Supplements for osteoarthritis: what’s the evidence?

By  | 

Many dietary supplements are recommended for veterinary patients with osteoarthritis.1-14 Very few have been evaluated in a controlled manner, and even fewer have been evaluated in dogs with osteoarthritis. In the Fall 2015 issue of IVC Journal, we addressed food-derived supplements. In this issue, we will review the scientific evidence and research on other supplements recommended for dogs with osteoarthritis, including Omega-3 fatty acids, S-adenosylmethionine (SAMe), vitamin E, boswellia serrate, chondroprotectants, Zeel®, and Phycox®.


These decrease inflammation and pain in dogs with osteoarthritis. They reduce expression of cyclooxygenase-2 (COX-2), lipoxygenase-5, aggrecanase, matrix metalloproteinase 3 and 13 (MMP-3, MMP-13), interleukin-1 and β (IL-1β, IL-1β), and tumor necrosis factor β (TNFβ).15-19 Novel oxygenated products, Resolvins (resolution phase interaction products) and docsatrienes, generated from n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), resolve inflammation.20-28 N-3 fatty acids support normal cartilage metabolism in the face of degradative enzymes, reducing inflammation and matrix degradative response elicited by chondrocytes during osteoarthritis progression.16-18,29 EPA appears to be more effective than DHA and-linolenic acid.15

There are several studies supporting use of n-3 fatty acids with osteoarthritis. An unpublished study performed in dogs showed lower serum concentrations of cholesterol, triglycerides, and phospholipids, lower synovial concentration of prostaglandin E2 (PGE2), better ground reaction forces, and less radiographic changes of osteoarthritis when dogs consumed a high n-3 diet than when dogs consumed a high n-6 diet.30,31 Owners perceive improvement in their pets’ arthritic symptoms when the animals are treated with fatty acids for various dermatologic problems.32

  • In a study of 127 dogs with osteoarthritis, dogs fed a high n-3 diet had improved ability to rise from a resting position and play, over a period of six months, than dogs fed a control diet.33 Dogs fed a diet containing 3.5% n-3 fatty acids for 90 days had improved peak vertical force values (PVF) and subjective improvement in lameness and weight-bearing when compared with dogs on a control diet.34
  • In a randomized, controlled clinical trial, dogs with stable chronic osteoarthritis treated with Carprofen could take a significantly decreased dosage when fed a diet supplemented with n-3 fatty acids, as compared to dogs on a control diet.35 Based on the results of these studies, there is a rationale for n-3 fatty acid supplementation, or feeding diets containing increased n-3 fatty acid levels to dogs with osteoarthritis.
  • A placebo-controlled double-blind study of 77 osteoarthritic dogs involved randomly assigning a fish oil supplement or corn oil with fish smell (placebo) to the dogs (added to food). Primary variables were PVF and impulse, the validated Helsinki Chronic Pain Index (HCPI) and the use of rescue non-steroidal anti-inflammatory drugs (NSAIDS). Secondary outcome variables also assessed included locomotion visual analog scale (VAS), Quality of Life questionnaire, veterinary assessment, owner assessment of outcome, as well as guessing the product given. After 16 weeks, there was no significant difference in the primary outcome variables, but owners of dogs in the fish oil supplementation group reported positive outcomes and did significantly better at identifying the supplement as compared to the placebo group. Blood sampling confirmed owner compliance, with significant increases in EPA and DHA and a decrease in arachadonic acid (AA) in the fish oil group, as compared to a significant decrease in AA in the placebo group. Possible study limits were reported: the dosing at 90mg EPA, 20mg DHA, and 10mg eicosatetraenoic acid (ETA) per kg BW could have been too low for this population, and/or the 16-week study period too short. When baselines were compared to the study-end values within the fish oil group, a small but significant improvement was reported in outcomes. The authors concluded that for patients not taking NSAIDs for osteoarthritis, fish oil supplements may provide true but limited relief in pain symptoms.36


