Oleuropein and rutin ± curcumin significantly slowed down the progression of spontaneous OA lesions in guinea pigs. While no additive effect was seen in the curcumin + rutin group, the differential effects of oleuropein and rutin on inflammatory and cartilage catabolic markers suggest an interesting combination for future studies in OA protection.

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available for 94% of all subjects at baseline, 78% after 1 year and 80% after 2.5 years. The glucosamine intervention had a non-significant effect on mean HbA1c level over 2.5 years, when analysed among all subjects (p ¼ 0.94), and in subjects with a normal (p ¼ 0.60) or elevated (p ¼ 0.82) HbA1c level at baseline (see table for stratified mean HbA1c values over the follow-up period). However, compared to placebo, subjects randomized to glucosamine sulphate had a significantly increased risk for attaining an elevated HbA1c level at follow-up (odds ratio 2.81 [95% CI 1.12 -7.04]). Conclusions: A 2.5 year oral glucosamine sulphate intervention did not affect mean HbA1c levels in overweight and obese women, but did lead to significant more women with increased levels of HbA1c (! 42 mmol/ mol). This HbA1c level is known to put people at 'high risk for developing diabetes'. Long-term follow-up should demonstrate whether these women will indeed develop diabetes at a higher rate and thus, whether this should be considered as a true side effect of glucosamine within this population.

Background:OLE provides oleuropein the most prevalent phenolic component in olive leaves and has been shown to have potent anti-inflammatory and anti-oxidant effects potentially interesting for joint health (1).Objectives:The aim of this study was to investigate the effects of a 6-month intervention with an Olive Leaf Extract (OLE) standardized for oleuropein content on knee functionality and biomarkers of bone/cartilage metabolism and inflammation.Methods:The study was a randomized, double-blind, placebo-controlled, multi-centric trial of 124 subjects with mild knee pain or mobility issues. Subjects were randomized equally to receive twice a day one capsule of either maltodextrin (control treatment, CT) or 125-mg OLE (BonoliveTM, an Olive Leaf Extract containing 50 mg of Oleuropein) for 6 months. The co-primary endpoints were Knee injury and Osteoarthritis Outcome Score (KOOS) using a self-administered questionnaire and serum Coll2-1NO2 specific biomarker of cartilage degradation. The secondary endpoints were each of the five sub-scales of the KOOS questionnaire, Knee pain VAS score at rest and at walking, OARSI core set of performance-based tests and serum biomarkers (Coll2-1, MPO, CTX1, osteocalcin, PGE2 and Vplex cytokines assay in serum) and concentration of Oleuropein’s metabolites in urine.Results:Primary (global KOOS score, biomarker Coll2-1 NO2) and secondary endpoints (the five subscales of the KOOS score) improved time dependently in both groups. OLE treatment showed significantly elevated urinary oleuropein metabolites (oleuropein aglycone, hydroxytyrosol, homovanillyl alcohol and isomer of homovanillyl alcohol), and was well tolerated without significant differences in number of subjects with adverse events. At 6 months, OLE group showed a higher global KOOS score compared to placebo (treatment difference = 3.73; 95% CI = [-4.08;11.54]; p = 0.34), without significant changes of inflammatory and cartilage remodeling biomarkers. Subgroup analyses demonstrated a large and significant treatment effect of OLE in subjects with high walking pain at baseline (14.4; 95% CI = [1.19;27.63], p=0.03). This was observed at 6 months for the global KOOS score and each different subscale and for pain at walking (-23.07;95% CI = [-41.8;-4.2];p=0.02). These treatment effects at 6 months were significant for KOOS score as well as for the subscales Pain and QoL and the pain at walking.Conclusion:OLE was not effective on joint discomfort in people with low to moderate pain at baseline but significantly benefited subjects with high pain at treatment initiation. As oleuropein is well-tolerated, OLE can be used to relieve knee joint pain and enhance mobility in subjects with articular pain the most painful subjects.References:[1] Horcajada MN, Sanchez C, Membrez Scalfo F, Drion P, Comblain F, Taralla S, Donneau AF, Offord EA, Henrotin Y. Oleuropein or rutin consumption decreases the spontaneous development of osteoarthritis in the Hartley guinea pig. Osteoarthritis Cartilage. 2015 Jan;23(1):94-102Disclosure of Interests:Marie-Noelle Horcajada Employee of: nestlé, Maurice Beaumont Employee of: nestle, Nicolas Sauvageot Employee of: Nestlé, Laure Poquet Employee of: Nestlé, Madleen Saboudjian Employee of: Nestlé, Anne-Christine Hick Employee of: Artialis SA, Berenice Costes Employee of: Artialis SA, Laetitia Garcia Employee of: Artialis, Yves Henrotin Grant/research support from: HEEL, TILMAN