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Antioxidants: Can you have too much of a good thing?

Reactive oxygen species (ROS) can damage the cells in our body, disrupting function. Exercise increases the production of ROS. So … antioxidant supplements that enhance in-built defences against ROS should be taken by athletes to protect against ROS, right?! NOT SO FAST!! As with everything in biology, it is not that simple. And of course, there is also so much we still do not know. In this blog, I summarise what we think we know, and consider why it seems you can have too much of a good thing …



ROS, Exercise and Antioxidant Supplements: The Background


ROS, as the name suggests, are very reactive derivatives of oxygen. They are a by-product of normal cell metabolism and, if left unchecked, whizz around our cells colliding with things and damaging them. We have in-built antioxidants … molecules that also whizz around the cell, mopping up and stabilising ROS so they can’t do damage. These are our so-called ‘oxidative defences’.


Exercise increases the production of ROS, essentially because our cells are working harder and doing more ‘metabolic stuff’ to give us the energy and mechanical force to contract our muscles (see Merry and Ristow 2016). It is thought that increased ROS, beyond what our oxidative defences can cope with, can contribute to fatigue during exercise and muscle soreness post exercise (as ROS induced damages triggers an inflammatory response) (see Merry and Ristow 2016).


In recent years, there has been a large increase in the number of athletes taking antioxidant supplements such as Vitamin C, Vitamin E, polyphenols, co-enzyme Q10, N-acetyl cysteine and spirulina. The theory is that by boosting our in-built defences with supplements we can remove the ROS produced by exercise faster, and so protect cells from damage. But, do antioxidant supplements protect against oxidative damage? And, if so, do they enhance health and / or performance?


What we know of the answer …


It is complex!


First, we must consider the benefits of ROS produced in exercise. Yes, you heard me right, the BENEFITS of these damage inducing molecules. It turns out that ROS seem to be important signalling molecules that help drive the training adaptations that make us stronger, faster, and fitter! This includes everything from muscle hypertrophy, to our ability to produce energy, to upregulation of our oxidative defences themselves so that we are better protected against excessive levels of ROS in future bouts of exercise (Gomez-Cabrera et al 2008).


So, whilst too much ROS causes damage, too little may also be less than ideal (see Merry and Ristow 2016)! If we take antioxidant supplements and reduce ROS to this ‘less than ideal’ low level, we may inhibit long term training adaptations and performance improvements. And at least with certain antioxidants this is what the research suggests (Malm et al 1996; Malm et al 1997; Lamprecht et al 2009; Texeira et al 2009; Paulsen et al 2014a; Paulsen et al 2014b), although not universally (Yfanti et al 2011; Bobeuf et al 2011).


Theoretically we might imagine that if we could get the dose of antioxidants just right, i.e. so we keep ROS in that optimal range for training adaptations and below a harmful level, they may be beneficial. This – currently at least – is not possible, as we are not even sure what the ‘optimal range’ is, how this might differ with different types of training and, indeed, the variation in ROS production between individuals and even within any one individual on different days. And that is without even considering that we don’t really know how much any one antioxidant reduces ROS, and the variability of this within and between individuals!


At this point it is also worth noting that many antioxidants become pro-oxidant at high levels, thus contributing further to ROS production and potentially tipping the balance to ‘too high’ ROS during exercise and beyond!


So, is it ever appropriate to take antioxidant supplements?


What we addressed above was the potential chronic impact of taking antioxidants. As ROS are thought to contribute to fatigue and muscle soreness, there is an argument that some antioxidant supplements may be beneficial in competition to reduce fatigue, and – where the competition involves events over several days – muscle soreness that may inhibit performance (Powers and Jackson 2008; Lamb and Westerblad 2011; Cobley et al 2011; Braakhuis and Hopkins 2015; Merry and Ristow 2016). More research is needed before this can be confirmed, including identifying the antioxidant supplements best suited to this.


There is also some evidence that Vitamin E may be beneficial to performance at altitudes above 5000m (Simon-Schnass and Pabst 1988). One type of damage that this antioxidant protects against is damage to cell membranes. It is thought that at altitude this is important at preserving red blood cells … which are vital at this high altitude where oxygen levels are so low that we really need all our red blood cells to carry all the oxygen possible!


