Glucosamine
is currently widely prescribed for the treatment of arthritis. There is however
no pharmacological basis to support its application in therapeutics, and proof
of its efficacy is lacking in the available pharmaco-medical literature.
The commonly
projected claim that glucosamine stimulates the regeneration of worn-out
cartilaginous tissues in the joints is dubious and not supported by any known
scientific evidence. Rather, what has been demonstrated is that glucosamine is
embedded in the structure of polymers which form the essential substance of
cartilaginous tissues, it occurring together with several other molecular
entities.
But between
the discovery of glucosamine in cartilage and its current usage as a drug in
treatment of arthritis there are still many unanswered scientific questions. A few
of these questions are the following: Knowing that glucosamine is a metabolite
of glucose how sure are we about the origin of the former in cartilage tissues?
Is glucosamine converted from glucose and subsequently embedded in cartilage,
or that already embedded glucose in cartilage is modified to glucosamine to
strengthen the tissue? Also, like mucus, is it not likely that cartilage itself
is an excretory product that is deposited on the bony surfaces at the joints,
and that glucosamine is an unwanted metabolite in the human body that through
evolutionary adaptation some mechanism has evolved to trap this molecule in
cartilage? Until these possibilities have been investigated and excluded we
cannot say for certain that glucosamine is a useful metabolite to the human
body, much less to talk of loading the body with it from an exogenous source in
an attempt to treat some disease condition.
The lack
of efficacy of glucosamine as an analgesic has already been established, and
there is currently no evidence for the claim that this substance stimulates the
regeneration of cartilage. This unfavourable analysis is compounded by evidence
accumulating to show that glucosamine is potentially toxic to the body.
Glucosamine
has been known for decades to cause insulin resistance in healthy humans and to
cause a deterioration of diabetic cases. On-going research and a lot of already
published scientific papers have dealt with this matter, only that the topic
has evaded general attention. Maybe it is because glucosamine was not used
widely in the past as now. And therefore with lots and lots of people taking
this substance now the subject matter merits a second look.
The first
inkling of probable toxicity of glucosamine will arise after juxtaposing the
structure of glucosamine against that of streptozotocin.
Streptozotocin
was first isolated from cultures of the microorganism Streptomyces achromogenes. In addition to the fermentation pathway
the compound is currently also synthesized through two other mechanisms, both
using glucosamine as a precursor molecule; either by synthesis from
tetra-O-acetylglucosamine hydrochloride, or by reaction of glucosamine with
N-nitrosomethylcarbamylazide or N-methylisocyanate.
Streptozotocin
is used in biomedical research to induce diabetes mellitus in healthy mammals. A
single intravenous injection of 50 – 200mg/Kg/BW of streptozotocin causes
destruction of pancreatic β-cells
resulting in classic diabetes mellitus in mammals including dogs, rodents and
monkeys.
The extent
to which the methylnitrosocarbamoyl substituent at position C2 of
streptozotocin contributes to its diabetogenic properties is uncertain, but
emerging evidence points to the fact that glucosamine itself induces insulin
resistance and impairs glucose uptake by skeletal muscles. Therefore a possible
mechanism to account for the effect of streptozotocin is that there is first a
cleavage by hydrolysis of the amide bond at position C2 forming free
glucosamine molecules after administration. Considering the fact that the dosage
level of streptozotocin stated above is more than twice the molar equivalent of
the usually recommended adult daily dose for glucosamine, that toxic dose could
result in a toxic response in the acute phase.
But what
if the said substituent is solely responsible for the diabetogenic action of
streptozotocin? Can we not reasonably anticipate the risk of that substituent
getting bonded to glucosamine in vivo by some yet unknown mechanism after
administration?
Time may
prove glucosamine an actual toxin and deficient of any real pharmacological
effect. For the present, however, we can only safely conclude that the usage of
glucosamine is attended with considerable hazards, and for a substance which
has not yet been proven to be effective, the prudent course of action is to
avoid it.
REFERENCE:
Baron AD, Zhu J-S, Zhu J-H, Weldon H, Maianu L, and Garvey T. Glucosamine induces insulin resistance in vivo by affecting GLUT4 translocation in skeletal muscle: Implications for glucose toxicity. J. Clin. Invest. 1995; 96: 2792 – 2801.
