Introduction

The global supplement market is a multi-billion pound industry which is rapidly expanding. Glucosamine combined with chondroitin is the key supplement promoted for the treatment of osteoarthritis, a debilitating joint condition that can cause severe knee pain. Numerous scientific studies have tried to establish if glucosamine can provide pain relief for an increasingly aging population with severe joint problems. 

• Is the supplement industry right in claiming the numerous benefits of glucosamine? 
• Or do patients waste their money and hopes on something that does not work?

Background information

Osteoarthritis

Osteoarthritis is a medical condition that causes joints to become stiff and painful. The most common symptom is arthritis, resulting in joint swelling, tenderness, grating and “crackling” upon movement. Although any joint can be affected, osteoarthritis mainly occurs in the knees, hips, and hands.

Joints are subject to constant wear and tear that require continuous repair by the body. However, in osteoarthritis, the protective layer of cartilage breaks down and abnormal bone growth, swelling, and redness can occur. The exact cause is unknown but risk factors include age, joint injury, obesity, damage caused by rheumatoid arthritis, and family history.

Treatment options

There is no cure for osteoarthritis and it can worsen with age. Living with osteoarthritis may mean restriction of movement. This could range from difficulty opening a jar, to more severe consequences such as restrictions in mobility and pain that impact quality of life.

Mild symptoms can be treated by regular exercise, losing weight, wearing suitable footwear, and using devices that alleviate pressure on affected joints.

For more severe forms of osteoarthritis pain painkillers and physiotherapy are normally sufficient, with surgery required in more severe cases. 

Additionally, non-steroidal anti-inflammatory drugs (NSAIDs) can be used to relieve joint pain and reduce inflammation. However, some NSAIDs are associated with side effects and are to be used with caution in particular if used over extended periods.

Glucosamine - an alternative to painkillers?

Glucosamine is a common monosaccharide, a glucose molecule with an attached amino group. It can form chitin and chitosan polysaccharides and is commercially produced by the fermentation of grain and corn.

The Task Force of the European League Against Rheumatism (EULAR) and the Osteoarthritis Research Society International (OARSI) have confirmed an acceptable safety level for glucosamine. Glucosamine is a non-NSAID with relatively minor known side effects although caution is advised for some health conditions and in individuals with shellfish allergies.

The body uses glucosamine to make the tendons and cartilage of our joints. 

• Would prescribed glucosamine noticeably improve joint health and slow down knee osteoarthritis?
• Can glucosamine reduce pain levels? 

Science - a confusing picture

A recent study conducted by Harvard shows a truly confusing picture. In 2016, a placebo-controlled study using glucosamine sulphate combined with chondroitin sulphate concluded that no pain relief or functional improvement for patients with knee osteoarthritis was detected after 6 months.¹

Moreover, in 2018, in a literature review covering 69 studies, glucosamine and chondroitin were ineffective and showed no clinically important benefits in mitigating hand, knee, and hip osteoarthritis.²

Subsequently, in 2022, a literature review including 3793 patients suffering from knee osteoarthritis concluded that glucosamine and chondroitin provided effective pain relief and improved stiffness and physical function. This combination was superior to other treatments, highly tolerable, and economical.³

However, the National Institute for Health and Care Excellence (NICE) recommends that GPs no longer prescribe glucosamine and chondroitin on the NHS because there is no strong evidence that they are effective as a treatment for osteoarthritis.

It works - some studies claim

Given mixed evidence, patients with osteoarthritis may be skeptical about the potential benefits of glucosamine. 

For over 20 years in vivo and in vitro studies have demonstrated that glucosamine modifies joint tissues and synovial fluid and has anti-inflammatory properties. These effects may only be achieved at very high doses whereas treatment doses (1500mg/day) may be insufficient for therapeutic effects on affected joints.

