Transcript Glucosamine

Glucosamine
Shinji Ogita
NUTR 547
7/20/06
Learning Objectives
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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
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Treatment of knee osteoarthritis
Repair and maintenance of joint
cartilage
Aid glycosaminoglycan (GAGs) synthesis
Reduce joint pain
Osteoarthritis
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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
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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
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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.
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Not recognized as a treatment by the Arthritis Foundation
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A nonpermissible supplement for institutions to provide to their
athletes by the NCAA.
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Approved as medical drug in some countries in Europe
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Glucosamine
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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
Glucosamine
3.
Glucosamine sulfate (most common form)
Glucosamine hydrochrolide
Glucosamine hydroiodide
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Commonly used with;
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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
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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
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Aminomonosaccharide synthesized from
glucose.
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Glucose + amino acid
C6H14NO5
Process in the body
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Fructose 6 phsophate+glutamine
Glucosamine 6 phosphate
UPD N-acetyl glucosamine
Mechanism of action
Dosage
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Adults
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500mg per tablets or capsules
1500mg/day
2000mg/day
Children
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Not enough scientific data
MSM (methylsulfonylmethane) and autism
Safety
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The clinical studies have consistently reported that
glucosamine appears safe.
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No allergic reactions have been reported although
glucosamine is derived from shellfish
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Allergy to shellfish may wish to avoid glucosamine.
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May not have acute oral toxicity in animal
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Glucosamine may increase on insulin resistance
Side effects
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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
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May increase risk of side effects
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Diuretics (lasix):
May increase risk of bleeding when taken
with drugs that increase the risk of bleeding
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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
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Lower the effectiveness that lower BG level
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May raise BG level
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Arginine, cocoa, and ephedra
Increased side effects of glucosamine when used with diuretic herbs or
supplements
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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.
Artichoke, celery, corn silk, dandelion, kava, couchgrass, elder flower,
horsetail, yarrow, uva ursi, shepherd’s purse
Increased risk of bleeding
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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 Osteoarthritis
by Clegg, D. O., et al., the New England Journal of
Medicine. Feb23, 2006
Objective
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Efficacy and safety as a treatment for knee pain from osteoarthritis
Study design
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Multicenter, double blind, placebo-, and celecoxib-controlled GAIT
Subjects
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1583 patients with symptomatic knee osteoarthritis(x-rays
documented)
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1500mg of glucosamine, 1200 mg of Chondroitin sulfate, both G & C,
200mg of celecoxib (NSAID: blocks the COX-2 enzyme), or placebo
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24 weeks
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>40 years old, Mean age 59 years old, 64 % women
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Subgroups: Mild n=1229, moderate to severe n=354
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Evaluation at 4, 8, 16, 24 weeks
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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 Osteoarthritis
by Clegg, D. O., et al., the New England Journal of
Medicine. Feb23, 2006
Locations
 16 study centers including University of Utah, etc
Outcome Measures
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20%reduction in pain in the summed score for the WOMAC pain
subscale
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Global assessment of disease status
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Soft tissue swelling, effusion, or both in the index knee
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Medical OutcomeStudy36-item Short-Form General Health
Survery (SF-36): Reflect the health related quality of life.
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Health Assessment questionnaire: reflect physical function
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Acetaminophen use
Glucosamine, Chondroitin Sulfate, and the Two in
Combination for Painful Knee Osteoarthritis
by 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
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Randomized, double blind, placebo-controlled
Subjects
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212 patients w/ mild-moderate osteoarthritis (106 subjects
each)
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1500mg glucosamine sulfate
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3 years
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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
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GS (68subjects)
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Placebo(71subjects)
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No average joint-space narrowing
improvement of symptoms in WOMAC score (34%difference)
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
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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
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It works if you think it
works!!!!!!