Glucosamine

Synonym(s): Glucosamine hydrochloride, Glucosamine sulphate

Nutrient group: Active agents for joints & tissues

Sources and physiological effects

Dietary sources
Glucosamine is an amino sugar that is a component of connective tissue, cartilage and synovial fluid in the human body. It is also found in the diet. Offal and fibrous meat contain concentrated amounts of glucosamine. However, these also contain inflammation-promoting arachidonic acid, which should limited, especially in the case of existing arthrosis. Crustacean shells are the primary source of glucosamine in commercial production of supplements.
Physiological effects
Cartilage and joints	Main building block for the synthesis of proteoglycans, the basic building material of cartilage, tendons and ligaments
Hyaluronic acid	Synthesis of hyaluronic acid – Hyaluronic acid is the backbone of the proteoglycan chain and a component of synovial fluid

Detailed information

Physiological function of glucosamine hydrochloride

Glucosamines serve as structure-building substances for both cartilage and connective tissue. They are also involved in building up the synovial fluid. Their water-binding properties ensure the elasticity and suppleness of the cartilage and the consistency and viscosity of the synovial fluid. Glucosamines are used preventively to maintain healthy cartilage mass and to repair constantly occurring micro-traumas. In addition, they serve to improve joint functions and reduce pain in degenerative joint diseases (1). The therapeutic use of glucosamine hydrochloride is as effective and safe as the use of other forms of glucosamine such as glucosamine sulphate (2).

Glucosamine sulfate and chondroitin: approved active ingredients in complementary therapy

There are now numerous controlled clinical studies demonstrating the efficacy of sulfur-containing glycoproteins in improving osteoarthritic damage. Both glucosamine and chondroitin lead to an increase in hyaluronic acid in the synovia. Due to its water-binding properties hyaluronic acid ensures elasticity and suppleness of the cartilage. This improves the buffer function and reduces pain (3) (4).
If glucosamines are taken regularly over a longer period of time, the joint functions improve (1), the inflammation parameters improve (5) and the pain subsides (6).
A significant slowdown in the progression of degenerative narrowing of the joint space width has also been observed in several long-term studies (7)(8)(9). An examination of postmenopausal women with knee osteoarthritis showed an improvement of all measured parameters by regular glucosamine sulfate intake (10). The positive results are stronger with a combination of glucosamine sulphate and chondroitin sulphate than with one of the substances alone (5). In addition, good tolerability without noticeable side effects is reported(6).
The latest studies point to the great potential of these endogenous substances in preventive and therapeutic use in medical practice. They are a suitable supplement to conventional medicines as they promote natural self-healing. In the course of a successful treatment, pain and anti-inflammatory medications may be reduced or discontinued after consultation with the practioner.

Glucosaminglycans to stabilize the periodontal matrix

The periodontium as an essential supporting and retaining tissue has an extracellular matrix that is reinforced with connective tissue structures. The anchoring of the teeth in the tooth compartments is stabilized by special collagen connective tissue fibers. This so-called gomphosis is a connective tissue bone connection (articulationes fibrosae) that is directly affected by degenerative processes of the periodontium (12). Essential components of these tissues are proteoglycans, which include glucosamine, chondroitin and hyaluronic acid. Special proteoglycans are also found in the matrix of the alveolar bones.Whereas glucosamine and chondroitin have so far been used therapeutically as nutritive measures mainly for the preservation and reconstruction of cartilage substance in joints, a positive interaction with the structures of the periodontal matrix is becoming increasingly apparent. Periodontopathies are associated with a significantly reduced proteoglycan and chondroitin status in the gingiva (13). Animal studies have shown that glucosamine glycans reduce degenerative connective tissue changes and promote regenerative processes (14).
Glucosamine and chondroitin can also be used to regenerate cartilage structures in the temporo-mandibular joint, a biochemical process that is now well documented by in vitro studies (15).

