Glucosamine hydrochloride (glucosamine HCl) is the most common form of glucosamine found in supplements. However, studies using glucosamine HCL have reported mostly nonsignificant results, suggesting that this form may not be as effective as other forms, particularly glucosamine sulfate.<a href="#ref-15" id="ref-link-15" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Vlad SC, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17599746" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine for pain in osteoarthritis: why do trial results differ
&lt;/a&gt;&lt;/p&gt;Arthritis Rheum (2007 Jul)&lt;/div&gt;'>[15]</a><a href="#ref-16" id="ref-link-16" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Henrotin Y, Mobasheri A, Marty M. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22293240" target="\_blank" rel="noopener noreferrer"&gt;Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?
&lt;/a&gt;&lt;/p&gt;Arthritis Res Ther (2012-Jan-30)&lt;/div&gt;'>[16]</a>
In comparison, glucosamine sulfate is thought to be more bioavailable when taken orally and has a reduced clearance from the body compared to glucosamine HCL.<a href="#ref-17" id="ref-link-17" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Meulyzer M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18295513" target="\_blank" rel="noopener noreferrer"&gt;Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride.
&lt;/a&gt;&lt;/p&gt;Osteoarthritis Cartilage (2008-Sep)&lt;/div&gt;'>[17]</a>
There is also a form of glucosamine available as a glucosamine sulfate-sodium chloride complex, with a 2:1:1:2 ratio of glucosamine:sulfate:chlorine:sodium. This formulation, patented by Rottafarma in Germany, is designed to be taken once a day; it is sometimes referred to as the “Rotta formulation”.<a href="#ref-3" id="ref-link-3" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Herrero-Beaumont G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17265490" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator
&lt;/a&gt;&lt;/p&gt;Arthritis Rheum (2007 Feb)&lt;/div&gt;'>[3]</a> One study compared the pharmacokinetics of the Rotta formulation and glucosamine sulfate, and found no significant difference.<a href="#ref-18" id="ref-link-18" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Chhavi Asthana, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/32901283" target="\_blank" rel="noopener noreferrer"&gt;Variation in the pharmacokinetics of glucosamine in healthy individuals
&lt;/a&gt;&lt;/p&gt;Rheumatology (Oxford) (2021 Mar 2)&lt;/div&gt;'>[18]</a> In terms of its efficacy, it’s still unclear whether this glucosamine sulfate salt complex is any more effective than glucosamine sulfate, and further research is needed to determine their comparative efficacy.

What is the difference between the various forms of glucosamine?

Glucosamine is an amino monosaccharide (a sugar molecule with a nitrogen group attached) that occurs naturally in almost all human tissues, but is highly concentrated in connective tissues (joints) and cartilage.<a href="#ref-4" id="ref-link-4" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Dahmer S, Schiller RM. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18756654" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine.
&lt;/a&gt;&lt;/p&gt;Am Fam Physician (2008-Aug-15)&lt;/div&gt;'>[4]</a>
The body uses glucosamine to synthesize glycoproteins and glycosaminoglycans. Notably, glycosaminoglycans are structural components present in both cartilage and joints, playing a crucial role in providing these tissues with elasticity, strength, and flexibility.<a href="#ref-4" id="ref-link-4" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Dahmer S, Schiller RM. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18756654" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine.
&lt;/a&gt;&lt;/p&gt;Am Fam Physician (2008-Aug-15)&lt;/div&gt;'>[4]</a>
Although glucosamine is not an FDA-approved treatment, glucosamine supplements are commonly used as adjunct therapy for the management of osteoarthritis. Nevertheless, studies investigating the effectiveness of glucosamine have produced conflicting results.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Williams C, Ampat G. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/32644356" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine Sulfate
&lt;/a&gt;&lt;/p&gt;StatPearls (2023-01)&lt;/div&gt;'>[1]</a>

What is glucosamine?

There is evidence to suggest that glucosamine supplementation may have beneficial effects on mobility and pain reduction in people with <a href="/conditions/kashin-beck-disease/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Kashin-Beck Disease&lt;/h6&gt;&lt;p&gt;Kashin-Beck disease is a joint and bone disease that normally affects children. Symptoms include stiffness and joint deformities. Its exact cause is yet to be determined.&lt;/p&gt;&lt;/div&gt;">Kashin-Beck disease</a> (KBD), a degenerative bone disease characterized by cartilage degradation, similar to osteoarthritis. In one double-blind study, it was observed that individuals with KBD who took 750 mg of glucosamine sulfate twice daily (a total of 1500 mg daily) for 6 weeks experienced reduced pain and improved physical functionality. Interestingly, the effects of glucosamine were comparable to those of the anti-inflammatory medications used in the control groups, which included diclofenac sodium (50 mg twice a day) and naproxen (300 mg twice a day).<a href="#ref-20" id="ref-link-20" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Liu W, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22157279" target="\_blank" rel="noopener noreferrer"&gt;Kashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trial
&lt;/a&gt;&lt;/p&gt;J Clin Rheumatol (2012 Jan)&lt;/div&gt;'>[20]</a>

What are the other benefits of glucosamine?

