Rethinking The Role Of Antioxydants in Sports

 by Charles Poliquin

This week’s guest blog article comes by way of John Meadows and his Mountain Dog Diet website. The website is known as one of the best in the bodybuilding world, and it’s easy to see why. When you join for less then 10 measly dollars you get to see the EXACT diets he has used with many of his top men and women competitors.

They are detailed and not something most coaches for allow others to see. The website also is loaded with brilliant articles such as the one his colleagues Bill Willis wrote that we are featuring this month. There is a Q & A where people can ask John and his team questions and they get answered on the site, as well as detailed descriptions of his insane but eloquently planned workouts. There are over 50 workouts on the site now.

Do yourself a favor and check it out.

Six Reasons to Avoid Taking Antioxidant Supplements 

By Bill Willis, PhD

On paper, at least, antioxidant supplements seem like a great idea. It has been known for quite some time that intense exercise increases the production of potentially toxic reactive oxygen species (ROS), which have been linked to aging and most chronic diseases, one way or another. If balls out training increases the production of damaging oxygen radicals than it makes perfect sense to limit oxidation as much as possible, right? This should limit muscle damage and decrease soreness, allowing us to train harder and recover faster. This was precisely the school of thought in the all-too recent dark ages of training science, when high doses of vitamin C were the state of the art in periworkout supplementation. Sore after training? Not recovering fast enough? Too much oxidation, bro. Take more antioxidants! Full disclosure from a guy who researches ROS for a living: I, too drank the Kool-aid, taking a couple grams of vitamin C before/after training for a period in the late 90’s. Fortunately, like most who experimented with high dose antioxidant supplementation, I ultimately stopped taking them; they just didn’t seem help with recovery or muscle soreness.

Thankfully in the present day, we know better. Although ROS levels increase during exercise, this is a good thing. Critical even, to get the most out of your training. Any attempt to decrease exercise-induced ROS production with antioxidant supplements is not only useless in terms increasing strength, performance, and recovery, but may be worse than useless(1), possibly canceling out much of your hard work in the gym. Want to get bigger, faster, and stronger to your maximum potential? ROS can be your best friend. Antioxidant supplements, more like your worst enemy.

Here are 6 good reasons to avoid them:

#1 Reduced ability to deal with metabolic stress

One of the major benefits of exercise (outside of the fact that it makes you jacked) is increased health and lifespan, made possible by increased protection from oxidative stress. Most, if not all chronic diseases are driven by inflammation and oxidation, which go hand and hand. The better our ability to overcome this type of metabolic stress, the more resilient we are to stress and disease. It may seem somewhat contradictory then that oxidative stress incurred during exercise actually increases our capacity to deal with future oxidative stress. In fact, we are hard-wired for this response, provided that we don’t screw it up with untimely antioxidant supplementation.

How exercise increases our ability to cope with metabolic stress:

Under non-stress conditions a transcription factor called NRF2 is sequestered in the cytosol by another protein called Keap1. When ROS levels increase, such as during a high volume Mountain Dog workout, Keap1 is degraded, releasing NRF2, which then moves into the nucleus. After entering the nucleus, NRF2 binds to and activates genes that have a special sequence called an “Antioxidant Response Element” (ARE) in their promoter. Think of this in terms of a lock and key; hundreds of stress-response genes in our DNA have a type of ‘lock’ that is opened by the same ‘key’, NRF2. In this way, NRF2 causes global activation of the antioxidant stress-response program, increasing the production of proteins important for defending against inflammation, oxidation, and metabolic stress (2-4). You can see an overview of how this works in the figure below:

While the increase in ROS production that occurs during training is stressful in and of itself, it is also a potent activator of this ARE/NRF2 stress-response pathway, which increases our capacity to deal with metabolic stress. Taking antioxidant supplements around training time quenches the ROS signal that activates this pathway, preventing the ROS signal from turning on this metabolic stress response program. It’s like taking weight off the bar and still expecting to grow.

Here’s the thing, the consequences of short-circuiting this pathway with antioxidants are not limited to increased health and longevity down the road. This oxidative stress response system is also needed to repair damage incurred during heavy training. Reduced ability to cope with metabolic stress results in less efficient recovery, limiting training progress in the long run.

#2 Antioxidants reduce the ability of exercise to increase insulin sensitivity

The lower your insulin levels are, the leaner you will tend to be. There are two ways to keep insulin levels consistently low. One is to limit carbohydrate intake. The other is to increase insulin sensitivity so that less insulin is needed to get the job done. This is where working out comes in; consistent, hard training plays a huge role in increasing insulin sensitivity. The effect this has on conditioning can’t be understated. Increased insulin sensitivity has a way transcending the amount of calories you take in or even macros; the more insulin sensitive you are the leaner, more anabolic you will be. Optimal insulin sensitivity also ensures that extra calories are used build new muscle tissue, rather than stored as bodyfat.

