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Extra-Virgin Olive Oil Improves Depression Symptoms Without Affecting Salivary Cortisol and Brain-Derived Neurotrophic Factor in Patients With Major Depression: A Double-Blind Randomized Controlled Trial

  • Sahar Foshati
    Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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  • Ahmad Ghanizadeh
    Department of Psychiatry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Department of Psychiatry, UCLA-Kern Psychiatry Residency Program, Kern Medical, CA
    Search for articles by this author
  • Masoumeh Akhlaghi
    Address correspondence to: Masoumeh Akhlaghi, PhD, School of Nutrition and Food Sciences, Razi Blvd, Shiraz, Iran.
    Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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Published:August 03, 2021DOI:



      Many patients with depression are reluctant to take psychiatric medications. Hence, complementary therapies such as nutritional considerations could be advantageous. The antidepressant potential of olive oil has been proved in observational studies.


      The effect of extra-virgin olive oil (EVOO) on depression symptoms and cortisol and brain-derived neurotrophic factor (BDNF) levels in patients with depression was examined.

      Design and participants

      This was a double-blind randomized controlled trial conducted on 73 patients suffering from major depressive disorder in Shiraz, Iran, in 2016.


      The patients were randomly assigned to intervention (EVOO) and control (sunflower oil) groups and consumed 25 mL/d of the corresponding oil for 52 days.

      Main outcome measures

      Depression symptoms were assessed by Beck Depression Inventory-II (BDI-II) and 7-item Hamilton Depression Rating Scale (HAMD-7). Salivary cortisol levels were determined immediately after awakening and 30 minutes later. Cortisol awakening response and the area under the curve with respect to ground and increase were computed. Serum BDNF concentrations were also measured.

      Statistical analyses performed

      Statistical analysis was conducted based on intention-to-treat and per-protocol approaches. Within-group changes were examined with repeated measures (for BDI-II and HAMD-7) and with paired t test (for other variables). Between-group comparisons were performed with analysis of covariance after adjustment for confounding factors.


      In intention-to-treat analysis, HAMD-7 score was the only variable with significant changes within and between groups, the latter as a greater decline in EVOO group (P = .001). BDI-II score did not show significant change in either group but the between-group comparison revealed a significant difference (P = .021). EVOO showed antidepressant effect in severely depressed patients (P = .017 for BDI-II and 0.008 for HAMD-7) but not in mild/moderate depression category. Serum BDNF concentrations, salivary cortisol levels at immediately after awakening (T0) and 30 minutes later, cortisol awakening response, the area under the curve with respect to ground and increase did not change within or between groups. Results of per-protocol analysis were not different.


      The results of this study suggested beneficial effects of EVOO on depression symptoms in patients with severe depression but not in those with mild to moderate depression. The effects were significant from both statistical and clinical points of view.


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      S. Foshati is a PhD student, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.


      A. Ghanizadeh is an associate professor of nutrition, Department of Psychiatry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, and the Department of Psychiatry, UCLA-Kern Psychiatry Residency Program, Kern Medical, CA.


      M. Akhlaghi is a professor, Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

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