Vegetarian, hypoallergenic, kosher glucosamine hydrochloride

Glucosamines are generally accepted as active substances for preventive and concomitant therapeutic use in degenerative and inflammatory joint diseases (11). Almost all forms of glucosamine are of animal origin. They either come directly from the green-lipped mussel, are made from shark cartilage or are obtained from the shells of crustaceans in several processing steps. Preparations containing these substances cannot be used in strict vegetarians or in patients who are allergic to fish protein. Vegetarian D-glucosamine hydrochloride is obtained from gluten-free corn starch in a propriety process and therefore relies on 100% renewable raw materials. In this production process, natural glucosamines from fermented corn starch are hydrolyzed and finally crystallized out in the form of glucosamine hydrochloride. The production is carried out according to HACCP (food safety) and is quality controlled by ISO 9000.

Dermial® - active complex with glucosamine to improve the dermal moisture content

A decrease in hyaluronic acid concentration in the dermis is seen as a cause for the loss of moisture, resilience and elasticity of the skin. Hyaluronic acid has an enormously high water-binding capacity. As a component of the extracellular matrix in which the collagen and elastic fibers are embedded in the connective tissue, it stimulates the formation of collagen and elastin. It also supports the supply of nutrients to the skin. In addition to the increase in skin thickness, studies also point to cytoprotective effects of hyaluronic acid and its fragments after UV exposure, due to its ability to reduce oxidative stress (16). The high-quality raw material Dermial®, a hyaluronic acid-glucosamine complex from the Spanish quality manufacturer Bioibérica, supplies the skin with hyaluronic acid and glucosamine and its derivative N-acetyl-glucosamine. These are amino sugars which serve as precursors for the biosynthesis of certain polymers such as glycosaminoglycans (e.g. hyaluronic acid) and proteoglycans. Several positive effects on the skin and skin cells have been documented for glucosamine compounds. By stimulating hyaluronic acid synthesis, glucosamine accelerates wound healing, reduces wrinkles and improves the moisture content of the skin. It also inhibits melanin formation by inhibiting tyrosinase activity and is a useful adjuvant for hyperpigmentation (17).
Cell studies with the high-quality raw material Dermial® show that the hyaluronic acid-glucosamine complex increases the intracellular hyaluronic acid concentration and can thus give the cells more moisture (18).

Reference values

Parameter

Substrate

Reference value

Description

COMP

blood

(serum)

< 12.0 U/l

< 12,0 U/l:
Low risk of aggressive joint destruction
12-15 V/l:
Increasing risk of aggressive joint destruction
> 15 U/l:
High risk of aggressive joint destruction

Indications

Dosage	Indication	Dosage
Physiological effects at a low intake	For degenerative and/or inflammatory joint diseases such as osteoarthritis or osteochondritis	1500 – 2000 mg/d
	To maintain and rebuild cartilage structures and improve joint function in degenerative joint diseases	1500 – 2000 mg/d
	For nutritive treatment of joint and cartilage injuries	1500 – 2000 mg/d
	To maintain cartilage tissue and joint functions under heavy strain, especially in older patients and high-performance athletes	1500 – 2000 mg/d
	For nutritive support in degenerative diseases of the periodontal apparatus	1500 – 2000 mg/d
	For nutritive support of the skin and skin structure, especially with decreasing skin tone and reduced water-binding capacity	500 - 1000 mg/d
		500 - 1000 mg/d

Administration

General mode of administration
When	Glucosamine should be taken between meals. Hint: For the treatment of degenerative joint diseases, 1500 mg glucosamine sulphate should be taken daily. On average, the symptoms are expected to improve after 8 weeks. In acute phase injuries 3000 mg daily for 1 week, then 1500 mg until complete healing.
Side effects
A possible interaction of glucosamine with anticoagulants is currently a matter of controversy and has not yet been conclusively clarified. However, it is recommended to inform the primary care physican about high doses and long-term use.
Contraindications
No relevant contraindications known to date.

