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Ingredient overview

Omega-3 (132mg total: EPA 62mg, DHA 44mg)

Omega-3 fatty acids are essential fatty acids, which means that mammalian species rely on their diet, or supplementation as a source. Omega-3 fatty acids help to soothe inflamed joints. Several studies demonstrate an improvement in arthritic dogs following dietary enrichment with Omega-31,2,3,4.

When considering supplementation with Omega-3, it is important to consider both the quantity and quality that is provided…

It can sometimes be difficult to determine the quantities of Omega-3 in some products, because only the quantity of the source of Omega-3 (e.g., fish oil, krill oil or green-lipped mussel) is provided; 100mg of green-lipped mussel, fish or krill oil does not equate to 100mg of Omega-3. The total Omega-3 content in Locox TT is 132mg per tab. Independent laboratory analysis found Locox TT to contain a greater Omega-3 content (143.5mg per tab) and up to 4.5x the amount of Omega-3s compared to the market leading joint supplement5.

The quality of Omega-3 is even more important and this will be influenced by the source. The 3 marine sources of Omega-3 include; fish oil, krill oil and green-lipped mussel. In a canine model of cartilage degradation, fish and krill oil demonstrated superior efficacy in comparison to green-lipped mussel6. The Omega-3 in Locox TT is from sustainably sourced fish oil (Friend of the Sea Certified).

Finally, there are many types of Omega-3 fatty acids, of which, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are most critical for joint health. EPA and DHA have been shown to reduce the expression and activity of inflammatory enzymes7,8. Locox TT contains the highest quantities of EPA (66mg) and DHA (44mg) when compared to competitor products.

References:

  1. Roush, J. K., Dodd, C. E., Fritsch, D. A., Allen, T. A., Jewell, D. E., Schoenherr, W. D., Richardson, D. C., Leventhal, P. S., & Hahn, K. A. (2010). Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. Journal of the American Veterinary Medical Association, 236(1), 59–66.
  2. Roush, J. K., Cross, A. R., Renberg, W. C., Dodd, C. E., Sixby, K. A., Fritsch, D. A., Allen, T. A., Jewell, D. E., Richardson, D. C., Leventhal, P. S., & Hahn, K. A. (2010). Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. Journal of the American Veterinary Medical Association, 236(1), 67–73.
  3. Fritsch, D. A., Allen, T. A., Dodd, C. E., Jewell, D. E., Sixby, K. A., Leventhal, P. S., Brejda, J., & Hahn, K. A. (2010). A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. Journal of the American Veterinary Medical Association, 236(5), 535–539.
  4. Moreau, M., Troncy, E., Del Castillo, J. R., Bédard, C., Gauvin, D., & Lussier, B. (2013). Effects of feeding a high omega-3 fatty acids diet in dogs with naturally occurring osteoarthritis. Journal of animal physiology and animal nutrition, 97(5), 830–837.
  5. Independent laboratory analysis of Omega 3 levels per tab. Results provided by Labexan. Laboratories, Cognac France, Feb 2021
  6. Buddhachat, K., Siengdee, P., Chomdej, S., Soontornvipart, K., & Nganvongpanit, K. (2017). Effects of different omega-3 sources, fish oil, krill oil, and green-lipped mussel against cytokine-mediated canine cartilage degradation. In vitro cellular & developmental biology. Animal, 53(5), 448–457
  7. Massaro, M., Habib, A., Lubrano, L., Del Turco, S., Lazzerini, G., Bourcier, T., Weksler, B. B., & De Caterina, R. (2006). The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC epsilon inhibition. Proceedings of the National Academy of Sciences of the United States of America, 103(41), 15184–15189.
  8. Li, X., Yu, Y. and Funk, C.D. (2013). Omega 3 polyunsaturated fatty acids modulate cyclooxygenase‐2 induction via interactions with GPR120. The FASEB Journal, 27: 813.7-813.7.

