Free Radicals, Exercise, and Antioxidants - Setanta College

Journal of Strength and Conditioning Research, 1999, 13(2), 175–183 

1999 National Strength & Conditioning Association 

Free Radicals, Exercise, and Antioxidants 

JEFFREY M. MCBRIDE 1 AND WILLIAM J. KRAEMER 2 

1 School of Exercise Science and Sport Management, Southern Cross University, P.O. Box 157, Lismore, NSW 

2480, Australia; 2 Center for Sports Medicine, The Pennsylvania State University, University Park, 

Pennsylvania 16802. 

ABSTRACT 

The relationship between free radicals, antioxidants, and exercise 

has become a current topic of interest. Most of the free 

radical production within the body involves oxygen, and 

thus the free radicals are often referred to as reactive or reduced 

oxygen species. Several mechanisms for the production 

of free radicals in the body have been proposed. The 

mitochondria and ischemia-reperfusion injury have been areas 

of focus. Free radicals cause cellular damage by reacting 

with the phospholipid bilayer of cellular membranes. This 

reaction results in the production of measurable end products, 

primarily malondialdehyde. Several studies have measured 

malondialdehyde as a marker for free radical production 

with exercise and have met with varying results. The 

contradiction of results in previous studies may be due to 

differences in the assay procedures or the physiological demand 

of the exercise protocols used. Vitamin E, vitamin C, 

and beta carotene have been suggested to combat the 

amount of cellular membrane breakdown that accompanies 

increases in free radical production. Studies have examined 

the effectiveness of acute antioxidant supplementation on 

single exercise bouts. Some evidence suggests that these vitamins 

combat the cellular damage caused by free radical 

production associated with exercise in an acute situation. 

However, the effectiveness of long-term antioxidant supplementation 

in relationship to free radical production and free 

radical–mediated tissue damage associated with long-term 

vigorous exercise programs is unknown. 

Key Words: vitamin E, ishcemia-reperfusion injury, 

malondialdehyde, cellular damage 

Reference Data: MCBride, J.M., and W.J. Kraemer. Free 

radicals, exercise, and antioxidants. J. Strength Cond. 

Res. 13(2):175–183. 1999. 

Introduction 

The possibility of increased free radical production 

with exercise and the effect of antioxidant supplementation 

has been the subject of recent study (33, 44, 

55, 57). The physiological role that free radicals may or 

may not play in the restructuring and adaptation to 

exercise has led to new areas of research. It is unknown 

if free radical production during exercise is an un- 

wanted by-product or if it is controlled by the body and 

serves a vital purpose in the restructuring of tissue in 

response to some types of physiological stress. It is likely 

that free radicals fill both roles. Free radical production 

as a result of an adverse physiological condition 

can result in nonfunctional and uncontrolled cellular 

damage (14, 20). However, we know that neutrophils, 

which migrate to the site of infection or injury, purposely 

and effectively use free radicals to clear the area 

of foreign invaders or unwanted debris (3). In an attempt 

to curtail damage to cellular membranes caused 

by free radicals in a biological system, the supplementation 

of known antioxidant vitamins has been implemented. 

Some studies have indicated a positive effect 

on the magnitude of damage after supplementation (3, 

33, 40, 64). The concept of free radicals provides a new 

interactive variable into exercise models. This variable 

must be considered for future study in the area of exercise-related 

tissue damage and adaptation. 

Chemistry of Free Radicals 

Any chemical species that possesses an unpaired electron 

or odd number of electrons may be labeled as a 

free radical. Free radicals exist in a state of thermodynamic 

instability. They are highly reactive and 

search to combine with another molecule to pair off 

its lone electron. These radicals can be formed by several 

mechanisms: electron transfer, heterolytic fission, 

and homolytic fission (10). There are 3 important steps 

in free radical reactions (29). The initial step is chain 

initiation in which a free radical is formed, usually by 

homolytic fission. Chain propagation, which is the 

next step, involves a reaction where a free radical is 

consumed but a new free radical is produced to continue 

the chain. As the reaction proceeds many radicals 

are present at once. The final step is when a chain 

termination reaction occurs when 2 free radicals combine, 

thus pairing off each other’s lone electron. 

