A closer look at OA supplements—Part 2

In this installment, we will discuss green-lipped mussel, turmeric, undenatured collagen II, CBD products, and a recent literature review of each active nutraceutical.

A radiograph image of a dog's leg.
Osteoarthritis in a stifle. Intramedullary pins present. Photo courtesy Dr. Vanessa Aberman

Osteoarthritis (OA) is a common condition in dogs and cats. It can be caused by various conditions, including injury, anatomical factors, and congenital issues.

OA can result in significant pain and mobility impairments and can impact the patient's quality of life. Nutraceuticals are often a part of OA management in cases, but there is a dearth of literature on effectiveness. Limitations of these studies include the small numbers of studies and subjects, lack of replication, lack of studies due to lack of regulation of these products, and the tendency for research on a single subject coming from one researcher or research group.1

Part 1 in the March 2025 issue of Veterinary Practice News discussed the benefits of EFAs such as fish oil and krill oil and less clear support for glucosamine products. In this installment, we will discuss green-lipped mussel, turmeric, undenatured collagen II, CBD products, and a recent literature review of each active nutraceutical.

Green-lipped mussel (GLM)

Green-lipped mussel (Perna canaliculus) extract has anti-inflammatory components, including glycosaminoglycans and n-3 fatty acids (FA).2 In one study, dogs with preexisting OA were given GLM and a placebo for 56 days. Those given the GLM improved over baseline by day 28, and improvement continued throughout the study. The dogs had improved clinical signs and marginally better musculoskeletal scores, though no objective analysis was done.3

Another study was performed with 23 dogs fed a balanced diet for 30 days and one with GLM for 60 days.4 After the GLM administration, peak vertical force improved.

In a different study, some clinical signs, such as joint pain, improved compared to the placebo group.2 There was no difference in mobility or reduction in range of joint movement.

In contrast, another study showed vertical analog assessments were significantly different from placebo treatment, but ground reaction forces were not significant from the placebo group for GLM.5

Some of these findings are incongruent and not all studies have shown efficacy. However, there appears to be some positive objective data. Current thinking is GLM may work similarly in these patients to EFAs.6

Undenatured collagen type II (UC-II)

Collagen for OA in dogs has been gaining popularity over recent years. The theory is that it may exert anabolic effects on osteoarthritic joint cartilage. In addition, it may have disease-modifying effects. Unfortunately, fewer studies demonstrated its efficacy, and one systemic review of collagen hydrolysates did not recommend its usage in 2012.7

Another systemic review was done in 2022, and based on its analysis, it could not recommend this formulation.8 However, a study was done with three groups of dogs (placebo, lower dose UC-II and higher dose of UC-II) for 90 days.9 Dogs receiving 1 mg/day (lower dose) or 10 mg UC-II/day (higher dose) for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion. Those on the higher dose showed the greatest improvement. These results were subjective, and it was a funded study. Because of these factors, it was considered lower-quality research.1

A dog and a cat lying down together on a white blanket.
A systematic review8 found strong evidence that omega-3-enriched diets and supplements provide clinical pain relief for osteoarthritic pets, while chondroitin-glucosamine showed no significant effect.

Three randomized, double-blind, placebo-controlled trials have been performed recently. In one, no changes were noted in objective outcomes.9

In a 2017 study, 42 dogs were fed either a control diet or one with curcuminoid extract, hydrolyzed collagen, and green tea extract for three months. No objective tracked variables demonstrated a significant difference between the two groups.10

Another study noted significant differences in peak vertical force, vertical impulse, and symmetry index for PVF for those on bioactive collagen peptides.11 Unfortunately, the study size was small (11 dogs with collagen supplementation and EFAs and nine dogs on placebo). It was also a funded study.11

In another study of 60 dogs comparing UC-II to robenacoxib for 30 days, there was clinical improvement in dogs receiving UC-II similar to the NSAID. However, no objective analysis was performed, and no placebo was given.12 The number of high-quality studies needs to increase before recommending this supplement.7

Turmeric

Turmeric, with the active ingredient curcumin, has been purportedly helpful for inflammation in people and animals. A high-quality study was done with both objective and subjective data points on an eight-week course of P54FP versus placebo.

