Glucosamine

Shinji OgitaNUTR 5477/20/06

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

Claims

Treatment of knee osteoarthritis Repair and maintenance of joint

cartilage Aid glycosaminoglycan (GAGs)

synthesis Reduce joint pain

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

Mechanism of osteoarthritis

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

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

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

Glucosamine1. Glucosamine sulfate (most common form)2. Glucosamine hydrochrolide3. 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.

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.

Chemical structure of glucosamine

Aminomonosaccharide synthesized from glucose.

Glucose + amino acid C6H14NO5

Process in the body1. Fructose 6 phsophate+glutamine2. Glucosamine 6 phosphate3. UPD N-acetyl glucosamine

Mechanism of action

Dosage Adults

500mg per tablets or capsules 1500mg/day 2000mg/day

Children Not enough scientific data MSM (methylsulfonylmethane) and

autism

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

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.

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)

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,

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.

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

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.

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

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.

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

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.

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

Conclusion

It works if you think it works!!!!!!