Oxygen-Derived Free Radicals 

The formation of free radicals in biological systems revolves 

around oxygen and has been previously reviewed 

(21, 25). These free radicals involving oxygen 

175

176 McBride and Kraemer 

have been named reactive or reduced oxygen species. 

These species include singlet oxygen, superoxide anions, 

and hydrogen peroxide (25). However, perhaps 

the most focused on has been the hydroxyl radical. 

This free radical is highly reactive and is the primary 

source of the destructive mechanisms behind free radical 

formation in biological systems. The hydroxyl radical 

is diffusion controlled, meaning it will not travel 

a significant distance in the cell before reacting. It has 

a short half-life but can cause an extreme amount of 

damage within a small radius of where it is produced 

(10, 54). The presence of ferrous iron and cuprous copper 

in biological systems results in the formation of 

the most highly reactive reduced oxygen species. This 

can occur by several reactions and is a major factor in 

oxidative tissue damage (63). 

Mechanisms for Free Radical Production 

Mitochondria. Most free radical generation within the 

cell occurs by electron transfer reactions (10). Electrons 

leaked from electron transport chains react with molecular 

oxygen. This process occurs within the mitochondria 

and endoplasmic reticulum of the cell. The 

steps between the negative end of the respiratory chain 

and cytochrome c are capable of producing a superoxide 

anion via electron transfer (66). This sequence 

can also lead to the formation of hydrogen peroxide. 

The presence of transition metal ions can lead to the 

formation of the highly reactive hydroxyl radical. Production 

of these free radicals in mitochondria has been 

shown to be a result of inhibition of the respiratory 

chain due to hyperoxia and calcium overload (66). 

Inflammation. Not all free radical formation in biological 

systems is accidental. Catalysis caused by some 

enzymes is the result of their use of a free radical at 

the active site in response to inflammation (10). These 

radicals are not truly free because they are targeted 

toward a specific reaction. However, the use of such 

enzymes may result in leakage of free radicals and 

subsequent uncontrolled tissue damage. There are 

many enzymes capable of generating free radicals. 

Two enzymes of current interest are nicotinamide adenine 

dinucleotide (NADPH) oxidase, which is found 

on the cell membrane and within phagocytic cells, and 

xanthine oxidase, which is found primarily in the liver 

and in some endothelial cells (71). 

Trauma-mediated agonists that bind to cell membrane 

receptors may cause free radical formation via 

NADPH oxidase release from phagocytic cells. These 

phagocytic cells, primarily neutrophils, are part of an 

organism’s immune response to infection or injury. 

Neutrophils migrate to the site of injury or infection 

by chemotaxis and act in 3 functional ways: to phagocytize 

foreign or damaged fragments, to release proteolytic 

enzymes via degranulation, and to release free 

radical–forming enzymes that act to break down foreign 

or damaged fragments (40). The latter function is 

Figure 1. Neutrophil activation can result in free radical 

formation via nicotinamide adenine dinucleotide oxidase. 

Damage to endothelial cells during ischemia via xanthine 

oxidase coupled with histamine enhancement can also result 

in free radical production. Modified from Ward et al. 

(71). 

known as the respiratory or oxidative burst, and the 

complete sequence of events involved in this function 

is still unclear. Xanthine oxidase is thought to be activated 

by ischemia. Histamine release by mast cells 

has also been suggested to enhance the catalytic ability 

of xanthine oxidase. Figure 1 shows how all these 

mechanisms may be related to the production of free 

radicals and subsequent tissue damage (71). 

Ischemia Reperfusion. All the previously mentioned 

mechanisms for free radical production can be related 

back to ischemia-reperfusion injury. Ischemia, from 

whatever cause, results in a decrease in oxygen and 

substrate availability. The lack of adenosine triphosphate 

(ATP) due to the inability of anaerobic means to 

maintain pace with energy demands results in damaging 

effects (46). The breakdown of ATP and the activation 

of xanthine oxidase from xanthine dehydrogenase 

(Figure 2) during ischemia have been related 

to production of free radicals and tissue damage during 

reperfusion. 

Ischemia also results in phagocytic cell responses 

via NADPH oxidase. The following reaction shows the 

formation of the superoxide anion and subsequent 

damaging free radicals (3). 

