The Science Behind Equine Joint Supplements - Part 2

Read Part 2 of our series on equine joint supplements reviewing the common ingredients found within joint supplements. Find out which ingredients are backed by scientific evidence, and if can they really do what the marketing says!

Chondroitin

Chondroitin sulfate is a vital component of cartilage, providing structural support and elasticity. It belongs to the family of glycosaminoglycans (GAGs), which are essential for maintaining joint health. Chondroitin sulfate helps attract fluid into the cartilage, enhancing its resilience and shock-absorbing properties. It also inhibits enzymes that break down cartilage.

A recent 2022 study by Yamada et al., showed that horses with experimentally-induced arthritis that were fed 1.9g of Chondroitin Sulfate and 4g Glucosamine twice daily 90 days, then once daily for 30 days, showed statistically significant reductions in visual lameness assessment, synovial concentrations of prostaglandin E2, and ultrasound examination findings, compared with the control group.13 A single-author case series published in 2006 showed that horses that were supplemented with Chondroitin and Glucosamine received less joint injections per year than horses not receiving any supplementation.14

Some studies have addressed absorbency concerns,15,16 due to the low oral bioavailability of low-molecular weight chondroitin sulfate of 22-30% in the horse.17  

Despite the low oral bioavailability, results from studies tend to suggest that supplementation of horses with Chondroitin Sulfate does have therapeutic effects on joint health.

Chondroitin supplements should be closely evaluated for molecular weight, as well as active constituents per fed dose to maximise cost value.

Glucosamine

Glucosamine is a naturally occurring amino sugar found within joint cartilage. Glucosamine promotes the synthesis of glycosaminoglycans and proteoglycans within joint cartilage, which increases the “sponginess” of the cartilage within the joint.

Several studies have investigated the effects of glucosamine supplementation on equine joint health. The recent Yamada et al. (2022) study showed that when fed with Chondroitin Sulfate, 4g of Glucosamine HCl daily appeared to have beneficial effect in horses with experimentally-induced arthritis.13

Glucosamine is present in supplements as either Glucosamine HCl or Glucosamine Sulfate, with one study in horses showing higher oral bioavailability of Glucosamine Sulfate (9.4%) compared to Glucosamine Hydrochloride (6.1%),18 with Glucosamine Sulfate also leading to higher concentrations of Glucosamine within joint fluid than Glucosamine HCl when given orally. Another study showed the oral bioavailability of Glucosamine to be around 3-6%.17

The science suggests that supplementation of horses with Glucosamine is likely to be of benefit to joint health. There seems to be evidence that suggests that supplementation with Glucosamine Sulfate is superior to Glucosamine HCl, which horse owners should take into consideration when selecting a supplement for their horse’s joint health.

Above: Studied improvements in clinical findings associated with lameness (e.g. lameness scores) in horses supplemented with nutraceuticals is rare, compared to improvements in biochemistry markers in blood or joint fluid.

MSM

Methylsulfonylmethane (MSM) is a naturally occurring sulphur-based molecule found within green plants, and is a natural derivative of DMSO.19 It has several studied actions, including:

  • Anti-inflammatory (reducing pro-inflammatory pathways in B cells)

  • Antioxidant (reducing production of free radicals)

  • Immune modulation (reducing inflammatory cytokine production)

Some studies have found that supplementation with MSM reduced pain in humans, and preservation of cartilage in mice and rabbits with induced arthritis that were supplemented with MSM.

There are very few studies relating to MSM in horses available. A small study sponsored by a company manufacturing an MSM product showed a reduction in muscle enzymes and muscle “inflammation” measured by thermography (a notoriously fickle and inaccurate measurement tool unless under strict controlled conditions) in horses supplemented with MSM (either 10g or 20g daily) when compared to the control group, however there was no statistical analysis of measured data leading to likely false positives.20

Another small study in a group of showjumping horses given either MSM or MSM + Vitamin C showed a decrease in the reduction of antioxidant enzymes with exercise in comparison to the control group, demonstrating that these products may reduce oxidative damage in supplemented horses.21

While laboratory studies and human studies have studied the relationship between MSM supplementation and arthritic conditions, there are no studies in horses to demonstrate any therapeutic effects. MSM may have antioxidant and anti-inflammatory actions, however there is no data to demonstrate the effectiveness of supplementing horses with MSM for joint health.

