Millions of people with osteoarthritis take glucosamine, often with chondroitin sulfate, making these two of the top-selling dietary supplements. Produced in the human body, these substances are involved in the production and maintenance of the cartilage that cushions joints, and it has been theorized that supplemental doses may slow or prevent the deterioration of cartilage that causes the most common form of arthritis and thus reduce pain and stiffness. The supplement glucosamine is usually made from shrimp or crab shells; chondroitin, usually from cow or pig cartilage.
But do these supplements really work? A decade ago, the findings of a landmark study threw cold water on the claims, but research has continued.
GAIT casts a big shadow
In 2006, the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) was published. This was a large, well-designed, $12-million government-sponsored clinical trial—a rarity in the field of dietary supplements. Nearly 1,600 people with osteoarthritis of the knee were randomly assigned to receive one of five treatments daily for 24 weeks: glucosamine hydrochloride alone, chondroitin sulfate alone, glucosamine and chondroitin combined, celecoxib (a prescription drug approved for arthritis pain), or a placebo (dummy pill).
Overall, neither glucosamine nor chondroitin, alone or in combination, reduced pain and other symptoms significantly better than the placebo. One surprising finding: The placebo provided relief of symptoms in 60 percent of people—double the expected placebo effect. Celecoxib did only modestly better, helping 70 percent of users.
The one positive result was that in the subset of participants with moderate to severe symptoms, 79 percent who took both supplements (not either one alone) reported significant relief, versus 54 percent who took the placebo. But because this group was small (just 70 people) and subgroup analyses can be misleading, the researchers said this finding was only “preliminary” and “exploratory” and needed to be confirmed by additional studies. Still, the supplement industry often touts this secondary finding, usually without mentioning the nearly-as-good response among the placebo takers.
What about the claim that these supplements slow or prevent the deterioration of joint-cushioning cartilage that is the hallmark of arthritis? In a 2008 follow-up GAIT study, participants continued treatment for an extra 18 months and had X-ray exams (before and after) to measure their cartilage. There were no significant differences in cartilage loss between the groups. Interestingly, glucosamine and chondroitin did worse when taken together than each alone, but nothing worked much better than the placebo.
Research machine keeps running
Since GAIT, dozens of additional studies of glucosamine, often with chondroitin, have been done. Here’s a sampling, focusing on well-designed research:
- In 2008, a Dutch study of 222 people with arthritis of the hip found that glucosamine sulfate, another form, did not reduce pain or stiffness better than a placebo, and X-rays revealed no differences.
- In 2010, a Norwegian study involving people with arthritis of the lower spine found that glucosamine sulfate, taken for six months, worked no better than a placebo.
- Also in 2010, longer-term findings from GAIT confirmed that glucosamine and chondroitin, taken singly or together for two years, were no better than a placebo at reducing pain.
- Later in 2010, a European meta-analysis also found that glucosamine and chondroitin, individually or in combination, worked no better than a placebo in reducing joint pain or joint space narrowing (that is, cartilage loss). In light of this and other research, the American College of Rheumatology, in its 2012 guidelines, recommended against glucosamine and chondroitin.
- In 2013, a meta-analysis in the International Journal of Clinical Practice looked at 19 trials and concluded that both glucosamine sulfate and glucosamine hydrochloride are ineffective for pain reduction in osteoporosis of the knee, though the sulfate form may help improve function.
- In 2014, a 24-week study from the University of Arizona found that glucosamine hydrochloride did not reduce knee cartilage damage (as seen in MRIs), relieve pain, or improve function better than a placebo in people with osteoarthritis of the knee.
- Also in 2014, an Australian study found that glucosamine sulfate and/or chondroitin sulfate did not reduce arthritic knee pain more than a placebo over a two-year period, but that the combination may reduce joint space narrowing.
- In 2015, an analysis of data from the long-term Osteoarthritis Initiative found that “three years of treatment with glucosamine/chondroitin did not appear to reduce symptoms or delay disease progression.”
- In 2016, a large European clinical trial in the Annals of Rheumatic Diseases found that glucosamine hydrochloride combined with chondroitin, taken for six months, was as effective as celecoxib in reducing pain, stiffness, functional limitation, and joint swelling in people with osteoarthritis of the knee. The treatments were not compared to a placebo, however.
- The newest study, a Spanish clinical trial in Arthritis & Rheumatology, found that glucosamine sulfate plus chondroitin sulfate worked no better than a placebo in reducing pain or improving physical function over six months in people with knee osteoarthritis.
Adverse effects: No serious side effects were reported in these studies. However, a small study reported in JAMA Ophthalmology in 2013 linked glucosamine supplements with increased intraocular pressure in people with glaucoma and suggested that this “deserves further exploration.” And people with shellfish allergy may have reactions to glucosamine made from shells.
Americans spend billions of dollars every year on unproven arthritis remedies. Everything seems to work for a while, at least in some people, largely because there’s such a strong placebo effect when it comes to pain. Moreover, arthritis pain waxes and wanes, and we tend to blame or credit whatever we are trying at the time. Anti-inflammatory pain relievers help many arthritis sufferers but don’t affect the underlying loss of cartilage.
We don’t recommend glucosamine and chondroitin—unless you’re willing to pay $20 to $30 or so a month for what is probably a placebo effect. If you already take these supplements and find they help, continue with them, but consider stopping for a while to see if there’s a difference.
Before taking any supplement for joint pain, consult your doctor for a diagnosis. The pain may be caused by rheumatoid arthritis (an autoimmune disorder), gout, or another condition for which there’s no reason to think these supplements could help.
If you have osteoarthritis, we can’t overemphasize the importance of losing weight if you are overweight, and exercising to maintain strength and flexibility. Both steps can help relieve pain and restore mobility.