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Cystic fibrosis (CF) is characterized by abnormal levels of essential fatty acids (EFA) in plasma phospholipids. The reduced availability of EFA has been reported to alter patterns of circulating and tissue esterified acids and may determine profound changes in membrane fluidity and cell signaling mechanisms. In the current study, the results of a new strategy aimed at the realization of a practical, low cost integrator, for daily use in the dietary management of FC subjects, are reported. We investigated the plasma phospholipids and triglycerides fatty acids composition of CF patients subjected to a dietary supplement constituted of a mixture of 50% extra virgin olive oil and 50% soybean oil and studied the clinical effects of this supplementation. The study included fourteen young subjects, aged between 6 and 15 years, affected by cystic fibrosis, with pancreatic insufficiency and heterozygotes or homozygotes for the delta F508 mutation. The subjects were matched by age and randomly assigned to either an oil mixture supplemented (OM) group (n = 7), or to a control (C) group (n = 7). In contrast to the control group, the patients with supplemented diet achieved significant increases of the relative amount of C18:1 in the triglycerides as well as a significant decrease in saturated fatty acids (C 16:0, C 17:0, C 18:0, C 22:0). Moreover, the ratio between LA acid and AA significantly increased in the triglycerides of the OM group. In the phospholipids of the OM group, the relative amount of C 18:1 and of palmitic acid increased significantly whereas the relative amount of the most important polyunsaturated fatty acids (PUFA) decreased. These results show that oleic acid can be absorbed and incorporated into the plasma triglycerides of CF patients receiving pancreatic enzymes, whereas poor incorporation of LA occurs. Despite the reduction in the relative amounts of phospholipid PUFA, the supplemented subjects did not reported adverse effects There were no significant differences between groups in the clinical indexes recorded (height, weight, BMI, Schwachman-Kulczycki score and FEV 1s). The results of this study showed that the supplementation with a mixture of extravirgin olive and soybean oil was safe in seven CF patients treated during a 2-months period and no negative clinical effects were evident. However, further clinical trials will be necessary in order to better evaluate the consequence of the observed changes in plasma fatty acids composition in a longer testing period.