ArticlePDF AvailableLiterature Review

Antioxidant Supplementation during Exercise Training: Beneficial or Detrimental?

Authors:

Abstract

High levels of reactive oxygen species (ROS) produced in skeletal muscle during exercise have been associated with muscle damage and impaired muscle function. Supporting endogenous defence systems with additional oral doses of antioxidants has received much attention as a noninvasive strategy to prevent or reduce oxidative stress, decrease muscle damage and improve exercise performance. Over 150 articles have been published on this topic, with almost all of these being small-scale, low-quality studies. The consistent finding is that antioxidant supplementation attenuates exercise-induced oxidative stress. However, any physiological implications of this have yet to be consistently demonstrated, with most studies reporting no effects on exercise-induced muscle damage and performance. Moreover, a growing body of evidence indicates detrimental effects of antioxidant supplementation on the health and performance benefits of exercise training. Indeed, although ROS are associated with harmful biological events, they are also essential to the development and optimal function of every cell. The aim of this review is to present and discuss 23 studies that have shown that antioxidant supplementation interferes with exercise training-induced adaptations. The main findings of these studies are that, in certain situations, loading the cell with high doses of antioxidants leads to a blunting of the positive effects of exercise training and interferes with important ROS-mediated physiological processes, such as vasodilation and insulin signalling. More research is needed to produce evidence-based guidelines regarding the use of antioxidant supplementation during exercise training. We recommend that an adequate intake of vitamins and minerals through a varied and balanced diet remains the best approach to maintain the optimal antioxidant status in exercising individuals.
Antioxidant Supplementation during
Exercise Training
Beneficial or Detrimental?
Tina-Tinkara Peternelj and Jeff S. Coombes
School of Human Movement Studies, The University of Queensland, Brisbane, QLD, Australia
Contents
Abstract.................................................................................1043
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
2. Basic Mechanisms of Oxidative Damage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
2.1 Redox Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
2.2 The Antioxidant Defence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045
2.3 Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1047
2.4 Beneficial Roles of Reactive Species. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1047
3. Exercise-Induced Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1048
3.1 Reactive Species in Skeletal Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1048
3.2 Adaptation to Exercise-Induced Oxidative Stress. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1048
3.3 Oxidative Stress and Muscle Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1049
4. Antioxidant Supplementation and Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1049
4.1 Overview ........................................................................1049
4.2 Antioxidant Supplementation and Exercise-Induced Oxidative Stress . . . . . . . . . . . . . . . . . . . . . 1049
4.3 Antioxidant Supplementation and Muscle Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
4.4 Antioxidant Supplements as Ergogenic Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
5. Antioxidant Supplementation Interferes with the Beneficial Effects of Exercise Training . . . . . . . . . . . 1051
5.1 Antioxidant Supplements Promote Exercise-Induced Oxidative Stress . . . . . . . . . . . . . . . . . . . . . 1057
5.2 Antioxidant Supplementation Hinders Cell Adaptation to Exercise-Induced Oxidative Stress. . . 1057
5.3 Reactive Oxygen Species Elimination and Physiological Processes. . . . . . . . . . . . . . . . . . . . . . . . 1058
6. Limitations of the Studies and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1059
7. Optimizing Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
7.1 Summary......................................................................... 1060
7.2 Current Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
8. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1061
Abstract High levels of reactive oxygen species (ROS) produced in skeletal muscle
during exercise have been associated with muscle damage and impaired
muscle function. Supporting endogenous defence systems with additional
oral doses of antioxidants has received much attention as a noninvasive
strategy to prevent or reduce oxidative stress, decrease muscle damage and
improve exercise performance. Over 150 articles have been published on this
topic, with almost all of these being small-scale, low-quality studies. The con-
sistent finding is that antioxidant supplementation attenuates exercise-induced
REVIEW ARTICLE Sports Med 2011; 41 (12): 1043-1069
0112-1642/11/0012-1043/$49.95/0
ª2011 Adis Data Information BV. All rights reserved.
oxidative stress. However, any physiological implications of this have yet to
be consistently demonstrated, with most studies reporting no effects on ex-
ercise-induced muscle damage and performance. Moreover, a growing body
of evidence indicates detrimental effects of antioxidant supplementation on
the health and performance benefits of exercise training. Indeed, although
ROS are associated with harmful biological events, they are also essential to
the development and optimal function of every cell. The aim of this review is
to present and discuss 23 studies that have shown that antioxidant supple-
mentation interferes with exercise training-induced adaptations. The main
findings of these studies are that, in certain situations, loading the cell with
high doses of antioxidants leads to a blunting of the positive effects of exercise
training and interferes with important ROS-mediated physiological process-
es, such as vasodilation and insulin signalling. More research is needed to
produce evidence-based guidelines regarding the use of antioxidant supple-
mentation during exercise training. We recommend that an adequate intake
of vitamins and minerals through a varied and balanced diet remains the best
approach to maintain the optimal antioxidant status in exercising individuals.
