No protective benefits of low dose acute L-glutamine supplementation on small intestinal permeability, epithelial injury and bacterial translocation biomarkers in response to subclinical exertional-heat stress: A randomized cross-over trial.

Exertional heat stress disrupts gastrointestinal permeability and, through subsequent bacterial translocation, can result in potentially fatal exertional heat stroke. Glutamine supplementation is a potential countermeasure although previously validated doses are not universally well tolerated. Ten males completed two 80-minute subclinical exertional heat stress tests (EHSTs) following either glutamine (0.3 g kg FFM-1) or placebo supplementation. Small intestinal permeability was assessed using the lactulose/rhamnose dual sugar absorption test and small intestinal epithelial injury using Intestinal Fatty-Acid Binding Protein (I-FABP). Bacterial translocation was assessed using the total 16S bacterial DNA and Bacteroides/total 16S DNA ratio. The glutamine bolus was well tolerated, with no participants reporting symptoms of gastrointestinal intolerance. Small intestinal permeability was not influenced by glutamine supplementation (p = 0.06) although a medium effect size favoring the placebo trial was observed (d = 0.73). Both small intestinal epithelial injury (p < 0.01) and Bacteroides/total 16S DNA (p = 0.04) increased following exertional heat stress, but were uninfluenced by glutamine supplementation. Low-dose acute oral glutamine supplementation does not protect gastrointestinal injury, permeability, or bacterial translocation in response to subclinical exertional heat stress.

A systematic review: Role of dietary supplements on markers of exercise-associated gut damage and permeability.

Nutrition strategies and supplements may have a role to play in diminishing exercise associated gastrointestinal cell damage and permeability. The aim of this systematic review was to determine the influence of dietary supplements on markers of exercise-induced gut endothelial cell damage and/or permeability. Five databases were searched through to February 2021. Studies were selected that evaluated indirect markers of gut endothelial cell damage and permeability in response to exercise with and without a specified supplement, including with and without water. Acute and chronic supplementation protocols were included. Twenty-seven studies were included. The studies investigated a wide range of supplements including bovine colostrum, glutamine, probiotics, supplemental carbohydrate and protein, nitrate or nitrate precursors and water across a variety of endurance exercise protocols. The majority of studies using bovine colostrum and glutamine demonstrated a reduction in selected markers of gut cell damage and permeability compared to placebo conditions. Carbohydrate intake before and during exercise and maintaining euhydration may partially mitigate gut damage and permeability but coincide with other performance nutrition strategies. Single strain probiotic strains showed some positive findings, but the results are likely strain, dosage and duration specific. Bovine colostrum, glutamine, carbohydrate supplementation and maintaining euhydration may reduce exercise-associated endothelial damage and improve gut permeability. In spite of a large heterogeneity across the selected studies, appropriate inclusion of different nutrition strategies could mitigate the initial phases of gastrointestinal cell disturbances in athletes associated with exercise. However, research is needed to clarify if this will contribute to improved athlete gastrointestinal and performance outcomes.

Acute L-glutamine supplementation does not improve gastrointestinal permeability, injury or microbial translocation in response to exhaustive high intensity exertional-heat stress.

