Monday, October 1, 2012

Supplements for Joint Support and Health in Dogs and Cats By Karen Choptain DVM For WCVM 4th Year Small Animal Nutrition Elective




The Use of Nutraceuticals and Dietary Supplements for
Joint Support and Health in Cats and Dogs


Presented to: Dr. Meg Smart, Small Animal Nutrition Elective
By: Karen Choptain



Introduction
The use of nutraceuticals and dietary supplements, either in manufactured pet foods or as adjuncts to diet, are not necessarily new to the domestic animal world. There have, however, been more recent use of advertisements and promotions of diets and supplements being sold that tout the benefit of such products to aid in the area of joint health and stabilization.  These products have become quite popular with the public, as they allow for adjunctive therapy or alternative therapy in cats and dogs that suffer from osteoarthritis (OA) or degenerative joint disease (DJD) (1).
What is a nutraceutical?  A nutraceutical, as defined by the North American Veterinary Nutraceutical Council, is “a nondrug substance that is produced in a purified or extracted form, administered orally, to provide compounds required for normal body structure and function with the intent of improving health and well-being” (1,2). More specifically, a nutraceutical used in the aspect of joint support can be referred to as a chondroprotectant.  This term has been applied to substances such as glucosamine, chondroitin sulfate, combination products of the two, New Zealand green-lipped mussels (GLM), omega-3 fatty acids, anti-oxidants such as Vitamin C and Vitamin E and other dietary compounds such as P54FP, Avocado/soybean oils, Boron, Boswellia Resin, Cat’s Claw, Creatine, and Special milk protein concentrate (3).  Chondroprotectant agents base their purpose on providing the following three primary effects: 1) to support or enhance metabolism of chondrocytes and synoviocytes, 2) inhibit degradative enzymes within synovial fluid and cartilage matrix, and 3) inhibit formation of thrombi in small blood vessels supplying the joint (1).
In humans, the use of dietary supplements is regulated under the Dietary Supplements Health and Education Act (1). This is in order to allow consumers the opportunity to purchase a variety of products that are marketed for joint health and support.  The products themselves must be safe; however, they do not have to achieve pre market approval, in contrast to pharmaceuticals or “drugs”.  The aforementioned act does not apply to dietary supplements in the veterinary market. While the Canadian Veterinary Medical Association withholds the right to remove products from the market, providing the product is safe and does not pose a threat to human safety it may be sold (1). The product also may not advertise claims such as being used to treat, cure, prevent or mitigate a disease (1).
In addition, label claims and quality control of these products has been documented (1, 4, 5). Due to the lack of quality assurance, the consumer cannot be guaranteed that the product itself is of the concentration listed on the label or of its purity (1).  A large variety of products are available to consumers.  Despite the number of products, there is a drastic lack of scientific evidence that promotes any of these products over the other.  This paper serves to provide some clarity to the commercial foods and supplements that are available to consumers and critically evaluate their efficacy for the use of joint support and health in cats and dogs.



Osteoarthritis  (OA)in Dogs and Cats
In order to fully appreciate and understand the proposed use of chondroprotectants one must first have an idea of the function of a healthy joint and how it differs from a diseased joint.  Understanding the pathophysiology of a diseased joint can help to show areas in which chondroprotectants may act to mitigate the disease process and alleviate the pain, discomfort, and debilitating effects of OA. 
Unlike in the human species where OA is attributed to a normal aging process, in our domestic species an underlying process is generally at play.  OA itself is defined as being a non inflammatory disorder of moveable joints (6, 7). In dogs and cats an underlying pathology is suspected to be the predisposing factor for the development of OA. Obesity causing excessive load bearing on joints, cruciate ligament tears, fractures, and developmental disorders such as Legg-Perthes-Calves disease, osteochondritis dessicans, osteochondral disease, hip dysplasia and patellar luxation are all factors which can lead to the development of OA (1, 6). 
The normal diarthrodial joint is composed of a joint capsule, synovial fluid, articular cartilage and subchondral bone (1).  The joint in question serves the purpose of providing a smooth surface that is able to distribute the load from one bone to another.  The two opposing bones are covered on the surface by an avascular and aneural articular cartilage. 
Articular Cartilage
The articular cartilage is divided histologically into multiple zones and is composed of chondrocytes surrounded by a matrix. This lies on top of the subchondral bone and assists in the deliverance of load bearing forces to the underlying bone. The chondrocytes themselves are the primary cell within the articular cartilage.  The matrix that is surrounding these cells is composed of 70-80% water with collagen and proteoglycans (PG) being the residual make up (6, 8). Chondrocytes produce the PG within the Golgi apparatus (6). They also are responsible for the production of the collagen within the matrix. These cells are essential as they possess little mitotic ability and thusly are not readily replaced as they die (1).The PGs make up 35% of the matrix on a dry matter basis and are composed of a core protein with side changes of glycosaminoglycan (GAG) molecules that make up a further 10% of the matrix (6, 9). The four primary GAGs present are chondroitin-4-sulfate, chondroitin-6-sulfate, keratin sulfate and dermatan sulfate (6).  The GAGs are made up of repeating disaccharide units of six unit sugars, primarily glucosamine or galactosamine that alternate with glucuronate, iduronate or galactose (11). The PGs present are linked by the protein hyaluronan and it is this protein that forms the backbone of the large molecule aggrecan (6, 10). The primary collagen types present in the cartilage are Type I and Type II with the later making up as much as 90% of the joint, however types III-XI are also present (6, 9, 10). 
A functioning joint serves for load bearing based on the makeup of the articular cartilage. When a load is applied to the joint, water is released from the cartilage. This helps to lubricate the joint and disperse the load to the underlying bone. When the force is released, the water returns to the articular cartilage. This process also serves the function of removing waste from the cartilage and returning nutrients to the chondrocytes.
In a diseased joint, loss of articular cartilage occurs. This contributes to pain and loss of function. On gross evaluation, articular loss can be seen with fibrillation, erosion and wear lines on the surface of the articular cartilage (11, 12). On radiographs, this can be seen as a narrowing of the joint space. In addition, other radiographic signs can be seen in OA which include periosteal bone proliferation, osteophyte/enthesophyte production, subchondral bone loss and effusion of the joint. It has been proposed that initial changes in load bearing forces leads to disruptions of the collagen cross-linkages and subsequent PG loss (6, 14). Another cause of the cartilage loss is due to degradation enzymes affecting the extracellular matrix leading to loss of PGs and Type II collagen (11, 13). These enzymes include matrix metalloproteinases (MMPs) and aggrecanses (11). These enzymes are normally present and aid in cartilage turnover. Their control is via tissue inhibitors of metalloproteinases (TIMPs) which unfortunately are decreased in production with OA (11). These substances are produced from the chondrocytes when inflammatory mediators are released from the synovial cel

Table1 Anatomy and biochemistry of the articukar cartilage
Histologically
·         Lies ontop of Sunchondral Bone
·         eliverance of load bearing to the underlying bone
·         load applied water releasaed lubricates and disperses the laod
·         released water returns removes wastes and delivers nutrients  to chondrocytes

Chondocytes little mitotic activity (1)
Produce (6)
Collagen
PG
Matrix (6,*)
70-80%water
Collagen (6,9,10)
Type 1
Type2 90%
Type 111-XI
Proteoglycans (PG)
Core protein +Protein hyaluron forms backbone of larw molecular aggrecans (6,10)
Glycosaminoglycans (GAG) (6,9)
-alternating sugars glucosamine,galactoamine, glucuronate, iduronate ,galactose (11)
Chondroitin-4-sulphate
Chondroitin-6-sulphate
Keratn Sulphate,
Dermatin sulphate