This co-substrate is involved in transmethylation, transsulfuration and aminopropylation reactions, which occur primarily in the liver. In controlled trials of humans with osteoarthritis, SAMe is as effective as NSAIDs and better than placebo in reducing pain and improving function, with a lower likelihood of side effects.37-44 However, no difference with an NSAID was found in one study.45 A systematic review was inconclusive and hampered by inclusion of small trials of questionable quality.46 No clinical trials of dogs have been published; however, an in vitro study showed SAMe adversely affected chondrocyte viability.47 SAMe may reduce inflammatory mediators, increase levels of the antioxidant glutathione, are chondroprotective, and maintain DNA methylation.48


  • A double-blinded randomized pilot study evaluated vitamin E in a dog OA model. Fifteen adult crossbred dogs, one to four years old, weighing 23.6kg to 30.5kg, were randomly assigned to control with placebo and treated with vitamin E as a liquid-tocopherol acetate at 0.044 ml/kg body weight, equating to about 400 IU vitamin E per dog once a day. This is about ten times the daily amount recommended by the Association of American Control Officials (AAFCO), but considered safe and non-toxic. All dogs were maintained on the same diet starting two months before the study and until the end, with amounts adjusted to maintain optimal weights.

After the two-month period, the dogs had transection of their cranial cruciate ligament and placebo and vitamin E treatment initiated next day. Lameness and pain were assessed on Days 0, 28 and 55 after CCL transection using the visual analog scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA). Blood vitamin E levels were measured at Days 0, 21, 42, 55 post-surgery. Synovial fluid and cartilage histological analysis was evaluated after the dogs were euthanized on day 56. VAS, NRS and EDA were lower in the test group and become statistically significant in the test group for VAS Day 55 and EDA Day 28. Concentrations of PGE2 and nitric oxides (NO) in the synovial fluid of the test group were lower and statistically significant as well as histological scoring and analysis of the cartilage. This study in dogs with OA suggests that higher doses of vitamin E may reduce inflammatory markers and histological expression as well as improve signs of pain.49

  • In another study, large breed puppies fed a diet proportionately higher in protein, calcium, n-3 fatty acids and antioxidants had increased lean body mass and improved cartilage turnover as maturity was attained.50 In greyhounds and sled dogs, supplementation is associated with increased plasma levels; however, there was no difference in muscle damage with exercise.51-53 In dogs, vitamin C administration was found to increase vitamin C plasma levels, but was associated with decreased racing performance in greyhounds.54 In a study of antioxidant cocktail administration in 48 dogs over six weeks, subjects were assigned to four groups: untrained/not supplemented, untrained/supplemented, trained/not supplemented, trained/supplemented. Metabolomic profiling showed that dogs receiving the antioxidant cocktail recovered to baseline values at 24 hours after exercise, while dogs not receiving supplementation did not; therefore, administration of an antioxidant cocktail facilitates recovery from exercise.55

BOSWELLIA SERRATA (INDIAN FRANKINCENSE) Boswellia, also known as Boswellin or Indian frankincense, comes from the Indian Boswellia serrata tree. Resin from the bark of this tree is purported to have anti-inflammatory properties derived primarily from 3-O-acetyl-11-keto-βboswellic acid (AKBA), which inhibits 5-lipoxygenase and matrix metalloproteinases, and decreases tumor necrosis factor and interleukin 1β.56,57 Boswellia resin has been evaluated in 24 dogs in an open multi-center study.58 Improvement in clinical signs, lameness, and pain was found in 17 of 24 dogs. In five dogs, diarrhea and flatulence occurred.

