5 new findings on oxidative stress in runners

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One of the themes that cropped up repeatedly at the American College of Sports Medicine annual meeting earlier this month in Boston was the delicate balance between oxidative stress and antioxidant defences.

While it might seem a simple contrast between bad (oxidative stress) and good (antioxidants), the picture is quite a bit more complex. Oxidative stress can be damaging, but it also signals your body to adapt, get fitter and enhance its own intrinsic antioxidant defences. Antioxidant supplements can help fight that stress, but too much can block some of those training gains. So how do you find the balance?

Here are five highlights from the conference:

1/ Is exercise an antioxidant?

In a word, yes. It has long been known that one of the consequences of getting fitter is that your body’s own antioxidant response becomes more effective. But do those benefits persist after many years of training?

presentation by researchers from Ecuador and Spain compared three groups of older men with an average age of 60: sedentary, recreationally active and long-term “amateur” masters athletes. The athletes had higher levels of glutathione peroxidase (a marker of antioxidant response) and lower levels of malondialdehyde (a marker of oxidative stress).

2/ What type of exercise is best?

I’m always a little hesitant to suggest that one particular type of workout is “best” based on a single study. For most outcomes, I suspect a varied training programme incorporating lots of different types of workouts is optimal.

With that preamble, a study from Northern Arizona University put subjects through two different cycling workouts: 30 minutes at 70 percent VO2max, and 7 x 1:00 all-out with 2:00 easy recovery (with a 9:00 warm-up to equalise total time and oxygen consumption).

The interval workout produced higher levels of two antioxidant markers (superoxide dismutase and glutathione reductase) with no increase in a marker of oxidative stress (F2-isoprostanes), suggesting that high intensity is a good way of triggering antioxidant response.

3/ Is cumulative oxidative stress bad?

Intuitively, the answer is obviously yes. But can measurements of oxidative stress predict negative outcomes?

study of female cross-country athletes at Quinnipiac University assessed runners every three weeks for a variety of measures, looking for links to their performance improvements (or decrements) throughout the season. One of the relationships that jumped out was that a measure of oxidative stress called the d-ROMs test, which quantifies levels of reactive oxygen metabolites, was a significant predictor of impending injury.

In studies like this that measure lots of different things and look for connections to lots of different outcome variables, it’s always hard to know which “significant” findings are real and which arise by chance. Still, it makes sense that elevated oxidative stress could be a marker of training overload that in turn predicts heightened injury risk. It would be interesting to see this pursued further.

4/ Can you manipulate the balance between oxidative stress and antioxidants?

Researchers at Skidmore College tried an interesting experiment. They had subjects complete three 5K cycling trials: once with placebo; once with an antioxidant cocktail (vitamins C and E plus alpha-lipoeic acid) to shift the balance toward antioxidants; and once while breathing 100-percent oxygen to shift the balance toward oxidative stress.

I’m a little dubious about the oxygen part of the experiment, since breathing pure oxygen has effects beyond oxygen stress - potentially increasing oxygen available to muscles, for example. As it turns out, the oxygen results were no different from placebo anyway.

The antioxidant supplement, on the other hand, slowed 5K times by 3.1 percent, with associated effects on ventilation, economy and perceived effort.

5/ Do antioxidants interfere with training response?

The four studies described above are all single poster presentations; take their results, in isolation, with a grain of salt. To draw firm conclusions, you need to take a bird’s eye view of all the studies addressing a given question.

That’s what Jeff Coombes, of the University of Queensland in Australia, did in an invited talk titled “Does Antioxidant Supplementation Promote or Impede Skeletal Muscle Mitochondrial Biogenesis?” Promoting the growth of mitochondria is one of the key goals of endurance training, so understanding whether antioxidants help or hurt this goal is important.

The first question in his title was easy to answer: there’s no evidence of any sort that antioxidants help promote mitochondrial biogenesis (i.e., the growth of new mitochondria).

As for the second question - does it hurt­? - Coombes emphasised the concept of hormesis: you need a little bit of oxidative stress to trigger adaptations, but it’s a delicate balance between too little and too much. That means that simply suppressing oxidative stress with antioxidants can easily backfire.

So what does the evidence say? By Coombes’s count, there are currently three studies that show antioxidants having no effect on mitochondrial gains and six studies showing negative effects. That’s not yet definitive, but it’s certainly suggestive.

Coombes also emphasised the “very, very strong” evidence that routine antioxidant supplementation can have negative health effects in large-scale epidemiological trials, raising the risk of conditions like heart failure, prostate cancer and all-cause mortality in some populations.

So where does that leave us? One of the things that jumped out at me in these presentations was that every single one used different markers of oxidative stress and antioxidant status - an indication of just how complex this area is. There isn’t one single oxidative molecule balanced against one single antioxidant mechanism - there are literally hundreds.

For example, Coombes mentioned Nrf2, a molecule inside cells that acts as a “master antioxidant regulator,” regulating more than 200 genes in response to oxidative stress. And what activates Nrf2, other than oxidative stress? Gingerol (from ginger), capsaicin (from hot peppers), lycopene (the red in tomatoes), curcumin (from turmeric), resveratrol (grapes), sulforaphane (broccoli)...

Drugs can also activate the Nrf2 pathway - but Coombes also mentioned a trial of a powerful Nrf2-activator (about 200 times more potent than the broccoli extract that Coombes has been studying) that was halted in 2012 after increased death rate in the treatment group. “Again, with hormesis,” Coombes pointed out, “you get the dose wrong and you’re in trouble.”

Get the picture? Eat food, especially fruits and vegetables.