Impacts of age, type 2 diabetes, and hypertension on circulating neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after prolonged work in the heat in men.

PURPOSE: Prolonged work in the heat increases the risk of acute kidney injury (AKI) in young men. Whether aging and age-associated chronic disease may exacerbate the risk of AKI remains unclear. METHODS: We evaluated plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum kidney injury molecule-1 (KIM1) before and after 180 min of moderate-intensity work (200 W/m2) in temperate (wet-bulb globe temperature [WBGT] 16 °C) and hot (32 °C) environments in healthy young (n = 13, 22 years) and older men (n = 12, 59 years), and older men with type 2 diabetes (T2D; n = 9, 60 years) or hypertension (HTN; n = 9, 60 years). RESULTS: There were no changes in NGAL or KIM1 concentrations following prolonged work in temperate conditions in any group. Despite a similar work tolerance, the relative change in NGAL was greater in the older group when compared to the young group following exercise in the hot condition (mean difference + 82 ng/mL; p < 0.001). Baseline concentrations of KIM1 were ~ 22 pg/mL higher in the older relative to young group, increasing by ~ 10 pg/mL in each group after exercise in the heat (both p ≤ 0.03). Despite a reduced work tolerance in the heat in older men with T2D (120 ± 40 min) and HTN (108 ± 42 min), elevations in NGAL and KIM1 were similar to their healthy counterparts. CONCLUSION: Age may be associated with greater renal stress following prolonged work in the heat. The similar biomarker responses in T2D and HTN compared to healthy older men, alongside reduced exercise tolerance in the heat, suggest these individuals may exhibit greater vulnerability to heat-induced AKI if work is prolonged.

New Zealand blackcurrant extract modulates the heat shock response in men during exercise in hot ambient conditions.

PURPOSE: To determine if 7d of New Zealand blackcurrant (NZBC) extract alters the heat shock, inflammatory and apoptotic response during prolonged exertional-heat stress. METHODS: Ten men (Age: 29 ± 2 years, Stature: 1.82 ± 0.02 m, Mass: 80.3 ± 2.7 kg, V̇O2max: 56 ± 2 mL·kg-1·min-1) ingested two capsules of CurraNZ™ (NZBC extract: 210 mg anthocyanins·day-1) or PLACEBO for 7d prior to 1 h treadmill run (65% V̇O2max) in hot ambient conditions (34 °C/40% RH). Blood samples were collected before (Pre), immediately after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise. Heat shock proteins (HSP90, HSP70, HSP32) were measured in plasma. HSP and protein markers of inflammatory capacity (TLR4, NF-κB) and apoptosis (BAX/BCL-2, Caspase 9) were measured in peripheral blood mononuclear cells (PBMC). RESULTS: eHSP32 was elevated at baseline in NZBC(+ 31%; p < 0.001). In PLACEBO HSP32 content in PBMC was elevated at 4-Post(+ 98%; p = 0.002), whereas in NZBC it fell at Post(- 45%; p = 0.030) and 1-Post(- 48%; p = 0.026). eHSP70 was increased at Post in PLACEBO(+ 55.6%, p = 0.001) and NZBC (+ 50.7%, p = 0.010). eHSP90 was increased at Post(+ 77.9%, p < 0.001) and 1-Post(+ 73.2%, p < 0.001) in PLACEBO, with similar increases being shown in NZBC (+ 49.0%, p = 0.006 and + 66.2%, p = 0.001; respectively). TLR4 and NF-κB were both elevated in NZBC at PRE(+ 54%, p = 0.003 and + 57%, p = 0.004; respectively). Main effects of study condition were also shown for BAX/BCL-2(p = 0.025) and Caspase 9 (p = 0.043); both were higher in NZBC. CONCLUSION: 7d of NZBC extract supplementation increased eHSP32 and PBMC HSP32 content. It also increased inflammatory and apoptotic markers in PBMC, suggesting that NZBC supports the putative inflammatory response that accompanies exertional-heat stress.

AAV gene therapy in companion dogs with severe hemophilia: Real-world long-term data on immunogenicity, efficacy, and quality of life.

