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Vol.5, No.11 November 2007

Antioxidants for Athletes
Reviewed by Patricia B. Rosen, MD, MPH

Introduction
Every athlete probably knows of antioxidants for their health benefits, but can antioxidants make an athlete faster? How do antioxidants fit into an athlete's regimen for performance and recovery? What exactly is an antioxidant? Tending to look first at products for performance and then at recovery systems, athletes often overlook antioxidants. Crucial not only for the health of the cardiovascular system, they can also aid in performance and recovery. For many years scientists as well as consumers have known of the antioxidant powers of vitamins E & C and selenium. Today, this category has expanded to include oligomeric proanthocyanidins (OPCs), Alpha Lipoic Acid, grape skin, grape seed, beta-carotene, lutein, tocopherols, tocoretinols and various other compounds. It can certainly be confusing since so many supplements, both traditional and newly introduced, can be classified as antioxidants.

What is an antioxidant?
An antioxidant slows or prevents oxidation of other molecules. Injury may occur when a substance with an incomplete electron shell (a free radical) attaches to another molecule such as a cell wall or the mitochondria. An antioxidant provides that missing electron to prevent this damage to cells.

What is oxidative stress and how does it affect me? Oxidative stress is the sum of all chemical reactions giving rise to free radicals or "reactive oxygen species" (ROS) in the body. ROS are generated when the body is exposed to a variety of different conditions and environments (see table 1 for examples). But it's not all bad news.

Table 1. Situations and/or Environments that Generate ROS
Pollutants (C02, N02)
UV Light
Increased oxygen consumption (high intensity activity)
Radiation
Inflammation
Altitude
Drugs
Smoking


Although we require oxygen for our existence, it is a highly reactive molecule. Consequently organisms have developed a network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cells. In general, these systems and enzymes prevent these reactive species from being formed or remove them before they cause damage. The use of oxygen to generate energy results in development of the superoxide anion as one of the byproduct which coenzyme Q is an important antioxidant to remove this unstable intermediate. Although in the strictest sense, oxidation and reduction refers to the chemical processes of donating or requiring an electron, oxygen itself can be the source of reactive intermediaries.

So then, what exactly are examples of some antioxidants? Keep in mind that free radicals have one or more unpaired electrons that try to remove an electron from a stable molecule in order to stabilize themselves. Therefore, an antioxidant is a nutrient that offers an electron-rich binding site for these damaging free radicals, giving them a preferential site to bind to and pair up with missing electrons. Antioxidants can be classified into water soluble and lipid soluble forms

Table 2. Examples of antioxidants

Water SolubleLipid Soluble
Ascorbic acid (vitamin C)?-tocopherol (vitamin E)
GlutathioneUbiquinol (coenzyme Q)
Lipoic Acid
Uric acid

Cells are protected against oxidative stress by a network of antioxidant enzymes. The processes usually involve the action of several enzymes in sequence such as superoxide dismutase and then catalase. Superoxide dismutase is present in almost all aerobic cells and in extracellualr fluids. These enzymes contain metal cofactors such as copper, zinc, iron and manganese, making these ions a part of the antioxidative process.

The thioredoxin system contains cysteines which provide a dithiol form to act as a reducing agent. After being oxidized, the thioredoxin is regenerated using NADPH. The glutathione system includes multiple enzymes which has selenium as a cofactor. There are several different forms of glutathione peroxidase isoenzymes in animals and the glutathione S-transferases offer another form of antioxidant enzyme

Antioxidants like Vitamin E, C and A, vitamins like compounds (glutathione, lipoic acid), and phytochemicals (flavonoids, polyphenols) play a role in our defense system when consumed in a balanced diet through foods or taken orally as dietary supplements. You probably recognize now that oxidative stress is unavoidable for humans, but of special concern to us as endurance athletes is the oxidative stress simply due to increased oxygen consumption during exercise. This is in addition to our higher exposure to environmental oxidative stress from altitude, the UV rays, inflammation from muscle damage, and pollution.

How do I best use antioxidants as an endurance athlete? Athletes who train competitively experience more oxidative stress than the average individual. Oxygen consumption can increase by a factor of more than 10 resulting in a large increase in oxidants and damage that contribute to muscle fatigue during and after exercise. . However, it is still not clear from all of the data whether strenuous exercise increases the need for additional antioxidants. One study showed that oxidative stress may account for the body’s ability to adapt to exercise stress. There is evidence that one of the adaptations from exercise is a strengthening of the body’s antioxidant defenses, in particular the glutathione system.