Nevertheless, in 2023, a review of 15 studies demonstrated that glucosamine reduced knee pain significantly when compared to placebo. However, only minimal benefits for pain, stiffness, and physical function were recorded when using the Western Ontario and McMaster Universities Arthritis Index.⁴

Glucosamine and chondroitin significantly reduced moderate-to-severe knee pain caused by osteoarthritis after 6 months of treatment. The reduction was statistically significant, as was the improvement in stiffness and function. The combination treatment performed as well as the NSAID Celecoxib.⁵

Some studies have shown that taking glucosamine not only leads to reduced pain levels but also structurally improves the joints. However, the results vary strongly, as does bioavailability in the joints. The benefits of glucosamine may extend further as some studies demonstrated that long-term glucosamine use may lead to decreased cardiovascular mortality. The effects on chronic inflammation may further widen the application of glucosamine.⁶

The BBC conducted an experiment where half of 74 volunteers with knee pain were told they were given food supplements and the other half were introduced to exercises to strengthen the muscles around the knee. After 2 months 80% of the exercise group reported a significant reduction in knee pain whereas the ‘supplement’ group reported an improvement of 55%. 

This small-scale experiment demonstrated convincingly the power of the placebo effect and raises the question of powerful placebo effects across various clinical studies.

Are glucosamine levels high enough?

Only high concentrations of up to 2000-fold the treatment concentration demonstrate the efficacy of glucosamine. However, at treatment concentration, the glucosamine competes with glucose for cellular uptake and hence only low concentrations are available to the joints. 

When glucosamine sulfate was given to healthy volunteers and patients with knee osteoarthritis at a dose of up to 3000 mg/day, glucosamine levels in the synovial fluid increased significantly but remained 10-100 times below the levels required to build new cartilage tissue.^7,8

Human cells can form glucosamine from glucose far in excess of that provided by oral administration.⁹

Does glucosamine work for the treatment of joint issues in animals? 

Glucosamine has also been given to dogs to treat joint problems. The results are very similar to those in humans in that some studies^10,11 have shown the efficacy of glucosamine with chondroitin while others failed to detect any benefits.¹²

In horses, studies could show that glucosamine levels increased in synovial fluid upon administration but remained 500-fold below the threshold needed to positively affect cartilage metabolism.^13,14,15 A three-month trial on aged horses concluded that glucosamine showed no signs of improving gait stiffness.¹⁶

The supplement industry - false claim lawsuits

The global supplement industry is worth billions. Glucosamine and chondroitin are flagship products for the treatment of osteoarthritis and their alleged benefits are actively promoted. In some cases, consumers have taken the producers of glucosamine to court as the products were advertised as being able to restore lost cartilage. This case ruled in favour of the consumers, requiring the supplement industry to pay out considerable sums.¹⁷

FAQ’s

Does glucosamine reduce pain for patients with osteoarthritis?

The available scientific picture is mixed as a considerable number of studies show no evidence of pain relief, however, some studies show significant improvements in pain, function and stiffness of knee joints. Many patients are convinced that glucosamine brought them noticeable pain relief.

Does glucosamine have side effects?

Side effects may include nausea, heartburn, diarrhea and constipation. Doctors’ advice may be needed for a number of medical conditions as well as pregnancy.

Do you need a prescription for glucosamine?

Glucosamine cannot be prescribed but is freely available over the counter.

Where does glucosamine come from?

Glucosamine originates from the shells of shellfish or is artificially made in a lab.

Do GPs prescribe glucosamine?

According to the National Institute for Health and Care Excellence (NICE) there is no strong evidence that glucosamine and chondroitin provide effective treatment therefore it is not available on the NHS.

Summary

In a sizable global market, glucosamine has been promoted by the supplement industry as an efficient treatment for osteoarthritis. However, numerous scientific papers investigating the benefits of glucosamine present contrasting evidence where many studies do not detect benefits at a clinical level. In sharp contrast, some clinical trials reported convincing pain relief and improved joint stiffness and function. Investigations into potential benefits for dogs and horses with joint problems failed to detect any improvements. These varying outcomes remain puzzling and further research is needed to explain their causes. As the debate about the potential benefits of glucosamine continues, the glucosamine industry may be more cautious with treatment claims of glucosamine given recent legal action.