Some Glucosamine Products Get Absorbed Poorly
Aug 18, 2005
Janis Kelly
Boston, MA - Osteoarthritis (OA) patients in large numbers began taking glucosamine supplements in the wake of randomized studies showing delayed radiographic progression with glucosamine compared with placebo [1,2]. Subsequent studies cast some doubt on this effect [3], and Dr Beth Anne Biggee (Tufts-New England Medical Center, Boston, MA) and colleagues have now published data showing that the amount of glucosamine in the serum after oral dosing is far below that needed for the chondroprotective mechanisms proposed to account for glucosamine's apparent benefits in OA [4].
My knowledge of the way that chondroitin sulfate is formed has made me highly skeptical that providing glucosamine orally can have any direct function on cartilage.
Senior author Dr Jeremiah E. Silbert (Harvard Medical School and Brigham and Women's Hospital, Boston, MA) tells rheumawire that the data were not a complete surprise.
"My knowledge of the way that chondroitin sulfate is formed has made me highly skeptical that providing glucosamine orally can have any direct function on cartilage. We have previously published two articles showing that mouse chondrocytes in culture and human chondrocytes in culture make their own glucosamine from glucose, with less than 0.2% coming from glucosamine added to the culture medium at the levels we find in serum," says Silbert, who has spent most of his research career studying glucosamine and chondroitin sulfate.
1500 M oral glucosamine, but only 11.5 M gets into serum
In this study 18 OA patients fasted overnight, then took 1500 M of commercial glucosamine sulfate. Silbert's team then used a new high-sensitivity method to measure glucosamine concentrations in serum samples drawn at baseline and every 15 to 30 minutes over three hours and additionally from two subjects at five hours and eight hours. The new method measures serum glucosamine concentrations as low as 0.5 M, much lower than possible in previous studies.
Biggee et al found that none of the subjects had detectable glucosamine levels at baseline. Of the 18 patients, 17 had detectable glucosamine after taking the oral supplement. Serum concentrations began to rise within 30 to 45 minutes after dosing and reached maximums of 1.9 to 11.5 M after 90 to 180 minutes.
"This maximum concentration of 11.5 M has previously been shown to contribute less than 2% of the galactosamine incorporated into chondroitin sulfate in incubations of glucosamine with cultured human chondrocytes and is a much lower concentration than the glucosamine concentrations claimed by other investigators to have various significant in vitro effects," the authors write.
They add, "This raises questions regarding current biologic rationales for glucosamine usage that were based on in vitro effects of glucosamine at much higher concentrations."
The extra amount is changing the miniscule into miniscule-plus-an-additional-miniscule and would still be far below any concentration that has been shown to have an effect on chondrocytes.
"The amounts in the serum are far lower than the amounts used experimentally by others to show effects. It is possible that there could be these other effects, but they need to be demonstrated at the concentrations found in serum to have validity. I doubt that this will be seen, but I keep an open mind," Silbert says.
The data also show an interesting divergence between subjects who had previous exposure to glucosamine and those who were glucosamine-naïve. Those who had previously used glucosamine had significantly faster appearance of glucosamine in the serum after oral ingestion, slower rate of rise to serum maximum levels, and higher serum maximum levels.
Silbert speculates that previous chronic glucosamine usage has modified liver cells in some undefined way, perhaps causing low-level liver damage, so that the uptake of glucosamine is lessened, which then allows more to spill out into the peripheral circulation. "However," he points out, "the extra amount is changing the miniscule into miniscule-plus-an-additional-miniscule and would still be far below any concentration that has been shown to have an effect on chondrocytes."
Sources
Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year randomized, placebo-controlled, double-blind study. Arch Intern Med 2002; 162:2113-2123.
Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 2001; 357:251-256.
Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology 2002; 41:279-284.
Biggee BA, Blinn C, McAlindon TE, et al. Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness. Ann Rheum Dis; DOI:10.1136/ard.2005.03 6368. Available at http://ard.bmjjournals.com.