The hemophilias are the most common severe inherited bleeding disorders and are caused by deficiency of clotting factor (F) VIII (hemophilia A) or FIX (hemophilia B). The resultant bleeding predisposition significantly increases morbidity and mortality. The ability to improve the bleeding phenotype with modest increases in clotting factor levels has enabled the development and regulatory approval of adeno-associated viral (AAV) vector gene therapies for people with hemophilia A and B. The canine hemophilia model has proven to be one of the best predictors of therapeutic response in humans. Here, we report long-term follow-up of 12 companion dogs with severe hemophilia that were treated in a real-world setting with AAV gene therapy. Despite more baseline bleeding than in research dogs, companion dogs demonstrated a 94% decrease in bleeding rates and 61% improvement in quality of life over a median of 4.1 years (range 2.6-8.9). No new anti-transgene immune responses were detected; one dog with a pre-existing anti-FVIII inhibitor achieved immune tolerance with gene therapy. Two dogs expressing 1%-5% FVIII post gene therapy experienced fatal bleeding events. These data suggest AAV liver-directed gene therapy is efficacious in a real-world setting but should target expression >5% and closely monitor those with levels in the 1%-5% range.

Changes in surrogate markers of intestinal epithelial injury and microbial translocation in young and older men during prolonged occupational heat stress in temperate and hot conditions.

PURPOSE: Exertional heat stress can cause damage to the intestinal epithelium and disrupt gastrointestinal barrier integrity, leading to microbial translocation (MT) linked to the development of heat stroke. This study aimed to assess age-related differences in markers of intestinal epithelial injury and MT following non-heat stress and high-heat stress exercise in healthy young and older men. METHODS: Markers of intestinal epithelial injury (intestinal fatty acid-binding protein-'IFABP') and MT (soluble cluster of differentiation 14-'sCD14'; and lipopolysaccharide-binding protein-'LBP') were assessed in healthy young (18-30 y, n = 13) and older (50-70 y) men (n = 12). Blood samples were collected before, after 180 min of moderate-intensity (metabolic rate: 200 W/m2) walking and following 60 min recovery in either a non-heat stress [temperate: 21.9 °C, 35% relative humidity (RH)] or high-heat stress (hot: 41.4 °C, 35% RH) environment. RESULTS: There were no differences in IFABP and sCD14 between the young and older groups in the temperate condition, while LBP was greater in the older group (+ 0.66 ug/mL; + 0.08 to + 1.24 ug/mL). In the hot condition, the older group experienced greater increases in IFABP compared to the young group (+ 712 pg/mL/hr; + 269 to + 1154 pg/mL/hr). However, there were no clear between-group differences for sCD14 (+ 0.24 ug/mL/hr, - 0.22 to + 0.70 ug/mL/hr) or LBP (+ 0.86 ug/mL/hr, - 0.73 to + 2.46 ug/mL/hr). CONCLUSION: While older men may experience greater intestinal epithelial injury following exercise in the heat; this did not lead to a greater magnitude of microbial translocation relative to their younger counterparts.

The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia.

PURPOSE: Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia. METHODS: Twenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 µg·mL-1 LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA. RESULTS: L:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001). CONCLUSIONS: Men present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases.

Anthocyanin-Rich Blackcurrant Extract Preserves Gastrointestinal Barrier Permeability and Reduces Enterocyte Damage but Has No Effect on Microbial Translocation and Inflammation After Exertional Heat Stress.

