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AND
WILLIAM J. KRAEMER2
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.
1
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
radicalmediated tissue damage associated with long-term
vigorous exercise programs is unknown.
Introduction
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).
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
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
Vitamer
RRR-D-alpha-tocopherol
RRR-D-beta-tocopherol
RRR-D-alpha-tocopherol acetate
RRR-D-alpha-tocopherol succinate
IUmg21
Tocopherol
equivalents
1.49
0.75
1.36
1.21
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.
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-
Conclusion
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-
21.
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