By Layne Norton, Ph.D

“He who does not see things in their depth should not call himself a radical.”
—Jose Marti

While Jose Marti was likely speaking of radicals in a political sense, the radicals that interest me are more on a cellular level. I am talking about free radicals, or reactive oxygen species (ROS). ROS, when increased beyond normal levels, can cause havoc by damaging cellular structures and even increasing cell death! ROS have been implicated in numerous pathologies including heart disease, type II diabetes, some cancers, and even erectile dysfunction!^1-4 In cases such as type II diabetes, antioxidants can reduce pathologies associated with the disease and even improve insulin sensitivity.⁵ Now I know what you are thinking, “That’s great Layne, but I’m reading MD because I want to get HUGE! Not because I want longevity advice! Besides, antioxidants are ‘girly’ supplements anyway. I am saving my money for the next big, overhyped, super supplement!” Well don’t get too frustrated with me, I am going to bring this all full circle and show you why antioxidant supplementation is not just for health freaks, but for muscle freaks as well.

While ROS can contribute to several different pathologies, there is also evidence that they may put the brakes on muscle growth if they are not properly controlled. In conditions of muscle wasting such as cancer, sarcopenia with aging, and type II diabetes, ROS may be a crucial player in the loss of muscle during the progression of these conditions.^5-7 Furthermore, ROS may contribute to the reduced anabolic response to a meal in the elderly!

Interestingly, a recent study by Marzani et al. demonstrated that the defective anabolic response to a meal could be restored in the elderly by supplementing with an antioxidant mixture containing rutin, vitamin E, vitamin A, zinc, and selenium.⁸ This suggests that muscle wasting could possibly be prevented during various pathologies simply by supplementing with antioxidants and consuming adequate protein and carbohydrate to maximize protein synthesis! At this point, I’m sure you are wondering what this has to do with you, the meathead. “I am not worried about preventing muscle wasting… I am worried about getting HUGE!” Well I am going to explain exactly why this is important for you.

We all know that resistance training increases muscle mass and strength over time when combined with a proper nutrition program. We also know that exercise in the short term is catabolic and actually decreases muscle anabolism. In order to properly recover from a workout, we must consume sufficient protein and carbohydrates to increase protein synthesis, restore muscle glycogen, and fully recover from the workout. Optimally we do this as quickly as possible in order to transition ourselves from a catabolic state into an anabolic state.

ROS concentrations increase in skeletal muscle during exercise and may contribute to the acute reduction in muscle anabolism in response to a workout. In fact, ROS have been shown to inhibit mTOR signaling, which is crucial for initiating muscle protein synthesis.^9,10 Furthermore, ROS have been shown to impair insulin signaling, which may further reduce anabolism and decrease insulin sensitivity in skeletal muscle. Interestingly, research has demonstrated that supplementing with antioxidants like alpha-lipoic acid (ALA) may restore defective insulin signaling and may enhance insulin sensitivity in skeletal muscle by reducing ROS concentrations.⁵

In a case study performed by Eric Satterwhite and myself in 2003, it was demonstrated that supplementing with 300 mg of lipoic acid could reduce post-meal blood glucose concentrations by approximately 30-40 percent, presumably through increased glucose uptake into skeletal muscle.¹¹ So supplementing with an antioxidant may not only help maximize mTOR signaling and restore muscle protein synthesis after a workout, it may also help enhance glucose uptake into muscle cells after a workout by increasing insulin sensitivity in skeletal muscle. One could also speculate that by increasing glucose uptake into muscle tissue, it is possible that less glucose will be available for update by fat tissue! To recap, antioxidants may help optimize protein synthesis, enhance insulin sensitivity, and increase glucose uptake into muscle tissue. These are all very good things in terms of recovery and limiting fat gain!

Now how exactly should this be put into practice? As of now there is little direct information on optimal dosages and timing of antioxidant supplementation in regard to exercise. To maximize recovery, I suggest that people consume a shake/meal containing sufficient protein and carbohydrate to maximize protein synthesis and restore muscle glycogen along with an antioxidant complex. The exact amounts of protein and carbohydrate to achieve this outcome is likely different for everyone, depending upon various factors, but in general, a meal containing 40-50 grams of protein and 50-100 grams of carbohydrate should achieve these outcomes.

I would suggest consuming an antioxidant complex with this meal composed of lipoic acid, selenium, vitamin A, zinc, and vitamin E. It may be easier to simply consume your multivitamin post-workout and add a small amount of ALA (100-300 mg) to it. Now before some of you meatheads go crazy and start taking five multivitamins and 10,000 mg of ALA with your post-workout, please remember that more is not better— better is better! This holds true particularly in the case of antioxidants. In fact, if your dosage of antioxidants is too high, it can actually have the opposite effect and they will act as pro-oxidants! So make sure you use a low/moderate dose of antioxidants.

Antioxidants may not seem as ‘sexy’ as many of the supplements out there like the next great super creatine, testosterone booster, or other ridiculously hyped-up supplement, but as often happens in the supplement industry, the most solid supplements may have the least hype surrounding them. Clearly, antioxidants are a supplement category that should warrant consideration in any serious bodybuilder’s supplement arsenal!

References:

1. Eleuteri E, Magno F, Gnemmi I, Carbone M, Colombo M, La Rocca G, Anzalone R, Genta FT, Zummo G, Di Stefano A, Giannuzzi P. Role of oxidative and nitrosative stress biomarkers in chronic heart failure. Front Biosci, 2009 Jan 1;14:2230-7.

2. Wei Y, Chen K, Whaley-Connell AT, Stump CS, Ibdah JA, Sowers JR. Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Am J Physiol Regul Integr Comp Physiol, 2008 Mar;294(3):R673-80.

3. Hitchler MJ, Domann FE. Metabolic defects provide a spark for the epigenetic switch in cancer. Free Radic Biol Med, 2009 Apr 10. [Epub ahead of print]

4. Jones RW, Rees RW, Minhas S, Ralph D, Persad RA, Jeremy JY. Oxygen free radicals and the penis. Expert Opin Pharmacother, 2002 Jul;3(7):889-97.

5. Maddux BA, See W, Lawrence JC Jr, Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes, 2001 Feb;50(2):404-10.

6. Huang JH, Hood DA. Age-associated mitochondrial dysfunction in skeletal muscle: Contributing factors and suggestions for long-term interventions. IUBMB Life, 2009 Mar;61(3):201-14.

7. Laviano A, Meguid MM, Preziosa I, Rossi Fanelli F. Oxidative stress and wasting in cancer. Curr Opin Clin Nutr Metab Care, 2007 Jul;10(4):449-56.

8. Marzani B, Balage M, Vénien A, Astruc T, Papet I, Dardevet D, Mosoni L. Antioxidant supplementation restores defective leucine stimulation of protein synthesis in skeletal muscle from old rats. J Nutr, 2008 Nov;138(11):2205-11.

9. Frost RA, Lang CH. Regulation of muscle growth by pathogen-associated molecules. J Anim Sci, 2008 Apr;86(14 Suppl):E84-93.

10.Viganò A, Ripamonti M, De Palma S, Capitanio D, Vasso M, Wait R, Lundby C, Cerretelli P, Gelfi C. Proteins modulation in human skeletal muscle in the early phase of adaptation to hypobaric hypoxia. Proteomics, 2008 Nov;8(22):4668-79.

11. Norton LE, Satterwhite E. The Lipoic Acid Project, http://www.bodybuilding.com/fun/layne25.htm