placebo-control (7 studies) or reference-control (4 studies) clinical trials ranging in duration from 1 to 36 months and including a total of 716 participants (in the glucosamine arms). Many of these trials presented incomplete information about the systematic collection of data on adverse effects, and many did not examine or report clinical laboratory values systematically. Many of the trials relied only on passive reporting. In the placebo-controlled trials, the incidence of adverse effects among the treatment arms was almost identical, while in the NSAID comparison trials, adverse effect rates were higher among those taking NSAIDs (range of 15–35 percent). In general, the adverse effects reported were mild and most often related to gastrointestinal complaints. No data are available on the safety of glucosamine use in pregnant or lactating women or in children.
Classical animal toxicity studies for glucosamine have not been published; however, reviewers citing only unpublished data state that no toxicity was observed with glucosamine administered by oral administration or by gavage. These findings are corroborated by findings of only minimal toxicity with glucosamine administered by other routes of administration. For glucosamine, as for other substances endogenous to the body, LD50 values could not be determined due to the lack of toxicity observed except when supraphysiologic amounts were administered.
Animal studies using infusion of glucosamine in rats at high doses (approaching 1 mM in blood) and in in vitro studies (using the addition of glucosamine to cell-culture media at high concentrations) found that glucosamine inhibited the ability of pancreatic islet cells to increase insulin secretion in response to an increased concentration of glucose. It should be emphasized that these studies were designed to test hypotheses about the intracellular signaling pathways by which glucose exerts its regulatory effects and were not designed to examine the “toxicity” of glucosamine per se.
The pharmacokinetics of glucosamine become important to assessing its risk, as discussed below. Orally ingested glucosamine appears to be rapidly absorbed, but it is largely metabolized before it reaches the bloodstream.
The primary source of glucosamine in the United States is chitin, derived from shellfish (e.g., shrimp, crab). There may be a risk for antigen exposure if the product is incompletely purified. There is no systematic surveillance of contaminants of these products, and only a subset of the manufacturers apparently comply with U.S. Pharmacopeia (USP) standards.
From the evaluation of the available data, there appears to be no evi-