Reference
Katsa ME, Ketselidi K, Kalliostra M, et al. Acute antiplatelet effects of an oleocanthal-rich olive oil in type II diabetic patients: a postprandial study. Int J Mol Sci. 2024;25(2):908.
Study Objective
To investigate whether incorporating oleocanthal-rich olive oils (OO) into a carbohydrate-rich meal affects postprandial dysmetabolism and platelet aggregation
Key Takeaway
Olive oil enhanced with 250 and 500 mg/kg of oleocanthal reduced the inflammatory and platelet effects of high-fat and high-carbohydrate meals in 5 female and 5 male participants with type 2 diabetes compared to the control meals of butter and olive oil.
Design
Randomized, single-blinded, crossover study
Participants
Non-insulin-dependent adults with type 2 diabetes diagnosed by an endocrinologist or pathologist according to American Diabetes Association criteria. Investigators screened 30 patients; they excluded 10 patients who were on insulin and 5 on anticoagulation therapy. Of these 15, 5 dropped out, and 10 (5 males, 5 females) completed the study. All were on biguanide (metformin, dose not stated), and 6 took a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (dose not stated). All came to the Metabolism Unit, Department of Nutrition and Dietetics, Harokopio University, Athens, Greece, for data collection and to consume their 5 meals, each meal at least 2 weeks apart.
Inclusion criteria included stable weight (+3 kg) for the last 2 months. No restrictions on smoking or menopause in females.
Exclusion criteria included anticoagulation or insulin therapy, diagnosis of chronic inflammatory disease, autoimmune disease, cancer, uncontrolled thyroid disease, and ingestion of food (nutritional) supplements in the last months.
Intervention
Each participant randomly consumed 5 isocaloric meals after a 12-hour overnight fast. Each meal included 120 g of white bread and 50 g of glucose with:
- BU+IB: 39 g butter and 400 mg ibuprofen (Nurofen),
- OO: 40 mL olive oil (mg of oleocanthal not stated),
- OO250: 40 mL oleocanthal-rich olive oil with additional 250 mg/kg oleocanthal, or
- OO500: 40 mL oleocanthal-rich olive oil with an additional 500 mg/kg oleocanthal.
According to the authors, “This set of meals allows several comparisons between saturated fatty acid and monounsaturated fatty acid rich meals (BU vs OO), between meals with olive oils both poor and rich in oleocanthal (OO vs OO250 and OO500) and between the administration of ibuprofen (as a positive control) and oleocanthal (BU-IBU vs OO250 and OO500).” For the meals, investigators used Karamolegos Pischatost, a crustless white bread, 5 slices; Lurpak unsalted butter, and olive oil from Olea europaea L, Kalamon variety, harvested in November from OMPHAX SA olive mill.
The 40 mL of olive oil equals 2.70512 US tablespoons.
Study Parameters Assessed
Investigators measured blood pressure, body mass index (BMI), waist circumference, dietary intake of kcal, percent fat, percent carbohydrate, percent protein, saturated fatty acids (g), monounsaturated fatty acids (g), polyunsaturated fatty acids (g), omega-3 fatty acids (g), and omega-6 fatty acids (g) at each visit. Investigators assessed fasting glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), C-peptide, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, uric acid, gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and homocysteine in serum prior to each meal.
Assessments after the meal, at 90 or 120 minutes, depending on the meal, included glucose, C-peptide, triglycerides, HDL, EC50 (half maximal effective concentration), LDL, uric acid, homocysteine, platelet-activity indices, adenosine diphosphate (ADP)–induced platelet aggregation, TRAP (thrombin receptor-activating peptide)–induced platelet aggregation, and sP-selectin (soluble platelet selectin). Investigators collected blood at baseline and at 30, 60, 90, 120, 180, and 240 minutes (4 hours) after each meal.
Data-collection and statistical tools included Research Randomizer, 24-hour dietary recall, semi-quantitative food frequency questionnaire, MedDiet Score, Nutritionist Pro software (version 2.2, Axxya Systems, Stafford, Texas), Kolmogorov-Smirnov test, t test, Mann-Whitney U test, analysis of variation (ANOVA), Pearson or Spearman correlation (SPSS v24, Chicago, Illinois), and area under the curve (AUC, using the GraphPad Prism 8.4.3). Significance was set at P<0.05.
Primary and Secondary Outcomes
Primary and secondary outcomes were not defined.
Key Findings
All meals increased glucose, insulin, and C-peptide postprandially, with a trend for higher insulin and C-peptide after the butter-ibuprofen meal.
All meals induced a mild postprandial increase in triglycerides, starting at 90 minutes and with no return to baseline after 240 minutes. A higher triglyceride response was found with the 250-mg oleocanthal compared to the 500-mg oleocanthal and the olive oil meal. The higher response to olive oil with 250-mg oleocanthal compared to olive oil with 500-mg oleocanthal and to control olive oil was unexpected.
All meals induced a decrease in uric acid and homocysteine (7%–11%) after 90 minutes. Homocysteine decline was significant at 90 minutes for butter, butter with ibuprofen, and olive oil and at 240 minutes for butter, olive oil, and olive oil with 500-mg oleocanthal.
