Sir
Mark Adams
mis-states the impact of a fairly low-dose intravenous glucosamine lucosamine infusion (0·1 mg kg−1 min−1) on insulin sensitivity in rats; his error is understandable since the abstract of the relevant paper is confusing. Baron and colleagues
reported a significant 17% reduction- not the 50% reduction cited by Adams-in the rate of glucose uptake during this infusion. In a more recent effort to confirm the effect of similar glucosamine doses on insulin sensitivity, Miles and colleagues
describe the effect as “marginal” and do not cite numbers. All the other recent studies of glucosamine infusion that we can trace used much higher doses of glucosamine that achieved plasma glucosamine concentrations of 1–2 mmol/L.
There are no reports that oral glucosamine affects insulin sensitivity in animals or human beings. After oral administration, a substantial portion of absorbed glucosamine is taken up by the liver in first-pass metabolism. There is little reason to believe that the clinical oral administration of glucosamine could replicate the high plasma concentrations achieved in rats with intravenous infusion protocols. If oral glucosamine can have any clinically relevant impact on insulin function, this effect will probably be exerted on the liver.
The thesis that glucosamine (or rather glucosamine-6-phosphate) is the physiological mediator of hyperglycaemia-induced insulin resistance is called into question by recent studies.
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If glucosamine plays any part at all in such resistance, it seems to be a subsidiary one. This conclusion has some real practical importance: if the presumably slight increases in tissue glucosamine-6-phosphate concentrations induced by hyperglycaemia did indeed have a significant pathogenic impact, the safety of glucosamine therapy could be doubted. Although we appreciate the logical basis of Adams’ concern, we believe that it is rooted in an erroneous hypothesis.
There are no published case reports that show that glucosamine precipitates or worsens insulin resistance. Since glucosamine provides relief to arthritis sufferers, without evident side-effects, we do not believe that it is appropriate to exclude its use in people with diabetes or others at risk of insulin resistance.
To date, every double-blind clinical study of glucosamine in arthritis of the knee or hip on MedLine shows that glucosamine relieves pain without evident side-effects. Controlled comparisons of glucosamine with nonsteroidal anti-inflammatory drugs (NSAIDs) show that the relief afforded by glucosamine (described by Adams as “mildly effective”) is at least comparable in magnitude to that achieved with NSAIDs. Furthermore, all these clinical studies note that onset of benefit is delayed, but is durable and persists for several weeks or months after glucosamine is discontinued. There are no reports that efficacy is lost during continuing use of glucosamine. Whether glucosamine is a “slow-acting drug” for osteoarthritis, or whether it can exert long-term favourable effects on cartilage structure, can be decided only in future clinical trials.
One of us (Alan L Russell), a specialist in pain management, has treated upwards of 600 osteoarthritic patients with glucosamine, usually in doses of 3 g daily or higher. He has, indeed, observed some interesting sideeffects: accelerated wound healing, relief from chronic vascular headaches, and symptomatic improvement in inflammatory bowel disease.
It seems evident that osteoarthritis is not the only clinical syndrome in which nutritional support for mucopolysaccharide synthesis can elicit benefits. However, although our experience provides no basis for concern, it will not be surprising if a few contraindications to glucosamine eventually emerge. We certainly concur with Adams that long-term evaluation of glucosamine’s effect on physiological function, in health and disease, should be a high research priority. What a different story it would be if glucosamine hydrochloride had a drug patent!