4O2 4NADPH → 4H 

4O2 4NADP 

Membrane ionic concentrations may also be disrupted 

during ischemia-reperfusion injury (46). Reperfusion 

causes an influx of calcium in exchange for 

previously influxed sodium due to membrane disruption 

(4, 53). This calcium influx could result in the active 

sequestering of calcium within the mitochondrial 

matrix, which may lead to dysfunction (66). This cal-

Figure 2. Ischemia-reperfusion injury has been shown to 

result in tissue damage via xanthine oxidase, which is the 

active form of xanthine dehydrogenase. This activation is 

the result of ischemic conditions. When reperfusion occurs 

the result is free radical formation and subsequent tissue 

damage. Modified from Ward et al. (71). 

cium influx results in an inhibition of the rate of 

NADH-supported electron flow, thus blocking the respiratory 

chain and subsequently stimulating superoxide 

and hydrogen peroxide production (66). Reperfusion 

may be essential for the salvage of reversibly 

damaged cells as a result of ischemia. However, the 

great increase in oxygen availability or hyperoxia may 

result in superoxide anion production from the electron 

transport system, resulting in more tissue damage 

(66). In one study examining free radical formation, 

it was demonstrated that free radical concentrations 

increased in rats that underwent 2 hours of ischemic 

conditions and 1 hour of reperfusion. In 

addition, these increases in free radicals were accompanied 

by significant increases in muscle water content 

and serum creatine kinase levels. These increases may 

indicate membrane disruption (59). Other studies have 

also suggested that ischemia-reperfusion injury may 

be mediated by free radical formation (23, 40). 

Mechanisms by Which Free Radicals Cause Tissue 

Damage 

The reaction of free radicals with cell membranes is 

one of the events that leads to tissue damage. Cell 

membranes are organizations of phospholipid molecules 

into a lipid bilayer consisting of a polar (negatively 

charged) phosphate group and 2 nonpolar (electrically 

neutral) fatty acid tails (43, 60). The inner region 

of the lipid bilayer consists of the hydrophobic 

polyunsaturated fatty acid tails, which readily cause 

free radical reactions (48, 52, 70). This chain reaction, 

as mentioned previously, is self-perpetuating. Hydroperoxides 

are the products formed as a result of the 

free radical reactions that occur with cell membranes 

(68). This process by which hydroperoxides are 

formed is identified as lipid peroxidation. Lipid peroxidation 

is a free radical chain reaction that can be 

initiated by the hydroxyl radical or transition metal 

Free Radicals 177 

Figure 3. This chain reaction is described as lipid peroxidation. 

This process involves the reaction of free radicals 

with the polyunsaturated fatty acids within the cell membrane. 

Measurable end products consist of aldehydes. The 

most abundant of the aldehydes formed is malondialdehyde. 

Modified from Cheeseman and Slater (10). 

Figure 4. The reaction of free radicals results in the disruption 

of the structural integrity of the cell membrane resulting 

in measurable end products. Modified from Sjodin 

et al. (61). 

complexes (2, 28, 67). The reactions in Figure 3 are the 

primary steps in the formation of hydroperoxides (10). 

In the initial reaction LH is the target polyunsaturated 

fatty acid and R is the ‘‘attacking’’ free radical. Oxidation 

of polyunsaturated fatty acids leads to the formation 

of a fatty acid radical (L ) and adds oxygen to 

form a fatty acid peroxyl radical (LOO ). Peroxyl radicals 

can oxidize other polyunsaturated fatty acids, 

which results in new chain reaction formation. This 

process results in the formation of lipid hydroperoxides 

(LOOH). These hydroperoxides can break down 

into other free radical species or other compounds, the 

most significant being aldehydes (18, 49). The decomposition 

of hydroperoxides results in formation of aldehydes 

of various chain lengths. Malondialdehyde 

(MDA), a 3-carbon-chain aldehyde, is one the primary 

aldehydes formed (61). Figure 4 shows how free radical 

reaction with the membrane results in MDA production. 

Measurement of MDA has become the most 

commonly used indicator of lipid peroxidation.


