Page 939 - Adams and Stashak's Lameness in Horses, 7th Edition

Principles of Therapy for Lameness 905

The quality of products that contain GLN has been time of onset of clinical improvement was slower with
questioned. One study compared the measured amount oral administration of CS. In a human study, response to
VetBooks.ir ments to levels listed on each product’s label. The greater at the end of the 3 months’ treatment and lasted
of GLN in commercially available equine oral supple-
treatment with oral CS appeared later (at 60 days) was
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study concluded that of the 23 products considered, 9
up to 3 months after the treatment, suggesting that
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(39.1%) contained less GLN than claimed by the manu- response not only may take time but also may last beyond
facturer and 4 (17.4%) contained less than 30% of the the last administration. In a study examining five CS
listed amount. In another study examining five GLN equine products, the actual composition of CS ranged
equine products, the actual composition of GLN varied from 22.5% to 155.7% of the label claim. 118
between 63.6% and 112.2% of the label claim. 118
A large variation in the average recommended daily
maintenance dose of GLN was also found in the product Glucosamine and Chondroitin Sulfate
labels, ranging from 1,800 to 12,000 mg GLN orally per Many equine nutraceuticals contain a combination of
day for an average sized mature horse. This variability GLN and CS. Synergistic effects have been suggested in
should be considered when evaluating the efficacy of a rabbit instability model in which the combination was
these products. 111 more efficacious in delaying cartilage lesions than with
either agent alone. It has also been shown that the
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Chondroitin Sulfate combination improves collagen synthesis in tenocytes
and ligament cells, and it may be important for use in
Chondroitin sulfate (CS) is a long‐chain polysaccha- accessory joint structures. 90
ride that is a normal constituent of aggrecan, and it con- In vitro studies demonstrated no detrimental effects of
stitutes about 80% of all glycosaminoglycans in articular GLN‐CS on cartilage metabolism. In vitro studies have
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cartilage. Within the cartilage it plays an important role also suggested that the combination inhibits proteolytic
in creating osmotic pressure due to its polyanionic activity, potentially via retardation of the molecular and
charge. CS is often derived from shark and bovine carti- biochemical events associated with proinflammatory
lage, and it is rather expensive to synthesize and extract. cytokines, including decreased PGE and NO levels while
2
The species or tissue of origin of CS can determine dif- also preventing GAG degradation. 19,32,113 These studies
ferences in the concentrations, pharmacokinetics profile, suggest that the GLN would be best for potentially inhib-
molecular composition and weight, metabolic fate, and iting OA progression, whereas CS may be best for con-
therapeutic results. 76,163 Therefore, it cannot be assumed trolling symptomatic action of OA.
that all formulations of CS have the same clinical effect. Oral administration of GLN‐CS at doses greater than
CS is orally absorbed in horses; however, the molecu- those recommended in horses is associated with a good
lar weight and source can have a direct influence on its safety profile, with no alterations in hematological or
permeability across the GI tract and its bioavailability. clotting profiles. In an induced synovitis model in
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37, 40 Studies in other species have shown that the GI horses, a GLN‐CS product showed no clinical detectable
mucosa contains a variety of glycosaminoglycan (GAG)‐ benefits. However, there was a significant treatment
158
degrading enzymes, suggesting that CS is not absorbed effect in other synovitis studies, with one showing an
as an intact molecule due to a potential enzymatic anti‐inflammatory effect (lower PGE than controls). 35,150
2
degradation. 88,89 It has been proposed that the liver can In studies of clinical cases treated with this compound,
further modify the final CS molecule prior to reaching the results are mixed but with more showing a generally
circulation. 54,88,89 Reports using radiolabeled CS have favorable response. When an oral mixed supplement
demonstrated that it achieves high concentrations in (GLN, CS, and methylsulfonylmethane [MSM]) was
plasma, articular cartilage, and synovial fluid. 24 administered to veteran horses for 3 months, there was
Exogenous CS has been shown in vitro to have no evidence of any substantial improvement of locomo-
no detrimental effects on normal articular cartilage tor performance in geriatric horses. In other clinical
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explants and to increase the synthesis, or decrease the studies, horses showed improved lameness, flexion, and
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turnover, of proteoglycans/GAGs. In vitro studies have stride length, while navicular horses showed significant
also demonstrated a profound anti‐inflammatory effect improvement in soundness compared with placebo con-
on several tissues involved with joint metabolism. This trols. 2,55,56 GLN‐CS was also evaluated in horses with
may be due in part to exogenous CS‐stimulating HA tarsal OA using gait analysis, demonstrating significant
synthesis in synoviocytes along with improved composi- improvement in the left‐to‐right symmetry of peak verti-
tion (viscosity) of HA. 23,119,125 In addition, anti‐inflam- cal ground reaction forces and impulses, as well as tarsal
matory effects may stem from a downregulation of PGE range of motion and joint energy generation during
2
as well as from NO production. 19,113 CS has also been stance. 21
shown to inhibit MMP and aggrecanase expression/
activity in a dose‐dependent manner. 113,125,135 Hyaluronic Acid
In a synovitis model in horses, CS was found to be mark-
edly less effective than polysulfated glycosaminoglycans Hyaluronic acid (HA) is a natural component of artic-
(PSGAG) administered intramuscularly (Adequan , ular cartilage synthesized by synoviocytes, fibroblasts,
®
Luitpold Pharmaceuticals, Inc., Shirley, NY) for relief of and chondrocytes. It is responsible for the viscoelastic
lameness, stride length, and carpal flexion. In another and lubricating properties of synovial fluid and plays an
160
study using the same model, there was evidence that CS important physiologic role in nutrition of the articular
had therapeutic value irrespective of the route of admin- cartilage. Many oral formulations of HA have become
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istration (oral or intramuscularly) by improving joint available for horses. There are several anecdotal reports
function and reducing lameness scores. However, the about the use of these products in horses, but scientific
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