Purpose: Exertional-heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), can result in potentially fatal exertional-heat stroke. Acute glutamine (GLN) supplementation is a potential nutritional countermeasure, although the practical value of current supplementation regimens is questionable.Method: Ten males completed two high-intensity exertional-heat stress tests (EHST) involving running in the heat (40°C and 40% relative humidity) at lactate threshold to volitional exhaustion. Participants ingested GLN (0.3 g kg FFM-1) or a non-calorific placebo (PLA) one hour prior to the EHST. Venous blood was drawn pre-, post- and one-hour post-EHST. GI permeability was assessed using a serum dual-sugar absorption test (DSAT) and small intestinal epithelial injury using plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using the Bacteroides/total 16S DNA ratio.Results: Volitional exhaustion occurred after 22:19 ± 2:22 (minutes: seconds) in both conditions, during which whole-body physiological responses and GI symptoms were not different (p > 0.05). GI permeability (serum DSAT) was greater following GLN (0.043 ± 0.020) than PLA (0.034 ± 0.019) (p = 0.02; d = 0.47), but small intestine epithelial injury (I-FABP) increased comparably (p = 0.22; ηp2 = 0.16) following the EHST in both trials (GLN Δ = 1.25 ± 0.63 ng ml-1; PLA Δ = 0.92 ± 0.44 ng ml-1). GI MT (Bacteroides/total 16S DNA ratio) was unchanged in either condition following the EHST (p = 0.43).Conclusion: Acute low-dose (0.3 g kg-1 fat free mass) GLN supplementation ingested one hour before high-intesity exertional-heat stress worsened GI permeability, but did not influence either small intestinal epithilial injury or microbial translocation.Abbreviations: ANOVA: Analysis of variance; CV: Coefficient of Variation; DSAT: Dual Sugar Absorption Test; EDTA: Ethylenediaminetetraacetic acid; EHST: Exertional Heat Stress Test; ELISA: Enzyme Linked Immunosorbent Assay; FFM: Fat Free Mass; GI: Gastrointestinal; GFR: Glomerular Filtration Rate; GLN: Glutamine; HPLC: High Performance Liquid Chromatography; HR: Heart Rate; I-FABP: Intestinal Fatty-Acid Binding Protein; ISAK: International Society for the Advancement of Anthropometric Kinanthropometry; L/R: Lactulose-to-Rhamnose; LT: Lactate Threshold; MT: Microbial Translocation; mVAS: Modified Visual Analogue Scale; PBS: Phosphate-Buffered Saline; PLA: Placebo; qPCR: Quantitative Polymerase Chain Reaction; RH: Relative Humidity; RPE: Rate of Perceived Exertion; SD: Standard Deviation; SEM: Sensor Electronics Module; Tcore: Core Body Temperature; Tbody: Mean Body Temperature; Tskin: Mean Skin Temperature; TS: Thermal Sensation; V̇O2max: Maximal Oxygen Uptake.Highlights The pathophysiology of exertional-heat stroke is widely hypothesised to be at least in part attributable to a systemic inflammatory response caused by the leak of gastrointestinal microbes into the circulating blood.Acute high-dose (0.9 g kg FFM-1) L-glutamine supplementation is widely promoted as a practical strategy to protect gastrointestinal barrier integrity during exertional-heat stress. However, previously validated doses are often poorly tolerated and cannot be recommended for widespread implementation.This study examined the efficacy of low-dose (0.30 g kg FFM-1; ∼20 grams) acute L-glutamine supplementation on small intestinal injury, permeability, and microbial translocation in response a high-intensity exertional-heat stress test to exhaustion (20-30 min). This type of exercise accounts for the majority of exertional-heat stroke cases in the military.Despite being universally well-tolerated across all participants, acute low-dose L-glutamine supplementation worsened gastrointestinal permeability, without influencing either small intestinal injury or microbial translocation. These findings do not support the application of low-dose L-glutamine supplementation to help prevent exertional-heat stroke.

The Use of Bovine Colostrum in Sport and Exercise.

There has been a great deal of interest in bovine colostrum within sports nutrition over the last 25 years. Studies have investigated the effects on body composition, physical performance, recovery, gut damage and permeability, immune function, and illness risk. This narrative review considers available evidence in each of these areas. Although some studies have shown protection against performance decrements caused by periods of intensified training, there is limited evidence for effects on body composition and physical performance. There is stronger evidence for benefit on gut permeability and damage markers and on immune function and illness risk, especially during periods of intensified training. The balance of available evidence for gut permeability and illness risk is positive, but further research is required to fully determine all mechanisms responsible for these effects. Early suggestions that supplementation with bovine colostrum products could increase systemic IGF-1 levels are not supported by the balance of available evidence examining a range of doses over both short- and long-term periods. Nevertheless, dose-response studies would be valuable for determining the minimum efficacious dose, although this is complicated by variability in bioactivity between products, making any dose-response findings applicable only to the specific products used in such studies.

Oral bovine colostrum supplementation does not increase circulating insulin-like growth factor-1 concentration in healthy adults: results from short- and long-term administration studies.

