly increased in RBC membranes of the intermediate- an d high-dose groups. Because of the higher concentration of this antiox idant in these groups, the susceptibility of RBC membranes to peroxida tion was decreased. However, after 180 d of treatment, alpha-tocophero l decreased to baseline values and AAPH-induced lipid peroxidation inc reased in a dose-dependent manner. These results show that high doses of dietary n-3 PUFAs, as well as long-time treatments, affect human RB C: susceptibility to lipid peroxidation by changes in fatty acid compo sition and tocopherol content.