6.1. INTRODUCTION

Every professional sport athlete and nearly every amateur frequently comes across some sort of advertisement, lay press article, TV advertisements and so forth touting the salubrious activities of polyphenols. The near totality of such pieces of ‘information’ underscores the need to add antioxidants to the athlete’s diet, pointing to polyphenol-rich food or supplements as a valuable source of free radical scavengers. From a mere scientific viewpoint, the reality is—currently—very different.

In this chapter, I will review the (scant) available evidence on the use of polyphenols as antioxidants in sport and try to discuss what the road ahead should look like.

6.2. WHY SHOULD WE INGEST ANTIOXIDANTS?

As also outlined in other chapters of this book, physical exercise induces oxidative stress (Nikolaidis et al. 2012b). Whether mild or severe, oxidative stress might provoke damage to cellular macrocomponents, namely lipids, protein, sugar and DNA (Nikolaidis et al. 2012b). Therefore, the hypothesis is being formulated that the ingestion of antioxidants would prevent such damage and, in addition, augments performance (Gomez-Cabrera et al. 2012).

Indeed, increased oxidative damage can be detected after physical exercise (see ad hoc chapters of this book) and—theoretically—this would translate into increased risk of degenerative diseases, where oxidative stress plays a role (Visioli and Davalos 2011, Visioli et al. 2011).

The problem here is that we are faced with several methodological limitations. The first and most important one is the correct assessment of oxidative damage (Halliwell 2012). To start with, there is—as of today—no proper and accurate way to measure free radical production. Free radicals are too short-lived to be measured in vivo (especially in humans), and therefore we try to fight an enemy that we cannot even see.

6.3. ANTIOXIDANTS ARE GOOD FOR OUR HEALTH, RIGHT?

Well, yes, in appropriate amounts that are very difficult to define. Please note that if we look at the results of clinical trials with antioxidants, the near totality of them showed null (Vivekananthan et al. 2003) or even harmful (Bjelakovic et al. 2007) effects. In other words, we do not have sufficient experimental evidence to suggest the intake of pharma-nutrition preparations based on antioxidants. In fact, the converse might be true and we probably should discourage their use (Nikolaidis et al. 2012a, Ristow et al. 2009, Bjelakovic et al. 2007). However, epidemiological studies are quite clear: higher intakes of antioxidants (vitamins, but also polyphenols) are associated with better prognosis (Visioli and Davalos 2011, Visioli et al. 2011).

Why this apparent conundrum? Probably, the foremost explanation is that we confuse in vitro with in vivo antioxidant activities. Whereas the former are fairly easy to assess and usually require simplified systems, the latter are nearly impossible to accurately establish. Moreover, in vitro activities do not take into account bioavailability issues: with the progress of our knowledge of polyphenol metabolism, we now know that these molecules undergo extensive first-pass metabolism and reach plasma and target organs in minute amounts (Visioli et al. 2011). Indeed, cellular concentrations of exogenous antioxidants probably do not add much weight to the antioxidant array (enzymes, but also glutathione, etc.) that we are endowed with. We should stress that human cells already contain several layers of antioxidants, some of which are enzymatic in nature, for example, superoxide dismutase and catalase. Intracellular antioxidants often reach millimolar concentrations, whereas polyphenols’ circulating concentrations normally do not exceed the low micromolar range (Lotito and Frei 2006).

6.4. WHAT ARE POLYPHENOLS?

Although an extensive discussion of polyphenols’ chemistry is beyond the scope of this chapter (appropriate reviews can be found elsewhere), readers might benefit from a quick overview of these nutritionally important molecules. Polyphenols are the product of plants’ secondary metabolism. These secondary metabolites are not required for plant development and growth, but they are essential to plant communication and defence (Iriti and Faoro 2009). Among their most important biological roles, polyphenols are involved in the interaction with pathogens, herbivores and other plants; they protect plants from ultraviolet radiation and oxidants, repel or poison predators and, finally, attract beneficial insects or microbes and are indispensable to pollination (Winkel-Shirley 2002). Indeed, according to plant biologists, stimulation of plant active defences, that is, secondary metabolic pathways, is a very important goal in crop production. Since agriculture was developed in 10,000 bc, humans have been modifying plant secondary metabolite profiles. By selecting fruit, flower and vegetable colours, farmers involuntarily elected higher anthocyanin content, whereas in selecting for scents they modified volatile phenolics. From a biosynthetic viewpoint, the enzyme phenylalanine ammonia lyase catalyses the deamination of phenylalanine to cinnamic acid, the precursor of the polyphenols (Iriti and Faoro 2004, 2009) (Figure 6.1). These include simple phenylpropanoids, flavonoids, stilbenes and tannins, which contain a second aromatic ring originated from three molecules of malonyl CoA (Figure 6.1).

FIGURE 6.1

Major polyphenol biosynthetic pathways in plants. (Adapted from Iriti, M., and F. Faoro. 2004. Curr Topics Nutr Res 2:47–65.)

It is important to underscore that, in addition to focused breeding, several molecular techniques can be employed to enhance the polyphenolic content of plants (Iriti and Faoro 2009).