Joint Capsule
The joint capsule is also several layers thick and surrounds the diarthrodial joint. The inner vascular and neural surface is lined with synovial cells called the synovium. The cells are broken down into Type A and Type B. Type B cells function to provide the makeup of the fluid within the joint. They serve to provide nourishment, remove waste products and lubricate the joint. Lubrication of the joint is provided by the production of hyaluronic acid and lubricin (6, 9).  Conversely, Type A cells serve the function of phagocytosis.
When loss of the articular cartilage begins with fibrillation, the synovium serves the purpose of phagocytosis and clearing of the cartilage fragments (6). This occurrence leads to inflammation of the synovium and is referred to as synovitis (6, 15, 16).  This inflammation leads to a cascade of effects within the joint. First, the inflammation leads to an increased vascular permeability which can contribute to edema within the joint (6, 9). Consequently, with the increased permeability, inflammatory cells are able to enter the joint space. The synovitis also leads to a number of cytokines released by the synovial cells. Synovial cells stimulate the production of the previously mentioned proteases (MMPs and aggrecanase) by chondrocytes (6, 17). The main MMPs are collagenase and stromelysin (6). Collagenase is responsible for the breakdown of collagen and stromelysin breaks down PGs (6, 18). In vitro studies have shown that stromelysin is also capable of breaking down Type II collagen (11, 22).The synovial cells, as well as chondrocytes and monocytes, are responsible for increased secretion of cytokine IL-1, IL-6 and TNF-α (6, 18, 19, 20). While these cytokines are normally present within the joint and help to maintain homeostasis, in OA they are secreted in excess.  IL-1 has been shown to have inhibitory effects on TIMP and thusly contributes to the overproduction of MMPs by the chondrocytes (6, 21). It has also been speculated that IL-1 decreases production of collagen and PG by chondrocytes and increases the production of PGE2 (6, 19, 20). IL-6 has been shown to decrease cartilage matrix synthesis and may stimulate TIMP (6).  Increased neutrophil migration into the joint space is detrimental, as these cell release elastase and cathepson-G which further degrade cartilage (6). Phospholipases can act on cell membranes to activate the COX and LOX cascade which results in production of prostaglandins (namely PGE2) and leukotrienes (6). These substances further exacerbate inflammation and can be attributed to the production of pain.
In vitro studies were carried out Siminaro and colleagues (23) and they reported increased secretion of MMP-2 and MMP-9 by arthritic chondrocytes.  They found that while increased MMP within tissue may also increase TIMP-1 secretion, the effect of NO and pro-inflammatory cytokines was inhibitory on TIMP-1.  In addition to this, they also found the IL-1, and TNF-α that were produces by chondrocytes, synoviocytes and macrophages leading to up-regulation of the MMP gene expression (23).
Treatment of OA in Dogs and Cats
While the disease processes underlying OA in dogs and cats are rather complex, understanding the signalling cascade present within the joints provides a basis for potential use of nutraceuticals in the aid of treatment of the disease.  A multimodal approach is preferred in treating these patients.  Correction of an underlying congenital abnormality or traumatic injury surgically must be considered. The use of NSAIDs, nutraceuticals, dietary supplements, physical therapy and weight loss are all also key to alleviating symptoms of the disease. Currently there is a large appeal to clients for using adjunctive therapy other than prescription medications for their pets. Nutraceuticals and dietary supplements are in the forefront of products which are available to consumers. Oral administration provides an easy method for people and their pets to employ. As an estimated >20% of dogs over 1 year of age are reported to be affected by OA (3), there is certainly a need for products that may help to decrease the pain associated with the disease.


Currently Reported Nutraceuticals/Dietary Supplements:
1) Glucosamine
Glucosamine is a mono amino monosaccharide that once modified to N-acetylglucosamine is a precursor to the disaccharide units of GAGs, hyaluronan and keratin sulfate (11). Conversion of glucosamine to galactosamine provides a component of chondroitin sulfate and dermatan sulfate (11). In vivo, glucosamine is produced by chondrocytes, however; in cases of OA, chondrocytes appear to have a decreased ability to synthesize glucosamine (1, 25, 26). There are no dietary sources of glucosamine, rather it is produced commercially from chitin; a component of the exoskeleton of shrimp lobsters and crabs (24). The product of glucosamine is available commercially in three forms: glucosamine sulfate, glucosamine hydrochloride and N-acetyl-glucosamine.
Mechanism of Action
Since glucosamine is a precursor for the formation of GAGs, it is been reported that supplementation may increase the production of PGs. Cell culture studies have shown the exogenous glucosamine stimulates the production of PG as well as collagen by chondrocytes (1, 27, 28). In a rabbit model, glucosamine was shown to significantly restore levels of GAGs within damaged cartilage (24, 29).  In cultured human OA chondrocytes, it was suggested that stimulation of messenger RNA and protein levels of aggrecan core protein, as well as inhibition of MMPs were possible mechanisms of action of glucosamine (24, 30).  In an abstract for a model of cartilage collage, lipoxidation was also inhibited by glucosamine thus attributing to the claims of its use for anti-inflammatory properties (24, 31).  Glucosamine has also been shown to reduce the transcription factors involved with IL-1 (11).
Bioavailability, Recommended Doses and Toxicity
In both dogs and cats the oral availability of glucosamine is rather high. An intestinal absorption rate of 87% has been documented (1, 32) with distribution to tissues being highest in the liver, kidney and articular cartilage (1, 33, 34). When evaluating in vitro effects and correlating the data with bioavailability, it was determined that the effective recommended dosage of glucosamine HCL be 22mg/kg (11, 35). Toxicity of glucosamine appears to be minimal.  At doses of 5g/kg the only reported adverse effect was mild gastrointestinal upset including flatulence.
It should be noted that glucosamine products are not required to be monitored.  In a review of 14 OTC products available, the amount of actual glucosamine present varied from 59-138% (24).
Evidence Based Medicine with Glucosamine
Human efficacy:
In a review by Neil and colleagues of a meta-analysis and quality assessment of 15 randomized double-blind placebo controlled studies, 14 out of the 15 studies revealed beneficial effects with regards to decreasing pain and improving mobility (11, 36). That being said, when glucosamine was compared to the use with glucosamine and chondroitin, benefits were greater in the later.
In a 3 year long administration of glucosamine vs. placebo, 20-25% improvement of pain and function were reported (11, 37, 38). This may however show bias, as when a similar short term trials were carried out, glucosamine showed no significant improvement.
In a randomized, controlled, double-blinded trial comparing placebo and glucosamine on knee OA, Hughes and Carr discovered that there were significant effects on glucosamine for lower pain and improving function (11). The trial was compared to a similar trial that had previously been carried out with the result that glucosamine had no significant effect.
 In 2010, the Annual rheumatoid Disease journal published the results of a 2 year study which attempted to show the clinical efficacy of glucosamine, chondroitin sulphate, a combo of the two, celecoxib and placebo (39). The trial was a double blinded, placebo controlled study of 583 patients followed over a 6 month period. The intent was to compare all groups and evaluate the ability to reduce pain and improve function based on the Western Ontario and McMaster University Osteoarthritis Index. Patients were then followed for a further 18 months to evaluate radiographic changes to joint space width.  Those in the glucosamine HCL group received 1500mg daily. There were no significant changes noted within any of the groups. There were however, trends that were noted within the study. In all groups (including that of the placebo group) improvement occurred within the first 18 weeks of treatment with celecoxib providing the most rapid results.  At the end point of the trial, glucosamine and celecoxib groups both showed a trend for being highest at the end point. With respect to the 2 year study, celecoxib showed the best pain and function repair.  There were also a group of patients that at the beginning of the trial showed the most intense symptoms. Of these patients it was shown that the combination of glucosamine and chondroitin showed the best effects.  Again, none of these results were statistically significant.
Canine efficacy:
There were no studies found that evaluated the use of glucosamine as a sole agent in dogs.  Clinical trials of canine patients all involved the administration of glucosamine in combination with chondroitin.  More information on these studies to follow. A study of the effect of glucosamine on experimental rat osteoarthritis was found.  After OA was surgically induced in rats, treatment groups were based on treatment with glucosamine, without glucosamine and a sham group. The rats receiving glucosamine were administered 1000 mg glucosamine HCL/kg/day. The elevated dose was based on poor metabolism of the drug and poor bioavailability in the species (46). Statistically significant reduction in degenerative changes on the surface of articular cartilage was seen in the group treated with glucosamine (46). In addition, biomarkers of OA were also decreased in the group treated with glucosamine (46).