ORAC=Antioxidant Quality: An analytical method developed by Dr. Cao and Dr. Ronald Priori in conjunction with the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, MA and Brunswick Laboratories, Inc., Wareham, MA measures the quality of an antioxidant. Oxygen Reactive Absorbency Capacity (ORAC) is a quantitative measure of an antioxidants ability to neutralize oxygen free radicals. The clinical data supporting this methodology has become the gold standard for the measurement of an antioxidants free radical scavenging ability. Foods that score high in an antioxidant analysis called ORAC help protect cells and their components from oxidative damage. So suggests the latest studies of animals and human blood at the Agricultural Research Service's Human Nutrition Research Center on Aging at Tufts University in Boston. The higher a food’s ORAC score, the better it is at helping our bodies fight against the damages of oxidative stress.

Previous research on antioxidants in athletes: Emerging evidence has indicated that fruit and vegetable consumption are directly correlated with antioxidant status. While this has been known for sometime, what is becoming more and more apparent is that some athletes are not obtaining adequate amounts of antioxidant compounds in their diet due to a low intake of fruits and vegetables.

While there is still debate among the literature regarding the efficacy of dietary supplementation of antioxidant compounds, there have been a few recent studies that are of special note.

One study compared the effects of normal antioxidant supplementation with reduced antioxidant supplementation in acute, high intensity exercise of up to 40 minutes. The reduced antioxidant group of athletes had a three-fold decrease in antioxidant intake and associated with a higher rating of perceived exertion, a lower antioxidant capacity and circulating antioxidant concentrations. However, time to fatigue was not significantly different and the authors concluded that supplemental antioxidants may not be necessary for athletes engaged in less than 40 minutes of high-intensity exercise as long as an antioxidant rich eating plan was followed.

Another study examining the effects of ultra-running (six long duration races in the desert) on antioxidant status in well trained endurance athletes found quite the opposite results. Blood draws before the race and 72 hours after the race showed significant decreases in erythrocyte superoxide dismutase activity and in plasma concentrations of retinol, beta-carotene and other carotenoids. However, there was an increase in erythrocyte glutathione and glutathione peroxidase was not significantly affected and tended to increase. Plasma concentration of vitamin C and alpha tocopheral were not significantly affected initially but did decrease after the athletes returned from their competition. Markers for lipid peroxidation did significantly increase. This caused an imbalance between oxidant and antioxidant protection in this extreme endurance competition, specifically, there was a decrease in superoxide dismutase whereas an increase in this enzymes has been previously observed. This was a small study of only 6 individuals.

Of interesting note on the same topic was a study done that evaluated the effects of antioxidant supplementation (vitamins C, E and beta-carotene) on the basal iron status of athletes prior to and following their training and competition season, which lasted for 3 months. They found that training decreased antioxidant defenses in the athletes who were not taking antioxidants; however, and they also found decreases in serum iron and iron saturation in these same athletes. This may indicate that antioxidant supplementation may prevent the decrease of iron stores and that iron status and oxidative stress are linked.

New Antioxidant Research (2005-2007): The newest original research articles on antioxidants in athletes are showing mixed results. Here are the findings from some reputable peer-reviewed scientific journals.

New evidence suggests that a combination of Vitamins C and E may prevent some cell damage in response to exercise training. One study showed that 28 days of Vitamin E (290IU alpha & 130IU gamma) and C (500mg) supplementation can reduce blood and muscle levels of heat shock protein 72 (cell level indicator of muscle damage) for 3-6hrs after a 3hr bout of knee extensor resistance exercise at 50% of max power (Fischer et al. 2006). Another study revealed that an antioxidant beverage (mix of fruit juices at 0.41mM Trolox) countered oxidative stress (measured by carbonyls and urinary excretion of 8-OHdG) induced by a 90min cycle test at 70%VO2max in moderately trained cyclists (Morillas-Ruiz et al. 2005).

