Equine 20TH ANNIVERSARY Compendium May 1999

CONSULTANT’S CORNER

“Should I recommend the use

of oral glycosaminoglycans?”

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

P
ractitioners commonly ask
questions about the use of oral
glycosaminoglycans (GAGs),
especially in terms of how they work
and which should be used. These
questions cannot be definitively an-
swered, however, because of the
paucity of scientific data on GAG
use in horses. Based on personal ex-
perience with using oral GAG prod-
ucts in horses and conversations with
other veterinarians who have used
GAGs, I feel that they are of benefit.
Mobility often improves and lame-
ness usually decreases in horses that
have received GAGs to treat an arthrit-
ic joint. Beyond that observation,
it is necessary to delve into the litera-
ture to look for answers for clients
regarding absorption and relative
efficacy of GAGs.
How Do Oral
Glycosaminoglycan
Products Work?
The ingredients of oral GAG prod-
ucts vary. The initial GAGs available
for horses included a purified chon-
droitin sulfate product from bovine
trachea (Flex-Free®; Vita-Flex Nutri-
traceutical (Cosequin ®; Nutramax absorption of intact chondroitin sul-
Laboratories, Baltimore, MD)—has fate has been presented.2
achieved considerable market share. Glucosamine is an amino-mono-
Most other products now on the saccharide that functions in the body
market consist of either chondroitin as the precursor of the disaccharide
sulfate or glucosamine hydrochloride. unit in GAGs. Normally, chondro-
Therefore a review of these two in- cytes synthesize glucosamine from
gredients is warranted. glucose. Supplying exogenous glucos-
Chondroitin sulfate is one of the amine provides the body with addi-
two principal GAGs that compose tional raw materials for matrix produc-
articular cartilage and provide com- tion. Glucosamine is the hexosamine
pressive stiffness. Loss of GAG is an present in the disaccharide unit of
early event of osteoarthritis, and keratan sulfate and the precursor of
therefore chondroitin sulfate supple- D-galactosamine (the hexosamine in
mentation has a logical rationale. In the disaccharide unit of chondroitin
addition, there is evidence that chon- sulfate). Glucosamine is also a sub-
droitin sulfate inhibits degradative strate for hyaluronic acid, which con-
enzymes that break down the carti- sists of repeating disaccharide units
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
asked by practitioners. Readers are encouraged to ask questions that they would like to
have answered, and experts are welcome to submit questions they would like to ad-
dress. The opinions expressed in this column are those of the author and do not neces-
sarily reflect the opinions of the publisher. For suggestions involving topics in equine
medicine, please contact James N. Moore, DVM, PhD, Department of Large Animal
Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
706-542-3325; fax 706-542-8833; email jmoore@cvm.vet.uga.edu.
Compendium May 1999 20TH ANNIVERSARY
of D-glucuronic acid and N-acetyl glucosamine. Adminis-
tration of exogenous glucosamine likely increases matrix
production of critical components. There is also evidence
that glucosamine has a mild antiinflammatory activity,
probably via a free radical scavenging effect.
In addition, there is good evidence for glucosamine ab-
sorption in both dogs and humans. Up to 87% absorption
has been reported after oral administration in humans.3 In
vitro studies have documented enhanced chondrocyte syn-
thesis of GAGs and collagen by glucosamine.4 It does not
matter whether glucosamine is given as a hydrochloride or
sulfate salt; both are well absorbed.
How do Oral Glycosaminoglycans
Compare with Adequan®?
Adequan® (Luitpold Pharmaceuticals, Shirley, NY) is a
polysulfated GAG that is administered intramuscularly or
intraarticularly. Intramuscular absorption of Adequan® has
been documented in horses via radioactive labeling
studies,5 and its efficacy in experimental models of arthritis
in horses has been documented.6 The drug is accepted as
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-
swer to this question.
Food products are not regulated by the Food and Drug
Administration unless they make a specific health claim.
Consequently, horse owners and equine veterinarians have
become the researchers and horses the research subjects. I
am unaware of any deleterious side effects associated with
oral GAGs or systemically administered Adequan®.
How Much Can We Extrapolate
from Human Experience?
Some good double-blinded studies investigating oral
glucosamine in humans have shown it to be beneficial.7,8
Benefits have also been demonstrated with the oral GAG
product from the New Zealand green-lipped mussel. A
well-controlled, double-blinded study that evaluated the
latter agent showed a 40% response in human patients
with osteoarthritis and a 68% response in patients with
rheumatoid arthritis.9 Because Adequan® is not licensed
for use in humans, human patients with osteoarthritis tend
Equine
to try these oral products that are becoming available at an
even faster rate than are equine oral products. At present,
the only recommendation equine or human practitioners
can effectively make is to tell the client to try a product
and see if it works.
Which Product Should I Choose?
There is stronger scientific evidence for absorption of
glucosamine than there is for chondroitin sulfate. If I had
to choose between these two agents only, I would recom-
mend glucosamine. In addition to chondroitin sulfate and
glucosamine hydrochloride, Cosequin® also contains man-
ganese and vitamin C. Manganese is an essential cofactor
in the synthesis of GAGs from glucosamine, and ascorbic
acid (vitamin C) is a necessary cofactor in the synthesis of
collagen. Using the combination product is logical.
Whether it provides any advantages over glucosamine
alone is not known because no comparative work has been
done in horses or humans. I believe that cost is a consider-
able issue and find it extremely difficult to tell the owner
whether Cosequin®, for example, is cost effective.
References
1. Trotter GW: Polysulfated glycosaminoglycan (Adequan™), in McIl-
wraith CW, Trotter GW (eds): Joint Disease in the Horse. Philadel-
phia, WB Saunders Co, 1996, pp 270–280.
2. Conte A, Volpi N, Palmier AL, et al: Biochemical and pharmacoki-
netic aspects of oral treatment with chondroitin sulfate. Arzneimit-
telforschung 45:918–925, 1995.
3. Setnikar I, Giacchetti C, Zanolo G: Pharmacokinetics of glucosamine
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.
In vitro studies on glucosamine and nonsteroidal anti-inflammatory
drugs. Pharmacol Res Commun 10:557–569, 1978.
5. Burba DJ, Collier M: In vivo kinetic study on uptake and distribu-
tion of intramuscular tritium-labeled polysulfated glycosaminoglycan
in equine synovial fluid and articular cartilage. Proc 37 AAEP:241–
242, 1991.
6. Yovich J, Trotter GW, McIlwraith CW, et al: Effects of polysulfated
glycosaminoglycan on chemical and physical defects in equine articu-
lar cartilage. Am J Vet Res 48:1407–1414, 1987.
7. Noack W, Fischer M, Forster KK, et al: Glucosamine sulfate in os-
teoarthritis of the knee. Osteoarthritis Cartilage 2:51–59, 1994.
8. Muller-Fabbender H, Bach GL, Hasse W, et al: Glucosamine sulfate
compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis
Cartilage 2:61–69, 1994.
9. Gibson RG, Gibson SLM, Conway V, Chappell D. Perna canaliculus
in the treatment of arthritis. Practitioner 224:955–960, 1980.