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The Antioxidant Conundrum

Everyone knows that oxidative stress is bad news: oxidative stress contributes to aging, diseases, and muscle damage associated with intense exercise.

The availability of high-quality antioxidant supplements provides a straightforward approach for athletes and the general population to reduce oxidative stress.

However, the discovery that reactive oxygen and nitrogen species play a critical role in many vital biological processes now casts doubt on the efficacy of antioxidant supplementation.

So, what’s the best way to prevent oxidative stress?

But First, What is Oxidative Stress?

Reactive oxygen and nitrogen species are highly reactive molecules that damage critical cellular structures like DNA, proteins, and cell membranes (1). Oxidative stress occurs when the number of reactive oxygen species (ROS) overwhelms your antioxidant defense systems (1).

What Causes Oxidative Stress?

Mitochondria are structures present within your cell that consumes oxygen to produce energy (1). Your mitochondria produce most of the reactive oxygen species in your cell as they produce energy from oxygen.

Unfortunately, your mitochondria are particularly vulnerable to being damaged by ROS. When mitochondria become damaged, they create more ROS, causing further mitochondrial damage (1). Thus, the vicious cycle of mitochondrial damage is responsible for the lion’s share of oxidative stress over your lifespan.

How Does Oxidative Stress Cause Aging?

Over time, ROS-mediated cellular damage accumulates to cause cell death and cellular senescence, which damages your organs, increases your frailty, and contributes to various disease states (Figure One) (1).

Cognitive Frailty

Your brain consumes 20% of your total oxygen, making your brain vulnerable to oxidative stress (2). Furthermore, because your neurons are long-lived cells that you can’t replace, they accumulate oxidative damage over time. Thus, oxidative stress is one of the critical drivers of age-related cognitive decline (2).

Cardiovascular Frailty

The heart is a very active organ. As a result, cells of the heart are packed with mitochondria, making them susceptible to oxidative stress (3). And indeed, your heart is vulnerable to oxidative damage as you age, as are the cells that make up your blood vessels (3). Thus, oxidative stress contributes to many cardiovascular diseases, including heart failure, stroke, and dementia caused by damage to your cerebral blood vessels (3).

Emotional Frailty

Even your emotional stability can be affected by oxidative stress! For example, depressed people often display elevated levels of oxidative stress and reduced levels of antioxidant defense (4). Further, antioxidant therapy can help alleviate symptoms of depression (4).

The Importance of Reactive Oxygen Species

Although it’s clear that oxidative stress is a driver of disease and aging, you may not appreciate that reactive oxygen species generated during exercise regulate the expression of genes that control your short and long-term adaptation to exercise.

Briefly, exercise-induced ROS help regulate the following adaptions to exercise:

  • Mitochondria production
  • Muscle hypertrophy
  • The creation of new blood vessels
  • Antioxidant defense systems
  • Antioxidant repair mechanisms

Thus, we face a problem. On the one hand, oxidative stress contributes to aging and is a driver in many serious diseases. But, on the other hand, reactive oxygen species play an essential role in many biological processes involved in positive adaptation to exercise.

Antioxidant Therapy: Pros and Cons

What about antioxidant supplementation?

A recent study looked at how vitamin C and E supplementation affects your ability to adapt to strength and endurance exercise (5). To do this, the authors pooled nine clinical trials investigating how antioxidant therapy affects strength gains and nine studies that examined how antioxidant supplementation affects endurance gains (5).

Overall, the authors found that antioxidant supplementation did not affect either strength or endurance adaptations (5). Therefore, given the absence of a clear beneficial impact on performance, the authors conclude that consuming vitamin C and E is unnecessary (5).

But what about antioxidant supplements for overall health and longevity?

Here we can be more definitive in our recommendations. First, there is a clear inverse association between serum antioxidants and cardiovascular disease, cancer, and all-cause mortality, suggesting that people deficient in one or more antioxidants are more likely to suffer illness and die young (6).

However, multiple randomized trials have demonstrated that antioxidant supplements (β-carotene, vitamin A, vitamin C, vitamin E and, selenium) have no beneficial effect on cancer, cardiovascular disease, and overall mortality (6). Worryingly, vitamin A, vitamin E, and selenium supplementation may increase overall mortality (6)!    

Thus, the emerging consensus is that you shouldn’t supplement with antioxidants unless you suffer from a specific vitamin deficiency (6).

Two Effective Ways to Protect Yourself from Oxidative Stress

1. Diet

Arguably the best way to optimize your intake of antioxidants is through a healthy diet. And by a nutritious diet, I mean a diet high in plant foods, including fruits, vegetables, whole grains, and legumes (6). There are several reasons why this is so.

First and foremost, a plat-rich diet significantly reduces the risk of coronary artery disease, stroke, cardiovascular disease, total cancer, and all-cause mortality (6).

Second, while a healthy diet supplies all of your antioxidant needs, it’s almost impossible to overdose on antioxidants by eating salad, fruit, whole grains, and legumes (7).

