A Randomized Clinical Trial of Greek High Phenolic Early Harvest Extra Virgin Olive Oil in Mild Cognitive Impairment: The MICOIL Pilot Study

J Alzheimers Dis. 2020;78(2):801-817. doi: 10.3233/JAD-200405.


Background: Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function.

Objective: To investigate for the first time the effect of Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) in people with mild cognitive impairment (MCI).

Methods: We conducted a randomized prospective study so as to examine the HP-EH-EVOO and MP-EVOO versus MeDi in MCI. Genetic predisposition (APOEɛ4) to Alzheimer's disease (AD) was tested and an extensive neuropsychological battery was administered at baseline and after 12 months. Each participant was randomized and assigned one of three groups: 1) Group 1 received the HP-EH-EVOO (50 mL/day); 2) Group 2 received the MP-EVOO (50 mL/day), and 3) Group 3 received only the MeDi instructions.

Results: Better follow-up performance was found in Group 1 compared to Group 2 and Group 3 in the almost all cognitive domains. Moreover, Group 2 showed also significant improvement compared to Group 3 in ADAS-cog (p = 0.001) and MMSE (p = 0.05), whereas Group 3 exhibited worse or similar to baseline performance in almost all domains. In particular, Group 1 and Group 2 had better outcomes with regards to ADAS-cog (p = 0.003), Digit Span (p = 0.006), and Letter fluency (p = 0.003). Moreover, there was a significant difference (p = 0.001) in the presence of APOEɛ4 between the Groups 1 and 2 versus Group 3.

Conclusion: Long-term intervention with HP-EH-EVOO or MP-EVOO was associated with significant improvement in cognitive function compared to MeDi, independent of the presence of APOEɛ4.

Keywords: APOE; Alzheimer’s disease; Mediterranean Diet; extra virgin olive oil; mild cognitive impairment; natural compounds; non-pharmaceutical interventions.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cognitive Dysfunction / diet therapy*
  • Cognitive Dysfunction / epidemiology*
  • Cognitive Dysfunction / psychology
  • Cohort Studies
  • Diet, Mediterranean*
  • Double-Blind Method
  • Female
  • Greece / epidemiology
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Olive Oil / administration & dosage*
  • Olive Oil / analysis
  • Phenols / administration & dosage*
  • Phenols / analysis
  • Pilot Projects
  • Prospective Studies


  • Olive Oil
  • Phenols