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Natural strategies to support intestinal integrity
My neighbor’s fence is beyond beautiful, but serves little to no practical purpose. With its widely spaced slats, the fence affords any passerby an only slightly fettered view of the yard and its goings-on. A cat, rat, or even small dog could easily pass back and forth across the gorgeous “wall” at the edge of the property. As I notice my neighbor sunning himself on the back porch, I can’t help but wonder why he didn’t design the fence differently.
Like a good fence, the lining of the human digestive tract should keep intruders out. Unfortunately, however, some of us have gut linings like my neighbor’s fence, with big gaps that allow dangerous players to cross into precious territory. This state of digestive affairs is known as increased intestinal permeability, or, as it’s more commonly known, “leaky gut.”
Like a good fence, the lining of the human digestive tract should keep intruders out.
Between the widely spaced slats of the leaky gut, troublesome agents like bacteria, toxins, undigested food, and other waste products can pass from the digestive tract into the body. These invaders can then make their way to the bloodstream, where they trigger the types of immune reactions and inflammation implicated in conditions such as ulcerative colitis, Crohn’s disease, celiac disease, food allergies, irritable bowel syndrome (IBS), and even obesity and cardiovascular disease.[1],[2],[3] Leaky gut has also been implicated in autoimmune diseases and even autism spectrum disorders and other learning disabilities.[4],[5]
In the earlier post, Leaky Gut 101, we explore the causes of leaky gut and explain why it can be so harmful to one’s health, and in Leaky Gut = Fatty Liver we dig even deeper, specifically exploring how intestinal permeability can contribute to liver disease. In this post, we take a look at some of the natural therapies targeted at soothing the gut and improving intestinal integrity.
Here are some tried and true strategies for patching up a leaky gut:
Zinc carnosine
Many a patient has heard the (now outdated) recommendation of taking a baby aspirin daily to prevent heart disease. This therapy is no longer recommended because not only does an aspirin a day fail to prevent cardiovascular events in those without a previous history, but it is also associated with a higher incidence of stomach and small intestine ulcers, many of which require hospitalization.[6] For this reason, long-term users (three months or longer) of low-dose aspirin (LDA) can make fantastic subjects for clinical trials on various therapies to prevent and treat ulcers and bleeds of the digestive tract.
In one such trial, long-term users of LDA were observed in a pilot randomized controlled study investigating the efficacy of zinc carnosine in protecting the small intestine. After undergoing a baseline capsule endoscopy to assess small intestine integrity, the participants with LDA-induced small intestine injury were divided into two groups: the control group received no treatment, and the experimental group was given zinc carnosine at a dosage of 150 mg per day. After four weeks, both groups underwent capsule endoscopy again, at which time it was found that those in the zinc carnosine treatment group had significantly fewer reddened lesions, erosions, and ulcers than at baseline, whereas no change was noted in the control group.[7]
In other words, zinc carnosine enhanced the healing of the digestive tract and also reduced the risk of new lesions. The benefits of zinc carnosine have been shown to extend to other settings of gastrointestinal damage as well, such as alcohol use, stress, and exercise.[8],[9],[10]
Those in the zinc carnosine treatment group had significantly fewer reddened lesions, erosions, and ulcers than at baseline, whereas no change was noted in the control group.
