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Posted in: Articles by ProSource, Supplement Articles, Antioxidants
By Anna Lepeley, PhD, CSCS, CISSN | Nov 15, 2013



Guard Against Free Radical Damage
With Powerful Antioxidant Resveratrol



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Optimizing the human body's antioxidant capacity is vital to protecting the integrity of our cells, resulting in enhanced immune system defenses, protection against illness and the cascade of physical and cognitive impairments that can result from high levels of physical stress.

High-intensity athletes are especially vulnerable to oxidative stress because free radicals (or reactive oxygen species) increase significantly after exercise, to the point where they may compromise immune response (thus leading to sickness and consequent missed workouts) and may also play a role in the development of muscle soreness and damage.

Let's take a look at how oxidative stress may be undermining your physique and performance, and then investigate a particularly promising means for combating this counterproductive physiological process.

Oxidative Stress and the High-Performance Athlete
Oxidative stress is induced by reactive oxygen species (ROS), posing threat of damage to cells.1 ROS production is stimulated by an array of environmental causes (i.e. air pollutants)2, psychological stress3, and exercise-induced activity within the mitochondria (reactive molecules produced from aerobic metabolism). Exercise-induced ROS activity within the mitochondria results in cellular damage much like that of ROS activity from environmental causes.4 Furthermore, inflammatory responses (resultant of aerobic and anaerobic exercise/activity) stimulate ROS production.5 The severity of oxidative damage is dictated by factors such as exercise intensity, exercise duration, training state and exercise protocol.6,7 Research has found free radical-induced muscle damage to be a contributing factor to muscle fatigue, impairing cell function and, subsequently, impeding the span of exercise duration and muscle recovery.7

If ROS production/oxidative stress supersedes the antioxidant defense system, oxidative damage will occur. Chronic oxidative stress and excessive ROS production can result in cell death, which underlies an increased risk for negative physiological outcomes.8-10

Glutathione (GSH), a thiol-containing tri-peptide abundantly present in almost all plant and animal cells, plays an essential role in scavenging free radials and inhibiting lipid peroxidation, maintaining tissue antioxidant defenses and regulation of immune responses. A primary combatant of ROS, GSH is involved with the detoxification of hydrogen and organic peroxides (i.e. lipid peroxide), resulting in increased levels of oxidized glutathione (GSSG).11 When oxidative stress is prominent, intracellular GSSG accumulates which, when in excessive concentrations and exceeding the rate of GSH formation, can present a threat of toxicity to cells.12 Thus, the ratio of GSH to GSSG is a key indicator in cellular health, representing the antioxidant status of the body.

The importance of enhancing antioxidant capacity, in both athletic and non-athletic populations, dictates various precursors to overall health. Supplements that increase glutathione levels may benefit antioxidant protection, providing less experienced oxidative damage from daily encounters with oxidative stress that can suppress the immune system. Athletic populations, in particular, benefit greatly from increasing their antioxidant capacity, significantly impacting exercise performance and recovery.

Resveratrol and Antioxidant Capacity
Found in the skin of red grapes, wine and other plant sources, resveratrol is a natural polyphenolic compound with a wide range of biological activities. Known as a phytoalexin with long history of use in China and Japan, resveratrol is synthesized by plants as a defense mechanism in the presence of fungal, bacterial or injurious threats.13-15 Research suggests that the antioxidant capacity of resveratrol induces the expression of multiple antioxidant enzymes.16 Research has observed resveratrol significantly increasing GSH levels of [human] red blood cells exposed to oxidative stress, providing noteworthy antioxidant protection. The protective benefits of resveratrol have been observed in a dose/concentration-dependent manner.17,18

Kode et al. (2008)19 examined the antioxidant benefit of resveratrol against oxidative stress and GSH depletion. The results demonstrated restoration of GSH levels via activation of nuclear erythroid-related factor (Nrf2), an essential protein and transcription factor responsible for activating genes within the antioxidant response element (ARE) that provides protection against ROS.20 Genes driven by Nrf2 play a vital role in promoting adequate levels of glutathione while decreasing levels of ROS.21

Resveratrol, Testosterone and Virility
Oxidative stress (i.e. environmental toxins) can inhibit spermatogenesis, possibly resulting in male infertility. The benefits of resveratrol have been attributed to its anti-estrogenic activity.22 Daily resveratrol intake has shown to significantly increase male testosterone and gonadotropin levels. In addition, long-term resveratrol intake has also been associated with the restoration and promotion of sperm production via stimulation of the pituitary-gonadal axis and c-kit protein expression levels.23,24

Shin et al. (2008)25 observed substantial increases in testosterone concentration, sperm count and sperm motility in male rats consuming an oral dose of resveratrol for 28 days. The researchers suggest that the benefits of resveratrol enhance male reproductive function by optimizing testosterone levels, testicular sperm production and penile erection.


