RESEARCH - Supplements deliver little glucosamine to serum

[Guest guest]

Supplements deliver little glucosamine to serum

Rheumawire

August 17, 2005

Janis

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].

Senior author Dr 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 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

1. 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.

2. 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.

3. 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.

4. 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.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org