Glucosamine
History
Glucosamine was first prepared in 1876 from the hydrolysis of chitin. The first reported use of glucosamine was via IV or IM injections for the treatment of osteoarthritis in 1969 by a group of German physicians. Since it was only available in IV form, it was used in veterinary medicine. It wasn’t until the late 1980’s that European studies and trials were done on pharmacokinetics properties making glucosamine available in tablet form. Funded by an Italian pharmaceutical company, glucosamine proved to be an effective agent in reducing pain and increasing mobility in arthritis patients. Although widely used in Europe, Dr. Jason Theodosakis’s book The Arthritis Cure helped glucosamine gain popularity in the US in the late 1990s.
Medicinal and Non Medicinal Use
Glucosamine is used orally for osteoarthritis, rheumatoid arthritis, glaucoma, TMJ arthritis, joint pain, back pain, and weight loss.
It may also allow for reduced doses of NSAIDs.
Major Components hypothesized to be the active ingredients
Commonly sold as the salt Glucosamine Hydrochloride; glucosamine (C6H13O5) is a naturally produced amino monosaccharide. It is found in humans, and in many crustaceans and arthropods. It is a key substrate in the biosynthesis of macromolecules that for articular cartilage.
Theorized Mechanism of Action
In humans with osteoarthritis, glucosamine plus arthroscopic debridement resulted in decreased expression of MMP-3 and the ratio of MMP-3 to TIMP-1, and increased expression of TIMP-1. Glucosamine and chondroitin-treated articular chondrocytes resulted in 31 altered proteins. The chaperone GRP78 was increased by glucosamine alone and in combination with chondroitin. This is suggested to be a mechanism for the anti-inflammatory effects of glucosamine. Superoxide dismutase-2 was significantly decreased by glucosamine and chondroitin, and this was also possibly involved in their anti-inflammatory effects. In chondrocytes, glucosamine increased the expression of the cartilage-specific genes aggrecan and collagen type II, reducing collagen type I mRNA. The IL-1beta-induced shift in gene expression was also antagonized. These changes resulted in decreased cellular proliferation and development of chondrocyte-specific cell morphology.
Clinical Issues
DDI-
Acetaminophen and glucosamine may decrease the amount of pain control, but this mechanism is unknown.
Antidiabetic drugs- It is suggested to glucosamine may increase insulin resistance or decrease. It is also suggested that glucosamine worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or hemoglobin A1C
Warfarin- will increase the anticoagulant effects causing an increased risk of bleeding or bruising
Antidepressants- has shown to elevate depressed mood while taking glucosamine
Caffeine, alcohol and nicotine may affect how glucosamine works but this has not been studied
Suggested Dosing
Dosing
For osteoarthritis and lumbar pain (general), 1000-2000 mg daily (500mg TID)
Knee osteoarthritis, bone density and rheumatoid arthritis- between 300-500mg
Glucosamine, glucosamine sulfate, or glucosamine hydrochloride in the form of tablets, capsules, or crystalline powder
Doses of 400mg are available IV, IM, Intra-articular.
Adverse effects/overdose
Reports of photosensitization, reversible systolic hypertension, proteinuria, and asymptomatic, reversible elevation of creatine phosphokinase levels have been cited with glucosamine supplementation.
Since glucosamine is derived from shells of shrimp, crab, and other shellfish, individuals with shellfish allergy or iodine hypersensitivity should avoid glucosamine
There have been other instances of digestive problems associated with glucosamine, as well as increased risk for cataract formation in bovine model. Evidence of any cataracts in humans is lacking
Use in special populations:
Not tested in pregnancy and children under 18
Efficacy vs. Safety
Evidence suggests it can be effective for providing subjective improvement in knee pain (glucosamine hydrochloride 2000 mg daily)
Conflicting evidence about effectiveness for general osteoarthritis -
Evidence supporting glucosamine primarily involves a specific combination product, which contains glucosamine hydrochloride, chondroitin sulfate, and manganese ascorbate. Some evidence has suggested that this combination can improve both objective and subjective measures of pain in patients with osteoarthritis of the knee. However, this combination might be more effective in patients with mild-to-moderate osteoarthritis compared to patients with severe osteoarthritis; in another trial, taking glucosamine hydrochloride in combination with chondroitin for 6 months did not significantly decrease pain or physical function in older adults with osteoarthritis; additional evidence suggested that taking glucosamine hydrochloride alone might reduce some subjective assessments of pain, but does not seem to reduce objective measures on the WOMAC (Western Ontario and McMaster Universities Arthritis Index) pain scale
Research has shown that a specific glucosamine hydrochloride product (Rohto Pharmaceutical Co.) 1500 mg daily significantly reduced rheumatoid arthritis pain compared to placebo after 12 weeks of treatment; however, patients did not exhibit improvement in swollen joints or inflammation.
