Exercise & the Antioxidant Network

Diet and Nutrition
21

Researchers have found that interfering with free radical metabolism by taking antioxidants may hamper useful adaptations to training and that exercise itself can be considered an antioxidant.

The researchers conclude" “In all likelihood, antioxidant supplements should not be recommended before training as they interfere with muscle cell adaptation”

Further, ROS act as signals in exercise because decreasing their formation prevents activation of important signaling pathways that cause useful adaptations in cells. Because these signals result in an upregulation of powerful antioxidant enzymes, exercise itself can be considered an antioxidant.

Physical exercise is a double-edged sword: when practiced strenuously (as in the case of the tour de france) it causes oxidative stress and cell damage; the study says that in this case antioxidants should be given. But when practiced in moderation (of which the definition is not given in the study), it increases the expression of antioxidant enzymes and thus should be considered an antioxidant.

Full study copy and pasted below.

22

[quote]TITLE
Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training

Mari-Carmen Gomez-Cabreraa, Elena Domenecha and Jose ViñaCorresponding Author Contact Information, a, E-mail The Corresponding Author

aDepartment of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez, 15, 46010 Valencia, Spain

Received 18 December 2006;
revised 29 January 2007;
accepted 1 February 2007.
Available online 9 February 2007.[/quote]

23

[quote]ABSTRACT

Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. However, there is increasing evidence that reactive oxygen species (ROS) not only are toxic but also play an important role in cell signaling and in the regulation of gene expression. Xanthine oxidase is involved in the generation of superoxide associated with exhaustive exercise. Allopurinol (an inhibitor of this enzyme) prevents muscle damage after exhaustive exercise, but also modifies cell signaling pathways associated with both moderate and exhaustive exercise in rats and humans. In gastrocnemius muscle from rats, exercise caused an activation of MAP kinases. This in turn activated the NF-κB pathway and consequently the expression of important enzymes associated with defense against ROS (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when ROS production was prevented by allopurinol. Thus ROS act as signals in exercise because decreasing their formation prevents activation of important signaling pathways that cause useful adaptations in cells. Because these signals result in an upregulation of powerful antioxidant enzymes, exercise itself can be considered an antioxidant. We have found that interfering with free radical metabolism with antioxidants may hamper useful adaptations to training.[/quote]

24

[quote] Free radicals in exhaustive physical exercise
The beneficial effects of regular, nonexhaustive physical exercise have been known for a long time. There is irrefutable evidence of the effectiveness of regular physical activity in the primary and secondary prevention of several chronic diseases (e.g., cardiovascular disease, diabetes, cancer, hypertension, obesity, depression, and osteoporosis) and premature death [1]. However, the beneficial effects of exercise are lost with exhaustion. It is well known that exhaustive exercise (especially when sporadic) causes structural damage to muscle cells or inflammatory reactions within the muscles, for instance, as evidenced by an increase in the plasma activity of cytosolic enzymes and sarcolemma and Z-line disruption [2]. Some of this damage is due to the production of free radicals and it may be prevented by optimizing nutrition, particularly by increasing the dietary content of nutritional antioxidants [3] and [4]. Moreover, free radicals are involved in the pathogenesis of many diseases, such as diabetes, cardiovascular diseases, inflammation, or pulmonary diseases. Free radicals are also involved in important physiological processes, such as aging. Research in this area started in the fifties when the first data showing that free radicals are present in muscle were published [5]. In 1980 Koren et al. showed that free radical content was elevated in limb muscles stimulated to contract repetitively [6]. It was in 1982 when it was shown by Davies et al. that there is free radical production in rat skeletal muscle after running until exhaustion [7]. Since then, research in the area has grown spectacularly. It is now clear that intense muscular contractile activity can result in oxidative stress as indicated by altered muscle and blood glutathione levels and an increase in protein, DNA oxidation, and in lipid peroxidation [8] and [9]. When proteins and lipids become oxidized by reactive oxygen species (ROS), muscle force production is diminished and fatigue may occur [10]. Our research group demonstrated in 1992 that a single bout of exhaustive exercise causes oxidative stress only when exhaustive. We found a linear correlation between the ratios of oxidized to reduced glutathione and lactate to pyruvate [11]. It has been generally accepted that increasing the intracellular levels of antioxidants within a muscle cell should provide greater protection against these oxidizing agents and reduce fatigue [12], [13] and [14].[/quote]

