The antioxidant activity of DPPH is dose-dependently displayed by glucosesamine (D-glucosamine) [2]. A 4-hour glucosamine treatment can decrease the phosphorylation of translation-related proteins p70S6K and S6 and inhibit HIF-1α at the protein level [3]. In obstructed kidneys and renal cells treated with TGF-β1, glucosesamine significantly lowers renal expression of fibronectin, type I collagen, and α-smooth muscle actin [4].

Absorption, Distribution and Excretion
In a pharmacokinetic study, glucosamine was absorbed 88.7% of its contents from the gastrointestinal tract. The absolute oral bioavailability was 44%, which may be related to the first-pass effect in the liver. In a pharmacokinetic study of 12 healthy adults, plasma concentrations increased to 30 times the baseline level after oral administration of crystalline glucosamine. At a once-daily dose of 1500 mg, the Cmax was 10 μM. The Tmax was approximately 3 hours. The AUC after a 15000 mg dose was 20216 ± 5021. In a pharmacokinetic study, the fecal excretion rate of glucosamine was 11.3% within 120 hours after administration. The urinary excretion rate was 1.19% within 8 hours after administration. A pharmacokinetic study of 12 healthy volunteers who took glucosamine sulfate soluble powder orally for three consecutive days showed that glucosamine was distributed in the extravascular space. Limited pharmacokinetic data on glucosamine in humans are available in the literature, but a large animal model study in horses showed an average apparent volume of distribution of 15.4 L/kg. Following intravenous administration, glucosamine concentrations ranged from 9 to 15 μM; following nasal administration, concentrations ranged from 0.3 to 0.7 μM. Twelve hours after administration, glucosamine concentrations in most horses remained within the 0.1–0.7 μM range, indicating that once-daily administration was effective. In rats and dogs, radioactive C-14-labeled glucosamine was detectable in the liver, kidneys, articular cartilage, and other tissues. Information on the absorption and serum pharmacokinetics of dietary glucosamine is very limited, and in some cases, existing data are contradictory. For example, in a series of studies, researchers administered (14)C-glucosamine orally to rats, dogs, and humans, and in all cases, the radiolabel was “effectively” absorbed, reaching peak plasma concentrations approximately 4 hours later. Approximately 35% of the radiolabel was excreted in urine, and similar amounts were found in exhaled breath. On the other hand, the laboratory conducting this experiment used chromatographic analysis with a detection limit of approximately 14 μM and failed to detect the chemical content in human serum after a single oral dose of 100 mg/kg (five times the clinical dose) of glucosamine. This indicates that at the normal recommended dose (20 mg/kg), the concentration of bioavailable glucosamine in human serum is far below 10 μM. Approximately 90% of orally administered glucosamine (in the form of glucosamine salts) is absorbed by the small intestine and then transported to the liver via the portal vein circulation. It appears that a significant portion of ingested glucosamine is broken down in the liver through first-pass metabolism. No free glucosamine was detected in serum after oral administration, and it is currently unclear how much of the ingested dose is absorbed by the human joints. Animal studies have shown some absorption in articular cartilage. Twelve healthy volunteers underwent an open-label, randomized, crossover study, receiving once-daily oral administration of 750 mg, 1500 mg, and 3000 mg of glucosamine sulfate soluble powder for three consecutive days. Plasma samples were collected within 48 hours of the last administration to determine glucosamine concentrations. ...Endogenous plasma glucosamine levels were detected (10.4-204 ng/ml, low intra-subject variability). Oral glucosamine is rapidly absorbed, and its pharmacokinetics are linear in the 750-1500 mg dose range, but not at the 3000 mg dose, where the plasma concentration-time curve is lower than expected based on dose-proportioning. Following a standard dose of 1500 mg once daily, plasma concentrations increased more than 30-fold from baseline, peaking at approximately 10 μM. Glucosamine distributes to the extravascular space, and its plasma concentrations remain above baseline until the last collection time. Eighteen patients with osteoarthritis received 1500 mg of commercially available glucosamine sulfate after an overnight fast. Serum samples were collected at baseline and every 15-30 minutes for the following 3 hours. Serum samples were also collected from two subjects at 5 and 8 hours, respectively. Urine samples were collected from three subjects at baseline and 3 hours after administration. All subjects had baseline glucosamine levels below the detection limit of 0.5 μmol/L. However, after ingestion, glucosamine was detectable in 17 of the 18 subjects, with concentrations rising from 30–45 minutes and peaking at 90–180 minutes, ranging from 1.9–11.5 μmol/L (0.34–2 μg/ml). For more complete data on absorption, distribution, and excretion of glucosamine (7 items), please visit the HSDB records page. Metabolism/Metabolites: Glucosamine is metabolized in the liver. Information on glucosamine metabolism is limited in the literature. Biological Half-Life: The estimated half-life of orally administered glucosamine is 15 hours. Following an intravenous bolus of 1005 mg of crystalline glucosamine sulfate, the apparent half-life of the drug was 1.11 hours. In 12 healthy volunteers, the elimination half-life of glucosamine was only preliminarily estimated as a mean of 15 hours.
...After intravenous administration, the radioactivity of glucosamine appears in the plasma and is rapidly eliminated, with an initial half-life of 0.28 hours.