2) Chondroitin Sulfate
Chondroitin Sulfate is a GAG composed of glucuronic acid and sulfated N-acetylgalactosamine (11).  Chondroitin is produced in vivo by chondrocytes of articular cartilage. Exogenous sources of cartilage can be used as a supplement.
Mechanism of Action
Use of chondroitin sulfate has been advocated as it has been determined it can decrease IL-1 production, block complement, inhibit MMPs, inhibit histamine-mediated inflammation and stimulate GAG and collagen synthesis (11, 40, 41).
Bioavailability, Recommended Dose and Toxicity
Oral absorption in dogs has been reported to be as high as 70% (11, 42). When evaluating in vitro effects and correlating the data with bioavailability, it was determined that the effective recommended dosage of 8.8mg/kg (11, 35).  Plumb’s Veterinary Handbook reports a dose of 13-15mg/kg for dogs and 15-20mg/kg for cats (43, 44). Chondroitin appears to accumulate in the serum leading to an estimated bioavailability of 200% (1, 33, 45).

The author was unable to find any evidence based medicine including the use of chondroitin alone.  The combination of chondroitin with glucosamine was available.  This is likely attributable to the fact that a great deal of products available have the two compounds supplied together.  A synergistic effect can be extrapolated by an in vitro study on equine cartilage. The use of the two components together decreased nitric oxide production, PG degradation and inhibited MMP-9 and MMP-13 (11, 45).
Human efficacy:
As previously mentioned, in 2010 a 2 year human study was carried out comparing glucosamine, chondroitin sulphate, a combination of the two, celecoxib and placebo.  While there was no scientific significance between groups, the chondroitin and glucosamine combination showed the most benefit in a subset of patients that had more severe signs attributed to OA (39).
Canine efficacy:
A randomised double-blinded, positive-controlled trial published in 2006 by McCarthy and colleagues showed the efficacy of glucosamine and chondroitin sulfate used in the treatment of OA in dogs.  The study included the use of 42 dogs recruited from private practice.  The dogs were in treatment groups receiving carprofen or Synoquin SA (glucosamine/chondroitin).  The dogs received the manufacturer’s recommended doses of active ingredient. Animals were assessed prior to initiation of treatment by both veterinarians and their owners and subsequently on days 14, 42, 70 and 98.   Dogs in the Synoquin SA group showed significant improvement in disease score at day 70 for pain, weight-bearing and overall condition when compared to pre-treatment score; however lameness and joint mobility were not significantly improved (47).  It should be noted that the Carprofen group had a greater mean reduction in disease. Limitations of this research are the lack of quantitative ground force reaction testing. The results are rather based on subjective assessment. The data of the placebo group was also not reported. There is no means of evaluating if a placebo effect was seen by either the clinicians or their owners.  Based on this data, one can extrapolate that while Synoquin SA did not provide a better means of improvement in OA over Carprofen, there were statistically significant changes seen. This supports the recommendation of this nutraceutical as an adjunct in the treatment of OA.
Conversely, in a review by Budsberg and Bartges (3) contradictory results were found. In a study by Moreau and colleagues, 71 dogs were evaluated in a prospective double-blind study (48). Dogs were divided into groups given glucosamine/chondroitin, carprofen and Meloxicam.  The evaluation was similar to the above study, however; ground force reaction was also measured.  Changes in the ground reaction forces were statistically significant in the dogs receiving the pharmaceuticals; however they were not in those receiving glucosamine/chondroitin (3). Clinicians felt that there had been an improvement with carprofen and Meloxicam, differing from the owners’ opinions that improvement was seen only with Meloxicam (3).
In another review by Aragon and colleges (49) a trial of 19 dogs receiving chondroitin, glucosamine and manganese ascorbate revealed no improvement either subjectively or objectively.


