Bodybuilders & Antioxidants

The Pros & Cons of Their Use

Are Antioxidants Radical?

Intense weight training results in production of reactive byproducts of metabolism that can be harmful to muscle cells. These byproducts are called free radicals and they are very reactive with tissues— causing oxidative damage to proteins, lipid cell membranes and DNA. Studies also link exercise-induced free radical production to muscular fatigue during prolonged exercise.¹ Knowing that exercised skeletal muscle produces free radicals motivates bodybuilders to seek antioxidant supplements in desire of preventing exercise-induced muscle damage and delay the onset of fatigue.

However, there is a highly debated topic here. Free radicals may be very important in acting as signaling molecules for promoting adaptations to exercise.² This suggests that using antioxidant supplements may be detrimental to the muscle-building athlete. A study in Stem Cells in 2010 by Li and Marban showed that physiological levels of reactive oxygen species are required to activate DNA repair pathways for maintaining genomic stability in stem cells.³ Additionally, these radicals are required for vasodilation, optimizing muscle contraction and initiation of cellular regeneration.⁴ With intense training over time, muscle adapts to oxidative stress by becoming more resistant to subsequent bouts of oxidative stress. However, there is a fine balance where low doses of oxidative stress can be beneficial and higher doses toxic.^4,5 You as a bodybuilder should be able to relate to this, as this parallels many principles in bodybuilding. For instance, high-intensity training is excellent for increasing testosterone levels and muscle growth. Doing too much training, however, leads to a drop in testosterone, elevation of cortisol, and other sequelae of overtraining.

N-acetylcysteine (NAC) is a supplement used for its antioxidant properties. NAC supports cellular resynthesis of a major antioxidant in skeletal muscle called glutathione. Glutathione is a buffer of free radicals produced during strenuous exercise. By supporting production of glutathione, NAC limits the rise of free radical activity in exercising muscle and delays fatigue. This was initially demonstrated in animal models of fatigue. More importantly, human studies have demonstrated high-dose (150 milligrams/kilogram) infusions may improve cycle performance in trained athletes.⁶ Unfortunately, oral intake of NAC to obtain similar plasma levels seen during infusion would be difficult and might lead to side effects such as nausea, bloating and diarrhea. To add insult to injury, Childs and colleagues found that combining the antioxidant vitamin C with NAC following an eccentric (negative) arm exercise increased oxidative stress and cell damage above and beyond that induced by the exercise alone⁷! When evaluating these articles, it is important to determine which scenario relates to you as a bodybuilder. In this situation, which relates to you: highly trained endurance cyclists who saw a slight but significant resistance to fatigue with NAC infusion OR eccentric arm training, inducing muscle injury and soreness potentially worsened by NAC ingestion?

The problem with all studies on antioxidants including vitamin C, vitamin E, polyphenols, NAC, CoQ10 and others is that they are of low quality and poorly randomized or controlled. Many factors may affect the benefit obtainable by supplementing with antioxidants. Timing of intake, level of training intensity, dietary factors, age, training experience, type of exercise and dosing can all affect the outcomes of these studies. Use of antioxidants must be thought of as performing a balancing act on a teeter-totter. The only problem is we can’t see how big the person is on the other side of the totter. One must think that antioxidant supplementation would be warranted when individuals are exposed to extraordinary levels of oxidative stress and struggle to meet their needs through a healthy diet. In bodybuilding, this may be during hard dieting for a show or after traumatic injury. Studies need to be done to show whether taking antioxidants before, after or remotely from training affects one’s influence on muscle healing.

NAC and EPO

N-acetylcysteine (NAC) is very well known for its antioxidant properties and as a major precursor to glutathione. As an anti“OXIDANT,” it is safe to assume that there may be a correlation to the function of this compound in relation to the oxygenation status and oxygen consumption by the body. Another substance that intimately corresponds to whole-body oxygenation is erythropoietin (EPO).

EPO is a protein produced predominantly in the kidneys and is increased during times of tissue hypoxia (low oxygen environment). When oxygen is low, the kidneys produce EPO— which stimulates the production of red blood cells (RBCs). With more circulating RBCs (increased hematocrit), the oxygen-carrying capacity of the blood is increased. This is the reason why endurance athletes, like those in the Tour de France, abuse this in the form of human recombinant EPO.

It is also well known amongst elite endurance athletes that a hypoxic environment, such as high altitude or low oxygen chambers, stimulates EPO production and thus, a rise in hematocrit. Interestingly, in a study where healthy well-trained athletes where given 1,200 milligrams of NAC for eight days, both glutathione and EPO concentrations increased.¹² NAC does this by stabilizing a hypoxia-inducible factor (HIF), which is responsible for activating EPO gene transcription (increased EPO protein production).

In fact, a recent study by Momeni et al. in Brussels, Belgium published in the European Journal of Applied Physiology last November demonstrated that NAC could cause a rise in EPO production even in a hyperoxic (high oxygen) environment.¹³ This study only administered one dose of 600 milligrams NAC and researchers were able to show a 20 to 30 percent rise in EPO over the course of 48 hours post-ingestion. Of note, this single dosing regimen did not cause a rise in RBC production as measured two weeks after the trial. As opposed to this, the eight-day, 1,200-milligram trial of NAC significantly elevated the level of glutathione (+33%), EPO (+26%) and hematocrit (+9%). Could this be a way for bodybuilders to increase blood volume for pre-contest vascularity?