Janis Kelly
Boston, MA - Osteoarthritis (OA) patients in large numbers began taking glucosamine supplements in the wake of randomized studies showing delayed radiographic progression with glucosamine compared with placebo [1,2]. Subsequent studies cast some doubt on this effect [3], and Dr Beth Anne Biggee (Tufts-New England Medical Center, Boston, MA) and colleagues have now published data showing that the amount of glucosamine in the serum after oral dosing is far below that needed for the chondroprotective mechanisms proposed to account for glucosamine's apparent benefits in OA [4].
My knowledge of the way that chondroitin sulfate is formed has made me highly skeptical that providing glucosamine orally can have any direct function on cartilage.
Senior author Dr Jeremiah E. Silbert (Harvard Medical School and Brigham and Women's Hospital, Boston, MA) tells rheumawire that the data were not a complete surprise.
"My knowledge of the way that chondroitin sulfate is formed has made me highly skeptical that providing glucosamine orally can have any direct function on cartilage. We have previously published two articles showing that mouse chondrocytes in culture and human chondrocytes in culture make their own glucosamine from glucose, with less than 0.2% coming from glucosamine added to the culture medium at the levels we find in serum," says Silbert, who has spent most of his research career studying glucosamine and chondroitin sulfate.
1500 M oral glucosamine, but only 11.5 M gets into serum
In this study 18 OA patients fasted overnight, then took 1500 M of commercial glucosamine sulfate. Silbert's team then used a new high-sensitivity method to measure glucosamine concentrations in serum samples drawn at baseline and every 15 to 30 minutes over three hours and additionally from two subjects at five hours and eight hours. The new method measures serum glucosamine concentrations as low as 0.5 M, much lower than possible in previous studies.
Biggee et al found that none of the subjects had detectable glucosamine levels at baseline. Of the 18 patients, 17 had detectable glucosamine after taking the oral supplement. Serum concentrations began to rise within 30 to 45 minutes after dosing and reached maximums of 1.9 to 11.5 M after 90 to 180 minutes.
"This maximum concentration of 11.5 M has previously been shown to contribute less than 2% of the galactosamine incorporated into chondroitin sulfate in incubations of glucosamine with cultured human chondrocytes and is a much lower concentration than the glucosamine concentrations claimed by other investigators to have various significant in vitro effects," the authors write.
They add, "This raises questions regarding current biologic rationales for glucosamine usage that were based on in vitro effects of glucosamine at much higher concentrations."
The extra amount is changing the miniscule into miniscule-plus-an-additional-miniscule and would still be far below any concentration that has been shown to have an effect on chondrocytes.
"The amounts in the serum are far lower than the amounts used experimentally by others to show effects. It is possible that there could be these other effects, but they need to be demonstrated at the concentrations found in serum to have validity. I doubt that this will be seen, but I keep an open mind," Silbert says.
The data also show an interesting divergence between subjects who had previous exposure to glucosamine and those who were glucosamine-naïve. Those who had previously used glucosamine had significantly faster appearance of glucosamine in the serum after oral ingestion, slower rate of rise to serum maximum levels, and higher serum maximum levels.
Silbert speculates that previous chronic glucosamine usage has modified liver cells in some undefined way, perhaps causing low-level liver damage, so that the uptake of glucosamine is lessened, which then allows more to spill out into the peripheral circulation. "However," he points out, "the extra amount is changing the miniscule into miniscule-plus-an-additional-miniscule and would still be far below any concentration that has been shown to have an effect on chondrocytes."
Sources
Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year randomized, placebo-controlled, double-blind study. Arch Intern Med 2002; 162:2113-2123.
Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 2001; 357:251-256.
Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology 2002; 41:279-284.
Biggee BA, Blinn C, McAlindon TE, et al. Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness. Ann Rheum Dis; DOI:10.1136/ard.2005.03 6368. Available at http://ard.bmjjournals.com.
posted by Ricardo Pocurull at 9:57 AM
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