What about antioxidants found naturally in the diet …


Many fruits and veggies are rich in antioxidants. We are not saying these are harmful to training adaptations!!! They contain lower levels than are typically taken in supplements, and are in the context of a complex plant structure where multiple antioxidants may be found together with other molecules that may interact with them and impact their digestion, absorption and utilisation in the body (see Braakhuis and Hopkins 2015). We don’t fully understand it yet, but there is no evidence that these naturally occurring antioxidants harm performance!! In fact, we know fruits and veggies contain other vitamins and minerals, plus fibre, that are vital for health and performance.


Conclusion


So far, I think the evidence points against the use of antioxidants to support performance. Maybe one day we will be in a position where we understand enough to use such supplements to manipulate ROS levels so they are optimal for supporting training adaptations without inducing damage … but we are nowhere close to that yet.


On a wider point, the story of ROS and antioxidants highlights the beauty and complexity of the human body … we must always think critically about the implications that altering the balance of one or more systems may have on health and / or performance. It also demonstrates the importance of investigating both the direct outcome of a supplement on performance, and what is happening at the cellular level. I believe it is only with this two-pronged approach to sports nutrition research that we really get closer to understanding exactly how nutrients and exercise interact … and so how we can use nutrition to maximally optimise performance!


References


Braakhuis, AJ and Hopkins, WG (2015). Impact of dietary antioxidants on sport performance: a review. Sports Medicine. 45:939-955.


Bobeuf, F, Labonte, M, Dionne, IJ and Khalil, A (2011). Combined effect of antioxidant supplementation and resistance training on oxidative stress markers, muscle and body composition in an elderly population. Journal of Nutrition and Healthy Ageing. 15:883–889.


Cobley, JN, McGlory, C, Morton, JP and Close GL (2011). N-Acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations. International Journal of Sport Nutrition and Exercise Metabolism. 21:451–461.


Gomez-Cabrera, MC, Domenech, E and Vina, J (2008). Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training. Free Radical Biology and Medicine. 44:126–131.


Lamb, GD and Westerblad, H (2011). Acute effects of reactive oxygen and nitrogen species on the contractile function of skeletal muscle. Journal of Physiology. 589:2119–2127.


Malm, C, Svensson, M, Ekblom, B and Sjodin, B (1997). Effects of ubiquinone-10 supplementation and high intensity training on physical performance in humans. Acta Physiologica Scandi. 161:379–384.


Malm, C, Svensson, M, Sjoberg, B, Ekblom, B and Sjodin, B (1996). Supplementation with ubiquinone-10 causes cellular damage during intense exercise. Acta Physiologica Scandi. 157:511–512.


Merry, TL and Ristow, M (2016). Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? Journal of Physiology. 18:5135-5147.

Lamprecht, M, Hoffman, P, Greilberger, JF, and Schwaberger, G (2009). Increased lipid peroxidation in trained men after 2 weeks of antioxidant supplementation. International Journal of Sports Nutrition and Exercise Metabolism. 19(4):385-399.


Paulsen, G, Cumming, KT, Holden, G et al. (2014). Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized controlled trial. Journal of Physiology. 592:1887–1901.


Paulsen, G, Hamarsland, H, Cumming, KT, Johansen, RE, Hulmi, JJ, Borsheim, E, Wiig, H, Garthe, I and Raastad, T (2014). Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training. Journal of Physiology. 592:5391–5408.


Powers, SK and Jackson, MJ (2008). Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiological Reviews. 88:1243–1276.


Simon-Schnass, I and Pabst, H (1988). Influence of vitamin E on physical performance. International Journal of Vitamin and Nutrient Research. 58(1):49–54.


Teixeira, VH, Valente, HF, Casal, SI, Marques, AF and Moreira, PA (2009). Antioxidants do not prevent post exercise peroxidation and may delay muscle recovery. Medicine and Science in Sports and Exercise. 41:1752–1760.


Yfanti, C, Nielsen, AR, Akerstrom, T, Nielsen, S, Rose, AJ, Richter, EA, Lykkesfeldt, J, Fischer, CP and Pedersen, BK (2011). Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training. American Journal of Physiology, Endocrinology and Metabolism. 300:E761–E770.

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