Nutraceuticals for canine OA - yes or no?

In this post we review the evidence since the publication in 2022 of Barbeau-Gregoire et al's systematic review and meta-analysis on this topic.

Findings from Barbeau-Gregoire (2022)

This study was a systematic review and meta-analysis which set out to test the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered to dogs and cats affected by osteoarthritis. The level of quality of each trial was assessed in order to determine if an efficacy assessment could be made. There was evidence of efficacy for omega-3 enriched diets, omega-3 supplements and cannabidiol. The analysis shows a weak effect of collagen and a very marked non-effect of glucosamine-chondroitin. The authors state that glucosamine chondroitin nutraceuticals should no longer be recommended for pain management in dogs & cats with osteoarthritis. Prior to the publication of this review three previous systematic reviews had been conducted and revealed disappointing quantity and quality of scientific evidence regarding fortified diets and nutraceuticals. The evidence provided by this previous work was not strong enough to adopt or support meaningful recommendations. In the current meta-analysis each therapeutic trial was assessed in a systematic independent and quantitative manner based on three evaluation criteria.

Quality of trials assessment

This tested 3 criteria;

-risk of bias

-methodological quality and

-strength of scientific evidence

All trials were classified into quality levels;

-Trials deemed to show analgesic effects were trials where the condition of the animal improved with treatments over time compared to a control group.

-Trials with improvement were trials where there was within group improvement in the condition over time

-Trials with non-effect did not show any improvement neither over time nor within groups

Trials were grouped into categories;

1.     Omega-3 enriched therapeutic diets

2.     Omega-3 based nutraceuticals

3.     Collagen based nutraceuticals

4.     Glucosamine chondroitin based nutraceuticals

5.     Cannabinoid based nutraceuticals

6.     Nutraceuticals based on hydroxycitric acid

7.     Nutraceuticals based on calcium fructoborate

8.     Composite nutraceuticals

9.     Others

In the analysis only categories one to five were reviewed further due to the lack of sufficiently large number of clinical trials for studies in categories 6 to 9. In the other category, analgesic effects were detected for special milk protein concentrate, elk velvet antler, avocado and soy usaponifiables and vitamin E. Three trials detected a non-effect for turmeric.

Comments by authors on quality of trials

Studies of collagen based and glucosamine chondroitin based nutraceuticals were lower quality trials. Omega 3 enriched therapies diets and omega 3 based nutraceuticals and cannabinoids were higher quality trials.

Enriched therapeutic diets and nutraceuticals based on omega-3 are highly effective

The main reason that collagen based nutraceuticals did not rate more highly in this work is the poor quality of trials used to evaluate.

Author’s conclusion

Our rigorous approach to meta-analysis allowed us to conclude with certainty that the use of omega-3 products beneficially modulates the painful condition of OA dogs and cats, while the intake of chondroitin-glucosamine has no analgesic effect. Further studies will be necessary to be able to state on the potential effects of collagen, cannabidiol and composite nutraceuticals, but these products seem promising.

Papers published since 2022

Undenatured collagen

Cabezas et al (2022) examined 6 months of supplementation of an undenatured type 2 collagen product, Flexadin Advanced. Their conclusion was ‘Flexadin^® Advanced, containing UC-II^®, can be considered as a good complementary feed to provide joint support in dogs with mild to moderate DJD’. This was a non-blinded study with subjective outcome measures and therefore the quality of the trial is considered low. This result could be inferred from their cautious conclusion.

Prior to this work by Gupta et al (2012) used force plate analysis and found a positive benefit to UC-II in dogs with OA over a period of 5 months. I am unable to access the full text of this paper so cannot assess if sample sizes were adequate to support the conclusions. This work was referenced by Barbeau-Gregoire and they drew the conclusion that quality if evidence is low for UC-II.

Another 2022 study (Stabile et al) compared UC-II, cimicoxib, and their combination compared to a control group. This work involved dogs with OA graded according to the COAST scoring system with a study period of 30 days. Outcome measures were LOAD scores and clinical assessment. A sample size calculation was performed and the required numbers of dogs completed the study. This study design shows a higher level of evidence, although objective outcome measures would increase this. The authors comment ‘the present findings prove that all the treatments used in the study (UC-II®, cimicoxib and their combination) provide significant reduction in clinical signs associated with OA and improve mobility in dogs’. This appears to be the highest quality study published currently for UC-II. The product used was Flexadin Advanced.

