Osteoarthritis (OA) is thought to be caused by breakdown of the
cartilage which cushions the ends of bones. Therefore when cartilage
is worn down it can expose the ends of the bones resulting in
friction and hence joint pain. OA is a progressive disease associated
with factors such as ageing, genetics, obesity and physical injury
(sport or otherwise). Often analgesics such as aspirin, paracetamol
or anti- inflammatory agents such as ibuprofen or more potent
prescriptive drugs are used in the management of osteoarthritis.
However, there is widespread belief that supplementation with
glucosamine can provide relief from OA knee pain without the side
effects these commonly used drug therapies may cause and some
research has even claimed glucosamine supplementation may even
help regenerated cartilage in the knee.
This article aims to explain what glucosamine is and to present
an overview of research which has made this supplement so popular,
however it also aims to highlight why so much uncertainty exists
as to its true effect.
What is Glucosamine Sulphate?
Glucosamine may prevent the breakdown of cartilage through several
mechanisms, it activates chondrocytes (specialised cells in cartilage)
to produce more collagen which holds the cartilage tissue together.
Glucosamine also pulls water into the cartilage (to maintain the
70% water content of cartilage) producing a gel-like sac providing
cushioning and flexibility in the joint. Therefore, in essence,
supplementation is thought to magnify the body's natural level
The supplements are derived from animal tissues; glucosamine
is taken from crab, lobster or shrimp shells, although it can
also be chemically synthesized. It is typically sold as glucosamine
sulphate or glucosamine hydrochloride. Glucosamine is often combined
with chondroitin sulphate which is found in and around the cartilage
cells and it has been suggested that this supplement, in combination
with glucosamine, may help further in repairing some of the damaged
joint. Chondroitin sulphate is extracted from animal cartilage
such as tracheas or shark cartilage.
What is the evidence?
In 2003 scientists reviewed the reported results of 15 studies
using either glucosamine or/and chondroitin on OA of the knee
and concluded that supplementation improved joint mobility for
1 in 5 patients and hinted that it may slow narrowing of joint
spaces. However, although the authors who reviewed these studies
concluded there does appear to be some degree of efficiency of
these supplements they did voice concerns with some flaws in all
of these studies including poor quality of research, bias due
to large company sponsorship, subjective reports of knee pain
and a small number of people being tested in the studies.
A further study in the British Journal Sport Medicine (2003)
gave subjects with regular knee pain 12 weeks of a glucosamine
supplement (2000mg per day). The results suggested that a glucosamine
supplement can provide some degree of pain relief and improved
mobility in subjects who experience regular, chronic knee pain
due to cartilage damage and/or possible osteoarthritis. 88% of
the glucosamine group did report less knee pain. However there
was no objective improvement between groups in the functional
tests and it should be noted that the reduction in knee pain was
Due to the mounting evidence from the above studies and others
suggesting glucosamine and chondroitin, separately or in combination,
may be effective in reducing pain and even improving functional
ability in patients with knee osteoarthritis an independent trial
was set up by the National Centre for Complementary and Alternative
Medicine in collaboration with the National Institute of Arthritis
in the United States of America. They called the trial ‘The
Glucosamine-Chondroitin Arthritis Intervention Trial’
(GAIT) which was the first multi-centre clinical trial which set
out to eliminate the major flaws in previous studies and to determine
whether glucosamine and chondroitin in combination or taken separately
for six months was effective in treating knee pain associated
The first phase of GAIT concluded that for a sub-set of patients
with moderate-severe knee pain, caused by OA, glucosamine combined
with chondroitin supplement did show significant pain relief (79%
had a 20% or more improvements in knee pain versus 54% in the
group not receiving these supplements) but there was lack of response
in patients with mild pain. However this pain was subjective and
the first phase of this study did not show if the supplements
actually slowed the progress of OA. However it did conclude that
glucosamine and chondroitin sulphate may be useful for patients
with moderate-severe pain but not those with mild pain, but the
researcher did also caution that due to the smaller number in
the moderate-severe group (354 compared to 1,229 in mild pain
group) “these findings should be considered as primary and
need to be confirmed by further studies”.
The second phase of GAIT (where those that took place in the
first phase where asked if they would like to continue in the
study for a further 18 months) looked at whether the supplements
slowed the destruction of the cartilage (using X ray data). However
the results were not so positive and it was concluded there was
no clinically important reduction in structural damage to the
knee between the placebo (those not taking the supplements) and
any of the supplements after two years. However they did see a
slight trend towards improvement in those with milder OA of the
knee in those taking glucosamine alone (the research did suggest
that perhaps taking both glucosamine & chondroitin together
may actually reduce the efficacy of the other) and future research
may reveal that those with less severe progression of OA may have
the greatest potential benefits with glucosamine. To conclude
in the words of the lead researcher of this trial “it would
be nice to answer the question definitively but we really couldn’t
If I decide to take glucosamine &/or chrondition sulphate
supplement what do I look for?
- Consult a doctor to find out if your knee pain is caused by
cartilage damage as the majority of studies on glucosamine &
chondroitin have only been studied in those with cartilage damage.
