Antioxidants and Free Radical Overview

Antioxidants are food components (vitamins, mineral, phytochemicals), and endogenous enzymes that quench free radicals, which prevents cellular damage. Free radicals have an unpaired electron and therefore, are very unstable and highly reactive. They react with other molecules, resulting in lipid membrane destruction and cell damage. The most common free radicals are oxygen based free radicals (reactive oxygen species) but can also be carbon or nitrogen based molecules. Free radicals are produced under normal physiological stress- such as exercise, and from environmental conditions- such as radiation from the sun, altitude, and air pollution. 

The presence of some free radicals is healthy for optimal physiological function. They take part in several different physiological processes, such as playing a role in killing infectious bacteria in monocytes, signal transductions, and the folding of new proteins within the endoplasmic reticulum, which requires a more oxidative environment. 

Oxidative stress occurs when there is an imbalance of free radicals and antioxidants, resulting in cellular damage. Considering exercise produces free radicals, concerns have risen about athletes being able to achieve enough antioxidants through their diets to prevent oxidative stress. Researchers have explored these concerns, examining the effects of antioxidant supplementation on physiological adaptations to training and performance. This page reviews oxidative stress during exercise and the concerns with taking antioxidant supplementation.

Oxidative Stress During Exercise

Exercise increases the production of free radicals through the oxidative metabolism in the electron transport chain (an energy production cycle). About 4-5% of the oxygen consumed may lead to reactive oxygen species. Additionally, muscle damage initiates activation of immune response, which can lead to reactive oxygen species and cause cell damage. In fact, the duration and intensity of the exercise is directly related to the free radical formation. Environmental conditions that you are training in, such as at high elevation, in pollution, and with excess sun exposure can lead to additional free radical production. It has been hypothesized that athletes have an increased need for antioxidants due to their increased free radical production, and that endogenous antioxidants may not be sufficient to terminate the increased free radical production, therefore leading to oxidative stress. There are a few considerations to make in refute of this hypothesis. First, as a result of the increased free radical production caused by exercise, the body compensated by increasing antioxidant activity. Additionally, if it is that case the dietary antioxidants needs increase, energy requirements also (generally) increase. Increased energy intake allows for opportunity to meet the potential increased need for antioxidants.

Sources of Antioxidants 

Antioxidants are present in a wide variety of foods. Vitamin C and E are both strong antioxidants Vitamin C is found in a wide variety of fruits and vegetables, whereas vitamin E is rich in vegetable oils. These vitamins are discussed in more detail below. The minerals selenium, zinc and copper have antioxidant functions. Some food sources of these minerals include meat, seafood, nuts,  and whole grains. Aside from the vitamins and minerals mentioned above that function as antioxidants, phytochemicals are another dietary source of antioxidants. Phytochemicals are compounds found in plants that do not contribute to our nourishment, but have demonstrated protective properties, such as their role in disease prevention. There are thousands of phytochemicals that have been identified, but some examples of well-known and researched phytochemicals include the carotenoids (e.g. lutein and lycopene) and many types of flavonoids (e.g. isoflavones, anthocyanidin).  

In addition to a variety of plant and animal- based foods providing antioxidants, the body has endogenous enzymatic and non-enzymatic antioxidants. The endogenous enzymes are dependent on certain minerals, including the antioxidant minerals, for them to provide their antioxidant roles. Some of the endogenous antioxidants are very important for the regeneration of other antioxidants to continue free radical termination. For example, glutathione and ubiquinones help in the regeneration of vitamin C, which is a powerful reducing agent. This is just one example of how many of the antioxidants work in synergy with one another. 

Antioxidant supplementation

Supplementation of antioxidants is not recommended, even for athletes. Whether it’s a single antioxidant supplement (e.g.vitamin C or vitamin E), or an antioxidant complex supplement (including multiple antioxidants). Supplementation may lead to poor health outcomes and will not improve your exercise performance. Supplements can throw off the natural and healthy balance of oxidation/reduction reactions of free radical production and termination. As mentioned above, the body needs some amount of reactive oxygen species for normal physiological function; this is also true to training adaptations to occur. Antioxidant supplementations can, therefore, act in the opposite manner as intended- as a pro-oxidant, causing additional oxidative damage through the production of free radicals. This is not what would be expected since insufficient amounts of antioxidants cause oxidative stress, while excess (through supplementation) also cause oxidative stress. This is referred to as the antioxidant paradox. 

While antioxidant supplements are not recommended, it’s important to consume plenty of foods rich in antioxidants. This is easily achieved by consuming adequate energy (calories) to meet your needs, and through a well-balanced diet including a variety of fruits, vegetables, healthy fats, whole grains, meat or vegetarian protein sources. 

Vitamin C

Functions of Vitamin C 

Vitamin C is a powerful antioxidant due to its strong reducing abilities. Inadequate vitamin C will not only lead to oxidative stress, but it may hinder your athletic performance- which is related to its other non-antioxidant roles. Vitamin C (ascorbic acid) is needed for the synthesis of norepinephrine and carnitine. Carnitine transports long-chain fatty acids from the cytosol to the mitochondria for β-oxidation. In other words, it’s needed to use fat as a fuel source! Additionally, vitamin C plays an essential role in synthesis of the structural protein collagen, which is needed for skin, tendons, connective tissue, wound healing (just to name a few). Considering these functions, it’s no wonder insufficient vitamin C intake can negatively impact exercise performance and overall health.

