Team Marketing | 01.12.20
Chondroprotective AgentsDespite the fact that anti-inflammatory drugs, such as phenylbutazone, are widely prescribed for joint disease in horses, these drugs have documented side-effects, including interfering with normal metabolism of the cells that form cartilage. And, to date, there has been little evidence that any pharmacological intervention can stop the progression of arthritis. As a result, a new class of compounds called Chondroprotective Agents is enjoying a great increase in popularity and availability. These agents may have the potential to reverse degeneration of articular cartilage and bone in arthritic joints. "Chondroprotective" was the term given to these compounds because it was widely believed that they could prevent cartilage damage and promote cartilage repair under certain conditions. The proposed mechanisms of chondroprotective agents are: • Reducing of inflammation by interfering with the inflammatory cascade. • Interfering with the action of cartilage-degrading enzymes. • Stimulating cartilage cells to produce new matrix and structural proteins. • Improvement of the quality of synovial fluid to enhance cartilage nutrition and lubrication. • Stimulating the production of free radical scavenging enzymes. • Improving the blood flow to joint tissues by preventing clots in small blood vessel. Of the chondroprotective supplements, the most studied equine pharmaceuticals are the polysulfated glycosaminoglycans. These formulations have proven efficacy in clinical trials and under certain, carefully controlled experimental conditions. These compounds work by the first three mechanisms shown above. There is clear experimental evidence that these compounds are inhibitors of metalloproteinase enzymes and prevent the softening of cartilage that occurs with inflammation. In addition, these compounds and related nutraceuticals probably provide molecular constituents needed to repair articular cartilage. However, there is much question surrounding the use of oral chondroprotective agents, as described below.
GlucosamineGlucosamine is glycosaminoglycan (GAG) precursor, and the substrate for many macromolecules involved in articulation, including Chondroitin and Hyaluronic acid, which are involved in collagen formation. It is produced naturally in the horse's body, however during times of stress and damage to the joint area, it seems the body can not naturally produce enough glucosamine, Additional glucosamine is usually administered orally as a salt (HCL or sulfate). The physical properties of glucosamine make it very easy to absorb when administered orally. It has a very small molecular weight, and is highly water-soluble. Absorption in humans is estimated at about 90%, and studies in dogs have shown absorption of about 87%. However, there have been no absorption studies in herbivores, and whilst it is conceivable that absorption may be different in these animals, there is no evidence to speak of.
ChondroitinChondroitin refers to a class of disaccharides belonging to the GAG group. It is also produced in the horse's body, and functions as a component of proteoglycans, which make up articular cartilage. Chondroitins can be highly variable, with differing molecular weights, chain lengths and location of sulfur groups. Studies in dogs and mice have shown that, for the most part, oral chondroitins are very poorly absorbed (0-8% absorption). It is possible to manufacture chondroitin to include only those with a very small chain length and subsequent low molecular weight, but those chondroitins showing clinical efficacy are those of the longer chain length. So those smaller chain chondroitins may be absorbed, but appear to have little measurable clinical consequence. Also, it is extremely difficult to extract pure chondroitin from raw material, and there is an alarmingly high incidence of contamination with other similar disaccharides.
Methylsulphonylmethane (MSM)There is very little objective information available on MSM. It appears that, possibly like glucosamine and chondroitin, it may act as a sulphur donors, or the sulphur groups may participate in molecular binding to enzymes and other proteins. Reduction of inflammation may occur in some situations but this may be a secondary effect. Methylsulfonylmethane (MSM) and its purported mechanisms of action are thought to be similar to DMSO including: membrane penetration, membrane transport, reduced formation of new connective (scar) tissue, anti-inflammation, free radical scavenging, nerve blockade (analgesia), Claims for efficacy against a broad spectrum of disease states are made but few controlled trials with objective outcomes are available. In the horse, MSM are widely prescribed in the management of joint injury, they probably act through their ability to reduce inflammation by stabilizing cell membranes, preventing the release of lipids that are the source of prostaglandins. In doing so, there is reduced production of secondary chemical messengers that intensify the pain, swelling, and joint effusion.
Amino AcidsThere is no literature on the benefits of amino acids in the growth and repair of joints, cartilage and connective tissue. However it is widely understood that several amino acids are required for this specific task within the body. Proline is an essential amino acid which is required for the configuration of collagens triple helix structure and, inturn, cartilage. Proline is generally deficient in most horse's diets and thus is essential to be included in any diet that requires joint repair. Methionine, which is a sulfur bearing amino acid aids in the synthesis of cartilage and connective tissue as does lysine. Methionine also is a precursor catalyst for the formation of niacinamide and inturn the natural formation of glucosamine.
