Critical Joint Relief is built around New Zealand green-lipped mussel, with glucosamine, MSM, sea cucumber, vitamins and botanicals, in a soft chew made with wild Alaskan pollock oil. Below is the independent research on those ingredients, with the species each study was carried out in.
Green-lipped mussel (Perna canaliculus)
Green-lipped mussel is the best-researched ingredient in this formula for dogs. In a double-blind study of 31 dogs, adding green-lipped mussel to the diet significantly improved total arthritis scores, joint pain and swelling. A randomized, placebo-controlled trial in 81 dogs found more dogs improved after 56 days on a mussel extract, with no toxicity. A force-plate study in dogs with clinical osteoarthritis measured an objective improvement in limb loading on a mussel-enriched diet. In two recent randomized trials in dogs with hip osteoarthritis, concentrated mussel lipid extracts improved weight bearing to a degree similar to carprofen and meloxicam. In cats, a diet combining mussel extract with omega-3s and glucosamine improved activity in cats with degenerative joint disease.
Research:
- Bui & Bierer (2003). Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs. Vet Ther. Study population: Dogs (31; arthritis). PubMed
- Pollard (2006). Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease. N Z Vet J. Study population: Dogs (81; DJD). PubMed
- Rialland (2013). Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis. Can J Vet Res. Study population: Dogs (30 enrolled; OA). PubMed
- Hielm-Bjorkman (2009). Evaluating Complementary Therapies for Canine Osteoarthritis Part I: Green-lipped Mussel (Perna canaliculus). Evid Based Complement Alternat Med. Study population: Dogs (45; OA). PubMed
- Kampa (2023). 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. Study population: Dogs, client-owned hip OA (n=75). PubMed
- Kampa (2024). Evaluation of the comparative efficacy of green lipped mussel plus krill oil extracts (EAB-277), Biota orientalis extracts or NSAIDs for the treatment of dogs with osteoarthritis associated pain: a blinded, placebo-controlled study. Front Vet Sci. Study population: Dogs, client-owned hip OA (n=101). PubMed
- Lascelles (2010). Evaluation of a therapeutic diet for feline degenerative joint disease. J Vet Intern Med. Study population: Cats, client-owned with DJD (n=40). PubMed
- Eason (2018). Greenshell Mussels: A Review of Veterinary Trials and Future Research Directions. Vet Sci. Study population: Dogs, cats, horses. PubMed
Omega-3 fatty acids (EPA and DHA from wild Alaskan pollock oil)
Omega-3 fatty acids are the one nutritional ingredient that two independent systematic reviews single out as having good evidence in canine osteoarthritis. In controlled trials in client-owned dogs, omega-3 enriched diets improved owners' ratings of rising, walking and playing, increased peak vertical force on a force plate, and allowed veterinarians to lower the dose of carprofen faster than in control dogs. Note that these trials used therapeutic diets with high omega-3 content; pollock oil is included in this chew as a supporting ingredient.
Research:
- Roush (2010). Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc. Study population: Dogs, client-owned OA (n=127). PubMed
- Roush (2010). 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. Study population: Dogs, client-owned OA (n=38). PubMed
- Fritsch (2010). 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. Study population: Dogs, client-owned OA on carprofen. PubMed
- Fritsch (2010). Dose-titration effects of fish oil in osteoarthritic dogs. J Vet Intern Med. Study population: Dogs, client-owned OA (n=177). PubMed
- Moreau (2013). Effects of feeding a high omega-3 fatty acids diet in dogs with naturally occurring osteoarthritis. J Anim Physiol Anim Nutr (Berl). Study population: Dogs, client-owned stifle or hip OA. PubMed
- Mehler (2016). A prospective randomized double blind placebo-controlled evaluation of the effects of eicosapentaenoic acid and docosahexaenoic acid on the clinical signs and erythrocyte membrane polyunsaturated fatty acid concentrations in dogs with osteoarthritis. Prostaglandins Leukot Essent Fatty Acids. Study population: Dogs (OA). PubMed
- Barbeau-Gregoire (2022). A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis. Int J Mol Sci. Study population: Dogs and cats, 72 trials in 57 articles. PubMed
- Vandeweerd (2012). Systematic review of efficacy of nutraceuticals to alleviate clinical signs of osteoarthritis. J Vet Intern Med. Study population: Horses, dogs and cats, 22 controlled trials. PubMed
Glucosamine sulfate
Glucosamine is a building block of cartilage glycosaminoglycans and is included here for cartilage support. In a surgically induced osteoarthritis model in dogs, oral glucosamine sulfate reduced histological cartilage damage, and a bioavailability study confirmed dogs absorb glucosamine from chews. Clinical trials of glucosamine for pain in dogs are mixed: one trial in client-owned dogs reported improvements in pain and weight bearing, while others did not, and a 2022 systematic review concluded glucosamine and chondroitin products do not relieve osteoarthritis pain in dogs and cats. We therefore describe glucosamine as cartilage support, not pain relief.