CHONDROPROTECTANTS These are considered to be slow-acting drugs in osteoarthritis (SADOA) and can be subdivided into symptomatic slow-acting drugs (SYSADOA) and disease-modifying osteoarthritis drugs (DMOAD). Beneficial effects may include a positive effect on cartilage matrix synthesis and hyaluronan synthesis by synovial membrane, as well as an inhibitory effect on catabolic enzymes in osteoarthritis joints.59 Compounds fall under two different categories. One group includes agents approved by the US Food and Drug Administration and can have label claims of clinical effects such as polysulfated glycosaminoglycan (GAG). The second group includes products that are considered to be nutritional supplements, which are not regulated, and legally cannot claim any medical benefits. Examples of this group include glucosamine and chondroitin sulfate. While many of these products are administered as a supplement or alternative treatment, some, such as glucosamine and green-lipped mussels, are incorporated into pet foods.


Glucosamine is a precursor for glycosaminoglycans and a major component of joint cartilage; supplemental glucosamine may help rebuild cartilage.60-66

  • In a randomized, double-blind, positive-controlled clinical trial comparing glucosamine hydrochloride and chondroitin sulfate to Carprofen in dogs with osteoarthritis, Carprofen-treated dogs had improvement in five subjective measures while dogs treated with glucosamine-chondroitin sulfate had improvement in three of five measures but only at the final assessment point.67
  • A 60-day, prospective, randomized, double-blinded, placebo-controlled trial of 71 dogs with osteoarthritis assessed subjective and objective measures comparing Carprofen, Meloxicam, glucosamine/chondroitin, and placebo. Results indicated that objectively measured variables improved significantly with Carprofen and Meloxicam, but not with glucosamine/chondroitin or placebo. Subjective findings of veterinarians agreed with the results of objective evaluation, but subjective assessment by owners identified improvement only with Meloxicam.68 Based on these results, there is weak clinical evidence of the benefits of glucosamine/chondroitin in dogs with osteoarthritis.69-71


This over-the-counter homeopathic preparation is based on highly diluted extracts from plants, animals, and minerals (sulfur) as well as defined biochemical substances including coenzyme A, DL-alphalipoic acid, sodium diethyl oxalate, and nicotinamide adenine dinucleotide.72,73 In one study in dogs aged >1 year diagnosed with osteoarthritis, Zeel was compared with Carprofen in a multi-center, prospective, observational open-label cohort study in 12 German veterinary clinics.93 In another study in dogs (n=44), aged >1 year diagnosed with osteoarthritis, it was compared with Carprofen and a placebo.73 Clinical signs and several measures of osteoarthritis improved significantly in both studies; however, in one study73, Zeel was not as effective as Carprofen. The composition of the products and the dosage of Zeel differed between the two studies, which confounds interpretation of results.


A study of the commercially available C-phycocyanin-based (CPC) nutraceutical (Phycox®), its individual constituents, and Carprofen was performed using an in-vitro model of canine osteoarthritis. CPC is a biliprotein containing chromophore derived from cyanobacteria, also known as blue-green algae. Inflammatory conditions were induced using IL-1β in normal canine articular chondrocytes, and 0 to 250 µg/ml concentrations of the nutraceutical, constituents, and Carprofen were evaluated for any reduction in inflammatory mediators and markers of catabolism of the extracellular matrix: PGE2, TNFβ, IL-6, MMP-3, nitric oxide and GAGs. Inhibition of COX1, COX-2 and LOX pathways were assessed using assay kits.

No statistical difference was seen in the nutraceutical as compared to Carprofen, in the inhibition of TNFβ, IL-6, MMP-3, nitrate, nitrite and GAGs production in the OA in-vitro canine model across the concentration ranges tested. Both the nutraceutical and Carprofen failed to significantly decrease the following mediators at the 0.1 to 10 mg/ml: TNF-a, IL-6, MMP-3, nitrate and nitrite.