Whey, Casein or Soy Protein Post-Workout?

Bodybuilders know the importance of a high-protein diet. The timing of the intake of these proteins that will be digested and absorbed into the bloodstream can be critical to the stimulation of post-exercise muscle protein synthesis. A number of studies have shown that adding the branched-chain amino acid leucine enhances muscle protein synthesis by substrate and signaling pathways. Furthermore, adding carbohydrate for a greater insulinotropic effect can further enhance this muscle anabolism. A study done by Pennings et al. published in the American Journal of Clinical Nutrition in May 2011 demonstrated that amino acid levels rose in circulation faster with a 20-gram whey protein meal versus a 20-gram casein meal.⁸ Micellar casein clumps together in the stomach, making large globules that empty from the stomach slowly— thus explaining the delayed absorption of amino acids. In addition, the results also showed a strong positive correlation to peak plasma leucine concentrations and muscle protein accretion.

So it would seem from the above information that the more rapid absorption of whey protein would make it more ideal than casein as an enhancer of post-workout muscle protein synthesis. A study at the Institute of Sports Medicine Copenhagen confirmed that assumption.⁹ Using radioactively labeled leucine in whey and casein, researchers were able to demonstrate that ingestion after heavy resistance training resulted in a similar muscle protein synthesis response over the course of a six-hour recovery period. They also observed that there was a trend toward a higher but temporally shorter response from whey ingestion versus casein, as expected from whey’s more rapid absorption.

So how does plant-derived soy protein stack up to milk-derived proteins of whey and casein? Stuart Phillips and colleagues at McMaster University in Ontario, Canada did a study to address that very question.¹⁰ In their study, they analyzed the incorporation of radioactively labeled amino acids in a single leg that was subjected to resistance and followed by ingesting a 10-gram protein drink containing whey hydrolysate, micellar casein or soy protein isolate. Whey protein was able to reach higher levels of blood essential amino acids, BCAAs (branched-chain amino acids) and perhaps more importantly, leucine, than either casein or soy. Muscle protein synthesis in the rested leg was higher with ingestion of faster absorbed proteins: whey > soy > casein. After exercise, this response was even greater in difference, with whey producing ~120 percent greater than casein and 30 percent greater than soy. Overall, whey protein was more anabolic at rest and after exercise, compared with still rapidly absorbed soy and slowly absorbed casein.

A confounding variable in this concept of rapid versus slowly absorbed protein is that whey and casein have different amounts of various essential and branched-chain amino acids. Dr. Phillips and colleagues took this into consideration and performed a study published in September 2007 in the American Journal of Clinical Nutrition.¹¹ To control for the difference in amino acid content, they used whey protein and manipulated its absorption by either giving a bolus of 25 grams or giving 10 2.5-gram drinks every 20 minutes after resistance exercise. The results were fairly consistent with what was previously suggested— rapid absorption is more effective in stimulating muscle protein synthesis than slow, pulsed absorption. In fact, the bolus of whey protein was more than two times as effective as the pulse dosing over the initial three hours, compared with the pulses of whey. The researchers concluded that rapid rises in blood amino acids in the early post-exercise interval enhanced muscle anabolism greater than small pulses of the same protein, mimicking slowly digested proteins. So, get your protein in after your workout and DO IT FAST!

Victor R. Prisk, MD is an Assistant Professor at University of Pittsburgh Medical Center and a member of the GNC Medical Advisory Board.

References:

1. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 2008;88:1243-76.

2. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 200;279(6):L1005-28.

3. Li T-S, Marban E. Physiological levels of reactive oxygen species are required to maintain genomic stability in stem cells. Stem Cells 2010; 28(7):1178-85.

4. Peternelji T-T, Coombes JS. Antioxidant supplementation during exercise training. Beneficial or detrimental? Sports Med 2011;41(12) 1043-69.

5. Radak Z, et al. Exercise, oxidative stress and hormesis. Aeging Res Rev 2008; Jan 7(1):34-42.

6. Medved, et al. N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance trained individuals. J App Physiol 2004;97:1477-85.

7. Childs A, et al. Supplementation with Vitamin C and NAC increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radic Biol Med 2001;31(6):745-53.

8. Pennings B, et al. Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. Am J Clin Nutr 2011; May;93(5):997-1005.

9. Reitelseder S, et al. Whey and casein labeled with L-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion. Am J Physiol Endocrinol Metab 2011; Jan;300(1):E231-42.

10. Tang JE, et al. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 2009; Sep;107(3):987-92.

11. West DW, et al. Rapid aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise. Am J Clin Nutr 2011; Sep;94(3):795-803.

12. Zembron-Lacny A, et al. The comparison of antioxidant and hematological properties of N-acetylcysteine and alpha-lipoic acid in physically active males. Physiol Res 2009;58(6):855-61.

13. Momeni M, et al. Effect of N-acetyl-cysteine and hyperoxia on erythropoietin production. Eur J Appl Physiol 2011; Nov;111(11):2681-6.