Interactions

Drug interactions
NSAIDs (e.g. diclofenac, ibuprofen)	Using glucosamine and/or chondroitin can reduce the need for NSAIDs.
Nutrient interactions
Polyphenols	Pycnogenol can be combined with glucosamine in adjuvant therapy due to its analgesic and anti-inflammatory effects.
Fatty acids	Omega-3 fatty acids and glucosamine complement each other in their anti-inflammatory effect in the therapy of inflammatory diseases of the locomotor system.
Trace elements	Manganese supports the effects of glucosamine and chondroitin.
Chondroitin	Synergistic effects with chondroitin on joint pain and –degradation.
Vitamin	Adequate vitamin C, E and D levels support the mode of action of glucosamine and chondroitin.
Methylsulfonylmethane (MSM)	In combination with glucosamine the anti-inflammatory effect can occur faster.

Description and related substances

Description of micronutrient

Glucosamine is an endogenous amino saccharide.

Connections

<Glucosamine sulfate:
etc;

Production from the shells of crustaceans and stabilization with a sulfur component.

Glucosamine hydrochloride:

Made by Aspergillus niger. Vegetarian. Novel Food approval. GRAS status in the USA (generally recognized as safe). brand raw material: Regenasure®.

References

1) Braham, R. et al. 2003. The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med. 37(1):45-9

2) Qiu, G. X. et al.2005. A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride/sulphate in the treatment of knee osteoarthritis. Zhonghua Yi Xue Za Zhi. 85(43):3067-70

3) Uitterlinden, E. J. al. 2008. Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants. BMC Musculoskelet Disord. 11;9:120.

4) David-Raoudi, M. et al. 2009. Chondroitin sulfate increases hyaluronan production by human synoviocytes through differential regulation of hyaluronan synthases: Role of p38 and Akt. Arthritis Rheum. 60(3):760-70.

5) Chou, M. M. et al. 2005. Effects of chondroitin and glucosamine sulphate in a dietary bar formulation on inflammation, interleukin-1beta, matrix metalloprotease-9, and cartilage damage in arthritis. Exp Biol Med. 230(4):255-62

6) Simanek, V. et al. 2005. The efficacy of glucosamine and chondroitin sulphate in the treatment of osteoarthritis: Are these saccharides drugs or nutriceuticals? Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 149(1):51-6

7) Pavelka, K. et al. 2002. Glucosamine sulphate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 162(18):2113-23

8) Poolsup, N. et al. 2005. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic overview of randomized controlled trials. Ann Pharmacother 39(6):1080-7

9) Michel, B. A. et al. 2005. Chondroitin 4 and 6 sulphate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum. 52(3):779-86

10) Bruyer, O. et al. 2004. Glucosamine sulphate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause.11(2): 138-43.

11) Goggs, R. et al. 2005. Nutraceutical therapies for degenerative joint disease: a critical review. Crit Rev Food Sci Nutr. 45(3):145-64

12) Ho, S. P. et al. 2007. The tooth attachment mechanism defined by structure, chemical composition and mechanical properties of collagen fibers in the periodontium. Biomaterials. 28(35):5238-45.

13) Vardar, S. et al. 2004. Total proteoglycan and chondroitin-4-sulfate levels in gingiva of patients with various types of periodontitis. J Periodontol. 75(3):393-8

14) Lallam-Laroye, C. et al. 2006. Periodontitis destructions are restored by synthetic glycosaminoglycan mimetic. J Biomed Mater Res A. 1;79(3):675-83

15) Wang, L., Detamore, M. S. 2008. Effects of growth factors and glucosamine on porcine mandibular condylar cartilage cells and hyaline cartilage cells for tissue engineering applications. Arch Oral Biol.

16) Stauber, G. 2009. Dermokosmetische Prävention vorzeitiger Hautalterung. Medicos.

17) Bissett, D. L. 2006. Glucosamine: an ingredient with skin and other benefits. J Cosmet Dermatol. 5(4):309-15.

18) Bioibérica: Study of dermial® on the synthesis of endogenous hyaluronic acid.

19) Bioibérica: Study of the protective effect of dermial® against the breakdown of collagen.

20) Shibata, K., Tsubouchi, R. 2008. Clinical effects of N-acetylglucosamine supplementation on dry skin. Aestetic

Dermatol, 18:91-99.

References Interactions:
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.

Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.

Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.