P54FP is an extract of Indian and Javanese turmeric, Curcuma domestica and Curcuma xanthorrhiza, respectively. There was no statistical difference in the objective data point of peak vertical force between the groups, and the owner assessment was not statistically significant. However, the evaluator assessment showed a statistical significant treatment effect in favor of P54FP.13

In another study, dogs with OA were given a diet or a diet supplemented with curcuminoid extract, hydrolyzed collagen, and green tea extract. After three months, objective data, such as peak vertical force and OA biomarkers and subjective data using owner and clinician assessment, was obtained. No change was noted in the OA biomarkers or the peak vertical force. There was some benefit noted in the veterinary orthopedic exam at the end of the trial (i.e. pain on manipulation) but no change in lameness, pain at palpation, or joint mobility.

Owner assessment showed an improvement with those fed over the control group with pain severity but not pain interference. So, while there may have been some change subjectively, the objective data wasn't supportive of this product.

Additionally, as with many nutraceutical studies, the product was not a single agent, so it would be difficult to determine which ingredient is most responsible for any positive change.10 Based on these studies, the evidence for efficacy is low.

A mixed breed dog lying down against a white background.
A double-blind study1 evaluated the effects of adding green-lipped mussel (GLM) to a complete dry diet for dogs with arthritis. After six weeks, dogs in the GLM group showed significant improvement in total arthritis scores, including reduced joint pain and
swelling, compared to the control group.

Cannabinoid products

Cannabis spp. contains cannabidiol (CBD), a substance that has been promoted as a potential treatment for a wide variety of inflammatory conditions. A recent systemic review of recent literature on the efficacy of CBD for the treatment of canine osteoarthritis was published.14 It was concluded, based on five studies, CBD may reduce pain scores, but the evidence is not strong enough to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA. ALP increase can be associated with CBD use in dogs, and it is unknown at this time what the causes this increase.14

In another systemic review, which looked at seven studies, the results were more promising.8 Six out of seven showed some improvement. The results were promising, but more investigation was needed to determine dose, formulations, and efficacy.8

In a study that was double-blinded, crossover, and placebo-controlled, there were no differences noted between groups at any time point for any of the recorded outcome measures. Outcome measures included objective gait analysis, activity counts (via accelerometry), and clinical metrology instruments.15

Unfortunately, there are a wide variety of formulations of nutraceuticals as well as disparate doses utilized in many studies. For instance, CBD can be administered in an oral oil, a tablet, or transmucosally. Some rely on subjective measures of success—either owner or clinician interpretation of clinical signs of improvement or lack thereof. This subjectivity has an impact on experimental bias. Those that utilize objective data, such as vertical peak force, also are not standardized in approach.

In others, multiple nutraceuticals are utilized in a single agent, so the extrapolation of which agent was most useful is impossible to know.

To accurately assess if these formulations are worthwhile for the practitioner, the design of the studies should be stricter with heavy analysis on objective data. That being said, there is promising evidence for the use of green-lipped mussel. There is much less evidence for using products with turmeric and UC-II. More studies on CBD need to be conducted, but some results thus far are promising.


Vanessa Aberman, DVM, DABVP (Canine/Feline) earned her veterinary degree from Ross University School of Veterinary Medicine in 2000 and became an ABVP diplomat in 2011. She has worked in private and corporate practices as associate veterinarian, relief veterinarian, medical director, and area medical director. Dr. Aberman's professional interests include surgery, dentistry, and pain management. She is currently the director of Medical Quality at Modern Animal. She ensures the veterinary teams practice the latest evidence-based guidelines. She is also a regular speaker at local and national venues.

