Ingredients that support joint health in horses
Joint health issues are a frequent complaint of multiple species, including humans, dogs, and horses. Several common factors, such as aging, overwork, inflammatory responses, and genetics can lead to joint changes that affect cartilage, tendons, and surrounding soft tissues. Maintaining joint structure and function is very important for patient comfort. This paper describes some of the research on ASU – one of the key ingredients in Cosequin® ASU that can be beneficial for both joint and tendon health – which has been investigated with both in vivo and in vitro studies.
Glucosamine (GLU) and Chondroitin Sulfate (CS)
Glucosamine (GLU) and chondroitin sulfate (CS) are compounds frequently used for maintaining cartilage and connective tissue health. GLU is a building block for glycosaminoglycans (GAGs) and the stimulation of chondrocytes. CS, the most abundant GAG in joint cartilage, inhibits cartilage degradative enzymes. Research has demonstrated that GLU+CS are synergistic chondrosupportive agents superior to either ingredient alone (Lipiello, 2000).
The beneficial effects of GLU+CS on cartilage health are well recognized; however, these compounds may also support tendon health. Lippiello et al.’s (2007) in vitro study showed that the combination of GLU+CS could be beneficial to tendon and ligament cells. “Though joint maintenance in horses is often concentrated on cartilage, it’s also critical to support the joints’ surrounding soft tissues,” explains Eric Shreves, DVM, a professional services veterinarian with Nutramax Laboratories. “Supporting the health of tendons and other connective tissue structures is key in helping to support joint longevity.”
Avocado/Soybean Unsaponifiables (ASU)
Avocado/Soybean Unsaponifiables (ASU) is a well-acknowledged ingredient that can be found in dog, cat and human supplements. The equine community is mostly unacquainted with ASU’s benefits for horse and are therefore unaware of its potential to help horses to feel their best. ASU has been examined through in vivo studies in several animal species, such as dogs, rats and horses, and in vitro studies using various types of cells, including equine chrondrocytes, synovial cells and tenocytes.
ASU significantly reduced tibial plateau lesions, decreased changes to the subchondral bone, and reduced synovial cellular infiltration in dogs with transected cruciate ligaments compared to a placebo-control group (Boileau, 2009). Rats with induced joint issues supplemented with ASU had less synovial, cartilage, and degenerative subchondral changes and reduced expression of specific inflammatory mediators (Al-Afify, 2018). Au et al. (2007), in a cell study using chrondrocytes as well as monocytes and macrophages, found that ASU can lower multiple inflammatory mediators such as TNF-α, IL-1β, COX-2, iNOS, and PGE2.
Combining the Compounds GLU+CS+ASU
Several cell culture studies show that ASU is synergistic with GLU and CS. Grzanna (2010) demonstrated through synovial cells that the combination of CS+ASU was more effective at inhibiting the expression of several inflammatory mediators, including as TNF-α, IL-1β, and PGE2, than either compound alone, supporting the use of both in joint health. GLU+CS+ASU incubated in equine cartilage cells lowered PGE2 as well as the degradative enzyme MMP-9 (Frondoza, 2009). Au (2007) studied the effects of a combination including FCHG49® GLU, TRH122® CS, and NMX1000® ASU on equine chondrocytes or osteoblasts. This study demonstrated decreased expression of cyclooxygenase-2, which regulates the production of the inflammatory mediator PGE2.
Tendons play a vital role in the maintenance of joint health. Therefore, several in vitro studies assessed the effects of GLU+CS+ASU on equine tendon-derived cells. Au et al. (2008) demonstrated the beneficial effects of FCHG49® GLU, TRH122® CS and NMX1000® ASU on tendon health in a cell culture study that decreased IL-1ß-induced COX-2 expression and PGE2 production in equine tenocytes.
Expanding support for the combination of GLU+CS+ASU on tendon health, Grzanna et al. (2019) performed an in vitro study of tendon-derived cells. By combining GLU+CS+ASU, IL-1b-induced COX-2 gene expression and PGE2 production were reduced significantly.