Research has explored the combination of glucosamine with various supplements, often used to address osteoarthritis and joint health.
<a href="/supplements/boswellia/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Boswellia&lt;/h6&gt;&lt;p&gt;An Ayurvedic herb also classified as a phytopharmaceutical (H15; Europe) which appears to be quite anti-inflammatory, helpful against osteoarthritis, and may help cerebral edema. &lt;em&gt;Boswellia serrata&lt;/em&gt; appears to have preliminary evidence for anti-inflammatory joint disorders.&lt;/p&gt;&lt;/div&gt;">Boswellia</a> is an ayurvedic herb that also appears to have anti-osteoarthritic properties. One animal study comparing the effect of oral supplementation of glucosamine to Boswellia serrata, alone and in combination with each other, found synergistic effects from the combination of the two supplements for chronic inflammation. However, the acute inflammatory response remained unchanged.<a href="#ref-21" id="ref-link-21" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Singh S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17481895" target="\_blank" rel="noopener noreferrer"&gt;Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats.
&lt;/a&gt;&lt;/p&gt;Bioorg Med Chem Lett (2007-Jul-01)&lt;/div&gt;'>[21]</a> The effect of the combination of glucosamine and Boswellia serrata on chronic inflammation seemed comparable to that of the reference anti-inflammatory drug ibuprofen, but it did not outperform it.
<a href="/supplements/fish-oil/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Fish Oil&lt;/h6&gt;&lt;p&gt;Fish oil is a source of omega-3 fatty acids. It reduces triglycerides, but does not seem to affect the rate of cardiovascular events. It seems to notably reduce the symptoms of depression and improve some painful, inflammatory conditions.&lt;/p&gt;&lt;/div&gt;">Fish oil</a> is another supplement often taken in conjunction with glucosamine. One study comparing 1500 mg of glucosamine sulfate to a combination of glucosamine sulfate with fish oil (1332 mg total with 600 mg omega-3 fatty acids) didn’t find any difference in the number of participants who obtained moderate (20%) pain relief, which was the study’s original endpoint. However, the study’s authors did note that if they looked only at the number of people who had substantial (80%) pain relief, slightly but significantly more people experienced this level of pain relief with the combination therapy than with glucosamine alone after 26 weeks of treatment.<a href="#ref-22" id="ref-link-22" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gruenwald J, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19756416" target="\_blank" rel="noopener noreferrer"&gt;Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis.
&lt;/a&gt;&lt;/p&gt;Adv Ther (2009-Sep)&lt;/div&gt;'>[22]</a>
<a href="/supplements/chondroitin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chondroitin&lt;/h6&gt;&lt;p&gt;Chondroitin is a naturally occurring glycosaminoglycan that is present in cartilage. It is frequently taken with glucosamine to help with joint pain and other symptoms of osteoarthritis.&lt;/p&gt;&lt;/div&gt;">Chondroitin</a>, another popular supplement for osteoarthritis management and joint health, is also often used alongside glucosamine. Current research does not support the notion that combining glucosamine and chondroitin leads to synergistic effects in reducing pain and osteoarthritis symptoms.<a href="#ref-6" id="ref-link-6" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zhu X, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29980200" target="\_blank" rel="noopener noreferrer"&gt;Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;J Orthop Surg Res (2018-Jul-06)&lt;/div&gt;'>[6]</a><a href="#ref-4" id="ref-link-4" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Dahmer S, Schiller RM. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18756654" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine.
&lt;/a&gt;&lt;/p&gt;Am Fam Physician (2008-Aug-15)&lt;/div&gt;'>[4]</a>

Can glucosamine be taken alongside other supplements?

Acetaminophen (also known as paracetamol) is often recommended as a first-line treatment for osteoarthritis. One study noted that 1500 mg of glucosamine sulfate taken once daily was approximately equivalent to 3000 mg of acetaminophen over a 6-month course of treatment, with both treatments being more effective than placebo.<a href="#ref-3" id="ref-link-3" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Herrero-Beaumont G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17265490" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator
&lt;/a&gt;&lt;/p&gt;Arthritis Rheum (2007 Feb)&lt;/div&gt;'>[3]</a>
Another meta-analysis compared the effectiveness of various treatments, including glucosamine, chondroitin, their combination, acetaminophen, and celecoxib (a non-steroidal anti-inflammatory drug), at managing pain, function, and stiffness in osteoarthritis. All interventions showed better pain relief than placebo, with celecoxib performing best, followed by the combination of glucosamine and chondroitin, then by chondroitin alone. With respect to physical function and stiffness, acetaminophen did not significantly outperform placebo, whereas glucosamine alone and celecoxib both had a significantly superior effect. Overall, acetaminophen was the least efficacious drug.<a href="#ref-23" id="ref-link-23" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zhu X, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29465368" target="\_blank" rel="noopener noreferrer"&gt;Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.
&lt;/a&gt;&lt;/p&gt;Clin Exp Rheumatol (2018)&lt;/div&gt;'>[23]</a>
Additionally, one study in people with mild to moderate knee osteoarthritis given glucosamine sulfate at 1500 mg daily, either alone or in combination with an NSAID drug (e.g., ibuprofen or piroxicam), observed that while glucosamine was effective in reducing pain at 12 weeks compared to baseline, the combination therapy outperformed glucosamine alone.<a href="#ref-24" id="ref-link-24" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Selvan T, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22577354" target="\_blank" rel="noopener noreferrer"&gt;A clinical study on glucosamine sulfate versus combination of glucosamine sulfate and NSAIDs in mild to moderate knee osteoarthritis.
&lt;/a&gt;&lt;/p&gt;ScientificWorldJournal (2012)&lt;/div&gt;'>[24]</a>

How does glucosamine compare to other treatments?

