Chondroitin remains one of the best-known supplements not only for joint health, but also as a “natural supplement” among mass market consumers. It is often consumers’ singular entry point into consuming condition-specific dietary supplements as part of normal preventative, self-care regimens.
But, not all chondroitin ingredients perform the same, nor do they fall into typical parameters of quality. IncaCartilagoTM, the brand name for a proprietary Chondroitin Sulfate-E (CS-E) available exclusively from leading branded ingredient supplier OptiPure, is a new, superior-performing chondroitin sulfate that has proven efficacy to support bone health as well as joint health. It is the only chondroitin source that effectively supports both systems, and is therefore genuinely revolutionary; consumers can now take one supplement that can support both bone and joint health, affording them greater convenience.
Unique Composition
During our extensive research and development of Humboldt squid-derived chondroitin, our team found that to date, there had been no thorough investigation about the differentiations between Chondroitins A, C and E, with the sole exception of where sulfation occurs. OptiPure’s innovative use of two-dimensional electrophoresis has been able to consistently both identify and quantify chondroitin types in our material, and is therefore groundbreaking 
in the industry.
IncaCartilagoTM is unique, as shown in assays, in being th only source known to have a full profile of active sulfates, giving it its dual support activities. A majority of chondroitin sulfates on the market in all channels of distribution are derived from bovine and porcine sources, and to a lesser but still significant extent, marine sources such as shark and salmon. Another marine source, the Humboldt Squid, found in abundance off the coast of South America, exhibits a characteristically superior chondroitin profile. IncaCartilagoTM chondroitin sulfate is the most potent on the market, with 60% guaranteed minimum of Total Chondroitin Sulfates, 40% minimum of Chondroitin Sulfate E, and 20% minimum Chondroitin Sulfates A & C. Such high percentages provide the consumer with the ultimate protective benefit of each type of chondroitin sulfate, effectively supporting BOTH bone and joint structures and functions—in one easy dosage form.
Humboldt squid-derived chondroitin sulfate (CS-E) is sulfated at carbons 4 and 6 of glucuronic acid—acetylgalactosamine; while that sourced from bovine, porcine (CS-A) or shark (CS-C) only exhibit one site of sulfation.
Bone Benefits
Age-related bone loss and development of osteoporosis is characterized by lowered osteoblast content and activity, and increased osteoclast content and activity. The breaking down of bone accelerates while the bone-building declines to keep up, resulting in more brittle bones with higher porosity.
Unlike other chondroitin sulfate sources, the unique composition of IncaCartilagoTM encourages osteoblastic and osteocalcin formation, replication and expression.
Following conclusions of a preliminary study indicating that CS-E binds to MC3T3-E1 cells (i.e., specific animal-derived bone cells), a more in-depth investigation using MC3T3-E1 osteoblastic cells compared various chondroitin sources. The study found that test sources CS-C (from shark), CS-D (from eel), heparin sulfate and heparin “had no positive or inhibitory effect on the growth of MC3T3-E1 cells”; however, CS-E (from Humboldt squid) “significantly enhanced the growth of the cells” (1).
CS-A, CS-C and CS-D produced no mineralization effect in cells seeded at low density. CS-E, however, actually enhanced the mineralization of the osteoblastic cells (1).
Favorable for joint health, testing demonstrated that CS-E enhanced collagen deposition by MC3T3-E1 cells, while CS-A and CS-C did not show any similar net positive effect (1).
This study utilized fluorescence correlation spectroscopy, which illuminated for the first time that oversulfated CS, such as CS-E or CPS, binds to a specific bone morphogenetic protein called MP-4. These sulfated glycosaminoglycans (GAGs) bind directly to the BMP-4 molecule resulting in the enhancement of mineralization. CS-E and CPS had strong affinity for BMP-4, whereas CS-D and monosulfated CS (CS-B or CS-C) did not. The results suggest that neither the E unit nor H unit is necessary to bind to BMP-4 and subsequent enhancement of the mineralization of MC3T3-E1 cells (1).