Hepatotoxicity
In controlled trials, neither glucosamine nor its combination with chondroitin was found to be associated with elevated serum enzymes or clinically significant liver injury. Furthermore, no clinically significant liver injury cases were reported in prospective trials. Recently, several case reports and small-sample study series have been published attributing clinically significant liver injury to glucosamine (with or without chondroitin), but the relationship between glucosamine itself and herbal or potential contaminants in other related products remains unclear, and some cases are considered only “possibly” related to glucosamine. Liver injury typically occurs within 1 to 4 weeks of starting the formulation, and the injury pattern is usually hepatocellular or mixed. At least one case of acute liver failure has been reported. Immune allergic reactions (rash, fever, eosinophilia) may occur, but are usually subtle. Most patients have reportedly recovered within 4 to 8 weeks after discontinuation of the drug. There are currently no case reports of re-use of glucosamine, nor are the purity and concentration of glucosamine in the products used reported. Probability Score: D (Possibly a rare cause of clinically significant liver injury).

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Impact During Pregnancy and Lactation
◉ Overview of Medications Used During Lactation
Glucosamine is an amino monosaccharide derived from shellfish or synthesized artificially. Glucosamine sulfate has no specific lactation-related uses. It is most commonly used to treat osteoarthritis. Glucosamine derivative N-acetylglucosamine is a normal component of human breast milk. Glucosamine sulfate is well tolerated, with occasional reports of gastrointestinal discomfort (such as diarrhea, heartburn, nausea, and vomiting). Although there are currently no studies on the use of glucosamine sulfate during lactation, it is unlikely that maternal use of glucosamine sulfate during lactation will have adverse effects on breastfed infants. Dietary supplements do not require extensive premarket approval from the U.S. Food and Drug Administration (FDA). Manufacturers are responsible for ensuring the safety of their products but are not required to prove their safety and efficacy before marketing them. Dietary supplements may contain multiple ingredients, and the ingredients listed on the label often differ from the actual ingredients or amounts. Manufacturers may commission independent agencies to verify the quality of their products or their ingredients, but this does not necessarily mean that the product has been certified as safe or effective. Given the above issues, clinical trial results for one product may not be applicable to other products. For more detailed information on dietary supplements, please visit other pages on the LactMed website.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

[1]. Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S12-7.

[2]. Protective effects of glucosamine hydrochloride against free radical-induced erythrocytes damage. Environ Toxicol Pharmacol. 2014 Jul;38(1):212-9.

[3]. Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells. Int J Oncol. 2014 May;44(5):1699-706.

[4]. Glucosamine hydrochloride exerts a protective effect against unilateral ureteral obstruction-induced renal fibrosis by attenuating TGF-β signaling. J Mol Med (Berl). 2013 Nov;91(11):1273-84.