ResearchDue to the great increase in interest in oral chondroprotective agents, there is a growing body of evidence to their efficacy in the scientific literature. In one of the few studies conducted on horses, one group of researchers investigated the effect of an oral (glucosamine-chondroitin composite) on 25 arthritic horses. They found that the horses had improved lameness grade, flexion tests and stride length after being supplemented for 2 weeks. And a further improvement in lameness grade was seen by 4 weeks1. An investigation of the same product in dogs also showed significant effect2. In this clinical report, 3/4 of the canine patients receiving the product showed clinical improvement, reduced dependency on anti-inflammatory drugs, increased mobility, and increase in muscle mass, with no identifiable adverse events. It was concluded that chondroprotective agents were effective in reducing trauma-induced osteoarthritis, iatrogenic cushings disease, and hip dysplasia. The American Journal of Veterinary Research also reported significant improvement in dogs treated with a glucosamine-chondroitin composite3 In a comprehensive analysis of a number of previous studies of glucosamine in arthritic humans published in 1998, it was found that there was evidence that glucosamine may provide pain relief, reduce tenderness, and improve mobility. However, it was also found that there were many experimental flaws in many of the studies, including small sample size, uncontrolled studies and poor experimental design, and there were no long-term efficacy and safety trials. This is a major problem to conduct large trials on equines as research of this type is quite expensive and resources generally are not available for this type of research. However, there are good quality studies out there if you go looking for them; a study presented at the 1999 Equine Nutrition and Physiology Society conference conducted an explant study utilizing varying concentrations of glucosamine in the presence of pro-inflammatory agents. The authors found a significant inhibition of Pro- inflammatories production. This study is one of the first published that has applied precise and objective scientific tools to the investigation of glucosamine as a chondroprotective agents.
Does this mean I should use chondroprotective agents on my horse?There can be a great deal of confusion when trying to understand scientific literature on natural supplements. One of the primary reasons is that research is often conducted under the auspices of a confidentiality agreement. Therefore, if the research results are not favourable, they are often not published. This creates a bias in the literature, as the positive research is usually more accessible than the not-so-positive research. In addition, most published studies use pharmaceutical-grade products, whereas most products available for sale to consumers contain lower grade material, which may or may not produce the same results. Unfortunately, the quality and grade of products in the stores is usually not specified. In addition, labels can be very confusing for consumers. Due to the regulatory framework afforded to natural supplements, which is rapidly changing, no claims are permitted on labels, so often consumers do not know exactly what the product can be used for, or what it should not be used for. Purity is also a major concern. A recent study investigating 6 products found more than 70% of products analysed for glucosamine or chondroitin did not meet their label specifications. This highlights the need for consumers to stick with suppliers who back up their products with research and information. Another source of confusion is the natural-sourced chondroprotective agents. Common reputed sources include shark cartilage, chicken cartilage, bovine cartilage, sea cucumber, perna mussel, and gelatin. When chondroprotective agents are derived from raw sources, the consumer has no guarantee of quality or milligram strength. And it is very difficult to research these natural sources due to wide variability in products. Though it is rumoured that GAGs are more digestible in these forms, it is actually not the case. For example, chondroitin sulfate is often bound to aggrecan in these natural sources, and is even more poorly available than the isolated substance. Also, many of these products (eg. Algae, gelatin) contain no glucosamine whatsoever. Remember, GAGs can be derived only from animal tissue. The key to maximizing the benefit that glucosamine and other chondroprotective agents provide your horse is to be very selective about your source of the product. Chose only those suppliers who have a credible reputation. Oral chondroprotective agents are enjoying great popularity in the human health and veterinary field, and there is an increasing amount of research available on some of these products. They have a great potential to alter the progression of joint disease in your horse, provided the product you are feeding is, in fact, the one you think you have paid for! When purchasing a product for joint relief for your horse it is wise to buy a product that has a combination of quality GAG precursors such as Glucosamine, quality amino acids including Proline as well as specific minerals such as copper, zinc and manganese which are preferably chelated to improve digestion, as well as an antioxidants (Vitamin C) such as HYGAIN FLEXION.
References and FurtherReading Equine Practice, 19(9):16-22, 1997 Canine Practice, 21(2):7-11, 1996 American Journal of Veterinary Research, 60(12):1552-1557, 1999 Annals of Pharmacotherapy, 32:580-587, 1998 Proceedings Equine Nutrition and Physiology Society (1999): 74-75 Natural Medicine Review: Chondroprotective Agents Explained, Nutraceutical Alliance (2001)
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