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Glucosamine and chondroitin: partners of the extracellular matrix

What are glucosamine and chondroitin?

Proteoglycan

Glucosamine is a monosaccharide that occurs naturally in our bodies. It is the precursor to a number of glycosaminoglycans such as hyaluronic acid, chondroitin and keratan sulphate, which in turn make up some important components of the extracellular matrix called aggrecans. Glucosamine can be found in certain foods, but we mostly get it from dietary supplements derived from chitin, found in the exoskeleton of crustaceans and the cell walls of mushrooms. To keep the molecule stable, glucosamine often comes in the form of a salt (sulphate or hydrochloride), which will be broken down in our digestive system. The sulphate form is often preferred because it occurs naturally in our bodies, and may also stimulate glycosaminoglycan synthesis in the cartilage. This is why we have chosen this form for our products.      

Chondroitin is the most abundant glycosaminoglycan in our cartilage. It helps to retain water in the tissue and, by doing so, to maintain its osmotic pressure, elasticity and flexibility. Though present in animal bones and cartilage, it is mainly found in dietary supplements.

A positive effect on osteoarthritis

The benefits of taking glucosamine sulphate and chondroitin for osteoarthritis have for a long time been the subject of studies and debate, due to inconsistent results and a placebo effect that is sometimes quite high. Nevertheless, most groups are now in agreement over the usefulness of these supplements, and also over their safety, as they are often better tolerated than some anti-inflammatory drugs. The 2006 GAIT study2 showed, based on 1583 patients, that taking glucosamine and chondroitin combined, reduced the everyday pain (OARSI-OMERACT score)3 of people with moderate or severe osteoarthritis. Other studies have highlighted that the combination of glucosamine and chondroitin reduced pain as effectively as opioid painkillers (2 x 50 mg Tramadol)4 or a COX-2 inhibitor non-steroidal anti-inflammatory drug (celecoxib)5, and increased joint mobility (in the jaw and knees). The combination has been associated with an improvement in Lequesne index scores,6 showing improved functioning in the problem joint, and a decreased WOMAC score7, which shows a reduction in pain during everyday activities. It also helps to reduce swelling, effusion and stiffness in the joints when the osteoarthritis is not too advanced8–11. By limiting the long-term progression of the disease and its symptoms, taking chondroitin and glucosamine reduces the risk of needing a total joint replacement (by up to half the number of knee replacements, for example)12. The improvement in symptoms may be even more significant if glucosamine and chondroitin are taken with a source of flavonoids13, such as rosehip, for example.       

Protective effects on the joints: by what mechanism?          

Analysing the properties of glucosamine and chondroitin sulphate in cells has shown that they alter the structure of joints,14 which explains why they may impede the progression of joint diseases. A 2014 report by Calamia et al.10 shows the effects of chondroitin and glucosamine on cartilage, stressing their anti-inflammatory and chondroprotective properties.

In particular, they may slow the degeneration of cartilage, by suppressing MMPs (metalloproteinases, which break down collagen and aggrecans), catabolic intermediates, and the oxidation of lipids and proteins. In addition, MMP-inhibitor enzymes (TIMPs) were shown to be activated in blood and synovial fluid. 10 A tissue culture of chondrocytes with glucosamine and chondroitin showed an increase in the production of hyaluronic acid by synovial cells, and of proteoglycans and collagen by chondrocytes. 10 The profile of proteins secreted by the chondrocytes showed a trend towards restoration of the cytoskeleton. At the onset of osteoarthritis, the sub-chondral bone is remodelled (e.g. osteophytes are formed) and the metabolism of osteoclasts is altered to encourage greater resorption. These mechanisms can be reversed by taking glucosamine and chondroitin together.15

Chondroitin and glucosamine also limit levels of inflammation markers (cytokines, prostaglandins, nitric oxide, C-reactive proteins, etc.) and inhibit activation of certain inflammatory cellular processes (e.g. those associated with COX-2 or NF-κB activation), which are chronically over-active in osteoarthritis. Synovial fluid samples showed a reduction in prostaglandin levels (inflammatory molecules) and a maintenance of low cytokine levels (in contrast with the increased levels in the osteoarthritis control group), demonstrating the anti-inflammatory power of chondroitin and glucosamine. The synergy of these two substances affects the proteins made by chondrocytes, particularly those associated with oxidative stress modulation, energy production, and cell metabolism. 10

The properties of glucosamine and chondroitin therefore enable a gradual, long-lasting reduction in pain and inflammation, and a stable improvement in joint function.

Chondroitin and glucosamine: how do they work?

As chondroitin is a fairly large molecule, it cannot get inside joint cells to have any effect. It owes its anti-inflammatory properties to its ability to form links with various receptors on the surface of chondrocytes (CD44 TLR4, ICAM-1) and to influence the activation of gene cascades, which cause the transcription process for certain genes to be activated. Firstly, this will cause inflammatory molecules, or those that break down the extracellular matrix, to be inhibited. Secondly, chondroitin will stimulate certain molecules involved in synthesising components of the matrix, such as hyaluronic acid or collagen, and will increase the formation of chondrocytes.

Glucosamine, on the other hand, can enter cells with the help of glucose transporter molecules. It will then be modified and made able to interact with certain cellular processes (e.g. to compete with the nuclear translocation of NF-κB), which will limit the expression of pro-inflammatory and proteolytic genes. It will also become a substrate in the synthesis of proteoglycans (among other molecules).