Glucosamine is shown to be possibly safe when used appropriately for short-term use
There is insufficient information about safety of long-term use; use in pregnancy and lactation should be avoided because of insufficient reliable information available.
Information about the standard of various preparations Available in two different tablet forms; either glucosamine hydrochloride or glucosamine sulfate. Oral crystalline glucosamine is also available. These can or cannot be mixed with an additional joint supplement called chondroitin. Intramuscular and Intravenous injections of glucosamine sulfate are also available, but are usually reserved to animals.
Cost
From Vitamin Shoppe: depending on strength, price ranges from about $22 to $32 for 120 tablets (40 day supply)
Compare to prescription Celebrex: without insurance, costs about $400 for a 1-month supply; $30-50 with insurance
Prevalence of Use
In most European countries, glucosamine is recognized as a medical drug. In the late 1990’s over one billion capsules were sold in the US. Between the years 2003-2009; US sales of glucosamine increased by 3% per year; whereas the worldwide increase was 10% per year. Regardless, in a survey done in the early 2000’s, glucosamine was ranked as one of the top supplements taken by Adults in the US.
Evidence Based Medicine
A meta-analysis that included two randomized controlled glucosamine trials and four chondroitin trials was conducted to evaluate the structural efficacies of glucosamine and chondroitin sulfate in patients with knee osteoarthritis. Glucosamine sulfate was dosed at 1,500mg once daily in both trials. At three years, a statistically significant small-to-moderate protective effect on joint space narrowing (JSN) was found.
A double-blind, randomized, placebo controlled trial of glucosamine in 80 patients with osteoarthritis was conducted. Patients received either oral glucosamine sulfate or placebo for 30 days. Scores for articular pain, joint tenderness, swelling, and restriction of movements were reported to be significantly lower in the treatment group at 14, 21, and 30 days. At the conclusion of the study, physicians rated improvements in 29 of 40 patients in the treatment group as excellent or good overall, compared with 17 of 40 for the placebo group.
Comparable precription or non prescription drugs
When compared with ibuprofen, studies show that glucosamine is better tolerated (less side effects) resulting in less dropouts than those taking ibuprofen for osteoarthritis pain. In terms of effectiveness, this study proved that glucosamine is just as effective as ibuprofen. Another study showed that once daily dosage of 1500mg glucosamine is more effective at treating knee osteoarthritis than acetaminophen and placebo. The glucosamine arthritis intervention trial resulted in showing
In the GAIT trial, participants taking celecoxib, experienced statistically significant pain relief versus placebo— Overall, the findings showed for a subset of participants with moderate-to-severe pain, glucosamine combined with chondroitin sulfate provided statistically significant pain relief compared with placebo. According to the researchers, because of the small size of this subgroup these findings should be considered preliminary and need to be confirmed in further studies.
Any regulatory issues
Classified as a dietary supplement in the United States; not approved by the FDA
Health stores or similar establishment employee; in particular find out the claims of what this product could be used for, safety issues and knowledge level for the employee about this product
I spoke with an employee at Vitamin Shoppe who told me that glucosamine is primarily used for joint pain. He mentioned it shouldn’t be taken if I have a shellfish allergy. He also mentioned the tablets should be taken with meals.
A pharmacist; in particular their knowledge level about the clinical issues as it related to the product and how comfortable she/he is to discuss this product with a patient
The pharmacist (Kenneth Newman) was very comfortable discussing this particular drug. He was aware of current studies and side effects of the medication. He had vast knowledge about glucosamine history in the US and stated that he would recommend this supplement to those experiencing arthritis in weight bearing joints such as the hip or knee. He is extremely comfortable talking about this with patients as it is something that many of them come in to ask about.
References:
http://www.naturalstandard.com.proxy.lib.umich.edu/databases/herbssupplements/glucosamine.asp?#bottomline
http://naturaldatabase.therapeuticresearch.com.proxy.lib.umich.edu/nd/Search.aspx?cs=&s=ND&pt=&sh=1
http://www.nutraingredients-usa.com/Markets/US-glucosamine-grows-slow-lags-global-sales
http://nccam.nih.gov/research/results/gait/qa.htm#results
Kenneth Newman, BS Pharmacy