This study investigated the effects of 7 days of 600 mg/day anthocyanin-rich blackcurrant extract intake on small intestinal permeability, enterocyte damage, microbial translocation, and inflammation following exertional heat stress. Twelve recreationally active men (maximal aerobic capacity = 55.6 ± 6.0 ml·kg-1·min-1) ran (70% VO2max) for 60 min in an environmental chamber (34 °C, 40% relative humidity) on two occasions (placebo/blackcurrant, randomized double-blind crossover). Permeability was assessed from a 4-hr urinary excretion of lactulose and rhamnose and expressed as a ratio of lactulose/rhamnose. Venous blood samples were taken at rest and 20, 60, and 240 min after exercise to measure enterocyte damage (intestinal fatty acid-binding protein); microbial translocation (soluble CD14, lipopolysaccharide-binding protein); and interleukins 6, interleukins 10, and interleukins 1 receptor antagonist. Exercise increased rectal temperature (by ∼2.8 °C) and heart rate (by ∼123 beats/min) in each condition. Blackcurrant supplementation led to a ∼12% reduction in lactulose/rhamnose ratio (p < .0034) and enterocyte damage (∼40% reduction in intestinal fatty acid-binding protein area under the curve; p < .0001) relative to placebo. No between-condition differences were observed immediately after exercise for lipopolysaccharide-binding protein (mean, 95% confidence interval [CI]; +80%, 95% CI [+61%, +99%]); soluble CD14 (+37%, 95% CI [+22%, +51%]); interleukins 6 (+494%, 95% CI [+394%, +690%]); interleukins 10 (+288%, 95% CI [+105%, +470%]); or interleukins 1 receptor antagonist (+47%, 95% CI [+13%, +80%]; all time main effects). No between-condition differences for these markers were observed after 60 or 240 min of recovery. Blackcurrant extract preserves the GI barrier; however, at subclinical levels, this had no effect on microbial translocation and downstream inflammatory processes.

Accuracy of Metabolic Cost Predictive Equations During Military Load Carriage.

ABSTRACT: Vine, CA, Coakley, SL, Blacker, SD, Doherty, J, Hale, B, Walker, EF, Rue, CA, Lee, BJ, Flood, TR, Knapik, JJ, Jackson, S, Greeves, JP, and Myers, SD. Accuracy of metabolic cost predictive equations during military load carriage. J Strength Cond Res 36(5): 1297-1303, 2022-To quantify the accuracy of 5 equations to predict the metabolic cost of load carriage under ecologically valid military speed and load combinations. Thirty-nine male serving infantry soldiers completed thirteen 20-minute bouts of overground load carriage comprising 2 speeds (2.5 and 4.8 km·h-1) and 6 carried equipment load combinations (25, 30, 40, 50, 60, and 70 kg), with 22 also completing a bout at 5.5 km·h-1 carrying 40 kg. For each speed-load combination, the metabolic cost was measured using the Douglas bag technique and compared with the metabolic cost predicted from 5 equations; Givoni and Goldman, 1971 (GG), Pandolf et al. 1997 (PAN), Santee et al. 2001 (SAN), American College of Sports Medicine 2013 (ACSM), and the Minimum-Mechanics Model (MMM) by Ludlow and Weyand, 2017. Comparisons between measured and predicted metabolic cost were made using repeated-measures analysis of variance and limits of agreement. All predictive equations, except for PAN, underpredicted the metabolic cost for all speed-load combinations (p < 0.001). The PAN equation accurately predicted metabolic cost for 40 and 50 kg at 4.8 km·h-1 (p > 0.05), underpredicted metabolic cost for all 2.5 km·h-1 speed-load combinations as well as 25 and 30 kg at 4.8 km·h-1, and overpredicted metabolic cost for 60 and 70 kg at 4.8 km·h-1 (p < 0.001). Most equations (GG, SAN, ACSM, and MMM) underpredicted metabolic cost while one (PAN) accurately predicted at moderate loads and speeds, but overpredicted or underpredicted at other speed-load combinations. Our findings indicate that caution should be applied when using these predictive equations to model military load carriage tasks.

Plasma uptake of selected phenolic acids following New Zealand blackcurrant extract supplementation in humans.

New Zealand blackcurrant (NZBC) extract is a rich source of anthocyanins and in order to exert physiological effects, the anthocyanin-derived metabolites need to be bioavailable in vivo. We examined the plasma uptake of selected phenolic acids following NZBC extract supplementation alongside maintaining a habitual diet (i.e. not restricting habitual polyphenol intake). Twenty healthy volunteers (nine females, age: 28 ± 7 years, height 1.73 ± 0.09 m, body mass 73 ± 11 kg) consumed a 300 mg NZBC extract capsule (CurraNZ®; anthocyanin content 105 mg) following an overnight fast. Venous blood samples were taken pre and 1, 1.5, 2, 3, 4, 5, and 6 h post-ingestion of the capsule. Reversed-phase high-performance liquid chromatography (HPLC) was used for analysis of two dihydroxybenzoic acids [i.e. vanillic acid (VA) and protocatechuic acid (PCA)] and one trihydroxybenzoic acid [i.e. gallic acid (GA)] in plasma following NZBC extract supplementation. Habitual anthocyanin intake was 168 (95%CI:68-404) mg⋅day-1 and no associations were observed between this and VA, PCA, and GA plasma uptake by the NZBC extract intake. Plasma time-concentration curves revealed that GA, and PCA were most abundant at 4, and 1.5 h post-ingestion, representing a 261% and 320% increase above baseline, respectively, with VA remaining unchanged. This is the first study to demonstrate that an NZBC extract supplement increases the plasma uptake of phenolic acids GA, and PCA even when a habitual diet is followed in the days preceding the experimental trial, although inter-individual variability is apparent.

