Glucosamine and Chondroitin for Arthritis:
Benefit is Unlikely

Stephen Barrett, M.D.

Osteoarthritis (OA), the most widespread type of arthritis, is a degenerative disease of the joints. Although sometimes capable of causing acute inflammation, it is most commonly a "wear-and-tear" disease involving degeneration of joint cartilage and formation of bony spurs within various joints. Trauma to the joints, repetitive occupational usage, and obesity are risk factors. Most people over 60 years of age have this affliction to some extent, with approximately 16 million sufferers requiring medical care. The main goal of treatment is to relieve pain.

Glucosamine and chondroitin have been widely promoted as a treatment for OA. Glucosamine, an amino sugar, is thought to promote the formation and repair of cartilage. Chondroitin, a carbohydrate, is a cartilage component that is thought to promote water retention and elasticity and to inhibit the enzymes that break down cartilage. Both compounds are manufactured by the body. Glucosamine supplements are derived from shellfish shells; chondroitin supplements are generally made from cow cartilage.

Research Findings

Laboratory studies suggest that glucosamine may stimulate production of cartilage-building proteins. Other research suggests that chondroitin may inhibit production of cartilage-destroying enzymes and fight inflammation too. Some human studies have found that either one may relieve arthritis pain and stiffness with fewer side effects than conventional arthritis drugs. Other studies have shown no benefit. As the research accumulated, expert review bodies have been cautious because, although positive reports outnumbered negative ones, the negative ones have been larger and better designed [1]. In addition, whether glucosamine offers any advantages over established drugs such as acetaminophen, traditional NSAIDS, or selective Cox-2 inhibitors has not been determined [2].

The largest and best-designed clinical trial is the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), which is funded by the National Institutes of Health. So far, the GAIT has produced two sets of negative results. In 2006, the researchers reported on a 24-week study that involved 1583 patients who were randomly assigned to receive 500 mg of glucosamine hydrochloride three times daily, 400 mg of sodium chondroitin sulfate three times daily, 500 mg of glucosamine plus 400 mg of chondroitin sulfate three times daily, 200 mg of celecoxib (Celebrex) daily, or a placebo. The study found that glucosamine and chondroitin, alone or together, did not reduce osteoarthritis knee pain more effectively than a placebo. The drug group did about 17% better than the placebo group [3].

The above-mentioned report was accompanied by an editorial which concluded:

[Based on this study], it seems prudent to prudent to tell our patients with symptomatic osteoarthritis of the knee that neither glucosamine hydrochloride nor chondroitin sulfate alone has been shown to be more efficacious than placebo for the treatment of knee pain. If patients choose to take dietary supplements to control their symptoms, they should be advised to take glucosamine sulfate rather than glucosamine hydrochloride and, for those with severe pain, that taking chondroitin sulfate with glucosamine sulfate may have an additive effect. Three months of treatment is a sufficient period for the evaluation of efficacy; if there is no clinically significant decrease in symptoms by this time, the supplements should be discontinued. Furthermore, there is no evidence that these agents prevent osteoarthritis in healthy persons or in persons with knee pain but normal radiographs [4].

In 2007, another well-designed study that involved 71 patients with osteoarthritis of the knee who were followed for one year. The study found no significant differences in function and pain between the treatment and placebo groups [5]. Later that year, a meta-analysis concluded: "Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged." [6]

To study whether the glucosamine and/or chondroitin could diminish the structural damage of osteoarthritis, interested GAIT patients were offered the opportunity to continue their original study treatment for 18 more months, for a total of two years [7]. About 570 patients enrolled. In 2008, the researchers reported that none of the treatment groups showed a significant structural benefit (slowing of the narrowing of the joint space). The researchers expressed hope that additional research might find that an as-yet-undefined subgroup of patients can benefit, but I don't share their optimism.

Two studies reported in 2010 found that patients with chronic pain experienced no benefit from taking 1500 mg/day of glucosamine. One study involved 250 adults with chronic low-back pain and degenerative osteoarthtiris who were followed for one year. Half of the patients took glucosamine and half received a placebo. The glucosamine group did no better than the placebo group [8]. The other study involved 662 GAIT participants with moderate-to-severe knee osteoarthritis who received either glucosamine (500 mg three times daily), chondroitin sulfate (400 mg three times daily), glucosamine and chondroitin sulfate combined (same doses), celecoxib (Celebrex, 200 mg once daily), or a placebo. There were no statistically significant differences among the groups [9].

Another study reported in 2014 found no evidence that glucosamine and chondroitin are effective in relieving knee symptoms or slowing disease progression among patients with osteoarthritis. Over a 4-year period, the researchers followed 1,625 patients, 18% of whom began using glucosamine and/or chondroitin during the study period. The users did no better than the non-users [10].

