Dietary Supplements for Osteoarthritis PHILIP J. GREGORY, PharmD; MORGAN SPERRY, PharmD; and AmY FRIEdmAN WILSON, PharmD Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska A large number of dietary supplements are promoted to patients with osteoarthritis and as many as one third of those patients have used a supplement to treat their condition. Glucosamine-containing supplements are among the most commonly used products for osteo- arthritis. Although the evidence is not entirely consistent, most research suggests that glucos- amine sulfate can improve symptoms of pain related to osteoarthritis, as well as slow disease progression in patients with osteoarthritis of the knee. Chondroitin sulfate also appears to reduce osteoarthritis symptoms and is often combined with glucosamine, but there is no reliable evi- dence that the combination is more effective than either agent alone. S-adenosylmethionine may reduce pain but high costs and product quality issues limit its use. Several other supplements are promoted for treating osteoarthritis, such as methylsulfonylmethane, Harpagophytum pro- cumbens (devil’s claw), Curcuma longa (turmeric), and Zingiber officinale (ginger), but there is insufficient reliable evidence regarding long-term safety or effectiveness. Am( Fam Physician. 2008;77(2):177-184. Copyright © 2008 American Academy of Family Physicians.) ietary supplements, commonly glycosaminoglycans, which are found in referred to as natural medicines, synovial fluid, ligaments, and other joint herbal medicines, or alternative structures. Exogenous glucosamine is derived medicines, account for nearly from marine exoskeletons or produced syn- D $20 billion in U.S. sales annually.1 These thetically. Exogenous glucosamine may have products have a unique regulatory status that anti-inflammatory effects and is thought to allows them to be marketed with little or no stimulate metabolism of chondrocytes.4 credible scientific research. Since 2000, more Glucosamine is available in multiple than 800 brand name dietary supplement forms. The most common are glucosamine formulations targeting patients with osteo- hydrochloride and glucosamine sulfate. arthritis have been introduced.2 Although a Some products contain a blend of these, and handful of these have some evidence of long- many combine one of the forms with a vari- term safety and effectiveness, most do not. ety of other ingredients. Approximately 30 percent of patients with osteoarthritis have used a supplement to EFFECTIVENESS treat their condition.3 Unlike many supplements that reach the This article is a review of dietary supple- market completely untested in clinical tri- ments commonly used by patients with als, glucosamine has been the subject of osteoarthritis (Table 1). Searches were done considerable research. More than 20 ran- using evidence-based databases (Natural domized controlled trials involving over Medicines Comprehensive Database and The 2,500 patients have evaluated the use of glu- Cochrane Library) and bibliographic data- cosamine for osteoarthritis.5-7 Most of the bases (PubMed, International Pharmaceuti- research has focused on glucosamine sulfate cal Abstracts, the International Bibliographic and its role in treating osteoarthritis of the Information on Dietary Supplements). knee and hip, the two most studied and most commonly afflicted joints. Glucosamine Despite extensive research, study findings Glucosamine is the supplement most com- have been inconsistent, possibly because of monly used by patients with osteoarthri- the different products and methodologies tis. It is an endogenous amino sugar that is used in trials and/or issues of publication required for synthesis of glycoproteins and or industry bias. In 2005, a high-quality Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2008 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Dietary Supplements SORT: KEY RecoMMendAtions for PRActice Evidence Clinical recommendation rating References Comments Glucosamine sulfate may be used for reducing B 5-7, 11, 12 Evidence mostly positive, but with some symptoms and possibly slowing disease progression inconsistencies in patients with osteoarthritis of the knee. Chondroitin may provide modest benefit in some B 7, 16-19 Inconsistent evidence; analysis of all studies patients with osteoarthritis, but it does not appear shows benefit, but analysis of higher- to offer any advantage over glucosamine sulfate. quality studies shows no benefit S-adenosylmethionine may reduce osteoarthritis B 23-29 Evidence consistently shows