Vitamin C is naturally found in a wide variety of fruits and vegetables, with some having higher amounts per serving than others. The RDA for vitamin C can easily be met through the consumption of the USDA’s minimum recommendation of 2 servings of fruits and 2.5 servings of vegetables per day.

Vitamin C and Exercise Performance

When vitamin C status is low, exercise performance can be negatively impacted, so it is important for athletes to remain in adequate vitamin C status by consuming fruits and vegetables each day, as part of a balanced diet. One of the reasons for decreased athletic performance when vitamin C status is low is due to compromised carnitine synthesis, decreasing fatty acid β-oxidation. In other words, the body has a decreased efficiency of using fat as fuel- which is the dominating fuel source in distance running, and other endurance sports. 

When the athlete has adequate amounts of vitamin C, supplementation will not improve performance. Additionally, supplementation (when taken short term) either in pre or post exercise, does not improve markers for inflammation, muscle damage, nor oxidative stress, but long term supplementation may. However, supplementation may inhibit training adaptations needed for improved performance (as discussed above).

Vitamin C supplementation

Many vitamin C supplements contain amounts exceeding the upper tolerable  limit of 2g/day, but even amounts less than that, such as 500mg may cause negative GI side effects. As the vitamin C dose increases, the absorption rate decreases. In high amounts (as with supplementation), all the vitamin C that goes unabsorbed passes through the digestive tract for excretion in the feces, and may cause osmotic diarrhea during the process. Some individuals experience other gastrointestinal (GI) side effects such as nausea, and cramping. 

As discussed above, once oxidative stress has begun, supplementation with vitamin C (or any antioxidants) can exacerbate the problem by generating more ROS. When oxidative stress occurs, the resulting cell damage causes the release of transition-metal ions. Vitamin C reduces the free metal ions, which then become free radicals (the antioxidant paradox). Additionally, many of the  antioxidants rely on each other for their functions and regeneration, therefore, it’s important to get sufficient amounts of vitamin C and other antioxidants from a healthy, well-balanced diet, rather than excess amounts by supplementation.

Vitamin E 

Functions of Vitamin E

Vitamin E has both antioxidant and non-antioxidant functions. It’s a membrane bound antioxidant, making it important for membrane integrity and free radical termination. Some of the non-antioxidant roles of vitamin E include cell signalling for both gene expression and enzyme functions. 

Food Sources of Vitamin E and Requirements (RDA)   

There are 2 classes of vitamin E- tocopherols and tocotrienols, with each class having 4 isomers. Only one isomer in each class is found naturally in foods (the RRR isomers); the other isomers are synthetic and are often in supplements. All the 8 possible isomers, fall under the umbrella term vitamin E. Tocopherols are present in a wider variety of foods than are tocotrienols, and they are also more bioavailability (absorbed and utilized more efficiently) than tocotrienols. 

Some of the food sources of vitamin E include wheat germ, vegetable oils, nuts, and avocados. The RDA for vitamin E is 15 mg/day for both men and women. This can be easily met through a well-balanced diet with sufficient energy and fat intake. Eating a variety of  healthy fat sources (e.g. olive oil, nuts, seeds, avocado) is a good way to meet your vitamin E requirements. Additionally, consuming fats regularly, as part of a balanced diet, contributes to meeting  your essential fatty acid needs, and aids in the absorption of fat soluble vitamins. 

Vitamin E Supplementation and Exercise 

Supplementation of vitamin E will not improve aerobic performance. There are mixed study results on vitamin E supplementation on strength training performance outcomes. Vitamin E supplementation (as with the other antioxidant supplements) can hinder performance by interfering with cell signaling of reactive oxygen species, negatively affecting muscle function. Additionally, chronic vitamin E supplementation has been associated with all-cause mortality. It is not recommended to supplement with vitamin E. 

 In summary

• Vitamin C functions (not an exhaustive list) 

  • Collagen synthesis

  • Antioxidant and Pro-oxidant 

  • Carnitine synthesis 

  • Non-heme iron absorption and transport 

  • Neurotransmitter synthesis 

  • Antihistamine properties- thought to mitigate cold severity 

• Vitamin E functions (not an exhaustive list) 

  • Membrane bound antioxidant 

  • Cell signaling 

• Athletes may have slightly increased antioxidant needs, which can be easily met by their overall increased energy intake 

• Exercise may be negatively impacted if vitamin C or vitamin E status is low/ inadequate

• Antioxidant supplementation does not improve athletic performance

  • Long term supplementation may decrease markers for inflammation, oxidative stress and muscle damage 

• Maintain adequate vitamin C status through frequent consumption of fruits and vegetables; aim for at least 5 servings/day, 9 servings/day is better) 

• Use vegetable based oils and consume other healthy fat sources to meet your vitamin E requirements (see page on fats!) 

• Avoid supplementation, unless you have a special circumstance that does not allow you to meet RDA and/or maintain adequate for antioxidant vitamins and minerals

 References

Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial. Nutrients. 2014 Jul 9;6(7):2572-83. doi: 10.3390/nu6072572. PMID: 25010554; PMCID: PMC4113757.

Peake, J. M. Vitamin C: Effects of Exercise and Requirements with Training (2003), International Journal of Sport Nutrition and Exercise Metabolism, 13(2), 125-151. 

Johnston, C.S., Corte, C. & Swan, P.D. Marginal vitamin C status is associated with reduced fat oxidation during submaximal exercise in young adults. Nutr Metab (Lond) 3, 35 (2006).

Nikolaidis MG, et al. Does vitamin C and E supplementation impair the favorable adaptations of regular exercise? Oxid Med Cell Longevity 2012.