Wikipedia has a useful survey of the history, studies, criticisms, and systematic reviews (https://en.wikipedia.org/wiki/Clinical_trials_on_glucosamine_and_chondroitin). It includes a long list of references. I won’t repeat all that here, I’ll just say the evidence is inconsistent and the consensus is that there is little or no clinical benefit.
Claims of Effectiveness
Misleading claims of effectiveness are often based on the GAIT trial (https://nccih.nih.gov/news/2006/022206.htm). That was a large, well-designed study of patients with knee pain from osteoarthritis. It compared glucosamine (G), chondroitin (C), both (G/C), celecoxib (a nonsteroidal anti-inflammatory drug or NSAID), and placebo. Only celecoxib outperformed placebo. Basically, the study showed that G, C, and G/C didn’t work; none of them were superior to placebo. But when they looked at subgroups, they found that the G/C combination appeared to work better than placebo for patients with moderate to severe pain: 79 percent had a 20 percent or greater pain reduction, compared to 54 percent for placebo. The study authors cautioned that it might be a statistical hiccup; the moderate-to-severe pain group was too small to draw any conclusions. The media reporting was mixed. Some newspaper headlines said, “New study shows that glucosamine and chondroitin don’t work.” Others trumpeted, “Glucosamine/chondroitin proven effective!” You would think they were reporting on two different studies!
That wasn’t the end of the GAIT study. The first phase had looked at pain levels. In the second phase, they looked at preventing joint damage in the knee over two years, and found G/C ineffective. Patients taking G/C had more joint space loss than those taking G or C alone, but the difference was not statistically significant. It was speculated that taking the two supplements together might limit their absorption (http://www.arthritis.org/living-with-arthritis/treatments/natural/supplements-herbs/glucosamine-chondroitin-osteoarthritis.php).
In the third phase lasting four years, the pain relief with G/C was no better than with placebo.
In 2013, the American Academy of Orthopaedic Surgeons (AAOS) issued a 1,200 page report evaluating the evidence for various treatments for knee osteoarthritis. They concluded, “We cannot recommend using glucosamine and chondroitin for patients with symptomatic osteoarthritis of the knee.” And they said their conclusion was based on “strong” evidence (http://www.aaos.org/research/guidelines/OAKSummaryofRecommendations.pdf).
A new study, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717399/, the MOVES trial, was published in January 2016. It looked only at patients with moderate-to-severe knee pain from osteoarthritis, and found that G/C was as effective as celecoxib at six months. That might sound impressive until you examine the details: celecoxib worked better than G/C for the first four months, and there was no placebo comparison group.
Reasons to Be Skeptical
- Why would a treatment work for moderate-to-severe pain but not for lesser levels of pain? That doesn’t make any sense. I don’t know of any other pain treatment that works that way. If it worked well for moderate-to-severe pain, shouldn’t it work even better for mild-to-moderate pain? Doesn’t aspirin work better for mild headaches than for severe ones?
- Synergistic effects are not unknown, but it is very rare for an effect to depend on combining two treatments.
- Both G and C are found naturally in the body. The amount in supplements is on the order of 1/1000th or 1/10,000th of the amount produced by the body itself. They are not essential nutrients like vitamins. How likely is it that such a small dose could produce a large effect?
- In a 2004 study (http://www.ncbi.nlm.nih.gov/pubmed/15478160) of patients who had reported relief from glucosamine, there was no difference between those who continued on glucosamine and those who were switched to a placebo substitute without their knowledge.
- When a treatment is truly effective, the evidence accumulates and becomes stronger over time. This has not happened with G/C.
So Why Do People Ignore the Evidence?
In a world of Vulcans like Mr. Spock, people would look at the evidence and conclude that G/C was probably not worth trying. But science and critical thinking don’t come naturally to humans. Evolution shaped us to prefer stories to studies, anecdotes to analyses, emotion to evidence. If you know someone who says G/C worked for them, that carries a disproportionate amount of weight. You can rationalize that the studies didn’t rule out the possibility that G/C was effective for some individuals. If you distrust authority, you may suspect that the evidence has been biased by doctors and scientists who are defending their turf (conventional mainstream medicine and the status quo). If you are a conspiracy buff, you might suspect that Big Pharma has been misleading patients for profit. If you are in pain, you would love to believe that there is something out there that will give you relief and that is safer and less expensive than prescription drugs. People want to believe in G/C, and they can easily find reasons to disregard the evidence. Hope springs eternal.
This article was originally published in the SkepDoc’s Corner column on the Committee for Skeptical Inquiry website.