25

[quote] Sources of free radicals in exercise

In setting out to determine the mechanism by which exercise causes an increased production of ROS, we came across the generally accepted idea that, because exercise causes an increase in oxygen consumption by mitochondria, it also causes an increase in free radical formation by these organelles. This, however, is based on the misconception that the proportion of ROS formed by mitochondria is in the range of 2% of the total oxygen consumed. Very early work by the group of Britton Chance [15] revealed that approximately 2% of oxygen used by mitochondria is converted to free radicals only when these mitochondria are at the resting state, State 4. However, when mitochondria are in State 3, i.e., actively producing ATP from ADP, with a high electron flow into oxygen, the proportion of oxygen converted to free radicals falls to a tenth of that found in the resting state. With these calculations in mind, the role of mitochondria in the formation of free radicals in exercise should be reconsidered and perhaps alternative sources of reactive oxygen species should be identified. Work by Michael Reid [16], Ylva Hellsten [17], and Malcolm Jackson [18] indicated that there might be extracellular sources of superoxide associated with exercise. We examined the role of xanthine oxidase (XO) and the possible effect of allopurinol, a well-known, widely used inhibitor of this enzyme. XO and xanthine dehydrogenase (XDH) are isoenzymes of xanthine oxidoreductase, which catalyzes the oxidation of hypoxanthine and xanthine to urate during purine catabolism in mammals. Whereas XDH preferentially transfers the electrons released during the oxidation process to NAD, XO utilizes molecular oxygen, thereby generating superoxide radical [19]. In experiments with animals we observed that allopurinol prevents oxidation of glutathione and lipoperoxidation associated with exhaustion [4]. Moreover, in a number of experiments which we performed with cyclists of the professional cycling team U.S. Postal during two editions of the Tour de France we found that oral administration of a dose of 300 mg of allopurinol prevented the increase in the activities of creatine kinase and aspartate aminotransferase in plasma only at the stage at which participants performed at their peak level of exertion, the Team Time Trial stage (see Fig. 1). We also found evidence of an increase in plasma malondialdehyde levels in all participants at the end of the race, but the increase was significantly greater in placebo group than in the allopurinol group. These results suggested that XO is involved in the tissue damage associated with exhaustive physical exercise in vivo [20]. We confirmed these data in a different study with marathon runners recruited from participants in the 23rd Marathon of Valencia. Marathon running induced a significant increase in plasma malondialdehyde levels that was prevented by treatment with allopurinol [21]. Our data demonstrate that XO is a relevant source of free radicals during aerobic exercise. Radak et al. found that XO has been implicated also in free radical production during anaerobic exercise (the correlation between XO and lactic acid after a single bout of exhaustive exercise was r = 0.87) [22]. In a similar fashion, we found that XO is also involved in free radical generation during resistance exercise (in weightlifters) [23].[/quote]

26

27

[quote]Role of free radicals in muscle adaptation to exercise

The idea of the deleterious effects of free radicals has been firmly entrenched in the minds of scientists for the past 30 years. However, there is now an appreciation that the reactive oxygen species generated during muscle contraction have a physiological role in the adaptation to exercise. In response to the free radical assault, the cell has developed a number of antioxidant defense systems such as superoxide dismutase, the peroxidases, the glutathione redox cycle with its associated constitutive enzymes, as well as glutathione itself, whose concentration is higher in the cell than that of glucose [24]. Therefore the cell has become well equipped to deal with the normal production of reactive oxygen species.

