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Dietary Supplements For Osteoarthritis as an Alternative to NSAIDS: Commentary on the Available Research.

This commentary will evaluate the current evidence to determine if dietary supplementation can serve as an alternative to NSAIDS for the treatment of osteoarthritis.


Regarding NSAID safety, the Arthritis, Rheumatism, and Aging Medical information System estimates that dverse effects due to NSAIDs are associated with more than 100,000 hospitalizations and more than 16,000 deaths in the U.S. each year. Both nonselective and selective COX-2 inhibitors have now been shown to be associated with an increased risk for cardiovascular events. These studies, together with the outcomes of the recent US Food and Drug administration decision to require 'black box' warnings regarding potential cardiovascular risks associated with NSAIDs, suggest that the use of COX-2 inhibitors as the sole strategy for gastro protection in patients with arthritis and other pain syndromes must be reconsidered, particularly among those at risk for cardiovascular events. (1)

A few studies have evaluated the risk of cardiovascular complications following the intake of NSAID's. In 2011, Trelle, et al, conducted a meta-analysis of 31 trials and 116,429 patients and found that compared to placebo rofecoxib was associated with the highest risk of myocardial infarction, followed by lumiracoxib. Ibuprofen was associated with the highest risk of stroke followed by diclofenac. Etoricoxib and diclofenac were associated with the highest risk of cardiovascular death. (2) These findings were confirmed by a systematic review conducted by Mcgettigan, et al in 2011. (3)

Finally, in 2013, Bhala, et al, conducted a metaanalysis of 280 trials of NSAIDs versus placebo (124,513 participants, 68,342 person-years) and 474 trials of one NSAID versus another NSAID (229,296 participants, 165,456 person-years). This study found that major vascular events were increased by about a third by a cox 2 inhibitor or diclofenac, mainly due to an increase in major coronary events. Ibuprofen also significantly increased major coronary events, but not major vascular events.

Compared with placebo, of 1000 patients allocated to a cox 2 inhibitor or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events. Vascular death was increased significantly by cox 2 inhibitors and diclofenac, non-significantly by ibuprofen, but not by naproxen. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (cox 2 inhibitors, diclofenac, ibuprofen, and naproxen. (4)

These studies lead to a recent official publication of the College of Family Physicians of Canada, Cyclooxygenase-2 (COX-2) inhibitors and traditional NSAIDs except naproxen increase the risk of serious cardiovascular events and death. When prescribing NSAIDs, patients' gastrointestinal (GI) and CV risks should be assessed, with naproxen or low-dose ibuprofen preferentially chosen for patients at risk of CV disease. (5)



In 2015, Bartels, et al, carried out a meta-analysis of five randomized controlled trials involving over 500 patients comparing oral ginger treatment with placebo in adult osteoarthritis patients. This study concluded ginger was modestly efficacious and reasonably safe for treatment of knee and hip osteoarthritis. (6)

Ginger vs NSAIDS: In 2001, Altman, et al, conducted a randomized, double-blind, placebo-controlled, multicenter, parallel-group of 247 patients with osteoarthritis of the knee and moderate-to-severe pain. In this study ginger extract had a statistically significant effect on reducing symptoms of osteoarthritis of the knee. Moreover, the reduction in intake of acetaminophen was greater in the ginger extract group. (7)

In 2012, Drozdov, et al, designed a randomized controlled trial of 43 patients with knee or hip osteoarthritis who were given ginger or diclofenac. This study showed that ginger is as effective as diclofenac but safer in treating osteoarthritis. Moreover, ginger has an increased mucosa-protective potential. (8)

In 2013, Paramdeep performed a randomized placebo-controlled open label study of 60 patients of osteoarthritis of the knee who were divided into a diclofenac, ginger and placebo group. The percentage improvement in pain score from baseline in the diclofenac group was 60.31% and 59.11% in the ginger group. (9)


Two studies will be referenced on the efficacy of glucosamine for osteoarthritis.

