After being absorbed from foods and supplements, magnesium passes through the gastrointestinal tract (GI) via the mouth, esophagus, stomach, and the small and large intestines. When the magnesium compound reaches the stomach, the acidic environment starts to dissociate magnesium ions which bind with water molecules. Magnesium is absorbed primarily in the lower part of the small intestines and passes from the villi, tiny finger-like surfaces inside the small intestine, and into capillaries, blood vessels surrounding the small intestine. Magnesium Absorption Categories: Magnesium that is not absorbed in the small intestine travels to the large intestine, where a small amount is
As research continues to grow, it becomes more evident just how crucial the integrity of the digestive system is to overall health. It is the main barrier and first defense between the outer world and inner body. From this basic standpoint, the importance of maintaining a healthy gut lining is monumental. Here is a closer look at some key nutritional therapeutics for the purpose of enhancing gut health:
L-Glutamine: Maintaining Gut Integrity
L-Glutamine is well known as a major fuel and nitrogen source for colonocytes, as well as a component of glutathione.1 These factors alone make it clear that the amino acid is a key nutrient in the intestinal mucosa and for combatting oxidative stress. Anecdotally, many practitioners swear by L-glutamine in its ability to heal the digestive tract under inflammatory circumstances and suboptimal gut integrity. However, research surrounding this topic is far from conclusive. Much research has shown L-glutamine to have positive applications in regulating or improving intestinal permeability. A double-blind trial of L-glutamine showed improvement in AIDS-related diarrhea in individuals taking antiretroviral drugs.2 Similarly, patients receiving chemotherapy have been shown to benefit from reduced frequency of diarrhea versus control groups without a decrease in the efficacy of chemotherapeutics.3,4Testing using the lactulose-manitol ratio test (the preferred measurement for determining the presence or absence of “Leaky Gut Syndrome”) confirmed measureable improvements in intestinal permeability with L-glutamine supplementation in these individuals. Again, in otherwise healthy children suffering from gastroenteritis, L-glutamine supplementation reduced the duration of acute diarrhea by 26% compared to placebo.5 Animal studies also show improved intestinal permeability and preserved gut mucosal integrity using L-glutamine, although an extraordinarily high dose of 500 mg/kg/day was administered in one particular study.6 Clearly, there is a role for L-glutamine in impaired intestinal permeability and diarrhea cases. The application of L-glutamine for Crohn’s Disease (CD) is less apparent. Despite multiple studies showing impaired glutamine levels in CD patients,7 oral supplementation with L-glutamine has not necessarily shown to be of benefit. One study found that glutamine did not help to improve intestinal permeability in individuals with CD,8 yet in vitro research shows a significant reduction in levels of inflammatory molecules after simultaneous exposure of glutamine and arginine to the colonocytes of CD.9Various practitioners and researchers have postulated that clinical trials have not shown a clear benefit in glutamine supplementation with Crohn’s patients for a few reasons: dosing is not adequate in various studies, glutamine must be studied in combination with other nutritional factors, and depleted glutamine may merely be a secondary marker for a separate causative factor.1,10 It is evident that more research is necessary to determine the exact role that L-glutamine plays in such inflammatory conditions of the digestive tract.Other applications for L-glutamine include decreasing the severity of chemotherapy-induced mucositis and gastrointestinal toxicity.10Also, parenteral administration of L-glutamine has shown promising application in those with acute pancreatitis (based on decreased complication rates and mortality rates).11,12
Essential Fatty Acids: Controversial Benefits
There are two types of essential fatty acids (EFA) that the human body cannot synthesize on its own: an omega-3 type, alpha-linolenic acid (ALA), and an omega-6 type, linoleic acid (LA). Both types serve a variety of crucial functions throughout the human physiology, most notably as precursors to various prostaglandins and leukotrienes (thereby regulating inflammatory pathways) and as components of cell membranes.13Although ALA is converted in the body to the biologically active eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA), its conversion rate is quite limited.13 As a result, health practitioners often recommend supplementation of EPA and DHA directly in the form of fish oil. From a digestive health focus, these crucial omega-3 fatty acids have shown possible benefit in Crohn’s Disease (CD), ulcerative colitis (UC), gastritis and proctitis,14,15 although the research is conflicting. For example, certain studies have shown supplementation with fish oil or EPA/DHA to prevent relapses in CD patients while in remission,6,17yet other studies have failed to find a significant effect, if any effect at all.18,19Nevertheless, some experts hypothesize that the minimum dose needed for such a condition appears to be quite high (9,12grams per day), possibly explaining the equivocal results as not all studies reached this dosage.1Similarly, research evaluating the efficacy of fish oil in UC patients has shown clinical improvement and decreased medication need,20 yet many studies show disappointing results.21Prospective cohort studies support a possible protective feature of increased omega-3 fatty acid intake for UC.22A systematic review was performed in 2012 to better evaluate whether omega-3 fatty acids are indeed useful in CD or UC patients. Researchers were unable to come to a conclusion on the recommendations for clinical use based on poor study design features (ie. inappropriate placebo, small number of participants, variable designs). Despite this, they did lean toward the idea that available data does not support the use of omega-3 supplementation for the treatment of active and inactive inflammatory bowel disease.23 A previous meta-analysis in 2011 came to similar conclusions.24For completion’s sake, it should be noted that supplementation with omega-6 oils has been shown to be clinically relevant as well, particularly in the form of gamma-linolenic acid (GLA, converted from LA within the body). Animal research has shown GLA to protect against induced ulcers25 and GLA does have antineoplastic activity against hepatocellular carcinoma in vitro.26 However, very little research has focused on digestive applications of GLA as opposed to other conditions such as arthritis and eczema. Finally, while the trend in modern medicine has been toward high dose omega-3 supplementation to counterbalance the low ratio of omega-3’s to omega-6’s found in today’s diet, some have posed the question of whether we are actually overdosing on omega-3 fatty acids.27 This theory is supported by the fact that EPA and DHA are only converted in small amounts within the body because that is all that we physiologically need. More clinical research must be performed to determine the optimal ratio of EFA’s for supplementation and dietary purposes, as well as the exact role in treating clinical conditions.