Glucosamine is a popular supplement for <a href="/conditions/osteoarthritis/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Osteoarthritis&lt;/h6&gt;&lt;p&gt;Osteoarthritis (OA) is a joint disease involving cartilage degradation. It’s not clear what exactly causes OA, but some risk factors include joint injury, overweight or obesity, aging, misaligned joints, and family history. Lots of supplements have been studied in people with OA, as have lifestyle interventions including weight loss and exercise.&lt;/p&gt;&lt;/div&gt;">osteoarthritis</a>, a disease characterized by excessive <a href="/supplements/type-ii-collagen/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Type-II Collagen&lt;/h6&gt;&lt;p&gt;Type II collagen (CII) is a protein and component of joint cartilage. Oral ingestion of CII in its undenatured form may reduce autoimmunity to the body's own CII, resulting in less joint inflammation in instances of osteoarthritis and rheumatism.&lt;/p&gt;&lt;/div&gt;">collagen</a> degradation. However, the evidence supporting its effectiveness is not robust, and study results vary. One trial, known as the Glucosamine Unum In Die Efficacy (GUIDE) trial, which compared supplementation with a glucosamine sulfate-sodium chloride complex to placebo and to acetaminophen (the reference drug for osteoarthritis), found that the glucosamine preparation outperformed both placebo and acetaminophen at reducing knee arthritis severity scores. Although it was well designed, this trial has been criticized as it was sponsored by the same company that manufactured the glucosamine salt used, who not only provided funding but also carried out the statistical analysis.<a href="#ref-3" id="ref-link-3" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Herrero-Beaumont G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17265490" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator
&lt;/a&gt;&lt;/p&gt;Arthritis Rheum (2007 Feb)&lt;/div&gt;'>[3]</a> In contrast, a larger trial of interventions for knee osteoarthritis found that glucosamine alone had no significant effect on pain scores or on the OMERACT-OARSI response, which is a way to categorize how a people with osteoarthritis respond to treatment in clinical trials that was measured as a secondary outcome. However, an exploratory subgroup analysis noted a significant OMERACT-OARSI response to glucosamine treatment in individuals with moderate to severe pain, but not in people with mild pain; since this analysis was exploratory, this finding would need to be confirmed by futher research.<a href="#ref-5" id="ref-link-5" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Clegg DO, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16495392" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis
&lt;/a&gt;&lt;/p&gt;N Engl J Med (2006 Feb 23)&lt;/div&gt;'>[5]</a> Finally, one meta-analysis of interventions for hip and knee arthritis found that glucosamine may improve stiffness but does not significantly affect pain or physical function, whether used alone or in combination with <a href="/supplements/chondroitin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chondroitin&lt;/h6&gt;&lt;p&gt;Chondroitin is a naturally occurring glycosaminoglycan that is present in cartilage. It is frequently taken with glucosamine to help with joint pain and other symptoms of osteoarthritis.&lt;/p&gt;&lt;/div&gt;">chondroitin</a> (another supplement often used for osteoarthritis and joint health).<a href="#ref-6" id="ref-link-6" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zhu X, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29980200" target="\_blank" rel="noopener noreferrer"&gt;Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;J Orthop Surg Res (2018-Jul-06)&lt;/div&gt;'>[6]</a> It’s also important to note that studies suggesting a positive impact of glucosamine on osteoarthritis indicate that it might slow down the disease progression rather than reverse it.
Research on soccer players and bicycle racers has found that in these athletic participants, glucosamine supplementation, particularly at a dose of 3 grams, was able to reduce levels of a biomarker associated with collagen breakdown, CPX-II. While collagen synthesis was not affected, these results suggest that glucosamine may help prevent <a href="/outcomes/coldegradation/" class="popover" data-tooltip='&lt;div&gt;&lt;h6&gt;Collagen Degradation&lt;/h6&gt;&lt;p&gt;Collagen is a protein that is found in a majority of connective tissues. "Collagen degradation" refers to the rate at which collagen is broken down, as opposed to "Collagen biosynthesis."&lt;/p&gt;&lt;/div&gt;'>collagen degradation</a>.<a href="#ref-2" id="ref-link-2" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Momomura R, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/23358550" target="\_blank" rel="noopener noreferrer"&gt;Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers
&lt;/a&gt;&lt;/p&gt;Mol Med Report (2013 Jan 25)&lt;/div&gt;'>[2]</a><a href="#ref-7" id="ref-link-7" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Yoshimura M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19724889" target="\_blank" rel="noopener noreferrer"&gt;Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players
&lt;/a&gt;&lt;/p&gt;Int J Mol Med (2009 Oct)&lt;/div&gt;'>[7]</a> Another study involving participants with knee osteoarthritis who underwent a 12-week strength training program compared glucosamine (1500 mg) to a non-steroidal anti-inflammatory drug (NSAID) (1200 mg of ibuprofen) and found that glucosamine reduced exercise-related pain but did not impact muscle growth or power.<a href="#ref-8" id="ref-link-8" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Petersen SG, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/21807137" target="\_blank" rel="noopener noreferrer"&gt;Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.
&lt;/a&gt;&lt;/p&gt;Arch Phys Med Rehabil (2011-Aug)&lt;/div&gt;'>[8]</a>
There are also potential uses for glucosamine sulfate in <a href="/outcomes/temporomandibular-disorders-tmd-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Temporomandibular Disorder (TMD) Symptoms&lt;/h6&gt;&lt;p&gt;Symptoms of temporomandibular osteoarthritis include jaw pain and discomfort, tight jaw muscles, difficulties with yawning or chewing, a grinding or cracking sensation in the jaw, headache, toothache, earache, and pain in the face or neck.&lt;/p&gt;&lt;/div&gt;">temporomandibular joint disorder</a> (TMD). Glucosamine appears to reduce pain associated with TMD and increase mouth opening, but only when taken for over 3 months. However, as with osteoarthritis, there isn’t enough scientific evidence to support the use of glucosamine sulfate for symptomatic relief of TMD or as a modifier of the disease’s progression.<a href="#ref-9" id="ref-link-9" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Derwich M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/36902359" target="\_blank" rel="noopener noreferrer"&gt;Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review.
&lt;/a&gt;&lt;/p&gt;Int J Mol Sci (2023-Mar-03)&lt;/div&gt;'>[9]</a>

What are glucosamine’s main benefits?

Shellfish allergy is commonly triggered by <a href="/outcomes/immunoglobulin-e/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Immunoglobulin E&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Immunoglobin E&lt;/em&gt; (IgE) is a type of antibody that plays an integral role in type I hypersensitivity, which is seen in allergic diseases like asthma, sinusitis, allergic rhinitis, food allergies, and certain types of urticaria and atopic dermatitis.&lt;/p&gt;&lt;/div&gt;">immunoglobulin E</a> (IgE) antibodies present in the flesh of the shellfish, rather than in the shell. Glucosamine supplements are typically derived from the shells of shellfish, which are not known to contain significant levels of IgE-triggering proteins. Some preliminary studies did not observe allergic reactions to glucosamine in individuals with shellfish allergy. However, it's essential to conduct larger, more comprehensive studies to ensure the safety of glucosamine supplements for people with shellfish allergy and to definitively rule out any potential contraindications.<a href="#ref-19" id="ref-link-19" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Heather C Gray, Patricia S Hutcheson, Raymond G Slavin. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/15341031" target="\_blank" rel="noopener noreferrer"&gt;Is glucosamine safe in patients with seafood allergy?
&lt;/a&gt;&lt;/p&gt;J Allergy Clin Immunol (2004 Aug)&lt;/div&gt;'>[19]</a>

Is glucosamine suitable for people with a shellfish allergy?

