Physiological free fatty acid concentrations do not increase free estradiol in plasma

Consumption of dietary fat has been linked to the high incidence of breast cancer. The in vitro effects of palmitate, oleate, linoleate, and eicosapentaenoate at supraphysiological concentrations [1.8-4.8 mM; endogenous (0.8) plus added (1-4)] on the binding of 17 beta-estradiol (E2) to sex hormone-binding globulin and albumin were evaluated in plasma, using centrifugal ultrafiltration. The E2-sex hormone-binding globulin complex was significantly dissociated by oleate, linoleate, eicosapentaenoate, and palmitate at 1.8 to 2.8-mM concentrations. The same FFA caused a significant increase in E2 binding to albumin at similar concentrations. However, only the unsaturated fatty acids at 3.8 to 4.8-mM concentrations (i.e. oleate, linoleate, and eicosapentaenoate) significantly increased the nonprotein-bound free E2 fraction. Thus, these results suggest that free E2 concentrations are not affected by physiological concentrations of FFA.