PURPOSE: Bovine colostrum is available in health food shops and as a sports food supplement and is rich in antibodies and growth factors including IGF-1. World Anti-Doping Agency advises athletes against taking colostrum for fear of causing increased plasma IGF-1. There are also concerns that colostrum may theoretically stimulate malignancy in organs which express IGF-1 receptors. We, therefore, determined changes in plasma IGF-1 levels in subjects taking colostrum or placebo for 1 day, 4 weeks, and 12 weeks. METHODS: Plasma IGF1 levels were determined in healthy males (n = 16) who ingested 40 g bovine colostrum or placebo along with undertaking moderate exercise for total period of 4.5 h. Two further studies followed changes in IGF1 using double-blind, parallel group, placebo-controlled, randomized trials of colostrum or placebo (N = 10 per arm, 20 g/day for 4 weeks and N = 25 colostrum, N = 29 placebo arm 20 g/day for 12 weeks). RESULTS: Baseline IGF1 levels 130 ± 36 ng/ml. 4.5 h protocol showed no effect of colostrum on plasma IGF1 (ANOVA, treatment group: p = 0.400, group × time: p = 0.498, time p = 0.602). Similarly, no effect of colostrum ingestion was seen following 4 week (ANOVA, group: p = 0.584, group × time interaction: p = 0.083, time p = 0.243) or 12 week (ANOVA, group: p = 0.400, group × time interaction: p = 0.498, time p = 0.602) protocol. CONCLUSIONS: Ingestion of standard recommended doses of colostrum does not increase IGF-1 levels in healthy adults, providing additional support for the safety profile of colostrum ingestion.

The effects of bovine colostrum supplementation on in vivo immunity following prolonged exercise: a randomised controlled trial.

BACKGROUND: Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction, but there is a lack of research with clinically relevant in vivo measures. AIM: To investigate the effects of COL supplementation on in vivo immunity following prolonged exercise using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS: In a double-blind design, 31 men were randomly assigned to COL (20 g/day) or placebo (PLA) for 58 days. Participants ran for 2 h at 60% maximal aerobic capacity on day 28 and received a primary DPCP exposure (sensitisation) 20 min after. On day 56, participants received a low-dose-series DPCP challenge to elicit recall of in vivo immune-specific memory (quantified by skinfold thickness 24 and 48 h later). Analysis of the dose-response curves allowed determination of the minimum dose required to elicit a positive response (i.e., sensitivity). RESULTS: There was no difference in summed skinfold thickness responses between COL and PLA at 24 h (p = 0.124) and 48 h (p = 0.405). However, sensitivity of in vivo immune responsiveness was greater with COL at 24 h (p < 0.001) and 48 h (p = 0.023) with doses ~ twofold greater required to elicit a positive response in PLA. CONCLUSIONS: COL blunts the prolonged exercise-induced decrease in clinically relevant in vivo immune responsiveness to a novel antigen, which may be a mechanism for reduced illness reports observed in the previous studies. These findings also suggest that CHS sensitivity is highly relevant to host defence.

The effect of bovine colostrum supplementation on intestinal injury and circulating intestinal bacterial DNA following exercise in the heat.

PURPOSE: Exercise-induced changes in intestinal permeability are exacerbated in the heat. The aim of this study was to determine the effect of 14 days of bovine colostrum (Col) supplementation on intestinal cell damage (plasma intestinal fatty acid-binding protein, I-FABP) and bacterial translocation (plasma bacterial DNA) following exercise in the heat. METHODS: In a double-blind, placebo-controlled, crossover design, 12 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac) consisting of 60 min treadmill running at 70% maximal aerobic capacity (30 °C, 60% relative humidity). Blood samples were collected pre-exercise (Pre-Ex), post-exercise (Post-Ex) and 1 h post-exercise (1 h Post-Ex) to determine plasma I-FABP concentration, and bacterial DNA (for an abundant gut species, Bacteroides). RESULTS: Two-way repeated measures ANOVA revealed an arm × time interaction for I-FABP (P = 0.005, with greater Post-Ex increase in Plac than Col, P = 0.01: Plac 407 ± 194% of Pre-Ex vs Col, 311 ± 134%) and 1 h Post-Ex (P = 0.036: Plac 265 ± 80% of Pre-Ex vs Col, 229 ± 56%). There was no interaction (P = 0.904) but there was a main effect of arm (P = 0.046) for plasma Bacteroides/total bacterial DNA, with lower overall levels evident in Col. CONCLUSION: This is the first investigation to demonstrate that Col can be effective at reducing intestinal injury following exercise in the heat, but exercise responses (temporal pattern) of bacterial DNA were not influenced by Col (although overall levels may be lower).

