What is 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.[4]
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.[4]
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.[1]
What are glucosamine’s main benefits?
Glucosamine is a popular supplement for osteoarthritis, a disease characterized by excessive collagen 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.[3] 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.[5] 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 chondroitin (another supplement often used for osteoarthritis and joint health).[6] 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 collagen degradation.[2][7] 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.[8]
There are also potential uses for glucosamine sulfate in temporomandibular joint disorder (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.[9]
What are glucosamine’s main drawbacks?
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 randomized controlled trials 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., diarrhea, abdominal pain, nausea).[10][6]
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.[11] 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.[12] Other clinical studies have concluded that glucosamine supplementation does not impact insulin sensitivity, so more research is needed to clarify these potential effects.
How does glucosamine work?
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 interleukin 1 (IL-1).[13]
Another proposed mechanism observed in vitro 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.[14] 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.[2][7]
What are other names for Glucosamine
- Glucosamine sulfate
- Glucosamine hydrochloride
- Glucose
- Chitosan
Dosage information
Glucosamine sulfate is typically taken as a 500 mg dose three times a day with food.[1]
The benefits of glucosamine are dose-dependent, and some studies on athletes used up to 2,000–3,000 mg a day, taken in divided doses.[2]
Glucosamine sulfate salts are usually taken as a one-a-day dose of 1500 mg glucosamine.[3]
Frequently asked questions
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.[4]
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.[4]
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.[1]
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.[15][16]
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.[17]
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”.[3] One study compared the pharmacokinetics of the Rotta formulation and glucosamine sulfate, and found no significant difference.[18] 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 a popular supplement for osteoarthritis, a disease characterized by excessive collagen 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.[3] 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.[5] 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 chondroitin (another supplement often used for osteoarthritis and joint health).[6] 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 collagen degradation.[2][7] 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.[8]
There are also potential uses for glucosamine sulfate in temporomandibular joint disorder (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.[9]
There is evidence to suggest that glucosamine supplementation may have beneficial effects on mobility and pain reduction in people with Kashin-Beck disease (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).[20]
Research has explored the combination of glucosamine with various supplements, often used to address osteoarthritis and joint health.
Boswellia 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.[21] 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.
Fish oil 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.[22]
Chondroitin, 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.[6][4]
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.[3]
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.[23]
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.[24]
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 randomized controlled trials 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., diarrhea, abdominal pain, nausea).[10][6]
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.[11] 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.[12] Other clinical studies have concluded that glucosamine supplementation does not impact insulin sensitivity, so more research is needed to clarify these potential effects.
Shellfish allergy is commonly triggered by immunoglobulin E (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.[19]
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 interleukin 1 (IL-1).[13]
Another proposed mechanism observed in vitro 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.[14] 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.[2][7]
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