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Equine joint supplements – what scientific evidence is there to support their use?

Equine joint supplements – what scientific evidence is there to support their use?

Dr David Marlin

Walk in to any human health food shop, pharmacy, supermarket or any pet store or tack shop and it won’t be long before you come across the dreaded “joint supplements”. Prepare to be amazed by the range of ingredients, dosages, presentations and claims. Medics, vets and scientists have tended to be sceptical of oral joints supplements and often for good reason. Appropriately designed studies demonstrating efficacy have tended to be few and far between, especially in supplements for cats, dogs and horses. There has also be suspicion amongst professionals given that over 80% of human joint supplements in one study did not meet the label claim for chondroitin sulphate (Adebowale et al.2000). Equine joint supplements faired slightly better with only 40% failing to meet label claims for glucosamine (Oke et al.2006). One could speculate the higher compliance for glucosamine in equine supplements is due to the fact that it is considerably less expensive as a raw material compared with chondroitin.

There has certainly been interest from scientists in the concept of oral joint supplements. A simple PUBMED search reveals over 1000 citations. One of the earliest studies involved feeding mice 4% cholesterol, although the result was not what makers of today’s joint supplements will want to hear; the supplement increased the incidence of osteoarthritis! (Silberberg, 1975).

Perhaps if we believe that oral joint supplements have little or no efficacy, we might consider that feeding them at least allows owners to feel they are doing something positive for their animals and that any improvement may be due to the placebo effect and therefore there is little risk. This may be true if owners follow the feeding recommendations although there appears to be little data on safety of joint supplements. However, there are reports in the literature of the fatal consequences of excessive intake of joint supplements both in dogs (Borchers et al.2014; Nobles and Khan, 2015). Furthermore, a recent study also showed that shark cartilage, an ingredient used in some joint supplements, may in fact have pro rather than anti-inflammatory action (Merly and Smith, 2015). A further concern, especially for those competing horses or dogs is the finding that a significant proportion of ingredients or products sold for management of joint pain in Korea were contaminated accidentally or intentionally with a range of steroids (Cho et al.2014).

When it comes to oral joint supplements for people there are perhaps not surprisingly a relatively large number of studies either on individual ingredients or combinations of ingredients in both experimental and commercial formulations. Clearly one of the problems in reviewing the large volume of literature is that publication in a peer-reviewed scientific journal does not guarantee good science. Publication only suggests that two or perhaps three reviewers and the editor did not object strongly to the content. On closer scrutiny many studies raise cause for concern based on simple mistakes such as lack of control groups, lack of blinding (use of a placebo), insufficient power (not enough subjects to demonstrate a significant effect even if one was present) and inappropriate statistics (for example, multiple t-tests without correction or use of parametric statistics on non-normally distributed data). Finally, if a study satisfies all the required criteria, we may still end up with a statistically significant but biologically insignificant finding; for example, a significant increase in range of motion of a joint by 1%. If you want to dig a little deeper than the marketing literature supplied by joint supplement manufacturer, you are essentially faced with one or more of the following options: run your own studies; review the literature; search for reviews and particular, studies which have applied a meta-analysis. The latter is an approach to critically review multiple independent publications with a view to eliminating publications that are “unsafe” and drawing conclusions from the volume of literature in an area considered “reliable”. This approach tends to give us a better overall view of the literature than trying to place weight on individual papers. It’s also attractive when you become aware that there are almost 3000 studies each of glucosamine and chondroitin “in vitro” alone.

A recent review of 43 randomised controlled trials of the use of chondroitin versus a placebo or other control for human knee osteoarthritis (Singh et al.2015) concluded that “chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne’s index [1] (range 0 to 24), both seeming clinically meaningful.” Although the authors also concluded that there was a need for more high-quality trials.

