Glucosamine and Chondroitin Pharmacokinetics Produce Unexpected Results

Intervention trial studies pharmacokinetic effects of glucosamine HCl and chondroitin sulfate.

By Steve Austin, ND

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Jackson CG, Plaas AH, Sandy JD, et al. The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination. Osteoarthritis Cartilage. 2010;18:297-302.


Intervention trial designed to study pharmacokinetic effects of glucosamine HCl (GHCl) and chondroitin sulfate (CS), either alone or in combination


29 healthy volunteers and 28 patients with “knee pain,” not specified as being radiographically diagnosed as osteoarthritis

Study Medication and Dosage

Single-doses of GHCl (1,500 mg), CS (1,200 mg), or the combination of the 2 (GHCl+CS) were administered to the healthy subjects. For subjects with knee pain, following 3 months of daily supplementation with GHCl (500 mg t.i.d.), CS (400 mg t.i.d.), or GHCl+CS, single doses were administered in amounts of 1,500 mg for GHCl and 1,200 mg for CS. In both groups, pharmacokinetic measurements were made after the administration of the single doses.

Primary Outcome Measures

Circulating levels of glucosamine and CS and the area under the curve (AUC) for each

Key Findings

Somewhat surprisingly, endogenous circulating levels of CS were not increased by CS supplementation regardless of whether it was administered alone or with GHCl. AUC for glucosamine was increased with supplementation of GHCl, but that rise in AUC was significantly blunted when GHCl was combined with CS.

Practice Implications

Much may be said by critics of natural medicine regarding the findings of this new report. However, I don’t believe these findings should affect how we practice. The subjects in the current trial were from the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT). GAIT, unlike most related trials, found essentially no clinical efficacy for CS or for glucosamine (from GHCl). Given that the clinical outcomes of GAIT were different from most published reports, we would not expect an exploration of the pharmacokinetics of the CS and GHCl used by GAIT researchers to point us toward likely therapeutic mechanisms. (It remains unclear why GAIT was unable to duplicate the findings of the positive randomized trials, though it is not completely alone in reporting negative effects. An examination of the GAIT findings shows that subjects given the combined therapies trended toward a better outcome, though none of the findings was clearly definitive.)

The current report finds that CS supplementation interferes with the pharmacokinetics of GHCl and therefore may interfere with the clinical effects of GHCl. This could well be true. Indeed, with or without the inclusion of CS, previous evidence supporting the use of GHCl remains inconsistent and scanty. As such, these new findings mostly serve to cast a further shadow on the use of GHCl, at least when combined with CS. They tell us little about the pharmacokinetics (or therapeutic effect) of the better-studied molecule glucosamine sulfate.

Although the current report does not mention justification for choosing GHCl over glucosamine sulfate, most trials that have used GHCl claim to have done so because it is the most commonly available form found in the market place.

Although the current report does not mention justification for choosing GHCl over glucosamine sulfate, most trials that have used GHCl claim to have done so because it is the most commonly available form found in the market place. Such a justification seems questionable, given that the bulk of scientific evidence supports a different molecule (glucosamine sulfate).

About the Author

Steve Austin, ND, is a naturopathic physician and co-author of the A-Z Guide to Drug-Herb-Vitamin Interactions; Breast Cancer: What You Should Know (But May Not Be Told) About Prevention, Diagnosis, and Treatment and The Natural Pharmacy, now in its second edition. Dr. Austin was the founding Chief Science Officer for the Healthnotes team of writers. He is also former Professor of Nutrition at National College of Naturopathic Medicine, in Portland, Oregon. Previously, Dr. Austin headed the nutrition departments at Bastyr University in Seattle and Western States Chiropractic College in Portland, and has been on the faculties of four of the five naturopathic colleges in North America. He is a contributor to the Textbook of Natural Medicine, and was nutrition editor of the Quarterly Review of Natural Medicine and the Healthnotes Review of Natural Medicine. Dr. Austin is also an international lecturer on topics related to clinical nutrition.