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 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]

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.

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]