Chondroitin and Glucosamine: Hype or Hope for Osteoarthritis?

[Guest guest]

Chondroitin and Glucosamine: Hype or Hope for Osteoarthritis?

http://www.medscape.com/viewprogram/7923_pnt

Chondroitin

Chondroitin and OA. Chondroitin sulfate is manufactured from shark or bovine

cartilage and is taken orally for the treatment of OA. It is available alone

or in combination with other compounds, such as manganese ascorbate,

glucosamine sulfate, or glucosamine hydrochloride, and is also available in

combination with iron for treating iron-deficiency anemia. The oral

preparation, an intravesical preparation for interstitial cystitis, and an

ophthalmic preparation are available in the United States.[1,2] A parenteral

formulation is not available in the United States.

Recommended oral dosages for adults for OA range from 800 to 1500 mg daily,

with the most common dosing, being 200-400 mg 2 or 3 times a day.[2-4] It

has been shown to be safe in studies ranging in duration from 2 months to 6

years.[2]

Despite previous reports of moderate to great effects of chondroitin on pain

in patients with OA,[5,6] recent large-scale trials did not find similar

effects. A 2007 comprehensive meta-analysis[7] that examined 20 trials with

3846 patients with knee OA revealed significant heterogeneity among studies.

When only high-quality trials were pooled for effect size, the symptomatic

benefit of chondroitin for knee OA was found to be minimal, corresponding to

a difference of 0.6 mm on a 10-cm visual analog scale. The contradictory

findings have been attributed to different populations studied, different

products used, high placebo responses of up to 60%, and different study

design.[8] The potency of commercial products has been found to be variable

and inconsistent, and contaminants have been identified in some samples.[9]

Chondroitin and Dry Eye Syndrome.

In a small study, topical chondroitin, in combination with hyaluronic acid,

was shown to be effective for dry eye syndrome, or keratoconjunctivitis

sicca.[10] Chondroitin ophthalmic solution is used as a corneal preservation

agent before corneal transplantation and as a surgical aid for cataract

extraction. Use of ophthalmic preparations should occur under the guidance

of an ophthalmologist.

Chondroitin and Coronary Artery Disease. Although early studies suggested a

beneficial effect for chondroitin on coronary artery disease, particularly

myocardial infarction prevention,[11-13] this effect has not been confirmed

and long-term studies are needed before evidence-based recommendations can

be offered for this indication.

Adverse Effects of Chondroitin. No known toxicity from chondroitin has been

reported for single oral doses of up to 3 g, but long-term toxicity is not

know. Adverse effects of chondroitin are rare, and those reported in

clinical trials include occasional epigastric pain and nausea, eyelid edema,

alopecia, and extrasystoles. Concerns have been expressed about interactions

with warfarin[14] and asthma exacerbation[15] when chondroitin is used in

combination with glucosamine. Despite worries about the presence of bovine

parts derived from beef cartilage,[16] there have been no reports so far of

bovine spongiform encephalitis disease from contaminated animal parts.

Glucosamine Alone and in Combination

Glucosamine is derived from marine exoskeletons or is manufactured

synthetically, and is believed to stimulate the metabolism of chondrocytes

in articular cartilage and of synovial cells in synovial tissue. Glucosamine

is available in hydrochloride and sulfate preparations. Both have been

examined in clinical trials on OA, although no head-to-head comparisons are

available.

For OA, a dose of 500 mg of glucosamine hydrochloride 3 times daily alone or

with chondroitin sulfate 400 mg 3 times daily has been recommended.[17] A

preparation containing 1500 mg/day of glucosamine hydrochloride and 1200

mg/day of chondroitin sulfate with 228 mg/day of manganese ascorbate is

available. However, caution is suggested when using combinations containing

manganese because of the potential for central nervous system toxicity. Of

note, the Food and Nutrition Board of the Institute of Medicine has set the

tolerable upper intake level of manganese for adults as 11 mg/day, which was

based on a no-observed-adverse-effect level for Western diets.[18]

Glucosamine sulfate alone has been examined for up to 3 years[19] with

demonstration of retardation of knee OA progression and little adverse

effect. A 2007 meta-analysis[20] examining 20 studies with 2570 patients,

however, found that a preparation of crystalline glucosamine sulfate (DONA

[Rotta Pharm; Wall, New Jersey]) was superior when compared with placebo or

non-Rotta preparations for pain and function in patients with OA. The

analysis found little benefit with other preparation.

