Glucosamine sulfate is a dietary supplement that is marketed as a treatment for
osteoarthritis. Recent evidence from animal and cell culture models have suggested that
glucosamine treatment can promote the misfolding of
proteins and the activation of the unfolded protein response (UPR). We investigated whether
glucosamine sulfate supplementation activates the UPR in circulating leukocytes of human subjects. Cultured Thp1 human monocytes were exposed to increasing concentrations of
glucosamine (0, 0.25, 1.0, 4.0 mmol · L(-1)) for 18 h. We observed a dose-dependent increase in intracellular
glucosamine levels as well as the activation of UPR. To test the effect of
glucosamine sulfate supplementation in humans, 14 healthy human subjects took 1500 mg · day(-1)
glucosamine sulfate for 14 days. Metabolic parameters and blood samples were collected before and after supplementation. In humans,
glucosamine sulfate supplementation did not alter metabolic parameters including
lipid levels and
glucose tolerance. Further,
glucosamine sulfate supplementation did not affect intracellular
glucosamine levels or activate the UPR in the leukocytes of human subjects. Our results indicate that in healthy human subjects, the recommended dose of
glucosamine sulfate (1500 mg · day(-1)) for 14 days does not significantly alter intracellular
glucosamine levels and does not activate the UPR in circulating leukocytes.