Glucosamine in Osteoarthritis

Introduction

Glucosamine is a naturally occurring compound that is found within humans and animals.^1,2 The primary function of this product is that it adds additional protection to cartilage, which is the connective tissue that helps cushion our joints.¹ This compound is naturally produced in our bodies and it mainly serves to maintain and develop the cartilage within our joints.² Glucosamine supplements are created from the cartilage of animals such as cows and pigs, and some supplements are even synthetically created in labs.^2,3 Sometimes, glucosamine is also created from shellfish shells, animal bones and fungi.² Glucosamine supplements are often sold in two different forms which include glucosamine sulfate and glucosamine hydrochloride.³

Typically, glucosamine is either taken orally, or applied topically as a cream.² Glucosamine commonly comes in products that include the ingredient, chondroitin, which is also a naturally occurring compound found in cartilage.¹ Chondroitin in combination with glucosamine will often produce synergistic effects on improving symptoms of pain and inflammation at the joint.¹ So far, glucosamine has mainly been used as a natural product alternative that is used to treat and prevent joint disorders, most commonly including osteoarthritis.²

Thousands of Americans use glucosamine to resolve their symptoms of osteoarthritis every day, and it continues to stay a very popular natural product that has been investigated for many years. Over the years, some studies have concluded that glucosamine has benefits for osteoarthritis, while others have determined that there is no benefit.⁴ Unfortunately, there is no known cure for osteoarthritis at this time, therefore, most individuals rely on using natural products like glucosamine for potential benefits.⁴

In the United States today, glucosamine is not an approved supplement by the Food and Drug Administration (FDA).⁵ Therefore, it is important to ensure that any individual who would like to try this product consults with a healthcare provider to assess the safety of using this product.

How Does Glucosamine Work?

The exact mechanism by which glucosamine works for improving symptoms of osteoarthritis is still unclear.^4,6 Scientists believe that naturally occurring glucosamine is responsible for protecting the cartilage inside of our joints.⁴ Some studies have suggested that glucosamine is responsible for reducing the breakdown of collagen as well.^7,8 Collagen is an essential protein in the body that promotes the growth and regeneration of tissue and cells in the body.^7,8 Therefore, by this mechanism glucosamine would be responsible for stopping the breakdown of this protein, and thereby promoting continued repair throughout the body. It is also understood that glucosamine is correlated with a reduction in inflammation as well. This means that glucosamine is likely to decrease inflammation at the joints in individuals with osteoarthritis.⁹

What is Osteoarthritis?

Osteoarthritis is a degenerative disease which occurs when the cartilage within an individual’s joints does not regenerate properly and quickly.⁴ Osteoarthritis is mainly caused by a significantly large amount of inflammation in the joints.⁴ Over time, this disease progressively gets worse and will cause many uncomfortable issues.⁴ When individuals suffer from osteoarthritis, the surface layer of the cartilage between the bones will wear down.² As the bones rub together, this can cause varying amounts of pain and swelling.² The areas of the body that are most often affected by osteoarthritis include the knees, hips, and hands.²

Glucosamine and Osteoarthritis

A 2007 randomized control study looked at 318 patients with osteoarthritis and each participant was assigned to either glucosamine, acetaminophen (also known as Tylenol), or a placebo pill.¹⁰ This study determined that glucosamine was more effective than the placebo group at improving symptoms such as pain and overall function of the joint.¹⁰ This study also determined that there was a similar reduction in pain and improved function when compared to acetaminophen. Additional studies have also shown that when taking glucosamine supplements daily, there has been increased improvement in overall symptoms.^11,12 These symptoms range between pain, stiffness and general function of the joint as well.^11,12

To date, it is not entirely understood how glucosamine reduces inflammation. However, there have been some studies conducted to determine whether there is a correlation between using glucosamine and improvement in inflammatory markers in the body that result from osteoarthritis. Since most glucosamine supplements contain chondroitin as well, the studies that have been conducted include both ingredients. One study done in 2014 determined that in a sample of 200 patients with osteoarthritis, individuals that were taking glucosamine showed a reduction in the biomarkers that are screened to assess level of inflammation.¹³ These inflammatory biomarkers include CRP and PGE, and both were reduced. However, the results of this study were not considered “statistically significant”. Therefore, more data is necessary to affirmatively state that the use of glucosamine resulted in decreased inflammation.

There are many additional studies that have shown the effectiveness of glucosamine in patients that have osteoarthritis. There have also been many studies that have shown that there is not relationship between glucosamine and improving osteoarthritis as well. Always consult with your healthcare provider prior to starting the use of any supplementations such as glucosamine.

How Do You Take Glucosamine?

