Crystalline Glucosamine Sulfate in the Treatment of Osteoarthritis: Evidence of Long-Term Cardiovascular Safety from Clinical Trials

Abstract

Background and Objective:Glucosamine is a safe and common treatment for osteoarthritis. Even so, literature data on the cardiovascular safety of glucosamine are limited. The objective of this paper is to investigate the long-term effects of crystalline glucosamine sulfate (CGS) on key measures of cardiovascular risk in patients with osteoarthritis.Methods: We analyzed safety data from two long-term (6-month and 3-year, respectively) randomized controlled trials of CGS. Mean changes in blood pressure, lipids, and glucose were calculated for all patients randomized to CGS or placebo in either study and for subgroups with abnormally elevated baseline values. Shift tables were used to analyze transitions from normal to abnormal levels, or vice versa.Results:This analysis on 428 osteoarthritis patients includes data from subjects who had, on average, high normal blood pressure or high cholesterol at baseline. There were no significant changes in mean blood pressure after 6 months on CGS (systolic: -5±15 mmHg; diastolic: -5±10 mmHg) or placebo (systolic: -7±14 mmHg; diastolic: -4±10 mmHg). Subgroup analysis did not show significant effects in subjects with hypertension. Likewise, blood lipids (total/LDL cholesterol) and blood glucose did not change over 3 years and 6 months of treatment, respectively, even in hypercholesterolemic or hyperglycemic subjects. The proportions of patients whose blood pressure or cholesterol levels shifted from normal to abnormal, or vice versa, were comparable in the CGS and placebo groups.Conclusions:Long-term use of CGS did not affect blood pressure, lipids, or glucose in patients with osteoarthritis. These findings further support the cardiovascular safety of CGS.

OARSI guidelines for the non-surgical management of knee osteoarthritis

“…Regarding disease modification, a SR found no statistically significant differences in minimum JSN between glucosamine and placebo at 1-year follow-up, though a moderate effect was detected at 3 years 48 . A 2011 safety review found that long-term use of glucosamine was not associated with cardiovascular (CV) safety risks 54 . Two more meta-analyses found no increase in overall adverse events relative to placebo 45,52 .…”

Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials

“…Among these, eight studies were excluded because of lack of a placebo-control (23)(24)(25)(26)(27)(28)(29)(30), two because they were not double-blinded (31,32) and one because it was not randomised (33). Six articles were ruled out as their outcomes measures were not relevant to the efficacy (34)(35)(36)(37)(38)(39), one article because of insufficient data (40), three because they were reports of other studies (41)(42)(43) and three because the intervention treatment was not glucosamine alone (44)(45)(46).…”

Supplementary Methods in the Nonsurgical Treatment of Osteoarthritis

“…29 Two more SRs found no increase in overall adverse events when compared with placebo. 5,6 Scroggie et al, 30 in an RCT evaluating glucosamine hydrochloride side effects, concluded that oral glucosamine supplementation did not adversely affect glycemic control when administered to patients with type 2 diabetes mellitus.…”