Glucosamine

If you have heard of glucosamine, you have likely been turned onto its potentially beneficial effects on joint health. However, there are many questions to consider when becoming more educated on a subject, and these questions should be answered clearly and with a strong scientific base. As such, this article will cover a variety of questions related to glucosamine from the chemical structure, types, what it does, how effective it is, dosages, among several others. So, let us get to it – glucosamine education, here we come!
 

What is Glucosamine?

Glucosamine is a molecule similar to monosaccharides (simple sugars) as it has a similar chemical structure to glucose (C6H12O6), however it is different in that it also has an amino group (glutamine, as evidenced by the nitrogen) attached to it like a protein (C6H13NO5); this being the case, it is a combination molecule referred to as an aminomonosaccharide or even as glycoprotein [1][2][3][17].

On the left is a glucose molecule and on the right is a glucosamine molecule. You can easily see the similarity between the two save for the nitrogen attached to the glucosamine molecule.

Types of Glucosamine

There are three main types of glucosamine from glucosamine sulfate, glucosamine hydrochloride, to N-acetyl-glucosamine [4]. The one we are discussing is the former (glucosamine sulfate) and happens to be the most popular form. These forms are all additive iterations of the same glucosamine molecule; for example, hydrochloride is added as opposed to sulfate and each has their own minute benefits from stability to amount needed to be ingested to see results. However, as a majority of supplements use glucosamine sulfate and as it is considered the superior version; these are the reasons we are covering it over the other versions.

What does it do?

Glucosamine sulfate (henceforth referred to as “glucosamine”) is widely thought to help slow the degeneration of cartilage in the knees, spine, and hip [4]. Not only that, but some believe that glucosamine can also reverse the process of osteoarthritis on cartilage [3].

How does it work?

Granted, there is a complex mechanism involved in which glucosamine is a key factor and this mechanism will be covered in a future article, one day, but will not be covered here. However, some detailed background on the matter might be interesting, nonetheless.

Glucosamine acts as a stimulant to the production of proteoglycans [6]. Proteoglycans happen to be one of the main building blocks to cartilage. So, if glucosamine is present, it is used to metabolize, via chrondrocytes (cartilage cells), foundational proteins (proteoglycans) that make up all cartilage [5]. If the addition of proteoglycans is greater than the loss of proteoglycans, then there is a thickening and strengthening of the cartilage between bone (simply put).

 

Pictured is a zoomed in picture of cartilage where the chrondrocytes are located. These cells use glucosamine to regenerate cartilage by synthesizing proteoglycans to create mass in the cartilage.

What are sources of Glucosamine?

Glucosamine can be found endogenously, meaning the body does synthesize it itself [3]. Using glucose and glutamine, this is made possible due to the aforementioned chrondrocytes [5][8].

On the other hand, it is also possible to supplement with glucosamine as there are no good food sources of viable glucosamine; these supplements are either synthetically made in a laboratory or taken from the shells of certain sea food, but either way they are effective ways of boosting glucosamine in the body [9]. Ingestion of glucosamine has a 90% bioavailability, meaning 90% is absorbed upon ingestion [11].


Why supplement with Glucosamine?

Well, it comes down to age. As we age, there is evidence that the enzymatic reactions responsible for converting an iteration of glucose (fructose-6-phosphate) to glucosamine decline to a point that the chrondrocytes cannot build cartilage faster than cartilage is broken down leading to chronic catabolism and a seemingly irreversible degradation of cartilage [10][11]. It is around the range 45-50 years of age that most people see cartilage decline due to greater catabolism [11]. Due to this, it has been assumed that supplementing glucosamine would, at least, slow down the degradation of cartilage leading to osteoarthritis.

How effective is it?

Well, first off, there are two areas that glucosamine is assumed to be beneficial; one, being pain relief from osteoarthritis and the second, being physical benefit toward decreasing and/or reversing the effects of osteoarthritis. However, what does the science say?

In terms of pain relief, there are a few studies that claim glucosamine is more beneficial than placebo (untreated, essentially)[12]. Yet, even so, reviews of a body of literature on glucosamine and its lessening impact on pain seem unconvinced that these results are substantiated when other variables are accounted [13]. It is possible some industry bias was at play, and if not that, the pain measuring systems used may be in question. So, due to the inconclusive results related to glucosamine’s positive impact on pain relief, we will conclude that it is doubtful glucosamine truly has an impact on pain relief.

On the other note, glucosamine has also been touted to have anti-degenerative benefits in terms of sparing cartilage. It does seem that glucosamine has a body of evidence in support of this theory. It seems that, compared to placebo (again, untreated, essentially), glucosamine supplementation, measured at 1 and 3 year marks show significant reduction in cartilage degradation. Placebo saw a loss of 0.19 – 0.31 mm in joint space while glucosamine supplementation saw an insignificant ~0.06 mm decrease in joint space [14][15][16]. Evidently, glucosamine does have a significant impact in decreasing degradation of cartilage between joints over a lengthy period of years.


Dosage?