A scoping review (Zapata & Fernandez-Parra 2023) produced a favourable view of UC-II, however the approach taken by these authors was not as rigorous as Barbeau-Gregoire et al. These authors do not reference Barbeau-Gregoire in their manuscript which raises suspicion.

Stabile et al (2024) examined a product containing UC-II and Boswellia (Flexadin Advanced) in a crossover study. Dogs with OA were examined over 8 weeks using the LOAD score and objective measures such as; orthopaedic examination at each visit, all dogs underwent radiography prior to starting the study, the grade of OA scored using the COAST tool, LOAD scores were assessed, a rescue analgesic plan was created and if the LOAD score increased by more than 20% baseline paracetamol 10mg/kg BID was administered for three days, mobility was assessed using a commercially available pressure mat walkway, activity was assessed using accelerometers placed on the dog's collar throughout all phases of the study, pain assessment used an electronic von Frey filament to assess the pain threshold of the most affected joint, synovial fluid was examined at the beginning and the end of the study. A total of 60 dogs with mobility problems were evaluated and enrolled however after the first screening only 17 dogs met the inclusion criteria. There were 9 dogs in the treatment group and 8 dogs in the placebo group.16 dogs completed the study. Regarding LOAD scores there was a significant reduction in absolute LOAD values during the supplementation. Compared to the baseline no significant differences were observed in the placebo group for LOAD. There was one dog that required rescue analgesia that dog was in the placebo group. The results of the mobility activity revealed no difference between groups. Pain thresholds improved after 4 weeks of supplementation. Values in the placebo group were significantly lower after 4 weeks The duration of this study was 8 weeks and treatment effects were noted after 4 weeks. Clinical examination, gait analysis and activity assessment were not different between the supplement and the placebo groups. The main benefit documented by this work was a reduction in LOAD scores. It should be noted that this small number of subjects in this work would classify the evidence quality as low. The conclusion by the authors was ‘results proved that UCII®+Boswellia serrata supplemented group over a period of eight weeks results in an improvement of mobility impairment, already at 4 weeks of administration, according to the owner´s evaluation’. Given the limited number of subjects in the study this conclusion overreaches and higher quality studies are required. 

Omega-3 fatty acids of marine origin

In 2019 Vijarnsorn et al published work examining the benefit of an omega-3 extract derived from green lipped mussel (GLM) in combination with firocoxib, documenting a benefit to the combination. This work was reviewed by Barbeau-Gregoire and contributed to their conclusions on omega-3 supplementation. In 2023 the same group (Kampa et al) examined krill extract, a further marine source of omega-3. Using objective (gait analysis PVF)) and subjective (orthopaedic examination) assessments these authors concluded the PCSO-524 (GLM) and EAB-277 (krill extract), but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after 4 weeks, and 6 weeks, and to a similar degree to that seen with carprofen. The product used in this study (Antinol Plus) is available in Australia & NZ, but not yet in Europe.

COAST guidelines

The COAST guidelines provide a framework to grade OA and detail the recommended approaches for treating each grade of OA.

The recommendations from COAST prioritise the use of omega 3 supplementation in the form of EPA (eicosapentaenoic acid) at 45-100 mg/kg/day. The recommendations of the COAST group are based on consensus from 9 subject matter experts and it appears that not all group members are appraised with the evidence contained in this document.

Conclusion

Since the publication of Barbeau-Gregoire there have been additional studies in support of omega 3 supplementation in the form of krill extract (Kampa et al 2023), and UC-II (Stabile et al 2022).

Recommendations for practitioners

• Grade the disease using the COAST guidelines. The COASTer grading does not require the use of radiography and is therefore accessible to many.

• Use an omega 3 supplemented food in dogs with OA.

• There is no evidence that any supplement has a disease modifying or chondroprotective effect. Despite this it is likely that supplements used early on in the course of disease will be more effective than in severe OA.

• Prescribe supplements with documented levels of evidence. The supplements detailed herein are Antinol (GLM PCSO 524), Antinol Plus (krill extract EAB 277) and Flexadin Advanced (UC-II). Antinol Plus is not yet available in Europe.

• Consider the use of cannabidiol as a supplement, as per recommendations from Barbeau-Gregoire.

• Do not use glucosamine chondroitin supplementation.

References

Barbeau-Grégoire M, Otis C, Cournoyer A, Moreau M, Lussier B, Troncy E. A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis. Int J Mol Sci. 2022 Sep 8;23(18):10384. doi: 10.3390/ijms231810384. PMID: 36142319; PMCID: PMC9499673.