Thermoregulation is not impaired in breast cancer survivors during moderate-intensity exercise performed in warm and hot environments.

This study aimed to assess how female breast cancer survivors (BCS) respond physiologically, hematologically, and perceptually to exercise under heat stress compared to females with no history of breast cancer (CON). Twenty-one females (9 BCS and 12 CON [age; 54 ± 7 years, stature; 167 ± 6 cm, body mass; 68.1 ± 7.62 kg, and body fat; 30.9 ± 3.8%]) completed a warm (25℃, 50% relative humidity, RH) and hot (35℃, 50%RH) trial in a repeated-measures crossover design. Trials consisted of 30 min of rest, 30 min of walking at 4 metabolic equivalents, and a 6-minute walk test (6MWT). Physiological measurements (core temperature (Tre ), skin temperature (Tskin ), heart rate (HR), and sweat analysis) and perceptual rating scales (ratings of perceived exertion, thermal sensation [whole body and localized], and thermal comfort) were taken at 5- and 10-min intervals throughout, respectively. Venous blood samples were taken before and after to assess; IL-6, IL-10, CRP, IFN-γ, and TGF-ß1 . All physiological markers were higher during the 35 versus 25℃ trial; Tre (~0.25℃, p = 0.002), Tskin (~3.8℃, p < 0.001), HR (~12 beats·min-1 , p = 0.023), and whole-body sweat rate (~0.4 L·hr-1 , p < 0.001), with no difference observed between groups in either condition (p > 0.05). Both groups covered a greater 6MWT distance in 25 versus 35℃ (by ~200 m; p = 0.003). Nevertheless, the control group covered more distance than BCS, regardless of environmental temperature (by ~400 m, p = 0.03). Thermoregulation was not disadvantaged in BCS compared to controls during moderate-intensity exercise under heat stress. However, self-paced exercise performance was reduced for BCS regardless of environmental temperature.

Field validation of The Heat Strain Decision Aid during military load carriage.

OBJECTIVES: We aimed to determine the agreement between actual and predicted core body temperature, using the Heat Strain Decision Aid (HSDA), in non-Ground Close Combat (GCC) personnel wearing multi terrain pattern clothing during two stages of load carriage in temperate conditions. DESIGN: Cross-sectional. METHODS: Sixty participants (men = 49, women = 11, age 31 ± 8 years; height 171.1 ± 9.0 cm; body mass 78.1 ± 11.5 kg) completed two stages of load carriage, of increasing metabolic rate, as part of the development of new British Army physical employment standards (PES). An ingestible gastrointestinal sensor was used to measure core temperature. Testing was completed in wet bulb globe temperature conditions; 1.2-12.6 °C. Predictive accuracy and precision were analysed using individual and group mean inputs. Assessments were evaluated by bias, limits of agreement (LoA), mean absolute error (MAE), and root mean square error (RMSE). Accuracy was evaluated using a prediction bias of ±0.27 °C and by comparing predictions to the standard deviation of the actual core temperature. RESULTS: Modelling individual predictions provided an acceptable level of accuracy based on bias criterion; where the total of all trials bias ± LoA was 0.08 ± 0.82 °C. Predicted values were in close agreement with the actual data: MAE 0.37 °C and RMSE 0.46 °C for the collective data. Modelling using group mean inputs were less accurate than using individual inputs, but within the mean observed. CONCLUSION: The HSDA acceptably predicts core temperature during load carriage to the new British Army non-GCC PES, in temperate conditions.

One night of sleep fragmentation does not affect exercise-induced leukocyte trafficking or mitogen-stimulated leukocyte oxidative burst in healthy men.

