I have been asked to explain the scientific reasons behind the ingredients in the Tendon EQ supplement from Uckele https://uckele.com/tendon-eq.html .
Tendons and ligaments are composed of interwoven strands of the structural protein collagen. It has been known since the 1950s that the major nonessential amino acid in collagen structure is glycine while the most abundant essential amino acid is lysine and its derivative, hydroxylysine.1
Glycine is classified as nonessential because the body is capable of manufacturing it from the amino acid serine but it has been shown that this is not sufficient to support collagen synthesis2 so supplementation is reasonable for support of tendons and ligaments.
Lysine is essential, meaning it must be obtained from food and cannot be produced by the horse’s body. It is commonly deficient in equine diets, making supplementation important.
Lysine is also the source of hydroxylysine, an amino acid which is only found in collagen. Studies have shown that dietary hydroxylysine is not used to make collagen; only hydroxylysine freshly synthesized from lysine. The enzyme responsible for the conversion of lysine to hydoxylysine is lysyl hydrolase. Another key enzyme, which creates the reinforcing cross-links in tendon and ligament structure, is lysyl oxidase. Copper is a required cofactor for both.3 Copper deficiency interferes with the activation of the two lysl enzymes.4
Copper is one of the most common deficiencies in equine diets and an important ingredient for tendon and ligament support. In addition to low dietary levels, bioavailability is compromised by high levels of iron. Iron competes with copper for absorption. Sulfates in water may cause problems because they bind copper and cause it to precipitate out.
Zinc is included in the Tendo EQ formula for several reasons. Zinc is another common equine dietary deficiency, one of the most common in fact, and it is always advisable to include zinc when supplementing copper as copper competes for absorption. Zinc additionally plays a key role in bone formation and is important for the integrity of the tendon or ligament insertion sites on bone.5 As a component of the superoxide dismutase enzyme system, zinc is a key antioxidant. Controlling oxidative stress supports efficient tissue maintenance without deposition of disorganized collagen. Adequate zinc is also needed for normal recruitment of tissue growth factors.6
Nitric oxide, NO, has emerged as a pivotal factor in the creation and maintenance of normal tendon and ligament tissue. NO is a simple gas – one nitrogen and one oxygen molecule – which is produced by three different enzyme systems7:
eNOS. Endogenous nitric oxide synthase, present in the endothelial cells lining blood vessels and responsible for normal vascular dilation plus the release of growth factors to stimulate tissue maintenance. This system is constantly active in healthy tissues.
iNOS. Inducible nitric oxide synthase, present in cells of the immune system and responsible for production of very large amounts of nitric oxide within damaged tissue. It serves as a signaling molecule for inflammation. It also robs eNOS of the substrates needed for NO production in vessels, resulting in poor perfusion of the tissues. This system is normally turned off in most tissues.
nNOS. Neuronal nitric oxide synthase, present in the nervous system where the production of NO acts as a neurotransmitter in certain cells.
Micro-tears in tendons and ligaments are a common occurrence for athletes8 and in the early stages can be effectively managed by the body before they cause any loss of function or serious damage. Research has shown that management of such normal exercise-related wear and tear and tear requires the coordinated activity of all three nitric oxide synthase enzyme isoforms, from iNOS for clean up and nNOS, eNOS to direct formation of normal tendon tissue.9 Jiaogulan (Gynostemma pentaphyllum) is an herb with the unique ability to support eNOS activity while assisting in modulation of iNOS.10, 11
Identifying potential nutritional weak links and providing support for the body’s own homeostatic mechanisms for tissue maintenance is an important weapon in the fight to maintain tendon and ligament integrity.
1. Eastoe JE. The amino acid composition of mammalian collagen and gelatin. Biochem J 1955 Dec; 61(4): 589–600.
2. Meléndez-Hevia, et al. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. Journal of Biosciences. 2009 Dec; (6): 853–72.
3. Rucker RB et al. Copper, lysyl oxidase, and extracellular matrix protein cross-linking. Am J Clin Nutr. 1998 May;67(5 Suppl):996S-1002S.
4. Rucker RB et al. Activation of chick tendon lysyl oxidase in response to dietary copper. Nutr. 1999 Dec;129(12):2143-6.
5. Yamaguchi M. Nutritional factors and bone homeostasis: synergistic effect with zinc and genistein in osteogenesis. Mol Cell Biochem. 2012 Jul;366(1-2):201-21.
6. Fukada T. The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways. PloS One. 2008;3(11):e3642.
7. Villanueva C, Giulivi C. Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease. Free Radic Biol Med. 2010 Aug 1;49(3):307-16.
8. Krolo I et al. The risk of sports activities–the injuries of the Achilles tendon in sportsmen. Coll Antropol. 2007 Mar;31(1):275-8.
9. Bokhan AR and Murrell GA. The role of nitric oxide in tendon healing. J Shoulder Elbow Surg. 2012 Feb;21(2):238-44.
10. Tanner MA et al. The direct release of nitric oxide by gypenosides derived from the herb Gynostemma pentaphyllum. Nitric Oxide. 1999 Oct;3(5):359-65.
11. Aktan F et al. Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression. Nitric Oxide. 2003 Jun;8(4):235-42.