Athletes with cartilage damage should keep in mind that there
is no evidence that this supplement works in athletes with cartilage
damage. Therefore its use is mainly due to media reports and
'hear- say' in athletic populations. Check with a sports medicine
doctor to see if you have appropriate clinical signs and symptoms.
- If you have knee pain caused by OA/cartilage damage you can
try supplementation but if you don’t experience any difference
in symptoms within 3 months, you will probably not get any relief
from the supplements. Bear in mind that the self reported evidence
for pain relief in the above studies is far stronger than any
evidence for slowing down the progression of OA/ structural
- People who are allergic to the chitin in shellfish from which
glucosamine is extracted should be wary. Although, most allergies
are caused by proteins in shellfish and not the chitin (the
carbohydrate from which glucosamine is extracted) such individuals
should consult with their doctor.
- There has been a concern raised whether glucosamine raises
blood sugar levels in diabetics although the recent GAIT study
found no evidence in change in glucose tolerance but because
it is a possibility and evidence for this is inconclusive so
do check with your doctor if you have impaired glucose intolerance
or are diabetic.
- Suggest using 1500mg per day of glucosamine rather than combining
with chondroitin as more recent research hints that taking both
supplements in combination may interfere with absorption.
- Choose products that are sold by large well established companies
as dietary supplements are poorly regulated; therefore quality
of supplements will vary. Make sure the ingredients list indicate
just the words glucosamine sulphate/K2CL or glucosamine hydrochloride
- Children, and women who are pregnant or breastfeeding should
avoid using glucosamine, as the effects are not known in these
- As yet minimal side effects appear to be rare. There are a
very small number of reports in complementary medicine books
and websites. These include skin rashes, headaches, drowsiness
and mild stomach symptoms such as diarrhoea and flatulence.
- The long term effects of these supplements are not known.
Definitions (Oxford Medical Dictionary (1998) & Oxford Dictionary
of Chemistry (1996))
Osteoarthritis - A degenerative disease of
joints resulting from wear of the articular cartilage.
The joints are painful and stiff with restricted movement. It
is recognized on x-ray by narrowing of the joint space (due to
loss of cartilage). People who suffer from severe cartilage damage
of the joints can progress to this degenerative condition.
Chondroitin Sulphate – A combination
of a protein and a sugar that forms an important constituent of
cartilage, bone and other connective tissues.
Connective tissue - Protects and connects cells
or organs. All types of connective tissue contain protein fibres
that are either tough or elastic.
Cartilage – A tough connective tissue.
In some joints it is the main cushion between the bones. In joints
with synovial sacs (see below), it covers the ends of the bones
and is called articular cartilage.
Synovial sac- A cushioning bag of lubricating
fluid of elastic connective tissue. For example, there is a synovial
sac in the knee joint.
Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum
Z, Royle P, homas S (2009). The clinical effectiveness of glucosamine
and chondroitin supplements in slowing or arresting progression
of osteoarthritis of the knee: a systematic review and economic
evaluation. Health Technology Assessment; 13 (52):1-148
Blakeley JA & Iberia VEO (2004). Glucosamine & Osteoarthritis.
American Journal of Nursing; 104 (2): 54-59.
Braham R, Dawson B, Goodman C (2003). The effect of glucosamine
supplementation on people experiencing regular knee pain. British
Journal of Sports Medicine; 37:45-49.
Chard J, Dieppe P (2001). Glucosamine for osteoarthritis: magic,
hype, or confusion? British Medical Journal; 322: 1439-1440.
McAlindon TE, La valley MP, Gulin JP, Felson DT (2000). Glucosamine
and chondroitin for treatment of osteoarthritis. Journal of American
Medical Association; 283 (11): 1469-475
Nahin RL, Straus SE (2001). Research into complementary and
alternative medicine: problems and potential. British Medical
Journal; 322: 161-164.
Ricky F, et al (2003). Structural and symptomatic efficacy of
glucosamine and chondroitin in knee osteoarthritis. A comprehensive
meta-analysis. Archives of Internal Medicine; 163 (13): 1514-1522.
Rovati L C, Annefeld M, Giacovelli G, Schmid K, Setnikar I (1999).
Correspondence: Glucosamine in osteoarthritis. Lancet; 354 (6):
Sawitzke AD, Shi H, Finco MF, Dunlop DD, Bingham CO 3rd, Harris
CL, Singer NG, Bradley JD, Silver D, Jackson CG, Lane NE, Oddis
CV, Wolfe F, Lisse J, Furst DE, Reda DJ, Moskowitz RW, Willaims
HJ, Clegg DO (2008).The effect of glucosamine and/or chondroitin
sulfate progression of knee osteoarthritis: a report from the
glucosamine/chondroitin arthritis intervention trial. Arthritis
Rheumatism Journal; 58 (10):3183-3191
The joints on Glucosamine (JOG) study: A randomized, double-blind,
placebo-controlled trial to assess the structural Benefit of glucosamine
in Knee Osteoarthritis On 3T MRI.
(American) Center for Complementary and Alternative Medicine