Nutritional Protocol for the Treatment of Intestinal Permeability Defects and Related Conditions

Under healthy conditions, the intestinal mucosa permits the absorption of vital nutrients from the gut lumen while presenting a barrier against the passage of pathogenic substances into the body. Leaky gut syndrome describes a pathological increase in permeability of the intestinal mucosa that causes increased absorption of intestinally derived endotoxin, antigens, inflammatory mediators, and, in some cases, intact bacteria. These agents can cause local and systemic reactions associated with a broad range of acute and chronic diseases. In some cases, atrophic changes in the mucosal epithelium can lead to the seemingly paradoxical condition of decreased permeability and malabsorption of essential nutrients concurrent with increased permeability and absorption of pathogenic macromolecules. Research indicates that certain nutritional factors may help to support mucosal health and promote normal intestinal permeability (IP). These factors include antioxidants, mucosal nutrients, digestive enzymes, probiotics, and dietary fiber. Some of these nutrients have also been shown to lead to improvement in diseases associated with leaky gut syndrome. This article outlines evidence of efficacy for a number of these agents. It also includes recommendations for a nutritional protocol to treat IP defects. A number of the recommendations in this article are based on double-blind, placebo-controlled clinical studies that show statistically significant benefit for certain dietary supplements in the treatment of IP defects and related conditions. In most cases, however, the recommendations are based on indirect evidence of efficacy from in vitro human studies or animal research. The nutritional protocol, nutrient forms and dosages presented are the author’s recommendations and have not been studied in controlled clinical trials. Introduction The human gut contains enough endotoxin, inflammatory mediators, and bacteria to kill the host many times over.1 A healthy functioning intestinal mucosa is the body’s primary line of defense against these potentially lethal agents. Catastrophic failure of the gut mucosal barrier has been identified as the main cause of multiple organ failure, the leading cause of death seen in surgical intensive care units with a mortality rate of approximately 70% .2 In critically ill individuals, toxins escaping from the gut lumen activate a local inflammatory response, which leads to further intestinal inflammation, tissue destruction, and production of cytokines and inflammatory mediators. Mucosal damage also causes increased IP with further release of inflammatory mediators and translocation of gut bacteria.3 Intestinally derived inflammatory mediators lead to a systemic inflammatory and autoimmune response. Circulating inflammatory mediators lead to further increases in gut permeability and the release of gut-derived mediators in a vicious cycle that can culminate in multiple organ failure and death. In addition to surgical emergencies, multiple organ failure can also be seen in response to trauma, burn injuries, sepsis, pancreatitis, and shock.4 Leaky gut syndrome represents a less severe example of pathologically increased IP that can often be seen in clinical practice. The resulting leakage of luminal toxins and inflammatory mediators is associated with a number of chronic inflammatory, autoimmune, and functional disorders. (See Table 1.) TABLE 1 Conditions Caused By Or Seen In Connection With Intestinal Permeability Defects Multiple organ failure5,6 Chronic fatigue syndrome7,8,9,10 Ulcerative colitis11,12 Crohn’s disease 13,14,15,16,17 Celiac disease18,19 Diarrhea-predominant irritable bowel syndrome20 Inflammatory joint disease 21,22,23,24 Ankylosing spondylitis25,26,27,28 Juvenile onset arthritis29 Psoriatic arthritis30 Food allergy31,32,33,34 Atopic dermatitis, eczema35 Chronic heart failure36,37 Psychological conditions38,39 HIV/AIDS40,41 Chemotherapy42,43 Pelvic radiotherapy44,45 TREATMENT PROTOCOL