Abstract
AimOleocanthal and oleacein (OC/OL) have important in vitro and in vivo antitumor properties; however, there is no data about their anticancer activity in humans. The aim of this pilot study was to test if patients at early stage of chronic lymphocytic leukemia (CLL) could adhere to and tolerate an intervention with high OC/OL extra virgin olive oil (EVOO) and if this intervention could lead to any changes in markers related to the disease.MethodsA pilot dietary intervention (DI) was made in patients with CLL in Rai stages 0–II who did not follow any treatment (NCT04215367). In the first intervention (DI1), 20 CLL patients were included in a blind randomized study and were separated into two groups. One group (A) of 10 patients consumed 40 ml/day of high OC/OL-EVOO (416 mg/Kg OC and 284 mg/kg OL) for 3 months. A second group (B) of 10 patients consumed 40 ml/day of low OC/OL (82 mg/kg OC and 33 mg/kg OL) for 3 months. After a washout period of 9–12 months, a second intervention (DI2) only with High OC/OL-EVOO for 6 months was performed with 22 randomly selected patients (16 from the DI1 (8 from each group) and 6 new). Hematological, biochemical, and apoptotic markers were analyzed in the serum of the patients. In addition, cellular proliferation and apoptosis markers were studied in isolated proteins from peripheral blood mononuclear cells.ResultsThe results of the DI1 showed beneficial effects on hematological and apoptotic markers only with High OC/OL-EVOO. During the DI2, a decrease in the white blood cell and lymphocyte count was observed (p ≤0.05), comparing 3 months before the intervention and 6 months after it. After 3 and 6 months of DI2, an increase (p ≤0.05) was observed in the apoptotic markers ccK18 and Apo1-Fas, and also in the cell cycle negative regulator p21, and also a decrease in the antiapoptotic protein Survivin, and in the cellular proliferation marker Cyclin D.ConclusionsThis is the first clinical trial with High OC/OL-EVOO that indicates that it could be a promising dietary feature for the improvement of CLL inducing the apoptosis of their cancer cells and improving the metabolism of the patients.Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT04215367, identifier: NCT04215367.
Highlights
Intake of extra virgin olive oil (EVOO), which is the major component of the Mediterranean diet, may be partly responsible for the increased life expectancy of the Mediterranean people [1]
During the first step of the dietary intervention (DI1) the participants consumed Low OC/OL-EVOO or High OC/OLEVOO for 3 months to explore its effect on the hematological markers and molecular apoptotic markers (Apo1-Fas, ccK18, and Survivin) at all the time points of the intervention
One of our main targets was to investigate the hypothesis that the biological activity of olive oil against cancer is related to its content in specific phenolic ingredients and especially in oleocanthal and oleacein, as we had recently shown for the inhibition of platelet aggregation [27] and for the improvement of cognitive function in people with mild cognitive impairment [2]
Summary
Intake of extra virgin olive oil (EVOO), which is the major component of the Mediterranean diet, may be partly responsible for the increased life expectancy of the Mediterranean people [1]. Chronic Lymphocytic Leukemia (CLL), the most commonly diagnosed adult leukemia in Western countries, is responsible for about 1 in 4 cases of all leukemias [4]. It is characterized by the accumulation of monoclonal B cells in bone marrow, peripheral blood, lymphatic tissues, and spleen, while it is often asymptomatic and slow in its development. Patients at early stages of CLL do not require immediate therapy, offering the opportunity to perform interventions which could prevent or delay the disease progression. The last one third of the patients start soon diseaserelated symptoms and require treatment at different times after diagnosis depending on external and genetic factors. There are not prognostic factors able to anticipate the disease progress [8]
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