Kristoffer T. Cumming

Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial

Recent studies have indicated that antioxidant supplementation may blunt adaptations to exercise, such as mitochondrial biogenesis induced by endurance training. However, studies in humans are sparse and results are conflicting. Isolated vitamin C and E supplements are widely used, and unravelling the interference of these vitamins in cellular and physiological adaptations to exercise is of interest to those who exercise for health purposes and to athletes. Our results show that vitamin C and E supplements blunted the endurance training‐induced increase of mitochondrial proteins (COX4), which is important for improving muscular endurance. Training‐induced increases in V̇O2 max and running performance were not detectably affected by the supplementation. The present study contributes to understanding of how antioxidants may interfere with adaptations to exercise in humans, and the results indicate that high dosages of vitamins C and E should be used with caution.

Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training

Although antioxidant supplements are generally believed to give health benefits, recent experiments show that they may adversely affect adaptations to endurance exercise. This study is the first to investigate the effects of high dosages of vitamins C and E on the cellular and physiological adaptations to strength training in humans. Here we report that vitamin C and E supplementation interfered with exercise‐induced signalling in muscle cells after a session of strength training, by reducing the phosphorylation of p70S6 kinase and mitogen‐activated protein kinases p38 and ERK1/2. The vitamin C and E supplement did not significantly blunt muscle hypertrophy during 10 weeks of training; however, some measurements of muscle strength revealed lower increases in the supplemented group than the placebo group. Even though the cellular events are not clearly reflected in physiological and performance measurements, this study implies that redox signalling is important for inducing skeletal muscle adaptations to strength training and that vitamin C and E supplements in high dosages should be avoided by healthy, young individuals engaged in strength training.

Acute response and subcellular movement of HSP27, αB-crystallin and HSP70 in human skeletal muscle after blood-flow-restricted low-load resistance exercise.

Heat‐shock proteins (HSP) are important chaperones for stressed and damaged proteins. Low‐load blood‐flow‐restricted resistance exercise (BFRE) is generally believed not to induce significant muscle damage, but is hitherto unverified with intracellular markers. Consequently, the aim of this study was to investigate the HSP response after BFRE in human skeletal muscle.

Blood flow-restricted strength training displays high functional and biological efficacy in women: a within-subject comparison with high-load strength training

Limited data exist on the efficacy of low-load blood flow-restricted strength training (BFR), as compared directly to heavy-load strength training (HST). Here, we show that 12 wk of twice-a-week unilateral BFR [30% of one repetition maximum (1RM) to exhaustion] and HST (6-10RM) of knee extensors provide similar increases in 1RM knee extension and cross-sectional area of distal parts of musculus quadriceps femoris in nine untrained women (age 22 ± 1 yr). The two protocols resulted in similar acute increases in serum levels of human growth hormone. On the cellular level, 12 wk of BFR and HST resulted in similar shifts in muscle fiber composition in musculus vastus lateralis, evident as increased MyHC2A proportions and decreased MyHC2X proportions. They also resulted in similar changes of the expression of 29 genes involved in skeletal muscle function, measured both in a rested state following 12 wk of training and subsequent to singular training sessions. Training had no effect on myonuclei proportions. Of particular interest, 1) gross adaptations to BFR and HST were greater in individuals with higher proportions of type 2 fibers, 2) both BFR and HST resulted in approximately four-fold increases in the expression of the novel exercise-responsive gene Syndecan-4, and 3) BFR provided lesser hypertrophy than HST in the proximal half of musculus quadriceps femoris and also in CSApeak, potentially being a consequence of pressure from the tourniquet utilized to achieve blood flow restriction. In conclusion, BFR and HST of knee extensors resulted in similar adaptations in functional, physiological, and cell biological parameters in untrained women.

Effects of vitamin C and E supplementation on endogenous antioxidant systems and heat shock proteins in response to endurance training.

Reactive oxygen and nitrogen species are important signal molecules for adaptations to training. Due to the antioxidant properties of vitamin C and E, supplementation has been shown to blunt adaptations to endurance training. In this study, we investigated the effects of vitamin C and E supplementation and endurance training on adaptations in endogenous antioxidants and heat shock proteins (HSP). Thirty seven males and females were randomly assigned to receive Vitamin C and E (C + E; C: 1000 mg, E: 235 mg daily) or placebo (PLA), and underwent endurance training for 11 weeks. After 5 weeks, a subgroup conducted a high intensity interval session to investigate acute stress responses. Muscle and blood samples were obtained to investigate changes in proteins and mRNA related to the antioxidant and HSP system. The acute response to the interval session revealed no effects of C + E supplementation on NFκB activation. However, higher stress responses to exercise in C + E group was indicated by larger translocation of HSPs and a more pronounced gene expression compared to PLA. Eleven weeks of endurance training decreased muscle GPx1, HSP27 and αB‐crystallin, while mnSOD, HSP70 and GSH remained unchanged, with no influence of supplementation. Plasma GSH increased in both groups, while uric acid decreased in the C + E group only. Our results showed that C + E did not affect long‐term training adaptations in the antioxidant‐ and HSP systems. However, the greater stress responses to exercise in the C + E group might indicate that long‐term adaptations occurs through different mechanisms in the two groups.

Effect of insulin and contraction on glycogen synthase phosphorylation and kinetic properties in epitrochlearis muscles from lean and obese Zucker rats.

