What is it?

Glucosamine sulphate and glucosamine hydrochloride are nutritional supplements. Animal studies have found that glucosamine can both delay the breakdown of and repair damaged cartilage. The results for the use of glucosamine for osteoarthritis are mixed and the size of the effect is modest. There’s some evidence that more recent trials and those using higher-quality methods are less likely to show a benefit. Evidence from trials on glucosamine hydrochloride is scarce and not convincing.

  • Family: Nutritional supplement
  • Scientific name: Glucosamine sulphate, glucosamine hydrochloride
  • Other names: GS, amino monosaccharide, sulfated monosaccharide, chitosamine, D-glucosamine

Glucosamine is an amino sugar made from shellfish or prepared in the laboratory. It’s available in two forms: glucosamine sulphate and glucosamine hydrochloride. You can buy both from high-street retailers.

How does it work?

Glucosamine is found naturally in your body. It plays an important role in making glycosaminoglycans and glycoproteins, which are essential building blocks of many parts of your joints, including ligaments, tendons, cartilage and synovial fluid. It’s been suggested that the way these parts of your joint are built and maintained contributes to the development and the progression of osteoarthritis.

Animal studies have found that giving glucosamine can delay the breakdown of cartilage as well as rebuild it.

Is it safe?

Side-effects, which are usually mild and infrequent, include:

  • stomach upsets
  • constipation
  • diarrhoea
  • headaches
  • rashes.

If you’re allergic to shellfish, you should make sure that you take the shellfish-free variety.

You should also be cautious about taking glucosamine if you have diabetes. Glucosamine might increase your blood sugar level and it may mean that you need to adjust your treatment to make sure it carried on working. There are several reports of interaction between glucosamine and anti-diabetic treatments. There are also some reports of possible interaction with chemotherapy drugs and drugs that lower blood cholesterol.

Most trials used a standard dose of 500 mg of glucosamine sulphate or glucosamine hydrochloride taken three times a day.

Glucosamine sulphate trials for osteoarthritis

A review article of 18 trials investigating the effectiveness of glucosamine sulphate in treating osteoarthritis was published in 2005. A further four trials published since 2007 evaluated the effect of glucosamine sulphate in the treatment of hip and knee osteoarthritis. A second review article compared the clinical effectiveness and safety of glucosamine sulphate with those of non-steroidal anti-inflammatory drugs (NSAIDs).

Review article (2005)

The number of participants in the RCTs included in this article ranged from 30 to 319. The trials lasted from three weeks to three years.

  • Seven trials out of 13 which compared glucosamine sulphate to a placebo found that the glucosamine sulphate was significantly better than the placebo in relieving pain.
  • In all 13 RCTs, the number and severity of side-effects reported by participants who were given glucosamine sulphate weren’t significantly different from those reported by participants who got the placebo.
  • Three trials out of five found that glucosamine sulphate was significantly better than the placebo in improving problems associated with walking and other daily activities.
  • No trials found that glucosamine sulphate was significantly effective, as compared to a placebo, in improving all the main osteoarthritis-related symptoms (pain, disability and joint stiffness).
  • Trials that used one company’s (Rotta Pharm) supplement showed a positive effect for pain and function while those that used other brands didn’t.
  • Trials that used the best methods to make sure participants didn’t know which treatment they were getting didn’t show significant benefits in pain relief and improved physical function in those who received glucosamine sulphate.

Trial 1

The first trial involved 222 people over two years. The supplement didn’t show any beneficial effects, compared to a placebo, in relieving pain and improving function.

Trial 2

In this six-month trial, which included 318 participants, glucosamine had a clear significant benefit over a placebo and an even stronger effect than paracetamol in improving both pain and function.

Trial 3‡

The 64 participants with osteoarthritis of the knee in this study received either 500 mg glucosamine sulphate three times a day or 400 mg vitamin E made from palm oil once a day for six months. Both groups improved in pain and function, but there was no difference between them.

Trial 4

60 participants with primary osteoarthritis in either one or both knees were randomised to receive a 1500 mg sachet of glucosamine sulphate or a placebo. After 12 weeks, there were no improvements in the placebo group but those who received glucosamine reported significant improvements in resting and moving pain, overall pain, stiffness and function. The improvements in these final three measures lasted for 20 weeks. In the treatment group, reported side-effects were heartburn and an all-over itch.

Review article

This review article summarised results of four trials:

  • Two trials out of three found that glucosamine sulphate was significantly more effective than NSAIDs in reducing pain, while the third found that both treatments had similar effects.
  • One trial out of two found that glucosamine sulphate was significantly better than NSAIDs in improving physical function, while the second trial found that both medications had similar effects.
  • Three trials out of four found that the number and severity of side-effects reported by participants taking glucosamine sulphate were significantly less than those reported by participants who were given NSAIDs.

‡ A trial of low quality. Results of this trial were given a lower weighting when we came to our conclusion about the compound.

Glucosamine hydrochloride trials for osteoarthritis

Two RCTs were conducted to evaluate the role of glucosamine hydrochloride in the treatment of knee osteoarthritis. A review article also looked at its effects for hip and knee osteoarthritis.

Trial 1

The first trial included 118 people and lasted 8 weeks. Participants were randomly selected to receive 1,500 mg a day of glucosamine hydrochloride or a placebo.

  • 49% of participants in the treatment group reported that they were ‘better than at the start of the trial’, but 40% of the participants who got placebo capsules said the same, which suggests that glucosamine hydrochloride isn’t significantly better than a placebo in improving osteoarthritis-related symptoms.
  • In addition, this trial found that glucosamine hydrochloride wasn’t significantly better than the placebo in reducing pain, stiffness and physical function.

Trial 2‡

In the second trial, 1,583 people with knee osteoarthritis were randomly assigned to receive one of the following treatments once a day for 24 weeks:

The trial found the following results:

  • Participants who received glucosamine hydrochloride or chondroitin sulphate didn’t report a significant improvement in pain, stiffness and physical function when compared to participants who were assigned the placebo.
  • The only groups who achieved significant improvement in osteoarthritis-related symptoms when compared to placebo were those who were assigned celecoxib, and those who had moderate-to-severe knee pain at the outset of the trial and were given the glucosamine hydrochloride/chondroitin sulphate combination.
  • Two years after treatment, 662 people were reassessed. None of the treatments were reported to give greater improvements than the placebo in pain and function measurements.

In RCTs generally, side-effects of glucosamine hydrochloride were only mild and infrequent.

Review article (2010)

Taking glucosamine (or its combination with chondroitin) didn’t result in a clinically meaningful reduction in joint pain or change clinical aspects of the joint.

‡ A trial of low quality. Results of this trial were given a lower weighting when we came to our conclusion about the compound.