The choice of zinc as the therapeutic intervention in such studies is not random: zinc is required for maintenance of the intestinal epithelial barrier – the layer of cells serving as the gut lining. Zinc is necessary for regulation of the proteins found in tight junctions, the structures in the gut wall that act like “nails” that secure the “pickets” of the fence.[11] In addition to protecting and healing the mucus membranes, zinc is also important for quenching the reactive oxygen species (ROS) that cause oxidative stress and inflammation in the gut.[12] Zinc complexed with carnosine may offer the additional benefit of the antioxidant effects of carnosine as well.[13]
Unsurprisingly, zinc deficiency has been shown to contribute to the progression of leaky gut,[14] and zinc supplementation has been used to treat not only leaky gut, but also gastric ulcers, gastritis, and other digestive disorders. Given that recent reports show that as high as 25% of the global population is at high risk of zinc deficiency, supplementation with this easy-to-find element may yield surprising benefits.[15],[16]
Aloe vera extract
Perhaps you’ve experienced the cooling, soothing effect of aloe vera while applying it to sunburned skin. Much like it supports the healing of the skin,[17] so too does this plant encourage the health of the gut, where it has anti-inflammatory effects.[18]
In addition to fighting inflammation, aloe vera may further help knit together a leaky gut (and heal gastrointestinal ulcers) by a number of different actions. By increasing mucus production, aloe vera helps ensure a protective coating remains on the digestive mucus membranes. It also has been shown to increase blood flow to these membranes and increase the phospholipid content of the mucus that coats them.[19] All of this translates into wound-healing and gut-healing effects.[20]
By increasing mucus production, aloe vera helps ensure a protective coating remains on the digestive mucus membranes.
Although it strengthens the barrier of the digestive tract, aloe vera extract has actually been shown to increase the absorption and bioavailability of vitamins C and E when co-administered with them.[21] Aloe vera thus restricts the absorption of toxicants, while increasing the absorption of nutrients.
N-acetyl glucosamine
Although digestive acids and enzymes are a normal part of the digestive process, they can nevertheless injure the gut lining upon exposed contact. A layer of mucus coating the digestive tract is thus key for protecting the sensitive lining of the gut. Like aloe vera, N-acetyl glucosamine (NAG) is a natural compound that supports healthy digestive mucus production.
NAG has also been shown to support the growth of bifidobacteria, a type of gut-protective bacteria that is often taken as a probiotic.
NAG is a naturally-occurring compound made in the body, often found in supplements for joint health. In addition to protecting the joints, however, glucosamine has been shown to reduce the inflammation caused by the inflammatory bowel diseases ulcerative colitis and Crohn’s disease.[22]
NAG has also been shown to support the growth of bifidobacteria, a type of gut-protective bacteria that is often taken as a probiotic.[23] It is perhaps for this reason that NAG has been shown to increase the efficacy of antibiotic therapy in eradicating Helicobacter pylori, the bacterium associated with stomach and small intestine ulcers.[24]
The above qualities of NAG may also explain why the compound has been shown to reduce food-sensitivity reactions. A study done in rats, for instance, demonstrates that NAG protects the intestines against the harmful effects of dietary gluten.[25]
Although most commercially-available NAG products are derived from shellfish, vegan formulations of this important compound are also available, offering those with plant-based diets or shellfish allergies a safe alternative.
Quercetin and rutin
Quercetin is a flavonoid found in many fruits and vegetables.[26] Shown to have antioxidant effects, quercetin is perhaps best known for its role in taming the histamine response seen in allergic conditions. If you’ve ever had an allergic reaction like hives, you’ve experienced the inflamed, itchy consequences of histamine release. The histamine response can also aggravate a leaky gut, irritating the digestive tract much like it does the skin.[27] Exposure to allergens can trigger the histamine-containing mast cells within the body to burst (or degranulate) and release histamine, causing symptoms of heat, redness, and pruritis (itchiness). Other things can cause a histamine response as well, like chronic stress and pro-inflammatory foods. By stabilizing mast cells, however, quercetin may prevent gut-damaging histamine reactions before they occur.[28]
Quercetin may also help prevent and manage leaky gut by fortifying the tight junctions that reinforce the integrity of the digestive tract.