There is growing evidence that the continued presence of a small stimulus such as low concentrations of reactive oxygen species is in fact able to induce the expression of antioxidant enzymes and other defense mechanisms. The basis for this phenomenon may be encompassed by the concept of hormesis [25], which can be characterized as a particular doseâ??response relationship in which a low dose of a substance is stimulatory and a high dose is inhibitory. In this context radicals may be seen as beneficial, as they act as signals to enhance defenses, rather than as deleterious as they are when cells are exposed to high levels of these radicals. Recently the hormesis theory has been extended to the ROS-generating effects of exercise [26] and [27]. In skeletal muscle hydrogen peroxide at a low concentration increases Ca2+ release from the sarcoplasmic reticulum and force production, whereas a massive increase in hydrogen peroxide concentration results in a sharp decrease in force output [28]. Animals frequently exposed to exercise (chronic training) have shown less oxidative damage after exhaustive exercise than untrained animals. This is largely due to the upregulation of endogenous antioxidant enzymes such as mitochondrial superoxide dismutase (MnSOD), glutathione peroxidase, and �³-glutamylcysteine synthetase (GCS) [29]. Because the adaptive response results from the cumulative effects of repeated exercise bouts, the initial signal for the stimulation leading to the long-term modulation must occur after each individual exercise bout [30]. As mentioned previously several oxidative stress-sensitive signaling pathways are operational in mammalian systems and play an important role in maintaining cellular oxidantâ??antioxidant balance. One of the most important involves the transcription factor nuclear factor �ºB (NF-�ºB) [31]. Several antioxidant enzymes contain NF-�ºB binding sites in their gene promoter region, such as MnSOD, inducible nitric oxide synthetase (iNOS), and GCS [32]. Therefore, they can be potential targets for exercise-activated upregulation via the NF-�ºB signaling pathway. Hollander et al. [33] first reported that an acute bout of treadmill running activated MnSOD gene expression in rat skeletal muscle, along with enhanced NF-�ºB binding in muscle nuclear extracts not, vert, similar 2 h after exercise. We investigated the effects of rigorous muscular contraction on the NF-�ºB signaling pathway in two separate studies: in rat skeletal muscle [34] and in peripheral lymphocytes of marathon runners [21]. In 2004 we studied the effects of an acute bout of physical exercise on the NF-�ºB signaling pathway in rat skeletal muscle. The time course of exercise-induced NF-�ºB activation was examined. The highest levels of NF-�ºB binding were observed at 2 h postexercise. Decreased cytosolic I�ºB and increased phospho-I �ºB content were found 0â??1 h postexercise, whereas p65 reached peak levels at 2â??4 h. These data suggested that the NF-�ºB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production [34] (see Fig. 2). From this study we concluded that ROS initiate a cascade of intracellular events that may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier (see Fig. 2) [30]. More recently we have demonstrated that marathon running induces activation of the p50 subunit of the NF-�ºB complex in lymphocytes [21]. This is prevented by treatment with allopurinol. In 2005 [8] we reported that ROS generated during exercise activate MAPKs (p38 and ERK1/ERK2), which in turn activate NF-�ºB, which results in an increased expression of important enzymes associated with cell defense (MnSOD and GPx) and adaptation to exercise (eNOS and iNOS). Prevention of ROS formation by inhibition of XO abolishes these effects. A schematic representation highlighting the role of ROS generated in moderate exercise in the upregulation of antioxidant enzymes and, thus, the fact that moderate exercise is an antioxidant, is shown in Fig. 3.[/quote]

28

29

30

[quote]Exercise and antioxidants

As described above ROS produced in exercise act as signals that regulate molecular events important in muscle cell adaptations to exercise. The practical consequence is that antioxidant administration prevents such adaptations and, thus, the recommendation of taking antioxidant supplements before moderate exercise should be revised as they may prevent useful adaptations induced by exercise. In 1993 Michael Reid and co-workers [10] showed that in unfatigued skeletal muscle ROS have a positive effect on excitationâ??contraction coupling and are obligatory for optimal contractile function. Specifically they demonstrated that addition of the antioxidant enzymes (i.e., catalase and SOD) resulted in a diminished in vitro muscle contractile performance in unfatigued muscle. The contractile losses during catalase exposure were reverted by the addition of hydrogen peroxide in a dose-dependent manner [10]. However, a massive increase in hydrogen peroxide concentration results in a sharp decrease in force output [33]. Further, the addition of strong synthetic antioxidants such as dithiothreitol and DMSO [13] and [35] to an organ bath containing skeletal muscle also results in depressed skeletal muscle force production. These data have been confirmed in other studies in which the introduction of a ROS-generating system (xanthine oxidase and hypoxanthine) resulted in an increase in low-frequency contractility of the unfatigued diaphragm. The exact mechanism involved in this process is not completely clear. ROS depletion is deleterious to excitationâ??contraction coupling [36]. On the basis of the existing literature, the most likely mechanism to explain the variation of force in response to the shifts in the redox balance seems to be mediated by changes in myofibrillar Ca2+ sensitivity [36] and by the reduction in calcium permeability of the sarcoplasmic reticulum [37], [38], [39] and [40]. The targets that determine Ca2+ sensitivity of the contractile process are troponin and the regulatory myosin light chain [41] and [42].

An important question is the effect of supplementation with antioxidants on exercise. It is estimated that 70% of the U.S. population uses antioxidant supplements at least occasionally and 40% uses them on a regular basis [43]. There is considerable debate regarding the beneficial health effects of this kind of supplementation in different types of patients and with different types of antioxidants. This point of view is partly supported by studies showing the detrimental effect of antioxidant supplementation on morbidity and mortality [44], [45] E. Lonn, J. Bosch, S. Yusuf, P. Sheridan, J. Pogue, J.M. Arnold, C. Ross, A. Arnold, P. Sleight, J. Probstfield and G.R. Dagenais, Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial, JAMA 293 (2005), pp. 1338â??1347. View Record in Scopus | Cited By in Scopus (291)[45] and [46].