In 2009, Black, et al, published a systematic review of 5 systematic reviews from 1950 to 2008 and found that there was evidence that glucosamine sulfate shows some clinical effectiveness in the treatment of osteoarthritis of the knee. (10)

In 2018, Ogata, et al, carried out a systematic review and meta-analysis of 18 articles written between 2003 and 2016. This study indicated that glucosamine is superior to a placebo in alleviating knee osteoarthritis symptoms. (11)

Glucosamine vs NSAIDS:

In 1994, Muller-Fassbender, et al, conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg vs ibuprofen 400 mg three times in a day orally for 4 weeks in 200 hospitalized patients with active osteoarthritis of the knee. In this study glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee osteoarthritis. Moreover, 35% of patients on ibuprofen reported adverse events, mainly of gastrointestinal origin, vs 6% adverse events with glucosamine. (12)

In 1998, Qiu, et al, performed a double-blind randomized, controlled trial of 178 patients suffering from osteoarthritis of the knee. This study revealed that glucosamine sulfate is as effective on the symptoms of the disease as ibuprofen. Moreover, only 6% of glucosamine sulfate patients reported adverse events compared to 16% for ibuprofen. (13)

In 2002, Ruane, et al, published a review of double-blind randomized controlled trials comparing glucosamine sulfate to ibuprofen with a combined number of participants in the studies of 218. This review showed glucosamine to be of similar efficacy to ibuprofen. (14)


Two studies will be cited on the effects of chondroitin for osteoarthritis of the knee and hip.

In 2008, Monfort, et al, conducted a review of 4 metaanalyses published between 1997 and 2007that limited their analysis to randomized controlled trials comparing chondroitin sulfate with placebo or no-treatment control. Four meta-analyses showed significant clinical effects of chondroitin sulfate for knee or hip osteoarthritis compared with placebo for pain and function measures and one demonstrated greater reduction of NSAID co-edication in patients assigned to the active treatment. (15)

In 2015, Singh, et al, carried out a literature review of 43 randomized clinical trials including over 4,000 participants lasting longer than two weeks and studying adults with osteoarthritis in any joint up to November 2013. The majority of trials were in knee osteoarthritis, with few in hip and hand osteoarthritis. This review revealed that chondroitin alone or in combination with glucosamine was better than placebo in improving pain in participants with osteoarthritis in short-term studies. Moreover, chondroitin had a lower risk of serious adverse events compared with control. (16)

Glucosamine and Chondroitin vs NSAIDS: In 2018, Zhu, et al, performed a meta-analysis of 61 randomized controlled trials of patients with knee and/or hip osteoarthritis. This study showed that the combination of glucosamine and chondroitin was more effective than acetaminophen and placebo on relieving pain and improving physical function. (17)


In 2016, Daily, et al, published a systematic review and meta-analysis of randomized controlled trials which provided scientific evidence that supports the efficacy of turmeric extract in the treatment of knee and hip osteoarthritis. (18)

Curcumin vs NSAIDS: In 2009, Kuptniratsaikul, et al, designed a single-blind randomized controlled trial to evaluate the efficacy of 2,000 mg/day of Curcuma domestica extracts compared with 800 mg/day of ibuprofen in 107 knee osteoarthritis patients for 6 weeks. This study found that curcumin domestica extracts seem to be similarly efficacious as ibuprofen. Moreover, the adverse events for curcumin was 33.3% compared to 44.2% for ibuprofen. (19)

In 2012, Kertia, et al, conducted a prospective randomized open end blinded study of 80 patients with knee osteoarthritis. This study demonstrated that Curcuma domestica extract was not significantly different compared to diclofenac sodium in suppressing the secretion of cycloxygenase-2 enzyme. (20)

In 2014, Kuptniratsaiku, et al, carried out a follow up with better methodology than the first study. This study was a double-blind randomized controlled trial of 367 knee osteoarthritis patients which indicated that curcuma domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. Moreover, the number of events of abdominal pain and discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group. (21)

In 2018, Bannuru, et al, performed a systematic review and meta-analysis of eleven randomized controlled trials involving over 1,000 patients. This study suggested that curcuminoids have no statistically significant differences in efficacy outcomes compared to NSAIDs. (22)


In 2002, Soeken, et al, published a meta-analysis of 11 randomized controlled trials of SAMe versus placebo or NSAIDS for the treatment of knee or hip osteoarthritis. This study concluded that SAMe appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with osteoarthritis. Moreover, those treated with SAMe were less likely to report adverse effects than those receiving NSAIDs. (23) SAM-e vs NSAIDS: In 2004, Najm, et al, designed a randomized double-blind cross-over study of 56 participants with knee osteoarthritis. This study demonstrated that SAMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. (24)


In 2004, Gagnier, et al, carried out a systematic review of 12 trials which revealed that there is moderate evidence of effectiveness for the use of a Harpagophytum powder at 60mg in the treatment of osteoarthritis of the spine, hip and knee. Moreover, the study provided strong evidence for the use of an aqueous Harpagophytum extract at a daily dose of 50mg in the treatment of acute exacerbations of chronic nonspecific low back pain. (25)

Devil's claw vs NSAIDS: The study by Gagnier, et al, also found that the use of an aqueous extract of Harpagophytum procumbens at 60 mg had similar efficacy to 12.5 mg of rofecoxib per day for chronic non-specific low-back pain in the short term.

