Glucosamine & Chonroitin
Get Smart About Glucosamine and Chondroitin Sulfate
By Mark Timon, M.S. Clin Nut.
An astute observer of nutritional breakthroughs may have noticed controversy over the efficacy of glucosamine hydrochloride (HCL) and chondroitin sulfate (CSA.) One faction of the nutrition industry has adopted the position that glucosamine sulfate is "the only form" of glucosamine that works. It's efficacy, they claim, is founded on mountains of research, while glucosamine hydrochloride is unproved and is, therefore, obviously inferior. This is a precarious assumption to make.
Just because a large body of research has accumulated around one specific form of a nutritional substance does not necessarily mean that that form is the best source of the nutrient. The largest body of research usually builds around the first form of a nutrient to be tested. Following scientific practice, one researcher's work must be corroborated by subsequent work from other researchers. In this way, a mountain of data builds that deals with the first form of the nutrient tested.
Nutritional science in particular is rife with cases where early research on one particular form of a nutrient only led the way to eventual discovery of better forms. A classic example is seen with calcium. The greatest amount of research on calcium has been conducted on calcium carbonate. The result has been to not only demonstrate calcium's roles in human nutrition, but also to prove that calcium carbonate is the least desirable form of calcium to ingest. We now know that calcium carbonate has the poorest bioavailability in comparison to nearly every other form of calcium tested. Furthermore, when calcium from calcium carbonate is absorbed by an individual, it has the unique ability to shut down bone remodeling, as shown by researcher, Dr. Robert Recker.
The history of calcium research should those arrayed against glucosamine HCL and chondroitin sulfate to the concept that the largest body of research does not necessarily mean that the substance researched is ultimately the best. Although the greatest amount of research has indeed been conducted on the first form of glucosamine to be tested, specifically glucosamine sulfate, recent research at John's Hopkins and the University of Toronto and other research centers have shown that glucosamine hydrochloride is not only efficacious but at least equally bioavailable to and possibly more bioavailable than glucosamine sulfate.
Such findings will not be a surprise. We have seen this before. The early research on vitamin B-1 centered on thiamin mononitrate. Subsequent research on thiamin hydrochloride demonstrated equal bioavailability and superior safety. It turned out that ingestion of thiamin mononitrate led to the formation of small amounts of carcinogenic nitrosamines in the stomach, while thiamin hydrochloride proved to be innocuous. Nutrients in the form of hydrochlorides in general tend to be highly compatible with human digestion. Sulfates and chlorides, on the other hand, tend to be irritating to gastrointestinal tissues. Potassium chloride and ferrous sulfate are well known examples.
I find it interesting that a number of former glucosamine sulfate manufacturers in Europe have switched to the manufacture of glucosamine HCL. Fine chemical manufacturers who made glucosamine sulfate and later switched to glucosamine HCL would not have done so if there were any question of its inferiority. The investment in converting to glucosamine HCL and the risk of lost sales should the product have proved inadequate would have dissuaded them from manufacturing glucosamine HCL. But their own clinical trials with animal models had undoubtedly shown that the new form of glucosamine was both safe and efficacious. In other words, the fine chemical manufacturers would NOT have turned to glucosamine HCL just on a whim or just to save some money. Biochemical knowledge and sound business decisions directed them down that path.
Glucosamine
and Arthritis
A deficiency of any one of a number of nutrients can lead to impaired cartilage
formation. This also means that glucosamine (in any form), being only one
nutrient that can be used by the cartilage-building cells called chondrocytes,
is not going to be able to effect complete, thorough reconstruction of
cartilage. More nutrients are needed than just glucosamine.
There are quite a few other supplemental nutrients and dietary modifications that could be employed in the treatment of osteoarthritis, If cartilage still remains between the joints, it can be thickened and improved. In fact , new cartilage can be rebuilt. Glucosamine has been shown to thicken cartilage by up to 37%. But do not be deceived into believing all that thickening is new cartilage. Let me explain.
Glucosamine re-hydrates cartilage, and the effect is transient. Glucosamine is taken into the chondrocytes, cells buried within cartilage that manufacture new cartilage. In the chondrocyte, glucosamine is used in the synthesis of the acidic mucopolysaccharide, hyaluronic acid. By-the-way, it is NOT glucosamine sulfate that is used. The sulfate portion is discarded and only the glucosamine is used. Similarly, when glucosamine HCL is taken in, the HCL is discarded and the chondrocyte uses the glucosamine. So at the cellular level, there is no intrinsic advantage to using glucosamine sulfate.
The hyaluronic acid thus produced is then sent from the cell to percolate out through the cartilage and eventually become a primary component of synovial fluid, the slippery lubricant bathing opposing plates of cartilage. You can see that the hyaluronic acid made from glucosamine is a transient component of cartilage. It is not immediately a structural member of new cartilage. But, since hyaluronic acid is a water magnet, it attracts and holds moisture to it. So as it wends its way very slowly through cartilage, it drags a lot of water with it.
