GLUCOSAMINE AND GLAUCOMA

People with ocular hypertension or glaucoma who take glucosamine supplements for osteoarthritis may be increasing their risk for glaucoma onset or progression, according to the results of a study by a team of researchers at the University of New England College of Osteopathic Medicine, Biddeford, Maine, US.

The retrospective study, reported in a research letter in the July 2013 issue of JAMA Ophthalmology, involved 17 patients with ocular hypertension or open- angle glaucoma who were also taking glucosamine supplements. The study showed that the patients' mean IOP rose significantly after they started talking the supplement and fell when they stopped taking it.

The study included six men and 11 women with a mean age of 76 years. The researchers divided the patients into two groups. One group was composed of 11 patients who had undergone at least one IOP measurement before they began glucosamine supplementation and the other group was composed of six patients who had no IOP measurements before they began taking the supplement. None of the patients had any changes in their medication regimens that might have confounded the study results.

“Once I began to notice a possible correlation between glucosamine and IOP, I began to ask patients if they would mind stopping their supplement and re-measure their IOP on the hunch that it might have a bearing on their problem. As I thought I was seeing a trend, I began to advise all of my patients where I suspected an association between the supplement and elevated IOP that if they chose to stop the glucosamine, I would recheck IOPs for them. After we tripped over 20 such patients, we decided to do a retrospective study in order to see if my hunch stood up to scientific scrutiny,” Edward Hall Jaccoma MD, the study’s principal investigator told EuroTimes in an interview.

In the patients with IOP measurements from before they began the supplementation, IOP increased significantly while they received the supplement (P=.001) and then decreased significantly when they stopped taking the supplement (P=.002). In the group with no IOP measurements prior to glucosamine supplementation IOP also decreased significantly following discontinuation of the supplement (P=.008). In the two cohorts combined, discontinuation of the supplement regimen resulted in a mean decrease in IOP of 2.8mmHg in right eyes, from 19.5 mmHg to 16.7 mmHg, and a mean decrease of 3.0 mmHg in left eyes, from 20.3 mmHg to 17.3 mmHg (P<.001).

“Many questions are raised by glucosamine supplementation-associated IOP changes. This study shows a reversible effect of those changes, which is reassuring. However, the possibility that permanent damage can result from prolonged use of glucosamine supplementation is not eliminated,” the authors concluded.

Role of glycosaminoglycans

The mechanism whereby glucosamine supplementation might cause IOP to rise may relate to its role in the body as precursor for glycosaminoglycans. There is some research which indicates that deposits of glycosaminoglycans in the trabecular meshwork restrict the outflow of aqueous. Alternatively, the release of high amounts of glycosaminoglycans into the aqueous may result in an osmotic effect that draws more water into the anterior chamber which in turn causes swelling and a decrease of pore size in the trabeculum leading ultimately to a resistance in outflow.

It remains to be seen whether pharmacologically modulating the glycosaminoglycan content of the eye could have therapeutic effects, Dr Jaccoma said.

“Glycosaminoglycans are a critical element of the trabecular meshwork and anything that can influence them, may also influence glaucoma - either for the good, in a therapeutic role, or for the bad, as may be the case with glucosamine for some patients,” he added. “Since the study I have continued to monitor patients who are taking glucosamine supplements and find that there is a great deal of variability in how patients' IOP is affected. It appears to follow the steroid link to glaucoma in that some patients appear totally unaffected while others can have significant IOP spikes on this supplement. It does seem to affect patients with known glaucoma more frequently than those who don’t. So far, like steroids, the affect appears to wear off - usually over a month or so, once the supplement is stopped.”

Glucosamine supplements are widely used as a non-prescription treatment for osteoarthritis, a condition that affects around 27 million adults in the US alone. If the findings of this study are borne out by further research, it could have important public health implications. Unlike most of Europe, where glucosamine is approved as a medical drug, glucosamine is regarded by the USA FDA as a dietary supplement and evidence of safety and efficacy is not required as long as it is not advertised as a treatment for a medical condition. There are a range of supplements for which the potential for adverse effects are largely unknown and which may also pose dangers to ocular health, Dr Jaccoma said.

“We already know that many supplements can influence bleeding times and there are others that influence how some medications are absorbed, or can compete with other medications - and there are so many out there in an unregulated way, that great potential exists for untoward side effects. I am not advocating supplements be stopped, but I do think we need to continue to study their effects, including side effects, and to add some greater degrees of regulation to this industry,” he added.