Zinc Carnosine: An Anti-ulcer Agent
It has long been known that zinc is essential for the human body in physiological processes such as wound healing, immune function and hormonal regulation.28 However, novel research has examined the role of zinc carnosine ([ZnC], zinc combined with the amino acids beta-alanine and histidine) for its gastroprotective capabilities and potential as a gastric ulcer treatment therapy. In fact, its application as an anti-ulcer drug has been in clinical use for quite some time now in Japan.29Numerous clinical studies of ZnC examining its anti-ulcer effects have shown great safety and efficacy through endoscopic measures. Optimum healing appears to be achieved after 8 weeks of treatment (as high as 72% achieving “remarkable improvement” in one study), although 4 weeks demonstrates great improvements as well.29 Another study showed that co-administration of ZnC with indomethacin (a Non-Steroidal Anti-Inflammatory Drug [NSAID]) eliminated the increase in gut permeability in humans when the NSAID was given alone. In addition, this coadministration also negated the formation of gastric ulcers in rats versus the damage seen when indomethacin was the sole therapy.30ZnC also shows strong potential as an anti-Helicobacter pylori agent (thereby adding to its role as an anti-ulcer supplement). In a clinical trial examining the efficacy of H. pylori eradication using ZnC in combination with triple therapy (lansoprazole, amoxicillin and clarithromycin), significant improvements were seen when compared to triple therapy alone.31 These results have been attributed to its bactericidal, anti-urease and anti-adhesive properties toward H. pylori specifically.32Aside from anti-bacterial action, the mechanism of action for ZnC appears quite complex and multi-targeted. L-carnosine specifically prevents gastric epithelial injury by inhibiting DNA fragmentation,33 whereas ZnC together acts as an antioxidant, induces the expression of Heat Shock Protein 72 (HSP72) and inhibits Nuclear Factor kB (NF-kB) in the colonic mucosa.34This increase in HSP72 activity and decreased NF-kB level has been shown to have cytoprotective effects on digestive organs. Other actions include the restoration of glutathione levels in injured gastric mucosa, promotion of growth factor formation, promotion of polyamine synthesis and inhibition of proinflammatory cytokine production (such as Tumor Necrosis Factor-alpha [TNF-α]) – all of which are essential processes in mucosal protection and ulcer healing in the gut.35 Overall, the actions of ZnC make it a suitable pairing for optimal gut health and protection. As an added benefit, ZnC has also shown application in improving taste sensitivity in cases of idiopathic taste disorders.36
Nitric Oxide: Not Just a Vasodilator
Classically, nitric oxide (NO) has been considered for its cardiovascular role as a potent vasodilator. However, many are unaware that the effects of NO are much more far reaching; it is also a proven anti-microbial, a necessary agent for tissue protection under ischemic circumstances and a gastroprotective agent.37 With this in mind, NO and its precursors (nitrates and nitrites) have tremendous therapeutic potential that is still yet to be fully realized.From a gastroprotective standpoint, research has focused on the ability of NO to prevent and treat gastric ulcers. More specifically, nitrates, nitrites and NO have been shown to mitigate gastric ulcerations commonly caused by non-steroidal anti-inflammatory drugs (NSAIDs), endotracheal intubation and Helicobacter pylorithrough a variety of mechanisms.38,39,40NO appears to mitigate epithelial permeability, reduce tissue inflammation, increase gastric mucosal blood flow and, subsequently, increase mucus generation.38,39 Collectively, these actions provide supportive protection in bacterial overgrowth and they help to offset the depletion of gastric NO due to common medical interventions.41