 3) New Zealand Green-Lipped Mussels
New Zealand Green-Lipped Mussels (GLM) has been known for some time as a dietary supplement in canine diets.  It was not until 1986 that dried mussel extracts were stabilized with a preservative (3). Prior to this date no there were no published studies able to provide evidence of beneficial effects of this substance and it has been speculated that the lack of stabilization of the product may be a contributing factor in contradictory results of clinical studies (3, 50).
Mechanism of Action
GLM are published to contain GAGs, omega-3 fatty acids, amino acids, vitamin and minerals (1, 51).  Despite these varied properties, the benefit of use of GLM in OA is thought to be from the anti-inflammatory effects of the omega-3 fatty acid tetrenoic acid (3, 51).
Canine efficacy:
As reviewed by Budsberg and Bartges (3), a randomized controlled clinical study of 31 dogs with OA was carried out with 0.3 % GLM powder added to a generic diet (52). The dogs were evaluated with subjective arthritis score for joint swelling, pain, crepitance and range of motion.  Statistically significant results for improvement of joint swelling and pain were seen in the dogs that received the GLM powder.  This article was also reviewed by Beale (1). In his review, he highlighted the points that the dogs included in the study were not officially diagnosed as having OA (1). Further to this, he also mentioned that control dogs showed worsening of their joint pain and swelling over the 6 week study period which is uncommon of the slowly progressive disease of OA (1). In another review by Johnston and colleagues (54), two trials conducted by Aragon and colleagues showed that in prospective and randomized trials of GLM showed a subjective positive effect on dogs with OA.  These trials however, did not have positive or negative controls and lacked scientific evidence (54).
In a second study reviewed by Budsberg and Bartges (3), 71 dogs were divided into groups of chondroitin sulfate, GLM and a placebo (53). The study included 58 dogs that completed the 12 week trial. In this trial it was reported that none of the groups showed any significant improvement of clinical signs (3).
4) P54FP
P54FP is an extract of Indian and Javanese tumerics with active ingredients that include curcuminoids and essential oils (3, 54).
Mechanism of Action
Evidence is present supporting the capability of anti-inflammatory effects of P54FP. Curcumin has been documented to inhibit PGE2 and cyclooxygenase-2 (3, 55, 56, 57).
Canine efficacy:
In a randomized, blind, placebo-controlled, parallel- group clinical trial 61 dogs were recruited (58). The dogs were allocated to the P54FP group and a placebo group for 8 weeks. Treatment was assessed using both clinical assessments of lameness and joint pain by the authors as well as quantitative measurements of affected joints, and overall response by the owners. No statistical significance was seen in the quantitative measurement of the affected joints (58). Interestingly, while the authors subjective assessment of improvement showed statistical significant, the assessment of the owners did not (3).
5) Boswellia Serrata
Resin extracted from the tree Boswellia serrata has been shown to decrease leukocyte infiltration, decrease antibody synthesis and inhibit the complement pathway (59).Sharma ML, Khajuria A, 1. Kaul A, et al. Effects of salai guggal ex-Boswellia serrata on cellular and humoral immune responses and leukocyte migration. Agents Actions 1988;24:161-164.
Budsberg and Bartges commented on a study of this compound. In an open, multicentric clinical trial of 29 dogs with OA 400mg per 10 kg was administered once daily for 6 weeks (3, 60). Statistically significant improvement was observed in 17 of the 24 dogs (3).
6) Avocado and Soybean Oils
The unsaponifiable fractions of both avocado and soybean oils have in vitro been shown to be beneficial in OA by inhibiting IL-1 and stimulating collagen synthesis (3, 61, 62). As reviewed by Budsberg and Bartges, clinical trials in humans have shown both positive effects and also no benefits for the alleviation of clinical symptoms of OA (3).
7) Boron
Boron deficiency in human diets has been suggested as a cause of arthridities in humans.  Budsberg and Bartges referred to a double-blind placebo and boron supplementation trial in 20 patients with OA (3). A significantly positive response was seen with diets supplemented with boron.
8) Cat’s Claw
Budsberg and Bartges refer to the plant Uncaria tomentosa. Although studies have not been reported in dogs with OA, based on the anti-inflammatory and antioxidant effects seen in humans with rheumatoid arthritis, they suggest its potential for the use in domestic pet species.
9) Creatine
Creatine has been used in instances of rheumatoid arthritis in human for the production of ATP and improvement of skeletal muscle weakness (3). Its evidence has not been published for dogs with OA.
10) Special Milk Protein Concentrate
Anti-inflammatory properties have been attributed to inhibition of neutrophil migration (3, 63). Components found within this concentrate have been immunoglobulins, cytokines, enzymes, hormones and growth factors (3). Budsberg and Bartges report that clinical trials have shown subjective improvement in dogs with OA when administered SMPC when compared to placebo (3).
11) Omega-3 fatty acids
Omega-3 and Omega-6 fatty acids have been considered essential nutrients for decades. The health benefits which have been attributed to their dietary addition have been on cardiac, renal, hepatic and integumentary health as well as the reduced in rate and recurrence of neoplasia. Omega-3 fatty acids have also been shown in clinical studies to aid in the support of joint health in those affected with OA.
The parent compound of omega-6 fatty acids in linoleic acid (18:2n-6) or LA. Primary sources of LA are vegetable oils, examples of which being soy, corn safflower and canola oils (64). LA can be metabolized by the body to form arachidonic acid (20:4n-6). In cats, the conversion is decreased and thus, they must receive some AA supplementation in their diets (65). AA can be provided with animal fats as well as the precursors to AA via black current, borage and evening primrose oils which contain γ-linoleic acid (18:3n6) (64).
The parent compound of omega-3 fatty acids is alpha linoleic acid (18:3n3). Dietary sources of ALA are from plants, flax and flaxseed oil (64). Metabolites of ALA include EPA, DPA and DHA. These three metabolites can be found in fish meal and cold water marine oils (64).
Bioavailability, Doses and Toxicity
Ranges in the ratios of omega6:3 fatty acids have ranged anywhere from 25:1 to 5:1 in the past. New research has shown that this ratio has steadily been decreasing in commercial pet foods.  Metabolism of LA and ALA are both via the same enzymes. Of these, a higher affinity is present for ALA leading to the higher recommended proportion of omega6:3. While a lower ratio has been advised, excessive levels of DHA of more than 1.5% can lead to reduced growth, reduced language development, behavioural changes, reduced cognitive function, and a delay in reflexes in rodents when an adequate amount of AA is not provided (65, 69, 70, 71, 72).
In a study reviewed by Bauer (66) comparing conversion of ALA, 84 dogs were fed with either a diet containing 3% sunflowers seed or 3% flaxseed (67). The sunflower seed diet had 9.3% calories as LA and 0.4% as ALA versus the flaxseed diet with 7.4% LA and 2.5% ALA (66). In the flax seed diet accumulation of EPA began after 4 days post initiation of the feeding trial with peak plasma levels reached at 28 days (66). DPA was also detected but did not accumulate in the plasma as DHA.
In humans, when flax oil was compared to fish oil, flax showed 7% efficiency in increasing plasma levels of EPA when compared to the fish oil (65). Fish oil was also able to increase not only EPA plasma levels, but also DPA levels.  Dogs appear to be even more less efficient than humans in the conversion of ALA to DHA (65).
Based on most research showing the inefficient conversion of ALA to DHA, a large proportion of diets promote the use of fish oils over flax seed oil. It has however been suggested that 1) DPA formed from ALA may be delivered to the cells directly, which then convert it to DHA limiting an accumulation within plasma and 2) DPA can be converted back to EPA and contributes to the accumulation of EPA plasma levels (66).
In a study reviewed by Bauer (66), dogs were fed diets containing ALA from flaxseed oil and EPA from fish oil, beef tallow and safflower oil (68). While diets containing fish and flax seed oil contained similar omega-6:3 ratios and both showed an increase in omega-3 incorporation into neutrophilic membranes, a higher level was seen with the fish oil diets (66).
In an unpublished study by Bauer and colleges, fish oil supplemented diet fed to dogs with OA resulted in significant increased in both EPA and DHA in the plasma and synovial fluid AND a decrease in AA. Reductions in MMP-2, MMP-9 and PGE2 were also seen (66).
Mechanism of action
Upon inflammatory insult, cytokines are released from the cell membranes. These cytokines can act as inflammatory mediators and stimulate the production of eicosanoids which further exacerbate inflammation. PGE2, IL-1, IL-6 and TNF-α levels all increase in plasma levels of OA patients.
EPA and DHA have been shown to decrease these inflammatory mediators (65, 73, 74, 75). As reviewed by Budsberg and Bartges (3), an unpublished study had 18 dogs randomly assigned into three groups with identical diets except for the omega-6:3 ratios. The dogs were fed the diet prior to and after surgical transaction of the cranial cruciate ligament. The group that consumed the diet that was highest in omega-3 (0.7:1.0) had lower serum cholesterol, triglycerides and phospholipids (3). They also had decreased levels of PGE2 in the synovial fluid and had stronger ground reaction forces (3).
In a prospective, uncontrolled study of 146 dogs with OA, 88% of the dogs showed clinical improvement in lameness after 2 months of being fed Purina JM which contains omega-3 fatty acids from a fish oil source at a dose of 250mg/100Kcal (65).
Antioxidants
Use of antioxidants in the clinical situation of OA has been described primarily in human literature.  Vitamin E and vitamin C have been reported in clinical trials; however they both have significant contradictory results. In addition, dogs are reported to be able to synthesize endogenous vitamin C and so its addition to diet would be redundant (3).
Commonly recommended nutraceuticals/dietary supplements:
In March, 2012 an unpublished, collaborative survey was conducted by the author and three other fourth year veterinary students in the small animal nutrition elective at the Western College of Veterinary Medicine.  The survey was conducted in order to establish what kinds of supplements and/or diets were being advised by both veterinarians and pet stores across Saskatoon. Of the 22 veterinary hospitals only 9 responded to the survey request.  Out of the 7 pet stores, 6 responded to the survey. The remaining store, Petsmart, refused to answer any of our questions as they were instructed not to by the store owner.  Our questions pertained to the products used (brand name) as well as if any products were advised to be purchased at health food stores. We also wanted to know why these particular products were advised, and where the information about the products in question was received.