2-Amino-2-deoxy-D-glucopyranose is a D-glucosamine whose structure contains a D-glucosamine with an amino substituent at the 2-position. It is an E. coli metabolite, a mouse metabolite, and an anti-aging agent. Functionally, it is related to D-glucosamine. It is the conjugate base of 2-amino-2-deoxy-D-glucopyranose. Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage loss, skeletal changes, and synovial inflammation. Treatment with chondroprotective agents (such as glucosamine sulfate) may offer additional benefits compared to using nonsteroidal anti-inflammatory drugs (NSAIDs) to treat OA pain symptoms. Glucosamine is commonly used over-the-counter for arthritis pain, but its acceptance as a drug therapy varies due to conflicting and clinically ambiguous results in clinical trials. Currently, glucosamine is not approved as a prescription drug by the U.S. Food and Drug Administration (FDA) but is widely available over-the-counter. Glucosamine is a metabolite found in or produced by E. coli (K12 strain, MG1655 strain).
Glucosamine is a commonly used nutritional supplement and a natural component of cartilage. It is often used in combination with chondroitin sulfate to treat osteoarthritis and nonspecific joint pain. Isolated case reports suggest that glucosamine may cause clinically significant liver damage, but it has not been confirmed that glucosamine, rather than other herbal ingredients or contaminants, is the causative factor, and liver damage caused by glucosamine or chondroitin sulfate, even if it occurs, is extremely rare.
D-Glucosamine has been reported in water fleas, cannabis, and other organisms with relevant data.
See also: Glucosamine hydrochloride (in salt form); Glucosamine sulfate (with active ingredient). Polyglucosamine (monomer)...see more...
Pharmaceutical Indications
Glucosamine is commonly used over-the-counter to treat symptoms of osteoarthritis and joint pain, often in combination with chondroitin sulfate and/or ibuprofen.
Mechanism of Action
The mechanism of action of glucosamine on joint health is not fully understood, but several possible mechanisms contribute to its therapeutic effects. Since glucosamine is a precursor to glycosaminoglycans, which are major components of articular cartilage, glucosamine supplementation may help rebuild cartilage and treat arthritis symptoms. Some in vitro studies have shown that glucosamine can reduce inflammation by inhibiting interferon-γ and nuclear factor-κB subunit 65 (NF-κB p65), thereby improving symptoms of arthritis and joint pain. Its clinical significance is currently unclear. When glucosamine is absorbed by living cells, it reacts with ATP to produce glucosamine-6-phosphate, which is a natural precursor to glycosaminoglycans (GAGs). Glycosaminoglycans include those containing N-acetylglucosamine (keratin sulfate and hyaluronic acid) and those containing N-acetylglucosamine (heparin sulfate and chondroitin sulfate). These glycosaminoglycans are polysaccharides composed of hexosamine and monosaccharides (such as galactose and glucuronic acid) arranged in linear chains of repeating disaccharide units (such as glucuronic acid and N-acetylglucosamine-6-sulfate in chondroitin sulfate). Besides hyaluronic acid, glycosaminoglycans do not exist alone in nature, but are bound to specific "core" proteins; this complex structure is called proteoglycan (protein-glycosaminoglycan). Hyaluronic acid and various proteoglycans (such as aggregated proteoglycans, versicans, and syndecans) are widely present in the body and play multiple functions.

