Is Glucosamine a Remedy or a Risk?
Osteoarthritis is the most common form of arthritis, affecting 40% of those over 60 years of age. It is the leading cause of physical disabilities, especially among older adult women. This senior population group dominates the United States demographics, and more than 60% of those 45–74 years of age are overweight (BMI > 25), a significant risk factor for diabetes, cardiovascular disease, hypertension, and arthritis-related disabilities.
Many of those diagnosed with osteoarthritis often take glucosamine—self-prescribed or advised by orthopedists—to reduce the symptoms associated with degenerative joint disease and arthralgia. However, the American College of Rheumatology in 2000 indicated that such advice was premature based on the body of scientific evidence.
An emerging issue surrounding the efficacy and utility of glucosamine is that it may contribute to insulin resistance and type 2 diabetes. Insulin resistance is a serious precursor to diabetes that affects 80 million in the U.S. This is a chronic condition typically characterized by dyslipidemia, elevated blood pressure, an android pattern of body fat distribution, and glucose intolerance. The latter clinical presentation may be the vulnerable mechanism through which continuous glucosamine challenge perturbates glucose metabolism and leads to type 2 diabetes.
At the heart of this issue is the potential impact of glucosamine on multiple tissues and organ systems. These multiple involvements amplify the clinical significance of potential health risks associated with obesity, insulin resistance, and type 2 diabetes. In addition, there is evidence that glucosamine can (1) increase oxidative injury and stress to pancreatic β cells (the cells responsible for insulin production) and may contribute to their deterioration and dysfunction, and (2) impair mobilization of glycogen (the storage form of glucose) from the liver, thus contributing to hepatic steatosis or non-alcoholic fatty liver disease (Cooksey et al., 1999).
A recent 90-day study among 22 well-controlled diabetics (mean age 68.6 years) suggested that daily supplementation with 1,500 mg of glucosamine did not significantly alter hemoglobin A1c (HbA1c) concentrations (Scroggie et al., 2003). HbA1c, a clinical indicator of glycemic control among diabetics and the main outcome measure of the study, calls into question the validity of the conclusions that glucosamine does not alter glucose metabolism in those with type 2 diabetes. While this biomarker certainly evaluates serum glucose stability, it is conventional wisdom that HbA1c is neither a sensitive nor a specific indirect indicator for insulin resistance.
Jain and McCormick (2004) pointed out that the well-controlled diabetic population studied by Scroggie et al. actually reflected unique subjects who had the capacity for a compensatory endogenous insulin response to the possible amplification in insulin resistance with oral glucosamine challenge. The authors cautioned that Scroggie et al.’s findings may be applicable only to early or well-controlled diabetics and not to a more representative obese population at risk to hyperglycemia, insulin resistance, type 2 diabetes, and osteoarthritis.
The National Research Council’s report on assessing the safety of dietary supplements (NRC, 2004) stated that there are many unresolved issues surrounding glucosamine, as well as many opportunities for future research. One of the unresolved issues centers on glucosamine intake possibly being associated with insulin resistance and liver disease. From a public health perspective, the report suggests that our knowledge of glucosamine impact on children and during pregnancy and lactation is unknown, and thus may place these vulnerable populations at risk for these conditions. Our understanding of the long-term consequences of glucosamine intake beyond three years, especially among pre diabetics and diabetics, is uncertain, and our comprehension of glucosamine metabolism remains unclear.
While glucosamine may provide some clinical benefits in terms of bone and joint health, there are also emerging risks with respect to obesity, diabetes, and liver disease that are associated with consuming pharmacological doses of this supplement.
by ROGER CLEMENS, Dr. P.H.
Director, Analytical Research & Services
Molecular Pharmacology & Toxicology
USC School of Pharmacy, Los Angeles, Calif
by PETER PRESSMAN, M.D.
Assistant Professor of Clinical Medicine
USC Keck School of Medicine, Los Angeles, Calif.
Cooksey, R.C., Hebert, L.F. Jr., Zhu, J.H., Wofford, P., Garvey, W.T., and McClain, D.A. 1999. Mechanism of hexosamine-induced insulin resistance in transgenic mice over-expressing glutamine:fructose-6-phosphate amidotransferase: Decreased glucose transporter GLUT4 translocation and reversal by treatment with thiazolidinedione. Endocrinology 140: 1151-1157.
Jain, R.K. and McCormick, J.C. 2004. Can glucosamine supplements be applied for all patients with type 2 diabetes with osteoarthritis? Arch. Intern. Med. 164: 807.
NRC. 2004. Prototype monograph on glucosamine In “Dietary Supplements: A Framework for Evaluating Safety.” National Academies, Inst. of Medicine, Natl. Res. Council, Washington, D.C.
Scroggie, D.A., Albright, A., and Harris, M.D. 2003. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. Arch. Intern. Med. 163: 1587-1590.