Glucosamine is known as an amino sugar, and is one of the most abundant monosaccharides (simple sugars) found in nature.
Now, you would expect this to be most commonly found in fruit and vegetable products, but it’s actually more common to find this compound in animals. It is produced in the exoskeletons – hard outer shells – of crustaceans, and is found in the bones and bone marrow of many other animals. It is, however, also found in smaller quantities in fermented grains, such as corn and wheat.
You would most likely know of the role that glucosamine has in joint health, which is one of the most common areas of application, however, with further research being conducted in many natural health supplements, we’ve seen that it is able to target many more parts of the body.
Therapeutic benefits of glucosamine
Glucosamine, most specifically, its amino derivative called N-acetyl glucosamine, is produced by the human body. It makes up an important part of compounds called glycoproteins, proteoglycans and glycosaminoglycans. While you don’t have to remember these names, or even know how to pronounce them, when we get into the parts of the body where a therapeutic application of glucosamine has been researched, it’ll become more obvious why these are important.
When used in the prevention and treatment of health issues, it’s how glucosamine affects inflammatory and oxidation processes that has captured the interest of researchers. With its ability to modulate inflammation through a process involving NF-kB, it is able to help the body to control the release of inflammatory molecules, called cytokines, which improves survival of the cell.
In a study conducted on mice (1), when inflammatory agents were injected into the mice, when glucosamine was administered alongside them, it reduced the migration of white blood cells and other inflammatory compounds to the sites of inflammation, which reduced the effects of these toxins. There was marked decrease in swelling at the sites, and generally reduced levels of inflammation as a result of the glucosamine use. What’s more, is that higher levels of glucosamine were observed to be well-tolerated by the mice.
In a trial conducted in healthy humans, 1,500 mg a day of glucosamine hydrochloride was given alongside 1,200 mg of chondroitin sulfate for 28 days as compared to the effects of a placebo. When four common inflammatory markers (CRP, IL-6, TNF 1 & 2) as well as two urinary inflammatory markers (PGE2 and F2ISO) were measured, the major change noted was that CRP was 23% lower with the glucosamine/chondroitin combination that the placebo (2).
Because of the therapeutic effects of glucosamine, it has become one of the most widely available natural supplements and is most commonly available in three forms: glucosamine hydrochloride, glucosamine sulphate and n-acetyl glucosamine.
With that in mind, let’s look into the benefits of glucosamine on preventing and treating common diseases and disorders, starting with the most well researched area, namely joint health.
When taken orally, glucosamine passes easily from the gut through the liver with most of the metabolised products being found in the liver, kidneys and cartilage. Glucosamine has also been found to be able to be distributed into the synovial fluid of the joint (3). For this reason, glucosamine has been widely studied in its effects in joint health, and particularly osteoarthritis.
Osteoarthritis is one of the most common degenerative joint diseases that affects the elderly. It is a disease associated with wear and tear of the joint capsule, with cartilage degeneration becoming so severe that the ends of the bone end up making contact. It is a severely disabling condition, associated with excruciating pain and poor quality of life.
Glucosamine as an over-the-counter agent, has long been used to modify the disease progression, as it has been found to reduce inflammation in affected joints in addition to protecting the cartilage. Studies have shown promising effects where 1,500mg of glucosamine a day significantly reduced pain and inflammation in the affected joint when compared to a placebo. In some studies, glucosamine has been suggested to have outperformed the therapeutic drug piroxicam in these areas (4).
In addition to working through regulation of NF-kB pathways of inflammation, research has proposed that glucosamine hydrochloride may improve the symptoms of osteoarthritis through regulation of the matrix metalloproteinase (MMP) system, which decreases inflammatory compound production and increased hyaluronic acid and cartilage protein stimulation. Hyaluronic acid is a substance that acts as a shock absorber in the joint capsule, which along with cartilage is essential for maintaining the smooth working of the joint (5).
Glucosamine plays an important role in protecting the joint cartilage, where it has also been found to inhibit the oxidation of cartilage proteins by superoxide dismutase (SOD). It acts on specific proteins within the joint cartilage that protects the cells from destruction in addition to increasing the supply of anti-inflammatory chemicals.
