Glucosamine:Does it Work? (Supplements: Reviewing the Evidence)

The full text is available online. It was a randomized double-blind study of patients with moderate to severe knee pain from osteoarthritis. A Medscape reporter contacted me about the new study because I had written a letter to the editor that was published in American Family Physician where I identified misconceptions about the GAIT trial.

She asked me several questions, and in the resulting article she devoted two paragraphs to my answers. I expressed my reservations and said I would withhold judgment until the weight of evidence falls more clearly on one side or the other. In the comments to the Medscape article, a pathologist said:.

I doubt that dietary glucosamine or chondroitin sulfate are absorbed from the gut as such. Further, human cartilage contains N-acetyl galactosamine, not glucosamine. Depending on source, the dietary CS may have a different structure than human CS.

It is all placebo effect, making lots of money for manufacturers. Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS Director of Base Medical Services and did everything from delivering babies to taking the controls of a B In North America, it is categorized as a nutraceutical, and its production and marketing may not be as strictly controlled.

If you are buying American supplements, choose those that have a quality certification from a third-party agency. Additionally, glucosamine is often sold in combination with chondroitin sulfate, a supplement also used to reduce the symptoms of osteoarthritis.

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Its effectiveness is debated, but some studies suggest it may reduce pain when used alone or in combination with glucosamine Doses usually range from — mg with each meal, adding up to a total daily dose of —1, mg. Most studies used 1, mg per day. Make sure to follow the instructions on the packaging. These supplements are considered safe and no serious side effects have been reported.

Flatulence is the most common complaint. Studies also indicate that glucosamine injections may worsen insulin sensitivity , but supplements do not seem to have the same effect Many studies have not detected any significant benefits, while others suggest the sulfate form may reduce the symptoms of osteoarthritis and delay or slow its development. Nevertheless, some scientists still doubt the effectiveness of glucosamine or consider its small benefits clinically irrelevant.

While glucosamine is no magic solution, others point out that supplements cannot hurt and may be better than no treatment at all. Beta-alanine is an amino acid that is often taken as a sports supplement. It can improve exercise performance and boost overall health. Many people don't eat enough veggies, and products like Super Greens seem like an easy way to get your fill. This article tells you whether greens…. Many people take fish oil supplements daily, but you may not know what's the right dosage for you.

This article discusses how much fish oil you should…. Antioxidant supplements are popular, but evidence suggests that they have several drawbacks. This article explains what antioxidant supplements are…. Wild lettuce is used by people interested in alternatives to conventional pain medications. Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans for example, hyaluronic acid and keratan sulfate in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical.

It has been approved for the treatment of osteoarthritis OA in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamine's mechanisms of action on articular tissues cartilage, synovial membrane and subchondral bone and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations.

However, results from clinical trials have raised many concerns. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Consequently, the published recommendations for the management of OA require revision.

Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA.

Glucosamine is an amino sugar that is essential for the biosynthesis of glycosylated proteins and lipids. It is a major constituent of extracellular matrix macromolecules such as glycosaminoglycans GAGs , glycolipids and glycoproteins in its acetylated form. It is present in high quantities in articular cartilage, intervertebral disc and synovial fluid [ 1 ].

Glucosamine can also be extracted from the chitosan and chitin exoskeleton of crustaceans such as shellfish and may be stabilized as a salt, glucosamine hydrochloride or glucosamine sulfate for oral administration. It has been used for many years in the treatment for osteoarthritis OA. In Europe it is a registered drug approved for the treatment of OA mainly for its symptomatic, slow acting effect in promoting cartilage and joint health.

It has been designated an 'over the counter' dietary supplement by the US Food and Drug Administration. Glucosamine was first thought to provide building blocks substrates for the biosynthesis of cartilage extracellular matrix. Subsequent investigations have found further explanations for its anti-inflammatory and anti-catabolic mechanisms of action. In vitro and in vivo studies have detailed different lines of evidence for how glucosamine can act on joint tissues from OA patients.

In addition, many clinical trials have demonstrated various degrees of efficacy for glucosamine in OA patients. None of the current guidelines have recommended the use of glucosamine hydrochloride, only glucosamine sulfate. Finally, it is important to point out that OARSI recommends that treatment with glusosamine sulfate is discontinued if no symptomatic response is apparent within 6 months of use.