The sport population is usually supplemented with high levels of antioxidants. However, data showing beneficial effects on muscle function of this type of widespread practice are elusive. In fact there is a growing number of papers showing the deleterious effects of the antioxidant treatment. As early as 1971 it was reported that vitamin E supplementation (400 IU daily for 6 weeks) had no beneficial, but did have unfavorable, effects on endurance performance [47]. Eight years later Brady and his colleagues showed that supplementation with selenium and vitamin E did not improve muscle performance in swimming rats [48]. In 1996 and 1997 two papers showing the deleterious effects of ubiquinone-10 supplementation in the performance of humans after a high-intensity training program were published in an Scandinavian journal [49] and [50]. Two years later, Nielsen and his colleagues showed no effect of antioxidant supplementation in triathletes on maximal oxygen uptake [51]. In 2001 Lester Packer’s group demonstrated that in unfatigued rat muscles vitamin E and α-lipoic acid supplementation in the diet for 8 weeks depressed muscle tetanic force at stimulation frequencies â?¤ 40 Hz [52]. One year later, in 2002, it was shown that supplementation of racing greyhounds with 1 g of vitamin C daily for 4 weeks slowed their speed significantly. The dogs ran, on average, 0.2 s slower when supplemented, equivalent to a lead of 3 m at the finish of a 500-m race [53]. More recently Close et al. have reported that ascorbic acid supplementation (1 g for 14 days) does not attenuate postexercise muscle soreness after muscle-damaging exercise but may delay the recovery process [54]. In a attempt to give a molecular explanation for all these data, a recent paper showed that supplementation with vitamin C (0.5 g a day) and E (400 IU a day) inhibited the release of interleukin-6 from contracting human skeletal muscle. The only supplementation with antioxidants that has reported beneficial effects is the use of a cysteine donor (NAC) to increase endogenous glutathione synthesis. In these studies an improvement in human tolerance to different types of exercise has been shown [13], [14] and [55].

Recently we have found that vitamin C supplementation very seriously decreases improvement in VO2 max and running capacity associated with training. In participants, the maximal rate of oxygen consumption increased 22% (p < 0.05) after 8 weeks of training. In the group that took vitamin C (1 g per day) the increase was 10% (nonsignificant). Untrained rats ran for 100 min (until exhaustion) and after 6 weeks of training they ran for 300 min. But the group of rats treated with vitamin C, after the same training period, ran for 120 min only. The research for a molecular explanation for this phenomenon is under way in our laboratory.[/quote]

31

[quote]Concluding remarks

These findings clearly indicate that ROS generated during exercise act as signals to increase the production of enzymes relevant to the adaptation of muscle cells to exercise. Moreover, these findings lead us to reconsider the â??wisdomâ?? of taking antioxidant supplements during training. In all likelihood, antioxidant supplements should not be recommended before training as they interfere with muscle cell adaptation. Indeed, when rats were trained, the expression of antioxidant enzymes and of other enzymes relevant to cell function was increased. When antioxidants were given, these adaptations were, however, hampered [8] and [21]. On the other hand, antioxidants may be administered before competition, when exercise is likely to be exhaustive and result in the generation of ROS that overwhelm the defensive mechanisms (i.e., causing oxidative stress). A clear example of this protective effect was found in the case of cyclists taking part in the Tour de France: when given allopurinol, they had lower increases in the activity of creatine kinase and aspartate aminotransferase [20].

Thus physical exercise is a double-edged sword: when practiced strenuously it causes oxidative stress and cell damage; in this case antioxidants should be given. But when practiced in moderation, it increases the expression of antioxidant enzymes and thus should be considered an antioxidant.[/quote]

32

[quote]References

[1] D.E. Warburton, C.W. Nicol and S.S. Bredin, Health benefits of physical activity: the evidence, Can. Med. Assoc. J. 174 (2006), pp. 801â??809. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (168)

[2] R.B. Armstrong, R.W. Ogilvie and J.A. Schwane, Eccentric exercise-induced injury to rat skeletal muscle, J. Appl. Physiol. 54 (1983), pp. 80â??93. View Record in Scopus | Cited By in Scopus (268)

