man holding knee

Glucosamine

July 2019

Which is the Best Glucosamine Supplement?

Check out our unbiased recommendation of the best products on the market using our rigorous methodology. We screen products for the right formulation, bioavailability, safety, and efficacy to bring you only the best supplements available in 2019.

Briefly about Glucosamine

As people age, they typically experience more aches and pains. Some of this discomfort may be caused by the body producing less glucosamine, a naturally-occurring amino sugar. Glucosamine helps to lubricate joints and maintain healthy cartilage; it is especially beneficial for people with osteoarthritis. This form of arthritis involves the deterioration of the cartilage that cushions joints, such as the knees. If you are tired of dealing with painful symptoms, such as joint stiffness, that are commonly associated with osteoarthritis, you may want to consider taking a glucosamine supplement.[1, 2, 3]

Here is an overview of what you need to know about glucosamine and glucosamine supplements:

  • Glucosamine is a substance that is vital for good joint health.
  • It is an amino sugar that supports the building of tendons, ligaments, and cartilage.
  • Although deficiency is rare, people produce less glucosamine as they age.
  • A lack of glucosamine may contribute to painful joint conditions.
  • Although there is no cure for osteoarthritis, a glucosamine supplement may help ease symptoms such as pain and stiffness.
  • Significant amounts of glucosamine are not naturally found in any food sources, although there may be trace amounts of glucosamine in shellfish and meat, particularly offal.
  • Research shows that the most effective glucosamine supplements also contain chondroitin sulfate, a complex sugar that is an important component of cartilage.
  • It is recommended that individuals with osteoarthritis take 500mg of glucosamine three times a day for up to three months or 1,500mg once a day for up to six months.
  • Since many glucosamine supplements are derived from the shells of crab and shrimp, people with shellfish sensitivities and allergies should not take them.

A Closer Look at Glucosamine

As the population ages and life expectancy increases, osteoarthritis of the knee and hip has become more widespread. About 5% of all people between the ages of 35 and 54 show signs of knee osteoarthritis, a painful condition in which the cartilage surrounding the joints erodes.[1, 4] That statistic climbs to 30% in people between the ages of 45 and 65.[2]
Osteoarthritis causes stiffness and pain, and can lead to the joints realigning, thus changing the way a person walks and moves. These symptoms cannot be reversed, but they can be managed to some extent with a glucosamine supplement. Glucosamine is a key building block of joints and helps the body to maintain healthy cartilage.[2]

Why Glucosamine is Crucial for Health

Glucosamine is critical for maintaining joint health. Glucosamine sulfate, a naturally-occurring chemical in the body, supports the building of cartilage, ligaments, and tendons. It is found in synovia, a thick, viscous fluid that surrounds joints throughout the body.[3]

Osteoarthritis is a condition that causes the cartilage that cushions joints, such as the knee, hip, and hand, to break down. Because this condition often impacts one side of the knee more than the other, it can lead to malalignment. It also causes frequent joint pain, stiffness, and leg buckling. Osteoarthritis typically affects older individuals due to a reduction in glucosamine levels that is part of the normal aging process. Obesity, genetic predisposition, serious joint injuries, and trauma are risk factors that can increase an individual’s likelihood of developing osteoarthritis.[4, 15]

In 2006, the National Institutes of Health studied the benefits of glucosamine and chondroitin sulfate for patients suffering from osteoarthritis of the knee. Patients with moderate-to-severe joint pain experienced a dramatic reduction in pain when taking 1,500mg of glucosamine and 1,200mg of chondroitin daily for six months. Evidence suggests that this kind of supplementation may also be beneficial for people suffering from other forms of osteoarthritis.[5]

Internal Processing of Glucosamine

Glucosamine stimulates the formation and repair of cartilage. As an amino sugar, glucosamine sulfate plays an important role in the biochemical pathways that synthesize lipids and glycosylated proteins.[7] Glycosylated proteins (also known as proteoglycans) are the large molecules that give cartilage its buffering properties. Glucosamine is also a primary component of hyaluronic acid and keratin sulfate, both of which are found in articular cartilage and synovial fluid that help joints function properly.

