Loren Cordain, Ph.D.
Glutamine as a Supplement for Multiple Sclerosis by Loren Cordain, Ph.D.
Glutamine is one of the structural building blocks of proteins called amino acids. It is necessary for the immune system to function appropriately, and glutamine also appears to be needed for normal brain function and digestion.3 While glutamine is the most abundant amino acid in the bloodstream, extreme physical stress (including injuries, surgery, infections and prolonged stress) can deplete glutamine levels when the body's ability to make it is exceeded.3
As a major fuel and important nitrogen source for the small intestinal cell, glutamine is key to maintaining mucosal cell integrity and gut barrier function.4 The contents of the gut lumen contain a toxic/antigenic load from which the body needs to be protected.5,6 The complex mechanisms that support one another to provide this protection include intestinal secretions (primarily mucus and secretory IgA), the mucosal epithelium, and intramural lymphocytes.5,6
An increasing body of literature has associated increased gut permeability with a number of autoimmune diseases, including multiple sclerosis (MS). Autoimmune diseases develop when the body's immune system loses the ability to distinguish between what is "self" and what is "non-self" and attacks healthy tissues and organs as if they were a foreign invader. There is an emerging consensus among scientists who study autoimmune disease that a number of autoimmune diseases have an environmental trigger that originates from a leaky gut thereby allowing microbe and food antigens continual access to the immune system.7-9 Foods containing substances called lectins and saponins, as a general rule, increase gut permeability. A number of common foods contain lectins and/or saponins such as tomatoes,10-12 potatoes,13-18 soy,19 alfalfa,20 quillaja,21 and quinoa.22 I believe these foods may promote autoimmune disease symptoms in genetically susceptible individuals.
In addition, common foods like the tomato act as adjuvants23 (substances that stimulate the immune system) to further exacerbate autoimmune disease symptoms. By eliminating such foods, many autoimmune disease patients have seen improvement in, and even complete remission of, their symptoms.
Although it has been suggested that MS patients should not take glutamine, there is a lot of evidence that glutamine can improve gut barrier function.24 Thus, I recommend autoimmune patients supplement with glutamine because it is a primary fuel source for cells lining the small intestine.
One concern with regard to glutamine supplementation has related to elevated glutamate/ glutamine concentrations seen in MS patients. Glutamine supplementation does not elevate glutamate concentrations,25 and it is the elevated glutamate that causes neuronal damage.26 Elevated glutamate/glutamine concentrations in MS patients result from excessive glutamate receptor up regulation, and the elevation of glutamine levels (which is not toxic to brain and nerve cells) results from increased activity of glutamine synthetase (an enzyme essential in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine) as it detoxifies glutamate. Glutamine is then exported outside of the blood brain barrier to peripheral circulation to be metabolized in muscle and other tissue. Thus, it appears that glutamine supplementation is alright for MS patients.
Dietary supplements, however, may require the supervision of a knowledgeable health care provider. With glutamine, in particular, some clinical studies suggest that it may stimulate the growth of certain tumors.3
The efficacy of glutamine supplements (which are usually in the form of L-glutamine) can be affected by moisture and heat. Moisture leads to the breakdown of glutamine supplements so they should be kept in a dry place, and glutamine powder should not be added to hot beverages because heat destroys glutamine.3
Dietary sources of glutamine include plant and animal proteins such as raw spinach, raw parsley, cabbage, beef, pork, poultry, milk, yogurt, ricotta cheese, and cottage cheese.3 As readers are aware, I have previously recommended a grain, dairy and legume free diet if you suffer from an autoimmune disease so I do not recommend dairy as a source of glutamine.
Next time, we'll look at the dramatic relief the Paleo Diet has brought to IBS patients. We'll also share suggestions for including more colorful summer fruits in your diet.
