October 1988: 54-56
Reprinted with permission of Chiropractic Products, ©1988
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.
What are mucopolysaccharides or glycosaminoglycans?
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.
Sources of GAGs
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.