Glucosamine supplements have been used to treat individuals suffering from certain types of arthritis, especially osteoarthritis, as these joint diseases typically result in decreased levels of glucosamine sulfate and chondroitin. Furthermore, research shows that glucosamine sulfate has anti-inflammatory effects that are similar to those of non-steroidal anti-inflammatory drugs such as ibuprofen or aspirin. Glucosamine is often viewed as an alternative treatment for people who cannot take those medications.
Only a handful of studies have examined how the human body absorbs, metabolizes, and excretes glucosamine. However, one study that tested the absorption of glucosamine in rats and dogs found that the majority was absorbed through the gastrointestinal tract. It is also understood that the liver quickly metabolizes leftover glucosamine that is not utilized for building and repairing cartilage.[10]

Deficiency

Since glucosamine is naturally produced in the body, deficiency is rare.[3, 7] However, as people age, their glucosamine levels decline. The size and quality of aggrecan core proteins, which are vital to cartilage structure and joint function, also diminish with age. Aggrecan levels begin to drop when people reach their 30s. By the time they reach their mid-60s, people only produce a quarter of the amount they made as young adults.[9] However, research shows that glucosamine can stimulate the buildup of mRNA and aggrecan core protein levels.

Aches and pains, joint stiffness, inflammation, and immobility may all be signs of a glucosamine deficiency. If the deficiency worsens, it can result in a reduction of muscle mass and strength, as well as a decrease in bone density. These symptoms make people more vulnerable to bone fractures and osteoarthritis. Unfortunately, the damage from degenerative joint disorders can never be reversed. Glucosamine supplements, however, can help prevent further damage and reduce symptoms.

Dietary Sources of Glucosamine

Glucosamine is found in the shells of shrimp, crab, and other shellfish. Only trace amounts are found in the flesh of the shellfish. The only dietary source with moderate amounts of glucosamine is animal cartilage or gristle, although this is not commonly eaten and it does not provide nearly as much glucosamine as a supplement.[3, 7]

Although dietary sources of glucosamine are extremely limited, it is beneficial to eat foods that support the body’s natural production of glucosamine, which is created when the amino acid glutamine is combined with glucose. Therefore, eating foods with large concentrations of glutamine, such as raw parsley and spinach, can be beneficial.

Glucosamine Supplementation

Research indicates that glucosamine supplementation can serve a useful purpose in the body, either by preventing the breakdown of cartilage and fluid surrounding the joints or by promoting the production of healthy cartilage and synovial fluid.[11] Although there are three types of glucosamine supplements on the market, the most common form that is studied and used is glucosamine sulfate. The other available forms are glucosamine hydrochloride and n-acetyl-glucosamine.[5, 7, 8]

One trial has shown that n-acetyl glucosamine (NAG) is effective in treating people with osteoarthritis and it also significantly enhanced joint damage prevention.[17] According to the study, the polymeric form of n-acetyl glucosamine may provide a source of serum glucosamine for treating osteoarthritis patients. The glucosamine serum levels of patients increased after taking 1 gram of n-acetyl glucosamine or its polymeric form after taking it for three days.

Nevertheless, some studies in animals have explored the effectiveness of the other forms. A study in horses showed that glucosamine sulfate was better absorbed than glucosamine hydrochloride.[18] Higher concentrations of glucosamine were found in the horses’ synovial fluid after ingesting glucosamine sulfate. However, another study showed that dogs with arthritis experienced less pain, a reduction in disease prevention, and improved weight bearing after taking a combination of glucosamine hydrochloride and chondroitin.[19]

In another study, N-acetylglucosamine was given via a 150 mg injection once per week to rabbits with osteoarthritis.[20] Evidence showed that it may help protect the integrity of articular cartilage but no additional statistical information was provided.

Due to the many clinical trials that have shown that glucosamine is effective in treating osteoarthritis patients, the Osteoarthritis Research Society International (OARSI) and the European League Against Rheumatism have recommended that patients with hip and knee osteoarthritis use glucosamine sulfate. The American College of Rheumatology (ACR) and the FDA however, don’t recommend the supplement due to its effectiveness and cost compared to other treatments.

Furthermore, OARSI recommended that treatment should be stopped if no change in symptoms occurred within six months of using glucosamine sulfate. No agency or established scientific group has recommended glucosamine hydrochloride or N-acetylglucosamine. But that is also due to them being newer forms with less research backing.

Research also indicates that supplements containing both glucosamine and chondroitin sulfate are the best form for individuals with osteoarthritis.[21] Although more research is needed on this subject, it is understood that chondroitin sulfate is an integral structural component of cartilage, which may explain why its presence improves the effectiveness of glucosamine supplementation.

People should avoid glucosamine supplements that contain the herbal additive Chinese skullcap, as there have been reports that supplements containing Chinese skullcap have caused liver damage.