reduced pain, pain, but it is a less appropriate treatment option but there are concerns about product for most patients. quality and high cost A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 131 or http:// www.aafp.org/afpsort.xml. Table 1. Selected Supplements for Osteoarthritis Supplement Typical dosage Comments Monthly cost* Glucosamine 1,500 mg once daily or Glucosamine sulfate preferred $9 to 35 (combination drugs appear 500 mg three times daily over glucosamine hydrochloride to be in the same price range) Chondroitin 200 to 400 mg two or Combination chondroitin/ $10 to 25 three times daily glucosamine no better than glucosamine sulfate alone S-adenosylmethionine 200 mg three times daily Butanedisulfonate salt form $60 to 120 preferred for best stability and bioavailability Methylsulfonylmethane 500 mg three times daily Not recommended because $5 to 35 to 3 g two times daily of insufficient evidence Harpagophytum 2.4 to 2.6 g daily Not recommended because $15 to 40 procumbens standardized extract of insufficient long-term (devil’s claw) safety data Curcuma longa No typical dosage for Not recommended because $8 to 23 (for one tablet daily) (turmeric) osteoarthritis of insufficient evidence Zingiber officinale 510 mg daily standardized Not recommended because $2 to 3 (ginger) extract of insufficient evidence *—Average retail cost (rounded to the nearest dollar) based on a search of common Internet vitamin stores, including http://www.vitacost.com and http://www.vitaminshoppe.com. Product quality may vary. systematic review of glucosamine trials for assessment of patients with osteoarthritis of osteoarthritis identified some interesting the knee or hip. The Lequesne index assesses patterns in the research.6 The pooled data pain and discomfort, maximal walking from all glucosamine trials, regardless of distance, and activities of daily living. The product type, trial quality, or assessment WOMAC index assesses pain, stiffness, and instrument, show that glucosamine sig- physical disability. One pooled analysis nificantly reduces pain. a previous meta- found that studies using the Lequesne index analysis found similar results.7 showed benefit, whereas those using the a subgroup analysis of studies shows dif- WOMAC index did not.6 However, a differ- ferent outcomes depending on whether the ent analysis did show improvement in out- study used the Lequesne index or the West- comes when using the WOMAC index as an ern Ontario and McMaster Universities assessment tool.7 (WOMAC) osteoarthritis index to assess The type of glucosamine product used outcomes. Both are validated scales for the appears to have a significant impact on 178 American Family Physician www.aafp.org/afp Volume 77, Number 2 ◆ January 15, 2008 Dietary Supplements outcomes. Many studies used a specific com- evidence and animal research suggesting mercial glucosamine sulfate product called increased insulin resistance. However, clin- Dona. Pooled findings from these stud- ical research shows that glucosamine does ies, regardless of the assessment scale used, not increase blood glucose suggest that this formulation significantly or A1C levels in patients with reduces osteoarthritis pain. Findings from type 2 diabetes.13,14 Because Glucosamine sulfate is studies using different formulations suggest glucosamine is derived from effective for reducing no significant improvement.6 the exoskeleton of shellfish, osteoarthritis pain and Consistent with this analysis are results of there is also concern that glu- improving function, and the highly-publicized Glucosamine/chon- cosamine may cause reactions might have disease- droitin Arthritis Intervention Trial, which in persons who are allergic to modifying effects. did not use a glucosamine sulfate formula- shellfish. However, shellfish tion, but rather a glucosamine hydrochlo- allergies are caused by antigens ride product.8 The investigators found that in the meat of the shellfish (not the shell) when used alone or in combination with and there have been no reports of reactions chondroitin, glucosamine hydrochloride in persons with shellfish allergies who take does not reduce symptoms of knee osteoar- glucosamine.15 thritis; however, subgroup analysis suggests that the combination does reduce pain in CLINICAL RECOMMENDATIONS patients with severe symptoms. Of note, the Overall, the evidence supports the use of placebo response rate in this trial was high; glucosamine sulfate for modestly reducing approximately 60 percent of patients in the osteoarthritis symptoms and possibly slow- placebo