Author
AGRAWAL, KARAN - University Of California | |
MELLIOU, ELENI - University Of Athens | |
LI, XUEQI - University Of California | |
PEDERSEN, THERESA - University Of California | |
WANG, SELINA - University Of California | |
MAGIATIS, PROKOPIOS - University Of Athens | |
Newman, John | |
HOLT, ROBERTA - University Of California |
Submitted to: Journal of Functional Foods
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/17/2017 Publication Date: 7/6/2017 Citation: Agrawal, K., Melliou, E., Li, X., Pedersen, T.L., Wang, S.C., Magiatis, P., Newman, J.W., Holt, R.R. 2017. Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial. Journal of Functional Foods. 36:84-93. doi: 10.1016/j.jff.2017.06.046. Interpretive Summary: The cardiovascular benefit of extra virgin olive oils (EVOOs) may increase with the total antioxidant capacity of the oil, or such benefits may be associated with the concentrations of specific natural products with unique health promoting effects. Oleocanthal and oleacin are two compounds found in EVOOs at different levels among olive oil varieties. These compounds are each antioxidants, but also have unique anti-inflammatory properties. For instance, oleocanthal has many properties similar to ibuprofen and may influence platelet aggregation. To compare the impact of acute oleocanthal-rich versus phenolic-equivalent but oleocanthal-poor EVOO consumption on platelet reactivity, we conducted a study where 9 men were fed one of 3 oils in random order without knowing which oil they consumed. Each participants consumed 40mL (~3 tablespoons) of the three EVOOs 1-week apart. The oils were matched in total phenolic content but provided different hydroxytyrosol and tyrosol derivative concentrations. Specifically, oils contained either 2:1 oleocanthal/oleacein (D2i2), 1:2 oleocanthal/oleacein (D2i0.5) or predominately tyrosol with undetectable oleocanthal and oleacein levels (D2i0). Ibuprofen (400 mg oral) provided an anti-platelet aggregation control. Blood samples for platelet aggregometry and untargeted metabolomics (a broad chemical survey of small molecules in the blood) were collected at baseline and 2hr post-EVOO intake, and the production of bioactive lipid mediators by activated platelets was measured by liquid chromatography and tandem mass spectrometry. Maximum platelet aggregation (Pmax) induced by low dose collagen was reduced for D2i2 and D2i0.5 compared to D2i0 at 2hr post-ingestion. Five of 9 participants exhibited >25% reduction in ' Pmax with D2i2 and D2i0.5 EVOO intake, and oil oleocanthal content best described this effect. Metabolomics data suggested that the “non-responders” may have been higher consumers of soy products, and possibly olive oil. Ultimately, this study showed that the platelet response to EVOO intake depends on the concentration and ratio of specific EVOO phenolics, not the oil antioxidant capacity, and may be influenced by diet. Technical Abstract: Objective: The cardiovascular benefit of extra virgin olive oils (EVOOs) may increase with their phenolic content or concentrations of specific phytochemicals. Oleocanthal and oleacin are EVOO phenolics, and as oleocanthal is a cyclooxygenase (COX) inhibitor, it may influence platelet aggregation. To compare acute oleocanthal-rich versus phenolic-equivalent but oleocanthal-poor EVOO consumption on platelet reactivity, we conducted a randomized double blind crossover trial of 9 healthy men. Approach and Results: Participants consumed 40mL of 3 EVOOs 1-week apart matched in total phenolic content but providing different hydroxytyrosol and tyrosol derivative concentrations. Oils contained either 2:1 oleocanthal/oleacein (D2i2), 1:2 oleocanthal/oleacein (D2i0.5) or predominately tyrosol with undetectable oleocanthal and oleacein levels (D2i0). Ibuprofen (400 mg oral) provided a COX inhibition control. Blood samples for platelet aggregometry and untargeted metabolomics were collected at baseline and 2hr post-EVOO intake, and activated platelet oxylipin production was measured by LC-MS/MS. Maximum platelet aggregation (Pmax) induced by 1 µg/mL collagen was reduced (p < 0.05, repeated measures ANOVA) for D2i2 and D2i0.5 compared to D2i0 2hr post-ingestion. Five of 9 participants exhibited >25% reduction in ' Pmax with D2i2 and D2i0.5 EVOO intake, and EVOO oleocanthal content best described this effect (R = 0.563, p = 0.0022), however oxylipin changes were inconsistent with a COX-mediated action. Metabolomics suggested “non-responders” to be higher consumers of soy products, and possibly olive oil. Conclusions: The platelet response to EVOO intake depends on the concentration and ratio of specific EVOO phenolics, not the oil antioxidant capacity, and may be influenced by diet. |