The control meals, butter (BU) or olive oil (OO), induced a similar mild hyperglycemia/hyperinsulinemia effect, which the authors assumed did not significantly affect molecular mechanisms of platelet activation.
The high oleocanthal consumption, OO250 and OO500, yielded a dose-dependent and sustained antiplatelet effect between 90 and 240 minutes after ingestion. The antiplatelet effect of both oleocanthal-enriched olive oil meals was comparable to the butter-with-ibuprofen (BU+IB) meal. The antiplatelet properties of oleocanthal were believed to be independent of their ability to alter the kinetics of metabolic markers and more associated with the direct effect of oleocanthal or its metabolites on circulating platelets.
Investigators found a sustained and dose-dependent reduction in platelet sensitivity to ADP (50%–100%) and TRAP (20%–50%) after the oleocanthal–olive oil meals (OO250 and OO500) compared to the control butter meal (BU)and control olive oil meal (OO). Oleocanthal-enriched olive oil reduced platelet activity during the postprandial period in type 2 diabetic patients not on insulin.
Transparency
Investigators noted author contributions to the various parts of this trial and paper at the end of the paper. There was no external funding, and the Ethic Committee of Harokopio University approved the study. Investigators obtained informed consent from the study participants. Data were not available due to privacy concerns. Nikolaos Kriminianiotis and Liva Groves provided the olives and olive oil, and the World Olive Center for Health provided a scholarship for MEK, the first author.
Investigators did not identify the source and precise amounts of oleocanthal added to the olive oil. The base amount of oleocanthal in the olive oil (OO) used in this trial was less than 40 mg/kg, and the final enriched olive oils used in this study contained 250 mg/kg (OO250) or 500 mg/kg (OO500) of oleocanthal.
Practice Implications and Limitations
In type 2 diabetic patients, meals high in carbohydrates and fats cause postprandial hyperglycemia and hypertriglyceridemia, as well as an increase in atherogenic apoB lipoproteins.1 Hyperglycemia and hypertriglyceridemia also trigger inflammation and oxidative stress, a phenomenon seen in the platelets of people with type 2 diabetes, obesity, and metabolic syndrome.1
Oleocanthal is 1 of more than 36 polyphenols in extra virgin olive oil (EVOO) and gives the oil a peppery taste at the back of the throat.2 It was first identified in 1993 as the source of the pepper throat irritation and was labeled decarboxy methyl ligstroside aglycone.2 Researchers later renamed it oleocanthal (oleo for olive, canth for sting, al for aldehyde), noted its ibuprofen-like activity, and classified it as a phenylethanoid.3 Some people are sensitive to oleocanthal at 54 mg/kg, while others require higher doses to identify the peppery sensation.3
Oleocanthal is 1 of more than 36 polyphenols in extra virgin olive oil (EVOO) and gives the oil a peppery taste at the back of the throat.
Oleocanthal inhibits cyclooxygenase 1 (COX-1) and COX-2, reducing production of inflammatory prostaglandins and thromboxane; thus, it has shown effects in multiple myeloma cell lines, mouse epidermal cell lines, breast and prostate cancer cells, and other malignancies.2,4 In addition, it is neuroprotective and may benefit patients with both osteoarthritis (OA) and rheumatoid arthritis (RA) since it inhibits interleukin 6 (IL-6) and other inflammatory cytokines.2,4, 6
Oleocanthal has antiplatelet activity and can inhibit cyclooxygenase activity and production of thromboxane.2,3 A 40-mL extra virgin olive oil containing 310 mg oleocanthal, consumed daily for 1 week, increased antiplatelet activity and reduced collagen-stimulated platelet aggregation in healthy men aged 20 to 50 years.5 Oleocanthal in olive oil naturally ranges from 0.2 mg/kg to 498 mg/kg. Italian EVOO has 191.8 mg/kg, and American EVOO has 22.6 mg/kg.7
Limitations
This current study under review assessed oleocanthal’s antiplatelet effects in non-insulin-dependent type 2 diabetics over 5 different meals, all of which were equal in fat and carbohydrates but from varied sources. Anthropomorphic data were missing, and there was no correlation between patient size and the dose of oleocanthal required for a positive outcome. In 2019, the average Greek adult male weighed 81 kg; 37.5% of all adults were overweight; 17.8% were obese; and 6% to 7% of adult males and females had been diagnosed with type 2 diabetes.8
This was a very small trial of 10 type 2 diabetics who served as their own controls. The study measured multiple metabolic markers, which is a positive, but investigators did not report anthropomorphic characteristics. The report contained multiple figures with some verbalization, but these required careful analysis to determine what was (and was not) significant. There was a heavy reliance on abbreviations to shorten the text. Investigators did not state the amount of oleocanthal added to the olive oil. For now, if one wants to consume or prescribe high-oleocanthal olive oil, a peppery taste may be the easiest way of identifying a higher-content oil from the grocery store, since oleocanthal content is not on the label. In the future, we may see oils or additives on the market touting oleocanthal.
Conflict of Interest
This author has no ties to the authors of this trial or access to oleocanthal. He is in private practice, faculty at CCNM and NUHS, and consults for the Vitazan Medical Advisory Panel.