Glucosamine appears to be overall safe and with minimal side effects at its most common dosage of 1500 mg a day. One systematic review of <a href="/glossary/randomized-controlled-trial/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Randomized controlled trial&lt;/h6&gt;&lt;p&gt;Randomized controlled trials (RCTs) are the gold standard for determining whether an intervention actually causes any effects. The use of randomization and control groups helps eliminate the effects of factors other than the treatment being studied.&lt;/p&gt;&lt;/div&gt;">randomized controlled trials</a> found no significant difference in the frequency of reported side effects between participants taking glucosamine and those in the placebo group. Although no serious side effects were reported, most adverse events associated with glucosamine supplementation affect the gastrointestinal tract (e.g., <a href="/outcomes/diarrhea-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Diarrhea Symptoms&lt;/h6&gt;&lt;p&gt;Diarrhea refers to loose, watery stools that may be caused by a virus, contaminated food, or disorders such as inflammatory bowel disease.&lt;/p&gt;&lt;/div&gt;">diarrhea</a>, <a href="/outcomes/abdominal-pain/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Abdominal Pain&lt;/h6&gt;&lt;p&gt;Abdominal pain is a pain that originates within the abdomen. It can occur due to a variety of factors that may be benign such as indigestion or more serious conditions such as colon cancer.&lt;/p&gt;&lt;/div&gt;">abdominal pain</a>, <a href="/outcomes/nausea-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nausea Symptoms&lt;/h6&gt;&lt;p&gt;Nausea is the feeling of acute sickness that may result in vomiting and loss of appetite. Some supplements are known as antiemetics, and are used to reduce the sensation of nausea when taken.&lt;/p&gt;&lt;/div&gt;">nausea</a>).<a href="#ref-10" id="ref-link-10" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Vo NX, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37489348" target="\_blank" rel="noopener noreferrer"&gt;Effectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review.
&lt;/a&gt;&lt;/p&gt;Pharmacy (Basel) (2023-Jul-14)&lt;/div&gt;'>[10]</a><a href="#ref-6" id="ref-link-6" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zhu X, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29980200" target="\_blank" rel="noopener noreferrer"&gt;Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;J Orthop Surg Res (2018-Jul-06)&lt;/div&gt;'>[6]</a>
There are no known interactions between glucosamine and medications. However, there was one reported case where glucosamine appeared to enhance the anticoagulant effect of warfarin, therefore increasing the risk of bleeding and bruising.<a href="#ref-11" id="ref-link-11" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Knudsen JF, Sokol GH. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18363538" target="\_blank" rel="noopener noreferrer"&gt;Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database.
&lt;/a&gt;&lt;/p&gt;Pharmacotherapy (2008-Apr)&lt;/div&gt;'>[11]</a> It’s important to note that this was an isolated case, and the person involved was taking a combination of glucosamine and chondroitin, which may also have been responsible for the interaction.
Additionally, animal studies observed an increase in insulin resistance after the administration of glucosamine. Clinical studies administering glucosamine intravenously have confirmed these results. However, this effect occurs at plasma concentrations higher than those achieved with oral supplementation, and to a lesser degree than observed in rat studies.<a href="#ref-12" id="ref-link-12" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Baron AD, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/8675649" target="\_blank" rel="noopener noreferrer"&gt;Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.
&lt;/a&gt;&lt;/p&gt;J Clin Invest (1995-Dec)&lt;/div&gt;'>[12]</a> Other clinical studies have concluded that glucosamine supplementation does not impact insulin sensitivity, so more research is needed to clarify these potential effects.

What are glucosamine’s main drawbacks?

Although glucosamine was initially thought to act as a substrate of collagen, this theory has since been discredited. Instead, it appears that glucosamine interferes with the inflammatory cascade involved in the degradation of collagen in arthritic tissues by downregulating the collagen-deteriorating effects of pro-inflammatory molecules, such as <a href="/outcomes/interleukin-1/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Interleukin 1&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Interleukin 1&lt;/em&gt; (IL-1) refers to a family of 11 cytokines (signaling molecules) that play a role in the immune and inflammatory responses in the body.&lt;/p&gt;&lt;/div&gt;">interleukin 1</a> (IL-1).<a href="#ref-13" id="ref-link-13" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Herrero-Beaumont G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17257091" target="\_blank" rel="noopener noreferrer"&gt;The reverse glucosamine sulfate pathway: application in knee osteoarthritis.
&lt;/a&gt;&lt;/p&gt;Expert Opin Pharmacother (2007-Feb)&lt;/div&gt;'>[13]</a>
Another proposed mechanism observed <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro</a> is that glucosamine sulfate increases collagen expression by promoting the synthesis of glycosaminoglycans. However, it’s important to specify that the concentrations used in this research were high and may not be directly applicable to human oral consumption.<a href="#ref-14" id="ref-link-14" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Block JA, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19733270" target="\_blank" rel="noopener noreferrer"&gt;The effects of oral glucosamine on joint health: is a change in research approach needed?
&lt;/a&gt;&lt;/p&gt;Osteoarthritis Cartilage (2010-Jan)&lt;/div&gt;'>[14]</a> Additionally, clinical studies attempting to measure a serum biomarker of collagen synthesis, type II collagen synthesis (CPII), did not observe a significant effect from glucosamine treatment.<a href="#ref-2" id="ref-link-2" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Momomura R, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/23358550" target="\_blank" rel="noopener noreferrer"&gt;Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers
&lt;/a&gt;&lt;/p&gt;Mol Med Report (2013 Jan 25)&lt;/div&gt;'>[2]</a><a href="#ref-7" id="ref-link-7" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Yoshimura M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19724889" target="\_blank" rel="noopener noreferrer"&gt;Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players
&lt;/a&gt;&lt;/p&gt;Int J Mol Med (2009 Oct)&lt;/div&gt;'>[7]</a>

How does glucosamine work?