[3] M.J. Jackson, Muscle damage during exercise: possible role of free radicals and protective effect of vitamin E, Proc. Nutr. 46 (1987), pp. 77â??80. View Record in Scopus | Cited By in Scopus (11)

[4] J. Vina, M.C. Gomez-Cabrera, A. Lloret, R. Marquez, J.B. Minana, F.V. Pallardo and J. Sastre, Free radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants, IUBMB Life 50 (2000), pp. 271â??277. View Record in Scopus | Cited By in Scopus (48)

[5] B. Commoner, J. Townsend and G.E. Pake, Free radicals in biological materials, Nature 174 (1954), pp. 689â??691. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (80)

[6] A. Koren, M. Schara and M. Sentjurc, EPR measurements of free radicals during tetanic contractions of frog skeletal muscle, Period. Biol. 82 (1980), pp. 399â??401.

[7] K.J. Davies, A.T. Quintanilha, G.A. Brooks and L. Packer, Free radicals and tissue damage produced by exercise, Biochem. Biophys. Res. Commun. 107 (1982), pp. 1198â??1205. Abstract | View Record in Scopus | Cited By in Scopus (598)

[8] M.C. Gomez-Cabrera, C. Borras, F.V. Pallardo, J. Sastre, L.L. Ji and J. Vina, Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats, J. Physiol. 567 (2005), pp. 113â??120. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (47)

[9] Z. Radak, J. Pucsok, S. Mecseki, T. Csont and P. Ferdinandy, Muscle soreness-induced reduction in force generation is accompanied by increased nitric oxide content and DNA damage in human skeletal muscle, Free Radic. Biol. Med. 26 (1999), pp. 1059â??1063. Article | PDF (93 K) | View Record in Scopus | Cited By in Scopus (40)

[10] M.B. Reid, F.A. Khawli and M.R. Moody, Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle, J. Appl. Physiol. 75 (1993), pp. 1081â??1087. View Record in Scopus | Cited By in Scopus (100)

[11] J. Sastre, M. Asensi, E. Gasco, F.V. Pallardo, J.A. Ferrero, T. Furukawa and J. Vina, Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration, Am. J. Physiol. 263 (1992), pp. R992â??R995. View Record in Scopus | Cited By in Scopus (118)

[12] M.B. Reid, D.S. Stoik, S.M. Koch, F.A. Khawli and A.A. Lois, N-acetylcysteine inhibits muscle fatigue in humans, J. Clin. Invest. 94 (1994), pp. 2468â??2474. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (92)

[13] F.A. Khawli and M.B. Reid, N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro, J. Appl. Physiol. 77 (1994), pp. 317â??324. View Record in Scopus | Cited By in Scopus (65)

[14] Y. Matuszczak, M. Farid, J. Jones, S. Lansdowne, M.A. Smith, A.A. Taylor and M.B. Reid, Effects of N-acetylcysteine on glutathione oxidation and fatigue during handgrip exercise, Muscle Nerve 32 (2005), pp. 633â??638. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (17)

[15] B. Chance, H. Sies and A. Boveris, Hydroperoxide metabolism in mammalian organs, Physiol. Rev. 59 (1979), pp. 527â??605. View Record in Scopus | Cited By in Scopus (1993)

[16] M. Reid, K. Haak and K. Francheck, Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro, J. Appl. Physiol. 73 (1992), p. 1797. View Record in Scopus | Cited By in Scopus (204)

[17] Y. Hellsten, G. Ahlborg, M. Jensen-Urstad and B. Sjodin, Indication of in vivo xanthine oxidase activity in human skeletal muscle during exercise, Acta Physiol. Scand. 134 (1988), pp. 159â??160. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (16)

[18] D.M. Pattwell, A. McArdle, J.E. Morgan, T.A. Patridge and M.J. Jackson, Release of reactive oxygen and nitrogen species from contracting skeletal muscle cells, Free Radic. Biol. Med. 37 (2004), pp. 1064â??1072.

[19] C.M. Harris, S.A. Sanders and V. Massey, Role of the flavin midpoint potential and NAD binding in determining NAD versus oxygen reactivity of xanthine oxidoreductase, J. Biol. Chem. 274 (1999), pp. 4561â??4569. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (15)

[20] M.C. Gomez-Cabrera, F.V. Pallardo, J. Sastre, J. Vina and L. Garcia-del-Moral, Allopurinol and markers of muscle damage among participants in the Tour de France, JAMA 289 (2003), pp. 2503â??2504. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (13)

[21] M.C. Gomez-Cabrera, A. Martinez, G. Santangelo, F.V. Pallardo, J. Sastre and J. Vina, Oxidative stress in marathon runners: interest of antioxidant supplementation, Br. J. Nutr. 96 (Suppl. 1) (2006), pp. S31â??S33.

