NUTRACEUTICALS COLUMN Editors: Gil Hardy, PhDErick Valencia, MD

Glucosamine: Con or Cure? Part IILouise Sutton, MPharm, Lisa Rapport, MPhil, MRPharmS, and

Brian Lockwood, PhD, MRPharmSFrom the School of Pharmacy and Pharmaceutical Sciences, University of Manchester,

Manchester, United Kingdom

In “Glucosamine: Con or Cure? Part I,”which appeared in the May 2002 issue, theusefulness of glucosamine in the treatmentof osteoarthritis was discussed andsummarized. —Editor

OTHER POSSIBLE APPLICATIONS

In addition to osteoarthritis, there has beensome evidence that glucosamine might beused to treat other ailments. During one clin-ical trial1 it was noted as a side effect that allpatients who normally suffered from migrainereported a change in their headaches. Thisinterested those conducting the trial, so an-other 10 patients became involved. These pa-tients were given glucosamine for 4 to 6 wk;the results were a substantial decrease in thefrequency of headaches and a reduction inheadache severity. The response was dose re-lated. The mechanism for this is not knownbut it is thought to relate to mucopolysaccha-ride synthesis. Mast cells are thought to play arole in the inflammation involved in thesetypes of headaches; heparin is produced bymast cells and its release may function todecrease mast cell activation and may haveanti-inflammatory properties. It is possiblethat glucosamine encourages mast cell hepa-rin synthesis, which would help to preventinflammation from occurring in the firstplace.1 No controlled studies have investi-gated whether this is the case. It has also beenlinked to the treatment of gastrointestinal dis-orders such as Crohn’s disease and ulcerativecolitis.2 Glucosamine stimulates proteoglycanproduction by chondrocytes; however, if itsimultaneously causes production by smoothmuscle cells, there could be an impact onlevels of atherosclerosis within the arteries.This would be of major importance becausemainly the elderly population, who also aremore likely to have atherosclerotic buildup,take glucosamine. The effects on atheroscle-rosis are mixed; there are protective and un-wanted effects. On the downside, an increasein concentration of arterial wall proteoglycans

might increase the risk of entrapment oflipoproteins. This would cause a greaterbuildup of atherosclerotic plaques. How-ever, glucosamine is also thought to reducemetalloproteinase production within athero-sclerosis, which would stabilize the plaques,thereby decreasing their risk of rupture.3

Further data from long-term use will need tobe examined to establish whether this posesan unacceptable risk to the user.

With the population of elderly people in-creasing every year, there is a related increasein the incidence of osteoarthritis and the needfor a reliable and effective therapy. Standardtreatments for osteoarthritis are outdated andneed developing. Current use of non-steroidalanti-inflammatory drugs as the first-line treat-ment for osteoarthritis needs to be reconsid-ered because they are not well tolerated andhave a high incidence of side effects. Neweragents, the cyclooxygenase-2 (COX-2) inhib-itors, are claimed to have a lower incidence ofside effects than the older non-steroidal anti-inflammatory drugs but have not been usedlong enough to assess the long-term effects.None of these products cure the disease stateand, with the high incidence of side effectsand contraindications, current treatment is notsatisfactory.

With all the evidence to date, it wouldseem that glucosamine sulfate should beconsidered as a possible replacement fornon-steroidal anti-inflammatory drugs in thetreatment of osteoarthritis because it islikely to have fewer side effects and have agreater therapeutic margin when comparedwith synthetic conventional treatment.

A Cochrane review performed in 1999studied 16 double-blind, randomized, con-trolled trials involving the use of glucosaminefor the treatment of osteoarthritis. The conclu-sion from this review was that glucosaminewas effective and safe for use in osteoarthritis.It also stated that long-term effectiveness andtoxicity could not be decided because the trialsinvolved were all of short duration.4

Further studies on glucosamine are re-quired and should be performed for severalreasons. The first is to demonstrate the effi-cacy of glucosamine for the treatment of os-teoarthritis to health professionals and thepublic. The second is that long-term studieswould be beneficial to prove safety concerns,show the level and nature of any side effects,

and establish any contraindications. To datethere are few long-term studies and thus littleinformation on long-term use of glucosamine.Other investigations should be performed toestablish any possible interactions of glu-cosamine with other drugs and also the effectof diet or interactions with nutritional sub-stances. It is currently recommended that pa-tients with osteoarthritis take 500 mg of glu-cosamine sulfate three times a day for 3 to 6wk initially. After this period it can be decidedwhether the treatment is beneficial and worthcontinuing. Dosage trials would be useful toprove this starting dose and to establishwhether a lower dose could be used for main-tenance once symptoms subside. In addition, adose could be established for acute episodesand also perhaps a dose as a preventativemeasure in susceptible or at-risk patients.These trials must be performed to the samestandards as those for conventional pharma-ceuticals because glucosamine is being ex-ploited for its pharmacologic effects on thebody and to aid credibility.

Patients also should be reminded thatosteoarthritis is a chronic condition causedby more than one factor and that theyshould, in addition to taking the medication,eat a healthy, balanced diet and take mod-erate exercise. Glucosamine is suitable foruse in a wider range of patients than con-ventional treatments including those withgastric, cardiac, or renal problems. It isprobably safer for the elderly who tend tohave multiple disorders and may take sev-eral different medications, although thereare no data on glucosamine interactionswith any other medication.

There is still much work to be carried outon glucosamine before it can be accepted asthe treatment of choice for patients with os-teoarthritis; however, the current data seem tosuggest that this work should be undertaken.

REFERENCES1. Russell AL, McCarthy MF. Glucosamine for mi-

graine prophylaxis. Med Hypotheses 2000;55:1952. Franzen P. Arthritis with nutritional rehabilitation. A

case report. Sports Chiropract Rehabil 1998;12:213. Goldstein R. Glucosamine sulphate and osteoarthritis.

Lancet 2001;357:16174. Towheed TE, Anastassiades TP, Shea B, et al. Glu-

cosamine therapy for treating osteoarthritis (Co-chrane review). Cochrane Library 2001;3. Oxford:Update Software

Correspondence to: Brain Lockwood, PhD,MRPharmS, School of Pharmacy and Pharmaceu-tical Sciences, University of Manchester, Manches-ter, M13 9PL, UK. E-mail: brian.lockwood@man.ac.uk

Nutrition 18:693, 2002 0899-9007/02/$22.00©Elsevier Science Inc., 2002. Printed in the United States. All rights reserved. PII S0899-9007(02)00777-3