oral glucosamine supplementation
TRANSCRIPT
Oral glucosamine supplementation, efficacy, and effects on gait parameters in aged horses.
Robyn StewartABAS 6100
Overview
• Importance• Joints• Glucosamine• Oral Efficacy• Gait Parameters• Summary• Future Research
Relevance • Lameness from osteoarthritis (USDA,
2000)–60%
• Supplements for joint health (Oke &McIlwraith, 2010) –34%
• Pet supplements contribute over $1 billion annually (Swirsley, 2015)
Supplement Use and Perceptions: A Survey of U.S. Horse Owners
• Swirsley, 2015• 2,087 respondents• 57% believed horse to have joint
issue–90% would treat with supplement
Joint Anatomy
• Synovial joints• Two bone ends
covered by articular cartilage
McIlwraith
American Association of Equine Practitioners Lameness Classification
• Grade 0-5 lameness–0 is sound–5 is minimal weight bearing/inability to
move• Grade 0-4 flexion–0 is sound–4 is non-supporting leg after flexion
Hanson et al., 1997.
Equine Joint Problems• Osteoarthritis–Degeneration of all joint tissue
• Osteochondrosis–Abnormal cartilage ossification
Fortier, Larson, Lipowitz
Treatment of Joint Problems
• Surgical intervention–Bone involvement
• Cause of cartilage breakdown–Intraarticular corticosteroids–Intraarticular hyaluronan–Polysulfated glycosaminoglycans–IRAP
McIlwraith, 2007.
Products average: 2000-8000mg/oz Hartog, 2009.
Glucosamine
• Amino derivative of glucose C6H13NO5• Precursor to glycosaminoglycans –Structural component of cartilage
• Different forms–Hydrochloride, Sulfate, N-acetyl-o
Nordqvist, 2014.
Glucosamine Manufacturing
• Manufactured–purest form, made in lab
• Isolated –Shellfish–Hydrolyzed collagen•Cattle and other refuse
Mechanism of Function• Glucosamine• Glycosaminoglycans• Hyaluronate
• Glycoaminoglycans • Proteoglycans• Aggrecan• Compressive
stiffness to articular cartilage
Oke, 2009.
How Oral Glucosamine Works
• Hydrochloride and sulfate forms–Salts• Dissolution in stomach creates glucosamine
free base • Percent glucosamine free base–50-60% from glucosamine sulfate–80% from glucosamine hydrochloride
Oke, 2009.
Ingested Glucosamine Efficacy
• Glucosamine free base absorbed into bloodstream• Uptake by joint tissues• Bioavailability?
Du et al., 2004• 10 adult horses• Two way crossover• Kept on pasture when not treated• Food withheld 3 hours prior to baseline and 3
hours post treatment
Du Cont’d
• Oral dose via nasogastric tube–Oral Glucosamine Hydrochloride 125mg/kg
• IV dose in jugular vein– IV Glucosamine Hydrochloride 9g
• Sampled:– -10, -5, 10, 15, 20, 30, 45 min– 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10 hrs post
Du Cont’d
• Results:– IV glucosamine declined quickly after
administration• Elimination half life of 0.83 hrs
–Oral glucosamine Cmax 10.6 micrograms/milliliter• Bioavailability 2.5%
Problems
• Cosequin Equine Powder makers• 2 horses in Glucosamine Study• High dose–125mg/kg (for 1000lb/453kg horse:
56,000mg)• No statistics cited
Du et al., 2004.
Laverty et al., 2005
• 8 mares, 6-15 years old• Two-way crossover• Fasted before administration• Glucosamine Hydrochloride –100mg/mL in sterile saline at
20mg/kg of body weight
Laverty et al., 2005
• Blood sampled at 0, 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes post • Synovial fluid sampled– within 48 hours pre treatment–1 hour post treatment from left radiocarpal–12 hours post treatment from right
radiocarpal
Laverty et al., 2005
• Results:–Plasma Glucosamine• IV: elevated 1-2hrs, baseline by 6-12hrs• NG: followed IV pattern but 30-fold less
concentrated–Synovial Fluid Glucosamine• UV light method• IV: 9uM to 15 uM • NG: 0.3uM to 0.7uM
Laverty et al., 2005
• Results:–<10% of glucosamine reached
synovial fluid–Detected in joint fluid when not
detectable in serum• Inefficient use of glucosamine
Bioavailability
• Oral glucosamine bioavailability 2.5% (Du et al., 2004.)
• Typically: 50-250 mg actually absorbed• Minimal evidence of use by joint
tissue (Laverty et al., 2005.)
Effect on Gait Parameters
• Practical application• Glucosamine may–Reduce
inflammation–Reduce stiffness–Improve cartilage
synthesis
Hanson et al., 1997
• 25 horses with degenerative joint disease • 6-20 years old• 3 week washout period prior to study
Hanson cont’d
• American Association of Equine Practitioners Classification–1 grade lameness and 2 grade flexion
minimum–Evaluated at 0, 2, 4, 6 weeks
Hanson Cont’d
• 9g or 12g manufactured supplement–Twice daily for 6 weeks–3g contained• 1800mg glucosamine hydrochloride
Hanson Cont’d
• Results:–Overall lameness grade improved
(p<0.0001)–Baseline – 2 weeks improved
(p=0.001)–2 – 4 weeks improved (p=0.04)–No difference between 4 and 6 weeks
Hanson Cont’d
• Results continued–Flexion score improved baseline – 2
weeks (p=0.0001)–Stride length improved baseline – 2
weeks (p=0.0001)
Problems?