In the year 2000, Chantre, et al, conducted a double-blind, randomized, multicenter clinical study of 122 patients in which 435 mg of powdered Harpagophytum procumbens was compared with diacerhein 100 mg/day (anthraquinone). This study showed that there was no difference in the efficacy of the two treatments and patients taking Harpagophytum were using significantly less NSAIDs. Furthermore, the most frequent adverse event reported was diarrhea, occurring in 8.1% of harpa-gophytum patients and 26.7% in diacerhein patients. (26)

About the Author:

Adrian Isaza is both a physician and an academic. As an academic he authored a chapter of the book "The Role of Fuctional Food Security in Global Health". He also wrote an anatomy and physiology book using his own teaching technique and recently earned his degree as a Doctor of philosophy. As a physician Adrian holds a diplomate in Nutrition.


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(6.) Bartels EM, Folmer VN. Bliddal H, et al. Efficacy and safety of ginger in osteoarthritis patients: a metaanalysis of randomized placebo-controlled trials. Osteoarthr Cartil. 2015;23(1): 13-21

(7.) Altman RD, Marcussen K.C. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum. 2001;44(11):2531-8.

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(9.) Paramdeep G. Efficacy and tolerability of ginger (Zingiber officinale) in patients of osteoarthritis of knee. Indian.J Physiol Pharmacol. 2013;57(2): 177-83.

(10.) Black C, Clar C, Henderson R, et al. 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 Technol Assess. 2009;13(52):1-I48.

(11.) Ogata T, Ideno Y, Akai M, et al. Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis. Clin Rheumatol. 2018;37(9):2479-2487.

(12.) Muller-fassbender H, Bach GL, Haase W, Rovati LC, Setnikar I. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthr Cartil. 1994;2(l):61-9.

(13.) Qiu GX, Gao SN, Giacovelli G, Rovati L, Setnikar I. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 1998;48 (5):469-74.

(14.) Ruane R. Griffiths P. Glucosamine therapy compared to ibuprofen for joint pain. Br J Community Nurs. 2002;7(3): 148-52.

(15.) Monfort J. Martel-pelletier J, Pelletier JP. Chondroitin sulphate for symptomatic osteoarthritis: critical appraisal of metaanalyses. Curr Med Res Opin. 2008;24(5): 1303-8.

(16.) Singh JA, Noorbaloochi S. Macdonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015-1:CD005614.

(17.) Zhu X, Wu D, Sang L, et al. Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network metaanalysis. Clin Exp Rheumatol. 2018;36(4):595-602.

(18.) Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016; 19(8):717-29.

(19.) Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009; 15(8):891-7.

(20.) Kertia N, Asdie AH, Rochmah W, Marsetyawan. Ability of curcuminoid compared to diclofenac sodium in reducing the secretion of cycloxygenase-2 enzyme by synovial fluid's monocytes of patients with osteoarthritis. Acta Med Indones. 2012;44(2):105-13.

(21.) Kuptniratsaikul V, Dajpratham P, Taechaarpomkul W, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451-8.

(22.) Bannuru RR, Osani MC, Al-eid F. Wang C. Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis. Semin Arthritis Rheum. 2018.

(23.) Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002;51(5):425-30.

(24.) Najm WI, Reinsch S, Hoehler F. Tobis JS, Harvey PW. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskelet Disord. 2004;5:6.

(25.) Gagnier JJ, Chrubasik S, Manheimer E. Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complement Altern Med. 2004;4:13.

Chantre P, Cappelaere A, Leblan D, Guedon D, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine. 2000;7(3):177-83.

by: Adrian Isaza, DC, DACBN, CCAP
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Title Annotation:non-steroidal anti-inflammatory drugs
Author:Isaza, Adrian
Publication:Original Internist
Article Type:Report
Date:Dec 1, 2018
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