[22] Z. Radak, K. Asano, M. Inoue, T. Kizaki, S. Oh-Ishi, K. Suzuki, N. Taniguchi and H. Ohno, Superoxide dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise, J. Appl. Physiol. 79 (1995), pp. 129â??135. View Record in Scopus | Cited By in Scopus (64)

[23] J. Viña, A. Gimeno, J. Sastre, C. Desco, M. Asensi, F.V. Pallardo, A. Cuesta, J.A. Ferrero, L.S. Terada and J.E. Repine, Mechanism of free radical production in exhaustive exercise in humans and rats: role of xanthine oxidase and protection by allopurinol, IUBMB Life 49 (2000), pp. 539â??544. View Record in Scopus | Cited By in Scopus (48)

[24] J. Viña, Glutathione metabolism and physiological functions, CRC Press, Boca Raton, FL (1990).

[25] E.J. Calabrese and L.A. Baldwin, Hormesis: the doseâ??response revolution, Annu. Rev. Pharmacol. Toxicol. 43 (2003), pp. 175â??197. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (104)

[26] Z. Radak, H.Y. Chung and S. Goto, Exercise and hormesis: oxidative stress-related adaptation for successful aging, Biogerontology 6 (2005), pp. 71â??75. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (42)

[27] L.L. Ji, M.C. Gomez-Cabrera and J. Vina, Exercise and hormesis: activation of cellular antioxidant signaling pathway, Ann. N. Y. Acad. Sci. 1067 (2006), pp. 425â??435. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (50)

[28] F.H. Andrade, M.B. Reid and H. Westerblad, Contractile response of skeletal muscle to low peroxide concentrations: myofibrillar calcium sensitivity as a likely target for redox-modulation, FASEB J. 15 (2001), pp. 309â??311. View Record in Scopus | Cited By in Scopus (38)

[29] A. Salminen and V. Vihko, Lipid peroxidation in exercise myopathy, Exp. Mol. Pathol. 38 (1983), pp. 380â??388. Abstract | View Record in Scopus | Cited By in Scopus (30)

[30] J. Hollander, R. Fiebig, M. Gore, T. Ookawara, H. Ohno and L.L. Ji, Superoxide dismutase gene expression is activated by a single bout of exercise in rat skeletal muscle, Pflugers Arch. 442 (2001), pp. 426â??434. View Record in Scopus | Cited By in Scopus (56)

[31] P.A. Baeuerle and D. Baltimore, Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor, Cell 53 (1988), pp. 211â??217. Abstract | View Record in Scopus | Cited By in Scopus (379)

[32] M.H. Laughlin, T. Simpson, W.L. Sexton, O.R. Brown, J.K. Smith and R.J. Korthuis, Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training, J. Appl. Physiol. 68 (1990), pp. 2337â??2343. View Record in Scopus | Cited By in Scopus (85)

[33] J. Hollander, R. Fiebig, M. Gore, J. Bejma, T. Ookawara, H. Ohno and L.L. Ji, Superoxide dismutase gene expression in skeletal muscle: fiber-specific adaptation to endurance training, Am. J. Physiol. 277 (1999), pp. R856â??R862. View Record in Scopus | Cited By in Scopus (41)

[34] L.L. Ji, M.C. Gomez-Cabrera, N. Steinhafel and J. Vina, Acute exercise activates nuclear factor (NF)-kappaB signaling pathway in rat skeletal muscle, FASEB J. 18 (2004), pp. 1499â??1506. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (51)

[35] W.M. Jr Sams Jr., N.V. Carroll and P.L. Crantz, Effect of dimethylsulfoxide on isolated-innervated skeletal, smooth, and cardiac muscle, Proc. Soc. Exp. Biol. Med. 122 (1966), pp. 103â??107.