In a small-scale human trial, with the results published in 2017, there was evidence to support the theory that glucosamine acts on inflammation and oxidation and may offer protective benefits for the heart. These factors are a risk for endothelial damage, with the effects being atherosclerosis and heart disease, as well both inflammation and oxidation being independent risk factors for cardiovascular disease.
Atherosclerosis is one of the leading causes of death across the globe. It is caused by an accumulation of plaques attached to the inside walls of the arteries, occluding blood flow. In experimental models testing the effects of glucosamine on atherosclerosis, it has been found that glucosamine acts on a compound caller perlecan, which when increased leads to reduced binding capacity of cells to the artery walls. This reduced adhesion reduces the ability of cholesterol plaques to congregate, reducing the risk of adverse events associated with atherosclerosis (6). Additionally, glucosamine reduces the oxidation of LDL cholesterol particles, which makes them highly susceptible to binding to artery cell walls, and it has also been shown to reduce inflammatory markers, such as CRP and IL-6, which are also highly associated with negative outcomes of atherosclerosis(7).
Glucosamine has additional benefits on endothelial tissues of the artery walls. In one study, glucosamine administered at a dose of 3,000 mg a day for 4 weeks significantly improved glutathione levels in blood cells, which was shown to have an impact on flow-mediated vasodilation (FMD), which is a measurement of endothelial function. Glucosamine increased the level of glutathione in the blood cells, which improves the production of nitric oxide, a compound that enables arterial dilation and is a modulator of blood pressure. The researchers suggested that this correlation between glucosamine, glutathione and NO is protective of intracellular oxidative stress, having a downstream effect on endothelial function and thus improved risk of FMD (8).
Other cardioprotective activity includes reduced effect of ischemic and perfusion injury through mechanisms involving modulation of protein and mitochondrial function. Tested in its effectiveness using a rat model, when glucosamine was administered during resuscitation events following a myocardial infarction (heart attack), glucosamine significantly improved heart function while decreasing the levels of inflammatory compounds and reducing destruction of cardiac cells (9).
Glucosamine has been implicated in improvements in memory and learning (10). Two of the major factors associated with poor cognitive performance, particularly in models of ageing, are oxidative stress and inflammation, which are both hallmarks of neurodegenerative diseases like dementia. The therapeutic effects of antioxidant nutrients, such as glucosamine, have been studied in Alzheimer’s disease, with promising evidence being gathered for their use in delaying the progression of the disease. While most of the research is being performed on animal models, glucosamine may provide similar benefits in humans.
Multiple sclerosis is an autoimmune condition that is associated with dysfunction of the nervous system. With the immunomodulatory effects known to be provided by glucosamine, it has been suggested that due to regulation of pro-inflammatory and anti-inflammatory chemicals, glucosamine may suppress Th1 immune responses and upregulate Th2 responses, which shows improved responses by the nervous system and reduced destruction of the myelin sheath that protects nervous tissue associated with cell signalling. These effects of glucosamine have been studied in an experimental model of MS in animals, with induction of a disease called autoimmune encephalomyelitis (EAE). Improved anti-inflammatory pathways, suppression of EAE and low or absent toxicity shows promise for human application (11), however, large-scale clinical trials need to be conducted.
In the early 50s, there was already evidence for the use of glucosamine for its anticancer effects. In experimental studies on mice that had developed tumours, glucosamine slowed the growth rate of these mutant cells while offering protection to healthy tissues from the toxins that the tumour cells exhibited.
The mechanisms through which glucosamine is believed to exhibit its anticancer effects included its ability to suppress the ability of tumor cells to proliferate, through the induction of apoptosis, or programed cell suicide, and improving the sensitivity of tumor cells to chemotherapy agents. Most importantly, the mechanism through which glucosamine suppresses inflammatory processes, is believed to have significant antitumor effects. We know that one of the greatest risk factors for cancer is chronic inflammation, which means any agent that successfully inhibits the associated processes may significantly reduce cancer risk.
More recently, studies of more than 75 000 people showed the combination of glucosamine and chondroitin to improve the risk of developing lung and colorectal cancer. Even without chondroitin, evidence shows that glucosamine lowers the risk of lung cancer by 51% (12).
Glucosamine may have positive effects against fungal infections like Candida albicans and has been shown to inhibit the growth of many different microorganisms, and may be useful in the treatment of viral and bacterial infections (13).