This past year, there were also several well-designed studies that found no benefits to antioxidant supplementation in athletes. One showed that Vitamin C supplementation (1g 2hr pre and 14d post) did not reduce delayed onset muscle soreness (DOMS) from downhill running and may even slightly inhibit the recovery of muscle function (Close et al. 2006). Another study found that six weeks of Vitamins C (1g) and E (300mg alpha) supplementation did not alter blood markers of muscle damage or maximum voluntary muscle contraction 2hr-6d post marathon (Mastaloudis et al. 2006). A very well designed study revealed that three weeks of antioxidant supplementation did not prevent the exercise induced stress response (a rise in plasma IL-6 or C reactive protein) 2-20hr after exercise at high altitude (4300m; Hagobian et al. 2006). Although, only a short study, 7 days of antioxidant supplementation did not prevent muscle cell damage following exhaustive exercise (Davison et al. 2005). This same scientist also showed that a sports beverage with CHO and Vitamin C did not change stress hormone or immune response to 2.5hr exercise at 60%VO2max relative to CHO alone (Davison et al. 2005).

The data for benefit from vitamin A and E are not clear. In one study there was not an effect on muscle damage in ultramarathon runners with exogenous vitamin A and E. However, vitamin C is important as a reducing agent and a substrate for antioxidants. Vitamin C has been found to decrease the incidence and severity of upper respiratory infections in a review that included a subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises.

Alpha lipoic acid and N-acetylcysteine help to maintain cysteine supplies and thus provide a means to replenish glutathione in the body. Glutathione helps to maintain a healthy redox state. Some studies have shown no effect on non-exercised muscle but improved performance with exercise. Others have shown a decrease in glutathione oxidation without an effect on muscle strength. The authors concluded in these studies that this represented an effect on fatigue. Another study showed an increase till the time of fatigue with pretreatment with N-acetylcysteine using a sample of cyclists exercising at 92% VO2 max. Glutathione is known to minimize lipid peroxidation of cellular membranes and other targets of oxidative stress. Lipid peroxidation decreases the ability of cells to take up glucose or to respond to varying levels of immune challenges. (Kerksick and Willoughby) Bioavailability of glutathione is limited due to the effect of hydrolytic enzymes that break down glutathione after ingestion. However, N-acetyl-cysteine provides cysteine which is the rate-limiting substrate for glutathione resynthesis.

Note that in one study that after extreme resistance training that a supplementation with vitamin C and N-acetylcysteine there was in increase in free iron, and markers of protein breakdown similar to that seen in those using placebo. (Childs)

A recent review of the above articles and more clarified some of the reasons that the literature is not entirely clear. It is important to also note that these articles refer primarily to antioxidant activity and not to other benefits or problems with vitamins or other antioxidants. It is also important to remember that other potential anti-oxidants have not been researched or reviewed as extensively as Vitamin A, C and E.

This recent review (Peake JM, Suzuki K) makes several significant points. One is that the dosing of different supplements may affect benefit. If the dose of Vitamin E or C is too high, there may be a pro-oxidant effect. This has been shown in some studies but not in all. The form of the vitamin makes a difference as well. RRR-alpha-tocopherol may attenuate release of some reactive species where as all-rac or DL-alpha tocopherol is less effective due to bioavailability. Thus the dose of the later or synthetic form would have to be twice as high to have comparable benefits. The time of dosing is important. It appears that for Vitamin C to be of benefit it must be given two weeks prior to an athletic event. Note that vitamin C if it is only given at the time of the event may not have any influence at all on oxidative stress.

The use of vitamins in combination appears in some studies to be more effective than when given alone. (Vitamin C and E) Fat content of the diet may affect one’s ability to absorb vitamin E so adequate fat intake may be necessary.

There were differences in the studies between the subjects evaluated. Since there is an upregulation of anti-oxidant enzymes in those with endurance training, supplementation may not be seen to be as beneficial as in those who are not trained. The type of training and exercise makes a difference. In eccentric testing, or isolated strength training, there is more muscle break down than in concentric training (cycling). The benefit of antioxidant supplementation may not be as significant when there is a great deal of muscle break down. The same is true in those who do utlra-endurance exercise. These individuals may require a much higher dose of antioxidants to note a benefit. It appears that when antioxidant systems are balanced, that pro-oxidant effects are less likely to be seen. Apparently this has to do in part with a decrease in benefit in association with greater muscle damage due to an overwhelming of these systems. Another question is whether muscle damage is the product of reactive oxidative action or whether the muscle damage is due to the action of reactive oxidative species. Regardless, anti-oxidants do attenuate evidence of oxidative injury in many of these studies.

