Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers

Background: Heavy exercise causes gut symptoms and, in extreme cases, heat stroke that is due to the increased intestinal permeability of luminal toxins. Objective: We examined whether zinc carnosine (ZnC), a health-food product taken alone or in combination with bovine colostrum (a natural source of growth factors), would moderate such effects. Design: Eight volunteers completed a 4-arm, double-blind, placebo-controlled crossover protocol (14 d of placebo, ZnC, colostrum, or ZnC plus colostrum) before undertaking standardized exercise 2 and 14 d after the start of treatment. Changes in epithelial resistance, apoptosis signaling molecules, and tight junction (TJ) protein phosphorylation in response to a 2 degrees C rise in body temperature were determined with the use of Caco-2 and HT29 intestinal cells. Results: Body temperature increased 2 degrees C, and gut permeability (5-h urinary lactulose: rhamnose ratios) increased 3-fold after exercise (from 0.32 +/- 0.016 baseline to 1.0 +/- 0.017 at 14 d; P < 0.01). ZnC or colostrum truncated the rise by 70% after 14 d of treatment. The combination treatment gave an additional benefit, and truncated exercise induced increase at 2 d (30% reduction; P < 0.01). A 2 degrees C temperature rise in in vitro studies caused the doubling of apoptosis and reduced epithelial resistance 3-4-fold. ZnC or colostrum truncated these effects (35-50%) with the greatest response seen with the combination treatment (all P < 0.01). Mechanisms of action included increasing heat shock protein 70 and truncating temperature-induced changes in B cell leukemia/lymphoma-2 associated X protein alpha and B cell lymphoma 2. ZnC also increased total occludin and reduced phosphorylated tyrosine claudin, phosphorylated tyrosine occludin, and phosphorylated serine occludin, thereby enhancing the TJ formation and stabilization. Conclusion: ZnC, taken alone or with colostrum, increased epithelial resistance and the TJ structure and may have value for athletes and in the prevention of heat stroke in military personnel.