Glucosamine sulfate and osteoarthritis

Glusomaine:

• osteoarthritis is a disease process that involves damage to, and loss of articular cartilage, and inflammation
• among the components of articular cartilage are glycosaminoglycans, whose structure includes glucosamine, a naturally occurring sulphated aminomonosaccharide sugar
• oral glucosamine is well absorbed from the gut and animal models suggest that circulating glucosamine can localise in cartilage (1); glucosamine supplements are sold as either glucosamine hydrochloride or sulfate - supplements are either derived from shells of shellfish or produced synthetically
• glucosamine appears to well tolerated, at least in the short term (1); however shell-fish derived preparation might cause allergic reactions in susceptible patients

Effectiveness of glucosamine and chondroitin sulfate in osteoarthritis:

• a systematic review by McAlindon et al (2) provides evidence that glucosamine and chondroitin are effective for improving function and relieving pain in patients with osteoarthritis
  • McAlindon et al included studies that were randomised controlled, double blind, trials that compared oral or parenteral glucosamine sulfate, glucosamine hydrochloride, or chondroitin sulfate with placebo for >= 4 weeks with placebo in patients with osteoarthritis of the hip or knee
  • in their conclusions, McAlindon et al stated that the magnitude of the effect of these treatments was unclear because of inconsistencies in study methods and dependence on industry support for study execution
• a systematic review with respect to the use of glucosamine in knee osteoarthritis concluded that "glucosamine has the potential to alleviate knee OA pain" (3)

* there are differing statements regarding the use of glucosamine products and in patients with a history of shell fish allergy:

• The Anaphylaxis Campaign advises people with a history of shellfish allergy who wish to take glucosamine to be cautious, and ask for shellfish-free preparations (4); similarly, the Summary of Product Characteristics (SPC) for the licensed brands of glucosamine (Alateris, Dolenio, Glusartel and YOINTY) all contraindicate use of glucosamine in patients allergic to shellfish (5)
• an NHS review stated (5):
  • "..Glucosamine supplements are either produced synthetically or derived from the shells of shellfish, and should not precipitate allergic reactions in patients sensitive to shellfish. However, some sources contraindicate or recommend cautious use of these products in patients allergic to shellfish...."

Other possible adverse effects outlined (5):

• Glucosamine supplements are widely used for relieving pain and symptoms associated with osteoarthritis. They appear to be well tolerated, with a reported frequency of adverse effects similar to that with placebo
  
  
• Mild gastrointestinal disturbance is the most common adverse effect. Other adverse effects include headache, drowsiness, insomnia and skin reactions.

• Glucosamine does not appear to adversely affect plasma blood glucose in patients without diabetes. However, data relating to its effects in patients with diabetes are lacking.
  • it would be prudent for patients with diabetes to monitor their blood glucose levels more closely if they start to take glucosamine, increase their dose or change the product taken.
    
    
• There are a few case reports of hepatotoxicity related to glucosamine, but the mechanism for this has not been established. If a patient develops increased liver enzymes, consider stopping glucosamine because of the risk of developing more severe liver injury with continued use.
  
  
• Glucosamine should be used with caution in patients with renal impairment or those taking nephrotoxic medications.

Notes:

• NICE suggest that "...use of glucosamine or chondroitin products is not recommended for the treatment of osteoarthritis.." (6)

Reference:

• (1) Drug and Therapeutics Bulletin (2002), 40(11),81-3.
• (2) McAlindon TE, La Valley MP, Gulin JP, et al (2000). Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta- analysis. JAMA, 283, 1469-75
• (3) Ogata T et al. Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis.Clin Rheumatol. 2018 Sep;37(9):2479-2487
• (4) Anaphylaxis Campaign. Shellfish Allergy: The Facts [Internet]. Last updated September 2019 [cited 10/2/20]. Available at www.anaphylaxis.org.uk/wp-content/uploads/2019/09/Shellfish-Sep-2019.pdf.
• (5) NHS Specialist Pharmacy Service (February 2020). Glucosamine – what are the adverse effects?
• (6) NICE (February 2008).Osteoarthritis The care and management of osteoarthritis in adults