The study authors assert that their findings support the concept that CS-E enhances mineralization induced by up-regulating BMP-4 activity. CS-E affects the phenotype of osteoblasts at the early stage of differentiation while osteoblasts secrete BMP-4 (1).
Overall, this study has shown a clear mechanism of oversulfated CS (such as CS-E) in bone formation as well as its importance in biomineralization processes, making IncaCartilagoTM a strong contender in the bone health supplement marketplace.
More recent research (“Osteoblast Model MC3T3-E1 BMP and Osteocalcin Induced”) presented at the 64th meeting of Japanese Society for Nutrition and Food Science (2010) validates this activity. After six days in the assay, CS-E outperformed other chondroitin sources in accelerating bone morphogenetic protein activity nearly three times as much as its closest competitor, CS-C. After day 12, CS-E still outperformed other chondroitins in addition to showing an exceptional rate of osteocalcin formation and expression by nearly 33% over its closest competitor, CS-C.
Joint Health
One of the persistent problems experienced by people with age-related joint degradation is pain and discomfort due to inflammation. This creates the need to address the pain instantaneously, as well as fuels the desire to suppress painful bouts in the future. CS-E has been studied to show solid performance in supporting against joint pain, making it highly attractive as a dietary supplement for those who are leery of the side effects of NSAIDs. IncaCartilagoTM is the first chondroitin shown in a particular study to affect the binding and action of midkines, the proliferation of which are responsible for pain sensation.
Studies have shown distinct evidence that CS-E selectively binds to midkines (MK), which are specific proteins that enhance cell proliferation, cell migration, angiogenesis and fibronlysis, and well as are activated in inflamed areas to instigate the migration of inflamed cells. MK binds heparin to promote growth, survival and migration of various target cells and is involved in the etiology of inflammatory disease, such as arthritis and in particular, rheumatoid arthritis. Although typical chondroitin sulfates do generally bond well to a specific MK receptor (PTPz), CS-E was demonstrated in a study to exhibit the most potent and swift ability to do so, thus inhibiting the migration of inflamed cells (2).
In this study, CS-E administered intraperitoneally (a quick site of absorption and utilization in the lining of the abdominal cavity), significantly suppressed antibody-induced arthritis. MK are known to promote antibody-induced arthritis by spurring the migration of inflammatory leukocytes and osteoclastic differentiation; CS-E had been previously shown to inhibit the migration of MK-dependent macrophages (2).
The study authors note that MK is a prime candidate for targeting by CS-E in the inhibition of antibody-induced arthritis. They concluded: “We found that intraperitoneally administered chondroitin sulfate E, but not chondroitin 4-sulfate [CS-A], inhibits the development of antibody-induced arthritis, a model of rheumatoid arthritis. The finding has clinical implications for the treatment of rheumatoid arthritis . . . As to the mechanism of action of chondroitin sulfate E, we suggest that inhibition of MK is involved, but actions to other cytokines are also likely . . . Chondroitin sulfate E can act systemically as well as locally in the joint” (2).
Conclusion
IncaCartilagoTM represents a groundbreaking evolution in the bone and joint support category, with applications to help millions of Americans safely address the preservation of their bones and joints in one effective, safe dosage form. Intensive clinical research is and will be ongoing to further validate its actions and thus strengthen its highly attractive market position for brand marketers.
References
1. T. Mizayaki, et al., “Oversulfated Chondroitin Sulfate-E Binds to BMP-4 and Enhances Osteoblast Differentiation,” J. Cell. Physiol. 217 (3), 769–777 (2008).
2. H. Yamamoto, et al., “Midkine as a Molecular Target: Comparison of Effects of Chondroitin Sulfate E and siRNA,” Biochem. Biophys. Res. Commun. 351 (4), 915–919 (2006).
Published in WholeFoods Magazine, March 2011