An earlier review but not a systematic meta-analysis (Ragle and Sawitzke, 2012) looked at evidence for glucosamine, chondroitin, collagen hydrolysates and avocado-soybean unsaponifiables. These authors concluded that the products had a “good safety profile” and that their use in selected patients is “appropriate”.

Low numbers of high quality studies is a problem when it comes to evaluating other ingredients. For example, a review of green-lipped mussel for treatment of osteoarthritis only identified 4 studies, of two failed to meet criteria for inclusion (Brien et al.2008). After reanalysing the data from the two remaining trials the authors concluded that green-lipped mussel may be better than placebo in treatment of mild to moderate osteoarthritis.

Finally, a meta-analysis investigated evidence for omega 3 PUFA in patients with inflammatory joint pain (Goldberg and Katz, 2007). The review of 17 studies concluded that omega-3 PUFA reduced reported joint pain, duration of morning stiffness, number of painful joints and NSAID consumption and the authors concluded that “The results suggest that omega-3 PUFAs are an attractive adjunctive treatment for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhoea”.

Thus, critical reviews do suggest that some commonly used joint supplement ingredients either alone or in combinations do show some degree of efficacy in human patients with arthritic conditions. Not surprisingly there are fewer studies on companion animals. Pearson and Lindinger (2009) conducted a review of the 15 papers published on in vivo equine studies of single ingredients or commercial products including Cosequin, Cortaflex, Synequin, Sasha’s EQ, Myristol, chondroitin sulphate, glucosamine sulphate and glucosamine hydrochloride. Only three of the papers met the minimum quality score to be considered further. The authors concluded “that the quality of studies in this area is generally low, prohibiting meaningful interpretation of the reported results.”

Since Pearson and Lindinger’s review, a further 6 studies on equine joint supplements have been published. These are summarised in Table 1 (see below). Two studies had a positive outcome but after 3 or 5 months of feeding. Two other studies showed no detectable effect of the supplements used. The remaining two studies by Murray et al. (2013 and 2014) used large numbers of horses and a range of different assessments including kinematics (video gait analysis), clinical assessment, physiotherapist assessment and handler assessment in a double-blind placebo controlled trial with a 5 component supplement (FlexAbility, Science Supplements) and found positive effects on soundness, range of motion, joint angles and handler scores after 3 weeks supplementation. This study has since been published as a full peer-reviewed paper in the Journal of Equine Veterinary Science.

joint supplement review table 1 ally gau

In summary, there is evidence to support the use of certain oral ingredients in arthritic conditions in horses. However, it is clear that the number and quality of studies is generally lower than would be expected for pharmaceuticals. This is partly due to the fact that the market is highly competitive and consumers have many choices. As such no company will have a significant share of the market making returns on investment low. At the same time, the relatively low retail pricing and low volume sales means that research and development investment will at most be modest and in the majority of cases, non- existent. The efficacy of different oral joint supplements will depend on the specific ingredients used and their individual efficacy, the number of different ingredients, the level at which the active ingredients are to be fed, whether the finished product on the shelf actually meets the label claims. For those with animals that are competing under National Federation rules, FEI rules or the rules of racing, there may also be concerns over contamination with prohibited substances beyond those covered by the BETA NOPS (naturally occurring prohibited substances) scheme; the latter provides a degree of reassurance with respect to substances that may commonly contaminate feed ingredients, for example morphine in linseed, but do not provide any surety with respect to for example, steroids or other pharmaceuticals. Finally, oral joint supplements should clearly not be viewed in the same way as recognised pharmaceutical management but in appropriate cases may provide additional benefit and or allow lower doses of pharmaceuticals to be used.

1 The Lequesne Index is a 10-question survey for patients with knee osteoarthritis. Five questions relate to pain/discomfort, one to distance walked and four questions about daily activities. A score between 0 to 24 is calculated and lower scores indicate less functional impairment.

References

Adebowale A, Cox D, Liang Z, Eddington N. (2000) Analysis of glucosamine and chondroitin sulfate content in marketed products and the Caco-2 permeability of chondroitin sulfate raw materials. J Am Nutr Assoc, 3(1):37-44.

