Chondroprotective Agents

 by Dr. Chris Piper
 
The role of nutrition is vital to the proper development and maintenance of joints. Chondroprotective agents (CPAs) have been shown to promote normalisation of cartilage and synovial fluid, and also slow down the degeneration of cartilage.

Considerable confusion exists regarding the therapeutic value of different CPAs and the most appropriate sources of these nutrients. This article attempts to clarify these issues. CPAs have the following attributes:

• support chondrocyte synthesis of collagen and proteoglycans in the matrix
• support the production of hyaluronans in joint fluid
• inhibit cartilage degradation enzymes
• prevent fibrin formation in synovial fluid and plaque formation in subchondral vessels

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Examples of compounds which exhibit these characteristics are glucosamine, chondroitins, and hyaluronic acid.

Cartilage is a very complex connective tissue composed of two elements; the cellular component, the chondrocytes (5%), and the extracellular component, the matrix (95%). The matrix (see fig.1) is composed of water (70%), collagen, and proteoglycan aggregates. The proteoglycan aggregates are composed of numerous proteoglycan monomers attached end on end to hyaluronic acid. Each proteoglycan is composed of numerous glycosaminoglycans attached to a core protein which in turn is joined to the hyaluronic acid molecule by a link protein. The predominant glycosaminoglycans (GAGs) of cartilage are chondroitin-4-sulphate, chondroitin-6-sulphate, hyaluronic acid, and keratan sulphate. Chondroitin sulphate is composed of repeating disaccharide units of glucosamine and galactosamine. Glucosamine is either preformed from nutritional supplementation or synthesised from glucose and amino acids, and galactosamine is formed from glucosamine by changing one of the hydroxyl groups. Galactosamine cannot be used as a nutritional supplement as it causes liver damage.

To summarise:
Glucose + amine => glucosamine + glactosamine => disaccharide + disaccharides => glycosaminoglycan + glycosaminoglycans + core protein => proteoglycan monomer + proteoglycan monomers + hyaluronic acid => proteoglycan aggregates + collagen => matrix + chondrocytes => cartilage

The integrity of cartilage is dependent on adequate structural support from the underlying subchondral bone, the joint capsule and its supply of synovial fluid., and proper support from the ligaments and muscles which maintain alignment of the opposing surfaces of the joint.

Many of the nutraceuticals available contain sources of chondroitins and glucosamine and often contain other cofactors (minerals and vitamins) as well. Some CPAs are provided in purified forms and others as animal extracts. Whatever the form, it is important to know what a product contains, and sufficient information should be present on the label or available from the manufacturer, to enable you to identify levels of specific ingredients. Many of the whole animal extracts will contain valuable nutrients apart from the chondroitins and glucosamine. In addition to chondroitins and glucosamine there is a need for collagen, hyaluronic acid, proteins, and sufficient cofactors to enable the body to synthesise the matrix.
There are several rich sources of these nutrients.

Glucosamine is extracted from chitin, the exoskeleton of crabs, shrimps, and lobsters. The preferred form is glucosamine hydrochloride, and it is readily absorbed from the gut - up to 98%. It also provides significantly more glucosamine than glucosamine sulphate and is much more stable.

Chondroitin sulphate is the most abundant GAG of cartilage although keratan sulphate, dermatan sulphate, and heparan sulphate are also present. Chondroitin 4 sulphate and chondroitin 6 sulphate are sourced from bovine, shark, and poultry tissues. Another marine source, green lipped muscle, is a poor source of GAGs (2-3%) despite appearing in the literature as a rich source of GAGs. Bovine tracheal cartilage contains 20-28% GAGs as chondroitin 4 sulphate and chondroitin 6 sulphate as well as 23% collagen and a source of calcium. Shark cartilage contains 7-25% GAGs mainly as chondroitin 6 sulphate (15% is keratan sulphate), 20% collagen, and 50% calcium hydroxyapatite. Hydroxyapatite is an essential ingredient of bone matrix.

A combination of glucosamine and chondroitin sulphate has been shown to be more effective than either agent alone.

Hyaluronic acid is poorly absorbed, however, up to 70% of chondroitin sulphate is absorbed, mostly as shorter chain polysaccharides. Partial or complete digestion may improve the availability of these nutrients. Whole extracts are likely to contain other important cofactors and will be less likely to have been damaged during extraction than those that have been purified. Freeze-drying is the best extraction process as it is a low temperature operation. Air drying and roller drying may cause heat damage.

Cofactors play a significant role in the production of cartilage including Vitamins E and C, and minerals/trace elements boron, zinc, copper, selenium, magnesium, and manganese. Trace elements, bound in chelated form, are more readily available to the body and less likely to interact and interfere with each other during absorption. Rich sources of amino acids, especially the sulphur containing ones (methyl sulphonyl methane) are important in the manufacture of cartilage matrix.
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Apart from the provision of nutrients and chondroprotective agents for cartilage maintenance and repair, there is an additional requirement for anti-inflammatory and anti-oxidant agents for the management of degenerative joint disease (arthritis). As the cartilage degenerates there is an increase in free radical damage and subsequent inflammation. While the CPAs have been shown to exert some anti-inflammatory effect there are other agents which are more effective. Vitamin A and E, green lipped mussel and some herbs are able to provide significant effects on joint function. It is likely that these agents will slow down the progression of disease and if used early enough, may prevent the development and progression of arthritis. Much work is still required to determine if this is possible. It is the author's opinion that the use of sufficient raw bone, cartilage and connective tissues in the diet, especially in the growth phase, are essential to the proper development and maintenance of cartilage.