Research:
- Wenz (2017). Effect of Glucosamine Sulfate on Osteoarthritis in the Cruciate-Deficient Canine Model of Osteoarthritis. Cartilage. Study population: Dogs, surgically induced OA. PubMed
- Maxwell (2016). Comparison of Glucosamine Absorption After Administration of Oral Liquid, Chewable, and Tablet Formulations to Dogs. J Am Anim Hosp Assoc. Study population: Dogs (n=8). PubMed
- McCarthy (2007). Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. Vet J. Study population: Dogs, client-owned, hip or elbow OA. PubMed
- Moreau (2003). Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. Vet Rec. Study population: Dogs, client-owned OA (n=71). PubMed
- Barbeau-Gregoire (2022). A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis. Int J Mol Sci. Study population: Dogs and cats, 72 trials in 57 articles. PubMed
MSM (methylsulfonylmethane)
MSM is a naturally occurring sulfur compound. A 12-week randomized trial in people with mild knee pain found a significant improvement in knee osteoarthritis scores with MSM versus placebo, and a meta-analysis of 69 trials rated its short-term pain effect as statistically significant. In horses, MSM changed muscle inflammatory gene expression after exercise. There are no published MSM trials in dogs, so we present it as a well-tolerated, researched supporting ingredient.
Research:
- Toguchi (2023). Methylsulfonylmethane Improves Knee Quality of Life in Participants with Mild Knee Pain: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. Study population: Humans with mild knee pain (n=88). PubMed
- Liu (2018). Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. Study population: Humans, 69 RCTs of 20 supplements. PubMed
- Barshick (2025). Methylsulfonylmethane (MSM) Supplementation in Adult Horses Supports Improved Skeletal Muscle Inflammatory Gene Expression Following Exercise. Animals (Basel). Study population: Horses, thoroughbred geldings (n=10). PubMed
- Butawan (2017). Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. Study population: Review (animal and human). PubMed
Sea cucumber, Angelica sinensis, Rehmannia and manganese
These ingredients are included for their cartilage and connective-tissue chemistry, and their evidence is laboratory and animal-model research rather than clinical trials in pets. Sea cucumber is a natural source of chondroitin sulfate, collagen and glycosaminoglycans, and an extract increased cartilage-matrix markers in cultured chondrocytes. Angelica sinensis polysaccharide protected chondrocytes and slowed cartilage degeneration in experimental osteoarthritis models, and Rehmannia extract reduced inflammatory cytokines and cartilage damage in a rabbit model. A dog study of a glucosamine, chondroitin and manganese ascorbate combination found changes in joint-fluid markers consistent with cartilage-matrix activity.
Research:
- Bordbar (2011). High-value components and bioactives from sea cucumbers for functional foods: a review. Mar Drugs. Study population: Review (constituents). Full text
- Mohd Heikal (2019). Stichopus chloronotus aqueous extract as a chondroprotective agent for human chondrocytes isolated from osteoarthitis articular cartilage in vitro. Cytotechnology. Study population: Human OA chondrocytes, in vitro. PubMed
- Yi (2026). Angelica sinensis polysaccharide inhibits pyroptosis and improves osteoarthritis through the collaborative power of PPARgamma and Nrf2. Front Pharmacol. Study population: Cell and animal OA models. Full text
- Ni (2023). Angelica sinensis polysaccharide improves mitochondrial metabolism of osteoarthritis chondrocytes through PPARgamma/SOD2/ROS pathways. Phytother Res. Study population: Rat OA model and rat chondrocytes. PubMed
- Yang (2025). Effect of Rehmanniae Radix Extract on Chondrocyte Apoptosis in the Rabbit Model of Knee Osteoarthritis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Study population: Rabbits, surgically induced knee OA. PubMed
- Johnson (2001). Effects of an orally administered mixture of chondroitin sulfate glucosamine hydrochloride and manganese ascorbate on synovial fluid markers in a canine cruciate ligament transection model of osteoarthritis. Osteoarthritis Cartilage. Study population: Dogs (CCL transection model). PubMed
For veterinarians
Three systematic reviews frame the evidence base for canine OA nutraceuticals (Aragon 2007, Vandeweerd 2012, Barbeau-Gregoire 2022). Across them, omega-3 enriched diets have the strongest and most consistent effect on pain and function, green-lipped mussel preparations have moderate support, and glucosamine/chondroitin has little or no analgesic effect; Barbeau-Gregoire 2022 recommends against glucosamine/chondroitin for pain in dogs and cats. The two Thai RCTs (Kampa 2023, 2024) used concentrated mussel lipid extracts (PCSO-524, EAB-277), not whole mussel powder. Vitamin E was negative for OA outcomes in a 57-dog RCT at doses far above the chew's 53 IU (Gordon 2023). Dogs synthesise vitamin C, and a guinea-pig OA model found long-term ascorbate worsened cartilage changes (Kraus 2004), so no joint claim is made for the calcium ascorbate in this formula. The finished product has not been evaluated in a controlled trial; the per-chew mussel, EPA and DHA amounts are within a proprietary blend. Wholesale for clinics is available through Vetcove.
About this research
Critical Joint Relief is a nutritional supplement, not a drug. The studies above were conducted by independent researchers on individual ingredients, not on the finished VetSmart Formulas product, and are provided so that pet owners and veterinarians can read the evidence for themselves. Results in one species or preparation do not guarantee the same result in another. This information is not intended to diagnose, treat, cure or prevent any disease. If your pet has a diagnosed condition or takes medication, talk to your veterinarian before adding a supplement.