Quercetin may also help prevent and manage leaky gut by fortifying the tight junctions that reinforce the integrity of the digestive tract.[29] Through this effect on tight junctions in the gut lining, quercetin has been shown to inhibit the intestine’s absorption of endotoxins, thus further protecting the body from infection, inflammation, and harm.[30]
When it’s combined with a sugar known as rutinose, quercetin forms a glycoside known as rutin. As with all flavonoids, rutin is a powerful antioxidant. It is perhaps best known for its effects on improving the integrity of blood vessels and enhancing circulation.[31] Rutin also has anti-inflammatory effects on the intestines.[32] Rutin has also been shown in rats to temper digestive inflammation and help maintain a healthy microbiome (optimal balance of good gut bacteria).[33]
Vitamin E
Vitamin E is an important nutrient with a myriad of benefits in all animal species, with immune function, heart health, and skin integrity at the top of the list. Although this essential and complex fat-soluble nutrient has many functions, vitamin E’s antioxidant function is perhaps its most important quality.
Understanding that oxidative stress plays a significant role in the aging of skin, it’s no surprise that vitamin E may help prevent ultraviolet (UV) skin damage.[34] Much like the epithelium found in the skin, the epithelium of the intestinal tract is highly sensitive to radiation. Because the cells lining the digestive tract are constantly regenerating, the gastrointestinal (GI) tract is in fact the second most radiosensitive critical organ system in the body.[35]
Vitamin E has been found to improve intestinal integrity and enhance the absorption of nutrients in mice exposed to radiation, in rats subjected to oxygen deprivation, and in humans undergoing radiation therapy to the pelvis.
Understanding this, researchers have explored the role of antioxidants like vitamin E in staving off radiation-induced injury to the digestive tract. Vitamin E has been found to improve intestinal integrity and enhance the absorption of nutrients in mice exposed to radiation, in rats subjected to oxygen deprivation, and in humans undergoing radiation therapy to the pelvis.[36], [37],[38] If vitamin E can protect the intestines radiation-associated injuries, the likelihood of it helping with other causes of GI distress is likely.
Conclusion
In addition to identifying and removing food intolerances or allergens, managing stress, balancing the microbiome, and implementing healthy lifestyle practices, the above natural therapies can help fortify the gut lining and take health to the next level. Soothing and supporting an inflamed gut entails much less heavy lifting than repairing a fence!
Check out Leaky Gut 101 to learn more about the causes of leaky gut, and read about some basic ways to prevent it from occurring.
Read Leaky Gut = Fatty Liver to understand how digestive integrity (or lack thereof) can wreck havoc on other vital organs.
Click here to see References
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[2] Teixeira TF, et al. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res. 2012 Sep;32(9):637-47.
[3] Bischoff SC, et al. Intestinal permeability-a new target for disease prevention and therapy. BMC Gastroenterol. 2014 Nov 18;14:189.
[4] Visser J, et al. Tight junctions, intestinal permeability, and autoimmunity. Ann NY Acad Sci 2009;1165:195-205.
[5] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.
[6] McNeil JJ, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018 Oct 18;379(16):1509-18.
[7] Watari I, et al. Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study. BMC Gastroenterol. 2013 Jul 4;13:108.
[8] Mahmood A, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb;56(2):168-75.
[9] Davison G, et al. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr. 2016 Aug;104(2):526-36.
[10] Seiki M, et al. [Studies on anti-ulcer effects of a new compound, zinc L-carnosine (Z-103)]. Nihon Yakurigaku Zasshi. 1990 May;95(5):257-69.
[11] Miyoshi Y, et al. Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression. Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G105-16.
[12] Palileo C, Kaunitz JD. Gastrointestinal defense mechanisms. Curr Opin Gastroenterol. 2011 Oct;27(6):543-8.
[13] Reddy VP, et al. Carnosine: a versatile antioxidant and antiglycating agent. Sci Aging Knowledge Environ. 2005 May 4;2005(18):pe12.
[14] Manary MJ, et al. Perturbed zinc homeostasis in rural 3-5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy. Pediatr Res. 2010 Jun;67(6):671-5.
[15] Mahmood A, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb;56(2):168-75.
[16] Higashimura Y, et al. [Zinc and gastrointestinal disorders]. Nihon Rinsho. 2016 Jul;74(7):1121-5.
