Oral glucosamine supplementation

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-

difference. (Accessed 27 March 2016.) Hanson, R. R., L. R. Smalley, G. K. Huff, S. White, and T. A. Hammad. 1997. Oral Treatment With a Glucosamine-Chondroitin Sulfate Compound for

Degenerative Joint Disease in Horses: 25 Cases. Equine Practice. 19,9. 16-20. Hartog, N. 2009. Joint Supplement Comparison Chart. http://www.horsehealthusa.com/jointsupcompare.html. (Accessed 27 March 2016.)Higler, M. H., H. Brommer, J. J. L’Ami, J. C. de Grauw, M. Nielen, P. R. van Weeren, S. Laverty, A. Barneveld, and W. Back. 2014. The effects of three-month

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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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