A 2006 large randomized clinical trial examined glucosamine alone,

chondroitin alone, and the 2 combined for their impact on painful knee OA in

older adults[21] and compared each with placebo or celecoxib. The response

was only slightly greater for the combination than for either agent alone

compared with placebo, but was lower than the response to celecoxib. Overall

the combination treatment was better for those with moderate-to-severe knee

pain compared with those with mild knee pain.

A topical preparation containing both glucosamine and chondroitin used in

the short term (4 weeks) has been found to be useful for pain control in

knee OA compared with placebo.[22]

Potential adverse effects of glucosamine, although uncommon, center around

metabolic effects with some evidence of glucose metabolism impairment,[23]

although long-term studies of up to 3 years did not indicate adverse effects

on A1c, glucose, or lipid levels.[24-27] Asthma exacerbation has been

described when glucosamine has been used in combination with

chondroitin.[16] Gastrointestinal effects also have been described.

The Cases

Case 1

A 56-year-old former marathon runner has had chronic bilateral knee pain for

2 years associated with moderately severe osteoarthritis (OA), confirmed by

x-rays. He would like to be able to walk 1-2 miles daily without pain but

wants to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) due to concerns

about peptic ulcer disease. Currently, he has stiffness most mornings, and

walking half a block brings on increasing pain at a level of 4-6 on a scale

of 0 (no pain) to 10 (worst pain ever experienced). He takes acetaminophen

as needed at a total dose of 1-3 g daily -- typically 3-4 times a week --

but it has been of limited benefit. Other than acetaminophen, he is on no

other medications, supplements, or herbs; eats a heart-healthy diet; is not

obese; has a normal lipid profile; and is generally healthy. Knee

replacement is an option he might consider later on, but not presently. He

is seeking advice about using chondroitin and glucosamine to prevent

progression of OA and to reduce pain. He would like to know whether they

work, and if so, whether he should take the supplements alone or in

combination, what dose to use for optimal efficacy, and what adverse effects

to anticipate.

Case 2

A 40-year-old active and healthy woman suffers from dry eyes. She has a

family history of myocardial infarction in both parents before the age of 50

years. She has heard that chondroitin is of benefit for dry eyes and can

also slow progression of atherosclerosis and prevent coronary artery

disease. What advice would you give her about using chondroitin for these

purposes?

Responses to Cases

Case 1

This former athlete is suffering moderate-to-severe symptoms that limit his

function; a screen for depression may be appropriate. Because OA is a

degenerative condition with little likelihood of remission, symptomatic

treatment is the mainstay of management until surgery with knee replacement

is indicated or is an acceptable option. On the basis of the most recent

high-quality research, the efficacy of chondroitin and glucosamine alone for

pain and function in knee OA is somewhat in question,[8,19] and in only 1

recent good-quality large randomized clinical trial[21] was some benefit

demonstrated for moderate-to-severe knee pain for a daily dose of 1500 mg

glucosamine and 1200 mg chondroitin sulfate in combination over 24 weeks,

compared with placebo. Because the adverse effects are minimal (restricted

to gastrointestinal symptoms), his general health is good (no history of

asthma), and no drug interactions are anticipated, a trial of combined oral

therapy for 3-6 months, with acetaminophen rescue, may be warranted in this

patient to determine efficacy for his condition. Symptom and function

monitoring with a diary will help gauge responsiveness to treatment.

Long-term efficacy studies have extended only to 3 years for both products

and no recommendations can be made about treatment beyond that period.

Topical glucosamine is a potential local treatment for pain exacerbation.

Although one meta-analysis found little benefit of topical NSAIDs for

treatment of OA,[28] topical diclofenac or ketoprofen may be beneficial for

acute exacerbations with minimal systemic effects, compared with those seen

with systemic NSAIDs.[29]

Before he resorts to knee replacement, this patient may also consider

acupuncture, for which emerging -- but still controversial --

evidence[30,31] suggests some long-term improvement of chronic knee pain and

function for true acupuncture compared with sham or no acupuncture.

Case 2

Chondroitin ophthalmic solution is available as a prescription in

combination with hyaluronic acid, and there is some evidence that it

improves symptoms of keratoconjunctivitis sicca. An ophthalmologist should

be consulted if use is anticipated.

Although there is some evidence[12,13] supporting a role for cardiovascular

protection by chondroitin, it is weak and has not been confirmed in larger

clinical trials. Oral chondroitin should not be recommended for this

indication.

Editor Carol Peckham

Carol Peckham, Director, Editorial Development, Medscape, LLC, New York, NY

Disclosure: Carol Peckham has disclosed no relevant financial relationships.