Charles L. Dumke

Muscle damage is linked to cytokine changes following a 160-km race

Muscle damage and perceived soreness following the 160-km Western States Endurance Run were related to changes in plasma cytokines and use of nonsteroidal anti-inflammatory drugs (NSAIDS). Subjects included 60 ultramarathoners (mean+/-SE, age 45.3 +/- 1.1 years) who finished the race in under 30 h (26.3 +/- 0.4 h). Blood samples were collected the morning prior to and immediately following the race, and subjects recorded muscle soreness during the week following the race using a 10-point Likert scale (DOMS). Seven plasma cytokines were measured including IL-6, IL-10, IL-8, IL-1ra, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1beta (MIP-1beta). Cytokine changes were compared between NSAID users and nonusers, and correlated with creatine phosphokinase (CPK) and DOMS. Significant increases were measured for all seven cytokines, with the greatest fold increases seen for IL-6 (125x), IL-10 (24x), and G-CSF (12x). CPK was correlated with changes in IL-6, G-CSF, IL-10, IL-1ra, and MCP-1 (r = .49-.68), (P < .001), but not IL-8 or MIP-1beta. DOMS averaged 7.1 +/- 0.3 the day after the race, and 5.0 +/- 0.3, 2.5 +/- 0.2, and 1.6 +/- 0.1 3 days, 5 days, and 7 days post-race, respectively, and each was correlated with CPK (r = .40-.63, P < .001) and changes in IL-6, G-CSF, IL-10, and MCP-1 (r = .28-.77, P < .05). A comparison of NSAID users (72% of athletes) and nonusers showed no differences in CPK or DOMS, but did reveal greater increases in five of seven cytokines in the NSAID users (P < .05). In conclusion, muscle damage in athletes competing in a 160-km race was significantly correlated with post-race DOMS and increases in five of seven cytokines. NSAID users did not experience a reduction in muscle damage or DOMS, but did have higher post-race plasma levels in five of seven cytokines.

Influence of Carbohydrate Ingestion on Oxidative Stress and Plasma Antioxidant Potential Following a 3 h Run

Concentrations of reactive oxygen species (ROS) increase during exercise secondary to increased oxygen uptake, xanthine oxidase activity, and immune system activation. Carbohydrate compared to placebo beverage ingestion is associated with an attenuated cortisol and catecholamine response. Catecholamines can undergo autooxidation to form ROS. We hypothesized that during intense exercise, ingestion of carbohydrate compared to placebo would diminish oxidative stress. Sixteen experienced marathoners ran on treadmills for 3 h at ∼70% VO2max on two occasions while receiving carbohydrate or placebo beverages (1 l/h, double-blinded) in a randomized, counterbalanced order. Blood samples were collected before and immediately after exercise, snap frozen in liquid nitrogen, and stored at -80°C until analysis. Plasma samples were analyzed for F2-isoprostanes (FIP) and lipid hydroperoxides (ROOH) as measures for lipid peroxidation, ferric reducing ability of plasma (FRAP) as a measure of plasma antioxidant potential and for cortisol. The pattern of change in cortisol was significantly different between carbohydrate and placebo conditions (P=0.024), with post-exercise levels higher in the placebo condition. Under both carbohydrate and placebo conditions, significant increases in FIP, ROOH, and FRAP were measured, but the pattern of increase was not different (FIP, interaction effect, P=0.472; ROOH, P=0.572; FRAP, P=0.668). Despite an attenuation in the cortisol response, carbohydrate compared to placebo ingestion does not counter the increase in oxidative stress or modulate plasma antioxidant potential in athletes running 3 h at 70% VO2max.

Effect of resistance exercise and carbohydrate ingestion on oxidative stress

Some research studies have produced data indicating that resistance exercise induces oxidative stress, despite minimal increases in VO2. These studies have primarily relied on oxidative stress markers with low sensitivity and debatable reliability. However, F2-isoprostanes as measured by gas chromatography mass spectrometry are considered to be a reliable and precise indicator of oxidative stress. Carbohydrate ingestion during exercise is associated with reduced levels of stress hormones, which may influence oxidative stress and plasma antioxidant potential. Therefore, the purpose of this study was to investigate the influence of carbohydrate ingestion during resistance training on F2-isoprostanes and plasma antioxidant potential. Thirty strength-trained subjects were randomized to carbohydrate (CHO) or placebo (PLA) groups that lifted weights for 2 h. Subjects received 10 ml kg− 1 h− 1 CHO (6%) or PLA beverages during the exercise. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise and analyzed for cortisol as a marker of general stress, F2-isoprostanes as a measure of oxidative stress, and ferric reducing ability of plasma (FRAP) as a measure of antioxidant potential, and for muscle glycogen, respectively. Decreases in muscle glycogen content did not differ between CHO and PLA. Cortisol and FRAP increased significantly in CHO and PLA (P = 0.008 and 0.044, respectively), but the pattern of change was not different between groups. F2-isoprostanes were unaffected by exercise. These results indicate that exhaustive resistance exercise and carbohydrate ingestion have no effect on oxidative stress or plasma antioxidant potential in trained subjects.

Quercetin does not affect rating of perceived exertion in athletes during the Western States endurance run.