Measurement of Lipid Peroxidation 

The assay used most often for the determination of 

products formed from lipid peroxidation is a procedure 

that uses thiobarbituric acid (TBA). The general 

procedure involves a sample heated with TBA at a low 

pH. A pink chromogen (TBA-MDA adduct) is formed 

and measured at an absorbance of 532 nm or by fluorescence 

at 553 nm (6). There have been criticisms of 

the TBA test that have been used in many studies looking 

at the production of lipid peroxidation products 

(27). It has been suggested that substances found in 

blood other than MDA also form adducts with TBA. 

This may contribute to high estimates of MDA, unless 

high-performance liquid chromatography (HPLC) is 

used to separate these substances (27). However, it has 

also been argued that many of these interfering compounds 

are not normal constituents of biological material 

(6). Two primary concerns for this assay are not 

to overheat the samples and to limit the use of metal 

catalyst, since both can lead to erroneously high estimates 

of serum or plasma MDA concentrations (6). 

Studies using an HPLC method typically report much 

lower MDA levels compared with spectrophotometric 

assays without the use of HPLC. It is unclear at this 

time which is the most effective. 

Free Radical Formation with Exercise 

Aerobic Exercise. There are many possible mechanisms 

for the production of free radicals during exercise. The 

first involves hyperoxic injury that may occur in highly 

intense aerobic exercise. During this type of exercise, 

oxygen consumption can increase up to 10–20 times 

resting levels (1). This may result in a flux of oxygen 

into exercising muscles by as much as 100–200 times 

above their resting state (35). As mentioned previously, 

mitochondria, or more specifically the electron transport 

system, is the likely site of free radical generation 

during adverse conditions in the body. Mitochondria 

subjected to a great influx of oxygen forms superoxide 

radicals that may lead to the formation of other more 

harmful radicals (72). It has been shown that as intracellular 

oxygen concentrations increase the rate of electron 

leakage to oxygen increases (66). However, in one 

animal model mitochondrial malfunction only occurred 

after 40–50 hours of exposure to 100% oxygen 

and most tissue damage occurred in the lungs (66). 

Another situation may involve intensities above 

100% of maximal oxygen consumption. Exercise at this 

intensity may result in a lack of ATP availability along 

with an increased rate of adenosine diphosphate production. 

This may activate free radical generation via 

the aforementioned mechanism involving xanthine oxidase 

(61). 

The most likely source of free radical production 

during aerobic exercise is the situation known as ischemia-reperfusion 

injury. During exercise many organs, 

such as the liver, kidneys, and the splanchnic 

region, may experience hypoxia. This hypoxia is due 

to the shunting of blood to working muscles (72). After 

exercise these organs are reperfused with oxygen after 

blood flow is returned to normal. This results in the 

formation of free radicals and lipid peroxidation products 

by the previously mentioned mechanisms seen in 

ischemia-reperfusion injury studies (34, 73). It has 

been suggested that most of the lipid peroxidation 

products that are measured during aerobic activity at 

above 100% of maximal oxygen consumption are from 

the liver (67). This is due to the finding that blood flow 

may be reduced to one-fifth of normal to the liver during 

exercise of this type (1). 

Several studies have looked at the effect of exercise 

above 100% of maximal oxygen consumption on the 

formation of free radicals by measuring lipid peroxidation 

products. Some studies found no difference in 

MDA concentrations before and after exercise (56, 64). 

Other studies indicated a significant increase with exercise 

(32, 39). It is not clear why the studies with aerobic 

exercise have contradicted each other. It may be 

possible that the physical demand of the exercise protocols 

used in the studies that did not show an increase 

in free radical production was inadequate. The 

studies that did indicate a significant increase in free 

radical production used much more vigorous exercise 

protocols, such as an 80-km race. A second possibility 

for the discrepancies is the assay for the detection of 

free radical formation. The types of procedures used 

for the TBA test have been controversial. The one 

study that used an HPLC method reported that MDA 

levels were below the detection limit of 0.1 mol·L 1 

in all samples (56). Methods used in other studies not 

using HPLC techniques have reported resting levels of 

2.26 nmol·ml 1 and postexercise values of up to 4.0 

nmol·ml 1 (32). It is unclear at this time which method 

would be best suited for determination of MDA in 

plasma. It has been suggested that resting levels may 

be around 0.5 mol·L 1 and that assays that strictly 

measure MDA content rarely find any in resting human 

plasma (27). 

