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

The Use of Nutraceuticals and Dietary Supplements for Joint Support and Health in Cats and DogsPresented to: Dr. Meg Smart, Small Animal Nutrition ElectiveBy: Karen Choptain IntroductionThe 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.Ā  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?Ā  A nutraceutical, as defined by the North American Veterinary Nutraceutical Council, is ā€œa 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-beingā€ (1,2). More specifically, a nutraceutical used in the aspect of joint support can be referred to as a chondroprotectant.Ā  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, Catā€™s Claw, Creatine, and Special milk protein concentrate (3).Ā  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.Ā  The products themselves must be safe; however, they do not have to achieve pre market approval, in contrast to pharmaceuticals or ā€œdrugsā€.Ā  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).Ā  A large variety of products are available to consumers.Ā  Despite the number of products, there is a drastic lack of scientific evidence that promotes any on of these products over the other.Ā  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 in Dogs and CatsIn 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.Ā  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.Ā  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.Ā  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).Ā  The normal diarthrodial joint is composed of a joint capsule, synovial fluid, articular cartilage and subchondral bone (1).Ā  The joint in question serves the purpose of providing a smooth surface that is able to distribute the load from one bone to another.Ā  The two opposing bones are covered on the surface by an avascular and aneural articular cartilage.Ā  Articular CartilageThe 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 t




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.Ā  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?Ā  A nutraceutical, as defined by the North American Veterinary Nutraceutical Council, is ā€œa 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-beingā€ (1,2). More specifically, a nutraceutical used in the aspect of joint support can be referred to as a chondroprotectant.Ā  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, Catā€™s Claw, Creatine, and Special milk protein concentrate (3).Ā  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.Ā  The products themselves must be safe; however, they do not have to achieve pre market approval, in contrast to pharmaceuticals or ā€œdrugsā€.Ā  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).Ā  A large variety of products are available to consumers.Ā  Despite the number of products, there is a drastic lack of scientific evidence that promotes any on of these products over the other.Ā  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 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.Ā  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.Ā 

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.Ā  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).Ā 

The normal diarthrodial joint is composed of a joint capsule, synovial fluid, articular cartilage and subchondral bone (1).Ā  The joint in question serves the purpose of providing a smooth surface that is able to distribute the load from one bone to another.Ā  The two opposing bones are covered on the surface by an avascular and aneural articular cartilage.Ā 

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.Ā  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).Ā  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).Ā 

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 cells (6).




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). Ā 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).Ā  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-Ī± (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.Ā  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). Ā 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.Ā  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.Ā  In addition to this, they also found the IL-1, and TNF-Ī± 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.Ā  A multimodal approach is preferred in treating these patients.Ā  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).Ā  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).Ā  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).Ā  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.Ā  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.Ā  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.

Ā 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.Ā  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.Ā  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.Ā  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.Ā  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.Ā  Clinical trials of canine patients all involved the administration of glucosamine in combination with chondroitin.Ā  More information on these studies to follow. A study of the effect of glucosamine on experimental rat osteoarthritis was found.Ā  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).Ā  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).Ā  Plumbā€™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.Ā  The combination of chondroitin with glucosamine was available.Ā  This is likely attributable to the fact that a great deal of products available have the two compounds supplied together.Ā  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.Ā  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.Ā  The study included the use of 42 dogs recruited from private practice.Ā  The dogs were in treatment groups receiving carprofen or Synoquin SA (glucosamine/chondroitin).Ā  The dogs received the manufacturerā€™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.Ā Ā  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).Ā  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.Ā  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.Ā  The evaluation was similar to the above study, however; ground force reaction was also measured.Ā  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 ownersā€™ 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.