Keeping in mind the crucial role that a well-balanced gut microflora plays in our digestive health, NO helps to regulate this ecosystem through its broad-spectrum antibiotic effect. In vitro, NO and nitrites have proven to combat Shigella, Yersinia and Salmonella species, as well as Helicobacter pylori, Clostridium botulinum and Pseudomonas aerguinosa.40,42,43 This inhibition of H. pylori by nitrites and NO may be a separate and additive protective mechanism for gastric ulcer prevention, while simultaneously promoting healing of the mucosal lining.43Therapeutically, the most effective way to increase NO levels in the body and provide gastrointestinal protection is to deliver nitrates directly and drive the nitrate–nitrite–nitric oxide pathway (also known as the “NOx3,2,1” pathway). This delivery method holds many advantages over the classic L-arginine-Nitric oxide pathway including stimulation of the entero-salivary nitrate cycle. In the most basic sense, this cycle allows nitrate conversion to nitrite in the oral cavity by commensal bacteria, followed by reduction to NO in the stomach.37 The cycle continues as nitrates and remaining nitrites are rapidly absorbed into the blood stream and recirculated to the salivary glands, where further reduction and activation of NO can take place.37Interestingly, animal research shows that the gastroprotective effect of nitrate supplementation is eliminated if topical antibiotics are used in the oral cavity to disrupt the oral microflora.44As a final note, administering NO precursors in a clinical setting may be contraindicated in patients suffering from reflux esophagitis, as NO also appears to trigger relaxation of the lower esophageal sphincter.45 However, given the gastroprotective effects discussed above, clinical judgment must be exercised, as this aggravating effect is merely theoretical.
1. Yarnell E. Natural approach to gastroenterology. WA, Healing Mountain Pub: 2011. pp 987-988.
2. Bushen, OY, Davenport JA, Lima AB, et al. Diarrhea and reduced levels of anti-retroviral drugs: improvement with glutamine or alanyl-glutamine in a randomized control trial in northeast Brazil. Clin Infect Dis. 2004; 38:1764-1770
3. Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: A double blind, placebo controlled, randomised trial. Gut. 2001; 48(1):28-33
4. Li Y, Yu Z, Liu F, et al. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor eff ect of chemotherapy in patients with breast cancer: A prospective randomized trial. Tumori. 2006; 92(5):396-401
5. Yalcin SS, Yurdakok K, Tezcan I, et al. Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2004; (38):494-501
6. Dos Santos RG, Viana ML, Generoso SV, et al. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model. JPEN J Parenter Enteral Nutr. 2010; 34(4):408-413
7. Balasubramanian K, Kumar S, Singh RR, et al. Metabolism of the colonic mucosa in patients with inflammatory bowel diseases: An in vitro proton magnetic resonance spectroscopy study. Magn Reson Imaging. 2009; 27(1):79-86
8. Hond ED, Hiele M, Peeters M, et al. 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
9. Lecleire S, Hassan A, Marion-Letellier R, et al. Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from crohn’s patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways. J Nutr. 2008; 38(12):2481-2486
10. Gaby, A. Nutritional medicine. Concord, N.H, Fritz Perlberg Publishing. 2011. Pp. 1221.
11. Sahin H, Mercanligil SM, Inanç N, et al. Effects of glutamine-enriched total parenteral nutrition on acute pancreatitis. Eur J Clin Nutr. 2007; 61:1429–1434
12. Fuentes-Orozco C, Cervantes-Guevara G, Mucino-Hernandez I, et al. L-alanyl-glutamine supplemented parental nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. JPEN J. Parenter Enteral Nutr 2008; 32:403-411
13. Gaby, A. Nutritional medicine. Concord, N.H, Fritz Perlberg Publishing. 2011. Pp 227-234
14. Almallah YZ, Richardson S, O’Hanrahan T, et al. Distal procto-colitis, natural cytotoxicity and essential fatty acids. Am J Gastroenterol. 1998; 93:804-809
15. Kremer JM, Malamood H, Maliakkal B, et al. Fish oil dietary supplementation for prevention of indomethacin induced gastric and small bowel toxicity in healthy volunteers. J Rheumatol. 1996; 23(10):1770-1773
16. Belluzzi A, Brignola C, Campierei M, et al. Effect of enteric-coated fish-oil preparation on relapses in crohn’s disease. N Engl J Med. 1996; 334(24):1557-1560
17. Romano C, Cucchiara S, Barabino et al. Usefullness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn’s disease: a double-blind, randomized, placebo-controlled study. World J Gastroenterol. 2005; 11:7118-7121