Glucosamine (200mg) and Chondroitin (134mg)

Glucosamine sulfate and chondroitin sulfate work synergistically to support cartilage and synovial fluid health. They contribute to the synthesis of glycosaminoglycans and proteoglycans – the building blocks of cartilage.

Glucosamine regulates the synthesis of collagen in cartilage and chondroitin inhibits destructive enzymes in joint fluid and cartilage1,2,3. Glucosamine and chondroitin can be absorbed in as little as 2 hours2. The glucosamine in Locox TT is in a crystalline form. Crystalline glucosamine sulfate has demonstrated improved bioavailability (absorption)4 compared to glucosamine hydrochloride (the form often found in joint supplements). Glucosamine sulfate is available both systemically5 and within joints6 and has demonstrated a reduction in arthritic symptoms7.

References:

  1. Bali, J.P. et al. (2001). Biochemical basis of the pharmacological action of chondroitin sulfate on the osteoarticular system. Arthritis and Rheumatism, 31(1): 58-68.
  2. Beale, B. S. (2004). Use of nutraceuticals and chondroprotectants in osteoarthritic dogs and cats. The Veterinary clinics of North America. Small animal practice, 34(1), 271–viii.
  3. Chan, P. et al. (2005). Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E2 in articular cartilage explants.
  4. Meulyzer, M., Vachon, P., Beaudry, F., Vinardell, T., Richard, H., Beauchamp, G., & Laverty, S. (2008). Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride. Osteoarthritis and cartilage, 16(9), 973–979.
  5. Persiani, S., Roda, E., Rovati, L.C., Locatelli, M., Giacovelli, G. and Roda, A. (2005). Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthritis Cartilage, 13(12), 1041-1049.
  6. Persiani S, Rotini R, Trisolino G, Rovati LC, Locatelli M, Paganini D, Antonioli D, Roda A. (2007). Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose. Osteoarthritis Cartilage. Jul;15(7):764-72. Epub 2007 Mar 13. PMID: 17353133.
  7. Herrero‐Beaumont, G., Ivorra, J.A.R., del Carmen Trabado, M., Blanco, F.J., Benito, P., Martín‐Mola, E., Paulino, J., Marenco, J.L., Porto, A., Laffon, A., Araújo, D., Figueroa, M. and Branco, J. (2007), Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double‐blind, placebo‐controlled study using acetaminophen as a side comparator. Arthritis & Rheumatism, 56: 555-567.

MSM (200mg)

MSM (Methyl-sulfonyl-methane) possesses antioxidant action, promotes cartilage production and soothes inflammation1,2. It is a naturally occurring organic sulphur that is rapidly absorbed and well distributed throughout the body3.

MSM downregulates the production of pro-inflammatory mediators, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)1,2. Suppression of NF-κB reduces translation expression of cytokines (IL-1, IL-6, TNF-α)4,5 inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX2)1. In animal models, MSM has demonstrated a reduction in cartilage degeneration6 and the development of osteoarthritis7.  A randomised, double-blind placebo-controlled study in humans, found that the combination of MSM, glucosamine and chondroitin to be effective in reducing osteoarthritic pain (when compared to glucosamine and chondroitin alone)8.

References:

  1. Kim, Y. H., Kim, D. H., Lim, H., Baek, D. Y., Shin, H. K., & Kim, J. K. (2009). The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages. Biological & pharmaceutical bulletin, 32(4), 651–656.
  2. Joung, Y. H., Darvin, P., Kang, D. Y., Sp, N., Byun, H. J., Lee, C. H., Lee, H. K., & Yang, Y. M. (2016). Methylsulfonylmethane Inhibits RANKL-Induced Osteoclastogenesis in BMMs by Suppressing NF-κB and STAT3 Activities. PloS one, 11(7), e0159891.
  3. Butawan, M., Benjamin, R. L., & Bloomer, R. J. (2017). Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients, 9(3), 290
  4. Ahn, H., Kim, J., Lee, M. J., Kim, Y. J., Cho, Y. W., & Lee, G. S. (2015). Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Cytokine, 71(2), 223–231.
  5. Oshima, Y., Amiel, D., Theodosakis, J. (2007) The effect of distilled methylsulfonylmethane (msm) on humanchondrocytes in vitro. Osteoarthr. Cartil.2007,15, C123.
  6. Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. (2013). Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab. Jan;31(1):16-25.
  7. Amiel, D., Healey, R.M. and Oshima, Y. (2008), Assessment of methylsulfonylmethane (MSM) on the development of osteoarthritis (OA): An animal study. FASEB J, 22: 1094.3-1094.3
  8. Lubis, A., Siagian, C., Wonggokusuma, E., Marsetyo, A. F., & Setyohadi, B. (2017). Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial. Acta medica Indonesiana, 49(2), 105–111.

Superoxide dismutase (25mg)

Superoxide dismutase (SOD) is a major enzyme in the anti-oxidant defence system that reduces the formation of reactive oxygen species (ROS) produced by metabolic processes1. SOD is naturally found in the body, but levels decline in patients with osteoarthritis2. Inadequate control of ROS contributes to the pathophysiology (progression and development) of OA3, furthermore exogenous supplementation of SOD may be beneficial in joint disease.

SOD in Locox TT is derived from the juice of a patented non-GMO Cantaloupe melon variety (Cucumis melo L). Supplementation with SOD, has been associated with anti-oxidant activity and down regulation of inflammatory processes4,5,6,7.

In addition, SOD protects Omega-3 fatty acids from lipid peroxidation (oxidative degradation of fats) cause by ROS8 , thereby preserving Locox TT’s high quality Omega-3 profile.

References

  1. Muth, C.M., Glenz, Y., Klaus, M., Radermacher, P., Speit, G., Leverve, X. (2004). Influence of an orally effective SOD on hyperbaric oxygen-related cell damage. Free Radic Res. Sep;38(9):927-32.
  2. Scott, J.L., Gabrielides, C., Davidson, R.K., Swingler, T.E., Clark, I.M., Wallis, G.A., Boot-Handford, R.P., Kirkwood, T.B., Taylor, R.W., Young, D.A. (2010). Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann Rheum Dis. Aug;69(8):1502-10
  3. Regan, E., Flannelly, J., Bowler, R., Tran, K., Nicks, M., Carbone, B. D., Glueck, D., Heijnen, H., Mason, R., & Crapo, J. (2005). Extracellular superoxide dismutase and oxidant damage in osteoarthritis. Arthritis and rheumatism, 52(11), 3479–3491.
  4. Kick, J., Hauser, B., Bracht, H. et al. (2007). Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping. Intensive Care Med. 33, 694–702.
  5. Vouldoukis, I., Lacan, D., Kamate C, Coste P, Calenda A, Mazier D, Conti M, Dugas B. (2004a). Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity. J Ethnopharmacol. Sep;94(1):67-75.
  6. Vouldoukis, I., Conti, M., Krauss, P., Kamaté, C., Blazquez, S., Tefit, M., Mazier, D., Calenda, A., Dugas, B. (2004b). Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Phytother Res. Dec;18(12):957-62.
  7. Notin, C., Vallon, L., Desbordes, F., & Leleu, C. (2010). Oral supplementation with superoxide dismutase in Standardbred trotters in training: a double-blind placebo-controlled study. Equine veterinary journal. Supplement, (38), 375–381.
  8. Roginsky, V. and Barsukova, T. (2001) Superoxide Dismutase Inhibits Lipid Peroxidation in Micelles. Chemistry and Physics of Lipids, 111, 87-91

Vitamin E (22mg), Manganese (7mg) and Zinc (10mg).

Vitamin E neutralises reactive oxygen species, downregulates inflammatory processes and supports healthy cartilage.
Zinc and manganese act as co-factors for anti-oxidant enzymes. Zinc and manganese are also considered anabolic, supporting collagen formation.

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