The nutraceutical did significantly reduce the concentration of PGE2 and GAG from the positive control. It was noted that the nutraceutical and many of its constituents appear to display selectivity for COX-2 inhibition and were poor LOX inhibitors. A multi-center in-vivo efficacy study has been undertaken by this laboratories.74


The pharmacological management of OA in dogs is dominated by NSAIDs, but adverse side effects can occur and there is concern over long-term administration of these drugs. NSAIDs have not been shown to slow the progression of the disease or to have a positive impact on joint degradation. Dietary supplements are being increasingly studied as the economics of osteoarthritis in the aging human population is a growing concern. This review is not exhaustive as there are many supplements being evaluated for the treatment of OA.

Translational research, new study methodology (nutrogenomics and metabololomics), and well-designed non-inferiority study design may open new horizons for the management of osteoarthritis in dogs. Practitioners need conclusive data to know how to select and integrate supplements into the multimodality management of their patients with osteoarthritis.

1De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford) 2011;50:911-920.

2Pirotta M. Arthritis disease – the use of complementary therapies. Aust Fam Physician 2010;39:638-640.

3Efthimiou P, Kukar M. Complementary and alternative medicine use in rheumatoid arthritis: proposed mechanism of action and efficacy of commonly used modalities. Rheumatol Int 2010;30:571-586.

4Marcus DM. Therapy: Herbals and supplements for rheumatic diseases. Nat Rev Rheumatol 2009;5:299-300.

5Vitetta L, Cicuttini F, Sali A. Alternative therapies for musculoskeletal conditions. Best Pract Res Clin Rheumatol 2008;22:499-522.

6Ernst E. Complementary treatments in rheumatic diseases. Rheum Dis Clin North Am 2008;34:455-467.

7Ernst E. Complementary or alternative therapies for osteoarthritis. Nat Clin Pract Rheumatol 2006;2:74-80.

8Rosenbaum CC, O’Mathuna DP, Chavez M, et al. Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis. Altern Ther Health Med 2010;16:32-40.

9Henrotin Y, Lambert C, Couchourel D, et al. Nutraceuticals: do they represent a new era in the management of osteoarthritis? – a narrative review from the lessons taken with five products. Osteoarthritis Cartilage 2011;19:1-21.

10Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther 2006;8:R127.

11Morelli V, Naquin C, Weaver V. Alternative therapies for traditional disease states: osteoarthritis. Am Fam Physician 2003;67:339-344.

12Li RW, Myers SP, Leach DN, et al. A cross-cultural study: anti-inflammatory activity of Australian and Chinese plants. J Ethnopharmacol 2003;85:25-32.

13Mathie RT, Baitson ES, Hansen L, et al. Homeopathic prescribing for chronic conditions in feline and canine veterinary practice. Homeopathy 2010;99:243-248.

14Clayton JJ. Nutraceuticals in the management of osteoarthritis. Orthopedics 2007;30:624-629; quiz 630-621.

15Hurst S, Zainal Z, Caterson B, et al. Dietary fatty acids and arthritis. Prostaglandins Leukot Essent Fatty Acids 2010;82:315-318.

16Curtis CL, Hughes CE, Flannery CR, et al. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem 2000;275:721-724.

17Curtis CL, Rees SG, Cramp J, et al. Effects of n-3 fatty acids on cartilage metabolism. Proc Nutr Soc 2002;61:381-389.

18Curtis CL, Rees SG, Little CB, et al. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum 2002;46:1544-1553.

19Zainal Z, Longman AJ, Hurst S, et al. Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis Cartilage 2009;17:896-905.

20Serhan CN, Arita M, Hong S, et al. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 2004;39:1125-1132.

21Hong S, Gronert K, Devchand PR, et al. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 2003;278:14677-14687.

22Meduri GU, Carratu P, Freire AX. Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS. Eur Respir J Suppl 2003;42:57s-64s.

23Xu ZZ, Ji RR. Resolvins are potent analgesics for arthritic pain. Br J Pharmacol 2011.

24Lima-Garcia J, Dutra R, da Silva K, et al. The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats. Br J Pharmacol 2011.

25Xu ZZ, Zhang L, Liu T, et al. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat Med 2010;16:592-597, 591p following 597.