Proper Dosage and Contraindications

Most people with healthy joints do not need to take a glucosamine supplement. However, it is recommended that people with osteoarthritis take 500mg of glucosamine three times per day for up to three months or 1,500mg once a day for up to six months.[3]

Although side effects from glucosamine supplementation are rare in otherwise healthy individuals, glucosamine may cause constipation, gas, coughing, diarrhea, dizziness, headache, heartburn, nausea, or vomiting. People with pre-existing gastrointestinal issues, such as peptic ulcers, may be more susceptible to side effects.

Research shows that it is safe to take a glucosamine supplement for up to three years; continuing supplementation for longer than three years may cause liver damage.[6]

Since glucosamine supplements are often made from shrimp, crab, or lobster shells, those with shellfish allergies or sensitivities should be careful in taking them although there is some evidence that people with seafood allergies are not affected by a pure glucosamine supplement.

Be on the lookout and avoid glucosamine supplements that contain the chemical element manganese. Manganese toxicity can cause weakness and lethargy and can eventually lead to impaired memory, hallucinations, and other psychological problems, which may be irreversible.[12]

There is some research that indicates that glucosamine may decrease insulin effectiveness, but studies remain mixed on both sides of the issue. Although this phenomenon has not yet been studied in humans, animal studies have shown a connection between insulin resistance and glucosamine levels, as glucosamine interferes with an enzyme that is required to balance blood glucose levels.[13]

According to a preliminary study, glucosamine supplements raised eye pressure in people who had open-angle glaucoma or elevated intra-ocular pressure. Thus, at-risk individuals should talk to a doctor before beginning a glucosamine supplement and monitor their eye pressure.[14]

Due to a lack of understanding of the in vitro effects of glucosamine supplementation, women who are pregnant or nursing should use glucosamine with caution and consult their physician.

People with high cholesterol, asthma or other breathing disorders, or liver disease should avoid taking glucosamine. Individuals who take blood-thinning medications such as warfarin should also avoid glucosamine supplements, as they may increase the risk of bleeding. Individuals who take blood thinners should be especially wary of glucosamine supplements containing ginkgo biloba, as there have been reports of bleeding following their use. There have been fewer such cases with glucosamine supplements that used fillers such as garlic or saw palmetto.[3]

Choosing A Supplement

Many factors should be considered when choosing a glucosamine supplement. It is important to talk to your doctor before beginning any type of supplementation. If you have a sensitivity to shellfish, consider a supplement from a manufacturer that uses reduced levels of shrimp allergens, or vegetarian and shellfish-free products.

In Europe, glucosamine has been approved for the treatment of osteoarthritis; it is prescribed to promote overall cartilage and joint health. In the United States, it is not considered a drug but rather a supplement and thus does not receive the same amount of scrutiny from the FDA for its sourcing and manufacturing. Since it does not fall under the category of “drug” in the United States, manufacturers and distributors do not need FDA approval to put glucosamine supplements on the market. Thus, it is the responsibility of the consumer to get detailed information about a supplement directly from the manufacturer.[3, 16]

Before choosing a supplement, consumers should look at the source, the molecular form, the way the compound was manipulated, and the reputation of the manufacturer. This degree of careful examination is necessary because supplements are not effectively regulated in the United States. We always analyze these factors when we apply our selection methodology.

To simplify the decision-making process for consumers, we look at the wide variety of supplements on the market to make our recommendations. We study scientific research, cross-reference it with cutting-edge industry news, and talk to experts to ensure that we have identified the best and safest products. Our evaluation process also entails reviewing supplements to ensure that they contain the doses, formulations, and concentrations that are advertised on their labels.

Which is the Best Glucosamine Supplement?

Check out our unbiased recommendation of the best products on the market using our rigorous methodology. We screen products for the right formulation, bioavailability, safety, and efficacy to bring you only the best supplements available in 2019.