References

  1. Vandeweerd JM, Coisnon C, Clegg P, C. Cambier C, Pierson A, Hontoir F, Saegerman C, . Gustin P, Buczinski S. Systematic review of efficacy of nutraceuticals to alleviate clinical signs of osteoarthritis. J Vet Intern Med Mar 2012; 26 (3):448-456.
  2. Bui LM, Bierer TL. Influence of Green Lipped Mussels (Perna canaliculus) in Alleviating Signs of Arthritis in Dogs. Veterinary Therapeutics 2001, 2(2):101-111.
  3. Pollard, B., Guilford, W., Ankenbauer-Perkins, K., & Hedderley, D. Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease. New Zealand Veterinary Journal 2006, 54(3), 114–118.
  4. Rialland, P, Bichot, S Lussier, B, Moreau, M, Beaudry, F, del Castillo, Jérôme RE, Gauvin, D, Troncy, E. Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis. Canadian Journal of Veterinary Research Jan 2013, 77(1): 66-74.
  5. Dobenecker, B, Beetz Y, Kienzle E. A Placebo-Controlled Double-Blind Study on the Effect of Nutraceuticals (Chondroitin Sulfate and Mussel Extract) in Dogs with Joint Diseases as Perceived by Their Owners. The Journal of Nutrition 2002, 132(6): 1690S - 1691S.
  6. Ratsch, BE, Levine D, Wakshlag JJ. Clinical Guide to Obesity and Nonherbal Nutraceuticals in Canine Orthopedic Conditions. Veterinary Clinics: Small Animal Practice 2022, 52(4): 939 - 958.
  7. Blees, N.R., Teunissen, M., Dobenecker, B., Prawitt, J., Tryfonidou, M.A. and Jan Corbee, R. Collagen Hydrolysates as Nutritional Support in Canine Osteoarthritis: A Narrative Review. Journal of Animal Physiology and Animal Nutrition 2024.
  8. Barbeau-Gregoire M, Otis C, Cournoyer A, Moreau M, Lussier B, Troncy E. A 2022 systemic review and meta-analysis of enriched therapeutic diets and nutraceuticals in canine and feline osteoarthritis. Int. J. Mol. Sci 2022, 23(18), 10384.
  9. Deparle LA, Gupta RC,. Canerdy TD, Goad JT, D'Altilio M, Bagchi M, Bagcchi D.Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J of Vet Phar and Ther 2005, 28: 385-390.
  10. Comblain, F., Barthélémy, N., Lefèbvre, M. et al. A randomized, double-blind, prospective, placebo-controlled study of the efficacy of a diet supplemented with curcuminoids extract, hydrolyzed collagen and green tea extract in owner's dogs with osteoarthritis. BMC Vet Res 2017; 13, 395.
  11. Britta Dobenecker B ,Böswald LF, Reese S, Steigmeier-Raith S, Oesser S, Schunck M, Meyer-Lindenberg A, Hugenberg J. The oral intake of specific Bioactive Collagen Peptides (BCP) improves gait and quality of life in canine osteoarthritis patients—A translational large animal model for a nutritional therapy option. PLOS ONE. Sept 2024.
  12. Stabile M, Samarelli R, Trerotoli P, Fracassi L, Lacitignola L, Crovace A, Staffieri F. Evaluation of the Effects of Undenatured Type II Collagen (UC-II) as Compared to Robenacoxib on the Mobility Impairment Induced by Osteoarthritis in Dogs. Vet Sci. 2019 Sep 4;6(3):72.
  13.  Innes, J.F., Fuller, C.J., Grover, E.R., Kelly, A.L. and Burn, J.F. (2003), Randomised, double-blind, placebo controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis. Veterinary Record, 152: 457-460.
  14. Patikorn C, Nerapusee O , Soontornvipart K , Lawonyawut K, Musikpodok K, Waleethanaphan K, Anantachoti P. Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies. Frontiers in Veterinary Science 2023; 10.
  15. Mejia, S, Duerr FM, Griffenhagen G,; Stephanie McGrath S. Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs . J Am Anim Hosp Assoc (2021) 57 (2): 81–90.

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