As a result, the cartilage becomes infused with water. It becomes more plump (thicker), and more able to cushion forces placed upon the joints. You can now see how supplemental glucosamine leads to the production of more hyaluronic acid which leads to the re-hydration of cartilage which leads to thicker, more protective cartilage. In this way, the condition of the joint is improved.
If glucosamine supplementation is not continued, then the hyaluronic acid will eventually work its way out of the cartilage and into the synovial fluid. Then, formerly re-hydrated cartilage gradually shrinks back again to its thinner, harder configuration.
There is some evidence that very long, continued use of glucosamine supplements may eventually lead to the actual construction of new cartilage, but that would come as a secondary effect. Chondrocytes driven to greater activity in the synthesis of hyaluronic acid will eventually also synthesize a little more of the proteoglycan base AND collagen fibers that form the structural parts of cartilage. That synthesis of new cartilage will be limited, however, by the availability of building materials (i.e. the amino acids required for collagen and chondroitin sulfate or its components.)
Chondroitin
sulfate (CSA)
One of those building materials is chondroitin sulfate. I know that some "there
is no additional benefit provided by chondroitin sulfate." Because the
chondroitin sulfate molecule is alleged to be too large for absorption. You will
recall that the same argument has been used to disparage a number of supplements
in our industry in the past, lecithin among them, and that the argument was
eventually proved wrong.
The clinical results for CSA do not support such negative commentary. Lester Morrison, M.D. and his colleagues at Loma Linda University published research in the 1970's dramatically demonstrating benefits of oral CSA consumption. In that research, published separately, and in two books (one for the scientific community and one for the lay public in the 1980's), Morrison discusses his successful treatment of heart disease with chondroitin sulfate. If chondroitin sulfate, taken orally, could be absorbed and utilized by his hundreds of human test subjects with stunningly positive results, then it was obviously bioavailable.
Morrison's patients realized greater elasticity in arterial tissue, lowered blood fats, and virtually no blood clot formation. Morrison was carrying out his landmark research in the 1960's, so you would think the question of whether chondroitin sulfate (CSA) is bioavailable or not would no longer be a question.
Another researcher, A. Conte, has published at least 11 papers dealing with chondroitin sulfate. In some of them he measures bioavailability through various means similar to those used by other researchers to evaluate glucosamine bioavailability. According to this work, CSA is quite readily absorbed and transported throughout the human body.
Pipitone, in his article titled "Chondroprotection with chondroitin sulfate", clearly states, "glycosaminoglycans [chondroitin sulfate]…play a crucial role in the physiology of joint cartilage … [S]upplementation might enable chondrocytes to replace the proteoglycans [the glue that holds cartilage together]…[It] exhibited good therapeutic efficacy …act[s] as an anti-inflammatory…[is] able to inhibit enzymes which may damage joint cartilage…[and] this drug is absorbed by the body…" This is strong evidence that says chondroitin sulfate is an efficacious treatment for osteoarthritic joints.
A. Baici has investigated both the bioavailability and efficacy of chondroitin sulfate. In his paper dealing with chondroitin sulfate's ability to inhibit the cartilage degrading enzyme, leucocyte elatase, Baici states, "The best inhibitory activity of chondroitin sulfate was found in fractions having at the same time a high proportion of chondroitin-6-sulfate relative to the corresponding 4-isomer and a high molecular mass." This statement casts doubt on arguments that chondroitin sulfate can't be absorbed because it is too large.
In a later study, Baici finds no elevation of chondroitin sulfate in blood serum, leading him to think that orally ingested chondroitin has failed to make it across the intestinal mucosa. Perhaps Baici was looking in the wrong place. Existing literature suggests that chondroitin sulfate does NOT float freely through the serum, but is instead bound to cell membranes and transported through the blood in that way. We must also remain aware that it is not unusual for the method of transportation of a nutrient through the blood to elude researchers long after it is known that something can be ingested and then found in tissues. For example, the transport mechanism for proanthocyanidins (OPCs) is not clearly elucidated even though it is well established that OPCs are transported to bodily tissues within minutes of ingestion. How they get from the gut to the muscles or the nerves or the eyes is still not clearly understood.
Just as radioactive tagging of OPCs verified its rapid bioavailability, radioactive tagging of chondroitin has been used to track its metabolic pathways and presence in tissues. Those studies clearly established not only that it can be absorbed, but that a high percentage of orally ingested chondroitin sulfate (e.g. 70%) can be absorbed within 2 hours. I suspect. given the larger consensus that CSA can and is absorbed, that Baici's crude hunt for CSA in blood plasma was a quick test that showed nothing and meant less in the overall scheme of science.
It has been proposed by others, however, that CSA may perhaps be degraded during digestion and absorbed in smaller fragments. If this is the case, it does not preclude the efficacy of CSA. The components of CSA could still be taken in by chondrocytes and used to synthesize the proteoglycan base of cartilage. The components of CSA could still be taken up by the connective tissue in arteries and employed in restoring flexibility and elasticity there. The work of Morrison, Pipitone and Baici demonstrates that whether absorbed intact or in its component parts, supplemental CSA appears to restore connective tissues, aid healing, and support cardiovascular health.