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dence that use of 1.5 g of glucosamine per day poses a substantial risk in nonpregnant adults. However, given the uncertainty of the minimum glucosamine exposure required for adverse effects on insulin regulation in individuals who are predisposed to glucose regulation problems, glucosamine may present a risk in individuals with, or at risk for, insulin resistance and/or glucose intolerance who ingest it as a dietary supplement for long periods of time. Notably, the available data do not include sufficient studies powered to evaluate safety parameters (e.g., studies measuring relevant blood chemistry parameters following oral administration to animals and humans). These conclusions are therefore based on (1) interpretation of animal and human data indicating that very little intact glucosamine is found in the bloodstream following oral ingestion and thus the secretion problems observed following millimolar blood concentrations in rats would not occur in humans following ingestion,2 and (2) lack of many consistent overt serious effects reported in clinical trials.

However, individuals with shellfish allergy should be cautious about use of glucosamine products, many of which are derived from shellfish.

C. Unresolved Issues and Uncertainties in the Available Data

  • As mentioned above, few animal or human studies have been designed for evaluating the safety of glucosamine intake. In some studies, data concerning adverse effects was obtained by passive reporting, which is not optimal.

  • The impact of increased glucosamine intake during pregnancy and lactation, especially in the context of insulin resistance, is unknown.

  • The impact of increased glucosamine intake in the individual with liver disease, especially in the context of insulin resistance, is unknown.

  • The impact of increased glucosamine intake in children is unknown.

D. Data Gaps and Future Research Recommended

  • The impact of glucosamine on insulin secretion needs further animal and human study at doses relevant to human oral intake.

  • Details of the metabolism of glucosamine are still unclear and, as mentioned above, the conclusions about glucosamine safety are dependent on glucosamine being only minimally bioavailable in the bloodstream.

2  

The highest blood concentration possible from ingestion of 1.5 g of glucosamine per day is 1 mM (assuming 7 liters blood volume), assuming no loss due to lack of absorption or metabolism. However, glucosamine does appear to be extensively metabolized.



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