Information about Cosequin® ASU
Substantive in vitro studies demonstrate that a combination of GLU+CS+ASU can positively support cartilage and tendon cells. Cosequin® ASU joint supplement is a proprietary combination of GLU+CS+ASU. The glucosamine/chondroitin sulfate combination has demonstrated a beneficial effect in supporting cartilage matrix components, while ASU acts synergistically with glucosamine and chondroitin sulfate for additional joint support (Au, R.Y., Au, A.Y., Rashmir-Raven, A. et al, 2007).
Equine joint durability is of particular concern with performance horses, as tendon and soft tissue injuries can result in significant time off or threaten a horse’s ability to perform in a chosen discipline. Dr. Shreves states that “starting [a joint supplement] early provides the best support for horses to keep their joints healthy.” ASU can be a key ingredient for supporting joint health, and its addition to GLU and CS in Cosequin® ASU helps maintain joint structure and function—greater than GLU + CS alone.
Au RY, al-Talib TK, Au AY, et al. (2007). Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages. Osteoarthritis Cartilage, 15, 1249-1255.
Au RY, Au AY, Cade M, et al. (2007). Down-regulation of pro-inflammatory markers in equine chondrocytes and osteoblasts by avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate. 2007 ACVS Veterinary Symposium: poster.
Au, R.Y., Au, A.Y., Rashmir-Raven, A. and Frondoza, C.G. (2007), Inhibition of Pro-inflammatory Gene Expression in Chondrocytes, Monocytes, and Fibroblasts by the Combination of Avocado Soybean Unsaponifiables, Glucosamine, and Chondroitin Sulfate. The FASEB Journal, 21: A736-A736.
Au RY, Grzanna MG, Au AY, et al. (2008). Regulation of pro-inflammatory COX-2 expression and prostaglandin E2 production in equine tenocyte culture models, in Proceedings. 35th Annual Conference Veterinary Orthopedic Society 2008:63.
Al-Afify ASA, El-Akabawy G, El-Sherif NM, El-Safty FEA, El-Habiiby MM (2018). Avocado soybean unsaponifiables ameliorates cartilage and subchondral bone degeneration in mono-iodoacetate- induced knee osteoarthritis in rats. Tissue and cell, 52, 108-115.
Boileau C, Martel-Pelletier J, Caron J et al (2009). Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog OA: inhibition of nitric oxide synthase and matrix metalloproteinase-13. Arthritis research and therapy, 11(2), R41
Clegg, P. D. (2012). Musculoskeletal disease and injury, now and in the future. Part 2: tendon and ligament injuries.Equine veterinary journal, 44(3), 371-375.
Frisbie, D. D., Kawcak, C. E., McIlwraith, C. W., Werpy. (2006). Evaluation of avocado and soybean unsaponifiables using an equine model of equine osteoarthritis. American Association of Equine Practitioners.
Frondoza CG, Heinecke L, Grzanna MW, et al. (2009) Modulation of metalloproteinase expression by the combination of avocado soy unsaponifiables, glucosamine hydrochloride, and chondroitin sulfate. ICRS 2009 – 8th World Congress of the International Cartilage Repair Society:P59.
Grzanna MW, Au RY, Au AY, Rashmir AM, Frondoza CG.(2019). Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination Inhibits Proinflammatory COX-2 Expression and Prostaglandin E2 Production in Tendon-Derived Cells. Journal of medicinal food, 23(2), 139-146.
Grzanna MW, Ownby SL, Heinecke LF, et al. (2010). Inhibition of cytokine expression and prostaglandin E2 production in monocyte/macrophage-like cells by avocado/soybean unsaponifiables and chondroitin sulfate. J Complement Integr Med;7(1), art 10.
Lippiello L, Woodward J, Karpman R, et al. (2000). In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate Clinical Orthopaedics and Related Research, 381, 229-240.
Lippiello L. Collagen synthesis in tenocytes, ligament cells and chondrocytes exposed to a combination of glucosamine HCl and chondroitin sulfate (2007). Evid Based Complement Alternat Med, 4(2), 219-224.
Ownby SL, Heinecke LF, Grzanna MW, et al. (2010).Reduction of pro-inflammatory gene expression in activated equine chondrocytes by avocado/soybean unsaponifiables, glucosamine, and chondroitin sulfate combination via inhibition of NF-κB activation, in Proceedings. 2010 ACVS Veterinary Symposium.
Article sponsored by: Nutramax Laboratories Veterinary Sciences, Inc., makers of Cosequin®.