The purpose of this study was to measure the influence of quercetin supplementation on ratings of perceived exertion in ultramarathon runners competing in the 160-km Western States Endurance Run (WSER). Sixty-three runners were randomized to quercetin (Q) and placebo (P) groups, and under double blinded methods ingested four supplements per day with or without 250 mg quercetin for 3 weeks before the WSER. Thirty-nine of the 63 subjects (quercetin N = 18, placebo N = 21) finished the race. At the completion of exercise ratings of perceived exertion (RPE) were assessed at aid stations located at 40, 90, 125, 150, and 160 km (finish line). The pattern of change in RPE over time was not significantly different between the Q and P groups. Ratings of perceived exertion (RPE) did not significantly increase throughout the race (15.2 ± 2.9 at 40 km –14.2 ± 4.0 at 160 km) for both groups combined. Race times were not different between the groups (Q = 26.4 ± 0.7 h and P = 27.5 ± 0.6 h). Significant time main effects (p < 0.001) were found for both serum glucose and cortisol throughout the race. Quercetin supplementation for 3 weeks prior to the WSER had no effect on RPE during competitive self-paced ultramarathon running. Ratings of perceived exertion (RPE) did not increase in a linear fashion but instead fluctuated nonmonotonically throughout the self-paced endurance running event.

Post-160-km Race Illness Rates and Decreases in Granulocyte Respiratory Burst and Salivary IgA Output are Not Countered by Quercetin Ingestion

This study measured the influence of the flavonoid quercetin on immune changes and incidence rates of upper respiratory tract infections in ultramarathoners competing in the 160-km Western States Endurance Run. Sixty-three runners were randomized to quercetin and placebo groups, and under double-blinded methods ingested 1000 mg/day quercetin for 3 wks before, during, and 2 wks after the race. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood and saliva samples the morning before the race and 15 - 30 min postrace. Upper respiratory tract infections were assessed during the week before and the 2-wk period after the race using an illness symptom checklist. Race times did not differ significantly between quercetin and placebo groups. Significant pre- to postrace decreases were measured for natural killer cells (43 %), granulocyte respiratory burst activity (55 %), and salivary IgA output (48 %), and increases for neutrophil (288 %) and monocyte (211 %) cell counts, with no significant group differences. Postrace illness rates did not differ between groups. In conclusion, quercetin supplementation for 3 wks before and 2 wks after the Western States Endurance Run had no effect on illness rates, perturbations in leukocyte subset counts, or decreases in granulocyte respiratory burst activity and salivary IgA.

INFLUENCE OF CARBOHYDRATE ON IMMUNE FUNCTION FOLLOWING 2 H CYCLING

The influence of carbohydrate compared with placebo ingestion on changes in immune cell counts and functions following 2 h intensive cycling was studied in 12 trained cyclists who functioned as their own controls. The subjects performed two tests 2 weeks apart where they cycled for 2 h at ∼64% Wattsmax while receiving 4 mL·kg−1·15 min−1 carbohydrate (6%) (Cho) or placebo (Pla) beverages. Blood samples were collected 30 min preexercise, and immediately and 1 h postexercise. The samples were assayed for plasma cortisol and epinephrine, blood leukocyte subset counts, PHA-induced lymphocyte proliferation, and natural killer cell activity (NKCA). Compared with Pla ingestion, Cho attenuated exercise-induced changes in plasma cortisol, blood neutrophil, and monocyte counts, but not in total blood lymphocyte, T cell, and NK cell counts, PHA-induced lymphocyte proliferation, and NKCA. Thus despite a strong attenuating influence of carbohydrate ingestion on exercise-induced changes in plasma cortisol and blood neutrophil and monocyte counts, other immune measures related to lymphocyte subset counts, and function were unaffected.

CARBOHYDRATE INGESTION INFLUENCES SKELETAL MUSCLE CYTOKINE mRNA AND PLASMA CYTOKINE LEVELS AFTER A 3-H RUN

Sixteen experienced marathoners ran on treadmills for 3 h at approximately 70% maximal oxygen consumption (Vo(2 max)) on two occasions while receiving 1 l/h carbohydrate (CHO) or placebo (Pla) beverages. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise. Plasma was analyzed for IL-6, IL-10, IL-1 receptor agonist (IL-1ra), IL-8, cortisol, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines by using real-time quantitative RT-PCR. Plasma glucose and insulin were higher, and cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO vs. Pla. Change in muscle glycogen content did not differ between CHO and Pla (P = 0.246). Muscle cytokine mRNA content was detected preexercise for seven cytokines in this order (highest to lowest): IL-15, TNF-alpha, IL-8, IL-1beta, IL-12p35, IL-6, and IFN-gamma. After subjects ran for 3 h, gene expression above prerun levels was measured for five of these cytokines: IL-1beta, IL-6, and IL-8 (large increases), and IL-10 and TNF-alpha (small increases). The increase in mRNA (fold difference from preexercise) was attenuated in CHO (15.9-fold) compared with Pla (35.2-fold) for IL-6 (P = 0.071) and IL-8 (CHO, 7.8-fold; Pla, 23.3-fold; P = 0.063). CHO compared with Pla beverage ingestion attenuates the increase in plasma IL-6, IL-10, and IL-1ra and gene expression for IL-6 and IL-8 in athletes running 3 h at 70% Vo(2 max) despite no differences in muscle glycogen content.