Is Glucosamine Effective for Treating Knee Osteoarthritis?

Glucosamine is a dietary supplement sometimes used to ease the pain of knee osteoarthritis (OA). Once quite popular, its use is now dwindling, mostly because of mixed results surrounding this supplement's true benefit.

If you take glucosamine or are considering a trial of the supplement (under the care of your healthcare provider, of course) here are five tidbits to keep in mind:

Glucosamine Is Naturally Found in Cartilage

Glucosamine is a natural substance (called an amino sugar) that is found in healthy articular cartilage and synovial fluid, both of which cushion your joints. In osteoarthritis, the articular cartilage in your joints deteriorates, causing pain and stiffness. The pain can be especially excruciating as the cartilage becomes so worn away that bones begin rubbing against each other.

Glucosamine Is Not Regulated as a Drug

In the United States, glucosamine is sold as a dietary supplement. This means that it's regulated by the Food and Drug Administration (FDA) as a food product, as opposed to a prescription or over-the-counter drug. 

With that, even though glucosamine is a natural component of cartilage, it does not mean that taking it is perfectly safe. In fact, glucosamine may alter blood sugar levels and may interact with some medications like the blood-thinner Coumadin (warfarin).

As always, be sure to only take a drug, including supplements, under the care of your personal healthcare provider. 

Glucosamine Is Not Recommended for Knee Osteoarthritis

While research studies on cartilage cells found that glucosamine can enhance the regrowth of cartilage and suppress inflammatory processes that lead to cartilage damage, this laboratory data has not translated into clinical benefit.

The first large study in the United States that examined the short-term effects of glucosamine (on knee osteoarthritis) was called the GAIT trial (Glucosamine Arthritis Intervention Trial). In GAIT, published in 2006, over 1500 participants with knee osteoarthritis were randomly assigned to one of five treatment groups:

• Glucosamine at 500 milligrams three times a day (total 1500 milligrams per day)
• Chondroitin sulfate (also a dietary supplement and a natural substance of cartilage) at 400 milligrams three times a day (1200 milligrams per day)
• Glucosamine and chondroitin sulfate in combination
• Celecoxib (a nonsteroidal anti-inflammatory, or NSAID) at 200 milligrams daily
• A placebo (a substance that is inactive) 

Results from the GAIT study showed that participants taking the NSAID celecoxib experienced statistically significant pain relief versus placebo. There were no significant differences between the other treatments tested and placebo.

In some of the study participants with moderate-to-severe pain, glucosamine combined with chondroitin sulfate provided significant pain relief when compared with placebo. Authors of the study, however, said that because the size of this subgroup of patients was so small, this finding should be considered preliminary and needs to be confirmed in future research studies.

For participants with mild knee pain (as opposed to moderate or severe) glucosamine and chondroitin sulfate together or alone did not provide significant pain relief.

There Are Two Types of Glucosamine

It's important to note that glucosamine can be given with two different types of salt, hydrochloride or sulfate. The GAIT study (mentioned above) used glucosamine hydrochloride. Interestingly, studies that have shown some potential, albeit small, used glucosamine sulfate to treat osteoarthritis instead of glucosamine hydrochloride.

For example, a large study in the International Journal of Clinical Practice analyzed over 3000 patients with knee osteoarthritis within 19 different trials. The authors of this study concluded that glucosamine hydrochloride was not beneficial in reducing pain (like the GAIT trial).

However, high doses of glucosamine sulfate (1500 milligrams per day) may have function-modifying effects when taken for more than six months. Function-modifying effects mean that the glucosamine sulfate may improve a person's ability to use their knee (or knees) with osteoarthritis. 

The American College of Rheumatology Doesn't Recommend It

In its guideline updated in 2020, the American College of Rheumatology (ACR) now strongly recommends against the use of glucosamine for knee osteoarthritis. (This is a change from its earlier conditional recommendation against its use.) After weighing the results of multiple studies, the authors found an overall lack of effectiveness and large placebo effects.

The ACR also recommends against the use of combination products that include glucosamine and chondroitin sulfate for osteoarthritis of the knee.

Instead, the ACR recommends the following medications:

• Tylenol (acetaminophen)
• NSAIDs (either by mouth or on your skin)
• Ultram (tramadol)
• Corticosteroid injections into the joint space
• Topical capsaicin
• Cymbalta (duloxetine)

In addition, a number of physical and mind-body measures can help symptoms of knee osteoarthritis. Among the measures the ACR strongly recommends are:

• Exercise
• Weight loss
• Tai chi
• Self-efficacy and self-management programs
• Knee bracing (tibiofemoral bracing)

The ACR conditionally recommends:

• Balance training
• Yoga
• Use of a cane
• Kinesiotaping
• Acupuncture
• Thermal interventions
• Radiofrequency ablation
• Cognitive behavioral therapy

A Word From Verywell

While the promise of glucosamine as an alternative therapy for knee osteoarthritis has not exactly panned out, some people still take it and find it works for them.

In the end, regardless of your current treatment plan for your knee osteoarthritis, it's important to see your healthcare provider for regular follow-up. This way you can modify your therapies as your joint health evolves and research unfolds.