Glucosamine is one of the most popular joint supplements, taken to reduce pain and stiffness of osteoarthritis, and to support joint repair in those taking part in active sports. But how does glucosamine work, and how effective is it?
What is glucosamine?
Glucosamine is a building block made by cartilage-forming cells (chondrocytes) from glucose and an amino acid, glutamine. Glucosamine is found in the highest concentration in joints, where it is used to make larger molecules (such as chondroitin sulphate and hyaluronic acid) that are needed for the production of new cartilage and synovial fluid.
Elsewhere, glucosamine contributes to the structure of tendons, ligaments, heart valves, mucous membranes lining your digestive and respiratory tracts, and to healthy skin and nails.
Glucosamine synthesis declines with age
The amount of glucosamine your cartilage cells make naturally falls with age. The amount of glucosamine-containing molecules (aggrecans) your joint cartilage cells make typically halves between the ages of 20 and 45; by the age of 69 you make just 25% of the amount made in your early 20s.
This decline in glucosamine production is associated with synovial fluid becoming thinner and less cushioning, and with cartilage becoming more brittle and cracking.
Glucosamine supplements are widely taken to help replenish falling levels and promote continued repair in ageing joints.
Glucosamine is not just a building block
Although glucosamine supplements provide building blocks for making new structural tissues and proteoglycans in joints, the concentrations achieved after taking supplements suggest this is not the main way in which it promotes healing and reduces joint pain and stiffness.
Glucosamine is now also known to act as a biological signal that switches on genes to stimulate the formation of new cartilage and synovial fluid, and to suppress the activity of immune cells involved in the inflammatory breakdown of cartilage.
Glucosamine also increases the level of hyaluronic acid in synovial fluid – a molecule which attracts up to 1000 times its weight in water, to make joint fluid more cushioning.
Glucosamine supplements were originally produced from the chitin shells of crustaceans (lobster, crab and prawns) but can now also be synthesised from vegetable sources such as corn, which is great for those who follow a plant-based diet, or who are allergic to seafood.
Two main forms of glucosamine are available: glucosamine sulphate and glucosamine hydrochloride. Glucosamine sulphate is digested by hydrochloric acid in the stomach so that around half dissociates into neutral glucosamine and half into ionised glucosamine. If recovered, most would be in the form of glucosamine hydrochloride which means there is little to choose between these two versions.
The advantage of taking glucosamine hydrochloride is that, weight for weight, it supplies 40% more glucosamine than glucosamine sulphate.
An advantage of taking glucosamine sulphate is that the sulphur component has an additional anti-inflammatory action which some people find beneficial.
Both forms of glucosamine are readily absorbed from the intestines, with more than 90% of an oral dose of glucosamine being deposited in joint cartilage. Because the molecules are small, they penetrate and diffuse through the cartilage matrix and are absorbed by cartilage cells to increase synthesis of joint building blocks (eg aggrecan).
However, as with many prescribed drugs such as paracetamol, ibuprofen and codeine, some people inherit genes that mean they do not respond as well to these biological signals as others. One study assessed the response of cartilage cells obtained from people with osteoarthritis who were undergoing joint surgery. They found that cartilage cells from 60% of patients responded well to the biological effects of glucosamine, but that 40% of samples did not show a significant response.
The only way to know if you are within the two out of three who will benefit is to try glucosamine supplements for three months to assess improvements in joint pain and stiffness.
If glucosamine alone doesn’t work (which is the most cost-effective option) then a combination supplement that provides glucosamine plus other joint active such as chondroitin and/or MSM may provide greater benefits.
NB Taking paracetamol (acetaminophen) may neutralise the therapeutic effect of glucosamine sulphate to reduce its effectiveness.
One of the first studies into glucosamine was published in The Lancet in which 212 people with knee osteoarthritis took either 1500mg glucosamine sulphate daily, or inactive placebo, for three years. As expected, those taking inactive placebo developed progressive narrowing of their knee-joint space and a gradual worsening of symptoms over the three-year trial period. Those taking glucosamine sulphate, however, showed no significant loss of joint space and enjoyed significant improvements in pain and disability.
A later analysis suggested that glucosamine sulphate was most effective in people whose joints still had significant amounts of cartilage present, which makes sense if glucosamine acts through an effect on live chondrocytes. Those who took 1500mg glucosamine sulphate for up to three years in these studies were then followed for a further 5 years, on average, after their supplements were stopped. Those who had taken glucosamine sulphate underwent fewer surgical knee replacements than those taking placebo, and also needed fewer painkillers and anti-inflammatory drugs to control their symptoms.
Recent glucosamine clinical trials
It is generally accepted that longer-term trials of at least 2 years (chondroitin) and 3 years (glucosamine) are needed to show significant reductions in joint space narrowing compared with placebo. The results from six randomised controlled trials involving 1,502 people who had taken glucosamine sulphate for at least three years show a moderate protective effect on minimum joint space narrowing, and a protective effect on severe joint space narrowing. The researchers concluded that glucosamine sulphate at a dose of 1,500mg per day for three years or more, may delay the natural progression of osteoarthritis of the knee.
The results from 54 studies, involving 16,427 people confirm that glucosamine alone or glucosamine plus chondroitin and the prescribed non-steroidal anti-inflammatory drug, celecoxib, are all more effective than placebo in relieving joint pain and improving joint function (eg ability to climb stairs, walk further etc).
All treatment options showed clinically significant improvements in joint pain, but only glucosamine plus chondroitin showed clinically significant improvements in joint function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. This large analysis of all the evidence confirms the benefits of glucosamine and glucosamine plus chondroitin in the treatment of knee osteoarthritis
It’s important to only select supplements made to a pharmaceutical standard known as GMP (Good Manufacturing Practice) to ensure tablets contain the correct ingredients, in a consistent dose.
Glucosamine may help you live longer!
Researchers from the University of Washington and the Fred Hutchinson Cancer Research Centre, found that, out of 77,719 people aged 50 to 76, those who were taking glucosamine on at least four days a week, for at least three years, were 17% less likely to die from any cause than non-users over the following five years.
When followed for an average of eight years use of glucosamine (with or without chondroitin) was associated an 18% lower risk of mortality compared with never-users.
Overall, current use of glucosamine was associated with a significant 13% decreased risk of death from cancer and a 41% reduced risk of death from respiratory disease.
The most widely recommended dose for glucosamine is 1500 mg a day, however up to 3g daily may be taken for additional benefits although some people develop digestive side effects at high doses.
Benefits are often seen within one month of starting glucosamine, but at least 12 weeks is needed to assess whether or not it will help you as an individual.
If, after 2 months, your symptoms are not sufficiently improved, you may wish to add in, or switch to, a chondroitin sulphate supplement to see if that suits you better.
Glucosamine side effects
Glucosamine is generally well-tolerated, and a Cochrane Review of 20 randomised controlled trials, involving almost 2,570 people, concluded that glucosamine is as safe as placebo in terms of the number of side effects.
If you have diabetes, always monitor blood glucose levels when making any dietary changes or starting a new supplement. Reassuringly, a study from 2011 found that glucosamine has no effect on fasting blood glucose levels in people with diabetes, or those with impaired glucose tolerance.
Do you take glucosamine?
I take glucosamine and notice a benefit. My knees, which were creaky and painful from running now feel as if they’re cushioned by soft cotton-wool, presumably due to better synovial oil production. Have you tried glucosamine supplements? Did you find them helpful? If you have any comments or questions, please use the form below and I’ll get back to you as soon as I can.
Image credits: frauke_feind/pixabay; pat_guiney/flickr