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(1) found that glucosamine supplementation was linked to significant, reversible increase in intraocular pressure , but the sample size of the study was small (n=17). The investigators could not exclude the potential for permanent damage.

I wonder:

  • whether the results of (1) have been confirmed by larger studies,
  • if so, whether the increase in intraocular pressure is reversible or permanent,
  • what other long-term side effects of glucosamine taken as a nutritional supplement are.

(1) Murphy RK, Ketzler L, Rice RE, Johnson SM, Doss MS, Jaccoma EH. Oral Glucosamine Supplements as a Possible Ocular Hypertensive Agent. JAMA Ophthalmol. 2013;131(7):955-957. doi:10.1001/jamaophthalmol.2013.227. ; http://archopht.jamanetwork.com/article.aspx?articleid=1690919

2

This long-term study states:

Reginster, J. Y., Deroisy, R., Rovati, L. C., Lee, R. L., & al, e. (2001). Long-term effects of glucosamine sulphate on osteoarthritis progression: A randomised, placebo-controlled clinical trial. The Lancet, 357(9252), 251-6. Retrieved from http://ezproxy.tcu.edu/docview/199008719?accountid=7090

There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups.

And used a secondary outcome (the primary was on the progression of osteoarthritis) was:

Secondary outcome measures were use of rescue medications as recorded in a daily diary; withdrawal rates; occurrence of adverse events; and routine safety laboratory tests, including testing for glucose homoeostasis assessed by fasting glucose concentrations at yearly intervals in all patients still receiving the study treatment.

Side Effects Reported:

Most patients reported at least one adverse event: 93% with placebo and 94% with glucosamine sulphate. There were no substantial differences between groups in frequency or pattern of events.

In about half the cases, these events were referred to the gastrointestinal system (mainly including abdominal pain and disturbed defecaton) and may be also referred to the rescue medication, without differences between groups.

Routine laboratory tests did not show any great abnormalities in system organs or metabolic functions in the two groups during the study. There was no change in glycaemic homoeostasis, with fasting plasma glucose concentrations decreasing slightly in the glucosamine sulphate group (data not shown).

I did not find any more studies of the ocular hypertensive effects of therapeutic glucosamine, but there are a few studies on effects of Glucosamine in laboratory animals that may indicate possible side-effects.

Amer NA, Al- Shawi Nada Naji. POSSIBLE ADVERSE EFFECTS OF ONCE-DAILY ORAL THERAPEUTIC DOSE OF EITHER GLUCOSAMINE SULFATE OR GLUCOSAMINE/CHONDROITIN SULFATE ON BLOOD CELLS COUNT IN RATS. International Research Journal of Pharmacy. 2013;4:24-29.

http://www.irjponline.com/admin/php/uploads/2024_pdf.pdf

Studied the effect of Glucosamine (GS) and Glucosamine (GS)/Chondroitin (CS) on various blood cell counts. They did find a

significant decrease in neutrophil percentage in both drug treatment groups

and a

statistically significant elevation in platelet count

However, this study only used 43 rats over 30 days and there were much more effects when comparing control to GS to GS/CS.

At beyond-therapeutic doses, there may be more nuanced and serious effects:

Mathieu Lafontaine-Lacasse, Geneviève Doré and Frédéric Picard. Hexosamines stimulate apoptosis by altering SIRT1 action and levels in rodent pancreatic β-cells. J Endocrinol January 1, 2011 208 41-49

both NIT-1 and min6 β-cells, genetic knockdown of Sirt1 expression resulted in higher susceptibility to HBP-stimulated apoptosis, whereas overexpression of Sirt1 had the opposite impact.

Many of the studies continue like this; there are few studies linking Glucosamine to any overt and wide-ranging side-effects, but many initmating that there are pathways that could lead to morbidity, especially in beyond therapeutic doses.

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