Heavy exercise causes gut symptoms and, in extreme cases, "heat stroke" partially due to increased intestinal permeability of luminal toxins. We examined bovine colostrum, a natural source of growth factors, as a potential moderator of such effects. Twelve volunteers completed a double-blind, placebo-controlled, crossover protocol (14 days colostrum/placebo) prior to standardized exercise. Gut permeability utilized 5 h urinary lactulose-to-rhamnose ratios. In vitro studies (T84, HT29, NCM460 human colon cell lines) examined colostrum effects on temperature-induced apoptosis (active caspase-3 and 9, Bax␣, Bcl-2), heat shock protein 70 (HSP70) expression and epithelial electrical resistance. In both study arms, exercise increased blood lactate, heart rate, core temperature (mean 1.4°C rise) by similar amounts. Gut hormone profiles were similar in both arms although GLP-1 levels rose following exercise in the placebo but not the colostrum arm (P ϭ 0.026). Intestinal permeability in the placebo arm increased 2.5-fold following exercise (0.38 Ϯ 0.012 baseline, to 0.92 Ϯ 0.014, P Ͻ 0.01), whereas colostrum truncated rise by 80% (0.38 Ϯ 0.012 baseline to 0.49 Ϯ 0.017) following exercise. In vitro apoptosis increased by 47-65% in response to increasing temperature by 2°C. This effect was truncated by 60% if colostrum was present (all P Ͻ 0.01). Similar results were obtained examining epithelial resistance (colostrum truncated temperature-induced fall in resistance by 64%, P Ͻ 0.01). Colostrum increased HSP70 expression at both 37 and 39°C (P Ͻ 0.001) and was truncated by addition of an EGF receptor-neutralizing antibody. Temperature-induced increase in Bax␣ and reduction in Bcl-2 was partially reversed by presence of colostrum. Colostrum may have value in enhancing athletic performance and preventing heat stroke.repair; gut growth; injury; clinical trial SEVERAL STRESSES AFFECT the integrity of the intestinal barrier. These include prolonged strenuous exercise (10), heat stress (11), and drugs such as nonsteroidal anti-inflammatory agents. Loss of intestinal barrier integrity leading to increased intestinal permeability may result in passage of luminal endotoxins into the circulation. This, in turn, results in an inflammatory cascade, exacerbating the loss of barrier function and, in severe cases, resulting in severe systemic effects.Severe cases of decompensation can result in the lifethreatening condition of exertional heat stroke, associated with hyperthermia, multiorgan failure, and endotoxemia. In addition, it is increasingly recognized that similar processes have relevance for many athletes involved in heavy exercise such as long-distance running. Gastrointestinal symptoms including cramps, diarrhea, nausea, and bleeding are commonly reported by long-distance runners (16). These symptoms are likely to be due to a combination of reduced splanchnic blood flow, hormonal changes, altered gut permeability, and increased body temperature.Pharmacological options to reduce these problems are limited, particularly in compe...

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.

This narrative review examines literature pertaining to possible physiological explanations for observed cognitive benefits stemming from improvements to cardiovascular fitness following chronic aerobic exercise. Studies regarding exercise and cardiovascular fitness, angiogenesis, neuroinflammation in relation to IGF-1 signalling, regulation of neurotrophins, neurogenesis and plasticity, cognitive training, are briefly described. We propose that current evidence points towards a mechanism by which cardiovascular fitness improvements act to promote long-term angiogenesis and cerebral circulation. This important adaptation allows for increased delivery and upregulation of neurotrophins along with supporting factors to the brain, particularly to the hippocampal neurogenic niche, following acute exercise bouts. We propose a sequential timeline and approximate time scale for this mechanism, describing how these stages generate increased support for neurogenesis and brain plasticity in combination with cognitive training to provide long-term cognitive benefits and protection against age-related cognitive decline. Influences from age, gender and other variables are considered, and methodological factors that could be utilised in future studies to further clarify the proposed model are discussed.

23Bovine colostrum (COL) has been advocated as a nutritional countermeasure to 24 exercise-induced immune dysfunction and increased risk of upper respiratory illness 25 (URI) in athletic populations, however, the mechanisms remain unclear. During winter 26 months, under double-blind procedures, 53 males (mean training load ± SD, 50.5 ± 27 28.9 MET-hweek -1 ) were randomized to daily supplementation of 20 g of COL (N = 28 25) or an isoenergetic/isomacronutrient placebo (PLA) (N = 28) for 12 weeks. Venous 29 blood was collected at baseline and at 12 weeks and unstimulated saliva samples at 30 4-week intervals. There was a significantly lower proportion of URI days and number 31 of URI episodes with COL compared to PLA over the 12 weeks (p < 0.05). There was 32

PurposeIntestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R).MethodsIn a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration.ResultsTwo-way repeated measures ANOVA revealed an arm × time interaction for L/R and I-FABP (P < 0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P < 0.001) and Col (148% of pre, P < 0.001) with post-exercise values significantly lower with Col (P < 0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P = 0.002) but not in the Col arm (107%, P = 0.862) with post-exercise values significantly lower with Col (P = 0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P = 0.044) but not visit two (P = 0.200) although overall plots/patterns do appear similar for each.ConclusionThese findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.