Short-Term High-Dose Vitamin C and E Supplementation Attenuates Muscle Damage and Inflammatory Responses to Repeated Taekwondo Competitions: A Randomized Placebo-Controlled Trial.

Background: Exercise-induced muscle damage during intensive sport events is a very common issue in sport medicine. Therefore, the purpose is to investigate the effects of short-term high-dose vitamin C and E supplementation on muscle damage, hemolysis, and inflammatory responses to simulated competitive Olympic Taekwondo (TKD) matches in elite athletes. Methods: Using a randomized placebo-controlled and double-blind study design, eighteen elite male TKD athletes were weight-matched and randomly assigned into either a vitamin C and E group (Vit C+E; N = 9) or placebo group (PLA; N = 9). Vit C+E or PLA supplements were taken daily (Vit C+E: 2000 mg/d vitamin C; 1400 U/d vitamin E) for 4 days (3 days before and on competition day) before taking part in 4 consecutive TKD matches on a single day. Plasma samples were obtained before each match and 24-hours after the first match for determination of markers of muscle damage, hemolysis, and systemic inflammatory state. Results: Myoglobin was lower in the Vit C+E group, compared to PLA, during the match day (area under curve, AUC -47.0% vs. PLA, p = 0.021). Plasma creatine kinase was lower in the Vit C+E group (AUC -57.5% vs. PLA, p = 0.017) and hemolysis was lower in the Vit C+E group (AUC -40.5% vs. PLA, p = 0.034). Conclusions: We demonstrated that short-term (4-days) vitamin C and E supplementation effectively attenuated exercise-induced tissue damage and inflammatory response during and after successive TKD matches.

Intestinal fatty acid-binding protein and gut permeability responses to exercise.

PURPOSE: Intestinal 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). METHODS: In 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. RESULTS: Two-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. CONCLUSION: These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.

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°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. 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. This trial was registered at www.isrctn.com as ISRCTN51159138.

Carbohydrate supplementation does not blunt the prolonged exercise-induced reduction of in vivo immunity.

BACKGROUND: Carbohydrate (CHO) supplementation during prolonged exercise is widely acknowledged to blunt in vitro immunoendocrine responses, but no study has investigated in vivo immunity. PURPOSE: To determine the effect of CHO supplementation during prolonged exercise on in vivo immune induction using experimental contact hypersensitivity with the novel antigen diphenylcyclopropenone (DPCP). METHODS: In a double-blind design, 32 subjects were randomly assigned to 120 min of treadmill exercise at 60 % [Formula: see text] with CHO (Ex-CHO) or placebo (Ex-PLA) supplementation. Responses were also compared to 16 resting control (CON) subjects from a previous study (for additional comparison with a resting non-exercise condition). Standardised diets (24 h pre-trial) and breakfasts (3.5 h pre-trial) were provided. Subjects received a primary DPCP exposure (sensitisation) 20 min after trial completion, and exactly 28 days later the strength of immune reactivity was quantified by magnitude of the cutaneous response (skin-fold thickness and erythema) to a low dose-series DPCP challenge. Stress hormones and leucocyte trafficking were also monitored. RESULTS: CHO supplementation blunted the cortisol and leucocyte trafficking responses, but there was no difference (P > 0.05) between Ex-CHO and Ex-PLA in the in vivo immune responses (e.g. both ~46 % lower than CON for skin-fold response). CONCLUSIONS: CHO supplementation does not influence the decrease in in vivo immunity seen after prolonged exercise. The effects with more stressful (or fasted) exercise remain to be determined. However, there appears to be no benefit under the conditions of the present study, which have practical relevance to what many athletes do in training or competition.

Nutritional and Physical Activity Interventions to Improve Immunity.

