Glucosamine

1. Glucosamine Shinji Ogita NUTR 547 7/20/06

2. Learning Objectives • Ideantify Health claims of glucosamine • Explain brief mechanism of osteoarthritis • Explain metabolic pathway of glucosamine • List side effects related to glucosamine • Describe correlation between glucosamine and insulin resistance

3. Claims • Treatment of knee osteoarthritis • Repair and maintenance of joint cartilage • Aid glycosaminoglycan (GAGs) synthesis • Reduce joint pain

4. Osteoarthritis • Degenerative joint disease on cartilage • Pain, swelling, loss of motion of the joint • Loss of normal shape in the long term • Different to rheumatoid arthritis (auto immune disease) • lacks blood vessels, lymphatic vessels, and nerves. • Low level of metabolic activity

5. Mechanism of osteoarthritis

6. osteoarthritis • Location: Fingers, neck, back, knees, hips • Causes: Overweight, aging, joint injury, sports activities, muscle imbalance. • Injury: stimulate degeneration of proteoglycans or suppress proteoglycan synthesis • Hereditary characteristics • approx 1 in 13 or 7.35% or 20 million people in USA Common treatment • Rest, exercise, medications, surgery, CAM

7. History of usage • The first published study from Germany in 69.  • Additional studies in Europe and Asia in the 80’s. • Comparison of glucosamine to NSAID    • In 1997,The Arthritis Cure, by Jason Theodasakis, MD.  • Not recognized as a treatment by the Arthritis Foundation • A nonpermissible supplement for institutions to provide to their athletes by the NCAA. • Approved as medical drug in some countries in Europe

8. Glucosamine • A building block for articular cartilage’s extracellular matrix • Used to produce GAGs and proteoglycans • Synthesized by chondrocytes • 90% absorption by oral administration • 26% available for processing by the body’s tissue

9. Glucosamine • Glucosamine sulfate (most common form) • Glucosamine hydrochrolide • Glucosamine hydroiodide • Commonly used with; • Chondroitin: a glycosaminoglycan derived from articular cartilage • Methylsulfonylmethane (MSM): sulfur compound and high-temperature solvent • Sulfur is an essential nutrient for the stabilization of the connective tissue matrix. • Glucosamie sulfate stimulates the uptake of sulfate ions -> indicater of GAG synthesis by chondrocytes. • Glucosamine also hinders hyaluronidase (tissue damaging enzyme) • Glucosamine sulfate improves the lubricant properties of synovial fluid.

10. Source • Present in meat, fish, poultry. • Synthesized in the body. • Manufactured from chitin, a substance found in shrimp, crab, and lobster shells. • marine exoskeletons. Synthetic glucosamine is also available • Chemically synthesized.

11. Chemical structure of glucosamine • Aminomonosaccharide synthesized from glucose. • Glucose + amino acid • C6H14NO5 Process in the body • Fructose 6 phsophate+glutamine • Glucosamine 6 phosphate • UPD N-acetyl glucosamine

12. Mechanism of action

13. Dosage • Adults • 500mg per tablets or capsules • 1500mg/day • 2000mg/day • Children • Not enough scientific data • MSM (methylsulfonylmethane) and autism

14. Safety • The clinical studies have consistently reported that glucosamine appears safe. • No allergic reactions have been reported although glucosamine is derived from shellfish • Allergy to shellfish may wish to avoid glucosamine. • May not have acute oral toxicity in animal • Glucosamine may increase on insulin resistance

15. Side effects • Upset stomach • Drowsiness • Insomnia • Headache • Skin reactions • Sun sensitivity • Nail toughening • Abdominal pain • Loss of appetite • Nausea and vomiting • Flatulence • Constipation and diarrhea • Palpitation (increased BP and HR) • May increase risk of bleeding (avoid drug increasing risk of bleeding) • Increased amounts of protein in urine: unclear • Increased blood level of creatine phosphokinase due to impurities in some products • May exacerbate asthma: Hx of asthma should avoid until it’s clear • Not recommended during pregnancy or breastfeeding due to lack of scientific evidence.

