A study in Siberian huskies found long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), like those in krill oil, are more effective at raising the n-3 index in dogs than short-chain PUFAs from flaxseed oil commonly found in pet food. 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 quality of life. Treatments include a variety of methods, including anti-inflammatory and analgesic medications, cartilage protective agents, physical therapy, weight control, nutrition, and dietary supplements. Often, the practitioner utilizes multimodal approaches to treatment, offering dietary supplements. In one systemic review, “The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs…The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs.”1 The authors touched on the limitations of these studies, including 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 This article, the first of two installments on OA nutraceuticals, discusses glucosamine/chondroitin as well as EFAs, including fish oil and krill oil. Glucosamine/chondrioitin sulfate Glucosamine and chondroitin sulfate treatments are likely the most commonly used nutraceutical therapies in veterinary management for osteoarthritis and have been so for decades. Glucosamine is a precursor to glycosaminoglycan, and because this is a large component of joint cartilage, it theoretically will help rebuild damaged cartilage. Chondroitin sulfate is also a precursor to major glycosaminoglycans. However, evidence of the efficacy of these products remains controversial. In a literature review of 22 articles, positive chondroprotective effects were identified in approximately only half of the evaluations (14 out of 25; 56 percent). As for the rest of the parameters, these dietary supplements did not appear to adequately suppress the subchondral bone changes, the synovial inflammation, or the osteophyte formation.2 Additionally, there appeared to be a correlation with better outcomes with higher doses and when combined with other therapies. For instance, in one study of dogs, a combined supplement of glucosamine hydrochloride (500 mg), chondroitin sulfate (400 mg), omega-3 fatty acids (300 mg), MAM (methylsulfonylmethane) (200 mg), and vitamin E (50 IU), and additional products was given to 29 dogs, while 28 dogs received a placebo for 12 weeks.3 The treatment group experienced less pain and increased mobility. Unfortunately, due to the design of this study, it is unclear which substances contributed to the improvement. In another study comparing glucosamine, placebo, carprofen, and the nonsteroidal anti-inflammatory drug (NSAID) meloxicam in 71 dogs for 60 days, the dogs on glucosamine and placebo did not improve significantly via objective variables, while those on NSAIDs did.4 Another study found that after 90 days, supplementation with a glucosamine/chondroitin product showed no benefit in pain control.5 With the conflicting literature on the efficacy of these products, many reviews have concluded the clinical benefit of glucosamine is weak.6 Based on the given data, clinical signs may not be improved, but these products may be efficacious as chondroprotectives in diseased joints. One literature review concluded glucosamine should not be prescribed for OA in dogs and cats due to lack of efficacy.7 A canine patient with bilateral medial luxated patellas. This condition predisposes the patient to OA. Photo courtesy Modern Animal Fish oil EFAs Unlike glucosamine/chondroitin products, there is good evidence essential fatty acids (EFAs) can help modulate the inflammatory response, especially omega-3 (n-3).7 Omega-3 FAs lower arachidonic acid concentrations and reduce the expression of cartilage-degrading enzymes, cyclooxygenase-2, and inflammatory cytokines, such as IL-1α, IL-1β and TNF-α.7,8 There needs to be a balance between omega-6 (n-6) FA and n-3 FA, though the exact ratio needs to be determined. It is known a high n-6:n-3 ratio may be proinflammatory. A single oil will likely not provide the ideal n-6 and n-3 FA requirements because not only are the requirements poorly defined, but they are also dependent on individual health and lifestage factors. Fish oils have long-chain n-3 FAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), while other sources of n-3 FA are plant-based, such as linoleic acid and flaxseed oil. There are also other marine sources of n-3 FA, including algal oil and krill oil.9 One study shows there was a correlation between the amount of EPA and DHA in the food and the level of serum.10 Further, dogs fed two to three times higher levels of DHA and EPA in their food showed modest improvement in clinical signs, including weight-bearing and lameness after 90 days. Additionally, the food with the highest level of fish oil significantly improved these two conditions. However, no objective parameters were utilized in this study.8 In one double-blinded study of dogs with OA using objective data, improvement in peak vertical force was seen in 82 percent of dogs taking fish oil n-3 enhanced food versus placebo, with 38 percent after 90 days. Additionally, the dogs receiving fish oil improved in lameness, weight-bearing, and mean peak vertical force.10 Based on current literature, the recommendation of fish oil nEFAs, especially n-3 FA, seems prudent for OA. Krill oil FAs Krill is a small crustacean harvested in the Southern Ocean and is a good source of long-chain n-3 FAs. One study in Siberian huskies demonstrated supplementation with long-chain n-3 polyunsaturated fatty acids (PUFAs), similar to those in krill oil, are a better method to increase the n-3 index in dogs in comparison to the short-chain n-3 PUFAs found in flaxseed oil, which is often found in pet food.11 A recent randomized, double-blinded, placebo-controlled trial was conducted. Seventy-five owned pet dogs with hip OA were assigned randomly into five treatment groups: PCSO-524, Glucosamine and chondroitin sulfate, EAB-277, carprofen, and placebo (sunflower oil). PCSO-524 is a marine based fatty acid compound comprised of a patented extract stabilized marine lipids from the New Zealand green-lipped mussel (Perna canaliculus). EAB-277 is a combination of phospholipids extracted from krill oil together with lipid fractions from the green-lipped mussel. The main difference between EAB-277 from PCSO-524 is it contains high concentrations of phospholipids extracted from Euphausia superba in addition to the components of PCSO4-524. Peak vertical force (PVF), an objective assessment, and subjective orthopedic assessment scores (OAS) were evaluated before treatment (week zero), and at weeks two, four, and six during treatment. PCSO-524 (GLM) and EAB-277 (krill oil and GLM), but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after four weeks, and six weeks, and to a similar degree to that seen with carprofen. EAB-277 appeared to produce results similar to those of carprofen and PCSO-524. NSAID carprofen demonstrated the fastest improvement in PVF. In addition, the placebo and the glucosamine/chondroitin groups performed the same (no benefit).12 A canine patient with bilateral degenerative joint disease in both coxofemoral joints. Photo courtesy Modern Animal What now? Unfortunately, there is a wide variety of formulations of nutraceuticals, as well as disparate doses utilized in many studies. Some rely on subjective measures of success—either the owner's or clinician's interpretation of clinical signs of improvement or lack thereof. This subjectivity has an impact on experimental bias. Those using objective data, such as vertical peak force, also are not standardized in approach. Different study designs utilized are cross-over, parallel, lack placebo control, lack of double-blind, etc., and this lack of standardization causes result ambiguity. In others, multiple nutraceuticals are utilized together versus a placebo, so extrapolating which agent was most useful is impossible to decipher. The design of the studies should be stricter and involve heavy analysis of objective data to accurately assess whether these formulations are worthwhile for the practitioner. That being said, there is promising evidence for the use of EFAs—be it fish oil or krill oil—as the source of n-3 FA. There is a lack of evidence on the utilization of glucosamine/chondroitin products. Vanessa Aberman, DVM, DABVP (c/f). Dr Aberman earned her veterinary degree from Ross University School of Veterinary Medicine in 2000 and became an ABVP diplomat in 2011. She has worked in both private and corporate practices, holding roles as associate veterinarian, relief veterinarian, medical director, and area medical director. 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.