Physical activity and nutrition are important in a healthy lifestyle with potential benefits to immunity often overlooked. Infection of the upper respiratory tract, and the associated symptoms, are the most frequent presentations to general practitioners and may have significant economic and social impact. In this review, we consider the role of physical activity and nutrition in improving immunity. Evidence suggests that regular moderate activity is particularly beneficial for immune enhancement and reducing the risk of infection. We also discuss some nutritional strategies. Unfortunately, the evidence for many is weak. Avoiding nutritional deficiencies seems the most pragmatic recommendation. This can be achieved with a balanced diet. Including a variety of fruits and vegetables may help ensure adequate intake of essential nutrients with little risk of excess intake of any single nutrient. Supplementation with individual nutrients is generally not recommended. Multinutrients may be beneficial for those with a preexisting deficiency but not if normal dietary intake is sufficient. Further benefit may be gained from some supplements including probiotics, bovine colostrum, and some plant-derived products (Echinacea, black elderberry, and some polyphenols) but only in specific situations/contexts. Individuals should consider their personal needs, use caution, and avoid the indiscriminate use of supplements.

Failure of oral tyrosine supplementation to improve exercise performance in the heat.

PURPOSE: Acute oral tyrosine administration has been associated with increased constant-load, submaximal exercise capacity in the heat. This study sought to determine whether self-paced exercise performance in the heat is enhanced with the same tyrosine dosage. METHODS: After familiarization, seven male endurance-trained volunteers, unacclimated to exercise in the heat, performed two experimental trials in 30°C (60% relative humidity) in a crossover fashion separated by at least 7 d. Subjects ingested 150 mg·kg(-1) body mass tyrosine (TYR) or an isocaloric quantity of whey powder (PLA) in 500 mL of sugar-free flavored water in a randomized, double-blind fashion. Sixty minutes after drink ingestion, the subjects cycled for 60 min at 57% ± 4% peak oxygen uptake (VO2peak) and then performed a simulated cycling time trial requiring completion of an individualized target work quantity (393.1 ± 39.8 kJ). RESULTS: The ratio of plasma tyrosine plus phenylalanine (tyrosine precursor) to amino acids competing for brain uptake (free-tryptophan, leucine, isoleucine, valine, methionine, threonine, and lysine) increased 2.5-fold from rest in TYR and remained elevated throughout exercise (P < 0.001), whereas it declined in PLA from rest to preexercise (P = 0.004). Time-trial power output (P = 0.869) and performance (34.8 ± 6.5 and 35.2 ± 8.3 min in TYR and PLA, respectively; P = 0.4167) were similar between trials. Thermal sensation (P > 0.05), RPE (P > 0.05), core temperature (P = 0.860), skin temperature (P = 0.822), and heart rate (P = 0.314) did not differ between trials. CONCLUSIONS: These data indicate that acute tyrosine administration did not influence self-paced endurance exercise performance in the heat. Plasma tyrosine availability is apparently not a key determinant of fatigue processes under these conditions.

Effects of bovine colostrum supplementation on upper respiratory illness in active males.

Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction and increased risk of upper respiratory illness (URI) in athletic populations, however, the mechanisms remain unclear. During winter months, under double-blind procedures, 53 males (mean training load±SD, 50.5±28.9 MET-hweek(-1)) were randomized to daily supplementation of 20g of COL (N=25) or an isoenergetic/isomacronutrient placebo (PLA) (N=28) for 12weeks. Venous blood was collected at baseline and at 12weeks and unstimulated saliva samples at 4 weeks intervals. There was a significantly lower proportion of URI days and number of URI episodes with COL compared to PLA over the 12weeks (p<0.05). There was no effect of COL on in vitro neutrophil oxidative burst, salivary secretory IgA or salivary antimicrobial peptides (p>0.05), which does not support previously suggested mechanisms. In a subset of participants (COL=14, PLA=17), real-time quantitative PCR, targeting the 16S rRNA gene showed there was an increase in salivary bacterial load over the 12 weeks period with PLA (p<0.05) which was not as evident with COL. Discriminant function analysis of outputs received from serum metabolomics showed changes across time but not between groups. This is the first study to demonstrate that COL limits the increased salivary bacterial load in physically active males during the winter months which may provide a novel mechanism of immune-modulation with COL and a relevant marker of in vivo (innate) immunity and risk of URI.

Bovine colostrum and immune function after exercise.