Body Compositional Effects of Resveratrol
High body fat is strongly correlated with oxidative stress, with an increased production of ROS in adipose tissue. Accumulation of body fat also increases the risk for an array of impedances on health. Studies have demonstrated significant effects of resveratrol on fat mobilization, decreasing adipocyte adipogenesis while promoting lipolysis.26,17 Animal models have shown that long-term, daily resveratrol consumption may increase basal metabolic rate and total daily energy expenditure.27-29 The results of these studies suggest a thermogenic effect of resveratrol that may support weight loss.

Resveratrol has been examined in research for its vasodilatory effects, improving the dynamic of blood flow. Resveratrol has demonstrated a positive effect on nitric oxide (NO) by directly inhibiting vascular NADH/NADPH oxidase (a multi-component enzyme associated with cardiovascular pathologies), resulting in decreased generation of superoxide radical. Decreasing superoxide radical production is conducive to NO synthesis, promoting vasodilation.

Research also supports the insulin-potentiating effects of resveratrol. Brasnyó et al. (2011)30 assigned type 2 diabetics to four weeks of daily resveratrol intake versus a placebo. The results showed a significant decrease in insulin resistance for patients taking resveratrol. The researchers suggest that the antioxidant properties of resveratrol may have increased the efficiency of insulin signaling via the Akt pathway, improving insulin sensitivity. Furthermore, additional research observing increased insulin sensitivity with resveratrol has also observed an associated increase in Nrf2 activation, further supporting the antioxidant association with its insulin-potentiating benefits.31
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Resveratrol intake, combined with consistent exercise, may promote mitochondrial biogenesis. This is of particular importance to aging populations. Aging is associated with decreases in general cellular activity and skeletal muscle mitochondrial volume. The loss of muscle mass and strength in older popular populations may be attributed to decreases in mitochondria.32 Decreases in mitochondria may also increase oxidative damage and disruptions in cellular dynamics.33 Thus, resveratrol may be of great benefit to older populations and populations of all ages who participate in regular exercise, improving exercise capacity, quality of life and overall health.

The benefits of the antioxidant activity of resveratrol may also extend to bone health. Resveratrol has shown to increase bone mineral density, enhancing the integrity and strength of bones while preventing bone loss. Thus, resveratrol may be of even greater benefit to individuals susceptible to osteoporosis (i.e. post-menopausal women).34,35

Resveratrol has also demonstrated significant anti-inflammatory effects by inhibiting inflammatory genes, nitric oxide synthase (NOS)-2 and cyclooxygenase (COX)-2, while decreasing prostaglandin production.36 Thus, resveratrol may provide protection from systemic inflammation.

Combat Oxidative Tress with ProSource Resveratrol
ProSource has developed a high potency extract of resveratrol, combining pure red wine extract with Japanese knotwood root, two rich, natural sources. ProSource's formulation of resveratrol provides a top-quality antioxidant-boosting supplement that will provide an array of benefits to your workouts (e.g. enhancing performance gains, hastening recovery and improving body composition) and your immune defenses. The anti-aging properties of resveratrol, accompanied by its testosterone-boosting effects, are vital to improving overall quality of life. The testosterone-boosting and estrogen-suppressing effects of resveratrol complement its antioxidant contributions, maximizing muscle hypertrophy, male virility and overall well-being.

ProSource's Resveratrol will help support the optimization of your body's antioxidant capacity to combat inevitable encounters with oxidative stress. Resveratrol in your supplement regimen allows you to train hard in the gym without the anticipated sick-days and excessive muscle soreness. Boost your immune defenses, muscle recovery and exercise performance with ProSource's Resveratrol.

Do you take an antioxidant supplement of any sort? How is it impacting your overall health and well-being? Let us know in the comments field below!

REFERENCES

1. Niess AM, Dickhuth HH, Northoff H, Fehrenbach E. (1999). Free radicals and oxidative stress in exercise-immunological aspects. Exerc Immunol Rev 5:22-56.

2. Oh SM, Kim HR, Park YJ, Lee SY, Chung KH. (2011). Organic extracts of urban air pollution particulate matter (PM2.5)-induced genotoxicity and oxidative stress in human lung bronchial epithelial cells (BSEAS-2B cells). Mutat Res. 723(2):142-51.

3. Bouayed J, Rammal H, Soulimani R. (2009). Oxidative stress and anxiety. Oxid Med Cell Longev. 2(2):63-67. 


4. Ji LL. Antioxidants and oxidative stress in exercise. (1999). Proc Soc Exp Biol Med 222:283-292.

5. Miyazaki H, Oh-ishi S, Ookawara T, Kizaki T, Toshinai K, Ha S, Haga S, Ji LL, Ohno H. (2001). Strenuous endurance training in humans reduces oxidative stress following exhausting exercise. Eur J Appl Physiol 84:1-6.

6. Witt EH, Reznick AZ, Viguie CA, Starke-Reed P, Packer L. (1992). Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr 122(3 Suppl):766-73.

7. Venditti P, Di Meo S. (1997). Effect of training on antioxidant capacity, tissue damage and endurance of adult male rats. Int J Sports Med 18(7):497-502.

8. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. (2007). Free radicals and antioxidants in normal physiological functions and human disease). Int J Biochem Cell Biol. 39(1):44-84.