It was only recently discovered that exercise-induced increases in insulin sensitivity are driven by increased ROS production (5), and totally suppressed by antioxidant supplements. In a study in 2009 by Ristow et al, the effects of supplementation with vitamin C (500mg twice/day) and vitamin E (400IU/day) on changes in insulin sensitivity caused by exercise were investigated in both beginners and those with prior training experience. All subjects participated in a 5 day/week training program for 4 weeks consisting of both cardio and weight training. As expected, insulin sensitivity increased over the course of the training program in both beginners and those with more training experience. This also correlated with a large increase in the expression of a number of signaling proteins that promote insulin sensitivity. Importantly, those who took antioxidant supplements during this 4-week training period showed no increases in insulin sensitivity; the antioxidants completely eliminated this response. Keep in mind this happened at ‘normal’ supplement doses used every day, and the effect also occurred in both beginners and experienced subjects, ruling out any type of ‘beginner-effect’.

#3 Antioxidant supplements limit endurance and mitochondrial biogenesis

As the cellular powerplants that provide ATP to fuel intense muscular contractions and even life itself, mitochondria are pretty important. The more mitochondria we have, the greater our capacity to oxidize fuels for energy. As a result, endurance is largely a function of how many mitochondria we have, and how well they work.
It has been known for some-time that antioxidant supplements have subtle performance-suppressing effect on endurance exercise events. One study noted that giving greyhounds 1g of vitamin C before racing significantly slowed racing time relative to dogs that did not receive antioxidants (6). Another study in the 70’s noted that vitamin E supplementation (400IU/day for 6wks) reduced endurance performance in swimmers (7).

How, exactly, antioxidants may limit endurance came to light more recently, in a study by Gomez-Cabrera et al (8). The effects of antioxidant supplementation on endurance performance were evaluated in 14 men age 27-36 during an 8 week endurance training program. 5 of these men received a 1000mg daily dose of vitamin C, while the rest received a placebo. The investigators found that vitamin C significantly suppressed endurance capacity, which was linked to a reduction in proteins that activate mitochondrial biogenesis. The ROS dependence of mitochondrial biogenesis induced by endurance training was later confirmed in a study by Kang et al, where antioxidants severely limited mitochondrial biogenesis in response to exercise (9).

I can hear it now: Endurance performance?!? *Before I lose you here, the fact that antioxidants reduce mitochondrial biogenesis is not only a concern for cardio-bunnies. Two additional studies noted decreased performance with ubiquinone-10 supplementation (a fat-soluble antioxidant) in humans after a high-intensity training program (10, 11). In this case, both aerobic, and anaerobic performance were affected. As with endurance training, resistance training also activates mitochondrial biogenesis (12). This is not a coincidence, as most proteins are synthesized in the proximity of mitochondria (13). The more mitochondria we have, and the better they work, the better the cellular infrastructure for cranking out new proteins to GROW.

Take-home: Oxidative stress during exercise sends signals that increase mitochondrial number and efficiency to support the energy demands of exercise. Avoid antioxidant supplements to maximize mitochondrial adaptations to training. This is important for both endurance and (indirectly) strength and size.

#4 You might grow less?

In addition to limiting the indirect effects of mitochondria on muscle growth, a recent animal study suggests that antioxidant supplements may play a more active role in limiting muscle growth (14). In this study in rats, a ‘synergist ablation’ overload model was used, where the gastroc and soleus muscles on the right hindlimb were surgically removed, overloading and activating growth in the plantaris muscle. The opposite, left hindlimb of rats in this study did not receive the procedure, which served as an experimental control. Rats in this study were then treated with vitamin C at 500mg/kg orally once/day or a placebo for 14 days. Although both the placebo and vitamin C treated rats experienced some new growth in the plantaris muscle, the vitamin C group experienced around 11% less muscle growth! This also correlated with reduced protein synthesis and increased protein breakdown.

Importantly, the results of this particular study need to be interpreted with a great degree of caution. Rats received a daily dose of 500 mg/kg vitamin C, which is equivalent to around 50g vitamin C in a 100 kg man. This is a HUGE amount of vitamin C, not to mention that fact that vitamin C in doses this high could actually increase ROS production. The synergist ablation model used for muscle overload in this study also is very much a ‘sledge-hammer’ approach that can’t easily be extrapolated to weight training in humans. Taken alone, I wouldn’t make much of this study; the dose of vitamin C was too high and the model too out there, at least relative to weight training in humans. This study is consistent with the larger picture, however, that antioxidant supplements can throw a metabolic wrench in the cell signaling machinery that drives the adaptive response to exercise. Along those lines, it was also recently shown that ROS function as important signaling molecules for muscle hypertrophy in vitro, where it was found that IGF-1 induced hypertrophy of myotubes in culture is suppressed by antioxidants (15).

Taken together, the current body of research teaches us a very important lesson when it comes to ROS signaling and muscle growth; the acute increase in ROS induced by training is an intrinsic part of the exercise stimulus that turns on the switch for muscle growth/adaptation.

#5: Antioxidant supplements could delay recovery.