Strenuous and/or prolonged exercise causes transient perturbations in immune function. It is well accepted that this is one mechanism contributing to the higher occurrence of infection (e.g. upper respiratory tract infection (URTI)) in athletes, especially endurance athletes. URTI or upper respiratory tract (URT) symptoms can negatively affect training and competition performance but athletes must train intensively to be successful. Therefore, interventions that can legitimately enhance immune function and reduce URTI risk can be of benefit to athletes. Bovine colostrum supplementation has been investigated as a possible nutritional countermeasure to enhance (or maintain) immune function, and reduce URTI risk, following strenuous or prolonged exercise and during intensive training periods. There is convincing evidence that daily supplementation with bovine colostrum, for a number of weeks (and preliminary evidence for acute effects after a single dose), can maintain intestinal barrier integrity, immune function and reduce the chances of suffering URTI or URT symptoms in athletes or those undertaking heavy training. The mechanisms are not fully understood at present but there is preliminary evidence suggesting that the effects on immune function are attributable, at least in part, to small bioactive components that survive digestion and are biologically available after consumption, but further work is required. In summary, the balance of existing evidence does support the notion that bovine colostrum is beneficial for certain groups of athletes, such as those involved in strenuous training (e.g. endurance athletes), in terms of immunity and resistance to infection.

Oral tyrosine supplementation improves exercise capacity in the heat.

Increased brain dopamine availability improves prolonged exercise tolerance in the heat. It is unclear whether supplementing the amino-acid precursor of dopamine increases exercise capacity in the heat. Eight healthy male volunteers [mean age 32 ± 11 (SD) years; body mass 75.3 ± 8.1 kg; peak oxygen uptake ([Formula: see text]) 3.5 ± 0.3 L min(-1)] performed two exercise trials separated by at least 7 days in a randomised, crossover design. Subjects consumed 500 mL of a flavoured sugar-free drink (PLA), or the same drink with 150 mg kg body mass(-1) tyrosine (TYR) in a double-blind manner 1 h before cycling to exhaustion at a constant exercise intensity equivalent to 68 ± 5% [Formula: see text] in 30°C and 60% relative humidity. Pre-exercise plasma tyrosine:large neutral amino acids increased 2.9-fold in TYR (P < 0.01), while there was no change in PLA (P > 0.05). Subjects cycled longer in TYR compared to PLA (80.3 ± 19.7 min vs. 69.2 ± 14.0 min; P < 0.01). Core temperature, mean weighted skin temperature, heart rate, ratings of perceived exertion and thermal sensation were similar in TYR and PLA during exercise and at exhaustion (P > 0.05) despite longer exercise time in TYR. The results show that acute tyrosine supplementation is associated with increased endurance capacity in the heat in moderately trained subjects. The results also suggest for the first time that the availability of tyrosine, a nutritional dopamine precursor, can influence the ability to subjectively tolerate prolonged submaximal constant-load exercise in the heat.

The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes.

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, Baxα, 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 = 0.026). Intestinal permeability in the placebo arm increased 2.5-fold following exercise (0.38 ± 0.012 baseline, to 0.92 ± 0.014, P < 0.01), whereas colostrum truncated rise by 80% (0.38 ± 0.012 baseline to 0.49 ± 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 < 0.01). Similar results were obtained examining epithelial resistance (colostrum truncated temperature-induced fall in resistance by 64%, P < 0.01). Colostrum increased HSP70 expression at both 37 and 39°C (P < 0.001) and was truncated by addition of an EGF receptor-neutralizing antibody. Temperature-induced increase in Baxα and reduction in Bcl-2 was partially reversed by presence of colostrum. Colostrum may have value in enhancing athletic performance and preventing heat stroke.

Bovine colostrum supplementation attenuates the decrease of salivary lysozyme and enhances the recovery of neutrophil function after prolonged exercise.

