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


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

Dermatan sulfates:

composed of L-iduronate (IdoA) of D-glucuronate (GlcA) plus GalNAc-4-sulfate; GlcA and IdoA sulfated; linkages is β(1,3) if GlcA, α(1,3) if IdoA
Structure of the disaccharide component of chondroitin sulfates

Chondroitin 4- and 6-sulfates:

composed of D-glucuronate (GlcA) 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 L-iduronate(IdoA: many with 2-sulfate) or D-glucuronate (GlcA: many with 2-sulfate) and N-sulfo-D-glucosamine-6-sulfate; linkage is α(1,4) if IdoA, β(1,4) if GlcA: heparans have less overall sulfate than heparins
Structure of the disaccharide component of keratan sulfates

Keratan sulfates:

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

GAG Localization Comments
Hyaluronate synovial fluid, vitreous humor,
ECM of loose connective tissue
large polymers; molecular weight can reach 1 million Daltons; high shock absorbing character; average person has 15 gm in body; 30% turned over every day; synthesized in plasma membrane by three hyaluronan synthases: HAS1, HAS2, and HAS3
Chondroitin sulfate cartilage, bone, heart valves most abundant GAG; principally associated with protein to form proteoglycans; the sulfation of chondroitin sulfates occurs on the C-2 position of the uronic acid residues and the C-4 and/or C-6 positions of GalNAc residues; the chondroitin sulfate proteoglycans form a family of molecules called lecticans and includes aggrecan, versican, brevican, and neurcan; major component of the ECM; loss of chondroitin sulfate from cartilage is a major cause of osteoarthritis
Heparan sulfate basement membranes, components of cell surfaces contains higher acetylated glucosamine than heparin; found associated with protein forming heparan sulfate proteoglycans (HSPG); major HSPG forms are the syndecans and GPI-linked glypicans; HSPG binds numerous ligands such as fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF), and heptocyte growth factor (HGF); HSPG also binds chylomicron remnants at the surface of heptocytes; HSPG derived from endothelial cells act as anti-coagulant molecules
Heparin component of intracellular granules of mast cells
lining the arteries of the lungs, liver and skin
more sulfated than heparan sulfates; clinically useful as an injectable anticoagulant although the precise role in vivo is likely defense against invading bacteria and foreign substances
Dermatan sulfate skin, blood vessels, heart valves was originally referred to as chrondroitin sulfate B which is a term no longer used; the sulfation of dermatan sulfates occurs on the C-2 position of the uronic acid residues and the C-4 and/or C-6 positions of GalNAc residues; may function in coagulation, wound repair, fibrosis, and infection; excess accumulation in the mitral valve can result in mitral valve prolapse
Keratan sulfate cornea, bone, cartilage aggregated with chondroitin sulfates usually associated with protein forming proteoglycans; keratan sulfate proteoglycans include lumican, keratocan, fibromodulin, aggrecan, osteoadherin, and prolargin

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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: January 16, 2017