Antioxidants & Pro-oxidants: Finding the Balance

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It seems like every time I make a trip to the supermarket I come across someone looking at a food product label and boisterously exclaiming, “Hey, it has antioxidants, those are good!” Chances are this enamored individual has no clue what an antioxidant actually is beyond the fact that they’re purportedly good for you. Naturally, I figured it would be prudent to write an in-depth article that takes a close look at what antioxidants and pro-oxidants are, how they work physiologically, what role they play in human health, and what foods to find them in.

What are antioxidants and free radicals?

Chemically speaking, antioxidants are molecules that act as electron donors to neutralize free radicals (no, not of the Republican variety, the other “radicals”). Some common antioxidants include: vitamin C (ascorbic acid), ubiquinol, and melatonin. Antioxidants are crucial in many organisms since oxidation pathways in the mitochondrial matrix of cells are constantly producing free radicals (see the stars in the figure 1 below):

Figure 1–Generation of Free Radicals in Mitochondria

Free radicals act as electron scavengers (since they have an open electron shell) and are necessary for certain cell signaling processes as well as phagocytosis of invading bacterial species.

However, herein lies the paradox biological systems face: many living organisms require molecular oxygen (O2) to subsist, yet it is also oxygen that leads to production of reactive oxygen species (of which include free radicals). An example of such a reactive oxygen species is the hydroxyl radical that readily reacts with many biological molecules.[1]

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How free radicals damage cells

Cells are constantly producing reactive intermediates (which include reactive oxygen species) but this is why biological systems have defense mechanisms to detoxify the cell of such moieties when necessary. However, when the flux shifts in favor free radicals (and other reactive oxygen species) the cell components are susceptible to oxidative stress.

Oxidative stress can cause DNA damage which can further lend itself to carcinogenic activity, among a myriad of other negative effects in cellular components. In figure 2 below you can see an overview of the long-term consequences of chronic oxidative stress:

Figure 2–Overview of Oxidative Stress Consequences

So naturally then, we want to ensure we have plenty of antioxidants to avoid oxidative stress, right? Well, yes and no; I’ll explain why below.

Pro-Oxidants: are they always a “bad” thing?

Like with many things in human health, just because a little bit of something may be beneficial, that doesn’t mean a superfluous amount is even better; antioxidants are no exception to this. As aforementioned, cells actually require some free radicals (and other reactive oxygen species) for metabolic processes.

However, certain antioxidants, such as vitamin C (ascorbic acid) can actually exhibit pro-oxidant activity when necessary (thus they are called conditional pro-oxidants). [3] What’s the problem with pro-oxidants, you ask?

In a nutshell, pro-oxidants are the inverse of antioxidants and actually induce oxidative stress by producing reactive oxygen species (and thus free radicals).

Moreover, it is hypothesized that taking excessive amounts of antioxidants could lead to critical depletion of endogenous free radicals, making cells susceptible to exogenous radical damage (since endogenous free radicals serve as a protective mechanism against exogenous radicals).[4]

Figure 3–Chemistry of Pro-oxidant Generation

Antioxidants: How much do we really need?

Before you run out the door looking to return all your antioxidant-boosting supplements to the nearest GNC, don’t take the preceding excerpt to mean that antioxidants are inherently “bad”; that couldn’t be further from the point being made here. Antioxidants in nominal doses are indeed essential and conducive to bettering your health and longevity.

To quantify the amounts of antioxidants humans can benefit from, the United States Department of Agriculture (USDA) previously used what’s known as the Oxygen Radical Absorbance Capacity (ORAC) value, which was developed by the National Institute of Health. [5] Without getting too off topic about what the ORAC entails, it is basically a chemical assay used to measure the antioxidant activity of a certain food.

However, this method of measuring the antioxidant content of foods was ditched by the USDA since food companies were abusing it to mislead consumers about the health benefits of their foods. Furthermore, scientific evidence continues to show that the ORAC actually has little carryover to the effects of specific bioactive compounds in vivo. [6]

That being said, it is still useful to consider that fruits (specifically berries) and vegetables are highly-dense sources of antioxidants, and for lack of a better modality to quantify antioxidant needs in humans, we will have to improvise a bit.

 

Just give me a damn number already!

I’m sure by now you’re just itching for an exact, tangible number so you can carry on with your day sucking down the necessary pills to hit your antioxidant quota; but for lack of a precise, reliable quantity in the literature all we can do is extrapolate. Meta-analysis have examined the link between antioxidant-rich food sources and mortality rates; literature continually shows that those who consume around four to five servings of fruit and/or vegetables per day are at a lower risk for a plethora of diseases and other health maladies, not to mention they tend to live longer. [7,8]

Granted, the issue with longitudinal studies is that the mechanisms behind what compounds exactly in respective fruits and vegetables prevent the onset of such a wide variety of diseases and health conditions remain to be elucidated. Essentially, we can draw correlation from such studies but not causation.

At this point, for active individuals, I would say it’s safe to aim for a minimum of three servings of fruit and/or vegetables per day and if you want more then have at it, but just don’t get carried away and subsist solely on said food sources (even if you’re a vegan/vegetarian).

Antioxidant supplements can be useful in instances where individuals greatly lack antioxidant-rich food sources (e.g. fruits and vegetables) in their diet, but they are not necessary much beyond that and may even be detrimental if overdone (as was discussed earlier in this article).

Also, this isn’t to say that all of your antioxidants will/should come solely from fruit and vegetable sources. Many foods, spices, plant extracts, etc. contain a good amount of antioxidants as well. As time goes on and research progresses/improves we will be able to draw more exact conclusions on quantitative antioxidant needs in humans.

References:

  1. Valko, M; Leibfritz, D; Moncol, J; Cronin, M; Mazur, M; Telser, J (2007). “Free radicals and antioxidants in normal physiological functions and human disease”. The International Journal of Biochemistry & Cell Biology,39(1): 44–84.
  2. Sies, H. (1997). Oxidative stress: oxidants and antioxidants. Experimental physiology82(2), 291-295.
  3. Carr, A., & Frei, B. (1999). Does vitamin C act as a pro-oxidant under physiological conditions?. The FASEB Journal13(9), 1007-1024.
  4. Bjelakovic G, Nikolova D, Gluud L, Simonetti RG, Gluud C. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. 2007;297(8):842-857..
  5. Holden, J. M., Bhagwat, S. A., Patterson, K. Y. (2002). Development of a multi-nutrient data quality evaluation system. J. Food Comp. Anal. 15, 339-348.
  6. Nutrient Data Products and Services. (n.d.). ARS : Home. Retrieved March 20, 2017, from http://www.ars.usda.gov/Services/docs.htm?docid=15866
  7. Bellavia, A., Larsson, S. C., Bottai, M., Wolk, A., & Orsini, N. (2013). Fruit and vegetable consumption and all-cause mortality: a dose-response analysis. The American journal of clinical nutrition98(2), 454-459.
  8. Dauchet, L., Amouyel, P., Hercberg, S., & Dallongeville, J. (2006). Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. The Journal of nutrition136(10), 2588-2593.

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