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Equine 20TH ANNIVERSARY Compendium May 1999


“Should I recommend the use

of oral glycosaminoglycans?”

tion Company, Staten Island, NY) lage matrix as well as the hyaluronan
C. Wayne McIlwraith, BVSc, PhD,
and a combination of glycosamines in synovial fluid.1 Another possible
FRCVS, Diplomate ACVS
and other nutrients from the sea mus- mechanism of action might be the
Department of Clinical Sciences sel (Perna canaliculus) (Syno-Flex®; prevention of fibrin thrombi in sy-
Orthopaedic Research Laboratory Vetri-Science Laboratories, Essex novial or subchondral microvascu-
College of Veterinary Medicine and Junction, VT). More recently, a com- lature. The relative absorption of
Biomedical Sciences bination of glucosamine hydrochlo- chondroitin sulfate after oral admin-
Colorado State University ride, chondroitin sulfate, manganese, istration is more controversial, how-
and vitamin C—marketed as a nu- ever. Supportive evidence for some

ractitioners commonly ask traceutical (Cosequin ®; Nutramax absorption of intact chondroitin sul-
questions about the use of oral Laboratories, Baltimore, MD)—has fate has been presented.2
glycosaminoglycans (GAGs), achieved considerable market share. Glucosamine is an amino-mono-
especially in terms of how they work Most other products now on the saccharide that functions in the body
and which should be used. These market consist of either chondroitin as the precursor of the disaccharide
questions cannot be definitively an- sulfate or glucosamine hydrochloride. unit in GAGs. Normally, chondro-
swered, however, because of the Therefore a review of these two in- cytes synthesize glucosamine from
paucity of scientific data on GAG gredients is warranted. glucose. Supplying exogenous glucos-
use in horses. Based on personal ex- Chondroitin sulfate is one of the amine provides the body with addi-
perience with using oral GAG prod- two principal GAGs that compose tional raw materials for matrix produc-
ucts in horses and conversations with articular cartilage and provide com- tion. Glucosamine is the hexosamine
other veterinarians who have used pressive stiffness. Loss of GAG is an present in the disaccharide unit of
GAGs, I feel that they are of benefit. early event of osteoarthritis, and keratan sulfate and the precursor of
Mobility often improves and lame- therefore chondroitin sulfate supple- D-galactosamine (the hexosamine in
ness usually decreases in horses that mentation has a logical rationale. In the disaccharide unit of chondroitin
have received GAGs to treat an arthrit- addition, there is evidence that chon- sulfate). Glucosamine is also a sub-
ic joint. Beyond that observation, droitin sulfate inhibits degradative strate for hyaluronic acid, which con-
it is necessary to delve into the litera- enzymes that break down the carti- sists of repeating disaccharide units
ture to look for answers for clients
regarding absorption and relative
efficacy of GAGs. Consultant’s Corner is a regular feature in the Equine section of Compendium. The
purpose of the column is to provide expert answers to questions that are frequently
How Do Oral asked by practitioners. Readers are encouraged to ask questions that they would like to
Glycosaminoglycan have answered, and experts are welcome to submit questions they would like to ad-
Products Work? dress. The opinions expressed in this column are those of the author and do not neces-
The ingredients of oral GAG prod- sarily reflect the opinions of the publisher. For suggestions involving topics in equine
ucts vary. The initial GAGs available medicine, please contact James N. Moore, DVM, PhD, Department of Large Animal
for horses included a purified chon- Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
droitin sulfate product from bovine 706-542-3325; fax 706-542-8833; email
trachea (Flex-Free®; Vita-Flex Nutri-
Compendium May 1999 20TH ANNIVERSARY Equine