Another variable that is not always taken into account is the dietary intake of the subjects. Participants may have been asked to avoid certain foodstuffs in these studies but prior dietary habits will have an effect on study results. Beyond a certain level of dietary intake, concentrations of antioxidants within the circulation and tissues are saturated.

Recommendations: It is estimated that only 10% of the U.S. population consumes five servings of fruits and vegetables per day. Due to the nature of aerobic training, endurance athletes may need further protection from the damage of oxidative stress. Some of the newest clinical research suggests that this oxidative protection may even lead to improved performance. With abundant formulas and antioxidant concoctions in the marketplace, don't rely on a single compound. Look for a formula or multi-vitamin that contains a variety of antioxidants. If you are shopping for antioxidant supplements consider vitamins such as C & E, and Beta-Carotene as well other antioxidants such as alpha-lipoic acid and N-acetylcysteine which function as gluthione precursors. Also consider the following in your search for an appropriate formula: grape seed extract, carotenoids, pycnogenol, lutein, lycopene, bioflavanoids, green tea, turmeric and quercetin. In some newer formulas you can also specifically find antioxidants which have been analyzed for their ORAC value.

Even though it's easier to take a handful of supplements, a healthy diet should be the basis of your antioxidant defense system: brightly colored fruits and vegetables along with certain grains, seeds, and nuts provide excellent sources of antioxidants to protect your cells from unwanted oxidative damage. As an athlete, your best bet is to eat fresh, whole foods on a regular basis so you're not relying solely on supplements for antioxidants. Note that the research also supports improved benefit when the source of the antioxidants comes from foods, potentially due to the added benefit of flavonoids with antioxidants. Clearly it is important to have adequate antioxidants in your system more than two weeks prior to an event. The use of supplements only at the time of the event is not likely to be of benefit.

Look at the table below for options to increase the color and antioxidant power in your diet.

Vitamin C rich foods Vitamin E-rich foods Carotenoid-rich foods
(beta carotene, lycopene, lutein)
Orange, orange juice Almonds Tomatoes
Cantaloupe Hazelnuts Sweet potatoes
Cranberry juice Sunflower seeds Carrots
Grapefruit, grapefruit juice Spinach Broccoli
Strawberries Sweet potato Brussel sprout
Kiwi Olive, sunflower, canola oils Spinach, Kale
Papaya Wheat germ Kale
Spinach Fortified cereals (some) Collard Greens
Broccoli   Cantaloupe
Sweet red peppers   Mango
Asparagus   Egg yolk


The damaging effects of oxidation can take years, even a lifetime to reveal their impact. Antioxidants should be viewed as insurance against this damage. With long-term consumption of antioxidants you will support healthy cells leading to healthy cellular respiration. If you train heavily day in and day out, antioxidants should be a staple in your training diet. Within a few months of increased consumption you should notice reduced incidence of infection, faster recovery and better workouts.

Taking into consideration all of the newest research on antioxidants and athletes, there appears to be a few take home messages:

1. Athletes may not eat enough fruits and vegetables to obtain adequate amounts of antioxidants
2. Antioxidant supplementation may not be of benefit if only used just prior or during an event and should be part of your daily routine and life style.
3. In ultra-endurance events, oxidative stress is high and antioxidant levels are compromised.
4. There may be an association between iron status and oxidative stress.
5. The combination of antioxidants available in natural food sources may have added benefit when compared to isolated vitamin supplementation.

Overall, the take home message of increasing fruit and vegetable intake to a minimum of 6-9 servings per day is still valid and will supply the athlete with a good amount of vitamins, minerals and antioxidants. However, if the athlete is competing in longer duration events, antioxidant supplementation may be of benefit and therefore the athlete should pay closer attention to their overall eating and supplementation program.

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Endurance Research Board
Sally Warner MA Ph.D.
Neal Henderson MS CSCS
Shawn Dolan RD Ph.D.
Bob Seebohar MS RD CSSD CSCS
Jeffrey Rocco MD
Patricia Rosen MD, MPH
Kris Walker MD




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