26James M, Proudman S, Cleland L. Fish oil and rheumatoid arthritis: past, present and future. Proc Nutr Soc 2010;69:316-323.

27Calder PC. Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on ‘Nutrition and autoimmune disease’ PUFA, inflammatory processes and rheumatoid arthritis. Proc Nutr Soc 2008;67:409-418.

28Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006;83:1505S-1519S.

29Curtis CL, Harwood JL, Dent CM, et al. Biological basis for the benefit of nutraceutical supplementation in arthritis. Drug Discov Today 2004;9:165-172.

30Bartges JW, Budsberg SC, Pazak HE, et al. Effects of different n6:n3 fatty acid ratio diets on canine stifle osteoarthritis. Orthopedic Research Society 47th Annual Meeting 2001.

31Budsberg SC, Bartges JW, Pazak HE, et al. Effects of different N6:N3 fatty acid diets on canine stifle osteoarthritis. Veterinary Orthopedic Society 28th Annual Meeting 2001.

32Miller WH, Scott DW, Wellington JR. Treatment of dogs with hip arthritis with a fatty acid supplement. Canine Pract 1992;17:6-8.

33Roush JK, Dodd CE, Fritsch DA, et al. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc 2010;236:59-66.

34Roush JK, Cross AR, Renberg WC, et al. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. J Am Vet Med Assoc 2010;236:67-73.

35Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc 2010;236:535-539.

36Hielm-Bjorkman A, Roine J, Elo K, et al. An un-commissioned randomized, placebo-controlled doubleblind study to test the effect of deep sea fish oil as a pain reliever for dogs suffering from canine OA. BMC Vet Res 2012;8:157.

37Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83:66-71.

38Maccagno A, Di Giorgio EE, Caston OL, et al. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83:72-77.

39Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5:39-49.

40Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83:81-83.

41Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83:78-80.

42Najm WI, Reinsch S, Hoehler F, et al. 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.

43Soeken KL, Lee WL, Bausell RB, et al. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 2002;51:425-430.

44De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology (Oxford) 2010;49:1063-1068.

45Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther 2009;31:2860-2872.

46Rutjes AW, Nuesch E, Reichenbach S, et al. S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 2009:CD007321.

47Steinmeyer J, Burton-Wurster N, Lust G. Eff ects of three antiarthritic drugs on fi bronectin and keratan sulfate synthesis by cultured canine articular cartilage chondrocytes. Am J Vet Res 1992;53:2077-2083.

48Hosea Blewett HJ. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis. Crit Rev Food Sci Nutr 2008;48:458-463.

49Rhouma M, de Oliveira El Warrak A, Troncy E, et al. Anti-infl ammatory response of dietary vitamin E and its eff ects on pain and joint structures during early stages of surgically induced osteoarthritis in dogs. Can J Vet Res 2013;77:191-198.

50Schoenherr WD, Macleay JM, Yamka RM. Evaluation of body composition and cartilage biomarkers in large-breed dogs fed two foods designed for growth. Am J Vet Res 2010;71:934-939.

51Scott KC, Hill RC, Lewis DD, et al. Eff ect of alpha-tocopheryl acetate supplementation on vitamin E concentrations in Greyhounds before and after a race. Am J Vet Res 2001;62:1118-1120.

52Piercy RJ, Hinchcliff  KW, DiSilvestro RA, et al. Eff ect of dietary supplements containing antioxidants on attenuation of muscle damage in exercising sled dogs. Am J Vet Res 2000;61:1438-1445.

53Baskin CR, Hinchcliff  KW, DiSilvestro RA, et al. Effects of dietary antioxidant supplementation on oxidative damage and resistance to oxidative damage during prolonged exercise in sled dogs. Am J Vet Res 2000;61:886-891.

54Marshall RJ, Scott KC, Hill RC, et al. Supplemental vitamin C appears to slow racing greyhounds. J Nutr 2002;132:1616S-1621S.