In the present study, the effects of insulin and contraction on glycogen synthase (GS) kinetic properties and phosphorylation were investigated in epitrochlearis muscles from lean and obese Zucker rats. Total GS activity and protein expression were ~15% lower in epitrochlearis from obese rats compared with lean rats. Insulin-stimulated GS fractional activity and affinity for UDP-glucose were lower (higher K(m)) in muscles from obese rats. GS Ser(641) and Ser(645,649,653,657) phosphorylation was higher in insulin-stimulated muscles from obese rats, which agreed with lower GS activation. Contraction-mediated GS dephosphorylation of Ser(641), Ser(641+645), Ser(645,649,653,657), and Ser(7+10) was normal in muscles from obese Zucker rats, and GS fractional activity increased to similar levels in epitrochlearis muscles from lean and obese rats. GS affinity for UDP glucose was ~0.8, ~0.4, and ~0.1 mM with assay buffers containing 0, 0.17, and 12 mM glucose 6-phosphate, respectively. Contraction increased affinity for UDP-glucose (reduced K(m)) at a physiological concentration of glucose 6-phosphate (0.17 mM) to ~0.2 mM in muscles from both lean and obese rats. Interestingly, in the absence of glucose 6-phosphate in the assay buffer, contraction (and insulin) did not influence GS affinity for UDP-glucose, indicating that affinity is regulated by sensitivity for glucose 6-phosphate. In conclusion, contraction-mediated activation and dephosphorylation of GS were normal in muscles from obese Zucker rats, whereas insulin-mediated GS activation and dephosphorylation were impaired.

Intake of Protein Plus Carbohydrate during the First Two Hours after Exhaustive Cycling Improves Performance the following Day

Intake of protein immediately after exercise stimulates protein synthesis but improved recovery of performance is not consistently observed. The primary aim of the present study was to compare performance 18 h after exhaustive cycling in a randomized diet-controlled study (175 kJ·kg-1 during 18 h) when subjects were supplemented with protein plus carbohydrate or carbohydrate only in a 2-h window starting immediately after exhaustive cycling. The second aim was to investigate the effect of no nutrition during the first 2 h and low total energy intake (113 kJ·kg-1 during 18 h) on performance when protein intake was similar. Eight endurance-trained subjects cycled at 237±6 Watt (~72% VO2max) until exhaustion (TTE) on three occasions, and supplemented with 1.2 g carbohydrate·kg-1·h-1 (CHO), 0.8 g carbohydrate + 0.4 g protein·kg-1·h-1 (CHO+PRO) or placebo without energy (PLA). Intake of CHO+PROT increased plasma glucose, insulin, and branch chained amino acids, whereas CHO only increased glucose and insulin. Eighteen hours later, subjects performed another TTE at 237±6 Watt. TTE was increased after intake of CHO+PROT compared to CHO (63.5±4.4 vs 49.8±5.4 min; p<0.05). PLA reduced TTE to 42.8±5.1 min (p<0.05 vs CHO). Nitrogen balance was positive in CHO+PROT, and negative in CHO and PLA. In conclusion, performance was higher 18 h after exhaustive cycling with intake of CHO+PROT compared to an isocaloric amount of carbohydrate during the first 2 h post exercise. Intake of a similar amount of protein but less carbohydrate during the 18 h recovery period reduced performance.

Acute and long-term effects of blood flow restricted training on heat shock proteins and endogenous antioxidant systems

Blood flow restricted exercise (BFRE) with low loads has been demonstrated to induce considerable stress to exercising muscles. Muscle cells have developed a series of defensive systems against exercise‐induced stress. However, little is known about acute and long‐term effects of BFRE training on these systems. Nine previously untrained females trained low‐load BFRE and heavy load strength training (HLS) on separate legs and on separate days to investigate acute and long‐term effects on heat shock proteins (HSP) and endogenous antioxidant systems in skeletal muscles. BFRE and HLS increased muscle strength similarly by 12 ± 7% and 12 ± 6%, respectively, after 12 weeks of training. Acutely after the first BFRE and HLS exercise session, αB‐crystallin and HSP27 content increased in cytoskeletal structures, accompanied by increased expression of several HSP genes. After 12 weeks of training, this acute HSP response was absent. Basal levels of αB‐crystallin, HSP27, HSP70, mnSOD, or GPx1 remained unchanged after 12 weeks of training, but HSP27 levels increased in the cytoskeleton. Marked translocation of HSP to cytoskeletal structures at the commencement of training indicates that these structures are highly stressed from BFRE and HLS. However, as the muscle gets used to this type of exercise, this response is abolished.

Vitamin C and E supplementation does not affect heat shock proteins or endogenous antioxidants in trained skeletal muscles during 12 weeks of strength training

BackgroundSupplementation with large doses of antioxidants, such as vitamin C and E, has been shown to blunt some adaptations to endurance training. The effects of antioxidant supplementation on adaptations to strength training is sparsely studied. Herein we investigated the effects of vitamin C and E supplementation on acute stress responses to exercise and adaptation to traditional heavy load strength training.MethodsIn a double blind placebo-controlled design, twenty-eight, young, trained males and females were randomly assigned to receive either vitamin C and E (C: 1000 mg, E: 235 mg, per day) or placebo supplements, and underwent strength training for 10 weeks. After five weeks, a subgroup conducted a strength training session to investigate acute stress responses. Muscle samples were obtained to investigate changes in stress responses and in proteins and mRNA related to the heat shock proteins (HSPs) or antioxidant enzymes.ResultsThe acute responses to the exercise session revealed activation of the NFκB pathway indicated by degradation of IκBα in both groups. Vitamin C and E supplementation had, however, no effects on the acute stress responses. Furthermore, ten weeks of strength training did not change muscle αB-crystallin, HSP27, HSP70, GPx1 or mnSOD levels, with no influence of supplementation.ConclusionsOur results showed that although vitamin C and E supplementation has been shown to interfere with training adaptations, it did not affect acute stress responses or long-term training adaptations in the HSPs or antioxidant enzymes in this study.