6.5. POLYPHENOLS: MUCH MORE THAN ANTIOXIDANTS (IN FACT, THEY PROBABLY ARE WEAK ANTIOXIDANTS ONCE INGESTED)

It is now thought more likely that some phytochemicals, including polyphenols, are processed by the body as xenobiotics. They stimulate stress-related cell-signalling pathways (Figure 6.2) that result in increased expression of genes encoding cytoprotective proteins. Nrf2 (NF-E2-related factor 2) is a transcription factor which binds to the antioxidant response element (ARE) in cells and thus regulates enzymes involved in antioxidant functions or detoxification (e.g. thioredoxin reductase-1 and glutathione peroxidases) (Shay et al. 2012). Polyphenols might increase gene transcription of Nrf2 mediated by such response elements (Chiva-Blanch and Visioli 2012). This provides grounds for the theory of hormesis, that is, when mild stress triggers defence mechanisms. In the case of polyphenols, it indicates that they could most likely have an indirect antioxidant action (Figure 6.2).

FIGURE 6.2

Polyphenols activate cellular stress-related signalling pathways, which lead to the mobilisation on nrf2 and the activation of the nuclear antioxidant response element (ARE). The ARE stimulates the production of Phase II enzymes and of antioxidants, namely (more...)

One human example of these effects has been reported by Visioli et al. (2009), who published a study in which 98 Chinese/Malay subjects ingested an olive preparation which was high in phenolics. After 1 h, no difference in plasma antioxidant capacity was observed, but a significant increase in total plasma glutathione concentration was measured. The authors postulated that the observed effects of the olive phenols on glutathione levels might be governed by the ARE-mediated increase in Phase II enzyme expression.

6.6. POLYPHENOLS IN SPORT: A REVIEW OF THE CURRENT EVIDENCE

As mentioned, the current hype on ‘antioxidants and health’ also involves polyphenols of natural origin. A marketing mix of real science, consumer demand, appeal and targeted advertisement is encouraging sport researchers to undertake experiments to assess the antioxidant virtues of raw mixtures or individual compounds in physical exercise.

The first thing to be said is that the near totality of studies aims at demonstrating some antioxidant action, even though when other antioxidant vitamins have been tested the outcomes have been really disappointing (see above). Indeed, if some conclusion can be drawn, it is that provision of antioxidant molecules to athletes or amateurs actually decreases performance and increases muscular damage (Childs et al. 2001, Ristow et al. 2009). Of note, these studies did not conduct performance diagnostics (only biochemical measurements); therefore, any inference on the actual effects of antioxidant supplementation on performance (either way) is premature (Nikolaidis et al. 2012a).

As of today, the vast majority of studies on polyphenols and physical exercise concerned green tea catechins. As an example, Jowko et al. tested the activities of green tea catechins in healthy individual (Jowko et al. 2011) and soccer players (Jowko et al. 2012). They report very modest protection from oxidative damage in the former and no effect in the latter. In addition, the question should be asked of whether provision of catechins increased or decreased performance, in addition to their putative cellular antioxidant activities. Kerksick et al. also tested a combination of epigallocatechin-gallate and N-acetylcysteine in healthy volunteers who performed eccentric exercise bouts (Kerksick et al. 2013). Again, no effect of this intervention was recorded.

In summary, despite the active search for ‘natural’, polyphenol-rich extracts that might enhance physical performance and decrease oxidative damage because they are antioxidants, the information we currently have is very limited and actually suggests the converse (Gomez-Cabrera et al. 2012).

6.7. CONCLUSIONS

The concept that physical activity induces oxidative stress which needs to be counteracted by increased intakes of antioxidants is—apparently—well anchored in professionals and amateurs. Though the first part might be true (intense exercise does induce oxidative stress in muscles and, probably, other tissues), provision of antioxidant vitamins at high doses apparently does more harm than good. In this respect, we should also move beyond the belief that polyphenols (many of which are indeed potent in vitro antioxidants) exert remarkable antioxidants activities in humans. As mentioned, these molecules are heavily metabolised and their true contribution to the cellular antioxidant array is most likely minimal. However, polyphenols stimulate the stress-related biochemical pathways that in the long run afford protection from subsequent insults. In short, it is time we break away from the equation polyphenols = antioxidants, because these molecules are endowed with several other activities (Visioli et al. 2011).

As of 2014, we should discuss ‘polyphenols in sport’ within the framework of hormesis and adaptive response (including effects on immunity). Even though hormesis is quite difficult to precisely define and quantify, emerging evidence strongly suggests that ‘controlled damage’ such as that induced by physical exercise stimulates resilience and, in turn, provides better health (Gaman et al. 2011, Calabrese et al. 2012, Ristow and Schmeisser 2011).

In conclusion, physical exercise and sport are essential to a healthy lifestyle despite the fact that they induce oxidative stress (or maybe even ‘because’ of that) (Nikolaidis et al. 2012b, Gomes et al. 2012). The current hype on polyphenols as antioxidant agents that would prevent muscular damage and enhance performance does not rest on solid ground and many more years of ad hoc studies are required to clarify their precise role in sport.

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