References:
1 Roos EM. “Joint injury causes knee osteoarthritis in young adults.” Curr Opin Rheumatol. 2005 Mar;17(2):195-200. Review. PubMed PMID: 15711235. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/15711235
2 Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F, for the National Arthritis Data Workgroup. “Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.” Arthritis Rheumatology. 2008 Jan;58(1):26–35. Accessed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266664/
3 “Glucosamine.” Mayo Clinic. October 14, 2017. Accessed through: http://www.mayoclinic.org/drugs-supplements/glucosamine/safety/hrb-20059572
4 “Osteoarthritis.” Mayo Clinic. 2017. Accessed through: http://www.mayoclinic.org/diseases-conditions/osteoarthritis/home/ovc-20198248
5 Clegg DO, Reda DJ, Harris CL, Klein MaA, et al. “Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis.” New England Journal of Medicine. 2006 Feb;354:795-808. DOI: 10.1056/NEJMoa052771. Accessed through: http://www.nejm.org/doi/full/10.1056/NEJMoa052771
6 “Glucosamine and Chondroitin.” LiverTox. Clinical and Research Information on Drug-Induced Liver Injury. June 2017. Accessed through: https://livertox.nih.gov/Glucosamine.htm
7 Henrotin Y, Mobasheri A, Marty M. “Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?” Arthritis Research & Therapy. 2012 Jan;14(1):201. doi: 10.1186/ar3657. Accessed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392795/
8 Vasiliadis H, Tsikopoulos K. “Glucosamine and chondroitin for the treatment of osteoarthritis.” World Journal of Orthopedics. 2017 Jan 18; 8(1):1–11. doi: 10.5312/wjo.v8.i1.1. Accessed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241539/
9 Dodge GR, Jimenez SA. “Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes.” Osteoarthritis Cartilage. 2003 Jun;11(6):424-32. PubMed PMID: 12801482. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/12801482
10 Setnikar I, Rovati LC. “Absorption, distribution, metabolism and excretion of glucosamine sulfate. A review.” Arzneimittelforschung. 2001 Sep;51(9):699-725. Review. PubMed PMID: 11642003. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/11642003
11 “Glucosamine Sulfate.” U.S. National Library of Medicine. April 22, 2016. Accessed through: https://medlineplus.gov/druginfo/natural/807.html
12 “Manganese Supplement (Oral Route, Parenteral Route).” Mayo Clinic. 2017. Accessed through: http://www.mayoclinic.org/drugs-supplements/manganese-supplement-oral-route-parenteral-route/description/drg-20070154
13 Liese AD, Mayer-Davis EJ, Haffner SM. “The development of the insulin resistance syndrome: an epidemiologic perspective.” Epidemiologic Review. 1998. Accessed through: https://academic.oup.com/epirev/article-pdf/20/2/157/6727618/20-2-157.pdf
14 Murphy RK, Ketzler L, Rice RDE, Johnson SM, Doss MS, Jaccoma EH. “Oral glucosamine supplements as a possible ocular hypertensive agent.” JAMA Ophthalmology. 2013;131(7):955-957. Doi: 10.1001/jamaophthalmol.2013.227. Accessed through: http://jamanetwork.com/journals/jamaophthalmology/fullarticle/1690919
15 U.S. Food and Drug Administration. “Guidance for Industry Clinical Development Programs for Drugs, Devices, and Biological Products Intended for the Treatment of Osteoarthritis (OA) Draft Guidance.” Accessed through: https://www.fda.gov/ohrms/dockets/ac/04/briefing/4045b1_05-conclusions.htm
16 “Dietary Supplements.” U.S. Food and Drug Administration. January 13, 2016. Accessed through: https://www.fda.gov/food/dietarysupplements/usingdietarysupplements/ucm480069.htm#FDA_role
17 Talent JM, Gracy RW. “Pilot study of oral polymeric N-acetyl-D-glucosamine as a potential treatment for patients with osteoarthritis.” Clin Ther. 1996 Nov-Dec;18(6):1184-90. PubMed PMID: 9001835. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/9001835
18 Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S. “Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride.” Osteoarthritis Cartilage. 2008 Sep;16(9):973-9. doi: 10.1016/j.joca.2008.01.006. Epub 2008 Mar 4. PubMed PMID: 18295513. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/18295513
19 McCarthy G, O’Donovan J, Jones B, McAllister H, Seed M, Mooney C. “Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis.” Vet J. 2007 Jul;174(1):54-61. Epub 2006 May 2. PubMed PMID: 16647870. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/16647870
20 Ozkan FU, Ozkan K, Ramadan S, Guven Z. “Chondroprotective effect of N-acetylglucosamine and hyaluronate in early stages of osteoarthritis–an experimental study in rabbits.” Bull NYU Hosp Jt Dis. 2009;67(4):352-7. PubMed PMID: 20001938. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/20001938
21 Vasiliadis HS, Tsikopoulos K.“Glucosamine and chondroitin for the treatment of osteoarthritis.” World J Orthop. 2017 Jan 18;8(1):1–11. doi: 10.5312/wjo.v8.i1.1. Accessed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241539/