Resistance Exercise. During resistance exercise ischemia 

reperfusion may occur within the active muscles, 

possibly even to a higher degree than within other 

organs. Muscles undergoing intense concentric and 

eccentric actions, which occur in muscles performing 

resistance exercise, may experience brief hypoxic conditions. 

Intense muscle actions temporarily decrease 

blood flow and thus oxygen availability. During muscle 

relaxation there is oxygen reperfusion. In addition, 

there has also been membrane disruption as indicated 

by a leakage of intramuscular enzymes into the blood 

such as creatine kinase (64). This could lead to ion fluxes 

such as increases in intracellular calcium levels (66). 

Calcium levels may also be increased due to fatiguerelated 

functional abnormalities in the sarcoplasmic 

reticulum. Increased calcium levels have been shown

to be one of the major factors in affecting mitochondrial 

function in producing free radicals (66). It is also 

likely that the trauma to muscle cells during high-intensity 

exercise results in the activation of inflammatory 

mediators. These mediators act through phagocytic- 

and endothelial-mast cell pathways of free radical 

generation (70). These possible mechanisms indicate 

that resistance exercise may result in free radical 

production beyond what has been measured with aerobic 

exercise. 

From the aforementioned mechanisms, the active 

muscle site in resistance training may result in a significant 

increase in the production of free radicals either 

during or after exercise. Therefore, it is possible 

that a resistance exercise protocol will result in measurable 

increases in lipid peroxidation. A previously 

proposed mechanism of free radical production during 

exercise, especially resistance exercise, is an ischemia-reperfusion 

environment at the muscle site. A 

study looked specifically at this concept using repetitive 

static muscle contractions. A knee extension exercise 

was used with a 10-second exertion phase and 

a 10-second resting phase protocol at 30% of maximal 

voluntary contraction force (55). It was reported that 

plasma MDA remained below the detection limit during 

all measurement times of the exercise protocol. 

This study involved a low-intensity resistance exercise 

protocol and may not be an effective stimulus for a 

significant measurable change in free radical production. 

Another study investigated the effects of eccentric 

and concentric muscle actions on free radical formation 

and related muscle damage (57). Forearm flexion 

and knee extension movements were used, and repetition 

ranges were reported to be 70–80. No significant 

changes in plasma thiobarbituric reactive material or 

muscle MDA content were reported after both concentric 

and eccentric muscle action protocols. This protocol 

involved a 70–80 repetition range, which in resistance 

exercise would also be labeled as low intensity. 

To our knowledge, only one study has looked at 

high-intensity resistance exercise and the effect on free 

radical production (44). This study used multiple 10repetition-maximum 

sets (10-RM set using resistance 

in which only 10 repetitions can be completed) involving 

all the body’s major muscle groups and found a 

significant increase in free radical production. It may 

be that a more demanding resistance training protocol 

is necessary to induce significant measurable changes 

in markers that indicate free radical reaction with cell 

membranes. Possible factors may include the stimulation 

of a greater amount of muscle mass at a higher 

intensity, resulting in considerably higher levels of 

muscle damage. 

The current evidence suggests that free radical production 

within the body depends on exercise intensity, 

whether one is referring to aerobic or resistance exercise. 

An exercise protocol must provide a significant 


disruption to the physiological state of the body. This 

may include significant ischemia-reperfusion conditions 

and muscle damage. 

Free Radicals and Muscle Damage 

Creatine kinase has been used as a marker for muscle 

damage in many studies (11, 12, 17, 42, 62). One study 

looked at creatine kinase responses and serum MDA 

content in runners after an 80-km race (32). A positive 

correlation was found between MDA and creatine kinase. 