These supplements are available in most grocery and convenience stores and are usually located in the over-the-counter supplement section. Most studies have supported the use of glucosamine sulfate rather than glucosamine hydrochloride. Therefore, using glucosamine sulfate is likely a better option due to this supplement having more data for its use. As mentioned above, glucosamine supplements are almost always combined with chondroitin. Both have been associated with improved symptoms of osteoarthritis; thus, a combination product is an appropriate option.⁵

Glucosamine comes in a variety of formulations. Most often, individuals prefer to take the oral tablets. These tablets come in varying doses that can range anywhere from 300 mg to 500 mg.⁴ Recommended doses also vary widely and the appropriate dosage for you should be discussed with your healthcare provider. Always read the instructions on the label prior to use.

As discussed, these supplements are not regulated by the FDA. Use caution when trying new glucosamine supplements and always use the same manufacturer once you have established which brand you prefer. This will help ensure that you are receiving a similar strength of the supplement with each use.

Safety of Glucosamine

As a natural product, this may seem like a wonderful option to try for individuals that do not think they are achieving appropriate relief from over-the-counter pain reducing medications. However, glucosamine may not be for everyone.

Side Effects

Glucosamine supplements are overall well tolerated by most individuals. However, there are some side effects that can occur. Possible side effects include the following gastrointestinal symptoms:

• Nausea and vomiting¹⁴
• Diarrhea¹⁴
• Heartburn¹⁴
• Abdominal pain¹⁴

There is not enough evidence to support whether glucosamine is safe for pregnant or breastfeeding mothers, thus, using this kind of supplement should be avoided entirely.⁴ Glucosamine has also been associated with increased blood sugar, so always use caution if you are a diabetic.⁴

Serious Side Effect

One of the most important things to remember before taking glucosamine supplements is to check the ingredients. As mentioned before, some glucosamine supplements can be created from shellfish shells, therefore, if you are someone who is allergic to shellfish you should avoid taking glucosamine to avoid serious anaphylactic reactions.

References:

1. Glucosamine and Chondroitin for Osteoarthritis. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/glucosamine-and-chondroitin-for-osteoarthritis. Updated on November, 2014. Accessed on October 15, 2020.
2. Does Glucosamine Work? Benefits, Dosage and Side Effects. https://www.healthline.com/nutrition/glucosamine. Updated on September 26, 2018.Accessed on October 15, 2020.
3. Glucosamine and Chondroitin for Osteoarthritis Pain. Arthritis Foundation. https://www.arthritis.org/health-wellness/treatment/complementary-therapies/supplements-and-vitamins/glucosamine-chondroitin-osteoarthritis-pain. Accessed on October 15, 2020.
4. Do Glucosamine Supplements Work for Arthritis? https://www.healthline.com/nutrition/glucosamine-and-arthritis. Updated on July 27, 2017. Accessed on October 15, 2020.
5. The Latest on Glucosamine/Chondroitin Supplements. Harvard Health Medical School Publishing. https://www.health.harvard.edu/blog/the-latest-on-glucosaminechondroitin-supplements-2016101710391. Updated on September 16, 2019. Accessed on October 15, 2020.
6. Kim MM, Mendis E, Rajapakse N, Kim SK. Glucosamine sulfate promotes osteoblastic differentiation of MG-63 cells via anti-inflammatory effect. Bioorg Med Chem Lett. 2007 Apr 1;17(7):1938-42. doi: 10.1016/j.bmcl.2007.01.030. Epub 2007 Jan 19. PMID: 17270442.
7. Momomura R, Naito K, Igarashi M, Watari T, Terakado A, Oike S, Sakamoto K, Nagaoka I, Kaneko K. Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers. Mol Med Rep. 2013 Mar;7(3):742-6. doi: 10.3892/mmr.2013.1289. Epub 2013 Jan 25. PMID: 23358550.
8. Yoshimura M, Sakamoto K, Tsuruta A, Yamamoto T, Ishida K, Yamaguchi H, Nagaoka I. Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players. Int J Mol Med. 2009 Oct;24(4):487-94. doi: 10.3892/ijmm_00000257. PMID: 19724889.
9. Herrero-Beaumont G, Rovati LC, Castañeda S, Alvarez-Soria MA, Largo R. The reverse glucosamine sulfate pathway: application in knee osteoarthritis. Expert Opin Pharmacother. 2007 Feb;8(2):215-25. doi: 10.1517/14656566.8.2.215. PMID: 17257091.
10. Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araújo D, Figueroa M, Branco J. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007 Feb;56(2):555-67. doi: 10.1002/art.22371. PMID: 17265490.
11. Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2002 Oct 14;162(18):2113-23. doi: 10.1001/archinte.162.18.2113. PMID: 12374520.
12. Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001 Jan 27;357(9252):251-6. doi: 10.1016/S0140-6736(00)03610-2. PMID: 11214126.
13. Kantor ED, Lampe JW, Navarro SL, Song X, Milne GL, White E. Associations between glucosamine and chondroitin supplement use and biomarkers of systemic inflammation. J Altern Complement Med. 2014 Jun;20(6):479-85. doi: 10.1089/acm.2013.0323. Epub 2014 Apr 16. PMID: 24738579; PMCID: PMC4048982.
14. National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 439213, D-Glucosamine. Retrieved October 15, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/D-Glucosamine.