One of the greatest risks we face when it comes to bacteria infections is the increasing prevalence of antibiotic-resistant strains. Bacteria mutate into forms called cryptic growth cells, which increases their resistance to antibiotics. Additionally, these converted bacteria are well known to increase the symptoms of bacterial-induced irritable bowel syndrome. Glucosamine prevents this conversion, which holds great promise for its therapeutic use in bacterial infections (14).
The most recent research that has delved into the antimicrobial benefits of glucosamine was conducted in 2019 on newer antibiotics that have been specifically developed to target the more antibiotic resistant strains of bacteria. Preliminary studies show that these new age antibiotics may be more effective when used in conjunction with the n-acetylglucosamine form to eradicate hard-to-treat bacterial infections.
While there has been no research conducted into the exact mechanisms of action on the ability of glucosamine to disrupt the bacterial cell walls which protect them from other antimicrobial therapies, the possibility of glucosamine in this use has also been hypothesised.
If it wasn’t enough that glucosamine has been shown to have protective effects on the heart, brain and other organs, you’ll find several skin benefits in the use of glucosamine. Oral administration of glucosamine may improve skin hydration, it may reduce the appearance of wrinkles, and even improve pigmentation (15).
When the skin is dehydrated, it appears dull and may increase the appearance of fine lines and wrinkles. Because glucosamine is made up of mucopolysaccharides, which are compounds in the body that help to maintain elasticity and moisture, the effects of supplementation with glucosamine may improve the appearance and health of skin. We also know from the research in joints that glucosamine has a positive effect on the production of hyaluronic acid, which is a compound that makes up the main structural component of skin cells. An increase in hyaluronic acid improved skin turgor and appearance (16).
Additionally, glucosamine through its mechanisms of increasing hyaluronic acids, may improve regeneration of skin cells, which has implications in improved wound healing.
When it comes to the visible signs of ageing, glucosamine may reduce the number of wrinkles and fine lines. One of the most important structural components of skin, which maintains the connective tissue that holds the cells together, is collagen. When collagen synthesis decreases, wrinkles and fine lines begin to appear. With glucosamine, particularly in its n-acetylglucosamine form, there is an increase in the activity of fibroblasts, which has been shown to improve the production of collagen. Glucosamine also inhibits an enzyme, which is known to break down collagen fibers, which is a hallmark of the effects of aging on the skin (17).
Glucosamine and longevity
One of the most prominent mechanisms through which glucosamine is believed to exert its anti-ageing effects is through its action on glucose metabolism and downstream effect on mitochondrial metabolism.
The significance of this is that blood sugar dysregulation and the subsequent development of type 2 diabetes not only increases in prevalence with increasing age, blood sugar imbalances are highly associated with inflammatory conditions. It can affect individuals of any age, which can induce system-wide low grade inflammation and promote early cellular ageing that affects longevity.
A suggested means of regulating blood sugar naturally is through a low-carb diet. It is, however, difficult to enforce long-term, and those following such a restrictive diet often resort to binge eating, particularly on unhealthy, refined and processed carbohydrates.
With low-carb diets having become one of the most popular ways to lose weight in the last two decades (18), and with implications in their use for disease management, particularly in the treatment of epilepsy in the pediatric population (19), glucosamine may provide a solution.
Glucosamine has been shown to mimic a low-carb diet, even when the diet contains the same amount of carbs (20).
By simulating the effects of a low-carb diet, glucosamine may help to improve cellular ageing due to reduced glucose and insulin levels.
Using a worm model of C. elegans, researchers in 2014 showed that with the addition of glucosamine, lifespan can be extended in this species due to the impairment of glucose metabolism, which has been found to be reduced by as much as 43%. Reduced glucose metabolism activates a mitochondrial pathway called AMPK, which is associated with health ageing (21,22).
Glucosamine is a well-established inhibitor of two enzymes that are involved in the breakdown of glucose in the liver, called hexokinase and glucokinase, through a process known as glycolysis. Where glycolysis is no longer the primary source of fuel, an energy deficit induces the need for an alternative fuel source, which is typically amino acid oxidation (the breakdown of protein building blocks).
