Joint Care Supplements

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What Are Joint Care Supplements?

The field of supplements to treat ailments of the joints is primarily focused on components of the natural lubricating substances in the joints. The structure and function of these substances is outlined in the next section. These supplements include glucosamine (usually as glucosamine sulfate), chondroitin (as chondroitin sulfate), and methylsulfonylmethane, MSM. Glucosamine and chondroitin are complex sugar (carbohydrate) compounds and MSM is a sulfur containing compound that is purported to be useful in promoting the formation of bioactive glucosamine and chondroitin sulfates in the joints. Aside from these major joint care supplements, consumtion of calcium and vitamin D are known to aid in the prevention of osteoporosis which can contribute to joint pain. Osteoporosis is a loss of bone mineral resulting in fragile easily fracturing bones.

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Natural Joint Lubricating Substances

The naturally occurring substances found in the joints that serve as "lubricating fluids" are extremely large complex sugars (carbohydrates) composed of repeating units of various disaccharide units. These complex structures are termed heteropolysaccharides. The most abundant heteropolysaccharides in the body are the glycosaminoglycans (GAGs). These molecules are long unbranched polysaccharides containing a repeating disaccharide unit. The disaccharide units contain either of two modified sugars, N-acetylgalactosamine (GalNAc) or N-acetylglucosamine (GlcNAc), and a uronic acid such as glucuronate or iduronate. GAGs are highly negatively charged molecules, with extended conformation that imparts high viscosity to the solution. GAGs are located primarily on the surface of cells or in the extracellular matrix (ECM). Along with the high viscosity of GAGs comes low compressibility, which makes these molecules ideal for a lubricating fluid in the joints. At the same time, their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration. The specific GAGs of physiological significance are hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, heparan sulfate, and keratan sulfate. Although each of these GAGs has a predominant disaccharide component (see Table below), heterogeneity does exist in the sugars present in the make-up of any given class of GAG.

Hyaluronic is unique among the GAGs in that it does not contain any sulfate and is not found covalently attached to proteins as a proteoglycan. It is, however, a component of non-covalently formed complexes with proteoglycans in the ECM. Hyaluronic acid polymers are very large (with molecular weights of 100,000–10,000,000) and can displace a large volume of water. This property makes them excellent lubricators and shock absorbers.

Structure of the disaccharide component of hyaluronates

Hyaluronates:

composed of D-glucuronate + GlcNAc
linkage is β(1, 3)
Structure of the disaccharide component of dermatan sulfates

Dermatan sulfates:

composed of L-iduronate (many are sulfated)
+ GalNAc-4-sulfate
linkages is α(1, 3)
Structure of the disaccharide component of chondroitin sulfates

Chondroitin 4- and 6-sulfates :

composed of D-glucuronate
and GalNAc-4- or 6-sulfate
linkage is β(1, 3)
(the figure contains GalNAc 4-sulfate)
Structure of the disaccharide component of heparins

Heparin and Heparan sulfates:

composed of iduronate-2-sulfate (D-glucuronate-2-sulfate)
and N-sulfo-D-glucosamine-6-sulfate
linkage is α(1, 4)
(heparans have less sulfate than heparins)
Structure of the disaccharide component of keratan sulfates

Keratan sulfates:

composed of galactose + GlcNAc-6-sulfate
linkage is β(1, 4)

GAG Localization Comments
Hyaluronate synovial fluid, vitreous humor,
ECM of loose connective tissue
large polymers, shock absorbing
Chondroitin sulfate cartilage, bone, heart valves most abundant GAG
Heparan sulfate basement membranes, components of cell surfaces contains higher acetylated
glucosamine than heparin
Heparin component of intracellular granules of mast cells
lining the arteries of the lungs, liver and skin
more sulfated than heparan sulfates
Dermatan sulfate skin, blood vessels, heart valves  
Keratan sulfate cornea, bone, cartilage aggregated with chondroitin sulfates  

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Joint Care Supplements

Little evidence suggests that glucosamine is superior to a placebo treatment in restoring articular cartilage (the smooth, white tissue that covers the ends of the bones where they come together to form a joint) in patients with damaged or osteoarthritic (OA) joints. Other studies have reported conflicting results regarding improvement in the pain and disability associated with OA with the use of glucosamine and chondroitin as single agents; however, when improvement has been demonstrated, the formulation has primarily been glucosamine sulfate combined with chondroitin sulfate.

In an analysis of five systematic reviews of the scientific literature as well as one clinical guideline it was found that there is only inconsistent conclusions with only modest effects on reported pain and function in patients taking glucosamine and/or chondroitin supplements. A reduction in joint space narrowing was more consistently observed, but the effect size was small and the clinical significance uncertain. A separate review of eight primary trials of >12 months' duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulfate, but the clinical importance of these differences was not clear. In two studies of glucosamine sulfate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect.

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Supporting Research

Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, Royle P, and Thomas S. 2009. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technol. Assess. 13(52):1-148.

Kirkham SG, and Samarasinghe RK 2009. Glucosamine. J. Orthop. Surg. 17(1):72-76

Fox BA, and Stephens MM 2009. Glucosamine/chondroitin/primorine combination therapy for osteoarthritis. Drugs Today 45(1):21-31


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Last modified: February 9, 2011