PURPOSE: This study examined whether one night of sleep fragmentation alters circulating leukocyte counts and mitogen-stimulated oxidative burst by leukocytes at rest and in response to an acute bout of vigorous exercise. METHODS: In a randomised crossover design, nine healthy men (mean ± SD: age 22 ± 2 years; BMI 24.9 ± 1.9 kg/m2) were exposed to one night of fragmented or uninterrupted sleep before cycling for 45 min at 71% ± 4% V̇O2peak. Finger-tip blood samples were collected at rest, immediately post-exercise and one-hour post-exercise. Total leukocytes, lymphocytes, monocytes and neutrophils were counted. Leukocyte oxidative burst was assessed in whole blood by measuring Reactive Oxygen Species (ROS) production with luminol-amplified chemiluminescence after stimulation with phorbol 12-myristate 13-acetate (PMA). RESULTS: Exercise elicited the expected trafficking pattern of leukocytes, lymphocytes, monocytes and neutrophils. Compared to rest, PMA-stimulated ROS production was increased one-hour post-exercise (+73% ± 65%; p = 0.019; data combined for fragmented and uninterrupted sleep). There were no statistically significant effects of fragmented sleep on leukocyte, lymphocyte, monocyte, and neutrophil counts or on ROS production at rest, immediately post-exercise or one-hour post-exercise (p > 0.05). However, with fragmented sleep, there was a +10% greater lymphocytosis immediately post-exercise (fragmented +40% ± 37%; uninterrupted +30% ± 35%; p = 0.51) and a -19% smaller neutrophilia by one-hour post-exercise (fragmented +103% ± 88%; uninterrupted +122% ± 131%; p = 0.72). CONCLUSION: Fragmented sleep did not substantially alter the magnitude or pattern of exercise-induced leukocyte trafficking or mitogen-stimulated oxidative burst by leukocytes.

Serum neurofilament light concentration does not increase following exposure to low velocity football heading.

Objectives: To investigate if heading frequency and impact biomechanics in a single session influence the concentration of serum neurofilament light (NF-L), a sensitive biomarker for axonal damage, up to 7 days after heading incident at ball velocities reflecting basic training drills.Methods: Forty-four males were randomized into either control (n = 8), 10 header (n = 12), 20 header (n = 12) or 40 header (n = 12) groups. Linear and angular head accelerations were quantified during heading. Venous blood samples were taken at baseline, 6 h, 24 h and 7 days after heading. Serum NF-L was quantified using Quanterix NF-L assay kit on the Simoa HD-1 Platform.Results: Serum NF-L did not alter over time (p = 0.44) and was not influenced by number of headers [p = 0.47; mean (95% CI) concentrations at baseline 6.00 pg · ml-1 (5.00-7.00 pg · ml-1); 6 h post 6.50 pg · ml-1 (5.70-7.29 pg · ml-1); 24 h post 6.07 pg · ml-1 (5.14-7.01 pg · ml-1); and 7 days post 6.46 pg · ml-1 (5.45-7.46 pg · ml-1)]. There was no relationship between percentage change in NF-L and summed session linear and angular head accelerations.Conclusion: In adult men, heading frequency or impact biomechanics did not affect NF-L response during a single session of headers at ball velocities reflective of basic training tasks.

No Effects of Different Doses of New Zealand Blackcurrant Extract on Cardiovascular Responses During Rest and Submaximal Exercise Across a Week in Trained Male Cyclists.

