Should glucosamine (Glucosamine) and chondroitin (Chondroitin) be taken routinely for many years or in intermittent bursts?

From the Guidelines

Glucosamine and chondroitin supplements should not be taken routinely for many years due to the lack of evidence supporting their long-term efficacy and potential for large placebo effects, as noted in the 2020 American College of Rheumatology guideline 1. When considering the use of glucosamine and chondroitin, it's essential to weigh the potential benefits against the lack of strong evidence supporting their effectiveness. The 2020 guideline strongly recommends against the use of glucosamine for patients with knee, hip, and/or hand osteoarthritis, citing discrepancies in efficacy reported in industry-sponsored versus publicly funded studies and a lack of clear biologic understanding of how efficacy would vary with the type of salt studied 1. Some key points to consider when deciding whether to use glucosamine and chondroitin supplements include:

• The potential for large placebo effects, which may lead patients to perceive benefits that are not actually due to the supplements themselves 1
• The lack of evidence supporting the long-term efficacy of these supplements, with most studies showing minimal or no benefit 1, 2
• The potential for interactions with other medications, such as blood thinners like warfarin 1
• The relatively low toxicity of glucosamine, although some patients may experience elevations in serum glucose levels 1 Given the current state of evidence, a reasonable approach would be to try these supplements for a short period, such as 2-3 months, to assess if they provide symptom relief, and then discontinue use if no benefit is observed 1, 2.

From the Research

Dosage and Treatment Duration

• The study 3 found that long-term oral treatment with glucosamine and chondroitin sulfate was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function, and quality of life in patients with knee and hip osteoarthritis.
• The treatment duration in this study was up to 54-64 weeks, with a total of 4 visits, and the patients received oral capsules of glucosamine hydrochloride 500 mg and chondroitin sulfate 400 mg.
• Another study 4 found that allocation to the glucosamine-chondroitin combination resulted in a statistically significant reduction in joint space narrowing at 2 years, but no significant symptomatic benefit above placebo was detected.

Treatment Regimens

• The study 4 compared the effects of glucosamine sulfate, chondroitin sulfate, and the combination of both on joint space narrowing and pain in patients with knee osteoarthritis.
• The study 5 found that the combined therapy with chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride did not improve joint damage in an experimental model of knee osteoarthritis in rabbits.
• A review of clinical trials 6 found that glucosamine, chondroitin, and the two in combination have been the most extensively studied, with significant improvements in pain, function, and structural outcomes demonstrated in some but not all studies.

Safety and Efficacy

• The study 3 found that treatment-related adverse events occurred in 2.8% of the patients, mainly including gastrointestinal disorders.
• A review of clinical trials 7 found that glucosamine sulfate and chondroitin sulfate have small-to-moderate symptomatic efficacy in osteoarthritis, although this is still debated, and there is compelling evidence that they may interfere with the progression of osteoarthritis.
• The review 6 also found that the safety of these nutraceuticals has been demonstrated across all of the reviewed trials, and there were no significant issues with tolerance.