Glucosamine | Supplementopedia

Overview

Glucosamine is a naturally occurring amino-sugar.
It serves as a building block for glycosaminoglycans, the major components of cartilage, synovial fluid, and connective-tissue matrix.
As a dietary supplement, it is most commonly used to support joint health and to help maintain the structural integrity of cartilage.

Extensive randomized-controlled trials (RCTs) and meta-analyses have shown that glucosamine (particularly the sulfate form) modestly reduces pain and improves function in people with mild-to-moderate knee osteoarthritis.
Effect sizes are comparable to non-steroidal anti-inflammatory drugs but with a more favorable safety profile.
Evidence suggests it may slow cartilage degradation by decreasing biomarkers of cartilage breakdown (e.g., urinary C-telopeptide of type II collagen).
Some studies indicate modest anti-inflammatory effects that could benefit low-grade systemic inflammation, though data on metabolic outcomes (e.g., insulin sensitivity) are inconclusive.
Small pilot studies have explored potential neuroprotective effects via O-GlcNAc-mediated signaling, but definitive clinical evidence is lacking.
Overall, the strongest evidence supports joint-related outcomes, while other systemic benefits remain investigational.

Glucosamine enters chondrocytes via sodium-dependent transporters and is phosphorylated to glucosamine-6-phosphate, entering the hexosamine biosynthetic pathway (HBP).
This pathway produces uridine diphosphate N-acetyl-glucosamine (UDP-GlcNAc), a substrate for glycosylation of proteins and lipids.
This is crucial for synthesizing proteoglycans (e.g., aggrecan) and hyaluronic acid that provide cartilage resilience and lubricate joints.
Glucosamine also modulates inflammatory signaling by reducing NF-κB activation and decreasing cytokines (IL-1β, TNF-α) in joint tissue.
Additionally, increased O-GlcNAcylation of intracellular proteins can modulate cellular stress responses, which may underlie reported anti-inflammatory and possibly neuroprotective effects.
The net result is enhanced extracellular-matrix synthesis and reduced catabolic cytokine activity.

The most studied regimen is 1,500 mg of glucosamine sulfate per day.
It is typically taken as a single 1,500-mg tablet or three 500-mg tablets spread across meals to improve absorption.
Glucosamine hydrochloride is used at a comparable dose (1,500 mg) but may have slightly lower bioavailability.
Clinical trials have used 1,200–1,800 mg/day for 8–12 weeks before assessing outcomes; longer-term use (up to 2 years) has shown sustained safety.
For athletes or individuals with higher body weight, a split dose (e.g., 750 mg twice daily) may be considered.
Combining glucosamine sulfate with 1,200 mg of chondroitin sulfate is common, but additive benefits are modest.
Patients with renal impairment should use the lower end of the range (1,200 mg) and monitor renal function.

Glucosamine is generally well-tolerated.
The most common adverse events are mild gastrointestinal symptoms (e.g., bloating, diarrhea) reported in ≤10 % of users.
Rare allergic reactions occur in individuals with shell-fish allergy, although most commercial preparations are purified to remove protein residues; a small subset may still react.
Glucosamine does not significantly raise blood-glucose levels, but diabetics should monitor glycemic control, especially when using hydrochloride forms that contain sodium.
Contraindications include known hypersensitivity to shell-fish or the specific formulation, pregnancy and lactation (insufficient data).
Potential drug interactions: it may potentiate warfarin’s anticoagulant effect (monitor INR) and could theoretically interfere with chemotherapy agents that target the HBP, though clinical reports are limited.
Renal impairment warrants dose reduction and periodic creatinine assessment.

Glucosamine is chemically 2‑amino‑2‑deoxy‑D‑glucose (IUPAC: (2R)-2‑amino‑2‑deoxy‑D‑glucose).
Its molecular formula is C₆H₁₃NO₅ with a molecular weight of 179.17 g·mol⁻¹.
The molecule consists of a hexose backbone with an amine group replacing the hydroxyl at C‑2, conferring basicity.
Two commercially used salts are glucosamine sulfate (often as the sodium or potassium salt of the sulphate) and glucosamine hydrochloride.
Glucosamine is water-soluble (≈50 g/L at 20 °C) and stable at pH 5–7; it is prone to oxidation, thus stabilizers (e.g., sodium chloride) are added in formulations.
The presence of a free amino group makes it a substrate for O‑GlcNAc transferase, linking it directly to protein‑glycosylation pathways.

Commercial glucosamine is primarily derived from chitin in the exoskeletons of crustaceans (shrimp, crab, lobster).
The standard extraction involves demineralization, deproteinization, and acid or enzymatic hydrolysis to liberate glucosamine, which is then purified, crystallized, and converted to either the sulfate or hydrochloride salt.
A growing proportion is produced by microbial fermentation (e.g., E. coli or Corynebacterium spp.) using glucose as a substrate, yielding a non-shell-fish (vegetarian) product that avoids allergen concerns.
Quality considerations include verification of ≥95 % purity, absence of heavy metals or shell-fish proteins, and compliance with USP‑NF or EFSA standards.
Third-party testing (e.g., NSF, ConsumerLab) is recommended to ensure consistent potency and to detect contaminants such as arsenic or lead.