Glucosamine

Joints & Bones

Glucosamine Sulfate

Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers

Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator

Glucosamine.

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis

Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.

Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players

Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.

Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review.

Effectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review.

Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database.

Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.

The reverse glucosamine sulfate pathway: application in knee osteoarthritis.

The effects of oral glucosamine on joint health: is a change in research approach needed?

Glucosamine for pain in osteoarthritis: why do trial results differ

Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?

Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride.

Variation in the pharmacokinetics of glucosamine in healthy individuals

Is glucosamine safe in patients with seafood allergy?

Kashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trial

Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats.

Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis.

Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.

A clinical study on glucosamine sulfate versus combination of glucosamine sulfate and NSAIDs in mild to moderate knee osteoarthritis.

Nick Milazzo

Natalka Roshak

Giulia Guerrini

Joint Health

Osteoarthritis

Osteoarthritis Symptoms

Pain

Lower Back Pain

Temporomandibular Disorder (TMD) Symptoms

Kashin-Beck Disease

Kashin-Beck Disease Symptoms

Bone Health

CTX-II

Chronic Low Back Pain

Acute Nonspecific Knee Pain

Injury Rehabilitation Rate

Range of Motion

Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial

Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis

Comparable clinical outcomes between glucosamine sulfate-potassium chloride and glucosamine sulfate sodium chloride in patients with mild and moderate knee osteoarthritis: a randomized, double-blind study

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis

Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee

Glucosamine therapy for treating osteoarthritis

Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis

Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis

Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial

Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial

Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study

A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee

Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee

Glucosamine sulfate in osteoarthritis of the knee

Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial

No effect of glucosamine sulfate on osteoarthritis in the temporomandibular joints--a randomized, controlled, short-term study

Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial

Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled study

Glucosamine administration in athletes: effects on recovery of acute knee injury

Glucosamine hydrochloride (glucosamine HCl) is the most common form of glucosamine found in supplements. However, studies using glucosamine HCL have reported mostly nonsignificant results, suggesting that this form may not be as effective as other forms, particularly glucosamine sulfate.[reference|url=https://pubmed.ncbi.nlm.nih.gov/17599746|title=Glucosamine for pain in osteoarthritis: why do trial results differ|published=2007 Jul|authors=Vlad SC, LaValley MP, McAlindon TE, Felson DT|journal=Arthritis Rheum|][reference|url=https://pubmed.ncbi.nlm.nih.gov/22293240|title=Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?|published=2012-Jan-30|authors=Henrotin Y, Mobasheri A, Marty M|journal=Arthritis Res Ther|]
In comparison, glucosamine sulfate is thought to be more bioavailable when taken orally and has a reduced clearance from the body compared to glucosamine HCL.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18295513|title=Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride.|published=2008-Sep|authors=Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S|journal=Osteoarthritis Cartilage|]
There is also a form of glucosamine available as a glucosamine sulfate-sodium chloride complex, with a 2:1:1:2 ratio of glucosamine:sulfate:chlorine:sodium. This formulation, patented by Rottafarma in Germany, is designed to be taken once a day; it is sometimes referred to as the “Rotta formulation”.[reference|url=https://pubmed.ncbi.nlm.nih.gov/17265490|title=Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator|published=2007 Feb|authors=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|journal=Arthritis Rheum|] One study compared the pharmacokinetics of the Rotta formulation and glucosamine sulfate, and found no significant difference.[reference|url=https://pubmed.ncbi.nlm.nih.gov/32901283|title=Variation in the pharmacokinetics of glucosamine in healthy individuals|published=2021 Mar 2|authors=Chhavi Asthana, Gregory M Peterson, Madhur D Shastri, Rahul P Patel|journal=Rheumatology (Oxford)|] In terms of its efficacy, it’s still unclear whether this glucosamine sulfate salt complex is any more effective than glucosamine sulfate, and further research is needed to determine their comparative efficacy.

Glucosamine is an amino monosaccharide (a sugar molecule with a nitrogen group attached) that occurs naturally in almost all human tissues, but is highly concentrated in connective tissues (joints) and cartilage.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18756654|title=Glucosamine.|published=2008-Aug-15|authors=Dahmer S, Schiller RM|journal=Am Fam Physician|]
The body uses glucosamine to synthesize glycoproteins and glycosaminoglycans. Notably, glycosaminoglycans are structural components present in both cartilage and joints, playing a crucial role in providing these tissues with elasticity, strength, and flexibility.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18756654|title=Glucosamine.|published=2008-Aug-15|authors=Dahmer S, Schiller RM|journal=Am Fam Physician|]
Although glucosamine is not an FDA-approved treatment, glucosamine supplements are commonly used as adjunct therapy for the management of osteoarthritis. Nevertheless, studies investigating the effectiveness of glucosamine have produced conflicting results.[reference|url=https://pubmed.ncbi.nlm.nih.gov/32644356|title=Glucosamine Sulfate|published=2023-01|authors=Williams C, Ampat G|journal=StatPearls|]

There is evidence to suggest that glucosamine supplementation may have beneficial effects on mobility and pain reduction in people with <a href="/conditions/kashin-beck-disease/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Kashin-Beck Disease&lt;/h6&gt;&lt;p&gt;Kashin-Beck disease is a joint and bone disease that normally affects children. Symptoms include stiffness and joint deformities. Its exact cause is yet to be determined.&lt;/p&gt;&lt;/div&gt;">Kashin-Beck disease</a> (KBD), a degenerative bone disease characterized by cartilage degradation, similar to osteoarthritis. In one double-blind study, it was observed that individuals with KBD who took 750 mg of glucosamine sulfate twice daily (a total of 1500 mg daily) for 6 weeks experienced reduced pain and improved physical functionality. Interestingly, the effects of glucosamine were comparable to those of the anti-inflammatory medications used in the control groups, which included diclofenac sodium (50 mg twice a day) and naproxen (300 mg twice a day).[reference|url=https://pubmed.ncbi.nlm.nih.gov/22157279|title=Kashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trial|published=2012 Jan|authors=Liu W, Liu G, Pei F, Liu Y, Zhou Z, Li J, Shen B, Kang P, Xie Q, Ma X|journal=J Clin Rheumatol|]