Veterinary Dispensed/Recommended Supplements:
All of the clinics that responded either advised or sold products containing glucosamine, glucosamine/chondroitin and omega-3 fatty acids. The majority of these products were sold in clinic.  A small number of clinics advised for them to be purchased at health food stores in the city. The main reason these products were recommended were because of published literature stating the significant effects of these products on joint health.  The table below lists the products that we were given brand names of. The most commonly sold products were glucosamine (56%), chondroitin (44%) and omega fatty acids (44%).
Veterinary diets were also highly advised by the veterinary hospitals surveyed. The diets were primarily the same for all clinics and were exclusively sold veterinary diets. The diets were recommended based on information supplied from the various food company representatives. The foods advised by the hospitals were Hill’s j/d (canine), Royal Canin/Medi-cal Mobility Support (canine and feline) and Purina JM.
The recommendation for the diets was apparent when there was a diagnosis of OA in patients. Omega-3 fatty acids and glucosamine/chondroitin were also recommended as supplements for apparently healthy animals as a preventative measure by more than 50% of the surveyed clinics.

Table 2 Brand Name Products Recommended by Veterinary Hospitals
Product
Company


Dasuquin
Nutramax

Laboratories
Cosequin
Nutramax

Laboratories
Omega Pro 3
Pro Concepts

Animal Health
Ubavet Liquid

Plus
Ubavet
Flexadin
Vetoquinol
Zukes Hip Action
Zuke's
Chondro Flex
Champion Alstoe

Animal Health

Pet store available supplements/diets:
7 pet stores were also surveyed within Saskatoon. Two were larger stores and five were more intimate/specialty pet food/supply stores.  The larger two, Petsmart and Petland, were unable to fully answer the survey but the products available in the store were reviewed. The small specialty stores were extremely knowledgeable about the products that they carry. We were informed that their information regarding the products was supplied by the manufacturers, nutritionists and own research. Local products seem to be more popular staff were more readily available to answer any questions. In addition, the sale of locally produced products was beneficial to the local economy. Suppliers also had personal experience using the products that they more readily advised to their clients.
Table 3 Brand Name Products Sold by Pet stores
Product
Company


Spring Meadows
Spring Meadows
liquid joint care



Naturvet Hip and
Naturvet
Joint Formula

Biologic Vet
Biologic Vet
joint support

Flax Forward
Juka
 Cetyl M
Response
Glucosamine +
21st Century Pet
Chondroitin

Halo hip and joint
Halo

The specialty pet supply stores advised the use of a high quality ingredient pet food.  One store advocated the use of raw diets, in particular the brand Spring Meadow’s. Their explanation is that they felt it provided the best products for a balanced diet and that the company was locally based with all ingredients being locally grown. If raw diets were not an option a fish based diet high in omega-3 fatty acids would be preferred. Brand names that were repeatedly brought up in all the specialty stores were Acana, Orijen and Horizon.
A Discussion on Commercial Veterinary Diets:
A trend become quite apparent in the veterinary hospitals in regards to the diets that they recommended.  All of the clinics suggested the use of a commercially available veterinary diet for the aid in treatment of dogs and cats with OA. A comparative look at the four main canine diets revealed that they did differ slightly in composition.  All of the diets compared claimed to improve mobility in affected dogs. They all advertised the presence of high omega-3 fatty acids. They all presented the aspect of being low in caloric density which would be beneficial in weight reduction. Two of the diets had the advertisement of having L-carnitine to maintain lean muscle mass. One of the diets contained GLM as a joint support ingredient and antioxidant.  All of the diets contained glucosamine and two of the diets also contained chondroitin. Table 4 outlines a comparison of the available information online for clients to view.  Added is the amount of glucosamine/chondroitin for Hill’s j/d and Purina JM. This data was received from the company representatives. Table 3 displays the advertising claims of the four diets reviewed.

Table 4 Claims Supporting Use of Commonly Prescribed/Recommended Veterinary Diets
Hill’s j/d
Purina JM
Medical Mobility
Support
Royal Canin Weight
& Osteo
1) Improve dog’s ability to run, walk, jump in as little as 21 days
1)improve mobility
1) improve mobility and reduce pain with omega fa ratio
1) enhance joint support

2) excellent source of omega-3 fatty acid EPA
2) high EPA and omega-3 fatty acids
2) high in omega 3 and 6 fatty acids
2) enriched with EPA and DHA
3) controlled calorie content
3) high protein/calorie ratio, moderate fat content
3) reduced calorie content
3) restricted calorie
4) added L-carnitine to maintain healthy weight
4) appropriate levels of omega 6 fatty acids
4) GLMP support joints and is anti-inflammatory
4) L-carnitine added

5) high levels of antioxidant vitamins E and C
5) omega3 and 6 promote healthy skin and coat
5) Vitamin E and C for antioxidant + taurine

6) natural source of glucosamine

6) glucosamine added

7) excellent palatability

7) highly digestible protein



8) aids in dental health





 Table 5
Comparison of Commonly Prescribed/Recommended Veterinary Diets for Joint Support/Health





Nutrient and Caloric
Hills J/D dry
Purina JM
Medi Cal Mobility Support
Royal Canin Weight & Osteo
Contents:




% dry matter




Protein
20.1
30
25
29
Fat
16.3
12
12
10
Carbohydrate
51.1



Crude Fiber
7.8
4
2.1
10.5
Calcium
0.71


0.81
Phosphorus
0.54


0.68
Potassium
0.79


0.62
Sodium
0.17


0.32
Magnesium
0.145


0.65
Carnitine
349 ppm



Vitamin C
203 mg/kg
100 mg/kg

199mg/kg
Vitamin E
582 IU/kg
800 IU/kg

597 IU/kg
EPA
0.493


0.25
ALA
2.73



LA



2.14
Omega -3 FA total
3.74
0.85
0.57
EPA/DHA
0.57
0.36
GLMP
0.3

Glucosamine/
980mg/kg:674mg/kg
1435 mg/kg
1000mg/kg
893mg/kg:100mg/kg
chondroitin sulfate





