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Journal of Strength and Conditioning Research, 1999, 13(2), 175183

q 1999 National Strength & Conditioning Association

Free Radicals, Exercise, and Antioxidants




School of Exercise Science and Sport Management, Southern Cross University, P.O. Box 157, Lismore, NSW
2480, Australia; 2Center for Sports Medicine, The Pennsylvania State University, University Park,
Pennsylvania 16802.

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
radicalmediated 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):175183. 1999.


he 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 others 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

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
organisms 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
radicalforming 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.

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 1 4NADPH 4H1 1 4O22 1 4NADP1
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-

Free Radicals 177

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
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

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 Rv is the attacking free radical. Oxidation of polyunsaturated fatty acids leads to the formation of a fatty acid radical (Lv) and adds oxygen to
form a fatty acid peroxyl radical (LOOv). 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.

178 McBride and Kraemer

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 1020 times
resting levels (1). This may result in a flux of oxygen
into exercising muscles by as much as 100200 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 4050 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 mmolL21
in all samples (56). Methods used in other studies not
using HPLC techniques have reported resting levels of
2.26 nmolml21 and postexercise values of up to 4.0
nmolml21 (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 mmolL21 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

Free Radicals 179

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 7080. 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 7080 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 bodys 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 muscles 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.
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
radicalgenerating reactions (25). It has also been
shown that cytochrome oxidase in the electron transport system acts to counter free radical production

180 McBride and Kraemer

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.

RRR-D-alpha-tocopherol acetate
RRR-D-alpha-tocopherol succinate





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 810 mgd21 as RRR-D-alpha-tocopherol,
8001,200 retinol equivalents (RE)d21, and 3080
mgd21 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 mgd21 (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 mg of beta carotene
as ingested orally as a precursor to vitamin A. However, 1 RE is equal to 12 mg 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

Free Radicals 181

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 24 weeks before
exercise. These studies give indication that these vitamins are effective in decreasing lipid peroxidation.
However, specific dosage recommendations cannot be
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 radicalmediated tissue damage. This is further supported by investigations reporting the effectiveness of antioxidant supplementation on decreasing free radicalmediated 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 1,2002,000 IU (equivalent to 8001,350 mg
of RRR-D-alpha-tocopherol or 8001,350 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 212 gd21. A consensus on reviews has
shown complete safety with dosages of vitamin C of
15 gd21 (8). For musculoskeletal healing dosages of
5001,000 mg 24 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
8001,200 REd21. Toxicity has been reported in rare
instances at levels of 25,000 IU, which is approximately
7,500 RE (7,500 mg of retinol, 9,000 mg of retinyl acetate, and 13,500 mg 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 REd21 is 1,000. This would equal 6 mgd21 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 mgd21 of beta carotene (8).

It now appears that free radicalmediated 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 radicalmediated 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 bodys 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-

182 McBride and Kraemer

bility of both short-term and long-term antioxidant

supplementation and its relation to prolonged involvement in vigorous exercise programs.



















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