In contrast, supplements (which often provide ten times your daily requirement of antioxidants) may megadose you with antioxidants and therefore suppress the generation of healthy levels of ROS required for optimal health (7).

Third, a healthy and balanced diet provides a cocktail of antioxidant molecules that work in combination. For example, fruit and vegetables supply vitamin C, vitamin E, β-carotene, and various antioxidant polyphenol molecules (6). This combination of antioxidants works together by going to different cellular locations and targeting other reactive oxygen molecules present in your body.

Finally, some classes of natural antioxidants, particularly those found in broccoli and other cruciferous vegetables, switch on your biological antioxidant defense systems (6). Crucially, enhancing your intrinsic antioxidant defenses may be essential for people whose natural antioxidant defenses are waning due to old age.

A crucial and oft-overlooked point regarding antioxidants is that many of them are fat-soluble. Thus, to maximize your absorption of dietary antioxidants, include some healthy fat with your salads, such as virgin olive oil and avocado.

For example, adding virgin olive oil and avocado to your salad increases the absorption of essential antioxidants and nutrients. It also tastes delicious!

2. Exercise

The second way to naturally and safely boost your antioxidant defenses is through regular aerobic exercise.

Exercise has three crucial roles to play in protecting you from oxidative stress.

First, exercise increases your levels of natural antioxidant defenses (8). However, as described above, a certain level of ROS generation is required for optimal health. Fortunately, exercise fine-tunes your antioxidant defenses to allow healthy ROS levels while protecting you from severe oxidative stress (8).

Second, aerobic exercise increases the production of mitochondria in your cells. Notably, the production of new, healthy mitochondria triggers the removal of unhealthy mitochondria. Thus exercise removes a significant source of oxidative stress: damaged mitochondria (8).

Finally, exercise also increases your ability to repair oxidative damage. In particular, exercise increases the activity of cellular systems that repair protein and DNA molecules damaged by oxidative stress (8).

Take-Home Message

Oxidative stress is one of the primary drivers of aging and human disease. However, there exists a Goldilock zone of oxidative reactions that are necessary for optimal health.

So how do you protect yourself from oxidative stress while allowing healthy oxidative reactions to occur?

One way of achieving this is to combine a healthy, plant-based diet with exercise.

A plant-based diet provides a cocktail of antioxidant molecules that reduces unhealthy oxidative stress without overdosing your body with antioxidants and suppressing healthy oxidation.

Exercise naturally increases your antioxidant defenses while creating new mitochondria, removing unhealthy mitochondria, and activating repair mechanisms that remove oxidative damage.

Antioxidant Figure
Figure One. How aging increases oxidative stress, leading to disease. Exercise reduces oxidative stress by strengthening your oxidative defense systems, creating new healthy mitochondria, removing old and damaged mitochondria, and activating repair mechanisms that fix molecules damaged by reactive oxygen species. In addition, a healthy, plant-based diet provides a cocktail of antioxidant molecules that increase your antioxidant defenses and remove reactive oxygen species without overloading your body.

References and Further Reading

1.            S. F. Vatner et al., Healthful aging mediated by inhibition of oxidative stress. Ageing Res Rev 64, 101194 (2020).

2.            A. Ionescu-Tucker, C. W. Cotman, Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiol Aging 107, 86-95 (2021).

3.            C. Izzo et al., The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases. Life (Basel) 11,  (2021).

4.            A. Shao et al., Oxidative Stress at the Crossroads of Aging, Stroke and Depression. Aging Dis 11, 1537-1566 (2020).

5.            T. Clifford, O. Jeffries, E. J. Stevenson, K. A. B. Davies, The effects of vitamin C and E on exercise-induced physiological adaptations: a systematic review and Meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 60, 3669-3679 (2020).

6.            D. Aune, Plant Foods, Antioxidant Biomarkers, and the Risk of Cardiovascular Disease, Cancer, and Mortality: A Review of the Evidence. Adv Nutr 10, S404-s421 (2019).

7.            M. R. Higgins, A. Izadi, M. Kaviani, Antioxidants and Exercise Performance: With a Focus on Vitamin E and C Supplementation. Int J Environ Res Public Health 17,  (2020).

8.            N. V. Margaritelis, V. Paschalis, A. A. Theodorou, A. Kyparos, M. G. Nikolaidis, Redox basis of exercise physiology. Redox Biol 35, 101499 (2020).


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Old Guy Looking Into Mirror

Why am I getting old? Molecular Changes Driving Old Age

Aging mechanisms interact within a network of complex feedback loops, leading to increased damage and degeneration over time.

Resilient Happy Older Woman

What is Positive Aging?

By applying the principles of Positive Aging, you can avoid disease and disability and lead a long, healthy, and fulfilling life.

Powerful Older Man

An Antidote Against Frailty

Frailty is preventable, and often reversible, if you are willing to put in the work and follow the four golden rules of resistance training.