Page 938 - Adams and Stashak's Lameness in Horses, 7th Edition

904 Chapter 8

consistency between batches. Although these products There are three commercially available forms of exogenous
are marketed with “guaranteed analysis,” only a small GLN: hydrochloride (HCl), sulfate, and N‐acetyl‐d‐
VetBooks.ir In fact, truth‐in‐labeling problems have been docu- ferences among the available GLN forms. For instance,
glucosamine. Several reports have demonstrated dif-
number have consistently met the label claims.
1, 86,87,118,144
in vitro studies have demonstrated that GLN HCl and
mented, in which ingredients listed on the package were
not present at the claimed concentration or purity. The GLN sulfate appear to inhibit cartilage degeneration
products that have the most inconsistency in concen- more consistently than N‐acteyl‐d‐glucosamine. 45,46,129
trations compared with the label claims tend to be The GLN sulfate form has been postulated to be more
those that state that they are a “complex,” “formula,” efficacious because serum and/or synovial fluid con-
or “blend” of ingredients with no weight of each com- centrations of sulfate increase after GLN sulfate
ponent listed. In general, products should be avoided administration. 59,65,102,130
144
if they do not have information on the quality, make Oral bioavailability of GLN HCl in the horse has been
exaggerated claims, or rely on testimonials. The pres- reported to range from 2.5% to 6.1%, which has been
142
ence of lot numbers and expiration dates generally attributed to a large volume of distribution, poor absorp-
offers some evidence of accuracy in labeling, but does tion from the GI tract, and extensive tissue uptake. 37,82
not guarantee it. 12 Radiolabeling studies have shown that there is good dis-
Many manufacturers with similar products attempt to tribution of GLN to articular cartilage with levels exceed-
128
compete in the market with claims based on research con- ing those in the plasma. However, GLN delivery to the
ducted by another company, even though there is no proof articular cartilage does not necessarily mean that it
of comparable efficacy. Efficacy of these products in the becomes incorporated into articular cartilage. In fact,
horse is hard to prove, even for those products in which after oral dosing in the horse, it has been shown that syn-
research was conducted; a systematic review of five stud- ovial fluid levels of GLN are less than 10% of those in the
ies using nutraceuticals for treating OA in horses stated serum at the same time. This indicates that GLN does
82
that the strength of evidence of efficacy to improve pain or not diffuse readily into the synovial fluid from the plasma,
gait abnormalities was poor. Because these products suggesting that the effects of GLN may lie in its effect on
152
are oral, it is also important to ensure that there is adequate nonarticular tissues. The presence of synovial inflamma-
82
evidence of absorption in the species of interest, or else the tion induced by LPS in carpal joints led to significantly
product is essentially useless. 142 As with many medica- higher synovial GLN concentrations compared with lev-
tions, each particular individual may respond in an adverse els attained in healthy joints following oral administra-
fashion to various ingredients within the product. This tion of GLN HCl, as well as the potential to mitigate
103
could be a reaction to the main ingredients, contaminants, production of inflammatory mediators and elicit repara-
or inert ingredients that are added to help disperse or tive processes to articular cartilage. 83
dilute the product. Unfortunately, to date, little to no Exogenous GLN has been shown in vitro to have no
12
information exists about these products, which is impor- detrimental effects on normal articular cartilage
tant to consider when discussing safety of the product explants or on chondrocyte metabolism after long‐
32
with a horse owner or trainer. Most of the information is term exposure. Many in vitro studies have generally
67
anecdotal and is based on the lack of any major adverse found that GLN induces the production of new cartilage
reactions after treatment. 142 while protecting cartilage that is already present. 6,32–34,71
One should not, and cannot, assume that these prod- GLN stimulates synthesis of proteoglycans (PG) and
ucts will not cause harm. Just because there is a lack of collagen while inhibiting PG degradation. This may
published adverse reactions to a nutraceutical does not occur partly via downregulation of matrix metallopro-
mean that one should extrapolate that the product is teinases (MMP) and aggrecanases. 110,128 The anti‐inflam-
safe. In fact, most manufacturers will not spend the matory effects are likely prostaglandin‐independent and
money to prove safety, so the lack of side effects does may be due to enhanced production of HA by synovio-
not mean that a product is safe. Unfortunately, even cytes. 44,66,82,115,131 In addition, GLN may protect against
142
when safety data is present on a particular product, the some of the negative effects of steroids on cartilage, as
variability in concentrations of the ingredients within demonstrated in an in vitro equine chondrocyte pellet
and between batches can make this data inaccurate. It is model in which GLN had a protective effect against
also worth noting that these products have only been the inhibition of proteoglycan production caused by
around for a few decades, so there is limited data regard- methylprednisolone. 14
ing the effects of long‐term administration. Few equine in vivo studies have used only GLN. Oral
The remainder of this section discusses the known sci- administration of GLN in young horses in training
entific effects of the most common compounds contained showed no significant treatment effect on serum bio-
in equine nutraceuticals that are currently available. marker concentrations of bone and cartilage metabo-
lism. 17,44 High levels of GLN used for in vitro experiments
Glucosamine that were effective have never been achieved in experi-
mental models in humans and animals. Therefore,
153
Glucosamine (GLN) is an aminosaccharide essential extrapolating the results from in vitro studies to the in
for normal growth and repair of articular cartilage. 115,139 vivo setting must be done with caution. The most con-
GLN compounds have been used as nutraceuticals in sistent information that can be extrapolated from
horses due to their possible role in stimulating chondro- human studies is that it appears to take 4–8 weeks
cyte metabolism and reducing inflammation in the before GLN begins to act and that GLN would likely
articular cartilage. give the best results when used preventatively – when
Exogenous GLN can be produced synthetically or minor lesions are present prior to the advancement of
derived from marine exoskeletons or beef carcasses. the disease process. 108