The impact of olive oil polyphenol supplementation on metabolic syndrome parameters The OleoMetS study: A randomized,...

Olive oil aldehydic phenols (OOPs), including oleocanthal, oleacein, oleuropein aglycone, and ligstroside aglycone, are highly bioactive secoiridoids with unique health-protective properties. Preclinical investigations have demonstrated that OOPs possess anti-inflammatory and antioxidant attributes. The aim of the study was to assess the direct health properties of OOPs as a food supplement in humans diagnosed with metabolic syndrome. Fasting Blood Glucose (FBG) and Hemoglobin A1c (HbA1c) were chosen as primary endpoints because they are key indicators of glucose control, a core aspect of metabolic syndrome. Their combined assessment offers a comprehensive view of both short-term and long-term glucose regulation, making them highly relevant for evaluating interventions.

This double-blind, randomized, controlled clinical trial screened 110 individuals for eligibility between September 16, 2024, and January 27, 2025. Eight did not meet the inclusion criteria for metabolic syndrome, and 102 eligible participants were randomly assigned to the OOPs supplement or placebo group using a computer-generated randomization sequence to receive either the OOPs supplement or placebo. The 12-week intervention provided either a 10 mg/day polyphenol-rich olive oil extract food supplement (80 % oleocanthal/oleacein, 18 % oleuropein aglycon/ligstroside aglycon) or a placebo. No changes to lifestyle were recommended, and diet and physical activity were assessed at week 6. Fasting blood glucose (FBG) and hemoglobin A1C (HbA1c) were the primary outcomes. Secondary outcomes included lipid profile, C-reactive protein (CRP), body mass index (BMI), blood pressure, waist circumference, liver function tests (LFTs), estimated glomerular filtration rate (eGFR), uric acid, and fatigue scores. Repeated measures ANOVA/Linear Mixed Models were used to compare the mean changes (12 weeks-baseline) in fasting blood glucose levels between the intervention group and the placebo arm. Similar analysis (changes since baseline) was conducted for the continuous secondary outcomes. For categorical outcomes, changes since baseline were compared using chi-square methods. Bonferroni adjustments were made for multiple comparisons as appropriate.

All 102 randomized participants completed the 12-week intervention and were included in the final analysis. The intervention group demonstrated significant improvements across various metabolic and physiological markers compared to the placebo group. Notable reductions were observed in FBG (mean difference: -7.06 mg/dL, p < 0.0001) and HbA1c (-0.29 %, p < 0.0001). Additionally, the intervention led to significant decreases in BMI (-1.15, p < 0.0001), systolic blood pressure (-7.66 mmHg, p = 0.004), triglycerides (-8.57, p = 0.0003), oxidized LDL (-5.01, p < 0.0001), uric acid (-1.04, p < 0.0001), ALT (-4.92, p = 0.0002), and fatigue scores (-16.88, p < 0.0001). A significant increase in eGFR was also noted (+3.38, p = 0.0002).

Supplementation with OOPs shows promise in improving key metabolic markers in patients with MetS. The intervention was well-tolerated, with no serious adverse events reported. Further studies with longer intervention periods, follow-ups, and even higher OOPs dosages are needed to assess the long-term durability and magnitude of the effect.

ClinicalTrials.gov Identifier: NCT07144488.