Placebo Beats Supplements for Arthritis Pain

Posted 27 January 2017

New York Times

Nicholas Bakalar Jan. 26, 2017

Many people take glucosamine and chondroitin supplements for arthritis pain, but a controlled trial has found no evidence that the combination works. In fact, in this study, the placebo worked better.

Spanish researchers randomized 164 men and women with knee osteoarthritis to take a single daily dose of 1,500 milligrams of glucosamine and 1,200 of chondroitin, or an identical looking placebo. The study is in Arthritis & Rheumatology.

The researchers used a scale that shows 10 faces with increasingly pained expressions and asks patients to say which picture matches their degree of pain. People who took the medicines had a 19 percent reduction in pain scores after six months on the regimen. But those who took the placebo had a 33 percent reduction.

In scales measuring how well the knee worked, there was no difference between the treatment and control groups.

“A lot of money is spent on these drugs, and people have thought they were useful to decrease pain and increase function,” said the senior author, Dr. Gabriel Herrero-Beaumont, a professor of medicine at the Autonomous University of Madrid. “But it’s difficult to demonstrate that they work. We have not found any kind of pharmacological effect of these drugs.”

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Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six-Month Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical

Jorge A. Roman-Blas, Santos Castañeda, Olga Sánchez-Pernaute, Raquel Largo, Gabriel Herrero-Beaumont, the CS/GS Combined Therapy Study Group

First published: 28 December 2016

DOI: 10.1002/art.39819View/save citation identifier: NCT01893905.

Supported by Tedec Meiji Farma SA, Madrid, Spain.


To assess the efficacy and safety of combination therapy with chondroitin sulfate (CS) and glucosamine sulfate (GS) compared to placebo in patients with symptomatic knee osteoarthritis (OA).

A multicenter, randomized, double-blind, placebo-controlled study was performed in 164 patients with Kellgren/Lawrence grade 2 or grade 3 radiographic knee OA and moderate-to-severe knee pain (mean ± SD global pain score 62.1 ± 11.3 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to receive either combined treatment with CS (1,200 mg) plus GS (1,500 mg) or placebo in a single oral daily dose for 6 months. The mean change from baseline in the VAS global pain score was set as the primary end point. Secondary outcomes included the mean change in the investigator’s global assessment of disease activity, total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain and function subscale scores on the WOMAC, responder rates based on the Outcome Measures in Rheumatology (OMERACT)–Osteoarthritis Research Society International (OARSI) 2004 response criteria, and rescue medication use. Adverse events were also recorded. A Data and Safety Monitoring Board was instituted to ensure patient safety and data accuracy.

Intriguingly, in the modified intent-to-treat (mITT) population, CS/GS combination therapy was inferior to placebo in the reduction of joint pain (mean ± SD change in VAS global pain score over 6 months −11.8 ± 2.4 mm [19% reduction] in patients receiving CS plus GS versus −20.5 ± 2.4 mm [33% reduction] in patients receiving placebo; peak between-group difference in global pain score at 6 months 8.7 mm [14.2%], P < 0.03), but no between-group differences were seen in the per-protocol completers. Both placebo treatment and CS/GS combination treatment improved to a similar extent the total WOMAC score as well as the pain and function WOMAC subscale scores, both in the mITT population and in the per-protocol completers. Neither the OMERACT–OARSI responder rate nor the frequency of rescue medication use differed between the treatment groups. Severe adverse events were uncommon and equally distributed.

The results of this trial demonstrate a lack of superiority of CS/GS combination therapy over placebo in terms of reducing joint pain and functional impairment in patients with symptomatic knee OA over 6 months. Further research might fully elucidate the suitability of CS/GS combination therapy in patients with OA.


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