In animal studies, glucosamine supplementation has been shown to be clinically useful for these conditions.
Mechanism: oral glucosamine increases production of heparan sulfate proteoglycans by the vascular endothelium,
thereby improving the endothelium’s barrier function. Extravasation of leukocytes and metastatic cancer cells
requires degradation of heparan sulfate. Heparan can inhibit neutrophil activation, adhesion, and chemotaxis and
like glucosamine has been reported to be ef ective for managing inflammatory bowel syndromes.
Interestingly, the metastatic capacity of cancer cells tends to correlate with their ability to produce heparanase. It is
concluded that heparan sulfate proteoglycans play an important role in stabilizing the subendothelial extracellular
matrix, cross-linking proteins and reducing their susceptibility to proteolytic degradation. Heparan therapy has been
successful in animals and humans with ulcerative colitis.
In both ulcerative colitis and Crohn’s disease there’s a marked deficiency in extracellular sulfated
glycosaminoglycans in the mucosa (ulcerative colitis) and submucosa (Crohn’s disease), as well as along the
vascular endothelium and subepithelial basal lamina.17-28
Dosage and Standardized Grade
For arthritic conditions and wound healing an oral dose of 500 mg taken three times per day is typical. In heavier
patients and those on diuretics, the total daily dosage should be 20 mg/kg body weight. For arthritic patients
improvement is usually noted within 8-12 weeks.
The best form of glucosamine is Glucosamine Sulfate.
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Toxicity and Contraindications
At the above recommended levels glucosamine sulfate is highly non toxic.
Rare side ef ects have included stomach upset, heartburn, diarrhea, nausea and indigestion. Patients with sulfa drug
or sulfite allergies can still take Glucosamine Sulfate. It is impossible to be allergic to sulfur because it is an essential
mineral for life. Individuals taking diuretics may need higher dosages (20 mg/kg body weight).29
There is some suggestion that glucosamine supplementation may increase insulin resistance in diabetics. The clinical
importance of this remains to be determined.30,31
Drug-Nutrient Interaction
There are no well-known drug-nutrient interactions for Glucosamine Sulfate.
1. Murray M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing; 1996. p. 336-42.
2. Marks DB, Marks AD, Smith CM, editors. Basic Medical Biochemistry: A clinical Approach. Baltimore, Maryland: Williams and Wilkins;
1996. p. 452-64.
3. McCarthy M. Neglect of glucosamine as a treatment for osteoarthritis-a personal perspective. Medical Hypotheses 1994;42:323-7.
4. McCarthy M. Glucosamine for wound healing. Medical Hypothesis 1996;47:273-5.
5. Palmoski MJ, Brankt KD. Effects of some nonsteroidal anti-inflammatory drugs on proteoglycan metabolism and organization in canine
articular cartilage. Arthritis Rheum 1980;23:1010-20.
6. Roden L. Effect of hexosamines on the synthesis of chondroitin sulphuric acid in vitro. Arc Kemi 1956;10:345-52.
7. Karzel K, Domenjoz R. Effects of hexosamine derivatives and uronic acid derivatives on glycosaminoglycan metabolism of fibroblast
cultures. Pharmacology 1971;5:337.
8. Kim JJ, Conrad HE. Effect of D-glucosamine concentration on the kinetics of mucopolysaccharides biosynthesis in cultured chick embryo
vertebral cartilage. J Biol Chem 1974;249:3091-7.
9. Matalon R, Dorfman A. The structure of acid mucolpolysaccharides produced by Hurler fibroblasts in tissue culture. Proc Nat Acad Sci
USA 1968;60:179-85.
10. Vidal RR, et al. Articular Cartilage Pharmacology: Parmacol Res Comm 10 1978;557-569.
Comment [c15]: Couldn’t find other authors
11. D'Ambrosia E, Casa B, Bompani R et al. Glucosamine sulphate. A controlled clinical investigation in arthrosis. Pharmacotherapeutica
Comment [c16]: Couldn’t find other authors
1982;2:504-8.