More recently, a change in evidence following a systematic cumulative update of research published through January has been reported by OARSI's treatment guidelines committee [ 7 ]. This meta-analysis reported a gradual decrease in the effect size ES when evidence from randomized controlled trials RCTs was chronologically evaluated. The study highlighted the controversy surrounding the efficacy of glucosamine in terms of both pain and structure modifications. The meta-analysis has highlighted the heterogeneity of outcomes in the different RCTs and the presence of publication bias.

From a scientific perspective, the new concerns raised by the recent meta-analyses will undoubtedly stimulate a re-evaluation of the mechanistic effects of glucosamine. The use of glucosamine in the management of OA remains controversial and its specific mechanism of action in OA pain and function modification are still unclear. The objective of this review is to address the question raised in the title: This review summarizes the effects of glucosamine in OA based on in vitro and in vivo results as well as recent clinical trials.

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Special attention is given to the pharmacokinetics of glucosamine, its side effects and the differences observed with different formulations and combination therapies. Finally, based on these observations, a conclusion is drawn on the role of glucosamine in the management of OA in the context of new compounds and new combinations. The anabolic effects of glucosamine were primarily thought to be attributable to its capacity for providing building blocks for the synthesis of GAGs by chondrocytes [ 8 - 10 ].

Another study confirmed the potency of glucosamine to inhibit the expression and activity of aggrecanase-2 a disintegrin and metalloproteinase with thrombospondin motifs 5 ADAMTS -5 in transiently transfected cell lines [ 13 ]. The authors suggested that the symptomatic and functional effects of glucosamine would be justified by the fact that glucosamine interferes with the matrix metalloproteinases responsible for proteoglycan degradation in OA.

Various properties were demonstrated for glucosamine in the three main tissues involved in OA, cartilage, synovial membrane and subchondral bone. The proteins affected by glucosamine are mainly involved in the signal transduction pathways, redox and stress response, protein synthesis and protein folding. In addition, glucosamine increased the expression of the GRP78 chaperone protein.

This observation supports the reported anti-inflammatory effect of glucosamine. This study also compared glucosamine to chondroitin sulfate; these compounds produced different patterns of protein modification when tested alone or in combination [ 20 ]. A synergistic effect for the modification of superoxide dismutase expression was demonstrated when cells were exposed to both compounds, implying a potent effect on oxidative stress in addition to the modulation of energy production and metabolic pathways produced by chondroitin sulfate.

The pro-anabolic effects of glucosamine were demonstrated in both human chondrocytes and synovial cells, where glucosamine was shown to induce the production of hyaluronic acid HA and to directly enter the GAG biosynthetic pathway that is, for the production of HA, keratan sulfate and sulfated GAGs [ 21 ]. The authors also proposed that the chondroprotective effect of glucosamine results from the modulation of enzymes responsible for HA synthesis. The potential of glucosamine to induce HA production in the synovial membrane was previously suggested in a study that used synovial explants [ 22 ].

In addition, cationic glucosamine derivatives were shown to produce an anti-inflammatory effect through the inhibition of mitogen-activated protein kinase signaling pathways in lipopolysaccharide-stimulated macrophages [ 23 ]. Glucosamine sulfate was also shown to be effective in human OA osteoblasts [ 24 ]. This effect was increased when glucosamine was used in combination with chondroitin sulfate. It is important to point out that these studies were performed in different culture systems, with various formulations and concentrations of glucosamine.

Furthermore, some of these studies compared the effects of two formulations of glucosamine in order to provide evidence for the superiority of one or another [ 21 , 22 , 25 , 26 ]. It was proposed that the differences, if they truly existed, might contribute to the different results observed in clinical trials with various glucosamine formulations. For example, glucosamine sulfate was shown to be a stronger inhibitor of gene expression than glucosamine hydrochloride [ 25 ]. Both formulations were commercially available from a lab supplier.