[17] Choi S-W, et al. The wound healing effect of a glycoprotein fraction isolated from aloe vera. Br. J. Dermatol. 2001, 145, 535-45.
[18] Prabjone R, et al. Anti-inflammatory effects of Aloe vera on leukocyte-endothelium interaction in the gastric microcirculation of Helicobacter pylori-infected rats. Clin. Hemorheol. Microcirc. 2006;35:359-66.
[19] Yusuf S, et al. The effect of Aloe vera A. berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats. J. Ethnopharmacol. 2004;93:33-7.
[20] Suvitayavat W, et al. Effects of Aloe preparation on the histamine-induced gastric secretion in rats. J. Ethnopharmacol. 2004:90:239-247.
[21] Vinson JA, et al. Effect of Aloe vera preparations on the human bioavailability of vitamins C and E. Phytomedicine 2005, 12, 760-5.
[22] Bak YK, et al. Effects of dietary supplementation of glucosamine sulfate on intestinal inflammation in a mouse model of experimental colitis. J Gastroenterol Hepatol. 2014 May;29(5):957-63.
[23] Garrido D, et al. Release and utilization of N-acetyl-D-glucosamine from human milk oligosaccharides by Bifidobacterium longum subsp. infantis. Anaerobe. 2012 Aug;18(4):430-5.
[24] Konorev MR. [Use of the immunopotentiator N-acetyl-glucosamine-N-acetylmuramyl dipeptide during triple anti-Helicobacter pylori therapy]. Ter Arkh. 2012;84(12):66-70.
[25] Auricchio S, et al. Prevention by mannan and other sugars of in vitro damage of rat fetal small intestine induced by cereal prolamin peptides toxic for human celiac intestine. Pediatr Res. 1987 Dec;22(6):703-7.
[26] Govers C, et al. Review of the health effects of berries and their phytochemicals on the digestive and immune systems. Nutrition Revs. 2018;76:29-46.
[27] Santos J, et al. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut. 2001;48:630-6.
[28] Pearce FL, et al. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol. 1984 Jun;73(6):819-23.
[29] Suzuki T, Haraa H. Role of flavonoids in intestinal tight junction regulation. Jour Nutr Biochem. May 2011;22(5):401-8.
[30] Suzuki T, Hara H. Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr. 2009 May;139(5):965-74.
[31] Bhandary B, et al. The protective effect of rutin against ischemia/reperfusion-associated hemodynamic alteration through antioxidant activity. Arch Pharm Res. 2012 Jun;35(6):1091-7.
[32] Mascaraque C, et al. Rutin has intestinal antiinflammatory effects in the CD4+ CD62L+ T cell transfer model of colitis. Pharmacol Res. 2014 Dec;90:48-57.
[33] Guo X, et al. Rutin and its combination with inulin attenuate gut dysbiosis, the inflammatory status and endoplasmic reticulum stress in paneth cells of obese mice induced by high-fat diet. Front Microbiol. 2018 Nov 5;9:2651.
[34] Rinnerthaler M, et al. Oxidative stress in aging human skin. Biomolecules. 2015 Apr 21;5(2):545-89.
[35] Potten CS, et al. Characterization of radiation-induced apoptosis in the small intestine and its biological implications. Int J Radiat Biol. 1994;65:71-8.
[36] Roche M, et al. Marked changes in endogenous antioxidant expression precede vitamin A, C and E-protectable, radiation-induced reductions in small intestinal nutrient transport. Free Radic Biol Med. 2011 Jan 1;50(1):55-65.
[37][37] Xu C, et al. Effect of vitamin e supplementation on intestinal barrier function in rats exposed to high altitude hypoxia environment. Korean J Physiol Pharmacol. 2014;18(4):313-20.
[38] Kennedy M, et al. Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E and C. Am J Gastroenterol. 2001 Apr; 96(4):1080-4.
The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
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Dr. Erica Zelfand
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