EVIDENCE-BASED ANSWER
Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance (SOR: A, consistent, good-quality patient-oriented evidence). Some preliminary evidence suggests that glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose intolerance or diabetes (SOR: C, extrapolation from disease-oriented evidence).
Long-term effects are unknown; however, no compelling theoretical or incidental data suggest that long-term results should be different (SOR: C, expert opinion). Further studies are required to clarify the effects of glucosamine on patients with poorly controlled diabetes or glucose intolerance.
CLINICAL COMMENTARY
These products seem to be a safe alternative to NSAIDs
Lisa Brandes, MD
University of Wyoming, Cheyenne
Glucosamine/chondroitin is a popular over-the-counter supplement used by many patients; it appears to be without any serious adverse affects or drug interactions. It does not seem to have much effect on blood sugar for patients with diabetes. It may relieve symptoms for some patients with pain due to osteoarthritis. As such, glucosamine/chondroitin seems to be a safe alternative to nonsteroidal antiinflammatory drugs (NSAIDs) for patients with osteoarthritis.
I would monitor blood sugars more frequently for patients with diabetes given the low numbers in the studies cited above. I would avoid glucosamine/chondroitin during pregnancy and lactation for the younger symptomatic female patient. The cost of this product varies widely, and this can be a factor for patients since they are paying out of pocket.
Evidence summary
Diabetes mellitus and osteoarthritis commonly overlap in patients, many of whom have looked to the nutritional supplement combination of glucosamine and chondroitin sulfates for pain relief. The effectiveness of these supplements in improving patient-oriented outcomes for osteoarthritis is still being evaluated. However, regardless of their effectiveness they remain popular supplements, representing up to a third of the specialized supplement market in the US.1
The mechanism by which glucosamine is hypothesized to affect blood glucose involves the roles of glucosamine and the hexosamine biosynthesis pathway in the regulation of glucose transport. Overexpression of enzymes involved in this pathway have led to high levels of glucose and insulin resistance in animals given huge doses of intravenous glucosamine (100–200 times higher than oral therapeutic doses in humans).2 Studies have specifically investigated the effects of intravenous glucosamine infusion in healthy humans, and it did not show any effect on insulin sensitivity or plasma glucose.
A Cochrane systematic review of 20 randomized controlled trials (RCTs) including 2570 patients in order to evaluate the effectiveness and toxicity of glucosamine in osteoarthritis found that glucosamine was as safe as placebo in terms of adverse reactions. However, they did not comment specifically on diabetic patients or hyperglycemia per se.3
An RCT published in 2004 tested whether glucose intolerance occurs when healthy adults consume normal, recommended dosages of glucosamine sulfate. Nineteen healthy adults were randomized to receive either 1500 mg of glucosamine sulfate or placebo orally each day for 12 weeks. Three-hour oral glucose tolerance tests were performed using 75 g of dextrose. These occurred before the study, at 6 weeks, and at 12 weeks. There were no significant differences between fasting levels of serum insulin or blood glucose.4 Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the tests. Limitations to the study include the small number of subjects, the short duration period, and the fact that the tests were performed before the patient’s daily glucosamine dosing.