Omega-3’s

Omega-3’s are a type of polyunsaturated fatty acid (PUFA) found in both plants and animal sources. Other fatty acids within this family include Omega-6’s and Omega-9’s. These fatty acids or PUFA’s are called ‘essential fatty acids’ because mammals cannot produce them, so they have to be consumed through the diet.

Omega-3’s are present in the long-chain form in plant sources, and as the short-chain, active forms (EPA & DHA) in marine-based sources.

The effects of EPA & DHA supplementation in animals with arthritis has been studied in both canine and equine models. There have been several high-quality studies in dogs, which showed a significant therapeutic effects in dogs with arthritis supplemented with EPA & DHA, including reduction of lameness, improvements in weight bearing and even reductions in prescribed dosages of non-steroidal anti-inflammatory medications!22,23

One study demonstrated that supplementation of arthritic horses with EPA & DHA showed a reduced concentration of inflammatory cells within arthritic joint fluid and decrease in blood inflammatory markers over a 90-day period.24 Other equine studies have demonstrated therapeutic effects of EPA & DHA supplementation in horses with asthma and gastric ulcers.25,26

The strength of canine studies demonstrating clinical effects of EPA & DHA supplementation in arthritis, as well as the demonstrated effects in horses provides scientific evidence to support supplementing horses with marine-based Omega-3’s.

Effects are dose-dependent,25,27 so it is recommended to feed a minimum of 1500mg of DHA daily to replicate the findings in the above studies.

Biota orientalis (Epiitalis®)

The Biota orientalis plant (common name: Oriental Arbor Vitae) has been used in Chinese medicine for many years, and has recently gained fame due to oils extracted from its seeds being used to produce a commercially-available arthritis supplement (Epiitalis®) used in horses, dogs and cats.

There have been a few studies on the effects of supplementation with Biota orientalis extract in veterinary patients. Canine studies have demonstrated improvements in owner and veterinarian-reported lameness scores in dogs supplemented with a combination of Biota orientalis, green-lipped mussel, abalone and shark cartilage,28 as well as improvements in weight bearing on their affected limb/s when supplemented with Biota orientalis extract alone.29

Equine studies have also shown positive effects. A small study which experimentally induced arthritis in 10 horses demonstrated a reduction in the expression of inflammatory enzymes in synovial fluid in horses receiving supplementation, compared to the control group.3

A similar study which experimentally induced arthritis in 16 horses showed a reduction in inflammatory cells and inflammatory enzymes within joint fluid, and a reduction in radiographic scores for signs of osteoarthritis in supplemented vs non-supplemented horses.30 However, this study did not demonstrate any differences between the two groups in MRI findings, clinical lameness findings or macroscopic/microscopic tissue changes of the articular cartilage.30

At present, there are no studies that demonstrate clinical effects (i.e. reduction in lameness) of horses supplemented with Biota orientalis extract, unlike canine studies.

While there are limited studies that demonstrate significant differences in joint fluid analysis in supplemented horses with experimentally-induced arthritis compared to a control group, there is no significant evidence to suggest that these findings carry clinical relevance, with studies showing no difference in observed lameness.

Biota orientalis extract may have immune-modulating and/or anti-inflammatory effects which result in joint fluid changes, however the evidence is not yet demonstrating a clear clinical effect for horses suffering with arthritis.

