Use of Nutraceuticals for Tendinopathies

© ISAKOS 2017
Gian Luigi Canata, Pieter d’Hooghe and Kenneth J. Hunt (eds.)Muscle and Tendon Injuries10.1007/978-3-662-54184-5_16

16. Use of Nutraceuticals for Tendinopathies

Marco Antônio Percope de Andrade1, 2  , Guilherme Moreira de Abreu-e-Silva1 and Túlio Vinícius Oliveira de Campos1

Orthopaedic Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

Departamento de Aparelho Locomotor, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 110, Santa Efigênia, CEP: 30130-100, Belo Horizonte, MG, Brazil



Marco Antônio Percope de Andrade

16.1 Introduction

The importance of tendinopathies in the clinical scenario has increased recently. It may be attributed to the increase of sport activities, life expectancy, and other factors such as environment, diet, systemic diseases, and some drug therapies (e.g., fluoroquinolones). In fact, not only athletes but also the general population suffer from inflammatory or degenerative tendon conditions which may be attributed to the quality of tendon tissue and mechanical overuse (Fusini et al. 2016).

Recently, basic and clinical researches have advocated the prescription of oral medication aiming to modulate pathways which determine tendon structure and resistance.

The term “nutraceutical” was coined from “nutrition” and “pharmaceutical” in 1989 by DeFelice and was originally defined as “a food that provides health benefits, including the prevention and/or treatment of a disease”. In general, nutraceuticals have late onset of action and should be devoid of adverse effects. They are not under rigorous control and licensing processes as drugs and do not require robust clinical support to be sold as treatment alternatives (Percope de Andrade et al. 2015).

Oral supplements of glucosamine and chondroitin sulfate, vitamin C, hydrolyzed type 1 collagen, L-arginine alpha-ketoglutarate, curcumin, boswellic acid, methylsulfonylmethane, and bromelain increase the concentration of beneficial compounds in tendon and may help to preserve, or even repair, the damaged structures.

The aim of the present chapter is to review the basic and clinical data that support the use of nutraceuticals in the management of tendon disease.

16.2 Basic Science

16.2.1 Glucosamine and Condroitin Sulfate

Lippiello demonstrated that bovine tenocytes were stimulated by the addition of a combination of glucosamine and chondroitin sulfate to the culture medium. That pair of substances increased collagen synthesis by 22% in tenocytes. After 48 h exposure, epitenon and tenocyte cells presented a greater production of radiolabeled hydroxyl-proline (Lippiello 2006).

Tenotomized rats treated with oral glucosamine and chondroitin supplements showed more organized collagen bundles and less inflammation than controls fed with placebo. After eight weeks, rats fed with glucosamine and chondroitin had greater tendon strength in biomechanical tests (Ozer et al. 2011).

Topical application of chondroitin has beneficial effects in rabbit’s tendon characteristics by preventing the degenerative cascade of proteases and inflammation on tendon structure induced by collagenase (Oryan et al. 2008).

16.2.2 Vitamin C

Vitamin C is a critical element in the synthesis of procollagen chains. It acts as coenzyme of proline hydroxylase. In fact, it is a cofactor of hydroxylation (Fusini et al. 2016).

Experimental research shows that tenocytes cultured in a medium without ascorbate synthesized collagen at only a third of the normal level. Addition of ascorbate to avian tendon cells increased procollagen translation by six times (Kao et al. 1976).

Vitamin C alone is not able to increase collagen synthesis and secretion. In fact, tenocytes treated with ascorbate maintained a large pool of procollagen despite changes in translation or secretion rate. These results are compatible with a possible feedback mechanism between the levels of internal procollagen pool and the rates of collagen synthesis and secretion (Schwarz et al. 1981).

Ascorbic acid may act as an antioxidant agent. Vitamin C increased reduced glutathione tissue quantity two weeks after injury, in comparison to a group treated with saline. The treatment with ascorbate also improved the gliding resistance of tendons and reduced the fibrotic scar at the site of injury (Hung et al. 2013).