12. Vas AL. Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulfate in the management of
osteoarthroses of the knee in out-patients. Current Med Res Opinion 1982;8:145-9.
13. Refinster JY, et al. Glucosamine sulfate significantly reduces progression of knee osteoarthritis (KOA). Arthritis Rheum 1999;42:292.
Comment [c17]: Couldn’t find other authors
14. Delafuente JC. Glucosamine in the treatment of osteoarthritis. Rheum. Dis Clin North Am 2000;26(1):1-11.
15. Gottleib MS. Conservative management of spinal osteoarthritis with glucosamine sulfate and chiropractic treatment. J Manipulative
Physiol Ther 1997;20(6):400-14.
16. Glucosamine Sulfate [monograph]. Altern Med Rev 1999;4(3):193-5.
17. Moriga M, Aono M, Murakami M, Uchino H. The activity of N-acetylglucosamine kinase in rat gastric mucosa. Gastroenterol Japonica
1980;15:7-13.
18. Vlodavsky I, Fuks Z, Bar-Ner M, et al. Lymphoma-cell-mediated degradation of sulfated proteoglycans in the subendothelial extracel ular
matrix: Relationship to tumor cell metastasis. Cancer Res 1983;43:2704-11.
19. Nakajima M, Irimura T, Di ferrante D, et al. Heparam sufate degradation: Relation to tumor invasion and metastsitc properties of mouse
Comment [c18]: Couldn’t find other authors
B16 melanoma sublines. Science 1983;220:611-2.
20. Ricovery W, Cappelletti R. Heparan sulfate endoglycosidase and metastatic potential in murine fibrosarcoma and melanoma. Cancer
Res 1986;45:3855-61.
21. Nakajima M, Irimura T, Nicolson GL. Heparanase and tumor metastasis. J Cell Biochem 1988;36:157-67.
22. Vlodavsky I, Eldor A, Bar-Ner M, et al. Heparan sufate degradation in tumor cell invasion and angiogenesis. Adv Exp Med Biol
Comment [c19]: Couldn’t find other authors
1988;233:201-10.
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Accessory Nutrients and Essential Oils
23. Clodavsky I, Korner G, Ishai-Michaeli R, et al. Extracellular matrix resident growth factors and enzymes: Possible involvement in tumor
Comment [c20]: Couldn’t find other authors
metastasis and angiogenesis. Cancer Metastasis Rev 9 1990;203-26.
24. Dwarakanath AD, Yu LG, Brookes C, et al. ‘Sticky’ neutropolis pathergic arthritis and response to heparin in pyoderma gangrenosum
Comment [c21]: Couldn’t find other authors
complicationg ulcerative colitis. Gut 1995;37:585-8.
25. Gaffney PR, O’Leary JJ, Doyle CT, et al. Response to heparin in patients with ulcerative colitis. Lancet 1991;337:238-9.
Comment [c22]: Couldn’t find other authors
26. Gaffney PR, Doyle CT, Hogan J, Gaffney A. Paradoxical response to heparin in 10 patients with ulcerative colitis. Gastroenterology
1993;104:A703.
27. Murch SH, MacDonald TT, Walder-Smith JA, et al. Disruption of sulfated glycosaminoglycans in intestinal inflammation. Lancet
Comment [c23]: Couldn’t find other authors
1993;341:711-4.
28. Lee JCL, Spittel JA Jr., Sauer WG, et al. Hypercoagulability associated with chronic ulcerative colitis: Changes in blood coagulation
Comment [c24]: Couldn’t find other authors
factors. Gastroenterology 1968;54:76-85.
29. Murray MT. The Healing Power of Herbs. 2nd Ed. Rocklin, CA: Prima Publishing; 1995.
30. Monauni T, Zenti MG, Cretti A, Daniels MC, Targher G, Caruso B, et al. Effects of glucosamine infusion on insulin secretion and insulin
action in humans. Diabetes. 2000;49(6):926-35.