1. Introduction
Antioxidant supplementation is a common
practice amongst both professional athletes and
amateur sportspersons, and the market offering
various nutrient supplements is immense.
[1]
Al-
though these products have been touted as a
means of preventing exercise-induced oxidative
damage and enhancing performance, consistent
evidence of their efficacy is lacking. Moreover, it
is clear that reactive oxygen species (ROS) pro-
duced during exercise play important roles in
various cellular processes and, therefore, sup-
pressing their formation with high doses of anti-
oxidants might have a deleterious impact on cell
function.
The studies included in the review were identified
by a systematic search using the PubMed database.
Search terms were ‘reactive oxygen species’, ‘oxi-
dative stress’, ‘antioxidant’, ‘exercise’, ‘skeletal
muscle’, ‘muscle damage’ and ‘performance’. Fur-
ther searching was performed by using the ‘related
citations’ function of PubMed and scanning of the
reference lists. We located over 150 studies in-
vestigating the effects of antioxidant supplementa-
tion on exercise-induced oxidative stress, muscle
damage, recovery and performance. A number of
excellent reviews are already available that contain
a greater discussion of these studies.
[2-11]
In addi-
tion, more detail on the effects of antioxidant ther-
apy in human disease was beyond the scope of this
review and can be found elsewhere.
[12-17]
The aim
of this review is to discuss the studies that have
shown negative effects of antioxidant supplements
in exercising individuals, thus demonstrating the
importance of ROS in skeletal muscle function.
2. Basic Mechanisms of Oxidative
Damage
2.1 Redox Reactions
Reactions of oxidation and reduction, known
as redox reactions, refer to all chemical reactions
in which an atom in a compound has its oxidation
number changed. The oxidation number is the
effective charge that the central atom in a com-
pound would have if all the ligands, including
shared electron pairs, were removed. Oxidation
can be explained as the loss of electrons, or more
accurately, an increase of the oxidation number.
Reduction is the gain of electrons or a decrease of
the oxidation number. An oxidant is a compound
that can accept electrons and is therefore reduced
causing another substance to be oxidized. A re-
ductant, on the other hand, donates electrons and
is oxidized causing another substance to be re-
duced. Oxidation and reduction, which represent
1044 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
the basis for numerous biochemical pathways,
always accompany one another in order to
transfer electrons between species. In a biological
environment, oxidants and reductants are often
called pro-oxidants and antioxidants, respectively.
A cell’s redox state describes the pro-oxidant/
antioxidant balance and plays an important role in
signalling and metabolic processes.
[18,19]
While oxygen is obviously vital for the life of
aerobic organisms, the by-products of its metab-
olism can be harmful to cells. During normal
metabolism, oxygen is utilized in the mitochon-
dria for energy production. In the process of
oxidative phosphorylation the majority of oxy-
gen consumed is bound to hydrogen to form
water. A small percentage of oxygen is not com-
pletely reduced, which leads to the production of
oxygen intermediates known as ROS.
[8]
When
reactants are derived from nitrogen, they are
called reactive nitrogen species. Reactive species
can be classified into two categories: free radicals
and nonradical derivatives. A radical is any che-
mical compound capable of independent exis-
tence possessing one or more unpaired electrons
in the outer-atomic or molecular orbital. These
species have an enhanced affinity to donate or
obtain another electron to become more stable,
which leads to the formation of new free radicals,
setting up a chain reaction. The free radical group
includes compounds such as the superoxide anion
radical (O
2
-
), nitric oxide radical (NO), nitric
dioxide radical (NO
2
), hydroxyl radical (OH),
alkoxyl (RO) and peroxyl (RO
2
) radicals. Most
typical nonradical reactive species relevant to
biological systems are singlet oxygen (
1
O
2
), ozone
(O
3
), hydrogen peroxide (H
2
O
2
), peroxynitrite
(ONO
2
-
), hypochlorous acid (HOCl), organic
peroxides and aldehydes. Reactive species readily
react with various organic substrates and play
important roles in biological environments.
[20]
Cells and extracellular spaces are exposed to a
large variety of reactive species from both exo-
genous and endogenous sources. The exogenous
sources include exposure to oxygen, radiation,
air pollutants, xenobiotics, drugs, alcohol, heavy
metals, bacteria, viruses, sunlight, food and
exercise. Nonetheless, exposure to endogenous
sources is much more important and extensive,
because it is a continuous process during the life
span. Reactive species are generated by all aero-
bic cells as part of normal metabolism. Mi-
tochondria have been known as the dominant
source of ROS production.
[18]
However, it has
been suggested that the actual fraction of oxygen
transformed into ROS accounts for only around
0.15%of total oxygen consumption ( .
VO
2
),
[21]
which is considerably less than original estimate
of 25%.
[22,23]
Enzymes, such as nicotinamide
adenine dinucleotide phosphate oxidase (NADPH
oxidase), nitric oxide synthase (NOS) and
xanthine oxidase (XO), are now recognized as the
main endogenous source of reactive species.