Above: Seeds from the Oriental Arbor Vitae (Biota orientalis) plant are used to produce Epiitalis®

References

  1. Miller MR, Abshirini M, Wolber FM, Tuterangiwhiu TR, Kruger MC. Greenshell Mussel Products: A Comprehensive Review of Sustainability, Traditional Use, and Efficacy. Sustainability. 2023; 15(5):3912. https://doi.org/10.3390/su15053912

  2. Cayzer J, Hedderley D, Gray S. A randomised, double-blinded, placebo-controlled study on the efficacy of a unique extract of green-lipped mussel (Perna canaliculus) in horses with chronic fetlock lameness attributed to osteoarthritis. Equine Vet J. 2012;44(4):393-398. doi:10.1111/j.2042-3306.2011.00455.x

  3. Pearson W, Orth MW, Lindinger MI. Evaluation of inflammatory responses induced via intra-articular injection of interleukin-1 in horses receiving a dietary nutraceutical and assessment of the clinical effects of long-term nutraceutical administration. Am J Vet Res. 2009;70(7):848-861. doi:10.2460/ajvr.70.7.848

  4. Carmona JU, Argüelles D, Deulofeu R, Martínez-Puig D, Prades M. Effect of the administration of an oral hyaluronan formulation on clinical and biochemical parameters in young horses with osteochondrosis. Vet Comp Orthop Traumatol. 2009;22(6):455-459. doi:10.3415/VCOT-09-01-0001

  5. Bergin BJ, Pierce SW, Bramlage LR, Stromberg A. Oral hyaluronan gel reduces post operative tarsocrural effusion in the yearling Thoroughbred. Equine Vet J. 2006;38(4):375-378. doi:10.2746/042516406777749218

  6. Serra Aguado CI, Ramos-Plá JJ, Soler C, Segarra S, Moratalla V, Redondo JI. Effects of Oral Hyaluronic Acid Administration in Dogs Following Tibial Tuberosity Advancement Surgery for Cranial Cruciate Ligament Injury. Animals (Basel). 2021;11(5):1264. Published 2021 Apr 27. doi:10.3390/ani11051264

  7. Young AE, Finno CJ. Current insights into equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy. Vet J. 2024;305:106129. doi:10.1016/j.tvjl.2024.106129. Available at: https://www.sciencedirect.com/science/article/pii/S1090023324000686.

  8. Fagan MM, Harris P, Adams A, et al. Form of Vitamin E Supplementation Affects Oxidative and Inflammatory Response in Exercising Horses. J Equine Vet Sci. 2020;91:103103. doi:10.1016/j.jevs.2020.103103

  9. University of California Davis - School of Veterinary Medicine. Vitamin E in horses. Available at: https://www.vetmed.ucdavis.edu/labs/finno-laboratory/vitamin-e-horses. Accessed July 11, 2024.

  10. Snow DH, Gash SP, Cornelius J. Oral administration of ascorbic acid to horses. Equine Vet J. 1987;19:520-523. doi:10.1111/j.2042-3306.1987.tb02664.x.

  11. Winther K, Kharazmi A, Hansen ASV, Falk-Rønne J. A randomized placebo-controlled double-blind study on the effect of subspecies of rose hip (Rosa canina) on the immune system, working capacity, and behaviour of horses. In: The Impact of Nutrition on the Health and Welfare of Horses. In press. doi:10.3920/978-90-8686-711-0_052.

  12. Winther K, Kharazmi A, Hansen ASV, Falk-Rønne J. The absorption of natural vitamin C in horses and antioxidative capacity: a randomized, controlled study on trotters during a three-month intervention period. Comp Exerc Physiol. 2012;8(3-4):195-201. doi:10.3920/CEP12006.

  13. Yamada ALM, do Prado Vendruscolo C, Marsiglia MF, et al. Effects of oral treatment with chondroitin sulfate and glucosamine in an experimental model of metacarpophalangeal osteoarthritis in horses. BMC Vet Res. 2022;18(1):215. Published 2022 Jun 9. doi:10.1186/s12917-022-03323-3

  14. Rodgers MR. Effects of oral glucosamine and chondroitin sulfates supplementation on frequency of intra-articular therapy of the horse tarsus. J Equine Vet Sci. 2005;25(2):47-51. doi:10.1016/j.jevs.2004.11.009.

