Glucosamine review

It’s a popular alternative treatment for osteoarthritis but does it really work?
 
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01 .Introduction

Glucosamine pills

Does glucosamine help relieve the pain of osteoarthritis? The latest research casts some doubt on the matter, suggesting that you're more likely to benefit from losing weight and doing regular exercise.

Taking glucosamine still helps some people, though. Clinical trials of pain relief in osteoarthritis consistently show a big placebo effect — this is when people feel less pain despite only taking dummy pills.

If you suffer from osteoarthritis, the chances are you’ve tried glucosamine. Many people swear by it, but does it really work? Or does it work better combined with chondroitin? And are some brands better than others?

CHOICE took a close look at the current state of the scientific evidence and tested 26 glucosamine products from supermarkets and big pharmacies.

Please note: this information was current as of May 2008 but is still a useful guide today.


What is glucosamine?

Glucosamine occurs naturally in the body, where it plays a role in the formation and repair of cartilage. The glucosamine in supplements is usually extracted from the shells of prawns and other crustaceans. There’s also 'vegetarian' glucosamine available that’s made from maize starch.

Glucosamine comes in different chemical forms, which can make it difficult to interpret labels and claims on products. The forms are:

  • Glucosamine itself is the form that's active in the body, but it’s never packaged as such because it’s unstable.
  • Glucosamine hydrochloride is a stable form that's used in more than half the products we tested.
  • Glucosamine sulphate is the form used in tablets and capsules, but it’s only stable when combined with potassium or sodium chloride.

Glucosamine sulphate potassium chloride complex contains only 75% glucosamine sulphate. While most manufacturers make this clear on the label (at least if you read the fine print), not all do.

Two products in our assessment don't say how much glucosamine sulphate they contain, and in fact their measured dosage is not high enough to be effective. (See How much to take?)

Chondroitin sulphate

Chondroitin sulphate also occurs naturally in the body. It’s a major component of cartilage and gives it the rubber-like characteristics that help to absorb mechanical impact on the joints from movement and activity. The chondroitin sulphate in supplements is mostly extracted from tracheas of slaughtered cattle or from pigs’ ears and snouts. Another source is shark cartilage.

There’s evidence — but it isn’t strong — that chondroitin sulphate helps relieve the pain of osteoarthritis and improve joint function. There’s also a possibility that it provides an additional benefit when glucosamine and chondroitin are taken in combination.

Osteoarthritis

Osteoarthritis is a major cause of pain and disability that affects more than 1.3 million Australians. It’s a condition where there’s loss or damage of cartilage tissue in the joints, and it most commonly affects hips, knees, hands and the spine.

Wear and tear is a major cause, so older people are more likely to suffer from osteoarthritis. There’s evidence that about 50% of those over 65 have it (though not necessarily severely enough for it to be obvious).

Osteoarthritis can’t be cured (other than by replacing the affected joint with a prosthesis) but there are various things you can do to reduce its impact (see Other remedies to try), and there are medications to reduce the pain and swelling.

The medications most often prescribed are paracetamol and the non-steroidal anti-inflammatory drugs (NSAIDs) celecoxib and meloxicam.

 
 

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The main criticism of complementary therapies has always been a lack of scientific evidence or the poor quality of published studies. But this isn't true of glucosamine. A recent overview of the subject identified 20 high-quality clinical trials.

To test how well glucosamine works, researchers typically compare the pain levels experienced by groups of arthritis sufferers who are given glucosamine, a placebo or a non-steroidal anti-inflammatory drug (NSAID).

Research of this nature is controversial, because humans are complex organisms and studies inevitably produce conflicting results. And more often than not there¡¦s some detail in the way a trial is conducted that lays it open to criticism. Considered alone, individual studies are often only pointers ¡X the way forward comes from systematic evaluation of the evidence as a whole.

When we tested glucosamine two years ago the evidence for its effectiveness was looking good. But since then new research findings have seriously muddied the waters.

Research findings

The UK-based Cochrane Collaboration looked at all published research up to January 2005 and concluded that the evidence is inconclusive because the research findings were inconsistent.