Caloric density
356 kcal/ cup
408 kcal/cup
324 kcal/cup
246 kcal/cup
























Ingredient List of Commonly prescribed/recommended Veterinary Diets

Hills j/d:
whole grain corn, chicken by-product meal, flaxseed, soybean mill run, brewers rice, soybean meal, pork fat
preserved with mixed tocopherols and citric acid), chicken liver flavour, powdered cellulose, fish oil, lactic acid
potassium chloride, L-lysine, calcium carbonate, choline chloride, iodized salt, DL-methionine,
vitamin E supplement, vitamins (L-Ascorbyl-2-polyphosphate (source of vitamin C), Vitamin E supplement, niacin,
thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine
hydrochloride, riboflavin, folic acid, vitamin D3 supplement,
), L-threonine, taurine, soy lecithin, glucosamine
hydrochloride, minerals (ferrous sulfate, zinc oxide, cupper sulfate, magnesium oxide, calcium iodate, sodium
selenite), L-tryptophan, L-carnitine, preserved with mixed tocopherols and citric acid
Purina JM:
brewers rice, salmon meal, corn gluten meal, poultry by-product meal (natural source of glucosamine), dried
egg product, oat fiber, animal digest, animal fat preserved with mixed tocopherols (form of Vitamin E)
fish oil, chicken, potassium chloride, vitamin E supplement, salt, choline chloride, taurine, zinc sulfate,
L-ascorbyl-2-polyphosphate (source of vitamin C), ferrous sulfate, manganese sulfate, niacin, calcium carbonate,
vitamin A supplement, calcium pantothenate, thiamine mononitrate, copper sulfate, riboflavin supplement,
vitamin B12 supplement, pyridoxine hydrochloride, folic acid, vitamin D3 supplement, calcium iodate, biotin
menadione sodium bisulfite complex (source of vitamin K activity), sodium selenite
Medi Cal Mobility
brewer's rice, chicken meal, brown rice, corn, corn gluten meal, natural flavour, chicken fat, diet beet pulp,
Support
fish oil, calcium carbonate, pea fibre, potassium chloride, vegetable oil, salt, green lipped mussel powder,
L-lysine, choline chloride, taurine, glucosamine hydrochloride, vitamins (DL-alpha-tocopherol (source of
vitamin E), L-ascorbyl-2-polyphosphate (source of vitamin C), biotin, D-calcium, pantothenate, pyridoxine
hydrochloride (vitamin B6), vitamin A acetate, niacin, thiamin mononitrate (vitamin B1), riboflavin (vitamin B12),
folic acid, vitamin B12 supplement and vitamin D3 supplement), trace minerals (zinc proteinate, manganese
proteinate, zinc oxide, ferrous sulphate, copper proteinate, copper sulphate, manganous oxide, calcium
iodate, and sodium selenite), marigold extract (source of lutein), and chondroitin sulphate. Naturally preserved
with mixed tocopherols, rosemary extract and citric acid.

Royal Canin
Weight & Osteo:
chicken meal, brown rice, wheat gluten, barley, powdered cellulose, rice, chicken fat, natural flavors, dried beet
pulp, fish oil, brewers dried yeast, sodium silica aluminate, potassium chloride, dried egg product, vegetable oil,
sodium tripolyphosphate, calcium sulfate, salt, choline chloride, DL-methionine, taurine, glucosamine
hydrochloride, marigold extract, vitamins (DL-alpha tocopherol acetate (source of vitamin E), L-Ascorbyl-2
polyphosphate (source of Vitamin C), biotin, D0calcium pantothenate, vitamin mononitrate (vitamin B1),
riboflavin supplement (vitamin B2), folic acid, vitamin B12 supplement, vitamin D3 supplement), L-carnitine,
trace minerals (zinc oxide, copper proteinate, manganese proteinate, copper sulfate, manganous oxide, copper
proteinate, calcium iodate, sodium selenite, tea (green tea extract), chondroitin sulfate, rosemary extract,
preserved with natural mixed tocopherols and citric acid.

Addressing the claims of these diets:
Hill’s j/d: The first claim provided by Hill’s was based on a randomized, double-masked, practice based 6 month feeding study (76). In this study, 131 completed the study which were representatives from 18 different veterinary hospitals.  The dogs were fed either a control food or the prescription diet Hill’s j/d in the dry form for 6 months. Results of the study showed a significant higher serum concentration of total omega-3 fatty acids and EPA in dogs fed Hill’s j/d (76). In addition, these dogs also had lower arachidonic acid (although not statistically significant) and a significant lower serum omega-6:3 ratios. Subjectively, dogs fed Hill’s j/d had significant improvement in their ability to rise from a resting position, running, and playing. In comparison, while the mean subjective scores given by clinicians improved with the Hill’s j/d diet, they were not statistically significant (76).
                Hill’s claimed to have an excellent source of omega-3 fatty acid EPA. This report is likely true as compared to the Royal Canin, the EPA levels were higher. This is likely attributed to the flaxseed present in the diet. The presence of DPA was not mentioned.
                The next claim of controlled calorie content is again questionable. This diet ranked third out of the four compared diets with a caloric density of 365 kcal/cup.
                The final claim was L-carnitine to maintain healthy weight. In dogs, the permitted maximum amount of L-carnitine is 750 ppm for dogs. Typically in diets it is supplied in a range of 100-350ppm. At the level of 349 ppm, this diet has a moderate amount which may be beneficial.
An important note is that the diet does contain glucosamine and chondroitin sulfate. This is not advertised as a benefit by the company. When contacted by the representative, it was stated that there is no scientifically proven benefit of this supplement in the diet, however; it has been placed in the food to be on the label for clients that want this supplement in the food.  Based on the feeding requirement for a large breed dog (40lbs) if supplying dry formulation 2 1/3 cups (230 g) - 3 1/4 cups (320 g) would need to be fed to meet the required daily intake. In this quantity of food 225.4mg-313.6mg of glucosamine and 155.02mg-215.68mg of chondroitin sulfate are present. Based on the advised doses of these, a dog of this size would require 400 mg of glucosamine and 272 mg of chondroitin sulfate. The diet thusly does not provide adequate amounts of either of these components as a supplement if fed at the recommended feed quantity of feed.
Purina JM:             Purina’s first claim is that the diet improves mobility. This claim is based on findings of an increased force plate gait analysis when dogs with OA were fed a diet with higher omega-3 fatty acids. P value for this study was 0.08 (77). In a two month long clinical feeding trial, subjective assessment of owners and clinicians felt that dogs with OA showed a significant improvement in mobility. Clinicians were more inclined to recommend the diet based on these observations.
                The diet claims to be high in EPA and total omega-3 fatty acids. The total EPA was not listed on their product website, however, information provided by company representatives stated that 8oz of diet contained 287mg of EPA and 445 mg of DHA. The total omega-3 fatty acid content was significantly less than Hill’s j/d.
                The diet touted its high protein/calorie ratio. Oddly, when comparing the data published on the product website to the literature provided by the company representative, inconsistencies were present with the nutrient composition. The provided information from the company (vs. the website) stated that the protein % was actually 34.25 and the fat was 14.18%. While the protein content was highest of all four diets, the caloric density was also the highest when using the website. The literature provided from the company did state that the caloric density was less than internet amount and was 351kcal/cup. This would then place the diet second for highest caloric density. It may be more beneficial to explain that the high quality meat protein would lead to a more digestible calorie source. This was not mentioned.
                The omega 6 fatty acid content could not be discussed as these levels were not provided in the diet analysis.
                The levels of vitamin C were lower than that of Hill’s j/d, but the levels of vitamin E were double. The internet product guide listed the vitamin E content as 800IU/kg but the provided data sheet listed it as 1000IU/kg. The vitamin C level was not provided but may potentially be higher as well.
                Glucosamine was not listed on the internet product guide; however literature stated it was 1435mg/kg. If we use the body weight of a 40lb dog once again 2 ¾ cups of feed is advised. With this volume the dog would receive approximately 360 mg of glucosamine.  This is actually more than Hill’s j/d but it still is not the adequate dose for that size of dog. The downside is that there is no chondroitin in the diet and as previously reported, the two supplements have been shown to act synergistically.
                The final claim was that of palatability. One can extrapolate that if dogs were fed this diet then it must have been palatable.  No reports of gastrointestinal upset or lack of product ingestion was found. On a personal note, this diet was fed to dogs owned by the author and it did seem to be extremely palatable.
Medical/Royal Canin Mobility Support:
                This diet also stated that it would improve mobility and reduce pain with the presence of omega-3 and omega-6 fatty acids. It also stated that it was high in these compounds. The information provided failed to state the % of omega-3 fatty acids on a dry matter basis so this statement could not be confirmed.
                The diet was decreased in caloric content when compared to the other commercial diet companies at 324kcal/cup.
                The diet contained GLM powdered and was advertised to support the joints and serve anti-inflammatory purposes. The diet contained 0.3% on a dry matter basis. Research has shown this compound to show a positive effect on joint health at levels of 0.3%.
                Although not advertised, the diet did contain glucosamine.  A feeding guideline of 3 2/3- 4 ¼ cups of the diet was recommended for a 40 lb dog. Based on this, the diet also does not contain significant glucosamine unless it is fed at the highest recommended volume (360-425mg).  It does not contain chondroitin.
Royal canine Weight & Osteo:
                This diet is one that is manufactured to be sold in pet stores. It states it has evidence of enhanced joint support. No evidenced based medicine could be found and none was able to be produced by the company when approached.
                While it has the lowest levels of Omega-3 fatty acids of the diets compared, it DOES have a large amount of LA (the precursor to inflammatory eicosanoids).  It also has less EPA and DHA than the veterinary produced version of Mobility Support.
                The diet claim to be restricted calorie is substantiated as it has the lowest caloric content of 246kcal/cup while maintaining a high protein level. The diet itself seemed to be beneficial for a weight loss protocol, which in turn may help to improve the load bearing on the joints and subsequently improve clinical signs associated with OA. L-carnitine is advertised to be added but is not listed in the nutrient profile.
                Vitamin C and vitamin E levels are consistent with the compared diets.
                Glucosamine and chondroitin are advertised components of the food. With the proposed feeding guidelines provided, a 40lb dog would only receive 225mg glucosamine and 25.3mg of chondroitin. Both below the recommended daily intake.
                The statement of the diet being palatable and supporting dental health could not be evaluated as there was no literature in regards to either claim.
Horizon Complete Senior and Weight Management:
                For curiosity, the diets above were compared to a locally produced, high ingredient grade pet food. The following information was obtained from the bag label.
Crude Protein (min) 24.0 %                                                        Mid range when compared to veterinary diets
Crude Fat (min) 10.0 %                                                                   lowest of all diets
Crude Fibre (max) 4.0 %                                                                lowest of all diets
Moisture (max) 10.0 %                                                                   
Calcium (min) 1.1%                                                                           slightly higher than other diets
Phosphorus (min) .85%                                                                   slightly higher than other diets
Omega 3 (min)** 0.44 %                                                               lowest of all diets
Omega 6 (min)** 3.62 %                                                              
Glucosamine* (min) 600 mg/kg                                                                        lowest of all diets
Chondroitin Sulphate* (min) 400 mg/kg                            highest of all diets