Supplementation with anthocyanin-rich blackcurrant increases blood flow, cardiac output, and stroke volume at rest. It is not known whether cardiovascular responses can be replicated over longer timeframes in fed trained cyclists. In a randomized, double-blind, crossover design, 13 male trained cyclists (age 39 ± 10 years, V˙O2max 55.3 ± 6.7 ml·kg-1·min-1) consumed two doses of New Zealand blackcurrant (NZBC) extract (300 and 600 mg/day for 1 week). Cardiovascular parameters were measured during rest and submaximal cycling (65% V˙O2max) on day 1 (D1), D4, and D7. Data were analyzed with an RM ANOVA using dose (placebo vs. 300 vs. 600 mg/day) by time point (D1, D4, and D7). Outcomes from placebo were averaged to determine the coefficient of variation within our experimental model, and 95% confidence interval (CI) was examined for differences between placebo and NZBC. There were no differences in cardiovascular responses at rest between conditions and between days. During submaximal exercise, no positive changes were observed on D1 and D4 after consuming NZBC extract. On D7, intake of 600 mg increased stroke volume (3.08 ml, 95% CI [-2.08, 8.26]; d = 0.16, p = .21), cardiac output (0.39 L/min, 95% CI [-1.39, .60]; d = 0.14, p = .40) (both +2.5%), and lowered total peripheral resistance by 6.5% (-0.46 mmHg·min/ml, 95% CI [-1.80, .89]; d = 0.18, p = .46). However, these changes were trivial and fell within the coefficient of variation of our study design. Therefore, we can conclude that NZBC extract was not effective in enhancing cardiovascular function during rest and submaximal exercise in endurance-trained fed cyclists.

No Effects of New Zealand Blackcurrant Extract on Physiological and Performance Responses in Trained Male Cyclists Undertaking Repeated Testing across a Week Period.

Anthocyanin supplements are receiving attention due to purported benefits to physiological, metabolic, and exercise responses in trained individuals. However, the efficacy of anthocyanin intake over multiple testing days is not known. We compared a placebo and two doses of anthocyanin-rich New Zealand blackcurrant (NZBC) extract (300 and 600 mg·day-1) on plasma lactate, substrate oxidation, and 16.1 km time trial (TT) performance on three occasions over 7-days in a fed state (day 1 (D1), D4, and D7). Thirteen male cyclists participated in a randomized, crossover, placebo-controlled double-blind design. There was no difference in plasma lactate and substrate oxidation between conditions and between days. A time difference was observed between D1 (1701 ± 163 s) and D4 (1682 ± 162 s) for 600 mg (p = 0.05), with an increment in average speed (D1 = 34.3 ± 3.4 vs. D4 = 34.8 ± 3.4 km·h-1, p = 0.04). However, there was no difference between the other days and between conditions. Overall, one week of intake of NZBC extract did not affect physiological and metabolic responses. Intake of 600 mg of NZBC extract showed inconsistent benefits in improving 16.1 km time trial performance over a week period in trained fed cyclists.

Addition of pectin-alginate to a carbohydrate beverage does not maintain gastrointestinal barrier function during exercise in hot-humid conditions better than carbohydrate ingestion alone.

The objective of this study was to compare the effects of consuming a 16% maltodextrin+fructose+pectin-alginate (MAL+FRU+PEC+ALG) drink against a nutrient-matched maltodextrin+fructose (MAL+FRU) drink on enterocyte damage and gastrointestinal permeability after cycling in hot and humid conditions. Fourteen recreational cyclists (7 men) completed 3 experimental trials in a randomized placebo-controlled design. Participants cycled for 90 min (45% maximal aerobic capacity) and completed a 15-min time-trial in hot (32 °C) humid (70% relative humidity) conditions. Every 15 min, cyclists consumed 143 mL of either (i) water; (ii) MAL+FRU+PEC+ALG (90 g·h-1 CHO/16% w/v); or (iii) a ratio-matched MAL+FRU drink (90 g·h-1 CHO/16% w/v). Blood was sampled before and after exercise and gastrointestinal (GI) permeability, which was determined by serum measurements of intestinal fatty acid binding protein (I-FABP) and the percent ratio of lactulose (5 g) to rhamnose (2 g) recovered in postexercise urine. Compared with water, I-FABP decreased by 349 ± 67pg·mL-1 with MAL+FRU+PEC+ALG (p = 0.007) and by 427 ± 56 pg·mL-1 with MAL+FRU (p = 0.02). GI permeability was reduced in both the MAL+FRU+PEC+ALG (by 0.019 ± 0.01, p = 0.0003) and MAL+FRU (by 0.014 ± 0.01, p = 0.002) conditions relative to water. In conclusion, both CHO beverages attenuated GI barrier damage to a similar extent relative to water. No metabolic, cardiovascular, thermoregulatory, or performance differences were observed between the CHO beverages. Novelty Consumption of multiple-transportable CHO, with or without hydrogel properties, preserves GI barrier integrity and reduces enterocyte damage during prolonged cycling in hot-humid conditions.

