Chiropractic Products, October 1988: 54-56
Reprinted with permission of Chiropractic Products, ©1988

Mucopolysaccharides (Chondroitin Sulfates) As Dietary Supplements: Sources, Production and Comparative Bioavailability
by Luke R. Bucci, Ph.D.

The previous column, which dealt with nutritional support for osteoarthritis, mentioned chondroitin sulfates. This installment will explore the class of products known as mucopolysaccharides or glycosaminoglycans. We will find out what product options are available, how these products are made and what that means to you and your patients.

Chiropractors are always in touch with connective tissue. Bones are surrounded by it, and in various forms, connective tissue holds us together on every scale from molecular to whole-body scales. Doctors frequently overlook the health of connective tissue because it is not a single, easily identifiable organ like a heart or liver, but is extracellular. Connective tissue is everywhere, and when connective tissues suffers, so do the organs involved. Practically every abnormal condition affects or alters connective tissue in some way. This pertains not only to joints, but also to blood vessels, skin, hair, eyes and all the compartments between bodily structures, like "ground substances" or basement membranes. For the interests of chiropractors, the next two columns will feature use of mucopolysaccharide products for connective tissue healing and cardio-vascular effects.

Connective tissues are made of three principle ingredients: water, collagens and proteoglycans. Collagen is a fibrillar protein that gives structural integrity to connective tissue. We will focus on proteoglycans, the updated name for mucopolysaccharides. Because connective tissue is physically strong and tough, scientists have had a difficult time correctly breaking down and characterizing proteo-glycans. Basically, proteoglycans are a combination of long chains of special, modified sugars (oligo-saccharides) known as glycosaminoglycans (GAGs) that are lashed together much like Oriental bamboo scaffolding by special, modified proteins. There are six separate GAGs: hyaluronic acid, chondroitin sulfates, dermatan sulfates, keratan sulfates, heparan sulfates and heparin (which is not structural and will be ignored). It is not really important to know exactly which modified sugars make up each GAG. It is important to know that chondrocytes must take dietary carbohydrates (sugars) and with enough energy, protein, vitamins and minerals, convert those sugars into the modified ones needed for GAG synthesis. A GAG must then be strung together, cast out into the extracellular matrix, worked over by enzymes that control 3-D structure of GAG and collagen chains, merged with other GAGs and collagen to form desired structures, then "cured" by other enzymes to harden and solidify the new connective tissue.

Major sources of GAGs for nutritional supplements include cartilage, shellfish and plants. An abundant supply of cartilage in the form of bovine trachea, aorta, nasal septa and other pieces is available from abattoirs. Cartilage from other animals (whales, pigs or sheep) are generally not routinely collected. Shark and ray skeletons are mostly cartilage, but supply is more erratic than beef trachea and is more subject to contamination (ever smell a day-old dead shark?). These sources of cartilage must be processed in order to achieve a stable, reproducible, workable powder. Usually, partial digestion of trachea or cartilage with acid and/or pepsin or other proteolytic enzymes is employed. Different suppliers use different methods, resulting in varying purities of GAGs, but all are referred to as trachea or cartilage powders.

Another source of GAG for products is the green-lipped mussel, Perna canaliculus, harvested from tidal pool farms in New Zealand. Normally, the contents of the entire mussel (minus the shell) are freeze-dried. Although claimed to be rich in GAGs, there is very little accessible scientific literature that has characterized Perna GAGs.

Many plant sources for GAGs are available, but digestion of these by humans is more difficult, meaning plants are usually poor sources for GAGs. The several different types of carageenans from seaweeds are one example.

Thus, beef trachea is the major source of cartilage powder for supplement products. However, the story does not end here, but continues with further purification of GAGs.

The major GAG in mammals is chondroitin sulfates (CS). Methods for commercial purification or enrichment of CS exist, and products containing purified CS have been available for over seven years. CS was shown to be the active fraction of cartilage powder, unlike the collagen portion (which when boiled becomes gelatin). When CS is purified from cartilage powders, several advantages are apparent. First, a known and reproducible entity is available. This is important for consistent dosing over long time periods, especially critical for medical research. Second, the uptake is reproducibly increased. Third, potential allergenicity from bovine collagen or its fragments is bypassed. Injectable cartilage powders caused allergic reactions in both animal and human studies, whereas purified CS has not elicited adverse reactions. Fourth, lesser amounts of CS are needed compared to cartilage powder, meaning patient compliance is improved .

Potential drawbacks of purified CS are: a higher cost than cartilage powder; and loss of minor GAGs such as keratan sulfate. Since purified CS is 3-10 times more effective than an equal amount of cartilage powder, the higher cost is actually negated, and purified CS is often more cost-effective. Loss of unique sugars from minor GAGs does not appear to dampen the effectiveness of purified CS, probably because chondrocytes can synthesize these unique sugars from those found in CS.

There are two forms of CS -- chondroitin-4-sulfate (CSA) and chondroitin-6-sulfate (CSC). CSB became dermatan sulfate. While there is still some controversy, as a dietary source for modified sugars, there appears to be no significant difference between the two types of CS. Usually CS-6 will predominate in purified CS products.

Purified CS is extracted from cartilage or cartilage powder by digestion of collagen with heat, acids or enzymes, followed by various salt or solvent extractions to recover CS. Since the end product is similar from each purification scheme, the only concern about the process would be possible use of toxic solvents.

Many cartilage preparations are not well-characterized. They can range from dried trachea to almost pure CS. As a result, uptake studies on cartilage powders are lacking. Hypothetically, more purity should give more absorption of modified sugars. Cross-linked collagen is very difficult to digest, and incomplete digestion would trap proteoglycans, rendering them unabsorbable. Therefore, absorption of GAGs from cartilage powders is likely to be highly variable, and is not predictable for a particular individual product.

In contrast, purified CS absorption has been studied in man and animals. Ninety percent of radioactivity (from radioactive sulfur) after a one gram dose of labeled CS was recovered in the urine of normal humans within four days. Eight percent of this radioactivity was attached to large molecular weight GAGs, while the remainder was degraded to free sulfate. This means that oral CS is absorbed from the digestive tract into blood and is taken up and metabolized by tissues, which obviously have the ability to uptake large molecules of CS. Other studies showed that CS was absorbed intact into the blood as well as partially and completely degraded pieces. Further results showed that absorbed CS stayed around in the body with a half-life of 12-24 hours, meaning once daily dosing may be sufficient to saturate tissues. What is still not well known is specific uptake of modified sugars by chondrocytes. Animal studies suggest that chondrocytes do utilize absorbed CS, and positive human clinical trails also offer support of this notion.

Mucopolysaccharides, now known as glycosaminoglycans (GAGs), are available in crude and purified forms. Crude forms include varying grades of cartilage powders (usually from beef trachea), dried mussels or seaweed extracts. Availability of active components (GAGs) is not well known for each crude preparation, but they still represent a useful dietary source for GAGs. On the other hand, purified chondroitin sulfates are also available. Absorption has been studied and shown to be nearly complete. For purposes of cost effectiveness, reproducibility of results, patient compliance and physician confidence, purified chondroitin sulfates products offer advantages over cartilage powders.