In a recent investigation a similar pattern of response 

between MDA and creatine kinase was also reported 

in association with resistance exercise (44). It 

has been suggested that the membrane disruption that 

occurs with high-intensity resistance exercise is, to a 

large extent, simply a result of the mechanical loads 

placed on the muscle. This would result in a disruption 

in the muscle’s structural integrity. However, a 

study by Kraemer et al. (36) that compared a group 

performing a resistance training protocol using 5-repetition-maximum 

sets (5-RM set using resistance in 

which only 5 repetitions can be completed) with 1 

minute of rest between sets (5/1) and a group performing 

the same exercises except with 10-RM sets 

and a 1-minute rest period between sets (10/1) has 

provided evidence to the contrary. This study reported 

that the 10/1 group had a significantly higher creatine 

kinase response. This group was subjected to lighter 

loads yet possibly had greater muscle membrane disruption 

despite the fact that total work was equivalent. 

Studies also have shown that creatine kinase responses 

often peak between 2 to 4 days after eccentric exercise 

protocols. This may indicate that some mechanism is 

continuing to cause damage even after the actual exercise 

bout is completed (12, 17, 45). Mechanisms other 

than just mechanical forces may be responsible for 

muscle membrane disruption after high-intensity exercise. 

The number of circulating neutrophils has been 

shown to continually increase for several hours after 

exercise (9). In addition, malfunctioning mitochondria, 

due to intramuscular increases in calcium, could continue 

to produce free radicals after exercise ceases. 

Free radical formation by previously described pathways 

may play a role in continuing the amount of 

muscle membrane disruption after exercise. 

Antioxidants 

An antioxidant has been defined as a substance that, 

when present in low concentrations in comparison to 

an oxidizable substrate, inhibits or delays the oxidation 

of that substrate (28). The human body has several naturally 

occurring antioxidants. Enzymes such as catalase 

and glutathione peroxidase can break down hydrogen 

peroxide, thereby stopping subsequent free 

radical–generating reactions (25). It has also been 

shown that cytochrome oxidase in the electron transport 

system acts to counter free radical production 

(34).


Vitamin E. There are several nonenzymatic antioxidant 

substances in the body that can be supplemented 

easily. Probably the most focused on and important is 

vitamin E (tocopherols). It has been shown that this 

lipid-soluble vitamin is an effective antioxidant within 

the cell membrane (7, 30). The ability of vitamin E to 

prevent oxidation of unsaturated fatty acids is believed 

to be its primary function in the body (26). The absence 

of vitamin E results in the abnormal structure and function 

of cellular organelles and the cell membrane itself 

(26). Vitamin E supplementation in humans originally 

developed in the search for a treatment of muscle diseases. 

In animal models muscular dystrophy is associated 

with vitamin E deficiency myopathy (5). The protective 

mechanism of vitamin E has been shown in several 

animal models that used contractile activity as a 

stimulus for muscle damage. Vitamin E status in rats 

has been highly correlated with the susceptibility of 

that animal to damage from muscle contractions (31). 

In addition, studies have shown the protective effect of 

oral vitamin E supplementation (51). 

As previously mentioned, models looking at the effects 

of vitamin E supplementation on muscle damage 

have involved muscle contraction. Vitamin E exerts its 

major effect by the oxidation of free radicals (65). The 

mechanisms of ischemia-reperfusion injury have been 

the foundation for which the damaging effects of free 

radical formation may be seen. In rats, tissue markers 

for free radical generation significantly increase during 

ischemia-reperfusion injury. Supplementation of free 

radical scavengers significantly decrease this marker 

(59). It has been shown that free radicals are mediators 

of ischemia-reperfusion injury and that antioxidants 

such as vitamin E are effective in attenuating this injury 

(14, 40). Inflammation that may accompany this 

type of injury is directly linked to the formation of free 

radicals, which results in tissue injury (71). Ischemia 

reperfusion and inflammation are 2 conditions that are 

related to in vivo environmental situations found at 

the site of the muscle during exercise. This may implicate 

vitamin E supplementation as an effective 

means of reducing exercise-induced muscle damage 

due to free radical formation. 

Vitamin C. Vitamin C or L-ascorbic acid has also 

been implicated as an antioxidant. Vitamin C may be 

involved in the regeneration of vitamin E (47). Ascorbic 

acid has been shown to be involved in a key pathway 

related to the generation of vitamin E (58). A recent 

study has shown that ascorbate is an effective antioxidant 

in human plasma (19). It is suggested that ascorbate 

is a potent reducing agent and that it is effective 

in the quenching of free radicals. In addition, ascorbate 

is vital in the protection of retinoids, carotenoids, tocopherols, 

B complex vitamins, and lipids (8). 