Products

In the United States, glucosamine and chondroitin products are marketed as "dietary supplements." Glucosamine is available in many forms, including glucosamine sulfate, glucosamine hydrochloride (HCl), and N-acetylglucosamine (NAG), and may also contain a potassium chloride or sodium chloride salt. However, there appears to be no conclusive evidence that one form is better than another. Chondroitin is typically sold as chondroitin sulfate.

In December 1999 and January 2000, ConsumerLab.com tested 25 brands of glucosamine, chondroitin and combination products and found that (a) all 10 glucosamine-only products, passed the test but 2 chondroitin-only and 6 out of 13 combination products did not (because their chondroitin levels were too low). In January 2001, one of the combination products was removed because its manganese level was judged to be too high [11]. ConsumerLab's latest report states that 8 out of 8 tested glucosamine products contained the label amount but 2 of 2 chondroitin products did not [12].

In 2001, Consumer Reports evaluated 19 products and reported:

Most . . . were reasonably well standardized, delivering at least 90 percent of the amount of glucosamine or chondroitin promised on the label, thereby meeting a new standard for the supplements proposed by the U.S. Pharmacopeia, which sets standards for drugs and proposes them for supplements. But four products —Now Double Strength Glucosamine & Chondroitin, ArthxDS Glucosamine Chondroitin, Solgar Extra Strength Glucosamine Chondroitin Complex, and Now Chondroitin Sulfate—failed to meet that standard. Two products—Solgar Extra Strength Glucosamine Chondroitin Complex and Twinlab CSA (Chondroitin Sulfate)—recommended too few pills per day to supply the dose used in the successful clinical trials. Several others listed the recommended number of pills as a range that permits consumers to take a dose that may be inadequate [13].

Safety Considerations

No study so far has found any serious side effects from either glucosamine or chondroitin. The most common side effects are increased intestinal gas and softened stools. However, animal research has raised the possibility that glucosamine may worsen insulin resistance, a major cause of diabetes. So far, studies in humans have not substantiated that risk. Nevertheless, people with diabetes should monitor their blood-sugar level particularly carefully when using that supplement. There have been no reports of allergic reactions to glucosamine. But because it is made from shellfish shells, people who are allergic to seafood should use it cautiously, watching for reactions, or avoid it entirely. As for chondroitin, it can cause bleeding in people who have a bleeding disorder or take a blood-thinning drug.

In 2001, Vital Nutrients recalled two products (Vital Nutrients Joint Ease and Verified Quality Joint Comfort) that had been found to contain aristolochic acid, a substance that can cause kidney toxicity and cancer [14].

In 2008, a Scottish newspaper reported that people had died of liver failure within weeks of taking glucosamine [15]. Although cause-and-effect cannot be proven, local physicians issued a warning.

The Bottom Line

Chondroitin appears to be useless. Whether glucosamine is useful is conflicting, but the best-designed studies are negative. This usually means that negative evidence will eventually prevail. Decisions to use glucosamine must be based on information that is less complete than is desirable. In addition, product quality control may be a significant problem. Here's my advice:

References

  1. Bausell RB. Snake Oil Science: The Truth about Alternative and Complementary Medicine. New York: Oxford University Press, 2007, pp 251.
  2. Update on glucosamine for osteoarthritis. Medical Letter 43:111-112, 2001.
  3. Clegg DO and others. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New England Journal of Medicine 354:795-808, 2006.
  4. Hochberg MC. Nutritional supplements for knee osteoarthritis—Still no resolution. New England Journal of medicine 354:848-850, 2006.
  5. Sawitzke AD and others. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the Glucosamine/chondroitin Arthritis Intervention Trial. Arthritis & Rheumatism 58:3183-3191, 2008.
  6. Reichenbach S, and others. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Annals of Internal Medicine 146:580-590, 2007.
  7. Messier SP and others. Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage 15:1256-1266, 2007.
  8. Wilkens P and others. Effect of glucosamine on pain-related disability in patients with chronic low back bain and degenerative lumbar osteoarthritis. JAMA 304:45-52, 2010.
  9. Sawitzke AD and others. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Annals of the Rheumatic Diseases 69:1459-1464, 2010.
  10. Yang S and others. Effects of glucosamine and chondroitin on treating knee osteoarthritis: An analysis with marginal structural models. Arthritis & Rheumatism, Nov 4. 2014.
  11. Product review: GLUCOSAMINE and CHONDROITIN. ConsumerLab Web site, accessed Jan 22, 2002.
  12. Product review: Joint supplements (glucosamine, chondroitin, and MSM). ConsumerLab Web site, updated Sep 22, 2007.
  13. Joint remedies. Consumer Reports, Jan 2002.
  14. Vital Nutrients recalls Joint Ease & Verified Quality Brand Joint Comfort Complex because of adverse health risk associated with aristolochic acid. News release, May 24, 2001.
  15. MacDermid A. Death sparks safety concern over popular pain remedy. The Herald (Glasgow, Scotland), March 4, 2008.

This article was revised on November 21. 2014.

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