The eight most rigorous clinical trials failed to show any benefits from glucosamine over a placebo, whereas a series of studies using a glucosamine sulphate product from the Italian pharmaceutical company Rottapharm consistently showed clear benefits.

A large government-sponsored study in the US (GAIT) that tested glucosamine hydrochloride again found that glucosamine gave no better pain relief than a placebo. It came to the same conclusion for chondroitin sulphate. The only clear benefit was from glucosamine and chondroitin in combination, and then only for a small subgroup of people with moderate to severe knee pain.

A smaller European trial concluded that glucosamine (given as glucosamine sulphate) relieved pain better than a placebo but this trial was sponsored by Rottapharm. A more recent European trial, independent of drug company support, found glucosamine sulphate was no better than a placebo for treating hip osteoarthritis.

Most recently, an extension of the GAIT study reported on loss of cartilage in osteoarthritis of the knee. The researchers tested 357 people (with 581arthritic knees) and measured joint narrowing (using x-rays) before and after two years of treatment with any one of the following:

  • Glucosamine hydrochloride (1500mg/day).
  • Chondroitin sulphate (1200mg/day).
  • A combination of glucosamine hydrochloride (1500mg/day) and chondroitin sulphate (1200mg/day).
  • The NSAID celecoxib (200mg/day).
  • Placebo.

The study suggested that glucosamine and chondroitin sulphate, together or alone, were no better than placebo in slowing loss of cartilage. (Though the researchers pointed out that interpretation is complicated because the placebo group fared better than expected based on previous research findings.)

Some experts now say glucosamine hydrochloride isn't effective at all, and question the apparent benefits from glucosamine sulphate as coming from bias caused by industry sponsorship. To complicate matters, clinical trials consistently show a big placebo effect, where people feel less pain despite only taking dummy pills.

But this hasn't stopped some claims in ads and on labels that the benefits from glucosamine are 'clinically proven'. In reality the jury is still out.

Is glucosamine safe?

The one thing that clinical trials have proved with reasonable certainty is that glucosamine and chondroitin are generally safe for most people. However, there are some exceptions:

  • If you suffer from an allergy to seafood you should avoid the majority of brands, where the glucosamine has been made from crustacean shells. Two brands ¡X Pretorius Professional Vegetarian Glucosamine 1500 and Bioorganics Vegetarian Glucosamine ¡X are of vegetable origin.
  • If you have diabetes, check with your GP before taking glucosamine. While it appears safe in the short term, there's evidence that in the long term glucosamine could make your diabetes worse.
  • People taking blood-thinning medicines, such as warfarin, should talk to their doctor before taking chondroitin, as it can increase the risk of bleeding. Chondroitin also occasionally causes stomach upsets.
Products   Amount per recommended maximum daily dose (from the label) Measured amount (%)
Brand (ranked by price within groups) Tablets or capsules? Glucosamine hydrochloride (mg) Glucosamine sulphate (mg) Chondroitin sulphate (mg) Measured glucosamine (% of the amount claimed on the label) Cost per maximum recommended daily dose ($)
Maximum daily dose 1500mg or more of glucosamine hydrochloride or glucosamine sulphate
Glucosoflex Glucosamine Hydrochloride 1500 Tablets 1500 0 0 100 0.16
Healthy Care Glucosamine HCL 1000 mg Capsules 2000 0 0 97 0.18
Nature's Way Maximum Strength Glucosamine 1500 Tablets 1500 0 0 102 0.25
Wagner 1000+ Glucosamine Capsules 0 1507 0 96 0.28
Thompson's Ultra Glucosamine 1500 Plus Tablets 1500 0 150 96 0.3
Bioorganics Glucosamine Sulfate Complex 1000 Capsules 0 1507 0 96 0.31
Bioglan Glucosamine Sulfate 1000 mg Tablets 0 1960 0 100 0.33
Cenovis Glucosamine 750 Capsules 1500 0 0 98 0.34
Nature's Own High Strength Glucosamine 1500 Tablets 1500 0 0 104 0.4
Blackmores Glucosamine 1500 Tablets 0 1505 (B) 0 94 0.44
Herron OsteoEze Tablets 1500 0 0 98 0.5
Herron Glucosamine 1000 Tablets 2000 0 0 99 0.51
Blackmores Joint Formula with Glucosamine and Chondroitin Capsules 1500 0 450 99 0.63
Pretorius Professional Vegetarian Glucosamine 1500 (A) Tablets 1500 0 0 98 0.65
Bioorganics Vegetarian Glucosamine (A) Capsules 1500 0 0 96 0.76
Naturopathica 24 hour Glucosamine Sustained Release Tablets 2000 0 0 94 0.77
Enervite Super Joint & Arthritic Relief 1100 mg Tablets 0 2260 1400  97 0.8
Microgenics Glucosamine 1500 Chondroitin Complex Tablets 3000 0 200 97 0.89
Herron OsteoEze Active Tablets 1500 0 1200  103 0.9
Nature's Way True Strength Glucosamine + Chondroitin Tablets 1500 0 500 95 1.13
GNC Glucosamine 750 Chondroitin 600 Tablets 1500 0 1200  95 1.17
Woolworths Select Glucosamine & Chondroitin Capsules 3000 0 1000 93 1.2
Bioglan Glucosamine & Chondroitin Plus Tablets 0 1507 960 95 2.25
Maximum daily dose less than 1500mg of glucosamine hydrochloride glucosamine sulphate
Woolworths Select Glucosamine Complex 500 mg Tablets 0 1130 0 98 0.28
Wagner Joint Formula Glucosamine & Chondroitin Capsules 0 1131 500