This effect has also been shown to be true in the mouse model of ageing (23,24).
It is noteworthy to mention that the above-mentioned study also showed that the process of increased mitochondrial biosynthesis increases mitochondrial respiration, which also increases the production of reactive oxygen species (ROS). This increase in ROS, however, has been observed to induce an endogenous adaptive response in C. elegans, which alleviates the risk of ROS after 7 days of implementation through increased production of ROS defense enzymes like SOD, for example (25).
It has also, however, been proposed that the induction of higher ROS production through higher mitochondrial respiration during the first hours of use of glucosamine may, perhaps, pose some benefit through hormetic effects. Hormesis, a process whereby small amounts of stress may have positive biological effects, has been suggested as promoting health- and lifespan (26,27).
More recently, the effects have been duplicated in human studies.
Research conducted on human tissues in vitro, when glucosamine was tested on human liver cancer cells, it was found that the reduction in ATP production by mitochondria was due to the inhibition of glycolysis. These reduced ATP levels have been implicated in the promotion of a process called autophagy. Autophagy is a process that has a crucial role in disease and in longevity, where it is involved in the breakdown and removal of intracellular components as a means to maintain energy and balances that protects the cell against stress (28).
Autophagy has been suggested as being dependant on a pathway, called mTOR, which is well-known for its role in the ageing process (29), however, a study published in 2010, suggests that the mechanism via which glucosamine exerts its effects on autophagy is independent of this pathway. Instead, it’s the amino sugar in glucosamine that is responsible for this life-span promoting activity (30).
There have also been studies to suggest a beneficial role of oral glucosamine use in reducing oxidative effects on the retinal pigment cells, aiding in improving the outcome of inflammatory lung conditions and reducing the impact of high iron concentrations by binding the mineral in the blood.
Glucosamine shows significant promise for use in reducing the risk of total mortality. In the conclusion of a 2019 study, researchers, who were evaluating the use of 13 natural supplements found there to be no correlation between the decrease in total mortality of their intake, except when it came to two of them, one of them being glucosamine. The cohort study, which collected data from participants for an average of 10-years indicated that those who had taken glucosamine in either high or low doses had an inverse correlation to mortality, where possible confounding factors were adjusted for (31).
Glucosamine is widely available in nature, and has been shown to have a generally high safety profile, even in doses of 1500 mg per day (32). These higher doses are often needed. While it has been shown in studies that 90% of glucosamine is quickly absorbed through the digestive system, when concentrations are measured in the blood, there is around 30% left after metabolism (33). For this reason, high doses should be continued to be taken for at least 4-8 weeks to increase plasma concentrations, and maximise its beneficial effects (34).
With this in mind, and the research that has already been conducted on its use in promoting health- and life-span, we look forward to more evidence being brought forward in future studies that reiterates the promising evidence we already have.
Selection of studies used for this article:
- Pires, A. et al. A novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuates acute cellular inflammation in mice. Inflammation Research. 2015. 65(1), 43–52.
- Navarro, S., et al. Randomized Trial of Glucosamine and Chondroitin Supplementation on Inflammation and Oxidative Stress Biomarkers and Plasma Proteomics Profiles in Healthy Humans. PLoS One. 2015; 10(2): e0117534.
- Persiani S, et al. Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose. Osteoarthritis Cartilage. 2007;15(7):764-72.
- Reginster JY, Bruyere O, Neuprez A. Current role of glucosamine in the treatment of osteoarthritis. Rheumatology. 2007;46(5):731-735.
- Petersen S, et al. Glucosamine but not ibuprofen alters cartilage turnover in osteoarthritis patients in response to physical training. Osteoarthritis Cartilage. 2010;18(115):34-40.
- Duan W, Paka L, Pillarisetti S. Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: evidence for a protective role for glucosamine in atherosclerosis. Cardiovasc Diabetol. 2005;4(115):16
- Largo R, et al. Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis. Am J Physiol Heart Circ Physiol. 2009;297(115):H268-76.
- Katoh, A., et al. Oral Administration of Glucosamine Improves Vascular Endothelial Function by Modulating Intracellular Redox State. Int Heart J 2017; 58: 926-932.
- Champattanachai V, Marchase RB, Chatham JC. Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2. Am J Physiol Cell Physiol. 2008;294(6):C1509-C20.