Dose is, of course, extremely important in terms of seeing benefit. As with most things, under-dosing leads to minimal results and overdosing will likely do nothing extra. Most studies used 1500 mg of glucosamine sulfate in a single dose form, once a day, every day, year after year [14][15][16]. However, some people, especially high impact athletes (runners, for example) may benefit from consuming upwards of 3000 mg/day [11]. Also, some recommend doses of 500mg, 3x a day, but as we see benefits from a single 1500 mg dose, it is unlikely to matter much [11].

In the end, take in 1500 mg/day and if a high impact athlete, consider going up to even 3000 mg/day.

Safety?

While, for healthy populations, there are little to no safety issues other than mild stomach discomfort, there are other populations that should, even more so, consult their physician. People that are diabetic or on blood thinner should consider consulting their doctor as glucosamine may have a minor effect on both [9][11]. Also, those with shellfish allergies should also consult a physician before taking glucosamine as glucosamine is sometimes extracted from the shells of certain seafood [9].

Bottom line, if you are in the healthy population (non-allergic, not taking medicine, not suffering from a condition) then glucosamine is likely fine to take; yet, it is always recommended (especially for non-normal population) to consult your physician before taking glucosamine regularly.


SUMMARY

Now that we’ve covered glucosamine we know that glucosamine is a molecule similar to glucose, but with special properties. Its presence in the body allows for an anabolic response by the body to create more cartilage in the spine, hips, and knees. Although pain relief is doubtful with glucosamine, there is evidence that glucosamine does reduce cartilage degradation, but does not reverse it; that said, it is recommended for people around the age of 45-50 to begin taking 1500 mg of glucosamine a day, slightly more if an athlete. Always consult your physician, but glucosamine has minor side effects for healthy populations that revolve around stomach discomfort, at worst.

Writer: Nicolas Verhoeven

                                                                                                           Citations

[1]D-Glucose | C6H12O6 - PubChem. (n.d.). Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/D-glucose

[2] beta-D-Glucosamine | C6H13NO5 - PubChem. (n.d.). Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/beta-D-Glucosamine

[3] Kaiser, M. (2003, May 12). Monograph Glucosamine [PDF]. Retrieved from http://www.ucdenver.edu/academics/colleges/pharmacy/currentstudents/OnCampusPharmDStudents/ExperientialProgram/Documents/nutr_monographs/Monograph-glucosamine.pdf

[4] Glucosamine sulfate: MedlinePlus Supplements. (2016). Retrieved from U.S. National Library of Medicine website: https://www.nlm.nih.gov/medlineplus/druginfo/natural/807.html

[5] Goldring, M. B. (2012). Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Therapeutic Advances in Musculoskeletal Disease, 4(4), 269-285. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403254/

[6] Stenlake, R. (n.d.). How does Glucosamine and Chondroitin Work. Retrieved from http://www.glucosamine-arthritis.org/glucosamine/how-does-glucosamine-chondroitin-work

[7] Sophia Fox, A. J. (2009). The Basic Science of Articular Cartilage. Sports Health, 1(6), 461-468. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445147/

[8] WU, G., HAYNES, T. E., LI, H., YAN, W., & MEININGER, C. J. (2001). Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis. Biochem. J, 353(2), 245-252. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11139387

[9] Glucosamine | University of Maryland Medical Center. (2015, June 22). Retrieved from http://umm.edu/health/medical/altmed/supplement/glucosamine

[10] Kato, N., Dasgupta, R., Smartt, C. T., & Christensen, B. M. (2002). Glucosamine:fructose-6-phosphate aminotransferase: gene characterization, chitin biosynthesis and peritrophic matrix formation in Aedes aegypti. Insect Molecular Biology, 11(3), 207-216. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12000639

[11] Glucosamine - Scientific Review on Usage, Dosage, Side Effects | Examine.com. (n.d.). Retrieved from https://examine.com/supplements/glucosamine/

[12] Herrero-Beaumont, G., Ivorra, J. A., Del Carmen Trabado, M., Blanco, F. J., Benito, P., Martín-Mola, E., … Branco, J. (2007). Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum, 56(2), 555-567. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17265490

[13] Vlad, S. C., LaValley, M. P., McAlindon, T. E., & Felson, D. T. (2007). Glucosamine for pain in osteoarthritis: Why do trial results differ?. Arthritis Rheum, 56(7), 2267-2277. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17599746

[14] Reginster, J. Y., Deroisy, R., Rovati, L. C., Lee, R. L., Lejeune, E., Bruyere, O., … Gossett, C. (2001). Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. The Lancet, 357(9252), 251-256. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11214126

[15] Pavelká, K., Gatterová, J., Olejarová, M., Machacek, S., Giacovelli, G., & Rovati, L. C. (2002). Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis. Arch Intern Med, 162(18), 2113. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12374520

[16] Wonggokusuma, E., Setyohadi, B., Siagian, C., & Lubis, A. M. (2014). Effects of Glucosamine-Chondroitin Sulfate, Glucosamine-Chondroitin Sulfate-Methylsulfonylmethane, or Placebo in Patients with First and Second Grade of Knee Osteoarthritis: A Double Blind Randomized Controlled Study. Orthopaedic Journal of Sports Medicine, 2(3 Suppl). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20649060

[17] FULOP, N., MARCHASE, R., & CHATHAM, J. (2007). Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system. Cardiovascular Research, 73(2), 288-297. doi:10.1016/j.cardiores.2006.07.018

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