[36] F.H. Andrade, M.B. Reid, D.G. Allen and H. Westerblad, Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse, J. Physiol. 509 (Pt 2) (1998), pp. 565â??575. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (118)

[37] J.J. Abramson and G. Salama, Critical sulfhydryls regulate calcium release from sarcoplasmic reticulum, J. Bioenerg. Biomembr. 21 (1989), pp. 283â??294. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (79)

[38] J. Stuart, I.N. Pessah, T.G. Favero and J.J. Abramson, Photooxidation of skeletal muscle sarcoplasmic reticulum induces rapid calcium release, Arch. Biochem. Biophys. 292 (1992), pp. 512â??521. Abstract | View Record in Scopus | Cited By in Scopus (25)

[39] H. Xiong, E. Buck, J. Stuart, I.N. Pessah, G. Salama and J.J. Abramson, Rose bengal activates the Ca2+ release channel from skeletal muscle sarcoplasmic reticulum, Arch. Biochem. Biophys. 292 (1992), pp. 522â??528. Abstract | View Record in Scopus | Cited By in Scopus (27)

[40] J.L. Trimm, G. Salama and J.J. Abramson, Limited tryptic modification stimulates activation of Ca2+ release from isolated sarcoplasmic reticulum vesicles, J. Biol. Chem. 263 (1988), pp. 17443â??17451. View Record in Scopus | Cited By in Scopus (3)

[41] B. Brenner, Effect of Ca2+ on cross-bridge turnover kinetics in skinned single rabbit psoas fibers: implications for regulation of muscle contraction, Proc. Natl. Acad. Sci. USA 85 (1988), pp. 3265â??3269. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (241)

[42] J.M. Metzger and R.L. Moss, Myosin light chain 2 modulates calcium-sensitive cross-bridge transitions in vertebrate skeletal muscle, Biophys. J. 63 (1992), pp. 460â??468. Abstract | PDF (1557 K) | View Record in Scopus | Cited By in Scopus (37)

[43] J.N. Hathcock, A. Azzi, J. Blumberg, T. Bray, A. Dickinson, B. Frei, I. Jialal, C.S. Johnston, F.J. Kelly, K. Kraemer, L. Packer, S. Parthasarathy, H. Sies and M.G. Traber, Vitamins E and C are safe across a broad range of intakes, Am. J. Clin. Nutr. 81 (2005), pp. 736â??745. View Record in Scopus | Cited By in Scopus (64)

[44] D.P. Vivekananthan, M.S. Penn, S.K. Sapp, A. Hsu and E.J. Topol, Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials, Lancet 361 (2003), pp. 2017â??2023. Article | PDF (104 K) | View Record in Scopus | Cited By in Scopus (337)

[45] E. Lonn, J. Bosch, S. Yusuf, P. Sheridan, J. Pogue, J.M. Arnold, C. Ross, A. Arnold, P. Sleight, J. Probstfield and G.R. Dagenais, Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial, JAMA 293 (2005), pp. 1338â??1347. View Record in Scopus | Cited By in Scopus (291)

[46] G. Bjelakovic, D. Nikolova, R.G. Simonetti and C. Gluud, Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis, Lancet 364 (2004), pp. 1219â??1228. Article | PDF (211 K) | View Record in Scopus | Cited By in Scopus (166)

[47] I.M. Sharman, M.G. Down and R.N. Sen, The effects of vitamin E and training on physiological function and athletic performance in adolescent swimmers, Br. J. Nutr. 26 (1971), pp. 265â??276. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (13)

[48] P.S. Brady, L.J. Brady and D.E. Ullrey, Selenium, vitamin E and the response to swimming stress in the rat, J. Nutr. 109 (1979), pp. 1103â??1109. View Record in Scopus | Cited By in Scopus (50)

[49] C. Malm, M. Svensson, B. Ekblom and B. Sjodin, Effects of ubiquinone-10 supplementation and high intensity training on physical performance in humans, Acta Physiol. Scand. 161 (1997), pp. 379â??384. View Record in Scopus | Cited By in Scopus (18)

[50] C. Malm, M. Svensson, B. Sjoberg, B. Ekblom and B. Sjodin, Supplementation with ubiquinone-10 causes cellular damage during intense exercise, Acta Physiol. Scand. 157 (1996), pp. 511â??512. View Record in Scopus | Cited By in Scopus (19)

[51] A.N. Nielsen, M. Mizuno, A. Ratkevicius, T. Mohr, M. Rohde, S.A. Mortensen and B. Quistorff, No effect of antioxidant supplementation in triathletes on maximal oxygen uptake, 31P-NMRS detected muscle energy metabolism and muscle fatigue, Int. J. Sports Med. 20 (1999), pp. 154â??158. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (19)

[52] J.S. Coombes, S.K. Powers, B. Rowell, K.L. Hamilton, S.L. Dodd, R.A. Shanely, C.K. Sen and L. Packer, Effects of vitamin E and alpha-lipoic acid on skeletal muscle contractile properties, J. Appl. Physiol. 90 (2001), pp. 1424â??1430. View Record in Scopus | Cited By in Scopus (21)

[53] R.J. Marshall, K.C. Scott, R.C. Hill, D.D. Lewis, D. Sundstrom, G.L. Jones and J. Harper, Supplemental vitamin C appears to slow racing greyhounds, J. Nutr. 132 (2002), pp. 1616Sâ??1621S.