- Jamialahmadi K, et al. Glucosamine alleviates scopolamine induced spatial learning and memory deficits in rats. Pathophysiology. 2013;20(4):263-7.
- Zhang, G., et al. Glucosamine Abrogates the Acute Phase of Experimental Autoimmune Encephalomyelitis by Induction of Th2 Response. The Journal of Immunology. 2005. 175 (11) 7202-7208.
- Brasky TM, Lampe JW, Slatore CG, White E. Use of glucosamine and chondroitin and lung cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Causes Control. 2011;22(9):1333-42.
- Xu Q, Liu J, Yuan Z. Use of acetyl-d-aminoglycosamine in treatment of local lesions and systemic symptoms related to infections of virus or bacteria. European patent EP 1609473. 2006 Jul 5.
- Xu Q, et al. Compound antibacterial drugs comprising n-acetyl-d-glucosamine. United State patent US 20070191291. 2007 Agu 16.
- Bissett DL. Glucosamine: an ingredient with skin and other benefits. J Cosmet Dermatol. 2006;5(4):309-15.
- Papakonstantinou E, et al. Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol. 2012;4(3):253-258.
- AL-NAIMI MMS, AAH. The effects of glucosamine sulphate on mice skin. Mustansiriya Medical Journal. 2006;6(115):49-57.
- A. Paoli, K. Grimaldi, D. D’Agostino, L. Cenci, T. Moro, A. Bianco, A. Palma. Ketogenic diet does not affect strength performance in elite artistic gymnasts. J. Int. Soc. Sports Nutr., 9 (2011), p. 34.
- E.G. Neal, H. Chaffe, R.H. Schwartz, M.S. Lawson, N. Edwards, G. Fitzsimmons, A. Whitney, J.H. Cross. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol., 7 (2008), pp. 500-506.
- Shintani, H., et al. Calorie Restriction Mimetics: Upstream-Type Compounds for Modulating Glucose Metabolism. 2018. Nutrients 10(12):1821.
- Apfeld, J., O’Connor, G., McDonagh, T., DiStefano, P. S. & Curtis, R. The AMP-activated protein kinase aak-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 18, 3004–3009 (2004).
- Hardie, D. G. AMP-activated protein kinase–an energy sensor that regulates all aspects of cell function. Genes Dev. 25, 1895–1908 (2011).
- Weimer, S., et al. D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nature Communications volume 5, Article number: 3563 (2014).
- Schlotterer, A. et al. C. elegans as model for the study of high glucose mediated lifespan reduction. Diabetes 58, 2450–2456 (2009).
- Ju, H. W. et al. Glucosamine causes overproduction of reactive oxygen species, leading to repression of hypocotyl elongation through a hexokinase-mediated mechanism in Arabidopsis. J. Plant Physiol. 166, 203–212 (2009).
- Sena, L. A. & Chandel, N. S. Physiological roles of mitochondrial reactive oxygen species. Mol. Cell 48, 158–167 (2012).
- Ristow, M. & Schmeisser, K. Mitohormesis: Promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response
- Hansen, M., et al. Autophagy as a promoter of longevity: insights from model organisms. Nature Reviews Molecular Cell Biologyvolume 19, pages 579–593 (2018).
- Weichhart, T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127-134.
- Shintani, T., Yamazaki, F., Katoh, T., Umekawa, M., Matahira, Y., Hori, S., … Ashida, H. (2010). Glucosamine induces autophagy via an mTOR-independent pathway. Biochemical and Biophysical Research Communications, 391(4), 1775–1779.
- Pocobelli, G., et al. Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr. 2010 Jun; 91(6): 1791–1800.
- Reginster, Jean Yves; Deroisy, Rita; Rovati, Lucio C; Lee, Richard L; Lejeune, Eric; Bruyere, Olivier; Giacovelli, Giampaolo; Henrotin, Yves; Dacre, Jane E; Gossett, Christiane (January 2011). “Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial”. The Lancet. 357 (9252): 251–256.
- Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol. 2005;43(115):187-201.
- Kirkham SG, Samarasinghe RK. Review article: Glucosamine. J Orthop Surg (Hong Kong). 2009;17(115):72-6.