Vitamin A. There has been recent confusion over 

how to identify vitamin A because of the varying 

forms that exist in nature (8). Vitamin A is a retinol 

Table 1. Forms of vitamin E and their biological activities. 

Vitamer IU·mg 1 

RRR-D-alpha-tocopherol 

RRR-D-beta-tocopherol 

RRR-D-alpha-tocopherol acetate 

RRR-D-alpha-tocopherol succinate 

1.49 

0.75 

1.36 

1.21 

Tocopherol 

equivalents 

1.00 

0.49 

1.03 

1.03 

and is related to but different from retinoids and carotenoids 

(8). Beta carotene, which is commonly mistaken 

as a vitamin A equivalent, is actually 2 retinols 

with the alcohol groups removed. It is classified as a 

carotenoid (8). Beta carotene has been identified as a 

possible antioxidant because of its ability to scavenge 

singlet oxygen (8, 33). On demand beta carotene can 

be broken down into 2 retinol equivalents (RE) if other 

sources of vitamin A are not available (8). This mechanism 

is how beta carotene has been identified as a 

vitamin A precursor. Much less work has been done 

with vitamin A compared with vitamin E and C as a 

protective antioxidant in relation to exercise. 

Antioxidant Supplementation and Exercise 

Several studies have focused attention on the effects of 

dietary antioxidants in relation to exercise (15, 22, 24, 

37, 41, 47, 69). The amount of each of these vitamins 

to be given has been questioned. The National Research 

Council recommendations for vitamins E, A, 

and C are 8–10 mg·d1 as RRR-D-alpha-tocopherol, 

800–1,200 retinol equivalents (RE)·d1 , and 30–80 

mg·d1 as ascorbic acid, respectively (8). There has 

been much confusion as to the appropriate units for 

these vitamins and how to express them. Vitamin E 

should be expressed in milligrams or tocopherol 

equivalents (TE). One TE is equivalent to 1 mg of RRRalpha-D-tocopherol 

(8). It must be noted that other 

forms of vitamin E are not based on a 1-mg to 1-TE 

ratio (Table 1). This means that milligram dosages 

from different vitamer forms result in different biological 

activities. Therefore, if reporting vitamin E dosages 

in milligrams the vitamer source must also be 

reported. Almost no toxicity or adverse effects have 

been reported with oral administration of vitamin E 

in any vitamer form in doses up to 1,600 mg·d1 (8). 

Vitamin A should be expressed in RE. Precursor 

forms have very different ratios in relation to 1 RE (8). 

One retinol equivalent is equal to 6 g of beta carotene 

as ingested orally as a precursor to vitamin A. However, 

1 RE is equal to 12 g of an ingested mixed provitamin 

A carotenoid (8). Beta carotene can be reported 

in milligrams. Vitamin C can also simply be referred 

to in units of milligrams but should be appropriately 

referred to as ascorbic acid. 

It has been suggested that doses over 1,000% of the 

recommended daily allowance (RDA) are not toxic for

all 3 vitamins (38). It is unclear at this time what the 

optimal dosage of these vitamins would be or in what 

combination to reduce lipid peroxidation during exercise. 

Few studies have looked carefully at comparing 

the effectiveness of each of these vitamins individually 

and in different combined ratios. This makes it unclear 

as to how antioxidant supplementation should be approached. 

One study reported that a mixture of 592 mg of 

vitamin E, 1,000 mg of vitamin C, and 30 mg of beta 

carotene resulted in a decreased level of a lipid peroxidation 

marker after exercise (33). A study involving 

vitamin E supplementation stated that 300 mg of vitamin 

E given for 4 weeks reduced exercise-induced 

lipid peroxidation (64). A study involving resistance 

exercise has also reported the effectiveness of vitamin 

E supplementation in reducing MDA and creatine kinase 

levels (44). In general, the supplementation has 

been implemented for a period of 2–4 weeks before 

exercise. These studies give indication that these vitamins 

are effective in decreasing lipid peroxidation. 

However, specific dosage recommendations cannot be 

made. 