[54] G.L. Close, T. Ashton, T. Cable, D. Doran, C. Holloway, F. McArdle and D.P. MacLaren, Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process, Br. J. Nutr. 95 (2006), pp. 976â??981. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (11)

[55] I. Medved, M.J. Brown, A.R. Bjorksten, K.T. Murphy, A.C. Petersen, S. Sostaric, X. Gong and M.J. McKenna, N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals, J. Appl. Physiol. 97 (2004), pp. 1477â??1485. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (23)[/quote]

33

way too many words. Can’t someone just make this into an article? Shorten it up a little, add some boobs here, and a thong there.

34

Basically, it all comes down to the same thing every time.

We’re going to die, but exercise, eat your fruits, veggies, and healthy meats and cross your fingers.

35

I guess you missed my point, likely due to the length of the piece. The above article is contrary to the norm, not the “same thing every time.” It goes against the normal position of supplementing with antioxidants.

In fact, the only supplementation with antioxidants that has reported beneficial effects is the use of a cysteine donor (NAC) to increase endogenous glutathione synthesis. In these studies an improvement in human tolerance to different types of exercise has been shown [13], [14] and [55]

Besides NAC for endurance performance Off-Campus Authentication @ Fresno State Library , antioxidants have continuously shown negative effects on exercise performance and other markers of health.

36

[quote]ucallthatbass wrote:
way too many words. Can’t someone just make this into an article? Shorten it up a little, add some boobs here, and a thong there.[/quote]

I’ll second that

37

[quote]BulletproofTiger wrote:
I guess you missed my point, likely due to the length of the piece. The above article is contrary to the norm, not the “same thing every time.” It goes against the normal position of supplementing with antioxidants. [/quote]

That’s what I’m saying-in the end the only thing known to work, every time, is exercise with a diet of fruit, veggies, and healthy meats, and crossing your fingers.

38

Interesting studies BT. Have you seen this?

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12064344&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

“The overall effect of the 10-week period without dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood proteins, and plasma lipids, concomitantly with marked changes in antioxidative defence.”

Read that again - counterintuitive to say the least. They also found that green tea extract didn’t do squat.

I’m beginning to suspect that even the antioxidants in fruits and vegs aren’t all they’re cracked up to be. Although some f&v are undoubtedly good sources of certain other micronutrients (potassium etc).

I’ll see if I can dig up some more, I remember seeing some other studies that put antioxidants in a rather negative light.

39

On flavonoids:

“We conclude that the large increase in plasma total antioxidant capacity observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, but is likely the consequence of increased uric acid levels.”

A propos uric acid:

“Prospective data suggest that consumption of sugar sweetened soft drinks and fructose is strongly associated with an increased risk of gout in men. Furthermore, fructose rich fruits and fruit juices may also increase the risk. Diet soft drinks were not associated with the risk of gout.”

Antioxidants and free radicals in worms:

"Unable to depend on glucose for energy, the long-lived worms ramped up the activity of cellular powerhouses known as mitochondria to fuel their bodies, Ristow said. That mitochondrial activity led to the increased production of reactive oxygen species, sometimes referred to as free radicals. In turn, the wormsâ?? defenses against â??oxidative stressâ?? increased, the researchers found.

Free radicals are usually considered harmful, Ristow said, and scientists have generally thought that exposure to them would shorten life span. The new findings suggest that, at least in some cases, the opposite may be true.

Indeed, even when the researchers returned the worms to their normal environment, allowing them to again use glucose for energy, the wormsâ?? increased defenses and longevity persisted, Ristow said. In contrast, treatment with antioxidant vitamins prevented the oxidative stress and the defenses against it, eliminating the life-boosting effects. Ristow called the result â??scaryâ?? because it means that, rather than being protective, antioxidant pills may actually leave the body more vulnerable by thwarting those natural defenses."

Discussion on a blog called “Plant Poisons and Rotten Stuff”, caveat lector and all that…

http://blog.plantpoisonsandrottenstuff.info/2007/09/25/studies-force-new-view-on-biology-of-flavonoids/

40

The problem is people still, to this day, look for a FOUNTAIN OF YOUTH.

These days it’s antioxidants. Years from now it maybe some other phyto flava bla bla bullshit.