Safety of a long-term intervention with oleanolic acid in type 2 diabetes patients

Oleanolic acid (OA), a plant-derived triterpene, has demonstrated anti-inflammatory and antidiabetic properties in preclinical models. However, concerns regarding its long-term safety in humans persist due to limited clinical data and conflicting results from animal research. This study evaluated the long-term safety and tolerability of OA therapeutic doses, formulated as OA-enriched olive oil, in patients with type 2 diabetes mellitus (T2DM), a population at high cardiometabolic risk. In this 12-month, double-blind, randomized pilot trial (n = 50), participants consumed either OA-enriched olive oil (600 mg OA/kg oil; 30 mg OA/day) or the same oil not reinforced in OA (control olive oil). Clinical safety was assessed through serum markers of liver and kidney function, coagulation parameters, and systemic inflammation. Non-invasive indices for hepatic steatosis and fibrosis were also calculated. The OA-enriched intervention was well tolerated, with no significant adverse changes in hepatic or renal biomarkers. The OA group, but not the control group, showed improved kidney function, including reduced serum creatinine concentration (-6.1% compared to baseline) and increased estimated glomerular filtration rate (5.3% compared to baseline) (p < 0.05). Hepatic enzyme levels remained stable, and no progression in liver steatosis or fibrosis scores was observed. Coagulation markers remained within normal ranges in both groups with no significant adverse events attributed to OA intake. These findings are derived from a pilot trial , and, therefore, larger studies should be necessary to confirm the results and assess their generalizability. Nonetheless, our outcomes provide an unprecedented clinical evidence that long-term consumption of OA-enriched olive oil, providing a highly bioavailable therapeutic dose of the triterpene, is safe and well tolerated by T2DM patients, underscoring its long-term feasibility and sustainability. The intervention may confer additional renal and metabolic benefits, supporting its potential as a functional food strategy in the management of chronic metabolic diseases. This dataset includes the raw data used in the elaboration of the results reported in the article (in press).