The fact that antioxidant supplementation could delay recovery was discovered pretty much by accident. We have known for some time that intense exercise generates increases ROS production and hard training is a well-known cause of delayed onset muscle soreness. Putting two and two together, it was once believed that most, if not all muscle soreness was caused by oxidative damage. This also suggested that by limiting oxidative stress, antioxidant supplements might reduce muscle damage, eliminating muscle soreness and promoting faster recovery. One research group set out to test just this hypothesis: 20 active males participated in downhill running, an exercise model well known to cause high levels of muscle soreness (16). Vitamin C supplementation at 1g/day not only failed to reduce soreness, but also delayed recovery relative to subjects that took a placebo. Although downhill running decreased muscle strength in both groups during the recovery period, the vitamin C group recovered much slower. Strength levels in the placebo group were reduced only up-to 4 days post-exercise, while strength levels in the vitamin C group were still significantly impaired at day 7 and 14, failing to return to baseline by the end of the study (16).

What is going on here?

The type of forces involved with downhill running are very damaging to muscle tissue. The immune system, by sending in special cells called macrophages and neutrophils, plays a big role in cleaning up this damage (17). These phagocytic cells use ROS as a tool to take up, digest, and clear out damaged tissue. A good analogy here is a house-fire. Assuming the firefighters were able to get the fire out before it completely burned to the ground, all damaged sections and debris need to be cleaned up/cleared out before construction workers can be called in with new materials to rebuild. The same holds true for muscle tissue, more or less. Immune cells infiltrate into the injured tissue to clear the area of damaged, oxidized, and degraded proteins, paving the way for later increased protein synthesis, rebuilding and recovery. This suggests that ROS produced during exercise may also be critical to muscle regeneration. Although very intense, heavy training increases ROS levels, this is precisely what is needed for optimal recovery.

Take-home: Avoid pre-or post workout antioxidant supplements like the plague to ensure prompt recovery from the most damaging workouts.

#6 You are shooting the messenger

The fact that antioxidants have a negative effect on so many aspects of the positive, adaptive response to exercise suggests that something much bigger, more fundamental, is going on here. Study-after study has demonstrated that the health-promoting effects of exercise are driven ROS production, which, as explained above, strengthens the natural antioxidant defense machinery, protects from metabolic stress, and may even promote increased lifespan (18-31). ROS are important signaling molecules for a number of different cell signaling pathways, particularly those associated with stress-response, and we are stress-response machines. From the primordial soup through the caveman days to the present day, surviving is stressful business. From the cellular level up, we are designed to sense, respond to, and mount the appropriate response to stress. This causes us to adapt, becoming better able to overcome future stresses and ensuring our survival. What doesn’t kill us truly does makes us stronger. In this way, the stress of weight training is the same as any other: ROS are key messengers for sensing, responding, and adapting to this stress. By taking antioxidant supplements in and around training, we are killing the messenger.

But wait, aren’t antioxidants good for me?

Where does all this leave us when it comes to antioxidants in general? When should we take them, how should we take them, or should be take them at all? I’ve picked on vitamin C a lot today, so some clarification is needed here. Most animals, fish, and reptiles can synthesize vitamin C in their kidneys or liver, but us humans lost the ability some time ago (32-34). It is therefore essential that we obtain vitamin C from our diets. Among other things, it is needed for collagen synthesis and good health, in general (35). Moreover, not getting enough vitamin C leads to a disease called scurvy (36), so maintenance of plasma and tissue levels essential to avoid a deficiency. The same goes for other antioxidants.

Practical recommendations:

It goes without saying that you should avoid taking any type of supplemental antioxidants in, or around training time. Bulk suppression of cellular ROS levels with high doses of single-antioxidant supplements around training time is like shooting the messenger that delivers the signal to adapt and grow. *This includes multivitamins, most of which are loaded with antioxidants. Secondly, it is best to get most of your antioxidants from whole-food sources. A medium orange might have 100mg of vitamin C, far less than the typical vitamin C pill. Now that we are on the subject, what about antioxidants in whole-food? Should you skip those blueberries in your pre-workout oatmeal? Probably not; antioxidants in whole-food tend to be better ‘packaged’ for assimilation in a way that is less likely to disrupt endogenous ROS signaling. Although I wouldn’t recommend a bushel of blueberries pre-training, ½ cup in your pre-workout oatmeal is probably not an issue, taking into account digestion/assimilation times. It should also be noted that the health benefits of consuming lots of antioxidant rich fruits and vegetables is well established, so be sure to include lots of these in your diet.

To summarize:

• Try to get most, if not all if your antioxidants from whole-food sources.
• Single-dose antioxidant supplements may be worse than useless, possibly having a number of detrimental effects on your gains. If you are taking a multivitamin, do not take it within a few hours pre- or post- training
• There is no evidence out there to suggest that food-sourced antioxidants have anything but positive effects. They absorbed more slowly, and packaged for optimal assimilation and health benefits.

Until next time,

Bill

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