86 (C)

0.45
Nutralife High Potency Joint Care Arthritis Formula with Glucosamine and Chondroitin Capsules 0 1131 500

90 (D)

0.7
 

Table notes

  • Only three products in our test would give you 1200mg/day or more of chondroitin sulphate. These figures are highlighted in green in the table.
  • Two products contain significantly less glucosamine than the label claims. These figures are highlighted in pink in the table.

Glucosamine sulphate
Some manufacturers only give the amount per tablet or capsule of glucosamine sulphate potassium chloride complex. In these cases we’ve calculated the amount of glucosamine sulphate.

Measured glucosamine
We measured the amount of glucosamine hydrochloride or sulphate (averaged over 10 tablets or capsules) and compared this as a percentage of the amount claimed on the label.

Cost per maximum recommended daily dose
This is based on the dose recommended on the label and prices we paid in Sydney supermarkets and pharmacies in December 2007. Larger sizes, which could be cheaper, may be available.

(A) Glucosamine made from maize starch.
(B) Glucosamine sulphate sodium chloride complex. Others are glucosamine sulphate potassium chloride complex.
(C) Manufacturer told us its testing gave 98%.
(D) Manufacturer told us its testing gave 100%.

If — despite the shaky scientific evidence — you still want to give glucosamine a try, which brand is best?

There’s plenty of choice. We tested 26 glucosamine products and combinations of glucosamine and chondroitin sulphate, all widely available in supermarkets and pharmacies (see the Products compared table for details).

There are big differences in price, but of more concern is that some products don’t give you enough glucosamine or chondroitin sulphate to reach the levels tested in clinical trials — even if you take the maximum recommended dose.

How much glucosamine?

Under government regulations, the amount of active ingredient per tablet or capsule must be not less than 92.5% (and not more than 107.5%) of the amount stated on the label.

We measured the amount of glucosamine per tablet or capsule and found that, while most were within the acceptable range, three of them (pictured right) don’t contain enough glucosamine to match the dose levels of 1500mg/day of glucosamine hydrochloride or glucosamine sulphate used in clinical trials, even according to their own labels. They are:

  • Nutralife High Potency Joint Care Arthritis Formula with Glucosamine and Chondroitin (90%)
  • Woolworths Select Glucosamine Complex 500mg
  • Wagner Joint Formula Glucosamine and Chondroitin (86%)

Compounding the problem, two of these products (Nutralife and Wagner) contain significantly less glucosamine than the label claims. The figures are highlighted in pink in the Products compared table.

