What are glucosamine and chondroitin?
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.
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
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
An effect on our cardiovascular and intestinal systems
Glucosamine, although frequently used for joint problems, seems to have other benefits for our bodies. Some studies have pointed to a benefit for the cardiovascular system, as taking glucosamine is associated with a reduced risk of coronary heart disease, stroke and death from cardiovascular problems.21 In addition to the cardiovascular impact, it appears to reduce all causes of death more broadly, as well as deaths from digestive diseases, respiratory diseases and cancers.22,23 For example, one study highlights that taking glucosamine and chondroitin in combination was associated with protection against the risk of colorectal cancers.24 Similarly, in terms of gut health, taking glucosamine and chondroitin is thought to reduce bloating and constipation, while influencing the bacteria of the gut microbiota. This is because glucosamine, like chondroitin, is mainly metabolised by the gut flora before it has any effect on our bodies. However, further, larger studies are needed to confirm these results.25,26
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Food supplements should not be used as a substitute for a varied diet. The recommended daily allowance should not be exceeded. In general, food supplements are not suitable for pregnant and nursing women, children and adolescents. Keep out of reach of children.
- 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).
- 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).
- 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).
- 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).
- 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).
- Indices algo-fonctionnels de Lequesne. Available at: http://www.rhumatologie.asso.fr/03-Services/instruments-pratiques/Lequesne.html. (Accessed: 11th November 2019)
- WOMAC Osteoarthritis Index – Physiopedia. Available at: https://www.physio-pedia.com/WOMAC_Osteoarthritis_Index. (Accessed: 18th October 2019)
- 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).
- 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).
- Calamia, V. et al. Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes. Arthritis Research and Therapy 12, (2010).
- 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).
- 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).
- 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).
- Bruyere, O. & Reginster, J.-Y. Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis. Drugs & aging 24, 573–80 (2007).
- 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).
- 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).
- 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).
- 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).
- Bissett, D. L. Glucosamine: An ingredient with skin and other benefits. Journal of Cosmetic Dermatology 5, 309–315 (2006).
- 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).
- Ma, H. et al. Association of habitual glucosamine use with risk of cardiovascular disease: Prospective study in UK Biobank. The BMJ 365, (2019).
- Li, Z. H. et al. Associations of regular glucosamine use with all-cause and cause-specific mortality: A large prospective cohort study. Annals of the Rheumatic Diseases 79, 829-836 (2020).
- Bell, G. A., Kantor, E. D., Lampe, J. W., Shen, D. D. & White, E. Use of glucosamine and chondroitin in relation to mortality. European Journal of Epidemiology 27, 593-603 (2012).
- 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).
- Moon, J. M. et al. Impact of Glucosamine Supplementation on Gut Health. Nutrients 13, 2180 (2021).
- Navarro, S. L., Levy, L., Curtis, K. R., Lampe, J. W. & Hullar, M. A. J. Modulation of gut microbiota by glucosamine and chondroitin in a randomized, double-blind pilot trial in humans. Microorganisms 7, (2019).