of D-glucuronic acid and N-acetyl glucosamine. Adminis- to try these oral products that are becoming available at an
tration of exogenous glucosamine likely increases matrix even faster rate than are equine oral products. At present,
production of critical components. There is also evidence the only recommendation equine or human practitioners
that glucosamine has a mild antiinflammatory activity, can effectively make is to tell the client to try a product
probably via a free radical scavenging effect. and see if it works.
In addition, there is good evidence for glucosamine ab-
sorption in both dogs and humans. Up to 87% absorption Which Product Should I Choose?
has been reported after oral administration in humans.3 In There is stronger scientific evidence for absorption of
vitro studies have documented enhanced chondrocyte syn- glucosamine than there is for chondroitin sulfate. If I had
thesis of GAGs and collagen by glucosamine.4 It does not to choose between these two agents only, I would recom-
matter whether glucosamine is given as a hydrochloride or mend glucosamine. In addition to chondroitin sulfate and
sulfate salt; both are well absorbed. glucosamine hydrochloride, Cosequin® also contains man-
ganese and vitamin C. Manganese is an essential cofactor
How do Oral Glycosaminoglycans in the synthesis of GAGs from glucosamine, and ascorbic
Compare with Adequan®? acid (vitamin C) is a necessary cofactor in the synthesis of
Adequan® (Luitpold Pharmaceuticals, Shirley, NY) is a collagen. Using the combination product is logical.
polysulfated GAG that is administered intramuscularly or Whether it provides any advantages over glucosamine
intraarticularly. Intramuscular absorption of Adequan® has alone is not known because no comparative work has been
been documented in horses via radioactive labeling done in horses or humans. I believe that cost is a consider-
studies,5 and its efficacy in experimental models of arthritis able issue and find it extremely difficult to tell the owner
in horses has been documented.6 The drug is accepted as whether Cosequin®, for example, is cost effective.
effective. Similar scientific studies, however, have not been
performed with any of the oral GAG products; until they
are, it is impossible to provide owners with an accurate an-
1. Trotter GW: Polysulfated glycosaminoglycan (Adequan™), in McIl-
swer to this question. wraith CW, Trotter GW (eds): Joint Disease in the Horse. Philadel-
Food products are not regulated by the Food and Drug phia, WB Saunders Co, 1996, pp 270–280.
Administration unless they make a specific health claim. 2. Conte A, Volpi N, Palmier AL, et al: Biochemical and pharmacoki-
netic aspects of oral treatment with chondroitin sulfate. Arzneimit-
Consequently, horse owners and equine veterinarians have telforschung 45:918–925, 1995.
become the researchers and horses the research subjects. I 3. Setnikar I, Giacchetti C, Zanolo G: Pharmacokinetics of glucosamine
am unaware of any deleterious side effects associated with in the dog and in man. Arzneim-Forsch Drug Res 36:729–735, 1986.
4. Plana RR, Bizzarri D, Rovati AL: Articular cartilage pharmacology: 1.
oral GAGs or systemically administered Adequan®. In vitro studies on glucosamine and nonsteroidal anti-inflammatory
drugs. Pharmacol Res Commun 10:557–569, 1978.
How Much Can We Extrapolate 5. Burba DJ, Collier M: In vivo kinetic study on uptake and distribu-
tion of intramuscular tritium-labeled polysulfated glycosaminoglycan
from Human Experience? in equine synovial fluid and articular cartilage. Proc 37 AAEP:241–
Some good double-blinded studies investigating oral 242, 1991.
glucosamine in humans have shown it to be beneficial.7,8 6. Yovich J, Trotter GW, McIlwraith CW, et al: Effects of polysulfated
Benefits have also been demonstrated with the oral GAG glycosaminoglycan on chemical and physical defects in equine articu-
lar cartilage. Am J Vet Res 48:1407–1414, 1987.
product from the New Zealand green-lipped mussel. A 7. Noack W, Fischer M, Forster KK, et al: Glucosamine sulfate in os-
well-controlled, double-blinded study that evaluated the teoarthritis of the knee. Osteoarthritis Cartilage 2:51–59, 1994.
latter agent showed a 40% response in human patients 8. Muller-Fabbender H, Bach GL, Hasse W, et al: Glucosamine sulfate
compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis
with osteoarthritis and a 68% response in patients with Cartilage 2:61–69, 1994.
rheumatoid arthritis.9 Because Adequan® is not licensed 9. Gibson RG, Gibson SLM, Conway V, Chappell D. Perna canaliculus
for use in humans, human patients with osteoarthritis tend in the treatment of arthritis. Practitioner 224:955–960, 1980.

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