Cabezas MÁ, Benito J, Ortega Á, Garcia-Pedraza E. Long-term supplementation with an undenatured type-II collagen (UC-II^®) formulation in dogs with degenerative joint disease: Exploratory study. Open Vet J. 2022 Jan-Feb;12(1):91-98. doi: 10.5455/OVJ.2022.v12.i1.11. Epub 2022 Feb 5. PMID: 35342740; PMCID: PMC8956235.

Cachon T, Frykman O, Innes JF, Lascelles BDX, Okumura M, Sousa P, Staffieri F, Steagall PV, Van Ryssen B. COAST Development Group's international consensus guidelines for the treatment of canine osteoarthritis. Front Vet Sci. 2023 Aug 3;10:1137888. doi: 10.3389/fvets.2023.1137888. PMID: 37601753; PMCID: PMC10436090.

Gupta RC, Canerdy TD, Lindley J, Konemann M, Minniear J, Carroll BA, Hendrick C, Goad JT, Rohde K, Doss R, Bagchi M, Bagchi D. Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate. J Anim Physiol Anim Nutr (Berl). 2012 Oct;96(5):770-7. doi: 10.1111/j.1439-0396.2011.01166.x. Epub 2011 May 30. PMID: 21623931.

Kampa N, Kaenkangploo D, Jitpean S, Srithunyarat T, Seesupa S, Hoisang S, Yongvanit K, Kamlangchai P, Tuchpramuk P, Lascelles BDX. Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Front Vet Sci. 2023 Feb 1;10:1033188. doi: 10.3389/fvets.2023.1033188. Erratum in: Front Vet Sci. 2023 Aug 02;10:1252778. doi: 10.3389/fvets.2023.1252778. PMID: 36816197; PMCID: PMC9929184.

Stabile M, Fracassi L, Lacitignola L, Garcia-Pedraza E, Girelli CR, Calculli C, D'Uggento AM, Ribecco N, Crovace A, Fanizzi FP, Staffieri F. Effects of a feed supplement, containing undenatured type II collagen (UC II®) and Boswellia Serrata, in the management of mild/moderate mobility disorders in dogs: A randomized, double-blind, placebo controlled, cross-over study. PLoS One. 2024 Oct 30;19(10):e0305697. doi: 10.1371/journal.pone.0305697. PMID: 39475935; PMCID: PMC11524509.

Stabile M, Fracassi L, Lacitignola L, Garcia-Pedraza E, Girelli CR, Calculli C, D'Uggento AM, Ribecco N, Crovace A, Fanizzi FP, Staffieri F. Effects of a feed supplement, containing undenatured type II collagen (UC II®) and Boswellia Serrata, in the management of mild/moderate mobility disorders in dogs: A randomized, double-blind, placebo controlled, cross-over study. PLoS One. 2024 Oct 30;19(10):e0305697. doi: 10.1371/journal.pone.0305697. PMID: 39475935; PMCID: PMC11524509.

Vijarnsorn M, Kwananocha I, Kashemsant N, Jarudecha T, Lekcharoensuk C, Beale B, et al. The effectiveness of marine based fatty acid compound (PCSO-524) and firocoxib in the treatment of canine osteoarthritis. BMC Vet Res. (2019) 15:349. doi: 10.1186/s12917-019-2110-7

Zapata A, Fernández-Parra R. Management of Osteoarthritis and Joint Support Using Feed Supplements: A Scoping Review of Undenatured Type II Collagen and Boswellia serrata. Animals (Basel). 2023 Feb 27;13(5):870. doi: 10.3390/ani13050870. PMID: 36899726; PMCID: PMC10000124.

Links to online articles

Gajanayake (2024) The use of fish oil supplements in small animal veterinary practice https://www.veterinary-practice.com/article/fish-oil-supplements

This post was written by Matt Gurney. We do not receive any financial incentives for writing this post.

Matt & Carl established Zero Pain Philosophy to provide educational resources & telemedicine to veterinary professionals globally, enabling optimal management of pain.

Matt sees referrals in the pain clinic at Eastcott Referrals. You can also receive telemedicine advice from us here if you have a pain case where you need a helping hand.

Matt Gurney is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and works at Anderson Moores Veterinary Specialists. Matt is Past President of the European College of Veterinary Anaesthesia & Analgesia and works at Eastcott Referrals in the UK.

Carl Bradbrook is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and is Past President of the Association of Veterinary Anaesthetists. Carl works at Anderson Moores Veterinary Specialists in the UK.