title: Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers.
abstract: 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.
  
  
  METHODS
  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°C rise in body temperature were determined with the use of Caco-2 and HT29 intestinal cells.
  
  
  RESULTS
  Body temperature increased 2°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°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 α 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.
  
  
  CONCLUSIONS
  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. This trial was registered at www.isrctn.com as ISRCTN51159138.
authors.affiliation: Endurance Research Group, School of Sport and Exercise Sciences, University of Kent, Kent, United Kingdom;
authors.forename: Glen
authors.identifier: http://orcid.org/0000-0003-4340-0074
authors.initials: G
authors.lastname: Davison
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom; Centre for Immunobiology, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine, Queen Mary, University of London, London, United Kingdom;
authors.forename: Tania
authors.identifier: http://orcid.org/0000-0003-2076-9098
authors.initials: T
authors.lastname: Marchbank
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; and.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: March
authors.affiliation: Institute of Biological Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, United Kingdom.
authors.forename: Rhys
authors.identifier: http://orcid.org/0000-0001-9971-5898
authors.initials: R
authors.lastname: Thatcher
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom; raymond.playford@plymouth.ac.uk.
authors.forename: Raymond J
authors.identifier: http://orcid.org/0000-0003-1235-8504
authors.initials: RJ
authors.lastname: Playford
mesh_terms: D000328:Adult; D000818:Animals; D018938:Caco-2 Cells; D002336:Carnosine / Q000494:pharmacology*; D002417:Cattle; D003126:Colostrum; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D019073:HT29 Cells; D064368:Healthy Volunteers; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010539:Permeability; D055815:Young Adult; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002336:Carnosine; D015032:Zinc
keywords: clinical trial; gut growth; injury; nutriceutical; repair