No Effect of New Zealand Blackcurrant Extract on Recovery of Muscle Damage Following Running a Half-Marathon.

New Zealand blackcurrant (NZBC) contains anthocyanins, known to moderate blood flow and display anti-inflammatory properties that may improve recovery from exercise-induced muscle damage. The authors examined whether NZBC extract supplementation enhances recovery from exercise-induced muscle damage after a half-marathon race. Following a randomized, double-blind, independent groups design, 20 (eight women) recreational runners (age 30 ± 6 years, height 1.73 ± 0.74 m, body mass 68.5 ± 7.8 kg, half-marathon finishing time 1:56:33 ± 0:18:08 hr:min:s) ingested either two 300-mg/day capsules of NZBC extract (CurraNZ™) or a visually matched placebo, for 7 days prior to and 2 days following a half-marathon. Countermovement jump performance variables, urine interleukin-6, and perceived muscle soreness and fatigue were measured pre, post, and at 24 and 48 hr after the half-marathon and analyzed using a mixed linear model with statistical significance set a priori at p < .05. The countermovement jump performance variables were reduced immediately post-half-marathon (p < .05), with all returning to pre-half-marathon levels by 48 hr, except the concentric and eccentric peak force and eccentric duration, with no difference in response between groups (p > .05). Urine interleukin-6 increased 48-hr post-half-marathon in the NZBC group only (p < .01) and remained unchanged compared with pre-half-marathon levels in the placebo group (p > .05). Perceived muscle soreness and fatigue increased immediately post-half-marathon (p < .01) and returned to pre-half-marathon levels by 48 hr, with no difference between groups (p > .05). Supplementation with NZBC extract had no effect on the recovery of countermovement jump variables and perceptions of muscle soreness or fatigue following a half-marathon in recreational runners.

Dietary supplementation with New Zealand blackcurrant extract enhances fat oxidation during submaximal exercise in the heat.

OBJECTIVES: This study investigated the effect of 7 days' supplementation with New Zealand blackcurrant extract on thermoregulation and substrate metabolism during running in the heat. DESIGN: Randomized, double-blind, cross-over study. METHODS: Twelve men and six women (mean±SD: Age 27±6 years, height 1.76±0.10m, mass 74±12kg, V̇O2max 53.4±7.0mLkg-1min-1) completed one assessment of maximal aerobic capacity and one familiarisation trial (18°C, 40% relative humidity, RH), before ingesting 2×300mgday-1 capsules of CurraNZ™ (each containing 105mg anthocyanin) or a visually matched placebo (2×300mg microcrystalline cellulose M102) for 7 days (washout 14 days). On day 7 of each supplementation period, participants completed 60min of fasted running at 65% V̇O2max in hot ambient conditions (34°C and 40% relative humidity). RESULTS: Carbohydrate oxidation was decreased in the NZBC trial [by 0.24gmin-1 (95% CI: 0.21-0.27gmin-1)] compared to placebo (p= 0.014, d=0.46), and fat oxidation was increased in the NZBC trial [by 0.12gmin-1 (95% CI: 0.10 to 0.15gmin-1)], compared to placebo (p=0.008, d=0.57). NZBC did not influence heart rate (p=0.963), rectal temperature (p=0.380), skin temperature (p=0.955), body temperature (p=0.214) or physiological strain index (p=0.705) during exercise. CONCLUSIONS: Seven-days intake of 600mg NZBC extract increased fat oxidation without influencing cardiorespiratory or thermoregulatory variables during prolonged moderate intensity running in hot conditions.

Prolonged treadmill running in normobaric hypoxia causes gastrointestinal barrier permeability and elevates circulating levels of pro- and anti-inflammatory cytokines.