55Waldron MK, Reynolds AJ, Kochhar S, et al. Metabolomic approach to assessing the effi  cacy of an antioxidant cocktail in trained and untrained dogs following an exercise bout. Compend Contin Educ Vet 2007;29:25 abstract.

56Sengupta K, Alluri KV, Satish AR, et al. A double blind, randomized, placebo controlled study of the effi cacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther 2008;10:R85.

57Ernst E. Frankincense: systematic review. BMJ 2008;337:a2813.

58Reichling J, Schmokel H, Fitzi J, et al. Dietary support with Boswellia resin in canine infl ammatory joint and spinal disease. Schweiz Arch Tierheilkd 2004;146:71-79.

59McNamara PS, Johnston SA, Todhunter RJ. Slow-acting, disease-modifying osteoarthritis agents. Vet Clin North Am Small Anim Pract 1997;27:863-881.

60Chan PS, Caron JP, Orth MW. Eff ects of glucosamine and chondroitin sulfate on bovine cartilage explants under long-term culture conditions. Am J Vet Res 2007;68:709-715.

61Lippiello L, Han MS, Henderson T. Protective eff ect of the chondroprotective agent Cosequin DS on bovine articular cartilage exposed in vitro to nonsteroidal antiinfl ammatory agents. Vet Ther 2002;3:128-135.

62Gouze JN, Bordji K, Gulberti S, et al. Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: infl uence of glucosamine on interleukin-1beta-mediated eff ects in rat chondrocytes. Arthritis Rheum 2001;44:351-360.

63Dodge GR, Jimenez SA. Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage 2003;11:424-432.

64Ali AA, Lewis SM, Badgley HL, et al. Oral glucosamine increases expression of transforming growth factor beta1 (TGFbeta1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: Implications for human efficacy and toxicity. Arch Biochem Biophys 2011.

65Phitak T, Pothacharoen P, Kongtawelert P. Comparison of glucose derivatives effects on cartilage degradation. BMC Musculoskelet Disord 2010;11:162.

66Silbert JE. Dietary glucosamine under question. Glycobiology 2009;19:564-567.

67McCarthy G, O’Donovan J, Jones B, et al. Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. Vet J 2007;174:54-61.

68Moreau M, Dupuis J, Bonneau NH, et al. Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. Vet Rec 2003;152:323-329.

69Aragon CL, Hofmeister EH, Budsberg SC. Systematic review of clinical trials of treatments for osteoarthritis in dogs. J Am Vet Med Assoc 2007;230:514-521.

70Sanderson RO, Beata C, Flipo RM, et al. Systematic review of the management of canine osteoarthritis. Vet Rec 2009;164:418-424.

71McKenzie BA. What is the evidence? There is only very weak clinical trial evidence to support the use of glucosamine and chondroitin supplements for osteoarthritis in dogs. J Am Vet Med Assoc 2010;237:1382-1383.

72Neumann S, Stolt P, Braun G, et al. Eff ectiveness of the homeopathic preparation Zeel compared with carprofen in dogs with osteoarthritis. J Am Anim Hosp Assoc 2011;47:12-20.

73Hielm-Bjorkman A, Tulamo RM, Salonen H, et al. Evaluating complementary therapies for canine osteoarthritis–Part II: a homeopathic combination preparation (Zeel). Evid Based Complement Alternat Med 2009;6:465-471.

74Martinez SE, Chen Y, Ho EA, et al. Pharmacological eff ects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis. Can J Vet Res 2015;79:241-249.

Dr. Donna Raditic received her BSc in Animal Science from Cornell University, then graduated with her Doctorate of Veterinary Medicine. She built her own practice in 1997 in western MA, offering integrative medicine while obtaining specialties in acupuncture, chiropractic, and botanical therapies. She is a Diplomat of the American College of Veterinary Nutrition and Assistant Professor in the Nutrition and Integrative Medicine services at the University of Tennessee College of Veterinary Medicine.