How glucosamine supplements may increase IOP

Glucosamine sulfate supplements widely used as an osteoarthritis treatment appear to increase IOP, researchers say.

The finding raises questions about whether the supplements could play a role in glaucoma, wrote H. Esfandiari of the University of Medical Sciences in Tehran, Iran and colleagues in the journal Eye.

Although the study did not have enough glaucoma patients to evaluate the effects of glucosamine in this population, “it’s a wise practice that ophthalmologists directly ask patients about its usage and carry out medication discontinuation trial[s] in uncontrolled cases,” the researchers wrote.

An amino monosccharide, glucosamine is an essential constituent of cartilage. Though evidence is lacking that it can improve symptoms of osteoarthritis, radiographic studies have shown that it slows joint space width loss. And since it appears to be safe, it is popular as a treatment.

However glucosamine is also abundant in corneal stroma and plays a role in the morphology and function of the trabecular meshwork. One small retrospective study showed an association between glucosamine supplement usage and intraocular pressure.

Other researchers have proposed that glucosamine could restore the extracellular matrix of cartilage or halt additional cartilage degradation. But “it’s no surprise” if changing  glycosaminoglycans could lead to changes in IOP or IOP measurement, the authors wrote.

To investigate this finding further, Esfandiari and colleagues recruited 88 patients with osteoarthritis who attended a rheumatology clinic from July 2014 to March 2015.

They excluded patients with ophthalmological diseases that might affect the biomechanics of the cornea, including any history of ocular surgery, corneal scar and dystrophies.

They randomly assigned 44 patients to take 750 mg glucosamine three times a day for 3 months and 44 patients to take gelatinous capsules filled with sugar as a placebo on the same schedule.

Sixty-seven of the patients were female and 21 were male. Their mean age was 57.7 years. The mean IOP of the glucosamine group was 12.4 mmHg at baseline and 13.0 mm Hg in the placebo group, differences that were not statistically significant (P = 0.329).

At month 1, IOP rose to 12.6 mmHg in the glucosamine group and fell to 12.9 mmHg in the placebo group. The differences were still not statistically significant (P = 0.868).

At month 3, IOP rose to 13.5 mmHg in the glucosamine group and 13.0 mm Hg in the placebo group. At that point, the difference reach statistical significance (P = 0.023).

In the glucosamine group, 34% of patients had an increase of more than 2 mm HG compared to 23.5% of patients in the placebo group.

There were no significant differences between the groups in ocular response analyser Goldmann-correlated IOP, cornea-compensated IOP, corneal hysteresis or corneal resistance factor.

The mean age in those with increases of 2 mm Hg IOP or more was 66 years, compared to 57.7 years in patients who had increases of less than 2 mm Hg.  But the risk of ocular hypertension was not associated with diabetes mellitus, cardiovascular disease and gender were not.

“The results of this study show that while glucosamine causes statistically significant increase in IOP in patients with [osteoarthritis], corneal biomechanics remain unchanged within 3 months of glucosamine supplement therapy,” the authors wrote.

Their results suggest that glucosamine supplementation could be “pathological” in the trabecular meshwork after 3 months, they wrote.

Glycosaminoglycans constitute the ground substance for the outermost part of the trabecular meshwork. Long, flexible chains of glycosaminoglycans interact with each other to form a system of entangled polyanionic macromolecules which act like a gel and contribute to outflow resistance.

Accumulated glycosaminoglycans in the ground substance of the trabecular meshwork outflow pathways, and increased constriction of the trabecular spaces could explain the rises in IOP seen with even short courses of steroid treatment, the authors wrote.

They also noted that a high concentration of glycosaminoglycans in acqueous fluid could draw more water into the anterior chamber through osmosis, inducing swelling and compromising pore sizes in a manner that increases IOP.

In an earlier retrospective study, researchers observed that IOP in patients with poorly controlled glaucoma experienced improvements when they discontinued glucosamine supplements.

Since glycosaminoglycans are also abundant in corneal stroma, a change in their concentration could also lead to errors in IOP measurement with Goldmann applanation tonometers, the authors cautioned.

They acknowledged that their study had a short follow-up period. And they noted that there were too few patients with glaucoma to evaluate the effects of glucosamine in this population.

“[The] clinical implication of this finding in glaucoma patients needs further evaluation in larger studies with longer follow-up and in more relevant population,” they concluded.