31. Shankar RR, Zhu JS, Baron AD. Glucosamine Infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes
mellitus. Metabolism 1998; 47(5):573-7.
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Accessory Nutrients and Essential Oils
Glutamine
General Features
L-Glutamine is the most abundant amino acid in the bloodstream and in the body. It is involved in more metabolic
processes than any other amino acid, fulfilling a number of biochemical needs. It operates as a nitrogen shut le, taking
up excess ammonia and forming urea. Ammonia, a by-product of certain normal biochemical reactions in the body
(including the brain) is toxic to the human body and thus glutamine serves an important function in helping to convert
ammonia into urea, a non toxic end product, which the body can easily eliminate. L-Glutamine can contribute to the
production of other amino acids, glucose, nucleotides, protein and glutathione. It is the principal metabolic fuel for the
epithelial cells that line the small intestine (enterocytes), and for certain immune cells, namely lymphocytes,
macrophages, and fibroblasts.1
Glutamine intake has been shown to enhance glutathione stores in conjunction with N-acetylcysteine, which may
forestall the progression of HIV infection to AIDS in afflicted patients.2 Glutamine supplementation has been shown to
help protect the gastrointestinal tract from damage by certain chemotherapy drugs (i.e. fluorouracil) and also prevents
diarrhea that these drugs are known to produce.1,3
Glutamine supplementation has been shown to enhance immune system function and result in a lower level of
infection and a shorter stay in hospital following surgery, radiation treatment, bone marrow transplantation, and in
patients suf ering from injury, compared with patients receiving Glutamine-free parenteral nutrition.4,5,6
Glutamine is a non-essential amino acid in that the body can synthesize it from the amino acid glutamic acid via the
Glutamine synthase enzyme.7
However, during periods of fasting, starvation, critical illness, cancer, AIDS and following trauma, radiation treatment,
surgery, bone marrow transplantation or in patients with a weakened immune system or catabolic stress, extra
Glutamine replenishment has been shown to be beneficial to re-establish homeostatis.7
Glutamine is also a main anti-catabolic agent in muscle, which when supplemented, may help preserve muscle tissue
(preventing its breakdown), during and after exercise. The heavier one trains, the greater the stress on the muscle
and the greater is the use of Glutamine.8
During and following exercise or trauma, large amounts of alanine and Glutamine are released from muscle. They then
travel through the blood stream to the liver where they can be used to form glucose and glycogen. The total loss of
alanine and Glutamine induced by exercise is above the amount available in muscle and represents more than 50
percent of the total loss of muscle amino acids and nitrogen loss from muscle tissue during exercise. Studies show
that during exercise other muscle amino acids (branched-chain amino acids) are used to donate their carbon skeletons
to make alanine and certain alpha ketoacids and amino acids, such as alpha ketogluturate and glutamic acid are
converted within the muscle to glutamine. Most notably, the branched-chain amino acid, leucine, isoleucine and valine
serve as a substrate for alanine synthesis, but higher levels of intramuscular glutamine (via supplementation) may help
to stop the catabolism of branched chain-amino acids, as glutamine can diffuse from the muscle and become a source
of glucose in the liver to help maintain blood glucose and liver glycogen levels during periods of stress (i.e.
exercise)8,9,10 This is also the role played by alanine, and thus, higher glutamine concentrations may reduce the
requirement for alanine synthesis in the muscle, and thereby spare the breakdown of muscle tissue (branched-chain
amino acid catabolism) during exercise and under other periods of catabolic stress (burn victims, infection, post
surgery etc). 8,9,10
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Meschino Health Comprehensive Guide to Accessory Nutrients and Essential Oils
Accessory Nutrients and Essential Oils
Supplementation Studies and Clinical Applications