The same group compared glucosamine hydro-chloride to N-acetylglucosamine [ 22 ] and observed no effect of N-acetylglucosamine on HA production whereas glucosamine hydrochloride appeared to modulate this parameter. The same conclusion was reached in the study by Igarashi and colleagues [ 21 ].

In contrast, another study compared the effect of native glucosamine and N-acetylglucosamine on the metabolic activity of human articular chondrocytes [ 26 ]. Indeed, N-acetylglucosamine appeared to accelerate the facilitated glucose uptake and increase both GAG and HA synthesis, suggesting that N-acetyl-glucosamine may be more efficient than native glucosamine.

Glucosamine has also been tested in combination with chondroitin sulfate in vitro. Some of the results have already been discussed above [ 20 , 24 ].

The effect of combinations of glucosamine and chondroitin was also reported by Chan and colleagues [ 27 - 30 ]. Glucosamine hydrochloride was tested in combination with chondroitin sulfate on bovine cartilage explants. The combination was shown to inhibit both inflammatory and catabolic intermediates and was slightly superior to glucosamine alone [ 27 , 28 ]. Finally, some authors have studied the contribution of exogenous glucosamine to the synthesis of chondroitin sulfate in human articular chondrocytes in culture [ 31 ].

They concluded that exogenous glucosamine cannot stimulate the synthesis of chondroitin sulfate. Furthermore, they showed that glucose can increase endogenous glucosamine to reach concentrations superior to those achieved after oral administration. In conclusion, many of the in vitro investigations carried out so far have been performed using high concentrations of glucosamine - concentrations that are unlikely to be achieved in plasma with oral doses of the drug.

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Several authors have proposed that the therapeutic doses used did not allow the identification of proteoglycan synthesis as a mechanism of action of glucosamine [ 31 , 32 ]. Therefore, extrapolation of the in vitro data to the in vivo situation should be done with great caution.

Several recent in vivo studies using different animal models have demonstrated varying potencies for glucosamine in OA. Glucosamine was shown to delay the progression and severity of OA cartilage lesions. The glucosamine treatment group showed a lower level of cartilage degradation and synovial inflammation compared to the control group. Glucosamine was also shown to modify nociception in OA rats. Mechanical allodynia and weight-bearing distribution were significantly improved by the treatment with glucosamine. The effect of glucosamine on cartilage degradation, synovial inflammation and bone resorption was recently tested in a model of collagenase-induced OA [ 35 ].

Does glucosamine really help joint pain?

This study also compared the efficacies of glucosamine hydrochloride and glucosamine sulfate. The authors showed a better efficacy for glucosamine hydrochloride but did not provide any explanation for this difference. Indeed, glucosamine sulfate demonstrated no effect on the histological score and the formation of osteophytes whereas glucosamine hydrochloride produced a significant reduction of these parameters; glucosamine sulfate was not further evaluated.

In the same study, glucosamine hydrochloride also reduced osteophyte formation and was shown to inhibit the production of the pro-inflammatory cytokine IL-6 and to upregulate the production of the anti-inflammatory cytokine IL by the synovial membrane. It was also tested on equine synovial inflammation induced by lipopolysac-charide injection [ 37 ]. This study revealed that glucosamine levels were increased in the synovium during inflammation in comparison to the healthy joint. The authors did not conclude if glucosamine produced a therapeutic effect or not.

Glucosamine - Scientific Review on Usage, Dosage, Side Effects | www.newyorkethnicfood.com

The same group has previously published results comparing the pharmacokinetics of glucosamine sulfate to glucosamine hydrochloride in horses [ 38 ]. They measured higher concentrations of glucosamine in synovial fluid after glucosamine sulfate administration than after glucosamine hydrochloride administration and concluded that glucosamine sulfate is better absorbed by the horse. Glucosamine hydrochloride was also tested in OA dogs in combination with chondroitin sulfate [ 39 ].

The combination of the two compounds reduced pain and improved weight bearing as well as reduced disease progression. This study suggested that glucosamine may preserve the integrity of articular cartilage but no statistical evidence was provided to support this suggestion. The results showed the superiority of the combination over glucosamine alone in the prevention of biochemical and histological cartilage modifications that occur in the rat OA model. Glucosamine has produced various effects in different in vivo models.