How much chondroitin sulphate?

 The generally recognised therapeutic dose is 800 to 1000mg per day and in the big US trial the dose level was 1200mg/day.

Only three products in our analysis would give you 1200mg/day or more of chondroitin sulphate if you take the maximum recommended dose — these are highlighted in green in the table. They are:

  • Herron OsteoEze Active
  • GNC Glucosamine 750 Chondroitin 600
  • Enervite Super Joint & Arthritic Relief 1100mg

Nimbler knees

PaulThe scientific evidence might be shaky but plenty of arthritis sufferers feel they’re getting some benefit from glucosamine. We asked members of CHOICE Online who’d tried glucosamine to tell us whether or not it had helped. About 75% thought it had worked for them.

Paul and his wife Ann take glucosamine with chondroitin. Paul has been able to stop taking Celebrex, and Ann has given up the Dichlofenec she had been taking.He thinks that given the potential risks from the two prescription medications, they’re well in front healthwise.

 

Judith Judith has osteoarthritis in her knees and ankles, which was treated with the NSAID Vioxx until it was withdrawnShe can’t take regular anti-inflammatories because she also has a hiatus hernia, so about five years ago she started taking one 1500mg glucosamine tablet a day.
While this hasn’t completely removed the pain or inflammation, she thinks it has reduced it. She now takes fish oil as well and thinks this has helped too

Can you help?

Australian research will eventually help to resolve the uncertainty as to whether or not glucosamine sulphate works in alleviating the pain of osteoarthritis. And you might be able to help.

The George Institute, affiliated with the University of Sydney, is recruiting people with painful knees for the LEGS Study. This study, funded by the National Health and Medical Research Council, will evaluate the effects of glucosamine, with and without chondroitin, on pain and cartilage loss.

If you're aged 45 to 75, have chronic knee pain and live in or near the Sydney region, go to this website for further information and contact details:www.thegeorgeinstitute.org/LEGS

The scientific evidence for glucosamine or glucosamine/chondroitin makes it seem doubtful that it's effective at relieving the pain of osteoarthritis.

However, plenty of people who suffer from osteoarthritis think it's worked for them, so it's still worth giving glucosamine and chondroitin a try, even if the only result is the placebo effect. If you get any effect at all, it's likely to take four to six weeks. On the other hand, exercise and weight loss are likely to benefit you more.

Use the Products compared table as a guide to what to choose.

It lists the products in the order of cost per maximum recommended daily dose, so start with one of the cheapest that has a dose of 1500mg/day or more of glucosamine. Avoid any that give you less than 1500mg/day of glucosamine.

If you think it's worthwhile trying the glucosamine/chondroitin combination, only three of the products (highlighted in green in the table) contain the level shown to be effective in the big US trial, and they're among the most expensive per daily dose.

Other remedies to try


Experts say that lifestyle changes are crucial in successfully treating osteoarthritis.

Regular exercise is one of the most effective treatments with the bonus that it will improve your health generally. Low-impact exercise, with less weight or force going through your joints, is best. Examples are walking, cycling and swimming.


A physiotherapist can suggest targeted exercises to reduce pain and improve the function of the affected joints.


Weight loss from exercise and diet can reduce the severity of symptoms, especially for people with knee osteoarthritis. It reduces the impact load on the joint and can improve joint flexibility and reduce pain.

Alternative treatments


We also checked out some other popular alternative treatments. They're included as an extra in some brands of glucosamine, but none of them has been as thoroughly researched as glucosamine and chondroitin.
Evidence suggests the following products are of little or no benefit:

willow bark
selenium
vitamins A, C, E
Here are some products that might help, but for which the evidence is inconclusive:

acupuncture
avocado-soybean unsaponifiables
capsaicin cream
New Zealand green-lipped mussels
ginger extract
As none of these therapies have been thoroughly tested, it's not known if they're safe or unsafe. Always talk to your doctor before trying them. Complementary medicines need to be treated with the same care and respect as prescription medicines. They can cause side effects and interfere with other medicines and make them less effective.

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