Borchers A, Epstein SE, Gindiciosi B, Cartoceti A, Puschner B. (2014) Acute enteral manganese intoxication with hepatic failure due to ingestion of a joint supplement overdose. J Vet Diagn Invest. Sep;26(5):658-63.

Brien S, Prescott P, Coghlan B, Bashir N, Lewith G. (2008) Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis. Quart J Med. Mar;101(3):167-79.

Cho SH, Park HJ, Lee JH, Kim HJ, Cho S, Yoon CY, Kim WS. (2014) Monitoring of 35 illegally added steroid compounds in foods and dietary supplements. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 4;31(9):1470-5.

Goldberg RJ and Katz J. (2007) A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain.
Pain. May;129(1-2):210-23.

Gupta RC, Canerdy TD, Skaggs P, (2009) Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses. J Vet Pharmacol Therap. 32(6):577-584.

Higler MH, Brommer H, L’Ami JJ, de Grauw JC, Nielen M, van Weeren PR, Laverty S, Barneveld A, Back W. (2014) The effects of three-month oral supplementation with a nutraceutical and exercise on the locomotor pattern of aged horses. Equine Vet J. Sep;46(5):611-7.

Lamprecht ED and Williams CA. (2012) Biomarkers of antioxidant status, inflammation, and cartilage metabolism are affected by acute intense exercise but not superoxide dismutase supplementation in horses. Oxid Med Cell Longev. 2012:920932.

Merly L and Smith SL. (2015) Pro-inflammatory properties of shark cartilage supplement. Immunopharmacol Immunotoxicol. Apr;37(2):140-7.

Murray R., Adams V., Walker V., Tranquille C., Copeman S., Spear J., Frost R. and Marlin D. (2013) To Determine the Effect of An Oral Joint Supplement on Orthopaedic, Physiotherapy and Handler Evaluation Scores in Horses Equine Vet J. Volume 45, Issue Supplement S44, page 3.

Murray R, Walker V, Tranquille C, Adams V and Frost R (2014) Effect of an Oral Joint Supplement on Orthopaedic Evaluation Scores and Limb Kinematics. Equine Vet J. Volume 46, Issue Supplement S46, page 44.

Murray, R., Walker, v., Tranquille, C., Spear, J. and Adams, V. (2017) A Randomized Blinded Crossover Clinical Trial to Determine the Effect of an Oral Joint Supplement on Equine Limb Kinematics, Orthopedic, Physiotherapy, and Handler Evaluation Scores. J Equine Vet Sci. Volume 50, Pages 121–128.

Nobles IJ and Khan S. (2015) Multiorgan dysfunction syndrome secondary to joint supplement overdosage in a dog. Can Vet J. 2015 Apr;56(4):361-4.

Oke S, Aghazadeh-Habashi A, Weese JS, Jamali F. (2006) Evaluation of glucosamine levels in commercial equine oral supplements for joints. Equine Vet J. Jan;38(1):93-5.

Pearson W and Lindinger M.(2009) Low quality of evidence for glucosamine-based nutraceuticals in equine joint disease: review of in vivo studies. Equine Vet J. Sep;41(7):706-12.

Pearson W, Orth MW and Lindinger MI (2009) 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. Jul;70(7):848-61.

Ragle RL and Sawitzke AD. (2012) Nutraceuticals in the management of osteoarthritis : a critical review. Drugs Aging. Sep;29(9):717-31.

Silberberg R. (1975) Skeletal effects of cholesterol feeding. Pathol Microbiol (Basel). 43(4):265-75.

Singh JA, Noorbaloochi S, MacDonald R and Maxwell LJ. (2015) Chondroitin for osteoarthritis. Cochrane Database Syst Rev. Jan 28;1:CD005614.

Date: January 08, 2016