18. Feagan BC, Sandborn WJ, Mittmann U, et al. Omega-3 free fatty acids for the maintenance of remission in crohn’s disease. The epic randomized controlled trials. JAMA. 2008; 299(14):1690-1697
19. Lorenz-Meyer H, Bauer P, Nicolay C, et al. Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn’s disease. N Engl J Med 1996; 334:1557-1560
20. Salomon P, Kornbluth AA, Janowitz HD. Treatment of ulcerative colitis with fish oil n-3-omega-fatty acid: an open trial. J Clin Gastroenterol. 1990; 12:157-161
21. Dichi I, Frenhane P, Dichi JB, et al. Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis. Nutrition. 2000;16:87-90
22. John S, Luben R, Srethsa SS et al. Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol. 2010 May; 22(5):602-6
23. Cabré E, Mañosa M, Gassull MA. Omega-3 fatty acids and inflammatory bowel diseases – a systematic review. Br J Nutr. 2012; 107(2):240-52
24. Turner D, Shah PS, Steinhart AH, et al. Maintenance of remission in inflammatory bowel disease using omega-3 fatty acids (fish oil): a systematic review and meta-analyses. Inflamm Bowel Dis. 2011; 17(1):336-45
25. Das UN, Reddy DN, Rao PN, et al. Essential fatty acids and peptic ulcer disease. Gut. 1987; 28:914-915
26. Itoh S, Taketomi A, Harimoto N, et al. Antineoplastic effects of gamma linolenic acid on hepatocellular carcinoma cell lines. J Clin Biochem Nutr. 2010; 47(1):81-90
27. Peskin BS, Habib A. The Hidden Story of Cancer Find Out Why Cancer Has Physicians on the Run and How a Simple Plan Based on New Science Can Prevent It. Pinnacle Pr. 2012.
28. Gaby A. Nutritional medicine. Concord, N.H, Fritz Perlberg Publishing. 2011. Pp 151.
29. Matsukura T, Tanaka H. Applicability of zinc complex of L-carnosine for medical use. Biochemistry. 2000; 65(7):817-823
30. Mahmood A, FitzGerald AJ, Marchbank T et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb; 56(2):168-175
31. Kashimura H, Suzuki K, Hassan M et al. Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxicillin and clarithromycin increases the cure rate of Helicobacter pylori infection. Aliment Pharmacol Ther. 1999; 13:483-487
32. Sunair M, Tanaka N, Kuwayama H, et al. Effect of Z-103, a new antiulcer agent, on Helicobacter pylori – antimicrobial, antiurease, and antiadhesive activities. Jpn Pharmacol Ther. 1994; 22(9):31-5
33. Suzuki H, Mori M, Seto K et al. Polaprezinc, a gastroprotective agent: attenuation of monochloramine-evoked gastric DNA fragmentation. J Gastroenterol. 1999; 34(11):43–6
34. Odashima M, Otaka M, Jin M et al. Zinc L-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kB activation. Life Sciences. 2006;79:2245–2250
35. Ko JK, Leung CC. Ginger extract and polaprezinc exert gastroprotective actions by anti-oxidant and growth factor modulating effects in rats. Gastroenterology and Hepatology. 2010; 25:1861-1869
36. Sakagami M, Ikeda M, Tomita H et al. A zinc-containing compound, Polaprezinc, is effective for patients with taste disorders: randomized, double-blind, placebo-controlled, multi-center study. Acta Otolaryngol. 2009 Oct; 129(10):1115-20
37. Lundberg, JO, Weitzberg, E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nature Publishing Group. 2008; Vol 7:156-167
38. Bjorne HH, Petersson J, Phillipson M,et al. Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J Clin Invest. 2004; 113:106-114
39. Petersson J, Phillipson, M, Jansson, E. A. et al. Dietary nitrate increases gastric mucosal blood flow and mucosal defense. Am J Physiol Gastrointest Liver Physiol. 2007; 292:718-724
40. Dykhuizen RD, Fraser A, McKenzie H, et al. Helicobacter pylori is killed by nitrite under acidic conditions. Gut. 1998; 42:334-337
41. Bjorne, H., Govoni, M., Tornberg, D. C. et al. Intragastric nitric oxide is abolished in intubated patients and restored by nitrite. Crit. Care Med. 2005; 33:1722–1727
42. Carlsson, S., Wiklund, N. P., Engstrand, L, et al. Effects of pH, nitrite, and ascorbic acid on nonenzymatic nitric oxide generation and bacterial growth in urine. Nitric Oxide. 2001; 5:580–586
43. Dykhuizen R, Frazer R, Duncan C, et al. Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defence. Antimicrob Agents Chemother. 1996; 40:1422–1425
44. Miyoshi, M, Kasahara E, Park AM, et al. Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat. Free Radic. Res. 2003; 37:85–90
45. Yarnell E. Natural approach to gastroenterology. WA. Healing Mountain Pub. 2011. Pp 1343.