This study examined the impact of treadmill running in normobaric hypoxia on gastrointestinal barrier permeability and the systemic inflammatory response. Ten recreationally active participants completed two 1-h bouts of matched-workload treadmill exercise (65% normoxic maximal oxygen consumption) in counterbalanced order. One bout was performed in normoxia (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and the other in normobaric hypoxia (HYP: FIO2 = 13.5%). Minute ventilation, respiratory rate (RR), tidal volume (VT), oxygen consumption, carbon dioxide production, respiratory exchange ratio (RER), and heart rate (HR) were measured with a metabolic cart. Peripheral oxygen saturation (SpO2) was measured with pulse oximetry. Absolute tissue saturation (StO2) was measured with near-infrared spectroscopy. Fatty acid-binding protein (I-FABP) and circulating cytokine concentrations (interleukin (IL)-1Ra, IL-6, IL-10) were assayed from plasma samples that were collected pre-exercise, postexercise, 1 h-postexercise, and 4 h-postexercise. Data were analyzed with 2-way (condition × time) repeated-measures ANOVAs. Newman-Keuls post hoc tests were run where appropriate (p < 0.05). As compared with NORM, 1 h of treadmill exercise in HYP caused greater (p < 0.05) changes in minute ventilation (+30%), RR (+16%), VT (+10%), carbon dioxide production (+18%), RER (+16%), HR (+4%), SpO2 (-16%), and StO2 (-10%). Gut barrier permeability and circulating cytokine concentrations were also greater (p < 0.05) following HYP exercise, where I-FABP was shown increased at postexercise (+68%) and IL-1Ra at 1 h-postexercise (+266%). I-FABP and IL-1Ra did not change (p > 0.05) following NORM exercise. IL-6 and IL-10 increased with exercise in both study conditions but were increased more (p < 0.05) following HYP at postexercise (+705% and +127%, respectively) and 1 h-postexercise (+400% and +128%, respectively). Novelty Normobaric hypoxia caused significant desaturation and increased most cardiopulmonary responses by 10%-30%. Significant gut barrier permeability and increased pro- and anti-inflammatory cytokine concentrations could promote an "open window" in the hours following HYP exercise.

Reduced inflammatory and phagocytotic responses following normobaric hypoxia exercise despite evidence supporting greater immune challenge.

This study examined changes in immune markers following sustained treadmill exercise in normobaric hypoxia. Ten subjects performed 1 h of treadmill exercise (65% maximal oxygen uptake) under normoxic (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and normobaric hypoxic (HYP: FIO2 = 13.5%) conditions. Blood samples, collected before, after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise, were assayed for plasma cytokines (interleukin (IL)-1RA/IL-1ß/IL-8/tumor necrosis factor alpha (TNF-α)) and markers of leukocyte activation (macrophage inflammatory protein-1ß (MIP-1ß)/myeloperoxidase (MPO)/soluble intercellular adhesion molecule-1 (sICAM-1)) using ELISA. Pro- to anti-inflammatory cytokine ratios (TNF-α/IL-1RA; IL-1ß/IL-1RA) were calculated. Peripheral blood mononuclear cells (PBMC) were analyzed for changes in inflammatory status (phosphorylated nuclear factor kappa B/nuclear factor kappa B) using Western Blot. Data were analyzed with 2-way (condition × time) repeated-measure ANOVAs with Newman-Keuls post hoc tests. MIP-1ß was elevated at 1-Post HYP exercise (+11%; p < 0.01) but did not increase following exercise in NORM. TNF-α/IL-1RA and IL-1ß/IL-1RA ratios were both reduced (p < 0.05) following HYP exercise (-16% and -52%, respectively, at 1-Post and -7% and -32%, respectively, at 4-Post). IL-8 increased (p < 0.05) at Post and 1-Post NORM (+33% and +57%, respectively) and HYP (+60% and +83%, respectively) exercise, but was not different between conditions (p > 0.05). Interestingly, plasma sICAM-1 did not increase (p > 0.05) following NORM exercise but was increased (p < 0.05) at Post (+17%), 1-Post (+16%), and 4-Post (+14%) HYP exercise. There was also a delayed peak in plasma MPO concentrations following HYP exercise and PBMC exhibited a reduced (p < 0.05) inflammatory capacity at Post (-38%) and 1-Post (-49%). Novelty Following HYP exercise, participants exhibited (i) circulatory bias towards anti-inflammation; (ii) elevated sICAM; (iii) delayed peak in plasma MPO; and (iv) diminished inflammatory response in PBMC. Collectively, these data suggest immunosuppression. This is undesirable, given that elevated MIP-1ß (reported here) and elevated intestinal fatty acid binding protein (reported previously) both suggest higher lipopolysaccharide concentrations following HYP exercise.