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Therapeutic Uses
Glucosamine and chondroitin sulfate are used to treat osteoarthritis. A multicenter, double-blind, placebo- and celecoxib-controlled glucosamine/chondroitin sulfate arthritis intervention trial (GAIT) evaluated their efficacy and safety in treating knee pain caused by osteoarthritis. 1583 patients with symptomatic knee osteoarthritis were randomized to receive the following treatments for 24 weeks: 1500 mg glucosamine daily, 1200 mg chondroitin sulfate daily, a combination of glucosamine and chondroitin sulfate, 200 mg celecoxib daily, or placebo. Up to 4000 mg of acetaminophen may be used daily as a rescue analgesic. Patients were stratified into mild [N=1229] and moderate-to-severe [N=354] groups based on the severity of knee pain. The primary efficacy endpoint was a 20% reduction in knee pain from baseline over 24 weeks. The mean age of patients was 59 years, and 64% were female. Overall, glucosamine and chondroitin sulfate were not significantly superior to placebo in reducing knee pain by 20%. Compared with the placebo group (60.1%), the glucosamine group had a 3.9 percentage point higher response rate (P=0.30), the chondroitin sulfate group had a 5.3 percentage point higher response rate (P=0.17), and the combination therapy group had a 6.5 percentage point higher response rate (P=0.09). The response rate in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the response rate in the combination therapy group was significantly higher than that in the placebo group (79.2% vs. 54.3%, P=0.002). Adverse events were mild, infrequent, and evenly distributed across groups. Glucosamine and chondroitin sulfate, alone or in combination, failed to effectively relieve pain in patients with knee osteoarthritis. Exploratory analyses suggest that combined glucosamine and chondroitin sulfate may be effective in a subgroup of patients with moderate to severe knee pain. Osteoarthritis (OA) is the most common type of arthritis, often leading to severe disability and decreased quality of life. To review all randomized controlled trials (RCTs) evaluating the efficacy and toxicity of glucosamine in treating OA, the authors searched the MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and CCTR databases, contacted relevant experts, and manually searched for identified RCTs and related review articles. All searches were updated in January 2005. Included studies met the following criteria: 1) RCTs evaluating the efficacy and safety of glucosamine in treating OA; 2) Both placebo-controlled and comparative studies met the inclusion criteria; 3) Both single-blind and double-blind studies met the inclusion criteria. Data extraction was performed independently by two researchers, and the consistency of results was compared. The quality of RCTs was assessed using the Gotzsche method and a validated tool. Continuous outcome measures were pooled using standardized mean difference (SMD) as the effect size measure. Dichotomous outcome measures were pooled using relative risk ratios (RR). Main results: Only eight studies with adequate allocation concealment were included in the analysis, showing no benefit of glucosamine for pain or WOMAC function scores. Overall, the 20 randomized controlled trials included in the analysis found that glucosamine was superior to placebo, with a 28% improvement in pain (from baseline, SMD -0.61, 95% CI -0.95, -0.28) and a 21% improvement in function assessed by the Lequesne index (from baseline, SMD -0.51, 95% CI -0.96, -0.05). However, the results were not entirely positive, and the reasons for this are unclear. WOMAC pain, function, and stiffness scores did not reach statistical significance. In 10 randomized controlled trials (RCTs) comparing Rotta's glucosamine formulation to placebo, glucosamine was superior to placebo in both pain relief (SMD -1.31, 95% CI -1.99, -0.64) and function assessed using the Lequesne index (SMD -0.51, 95% CI -0.96, -0.05). In RCTs comparing non-Rotta glucosamine formulations to placebo, pooled analysis showed that glucosamine did not reach statistical significance in pain relief (SMD -0.15, 95% CI -0.35, 0.05) and function assessed using the WOMAC index (SMD 0.03, 95% CI -0.18, 0.25). In four RCTs comparing Rotta's glucosamine formulation to nonsteroidal anti-inflammatory drugs (NSAIDs), glucosamine was superior in two trials and comparable in the other two. Two randomized controlled trials (RCTs) using Rotta formulations showed that glucosamine delayed radiographic progression of knee osteoarthritis (OA) over three years (SMD 0.24, 95% CI 0.04–0.43). In terms of the number of subjects reporting adverse events, glucosamine was as safe as placebo (RR = 0.97, 95% CI 0.88–1.08). This update includes 20 studies involving 2570 patients. Pooled results from studies using non-Rotta formulations or with adequate allocation concealment failed to show benefit in pain and WOMAC functional scores, while studies evaluating Rotta formulations showed that glucosamine was superior to placebo in treating pain and functional impairment associated with symptomatic OA. WOMAC scores showed no superiority of Rotta formulations over placebo in terms of pain, stiffness, and function. Glucosamine is as safe as placebo. Glucosamine can be used for the treatment and prevention of osteoarthritis, either alone or in combination with chondroitin sulfate.
Drug Warnings
Individuals with type 2 diabetes, as well as those who are overweight or have impaired glucose tolerance, should closely monitor their blood glucose levels if taking glucosamine supplements. Due to insufficient safety data, children, pregnant women, and breastfeeding women should avoid using glucosamine.
Reported side effects are primarily mild gastrointestinal discomfort, such as heartburn, upper abdominal discomfort, and diarrhea. No allergic reactions have been reported, including allergic reactions to sulfonamides associated with glucosamine sulfate. Glucosamine Sulfate
Glucosamine may increase insulin resistance, thereby affecting glucose tolerance. Diabetic patients who decide to take glucosamine supplements need to monitor their blood glucose levels and may need to adjust the dosage of medications used to control their blood glucose.
Published studies have shown that glucosamine has a generally good safety profile, comparable to placebo. A few reports of mild adverse reactions include gastrointestinal discomfort such as heartburn, diarrhea, constipation, upper abdominal pain, and nausea. One concern with the use of glucosamine is that it may cause or worsen diabetes. In animal models, elevated intracellular glucosamine levels have been associated with insulin resistance (a major factor in the development of type 2 diabetes) and altered insulin secretion.

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Pharmacodynamics
Theoretically, glucosamine administration can provide raw materials for the synthesis of glycosaminoglycans, thereby slowing the progression of osteoarthritis and relieving joint pain symptoms. To date, research results on the efficacy of glucosamine sulfate are inconclusive. Glycosaminoglycans help maintain the elasticity, strength, and flexibility of articular cartilage. A systematic review of multiple studies and guidelines found slight improvements in joint pain and function in patients taking glucosamine. A persistent narrowing of the joint space was observed, but its clinical significance remains unclear.

C6H13NO5

179.17

179.079

3416-24-8

Glucosamine sulfate;29031-19-4;Glucosamine hydrochloride;66-84-2

439213

White to off-white solid powder

1.5±0.1 g/cm3

532.5±50.0 °C at 760 mmHg

88ºC

275.8±30.1 °C

0.0±3.2 mmHg at 25°C

1.572

-2.38

5

6

1

12

155

4

C([C@@H]1[C@H]([C@@H]([C@H](C(O1)O)N)O)O)O

MSWZFWKMSRAUBD-IVMDWMLBSA-N

InChI=1S/C6H13NO5/c7-3-5(10)4(9)2(1-8)12-6(3)11/h2-6,8-11H,1,7H2/t2-,3-,4-,5-,6?/m1/s1

(3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~558.13 mM)
DMSO : ~3.33 mg/mL (~18.59 mM)

Solubility in Formulation 1: 50 mg/mL (279.06 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)