High rates of absorption and concentration in tissue

In order to record intestinal absorption after taking oral glucosamine sulphate, fluorescent molecules were given to horses, and blood and synovial fluid samples taken regularly. Plasma glucosamine levels were elevated between 30 mins and 4 hrs of administration, and remained so in synovial fluid for over 12 hrs.16 Regarding radioactive chondroitin sulphate administered orally (to dogs and rats), around 70% is absorbed, a significant proportion of which is in the form of intact polymers (probably through pinocytosis).17It rapidly increases in the plasma before reaching a long plateau (highest at 14 and 28 hrs), and a high concentration has been observed in the cartilage and joints.18

It is therefore now clear that by taking these molecules orally, the substance can reach and get to work on our tissue.

Glucosamine and chondroitin: your skin benefits, too

Glucosamine, as a precursor to glycosaminoglycans and proteoglycans, helps to improve the skin’s hydration and reduce wrinkles. As it inhibits tyrosinase, it can regulate the production of melanin and may be useful for treating hyperpigmentation.19 Chondroitin can also help to accelerate wound healing, particularly in burns.19,20

All-over benefits

As well as having helpful properties for joints and skin, chondroitin and glucosamine are friends to your entire body.

Other clinical uses of glucosamine and chondroitin have been suggested, for example, in inflammatory bowel disease (IBD), migraines and viral infections.19 Some studies have found a correlation between taking these supplements and a reduced risk of colorectal cancers21, but more research is needed in this area.

 

#ExtraCellMatrix #CondroCollagen  #ExtraCellWoman #BeautyCollagenMatrix

 

For allergy sufferers: Our glucosamine from crustaceans has been tested as allergen-free, and several studies have shown that glucosamine should not trigger a reaction in those with crustacean allergies because it is highly purified and has been separated from its allergenic molecules.22,23  However, ChondroCollagen contains vegan glucosamine sulphate for persons at risk.

 

 

  1. Jerosch, J. Effects of glucosamine and chondroitin sulfate on cartilage metabolism in OA: Outlook on other nutrient partners especially omega-3 fatty acids. International Journal of Rheumatology 2011, (2011).
  2. Clegg, D. O. et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New England Journal of Medicine 354, 795–808 (2006).
  3. Hawker, G. A. et al. Development and preliminary psychometric testing of a new OA pain measure : an OARSI/OMERACT initiative International Cartilage Repair Society. Osteoarthritis and Cartilage 16, 409–414 (2008).
  4. Damlar, İ., Esen, E. & Tatli, U. Effects of glucosamine-chondroitin combination on synovial fluid IL-1β, IL-6, TNF-α and PGE2 levels in internal derangements of temporomandibular joint. Medicina Oral, Patologia Oral y Cirugia Bucal 20, e278–e283 (2015).
  5. Hochberg, M. C. et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: A multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Annals of the Rheumatic Diseases 75, 37–44 (2016).
  6. Indices algo-fonctionnels de Lequesne. Available at: http://www.rhumatologie.asso.fr/03-Services/instruments-pratiques/Lequesne.html. (Accessed: 11th November 2019)
  7. WOMAC Osteoarthritis Index – Physiopedia. Available at: https://www.physio-pedia.com/WOMAC_Osteoarthritis_Index. (Accessed: 18th October 2019)
  8. Vangsness, C. T., Spiker, W. & Erickson, J. A Review of Evidence-Based Medicine for Glucosamine and Chondroitin Sulfate Use in Knee Osteoarthritis. Arthroscopy – Journal of Arthroscopic and Related Surgery 25, 86–94 (2009).
  9. Mazieres, B., Combe, B., Van, A. P., Tondut, J. & Grynfeltt, M. Chondroitin sulfate in osteoarthritis of the knee: A prospective, double blind, placebo controlled multicenter clinical study. Journal of Rheumatology 28, 173–181 (2001).
  10. Calamia, V. et al. Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes. Arthritis Research and Therapy 12, (2010).
  11. Herrero-Beaumont, G. et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis and Rheumatism 56, 555–567 (2007).
  12. Bruyere, O. et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteoarthritis and Cartilage 16, 254–260 (2008).
  13. Kanzaki, N. et al. Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: A randomized, double-blind, placebo-controlled study. Journal of the Science of Food and Agriculture 92, 862–869 (2012).
  14. Bruyere, O. & Reginster, J.-Y. Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis. Drugs & aging 24, 573–80 (2007).
  15. Tat, S. K. et al. Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: A basic science study. Arthritis Research and Therapy 9, (2007).
  16. Laverty, S. et al. Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses. Arthritis and Rheumatism 52, 181–191 (2005).
  17. McCarty, M. F., Russell, A. L. & Seed, M. P. Sulfated glycosaminsglycan and glucosamine may synergize in promoting synovial hyaluronic acid synthesis. Medical Hypotheses 54, 798–802 (2000).
  18. Palmieri, L., Conte, A., Giovannini, L., Lualdi, P. & Ronca, G. Metabolic fate of exogenous chondroitin sulfate in the experimental animal. Arzneimittel-Forschung 40, 319–23 (1990).
  19. Bissett, D. L. Glucosamine: An ingredient with skin and other benefits. Journal of Cosmetic Dermatology 5, 309–315 (2006).
  20. Wang, T. W. et al. The effect of gelatin-chondroitin sulfate-hyaluronic acid skin substitute on wound healing in SCID mice. Biomaterials 27, 5689–5697 (2006).
  21. Kantor, E. D. et al. Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses’ Health Study and Health Professionals follow-up study. International Journal of Cancer 139, 1949–1957 (2016).
  22. Villacis, J. et al. Do shrimp-allergic individuals tolerate shrimp-derived glucosamine? Clinical and Experimental Allergy 36, 1457–1461 (2006).
  23. Muzzarelli, R. A. A. Chitins and chitosans as immunoadjuvants and non-allergenic drug carriers. Marine Drugs 8, 292–312 (2010).

 

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