16. Interactions with Drugs • May increase risk of side effects • Diuretics (lasix): • May increase risk of bleeding when taken with drugs that increase the risk of bleeding • Aspirin, • anticoagulants (blood thinners): warfarin, (coumadin) or heparin, • anti-platelet: clopidogrel, (plavix), • non-steroidal anti-inflammatory: ibuprofen (Motrin, Advil) or naproxen (Naprosyn, Aleve)

17. Interaction with Herbs and Dietary Supplements • Lower the effectiveness that lower BG level • Aloe vera, American ginseng, bilberry, bitter melon, burdock fenugreek, fish oil, gymnema, horse chestnut seed extract, marshmallow, milk thistle, panax ginseng, rosemary, Siberian ginseng, stinging nettle and white horehound. • May raise BG level • Arginine, cocoa, and ephedra • Increased side effects of glucosamine when used with diuretic herbs or supplements • Artichoke, celery, corn silk, dandelion, kava, couchgrass, elder flower, horsetail, yarrow, uva ursi, shepherd’s purse • Increased risk of bleeding • Ginkgo biloba, garlic, alfalfa, ginseng, black cohosh, celery, devil’s claw, EPA, fish oil, ginger, grapefruit juice, green tea, melatonin, omega-3 FA, onion, parsley, vitamin E, wild willow, wild carrot, wild lettuce,

18. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritisby Clegg, D. O., et al., the New England Journal of Medicine. Feb23, 2006 Objective • Efficacy and safety as a treatment for knee pain from osteoarthritis Study design • Multicenter, double blind, placebo-, and celecoxib-controlled GAIT Subjects • 1583 patients with symptomatic knee osteoarthritis(x-rays documented) • 1500mg of glucosamine, 1200 mg of Chondroitin sulfate, both G & C, 200mg of celecoxib (NSAID: blocks the COX-2 enzyme), or placebo • 24 weeks • >40 years old, Mean age 59 years old, 64 % women • Subgroups: Mild n=1229, moderate to severe n=354 • Evaluation at 4, 8, 16, 24 weeks • Up to 4000mg of acetaminophen daily as option, except for the24hours before pain was assessed.

19. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritisby Clegg, D. O., et al., the New England Journal of Medicine. Feb23, 2006 Locations • 16 study centers including University of Utah, etc Outcome Measures • 20%reduction in pain in the summed score for the WOMAC pain subscale • Global assessment of disease status • Soft tissue swelling, effusion, or both in the index knee • Medical OutcomeStudy36-item Short-Form General Health Survery (SF-36): Reflect the health related quality of life. • Health Assessment questionnaire: reflect physical function • Acetaminophen use

20. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritisby Clegg, D. O., et al., the New England Journal of Medicine. Feb23, 2006 Results • Participants used acetaminophen fewer than two 500mg tablets per day • Celecoxib: >20% reduction in 70%, 60% in placebo • No significant differences between placebo and others. • Moderate-to-severe pain with G&C: 79% in G&C, 54% in placebo • Mild pain with G&C: 62.9% in G&C, 61.7% in placebo • 77 reports of mild side effects • Additional 18 months for half of the participants.

21. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled crinical trial by Reginster, J.Y; et al. The Lancet; Jan27,2001;357 Objective • Effect of long-term use of glucosamine to change joint structure and symptoms Study design • Randomized, double blind, placebo-controlled Subjects • 212 patients w/ mild-moderate osteoarthritis (106 subjects each) • 1500mg glucosamine sulfate • 3 years • Consumption of the pure analgesic or a NSAIS, average one of every 6 days

22. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled clinical trial by Reginster, J.Y; et al. The Lancet; Jan27,2001;357 Outcome measures • The Western Ontario and McMaster Universities (WOMAC) osteoarthritis index Results • GS (68subjects) • No average joint-space narrowing • improvement of symptoms in WOMAC score (34%difference) • Placebo(71subjects) • A progressive joint-space narrowing • Symptoms slightly worsened • Most patient reported at least 1 mild adverse event.

23. The effect of oral glucosamine sulfate on insulin sensitivy in human subjects. Yu, JG., Boies, SM., Olefsky, JM. Diabetes Care. Jun2003. Objective • Effect of recommended dosage of glucosamine on insulin resistance. Study design • Not specified Subjects • 7 obese (BMI>27) and 7 lean (BMI<27) • IGT in 3 of obese and 2 of lean subjects • Glucosamine 1500mg for 4weeks

24. The effect of oral glucosamine sulfate on insulin sensitivy in human subjects. Yu, JG., Boies, SM., Olefsky, JM. Diabetes Care. Jun2003. Outcome measures • Comparison of fasting plasma glucose and insulin levels at baseline • 4-h plasma glucose curve • 4-h meal tolerance test (MTT) plasma insulin curve Results • No changes in fasting plasma glucose, insulin, or lipoprotein levels • Recommended dosage of glucosamine was not detrimental to glucose metabolism in humans.

25. conclusion • Glucosamine appears to be more effective than placebo • Glucosamine appears to be more effective in long term use • Combination with chondroitin seems to be more effective. • Short term use of glucosamine may not affect insulin resistance • Used it under supervision of physician

26. Conclusion • It works if you think it works!!!!!!