9. Aitken RJ, Roman SD. (2008). Antioxidant systems and oxidative stress in the testes. Oxidative Medicine and Cellular Longevity. 1:15-24.
10. Kuznetsov AV, Kehrer I, Kozlov AV, Haller M, Redl H, Hermann M, Grimm M, Troppmair J. (2011). Mitochondrial ROS production under cellular stress: comparison of different detection methods. Anal Bioanal Chem. 400(8):2383-90.

11. Owen JB and Butterfield DA. (2010). Measurement of oxidized/reduced glutathione ratio. Methods Mol Biol. 648:269-77.

12. Sen CK and Packer L. (2000). Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 72 (Suppl):653-69.

13. Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. (2002). Plant foods and herbal sources of resveratrol. J Agric Food Chem. 50(11):3337-40.

14. González-Lamothe R, Mitchell G, Gattuso M, Diarra MS, Malouin F, Bouarab K. (2009). Plant antimicrobial agents and their effects on plant and human pathogens. Int J Mol Sci.10(8):3400-3419.

15. Sadruddin S, Arora R. (2009). Resveratrol: biologic and therapeutic implications. Cardiometab Syndr. 4(2):102-6.

16. Halliwell B. (2007). Dietary polyphenols: good, bad, or indifferent for your health? Cardiovasc Res. 73(2):341-7.

17. Rayalam S, Della-Fera MA, Yang JY, Park HJ, Ambati S, Baile CA. (2007). Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J Nutr. 137(12):2668-73.

18. Pandey, KB, Rizvi SI. (2010). Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to vitro oxidative insult. Phytother Res. 24(1):11-4.

19. Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I. (2008). Resveratrol induces GSH synthesis by activation of Nrf2 and protects again cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 294(3):478-88.

20. Chen KL, Dodd G, Thomas S, Zhang X, Wasserman MA, Rovin BH, Kunsch C. (2006). Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression. Am J Physiol Heart Circ Physiol. 290:H1862-H1870.

21. Calkins MJ, Johnson DA, Townsend JA, Vargas MR, Dowell JA, Williamson TP, Kraft AD, Lee JM, Li Jiang, Johnson JA. (2009). The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative diseases. Antioxid Redox Signal. 11(3):497-508.

22. Turner RT, Evans GL, Zhang M, Maran A, Sibonga JD. (1999). Is resveratrol an estrogen agonist in growing rats? Endocrinology. 140(1):50-4.

23. Juan ME, González-Pons E, Munuera T, Ballester J, Rodríguez-Gil JE, Planas JM. Trans-Resveratrol, a natural antioxidant from grapes, increases sperm output in healthy rats. J Nutr. 135(4):757-60.

24. Jiang YG, Peng T, Luo Y, Li MC, Lin YH. (2008). Resveratrol reestablishes spermatogenesis after testicular injury in rats caused by 2, 5-hexanedione. Chin Med J (Engl). 121(13):1204-9.

25. Shin S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB. (2008). Trans-Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo. Arch Pharm Res. 31(1):83-7.

26. Baile CA, Yang JY, Rayalam S, Hartzell DL, Lai CY, Andersen C, Della-Fera MA. (2011). Effect of resveratrol on fat mobilization. Ann N Y Acad Sci. 1215:40-7.

27. Alberdi G, Rodríguez VM, Miranda J, Macarulla MT, Churruca I, Portillo MP. (2013). Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food Chem. 141(2):1530-5.

28. Dal-Pan A, Blanc S, Aujard F. (2010). Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol. 10:11.

29. Dal-Pan A, Terrien J, Pifferi F, Botalla R, Hardy I, Marchal J, Zahariev A, Chery I, Zizzari P, Perret M, Picq JL, Epelbaum J, Blanc S, Aujard F. (2011). Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus. Age (Dordr). 33:15–31.

30. Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann I. (2011). Resveratrol improves insulin sensitivity, reduces oxidate stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 106(3):383-9.

31. Bagul PK, Middela H, Matapally S, Padiya R, Bastia T, Madhusudana K, Reddy BR, Chakravarty S, Banerjee SK. (2012). Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats. Pharmacol Res. 66(3):260-8.

32. Menzies KJ, Singh K, Saleem A, Hood DA. (2013). Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis. J Biol Chem. 288(10):6968-79.

33. Peterson CM, Johannsen DL, Ravussin E. (2012). Skeletal muscle mitochondria and aging: a review. Journal of Aging Research. 2012:1-20.

34. Lin ZP, Li WX, Yu B, Huang J, Sun J, Huo JS, Liu CX. (2005). Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the overiectomized rat model. J Med Food. 8(1):14-9.

35. Lin Q, Huang Y, Xiao B, Ren G. (2005). Effects of resveratrol on bone mineral density in overectomized rats. Int J Biomed Sci. 1(1):76-81.

36. Leiro J, Alvarez E, Arranz JA, Laguna R, Uriarte E, Orallo F. (2004). Effects of cis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes. J Leukoc Biol. 75(6):1156-65.


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