  15. Welch CA, Potter GD, Gibbs PG, Eller EM. Plasma concentration of glucosamine and chondroitin sulfate in horses after an oral dose. J Equine Vet Sci. 2011;31(11-12):659-662. doi:10.1016/j.jevs.2011.08.004.

  16. Montgomery M. Evaluation of the safety and efficacy of the dietary supplement Actistatin(R) on established glucosamine and chondroitin therapy in the horse. J Appl Res Vet Med. 2011;9:101-119.

  17. Du J, White N, Eddington ND. The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. Biopharm Drug Dispos. 2004;25(3):109-116. doi:10.1002/bdd.392

  18. Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S. Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride. Am J Vet Res. 2008;69(6):821-825. doi:10.2460/ajvr.69.6.821.

  19. Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. 2017;9(3):290. Published 2017 Mar 16. doi:10.3390/nu9030290

  20. Riegel RJ. The correlation of training times, thermographic and serum chemistry levels to provide evidence as to the effectiveness of the use of oral Alavis MSM (methylsulfonylmethane) upon the musculature of the racing Standardbred. In: Nutraceutical Alliance Conference Proceedings. Carolwood Corp.; 2001

  21. Marañón G, Muñoz-Escassi B, Manley W, et al. The effect of methyl sulphonyl methane supplementation on biomarkers of oxidative stress in sport horses following jumping exercise. Acta Vet Scand. 2008;50(1):45. Published 2008 Nov 7. doi:10.1186/1751-0147-50-45

  22. Fritsch D, Allen TA, Dodd CE, et al. Dose-titration effects of fish oil in osteoarthritic dogs. J Vet Intern Med. 2010;24(5):1020-1026. doi:10.1111/j.1939-1676.2010.0572.x

  23. Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc. 2010;236(5):535-539. doi:10.2460/javma.236.5.535

  24. Manhart DR, Scott BD, Gibbs PG, et al. Markers of inflammation in arthritic horses fed omega-3 fatty acids. Prof Anim Sci. 2009;25(2):155-160. doi:10.15232/S1080-7446(15)30702-6

  25. Nogradi N, Couetil LL, Messick J, Stochelski MA, Burgess JR. Omega-3 fatty acid supplementation provides an additional benefit to a low-dust diet in the management of horses with chronic lower airway inflammatory disease. J Vet Intern Med. 2015;29(1):299-306. doi:10.1111/jvim.12488

  26. Pagan JD, Hauss AA, Pagan EC, Simons JL, Waldridge BM. Long-chain polyunsaturated fatty acid supplementation increases levels in red blood cells and reduces the prevalence and severity of squamous gastric ulcers in exercised Thoroughbreds. J Am Vet Med Assoc. doi:10.2460/javma.22.06.0275

  27. Pearson G, Goodale M, Wakshlag J, Fortier L. Dose-dependent increase in whole blood omega-3 fatty acid concentration in horses receiving a marine-based fatty-acid supplement. J Equine Vet Sci. 2022;108:103781. doi:10.1016/j.jevs.2021.103781

  28. Whittem T, Richards L, Alexander J, et al. A randomised controlled masked clinical trial of two treatments for osteoarthritis in dogs. Aust Vet J. 2021;99(1-2):31-36. doi:10.1111/avj.13066

  29. Beths T, Munn R, Bauquier S, Mitchell P, Whittem T. A pilot study of 4CYTE™ Epiitalis® Forte, a novel nutraceutical, in the management of naturally occurring osteoarthritis in dogs. Aust Vet J. 2020;98(12):591-595. doi:10.1111/avj.13024

  30. Seabaugh KA, Barrett MF, Rao S, McIlwraith CW, Frisbie DD. Examining the effects of the oral supplement Biota orientalis in the osteochondral fragment-exercise model of osteoarthritis in the horse. Front Vet Sci. 2022;9:858391. doi:10.3389/fvets.2022.858391

If you want to discuss more about arthritis treatment for your horse, please contact the clinic to book an appointment. You can email us at hello@capeequine.com.au or contact us by phone at (08) 9758 9288.

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The Science Behind Equine Joint Supplements - Part 1