It must be noted that to compare dosages studies 

need to more accurately report the exact form from 

which these vitamins were derived. As shown previously, 

different precursor forms of vitamins result in 

varying ratios of actual vitamin formation in the body. 

Many studies have reported vitamin dosages in an improper 

form. 

Practical Applications 

The literature reviewed suggests that high-intensity 

exercise can result in the production of free radicals 

(32, 39, 44). In addition, it appears that at a minimum 

these free radicals can cause significant disruption to 

muscle cell membranes (32, 44). This may indicate that, 

especially in the early phases of a new and unfamiliar 

exercise program, antioxidant supplementation is necessary 

to combat excessive free radical–mediated tissue 

damage. This is further supported by investigations 

reporting the effectiveness of antioxidant supplementation 

on decreasing free radical–mediated tissue 

damage with intense exercise (33, 44, 64). Vitamin E, 

vitamin C, and beta carotene have been identified as 

potent antioxidants, as covered previously. The following 

provides some information pertaining to an antioxidant 

supplementation program. 

Vitamin E 

Five times the RDA for vitamin E may be necessary 

for prevention of free radical damage (16). Intense exercise 

by athletes may result in free radical production 

3 times that of sedentary individuals (50). Because of 

these findings, it has been stated at the Colgan Institute 

that 1,200–2,000 IU (equivalent to 800–1,350 mg 

of RRR-D-alpha-tocopherol or 800–1,350 TE) of vita- 


min E have been taken daily by athletes (13). This may 

be a necessary dosage to counter free radical formation 

during exercise. 

Vitamin C 

As stated earlier the RDA for vitamin C is 60 mg. It 

has been suggested that this is based on an inaccurate 

and antiquated method for calculating vitamin C requirements 

(13). Dosages given to athletes have been 

reported to be 2–12 g·d 1 . A consensus on reviews has 

shown complete safety with dosages of vitamin C of 

1–5 g·d 1 (8). For musculoskeletal healing dosages of 

500–1,000 mg 2–4 times daily have been taken in the 

form of ascorbic acid (8). 

Beta Carotene 

The amount of beta carotene that would be necessary 

for it to be a significant contributor to antioxidation is 

unknown. The RDA for vitamin A is approximately 

800–1,200 RE·d 1 . Toxicity has been reported in rare 

instances at levels of 25,000 IU, which is approximately 

7,500 RE (7,500 g of retinol, 9,000 g of retinyl acetate, 

and 13,500 g of retinyl palmitate) (8, 23). A safe 

dosage would fall somewhere between these 2 values. 

However, it is beta carotene and not vitamin A that 

acts as an antioxidant, but specific values for beta carotene 

are not clear. Recommended dosage for vitamin 

A in RE·d 1 is 1,000. This would equal 6 mg·d 1 of 

beta carotene. Beta carotene has been shown to be safe 

at any dose. Adverse effects such as oily diarrhea have 

been reported but only at absurdly high levels (8). The 

suggested dosage of vitamin A for effective injury repair 

assistance is 25,000 IUs or 7,500 REs, which would 

be approximately 45 mg·d 1 of beta carotene (8). 

Conclusion 

It now appears that free radical–mediated tissue damage 

may be a new variable in the way tissue remodeling 

occurs after intense exercise (44). Thus, future 

areas of research must focus on the effect of antioxidant 

supplementation and determine if it is in fact desirable 

to curtail tissue damage after intense exercise. 

It is possible that free radical–mediated tissue damage 

is a vital and necessary component of the tissue remodeling 

process. However, it is most likely that the 

shock of a new and unfamiliar exercise bout leads the 

body to overcompensate in the restructuring phase of 

muscle tissue following exercise (12, 17, 45). Excessive 

free radical production during intense exercise or from 

the oxidative burst of neutrophils following exercise 

could lead to damage far beyond what was caused by 

the mechanical forces of the exercise bout (36). High 

doses of anitoxidants before an unfamiliar exercise 

bout may combat the body’s natural overcompensation 

response due to the fact that free radical production 

may be a primary player in this overcompensation 

mechanism. Future study will need to assess the via-


bility of both short-term and long-term antioxidant 

supplementation and its relation to prolonged involvement 

in vigorous exercise programs. 

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