Research has explored the combination of glucosamine with various supplements, often used to address osteoarthritis and joint health.
<a href="/supplements/boswellia/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Boswellia&lt;/h6&gt;&lt;p&gt;An Ayurvedic herb also classified as a phytopharmaceutical (H15; Europe) which appears to be quite anti-inflammatory, helpful against osteoarthritis, and may help cerebral edema. &lt;em&gt;Boswellia serrata&lt;/em&gt; appears to have preliminary evidence for anti-inflammatory joint disorders.&lt;/p&gt;&lt;/div&gt;">Boswellia</a> is an ayurvedic herb that also appears to have anti-osteoarthritic properties. One animal study comparing the effect of oral supplementation of glucosamine to Boswellia serrata, alone and in combination with each other, found synergistic effects from the combination of the two supplements for chronic inflammation. However, the acute inflammatory response remained unchanged.[reference|url=https://pubmed.ncbi.nlm.nih.gov/17481895|title=Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats.|published=2007-Jul-01|authors=Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Qazi GN|journal=Bioorg Med Chem Lett|] The effect of the combination of glucosamine and Boswellia serrata on chronic inflammation seemed comparable to that of the reference anti-inflammatory drug ibuprofen, but it did not outperform it.
<a href="/supplements/fish-oil/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Fish Oil&lt;/h6&gt;&lt;p&gt;Fish oil is a source of omega-3 fatty acids. It reduces triglycerides, but does not seem to affect the rate of cardiovascular events. It seems to notably reduce the symptoms of depression and improve some painful, inflammatory conditions.&lt;/p&gt;&lt;/div&gt;">Fish oil</a> is another supplement often taken in conjunction with glucosamine. One study comparing 1500 mg of glucosamine sulfate to a combination of glucosamine sulfate with fish oil (1332 mg total with 600 mg omega-3 fatty acids) didn’t find any difference in the number of participants who obtained moderate (20%) pain relief, which was the study’s original endpoint. However, the study’s authors did note that if they looked only at the number of people who had substantial (80%) pain relief, slightly but significantly more people experienced this level of pain relief with the combination therapy than with glucosamine alone after 26 weeks of treatment.[reference|url=https://pubmed.ncbi.nlm.nih.gov/19756416|title=Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis.|published=2009-Sep|authors=Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ|journal=Adv Ther|]
<a href="/supplements/chondroitin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chondroitin&lt;/h6&gt;&lt;p&gt;Chondroitin is a naturally occurring glycosaminoglycan that is present in cartilage. It is frequently taken with glucosamine to help with joint pain and other symptoms of osteoarthritis.&lt;/p&gt;&lt;/div&gt;">Chondroitin</a>, another popular supplement for osteoarthritis management and joint health, is also often used alongside glucosamine. Current research does not support the notion that combining glucosamine and chondroitin leads to synergistic effects in reducing pain and osteoarthritis symptoms.[reference|url=https://pubmed.ncbi.nlm.nih.gov/29980200|title=Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.|published=2018-Jul-06|authors=Zhu X, Sang L, Wu D, Rong J, Jiang L|journal=J Orthop Surg Res|][reference|url=https://pubmed.ncbi.nlm.nih.gov/18756654|title=Glucosamine.|published=2008-Aug-15|authors=Dahmer S, Schiller RM|journal=Am Fam Physician|]

Acetaminophen (also known as paracetamol) is often recommended as a first-line treatment for osteoarthritis. One study noted that 1500 mg of glucosamine sulfate taken once daily was approximately equivalent to 3000 mg of acetaminophen over a 6-month course of treatment, with both treatments being more effective than placebo.[reference|url=https://pubmed.ncbi.nlm.nih.gov/17265490|title=Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator|published=2007 Feb|authors=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|journal=Arthritis Rheum|]
Another meta-analysis compared the effectiveness of various treatments, including glucosamine, chondroitin, their combination, acetaminophen, and celecoxib (a non-steroidal anti-inflammatory drug), at managing pain, function, and stiffness in osteoarthritis. All interventions showed better pain relief than placebo, with celecoxib performing best, followed by the combination of glucosamine and chondroitin, then by chondroitin alone. With respect to physical function and stiffness, acetaminophen did not significantly outperform placebo, whereas glucosamine alone and celecoxib both had a significantly superior effect. Overall, acetaminophen was the least efficacious drug.[reference|url=https://pubmed.ncbi.nlm.nih.gov/29465368|title=Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.|published=2018|authors=Zhu X, Wu D, Sang L, Wang Y, Shen Y, Zhuang X, Chu M, Jiang L|journal=Clin Exp Rheumatol|]
Additionally, one study in people with mild to moderate knee osteoarthritis given glucosamine sulfate at 1500 mg daily, either alone or in combination with an NSAID drug (e.g., ibuprofen or piroxicam), observed that while glucosamine was effective in reducing pain at 12 weeks compared to baseline, the combination therapy outperformed glucosamine alone.[reference|url=https://pubmed.ncbi.nlm.nih.gov/22577354|title=A clinical study on glucosamine sulfate versus combination of glucosamine sulfate and NSAIDs in mild to moderate knee osteoarthritis.|published=2012|authors=Selvan T, Rajiah K, Nainar MS, Mathew EM|journal=ScientificWorldJournal|]