Ā 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.Ā  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). Ā 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.Ā  Statistically significant results for improvement of joint swelling and pain were seen in the dogs that received the GLM powder.Ā  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.Ā  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.Ā  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) Catā€™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 Ī³-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. Ā 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.Ā  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-Ī± 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.Ā  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.Ā  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.Ā  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.Ā  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.Ā  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.Ā  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 Hillā€™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 1 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.Ā  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 2 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

Ā 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.Ā  One store advocated the use of raw diets, in particular the brand Spring Meadowā€™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.Ā  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.Ā  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.Ā  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.Ā  Added is the amount of glucosamine/chondroitin for Hillā€™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 3 Claims Supporting Use of Commonly Prescribed/Recommended Veterinary Diets

Hillā€™s j/d

Purina JM

Medical Mobility

Support

Royal Canin Weight

& Osteo

1) Improve dogā€™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





Ā Table 4

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:

Hillā€™s j/d:Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  The first claim provided by Hillā€™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. Ā The dogs were fed either a control food or the prescription diet Hillā€™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 Hillā€™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 Hillā€™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 Hillā€™s j/d diet, they were not statistically significant (76).

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  Hillā€™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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.Ā  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:Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  Purinaā€™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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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 Hillā€™s j/d.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  The omega 6 fatty acid content could not be discussed as these levels were not provided in the diet analysis.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  The levels of vitamin C were lower than that of Hillā€™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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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 Ā¾ cups of feed is advised. With this volume the dog would receive approximately 360 mg of glucosamine.Ā  This is actually more than Hillā€™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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  The final claim was that of palatability. One can extrapolate that if dogs were fed this diet then it must have been palatable.Ā  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:

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  The diet was decreased in caloric content when compared to the other commercial diet companies at 324kcal/cup.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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%.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  Although not advertised, the diet did contain glucosamine.Ā  A feeding guideline of 3 2/3- 4 Ā¼ 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). Ā It does not contain chondroitin.

Royal canine Weight & Osteo:

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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).Ā  It also has less EPA and DHA than the veterinary produced version of Mobility Support.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  Vitamin C and vitamin E levels are consistent with the compared diets.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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:

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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 %Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  Mid range when compared to veterinary diets
Crude Fat (min) 10.0 %Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  lowest of all diets
Crude Fibre (max) 4.0 %Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  lowest of all diets
Moisture (max) 10.0 %Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā 
Calcium (min) 1.1%Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  slightly higher than other diets
Phosphorus (min) .85%Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  slightly higher than other diets
Omega 3 (min)** 0.44 %Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  lowest of all diets
Omega 6 (min)** 3.62 %Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā 
Glucosamine* (min) 600 mg/kgĀ Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  lowest of all diets
Chondroitin Sulphate* (min) 400 mg/kgĀ Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  highest of all diets


Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  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.

Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā  Ā 

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.Ā  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 mgā€ 

250 mgā€ 

Avocado/Soybean Unsaponifiables* (ASU) Powder

90 mgā€”

45 mgā€”


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 mgā€ 

250 mgā€ 

Avocado/Soybean Unsaponifiables* (ASU) Powder

90 mgā€”

45 mgā€”


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 mgā€ 

Avocado/Soybean Unsaponifiables* (ASU) Powder

25 mgā€”



Cosequin DS (http://www.nutramaxlabs.com/Vet/Products): Cosequin is another joint support product that is manufactured by Nutramax laboratories.Ā  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 mgā€ 

Manganese minimum

1 mg**

Ā *Ā  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 mgā€ 

Manganese

5 mg**


Cosequin DS + DSM Each Chewable Tablet Contains:

Glucosamine Hydrochloride*

600 mg

Sodium Chondroitin Sulfate*

300 mgā€ 

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 mgā€ 


Cosequin Regular strength Each Capsule Contains:

Glucosamine Hydrochloride*

250 mg

Sodium Chondroitin Sulfate*

200 mgā€ 

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

Devilā€™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.Ā  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.Ā  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 Zukeā€™s. The product is advertised for the use in dogs and comes in a variety of flavours.Ā  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.Ā  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 5 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





Table 6 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.Ā  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.Ā  More research in the area of dietary supplements is most definitely needed.Ā  Despite the lack of scientific data unequivocally supporting the use of supplements, the numerous subjective reports by owners and clinicians cannot be ignored.Ā  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.



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