• Supplement contained –Chondroitin sulfate
• Return to work after 2 weeks
Forsyth et al., 2006
• Twenty sound veteran horses–15-35 years old
• 15 treatment, 5 placebo• 4 week washout period• Dose contained:–5000mg 99% pure Glucosamine
Hydrochloride–500mg N-acetyl-D Glucosamine
Forsyth Cont’d
• Filmed 0 and 4 week intervals• Walk and trot on treadmill• Analyzed for–range of motion, stride length,
swing/stance duration
Forsyth Cont’d
• Results:•Range of motion increase in elbow
(p<0.05), stifle (p<0.01), hind fetlock (p<0.01)• Stride length increased at week 8
(p<0.05) and week 12 (p<0.01)• Swing duration at week 12 increased
(p<0.05)
Higler et al., 2014
• 24 horses and ponies–29 years +/- 4–Maintained exercise and
turnout pattern• Treatment received –9000mg/100ml
Glucosamine –dosed at 100ml/500kg bw
Higler Cont’d
• AAEP Lameness grade 0-5 –maximum 1 accepted for study
• Treadmill evaluation–Baseline & 3 months later
• Analyzed–Stride length, carpal flexion, fore
fetlock extension, tarsal range of motion
Higler Cont’d
• Results–Baseline: no difference–No change in: stride length, fetlock
extension, or tarsal range of motion–Control group: improved carpal
flexion
Effect on Gait Parameters
• Sound horses showed no difference between treated and control (Higler et al., 2014.)
• Lame horses showed improvement on glucosamine (Hanson et al., 1997 and Forsyth et al., 2006. )
Conflicting Information• Glucosamine bioavailability is low (2.5%) –May not reach joints–Not absorbed by joint tissuesBUT
• Gait kinematics improve with supplementation–Lame horses improve
(Du et al., 2004; Laverty et al., 2005; Forsyth et al., 2006.)
Glucosamine on Inflammatory Response
• Panicker et al., 2009• Effects of glucosamine
supplementation in mice–Liver and lymphocytes–100mg/kg day
Panicker et al., 2009
• Methods–Papain degraded carpus joints–Circulatory inflammatory cytokines–Mesenteric lymph node activation
Panicker Cont’d
• Results–Glucosamine caused •Elevated cytokine response• Faster cytokine response• Faster return to baseline
• Improved inflammatory response
Summary
• Glucosamine not absorbed well by horse–Huge doses–Not used by joint tissues
• Gait does improve when supplemented–Anti-inflammatory effect
• Treat lame horses as opposed to prevent lameness
Recommendation for future research
• Glucosamine effects on inflammatory response in equine model• Long-term study on whether
glucosamine slows joint deterioration over time • Increasing bioavailability and
absorption of glucosamine
Du, J., N. White, and N. D., Eddington. 2004. The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. Biopharmeceutics & Drug Disposition. 25,3. 109-116. DOI: 10.1002/bdd.392.
Equisearch. 2007. Horse Joint Supplement Guide. http://www.equisearch.com/article/joint-supplements-horses-18712.Forsyth, R. K., C. V. Brigden, and A. J. Northrop. 2006. Double blind investigation of the effects of oral supplementation of combined glucosamine
hydrochloride (GHCL) and chondroitin sulfate (CS) on stride characteristics of veteran horses. Equine Vet. Journal. 38,S36. 622-625. DOI: 10.1111/j. 2042-3306.2006.tb05615.x.Fortier, L. A. Osteoarthritis Versus Arthritis: What’s the Difference? https://www.thehorse.com/articles/30827/osteoarthritis-versus-arthritis-whats-the-
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academics/clinsci/equine-orthopaedic-research-center/orthopaedic-topics/Pages/equine-joints.aspx. (Accessed 27 March 2016.) Nordqvist, C. 2014. What Is Glucosamine? http://www.medicalnewstoday.com/articles/265748.php. (Accessed 27 March 2016.)Oke, S. 2009. Oral Joint Health Supplements: Chemistry, Pharmacology, and Administration Guidelines. Compendium Equine: Continuing Education for
Veterinarians. Vol 4. http://www.vetfolio.com/alternative-medicine/oral-joint-health-supplements-chemistry-pharmacology-and-administration- guidelines. (Accessed 27 March 2016.)Oke, S. and W. McIlwraith. 2010. Review of the Economic Impact of Osteoarthritis and Oral Joint-Health Supplements in Horses. Joints AAEP. Panicker, S. J. Borgia, C. Fheid, K. Mikecz, T. R. Oegema. 2009. Oral glucosamine modulates the response of the liver and lymphocytes of the mesenteric
lymph nodes in a papain-induced model of joint damage and repair. Osteoarthritis and Cartilage. 17, 8, 1014-1021. DOI: http://dx.doi.org/10.1016/ j.joca.2009.01.011.Swirsley, N. 2015. Supplement Use and Perceptions: A Survey of U.S. Horse Owners. M.S. Thesis. Middle Tennessee State University, Murfreesboro, TN.United States Department of Agriculture. 2000. Lameness and laminitis in U.S. Horses. National Animal Health Monitoring System. http://www.aphis.usda.gov/animal_health/nahms/equine/downloads/equine98/Equine98_dr_Lameness.pdf (Accessed 28 March 2016.)
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