                While the diet did not contain as much omega-3 fatty acids as the veterinary diets, it is one of lower end diets of this company. It also contained significantly higher amounts of chondroitin sulphate.
                 
Commercially available supplements sold or recommended by the veterinary hospitals and pet stores in our survey:
Dasoquin (http://www.nutramaxlabs.com/vet/Products/Dasuquin-for-dogs.aspx): Dasoquin is a veterinary exclusive product that is manufactured by Nutramax laboratories.  The product is available for both dogs and cats. It contains not only glucosamine HCl and chondroitin sulfate, but also avocado/soy unsaponifiables. The product for dogs is supplied in either a chewable treat or chewable tablets. The feline product is in the form of a capsule that can be given directly or sprinkled onto the food.

Canine chewable treats contain:

Ingredient
Large Dogs
Small to Medium Dogs
Glucosamine Hydrochloride* 99%
900 mg
600 mg
Sodium Chondroitin Sulfate*
350 mg
250 mg
Avocado/Soybean Unsaponifiables* (ASU) Powder
90 mg
45 mg

Canine Chewable tablets: Each Chewable Tablet Contains:

Ingredient
Large Dogs
Small to Medium Dogs
Glucosamine Hydrochloride* 99%
900 mg
600 mg
Sodium Chondroitin Sulfate* (Low Molecular Weight)
350 mg
250 mg
Avocado/Soybean Unsaponifiables* (ASU) Powder
90 mg
45 mg

Recommended daily doses are 1-2 daily (based on body weight) for the initial 4-6 weeks and then decreased to half daily.

Feline Capsules: Each Capsule Contains:

Glucosamine Hydrochloride* 99%
125 mg
Sodium Chondroitin Sulfate* (Low Molecular Weight)
100 mg
Avocado/Soybean Unsaponifiables* (ASU) Powder
25 mg


Cosequin DS (http://www.nutramaxlabs.com/Vet/Products): Cosequin is another joint support product that is manufactured by Nutramax laboratories.  In contrast to Dasoquin, this product is not veterinary exclusive which make it more readily available to consumers and also at a lower cost. In contrast to Dasoquin, this product does not contain the unsaponifiables.

Feline Cosequin: Each Capsule Contains:

Glucosamine Hydrochloride* minimum
125 mg
Sodium Chondroitin Sulfate* minimum
100 mg
Manganese minimum
1 mg**
 *  manganese is a cofactor for multiple enzyme functions and detoxification of superoxide free radicals

Canine Cosequin: Each Chewable Tablet/capsule Contains:

Glucosamine Hydrochloride*
500 mg
Sodium Chondroitin Sulfate*
400 mg
Manganese
5 mg**

Cosequin DS + DSM Each Chewable Tablet Contains:

Glucosamine Hydrochloride*
600 mg
Sodium Chondroitin Sulfate*
300 mg
Methylsulfonylmethane (MSM)
250 mg
Manganese
5 mg**
* MSM adds sulfur and has reported anti-inflammatory properties
Cosequin DS Each Soft Chew Contains:
Glucosamine Hydrochloride*
600 mg
Sodium Chondroitin Sulfate*
300 mg

Cosequin Regular strength Each Capsule Contains:
Glucosamine Hydrochloride*
250 mg
Sodium Chondroitin Sulfate*
200 mg
Manganese
2 mg**

Comparatively, these products all contain relatively similar amounts of glucosamine and chondroitin. The variety of products is likely to provide appeal to clients. The differing product lines also allow for distribution of various markets.
The company states that their production is carried out with similar standards to the pharmaceutical industry. It also advertises that the product has been shown to be safe, effective, and bioavailable in the labelled amounts as per peer reviewed studies. Evidence of these studies could not be located.
Flexadin (http://www.vetuk.co.uk/joint-supplements-flexadin-for-dogs-and-cats-c-4_243/flexadin-tablets-for-dogs-and-cats): Flexadin is a veterinary exclusive product that is manufactured by Vetoquinol. The tablet is advertised for the use in both dogs and cats.
Each tablet contains:
Glucosamine HCl
500mg
Chondroitin Sulfate
400mg
Devil’s Claw
150mg
Manganese
10mg