A study with 42 healthy female Wistar albino rats proved that high-dose vitamin C supplementation every 2 days may have stimulating effects on healing of a full-thickness Achilles tendon rupture (Omeroglu et al. 2009).

16.2.3 Hydrolyzed Type 1 Collagen

The role of collagen 1 on tenocyte or tenoblast culture is unknown.

Investigation of the effects of collagen peptide ingestion on rabbit’s tendon extracellular matrix demonstrates that hydrolyzed type 1 collagen peptides affect the size of collagen fibrils and composition of glycosaminoglycans in Achilles tendon. The ingestion of type 1 collagen increased the amount of dermatan sulfate and lowered the percentage of hyaluronic acid. The rise of this biochemical component would enhance the mechanical properties of Achilles tendon (Minaguchi et al. 2005).

16.2.4 L-Arginine Alfa-Ketoglutarate

L-arginine is an essential amino acid required by the enzymatic family of nitric oxide synthase (NOS) to produce nitric oxide (NO) which is a crucial factor in tendon healing process.

In a rat model, uninjured tendons did not present NOS activity. After surgical tenotomy, NOS enzyme increased its activity reaching a maximum after 7 days, with reduction near baseline levels at day 14 (Murrell 2007a).

Inhibition of NOS activity with oral administration of an analogue of L-arginine-N ω-nitro-L-arginine methyl ester (L-NAME) resulted in significant reduction of cross-sectional area and failure load of injured Achilles tendons (Murrell et al. 1997).

In animal models, the addition of competitive NOS inhibitors impaired tendon healing, while the addition of NO enhanced tendon healing (Murrell 2007b).

The levels of transforming growth factor (TGF) β undergo a change during physiological repair process. At the beginning they rise, and after about 3 weeks, they gradually decrease to slowly reach control levels. Conversely, if L-NAME is given at injury time, the macrophage infiltrates continue to express high level of TGF-β. Following an injury, iNOS activity increases during the acute phase of inflammation, and then gradually tends to normalize. Treatment of injured tendon with L-NAME, however, inhibits iNOS activity. L-NAME-treated rats showed increased adhesion of peritoneal macrophages to epitenon monolayers in vitro. In addition, the treatment of acute tendon injury with NO inhibitor causes a long-lasting and wide accumulation of many inflammatory cells in the subcutaneous tissue, muscle, and tendon as a response of chronic inflammation. Thus, the formation of NO is a key event for tendon healing process because its inhibition increases the level of TGF-β and development of fibrosis and chronic inflammation (Darmani et al. 2004).

16.2.5 Curcumin

Curcumin is an antioxidant extracted from Curcuma longa which has a potential role in prevention of oxidative stress damage. Increased vascularization is a very common finding in tendinopathy. Curcumin inhibits the formation of new blood vessels in a mouse model (Arbiser et al. 1998).

Long-term oral administration of curcumin decreased cross-linking of collagen and restored its original characteristics (Pari and Murugan 2007; Sajithlal et al. 1998).

Curcumin targets NF-κB signaling pathway by inhibiting inflammation and apoptosis induced by IL-1β in vitro. Curcumin achieves its anti-inflammatory effects by downregulation of matrix metalloproteinase-1, metalloproteinase-9, and metalloproteinase-13, cyclooxygenase-2, inhibition of caspase-3, and Bax pathway leading to apoptosis. It also stimulates cell survival by promoting Bcl-2 pathway (Buhrmann et al. 2011).

Oral administration of curcumin (100 mg/kg of body weight) has been tested to manage patellar tendon injury in Sprague-Dawley rats. Histological examination revealed deposition of well-organized collagen fibers and improvement of tendon biomechanical properties (Jiang et al. 2016).

16.2.6 Boswellic Acid

Boswellic acid (BA), extracted from Boswellia serrata, is considered an active treatment for chronic inflammatory diseases. Although BA is often used in combination with other nutraceuticals, we could not find articles describing the effects of BA on tenocytes.

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Sep 6, 2017 | Posted by in ORTHOPEDIC | Comments Off on Use of Nutraceuticals for Tendinopathies

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