Glucosamine is a popular supplement for <a href="/conditions/osteoarthritis/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Osteoarthritis&lt;/h6&gt;&lt;p&gt;Osteoarthritis (OA) is a joint disease involving cartilage degradation. It’s not clear what exactly causes OA, but some risk factors include joint injury, overweight or obesity, aging, misaligned joints, and family history. Lots of supplements have been studied in people with OA, as have lifestyle interventions including weight loss and exercise.&lt;/p&gt;&lt;/div&gt;">osteoarthritis</a>, a disease characterized by excessive <a href="/supplements/type-ii-collagen/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Type-II Collagen&lt;/h6&gt;&lt;p&gt;Type II collagen (CII) is a protein and component of joint cartilage. Oral ingestion of CII in its undenatured form may reduce autoimmunity to the body's own CII, resulting in less joint inflammation in instances of osteoarthritis and rheumatism.&lt;/p&gt;&lt;/div&gt;">collagen</a> degradation. However, the evidence supporting its effectiveness is not robust, and study results vary. One trial, known as the Glucosamine Unum In Die Efficacy (GUIDE) trial, which compared supplementation with a glucosamine sulfate-sodium chloride complex to placebo and to acetaminophen (the reference drug for osteoarthritis), found that the glucosamine preparation outperformed both placebo and acetaminophen at reducing knee arthritis severity scores. Although it was well designed, this trial has been criticized as it was sponsored by the same company that manufactured the glucosamine salt used, who not only provided funding but also carried out the statistical analysis.[reference|url=https://pubmed.ncbi.nlm.nih.gov/17265490|title=Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator|published=2007 Feb|authors=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|journal=Arthritis Rheum|] In contrast, a larger trial of interventions for knee osteoarthritis found that glucosamine alone had no significant effect on pain scores or on the OMERACT-OARSI response, which is a way to categorize how a people with osteoarthritis respond to treatment in clinical trials that was measured as a secondary outcome. However, an exploratory subgroup analysis noted a significant OMERACT-OARSI response to glucosamine treatment in individuals with moderate to severe pain, but not in people with mild pain; since this analysis was exploratory, this finding would need to be confirmed by futher research.[reference|url=https://pubmed.ncbi.nlm.nih.gov/16495392|title=Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis|published=2006 Feb 23|authors=Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ|journal=N Engl J Med|] Finally, one meta-analysis of interventions for hip and knee arthritis found that glucosamine may improve stiffness but does not significantly affect pain or physical function, whether used alone or in combination with <a href="/supplements/chondroitin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chondroitin&lt;/h6&gt;&lt;p&gt;Chondroitin is a naturally occurring glycosaminoglycan that is present in cartilage. It is frequently taken with glucosamine to help with joint pain and other symptoms of osteoarthritis.&lt;/p&gt;&lt;/div&gt;">chondroitin</a> (another supplement often used for osteoarthritis and joint health).[reference|url=https://pubmed.ncbi.nlm.nih.gov/29980200|title=Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.|published=2018-Jul-06|authors=Zhu X, Sang L, Wu D, Rong J, Jiang L|journal=J Orthop Surg Res|] It’s also important to note that studies suggesting a positive impact of glucosamine on osteoarthritis indicate that it might slow down the disease progression rather than reverse it.
Research on soccer players and bicycle racers has found that in these athletic participants, glucosamine supplementation, particularly at a dose of 3 grams, was able to reduce levels of a biomarker associated with collagen breakdown, CPX-II. While collagen synthesis was not affected, these results suggest that glucosamine may help prevent <a href="/outcomes/coldegradation/" class="popover" data-tooltip='&lt;div&gt;&lt;h6&gt;Collagen Degradation&lt;/h6&gt;&lt;p&gt;Collagen is a protein that is found in a majority of connective tissues. "Collagen degradation" refers to the rate at which collagen is broken down, as opposed to "Collagen biosynthesis."&lt;/p&gt;&lt;/div&gt;'>collagen degradation</a>.[reference|url=https://pubmed.ncbi.nlm.nih.gov/23358550|title=Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers|published=2013 Jan 25|authors=Momomura R, Naito K, Igarashi M, Watari T, Terakado A, Oike S, Sakamoto K, Nagaoka I, Kaneko K|journal=Mol Med Report|][reference|url=https://pubmed.ncbi.nlm.nih.gov/19724889|title=Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players|published=2009 Oct|authors=Yoshimura M, Sakamoto K, Tsuruta A, Yamamoto T, Ishida K, Yamaguchi H, Nagaoka I|journal=Int J Mol Med|] Another study involving participants with knee osteoarthritis who underwent a 12-week strength training program compared glucosamine (1500 mg) to a non-steroidal anti-inflammatory drug (NSAID) (1200 mg of ibuprofen) and found that glucosamine reduced exercise-related pain but did not impact muscle growth or power.[reference|url=https://pubmed.ncbi.nlm.nih.gov/21807137|title=Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.|published=2011-Aug|authors=Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M|journal=Arch Phys Med Rehabil|]
There are also potential uses for glucosamine sulfate in <a href="/outcomes/temporomandibular-disorders-tmd-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Temporomandibular Disorder (TMD) Symptoms&lt;/h6&gt;&lt;p&gt;Symptoms of temporomandibular osteoarthritis include jaw pain and discomfort, tight jaw muscles, difficulties with yawning or chewing, a grinding or cracking sensation in the jaw, headache, toothache, earache, and pain in the face or neck.&lt;/p&gt;&lt;/div&gt;">temporomandibular joint disorder</a> (TMD). Glucosamine appears to reduce pain associated with TMD and increase mouth opening, but only when taken for over 3 months. However, as with osteoarthritis, there isn’t enough scientific evidence to support the use of glucosamine sulfate for symptomatic relief of TMD or as a modifier of the disease’s progression.[reference|url=https://pubmed.ncbi.nlm.nih.gov/36902359|title=Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review.|published=2023-Mar-03|authors=Derwich M, Górski B, Amm E, Pawłowska E|journal=Int J Mol Sci|]

Shellfish allergy is commonly triggered by <a href="/outcomes/immunoglobulin-e/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Immunoglobulin E&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Immunoglobin E&lt;/em&gt; (IgE) is a type of antibody that plays an integral role in type I hypersensitivity, which is seen in allergic diseases like asthma, sinusitis, allergic rhinitis, food allergies, and certain types of urticaria and atopic dermatitis.&lt;/p&gt;&lt;/div&gt;">immunoglobulin E</a> (IgE) antibodies present in the flesh of the shellfish, rather than in the shell. Glucosamine supplements are typically derived from the shells of shellfish, which are not known to contain significant levels of IgE-triggering proteins. Some preliminary studies did not observe allergic reactions to glucosamine in individuals with shellfish allergy. However, it's essential to conduct larger, more comprehensive studies to ensure the safety of glucosamine supplements for people with shellfish allergy and to definitively rule out any potential contraindications.[reference|url=https://pubmed.ncbi.nlm.nih.gov/15341031|title=Is glucosamine safe in patients with seafood allergy?|published=2004 Aug|authors=Heather C Gray, Patricia S Hutcheson, Raymond G Slavin|journal=J Allergy Clin Immunol|]