The recommended dose is one tablet per 20 kg of body weight daily, with loading dose of twice that for the first 2-4 weeks.
Chondroflex (http://www.drugs.com/vet/chondro-flex-ds-soft-chews-can.html): Is a veterinary exclusive product that is manufactured by Champion Alstoe Animal Health.  The product is advertised for the use in both dogs and cats.
Each tablet contains:
Glucosamine HCl
500mg
Chondroitin Sulfate
400mg
Methylsulfonylmethane
500mg
Ascorbate (as Manganese Ascorbate)
66mg
Manganese (as Manganese Ascorbate)
10mg

Liquid Plus (http://www.ubavet.com/ubaeng.html): Produced by Ubavet, this product is advertised for the use in all pets. It contains not only glucosamine, chondroitin, manganese and MSM, but also contains GLM, bioflavinoids, as well as a number of herbs.
Each 5mL of product contains:
Glucosamine HCl
1000mg
Chondroitin Sulfate
250mg
Manganese
10mg
MSM
200mg
Ascorbic Acid
70mg
GLM
10mg
Selenium
5mg
Bioflavinoids
10mg

OmegaPro-3 (http://www.drugs.com/vet/omegapro-3-liquid-can.html): OmegaPro-3 is a veterinary exclusive product produced by Pro Concepts Animal Health.  With fish oil being the source of omega-3 fatty acids, the product it advised for the use in dogs and cats.
Each 1mL pump (300mg) contains:
Vitamin A
200 IU
Vitamin D
50 IU
Vitamin E
4 IU
Eicosapentaneoic Acid
180 mg
Docosahexaenoic Acid
120mg

Hip Action (http://www.zukes.com/woof/hip-action.html): Hip Action is a chewable supplement produced by Zuke’s. The product is advertised for the use in dogs and comes in a variety of flavours.  The chewable treats are noted to contain 24 kcal per treat.
Each chewable contains:
Glucosamine
300mg
Chondroitin Sulfate
50mg

Preceding products are summarized in the following table.  Due to the number of products that were available at pet stores within Saskatoon, the products and contents are also supplied summarized in a table.













Table 6 Summary of Advised Supplements for Joint Health by Local Veterinarians



Product
Chondroflex
Cosequin (K9)
Cosequin DS
Dasuquin
Flexadin
Liquid Plus
OmegaPro-3
Hip Action
Manufacturer
Champion Alstoe Animal Health
Nutramax
Nutramax
Nutramax
Vetoquinol
Ubavet
Pro Concepts Animal Health
Zuke's
Country
Canada
US
US
US
Canada
Canada
Canada
US
Volume
1 tablet
1 tablet
1 tablet
1 tablet
1 tablet
5mL
1mL
1 chew
Glucosamine
500mg
250mg
600mg
600-900mg
500mg
1000mg

300mg
Chondroitin
300mg
200mg
300mg
250-350mg
400mg
250mg

50mg
Manganese
10mg
2mg


10mg
10mg


MSM
500mg




200mg


GLM





10mg


ASU powder



45-90mg




Devil's Claw




150mg



Selenium





5mg


Bioflavinoids





10mg


Ascorbic acid





70mg


Vitamin A






200 IU

Vitamin E






50 IU

EPA






180 mg

DHA






120 mg





Table7  Summary of Products Available of Local Pet Stores in Saskatoon, SK





Product
Manufacturer
MSM
dose
Gluc
Cetyl M
Garlic root
Bromelain
Ginger Root
Chondroitin
Ascorbic Acid
Mang.
Advanced Cetyl M
Response

1 tablet
250mg
250mg
15 mg
10mg
7.5mg



Biojoint*
Biologic Vet
200mg
5g 1scoop
200mg


144 GDU

80mg

0.5mg
Cosequin feline
Nutramax

1 tablet
125mg




100
mg

1mg
Cosequin DS
Nutramax

1 tablet
500mg




400
mg

5mg
Flax Forward+
Juka Organics










Glucosamine/
chondroitin**
21st Century
10mg
1 tablet
500mg




100
mg
10mg
5mg
Glucosamine HCL
Ubavet

1 tablet
725mg




375
mg
100mg
5mg
Hip+Joint Plus paw gel++
Nutri-Vet
7.5mg






1.5
mg


Hip+Joint Level 2 canine+++
Nutri-Vet
400mg
1 tablet
400mg







Hip+Joint Level 3 canine
Nutri-Vet
50mg
1 tablet
500mg




400
mg


Hip + Joint
Pet Naturals
200mg
1 tablet
500mg




200
mg
50mg
2.5mg
Joint Stress
Homeopet
contains monkshood, leopard`s bane, pot marigold, witch hazel, st. John`s wort, chick pea and poison oak









Liquid Joint Care!
Spring Meadows

ounce
2ooo
mg


200
mg

80mg

24mg
Stride Powder
TRM Pet Products
2000mg
10 g
1080
mg




240
mg
48mg
76mg
Muscle & Joint!!
Vet`s Best
200mg




2400gdu




Vita-Glo Hip + Joint
Halo


340mg/kg




272
mg/kg
250
mg/kg













(*) also contains Boswellia serrata Extract, Vitamin C, Grape Seed extract, Vitamin D3
(+) contains flax oil and flax solids (product ingredients unavailable online)
(**) also contains zinc, copper, hyaluronic acid and vitamin E
(++) also contains yucca schidegera extract, sea kelp and vitamin C
(+++) all hip and joint canine products also contain vitamin C, antioxidants, zinc, manganese and copper
as well as GLM (500mg)
(!) also contains yucca schidegera, collagen, grape seed extract, citrus bioflavinoids, copper, zinc and calcium
(!!) also contains Boswellia extract, tumeric extract, yucca extract, rosemary extract, antioxidants
Conclusion
As one can seen, there are a large amount of choices available to consumers. While there is scientifically significant data supporting the use of a lot of the aforementioned supplements, there are equally confounding results that have been published. An educated client on the causes of OA and the consequences of it may help to make them more informed about treatment additives. It is the opinion of the author that glucosamine/chondroitin, omega-3 fatty acids have the most convincing evidence supporting their use as adjuncts in the treatment of OA. If an animal is on a diet that the owner feels it does well on I do not advocate changing the food. Instead, the addition of glucosamine at 22mg/kg, chondroitin 15-20 mg/kg and a supplement of omega-3 fatty acids (both fish and flax seed oils) should be considered.  Conversely, if the owner is open to diet change, the recommendation of Purina JM can be considered. Glucosamine and chondroitin supplementation should still be considered.  More research in the area of dietary supplements is most definitely needed.  Despite the lack of scientific data unequivocally supporting the use of supplements, the numerous subjective reports by owners and clinicians cannot be ignored.  These substances are not detrimental to the animal. Despite the fact that they MAY not actually be contributing to the improvement of a given animal, they are not detrimental. As there seems to be a chance that they can contribute to joint health and the overall improvement of animals with OA, the use of these supplements can be justified.



References
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[4] Adebowale A, Cox D, Liang Z, et al. Analysis of glucosamine and chondroitin sulfate content in marketed products and the Caco-2 permeability of chondroitin sulfate raw materials. JANA 2000;3:37-44.
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[6] Renberg, WC. Pathophysiology and Management of Arthritis. Vet Clin Small Anim 2005;25:1073-1091.
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