Oral supplementation with bovine colostrum (COL) has been shown to enhance immunity in human subjects. However, there is limited research on the use of bovine COL supplementation to counter exercise-induced immunodepression, as a model of stress-induced immunodepression, and previous research has focused primarily on salivary IgA. The aim of the present study was to determine the effects of bovine COL supplementation on exercise-induced changes in innate immunity (neutrophil function and salivary lysozyme) in addition to salivary IgA. Twenty healthy, active men cycled for 2 h at approximately 64 % maximal oxygen uptake after 4 weeks of daily bovine COL (n 10) or placebo (PLA, n 10) supplementation. Blood and saliva samples were obtained before and after supplementation, before and after exercise. Exercise induced significant increases in markers of physiological stress and stress to the immune system (circulating neutrophils, neutrophil:lymphocyte ratio, immature granulocytes, atypical lymphocytes and plasma cortisol), but there were no differences between the COL and PLA groups. Significant group x time interactions (two-way mixed model ANOVA) were observed for neutrophil function (stimulated degranulation) and salivary lysozyme concentration and release (P < 0.05). Significant exercise-induced decreases were observed in these parameters, and bovine COL supplementation either speeded the recovery (neutrophil function) or prevented the decrease (salivary lysozyme) in these measures of innate immunity. These results suggest that 4 weeks of bovine COL supplementation limits the immunodepressive effects induced by an acute prolonged physical stressor, such as exercise, which may confer some benefits to host defence.

Antioxidant supplementation and immunoendocrine responses to prolonged exercise.

PURPOSE: Antioxidant supplementation may modulate systemic cortisol and interleukin-6 (IL-6) responses to prolonged exercise, but it is unclear whether such effects are also associated with a reduction in the magnitude of immunodepression. The purpose of the present study was to examine the effects of daily vitamin C (L-ascorbic acid, 1000 mg x d(-1)) and vitamin E (RRR-alpha-tocopherol, 400 IU x d(-1)) supplementation on immunoendocrine responses to prolonged exercise. METHODS: Twenty healthy, recreationally active males cycled for 2.5 h at approximately 60% of maximal oxygen uptake after 4 wk of placebo (PLA, N=10) or antioxidant (AO, N=10) supplementation. RESULTS: A significant group x time interaction was observed for plasma cortisol concentration (P=0.008), and the postexercise increase was greater (P<0.05) in the PLA compared with AO group (approximately 170% compared with an approximately 120% increase above baseline). Plasma IL-6 concentration was significantly increased after exercise to a similar extent in both groups. Plasma free F2-isoprostane concentration was significantly increased after exercise and was unaffected by AO supplementation, whereas plasma TBARS was unaffected by exercise in the PLA group but was lower after exercise in the AO group than in the PLA group. Circulating neutrophil count was significantly increased after exercise, and in vitro bacteria-stimulated elastase release per neutrophil was significantly decreased to a similar extent in both groups. CONCLUSIONS: These results suggest that 4 wk of AO supplementation may blunt the cortisol response to a single 2.5-h bout of prolonged exercise independently of changes in oxidative stress or plasma IL-6 concentration, but it is not effective at modulating the exercise-induced neutrophilia or depression of neutrophil function.

The effect of 2 weeks vitamin C supplementation on immunoendocrine responses to 2.5 h cycling exercise in man.

An increased systemic concentration of stress hormones (of the hypothalamic-pituitary adrenal axis) and some cytokines may contribute to the depression of immune cell function typically observed after prolonged exercise. The aim of the present study was to determine the effect of 2 weeks of supplementation with vitamin C (VC) on cortisol, adrenocorticotrophic hormone, interleukin-6, oxidative stress and neutrophil responses to a single bout of endurance exercise. Nine healthy endurance-trained males exercised for 2.5 h at 60% VO2max after 2 weeks of placebo (PLA) or VC (1,000 mg day(-1)) supplementation. All participants completed both trials utilising a randomised crossover design with a minimum 14 day washout period between trials. There was a significant trial x time interaction effect for plasma cortisol concentration (P = 0.039) which tended to be lower in the VC trial but post hoc analysis found no specific between trial differences. There was a significantly lower post-exercise neutrophilia (P < 0.014) in the VC trial, compared with the PLA trial. There was no trial x time interaction for measures of neutrophil function (bacteria-stimulated elastase release, fMLP or PMA-stimulated oxidative burst). However, there was a trend for higher fMLP-stimulated neutrophil oxidative burst in the VC compared with PLA trial (trial x time interaction, P = 0.075). These results suggest that supplementation with VC for a period of up to 2 weeks provides little to no protection against the depression of neutrophil function which typically occurs after endurance exercise.