1. Progress in Autoimmune Disease Research. The Autoimmune Disease Coordinating Committee Report to Congress. U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases. Bethesda (MD), 2005. Website: http://www3.niaid.nih.gov/topics/autoimmune/PDF/ADCCFinal.pdf
2. Fairweather D, Rose NR. Women and autoimmune disease. Emerg Infect Dis 2004;10:2005-2011. Website: http://www.cdc.gov/ncidod/EID/vol10no11/04-0367.htm
3. University of Maryland Medical Center (UMMC). (2009) Glutamine. Website: http://www.umm.edu/altmed/articles/glutamine-000307.htm
4. Den Hond, E. Hiele M, Peeters M, Ghoos Y, Rutgeerts P. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN: J Parenter Enteral Nutr. 1999;23:7-11
5. Galland, L. (1995) Leaky Gut Syndromes: Breaking the Vicious Cycle. Website: http://www.healthy.net/scr/Article.asp?Id=425&xcntr=1
6. Crissinger, K.D., P.R. Kvietys, and D.N. Granger, Pathophysiology of gastrointestinal mucosal permeability. J Intern Med Suppl, 1990. 732: p. 145-54
7. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Brit J Nutr 2000, 83:207-217
8. Arrieta MC, Bistritz L, Meddings JB.Alterations in intestinal permeability. Gut. 2006 Oct;55(10):1512-20
9. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52
10. Johnson IT, Gee JM, Price K, Curl C, Fenwick GR. Influence of saponins on gut permeability and active nutrient transport in vitro. J Nutr. 1986 Nov; 116(11):2270-7
11. Gee J.M.; Wortley G.M.; Johnson I.T.; Price K.R.; Rutten A.A.J.J.L.; Houben G.F.; Penninks A.H. Effects of saponins and glycoalkaloids on the permeability and viability of mammalian intestinal cells and on the integrity of tissue preparations in vitro. Toxicol in Vitro 1996;10: 117-128
12. Keukens EA, de Vrije T, van den Boom C, de Waard P, Plasman HH, Thiel F, Chupin V, Jongen WM, de Kruijff B. Molecular basis of glycoalkaloid induced membrane disruption. Biochim Biophys Acta. 1995 Dec 13;1240(2):216-28
13. Gee J.M.; Wortley G.M.; Johnson I.T.; Price K.R.; Rutten A.A.J.J.L.; Houben G.F.; Penninks A.H. Effects of saponins and glycoalkaloids on the permeability and viability of mammalian intestinal cells and on the integrity of tissue preparations in vitro. Toxicol in Vitro 1996;10: 117-128
14. Keukens EA, de Vrije T, van den Boom C, de Waard P, Plasman HH, Thiel F, Chupin V, Jongen WM, de Kruijff B. Molecular basis of glycoalkaloid induced membrane disruption. Biochim Biophys Acta. 1995 Dec 13;1240(2):216-28
15. Patel B, Schutte R, Sporns P, Doyle J, Jewel L, Fedorak RN. Potato glycoalkaloids adversely affect intestinal permeability and aggravate inflammatory bowel disease. Inflamm Bowel Dis. 2002 Sep;8(5):340-6
16. Mandimika T, Baykus H, Vissers Y, Jeurink P, Poortman J, Garza C, Kuiper H, Peijnenburg A. Differential gene expression in intestinal epithelial cells induced by single and mixtures of potato glycoalkaloids. J Agric Food Chem. 2007 Nov 28;55(24):10055-66
17. Hellenäs KE, Nyman A, Slanina P, Lööf L, Gabrielsson J. Determination of potato glycoalkaloids and their aglycone in blood serum by high-performance liquid chromatography. Application to pharmacokinetic studies in humans. J Chromatogr. 1992 Jan 3;573(1):69-78
18. Harvey MH, Morris BA, McMillan M, Marks V. Measurement of potato steroidal alkaloids in human serum and saliva by radioimmunoassay. Hum Toxicol. 1985 Sep;4(5):503-12
19. Alvarez JR, Torres-Pinedo R. Interactions of soybean lectin, soyasaponins, and glycinin with rabbit jejuna mucosa in vivo. Pediatr Res 1982;16:728-31
20. Story JA, LePage SL, Petro MS, West LG, Cassidy MM, Lightfoot FG, Vahouny GV. Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats. Am J Clin Nutr. 1984 Jun;39(6):917-29
21. Chao AC, Nguyen JV, Broughall M, Recchia J, Kensil CR, Daddona PE, Fix JA. Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin. J Pharm Sci. 1998 Nov;87(11):1395-9
22. J. M. Gee, K. R. Price, C. L. Ridout, G. M. Wortley, R. F. Hurrell, I. T. Johnson. Saponins of quinoa (Chenopodium quinoa): Effects of processing on their abundance in quinoa products and their biological effects on intestinal mucosal tissue. J Sci Food Agric 1993;63(2):201-09
23. Friedman M. Tomato glycoalkaloids: role in the plant and in the diet. J Agric Food Chem 82002;50: 5751-5780
24. Hall, JC et al. Br J Surg 1996 Mar;83(3):305-312
25. Berg A, Bellander BM, Wanecek M, Norberg A, Ungerstedt U, Rooyackers O, Wernerman J. The pattern of amino acid exchange across the brain is unaffected by intravenous glutamine supplementation in head trauma patients. Clin Nutr. 2008 Dec;27(6):816-21
26. Sheldon AL, Robinson MB. The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int. 2007 Nov-Dec;51(6-7):333-55