Dietary integration with chondroitin sulfate/glucosamine hydrochloride in osteoarthritis: a critical review of available evidence

INTRODUCTION: Despite recent advances on molecular mechanisms leading to joint pain and functional impairment in osteoarthritis (OA), non-steroidal anti-inflammatory and painkiller drugs are still the most prescribed therapies to achieve symptomatic improvement. In recent years, other approaches have been under investigation. In particular, chondroitin sulphate/glucosamine hydrochloride (CS/GH) combination, alone or administered together different nutraceuticals (e.g. turmeric extracts) are emerging as effective and safer alternatives. However, scarcity of well-conducted clinical research, characterized by conflicting results, prevent guidelines from formulate definite recommendations on their use on clinical ground. We conducted an extensive analysis of available evidence to identify type and magnitude of relevant outcomes possibly affected by these therapies, to verify strength of published results and to provide suggestions for further clinical research.EVIDENCE ACQUISITION: Search has been conducted on MEDLINE and SCOPUS using the following string: "glu-cosamine hydrochloride" AND "chondroitin sulfate;" limits: humans. Manual search was also performed, based on refer-ences from narrative and systematic reviews, guidelines and pertinent trials. Studies reporting data on clinical outcomes from more than one patient affected by OA or by combination of the CS/GH association with turmeric derivatives have been selected.EVIDENCE SYNTHESIS: Systematic scan of the literature retrieved 17 pertinent papers (10 randomized trials, 1 single cohort study, 3 qualitative systematic reviews, 3 systematic reviews with meta-analysis), focused on CS/GH or CS/GH plus turmeric extracts. Evidence tables are provided. In synthesis, despite a large number of methodological flaws, which are detailed discussed, and a surprisingly large placebo effect, evident across all main studies, research results confirm CS/GH beneficial effect on articular pain in patients affected by knee OA. Moreover, association with curcumin and maybe other nutraceuticals could increase magnitude of clinical benefit. However, many fundamental aspects remain to be clarified. In particular, which patients can beneficial more from which of these interventions, which doses, schedules of administration, types of formulation warrant maximum efficacy and what is the true magnitude of the expected effect overtime are still unanswered questions.CONCLUSIONS: Current literature suggests CS/GH alone or combined with turmeric extracts could be beneficial in OA, but large and well-conducted trials are needed to clarify many critical aspects.