Glucosamine appears to be overall safe and with minimal side effects at its most common dosage of 1500 mg a day. One systematic review of <a href="/glossary/randomized-controlled-trial/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Randomized controlled trial&lt;/h6&gt;&lt;p&gt;Randomized controlled trials (RCTs) are the gold standard for determining whether an intervention actually causes any effects. The use of randomization and control groups helps eliminate the effects of factors other than the treatment being studied.&lt;/p&gt;&lt;/div&gt;">randomized controlled trials</a> found no significant difference in the frequency of reported side effects between participants taking glucosamine and those in the placebo group. Although no serious side effects were reported, most adverse events associated with glucosamine supplementation affect the gastrointestinal tract (e.g., <a href="/outcomes/diarrhea-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Diarrhea Symptoms&lt;/h6&gt;&lt;p&gt;Diarrhea refers to loose, watery stools that may be caused by a virus, contaminated food, or disorders such as inflammatory bowel disease.&lt;/p&gt;&lt;/div&gt;">diarrhea</a>, <a href="/outcomes/abdominal-pain/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Abdominal Pain&lt;/h6&gt;&lt;p&gt;Abdominal pain is a pain that originates within the abdomen. It can occur due to a variety of factors that may be benign such as indigestion or more serious conditions such as colon cancer.&lt;/p&gt;&lt;/div&gt;">abdominal pain</a>, <a href="/outcomes/nausea-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nausea Symptoms&lt;/h6&gt;&lt;p&gt;Nausea is the feeling of acute sickness that may result in vomiting and loss of appetite. Some supplements are known as antiemetics, and are used to reduce the sensation of nausea when taken.&lt;/p&gt;&lt;/div&gt;">nausea</a>).[reference|url=https://pubmed.ncbi.nlm.nih.gov/37489348|title=Effectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review.|published=2023-Jul-14|authors=Vo NX, Le NNH, Chu TDP, Pham HL, Dinh KXA, Che UTT, Ngo TTT, Bui TT|journal=Pharmacy (Basel)|][reference|url=https://pubmed.ncbi.nlm.nih.gov/29980200|title=Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.|published=2018-Jul-06|authors=Zhu X, Sang L, Wu D, Rong J, Jiang L|journal=J Orthop Surg Res|]
There are no known interactions between glucosamine and medications. However, there was one reported case where glucosamine appeared to enhance the anticoagulant effect of warfarin, therefore increasing the risk of bleeding and bruising.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18363538|title=Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database.|published=2008-Apr|authors=Knudsen JF, Sokol GH|journal=Pharmacotherapy|] It’s important to note that this was an isolated case, and the person involved was taking a combination of glucosamine and chondroitin, which may also have been responsible for the interaction.
Additionally, animal studies observed an increase in insulin resistance after the administration of glucosamine. Clinical studies administering glucosamine intravenously have confirmed these results. However, this effect occurs at plasma concentrations higher than those achieved with oral supplementation, and to a lesser degree than observed in rat studies.[reference|url=https://pubmed.ncbi.nlm.nih.gov/8675649|title=Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.|published=1995-Dec|authors=Baron AD, Zhu JS, Zhu JH, Weldon H, Maianu L, Garvey WT|journal=J Clin Invest|] Other clinical studies have concluded that glucosamine supplementation does not impact insulin sensitivity, so more research is needed to clarify these potential effects.

Although glucosamine was initially thought to act as a substrate of collagen, this theory has since been discredited. Instead, it appears that glucosamine interferes with the inflammatory cascade involved in the degradation of collagen in arthritic tissues by downregulating the collagen-deteriorating effects of pro-inflammatory molecules, such as <a href="/outcomes/interleukin-1/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Interleukin 1&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Interleukin 1&lt;/em&gt; (IL-1) refers to a family of 11 cytokines (signaling molecules) that play a role in the immune and inflammatory responses in the body.&lt;/p&gt;&lt;/div&gt;">interleukin 1</a> (IL-1).[reference|url=https://pubmed.ncbi.nlm.nih.gov/17257091|title=The reverse glucosamine sulfate pathway: application in knee osteoarthritis.|published=2007-Feb|authors=Herrero-Beaumont G, Rovati LC, Castañeda S, Alvarez-Soria MA, Largo R|journal=Expert Opin Pharmacother|]
Another proposed mechanism observed <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro</a> is that glucosamine sulfate increases collagen expression by promoting the synthesis of glycosaminoglycans. However, it’s important to specify that the concentrations used in this research were high and may not be directly applicable to human oral consumption.[reference|url=https://pubmed.ncbi.nlm.nih.gov/19733270|title=The effects of oral glucosamine on joint health: is a change in research approach needed?|published=2010-Jan|authors=Block JA, Oegema TR, Sandy JD, Plaas A|journal=Osteoarthritis Cartilage|] Additionally, clinical studies attempting to measure a serum biomarker of collagen synthesis, type II collagen synthesis (CPII), did not observe a significant effect from glucosamine treatment.[reference|url=https://pubmed.ncbi.nlm.nih.gov/23358550|title=Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers|published=2013 Jan 25|authors=Momomura R, Naito K, Igarashi M, Watari T, Terakado A, Oike S, Sakamoto K, Nagaoka I, Kaneko K|journal=Mol Med Report|][reference|url=https://pubmed.ncbi.nlm.nih.gov/19724889|title=Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players|published=2009 Oct|authors=Yoshimura M, Sakamoto K, Tsuruta A, Yamamoto T, Ishida K, Yamaguchi H, Nagaoka I|journal=Int J Mol Med|]

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