[24]
Furthermore, transition metals have been shown
to catalyze ROS formation
[25]
and in order to
combat bacteria and other invaders white blood
cells also produce a significant amount of reactive
species.
[26]
The most vulnerable targets of reactive species
are proteins, lipids and DNA.
[27]
ROS can oxidize
proteins and alter their structure, impair their
function and affect genetic transcription.
[28,29]
Fragmentation or loss of certain amino acids and
aggregation make proteins more susceptible to
proteolytic degradation.
[30]
Reactive species have
the ability to oxidize polyunsaturated free fatty
acids and initiate lipoprotein oxidation.
[31]
Dis-
ruption of the lipid bilayer changes fluidity and
permeability of the cell membrane and may lead
to inactivity of membrane bound proteins. Free
radicals cause DNA strand breaks, loss of pur-
ines and damage to deoxyribose sugar.
[32]
They
can impair the DNA repair system and provoke
mutagenesis. Oxidative damage promotes in-
flammation
[33]
and apoptosis
[34]
and may even-
tually lead to decreased cellular and physiological
functioning.
2.2 The Antioxidant Defence
To counter reactive species, we are equipped
with highly effective antioxidant defence systems.
These include nonenzymatic, enzymatic and diet-
ary antioxidants. Glutathione, uric acid, lipoic
acid, bilirubin and coenzyme Q
10
are examples of
nonenzymatic antioxidants that originate from
endogenous sources and are often by-products of
Antioxidant Supplementation in Exercise Training 1045
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
cellular metabolism. Principal enzymatic antioxi-
dants are superoxide dismuatse (SOD), catalase,
glutathione peroxidase (GPX) and glutathione re-
ductase, while most known examples of dietary
antioxidants are tocopherols (vitamin E), ascorbic
acid (vitamin C) and carotenoids (b-carotene).
In addition, various polyphenolic compounds
have recently been promoted as nutrient anti-
oxidants. a-Lipoic acid and pharmaceuticals
N-acetylcysteine and allopurinol have also been
used in supplementation studies.
Vitamin E refers to a group of fat-soluble
compounds that include tocopherols and toco-
trienols. a-Tocopherol is the most biologically
active form, and has been shown to protect the
cells from lipid peroxidation
[35,36]
and play a role
in prevention of chronic diseases associated with
oxidative stress.
[37,38]
The oxidized form can be
recycled back to the active form by other anti-
oxidants, such as vitamin C, retinol, ubiquinol,
glutathione, cysteine and a-lipoic acid.
[39]
It
has been suggested that vitamin E has other func-
tions apart from its antioxidative one. For in-
stance, g-tocopherol acts as a nucleophile and is
able to trap electrophilic mutagens in lipophilic
compartments.
[40]
Vitamin C or L-ascorbic acid is an antioxidant
and a co-factor in a range of essential metabolic
reactions in humans (e.g. collagen synthesis).
[41]
This water-soluble vitamin is produced endo-
genously by almost all organisms, excluding hu-
mans, several other mammalian groups and some
species of birds and fish. L-ascorbate, an ion form
of ascorbic acid, is a strong reducing agent and its
oxidized form is reduced back by enzymes and
glutathione.
b-Carotene belongs to a group of red, orange
and yellow pigments called carotenoids.
[42]
Others
include a-carotene, b-cryptoxanthin, lycopene,
lutein and zeaxanthin. These fat-soluble sub-
stances are found in plants and play a part in
photosynthesis. b-Carotene is the most active
carotenoid; after consumption it converts to
retinol, a readily usable form of vitamin A. In
addition to its provitamin A function, b-carotene
is believed to have antioxidant properties,
[43]
and
may positively impact the immune system
[44]
and
exhibit anticancerogenic effects.
[37]
Coenzyme Q
10
, also known as ubiquinone, is a
fat-soluble, vitamin-like substance, present in most
eukaryotic cells, primarily in mitochondria.
[45]
It is
a component of the electron transport chain and
plays a part in the energy production of a cell. Its
reduced form, ubiquinol, acts as an important an-
tioxidant in the body. Coenzyme Q
10
is synthesized
endogenously, and its dietary uptake is limited.
Polyphenols are a group of water-soluble,
plant-derived substances, characterized by the
presence of more than one phenolic group.
[46]
Several thousand polyphenols have been identi-
fied and they are divided into different groups
according to their structure and complexity
(flavonoids, lignans, stilbenes, coumarins and
tannins). Flavonoids are the largest group of
phenolic compounds and include anthocyanins,
flavones, isoflavones, flavonols, flavanones and
flavanols. Fruits and vegetables are a particularly
rich source of polyphenols. For instance, red
wine contains various polyphenolic compounds,
such as stilbene resveratrol and flavonol querce-
tin, which have been well studied and have been
shown to possess pharmacological properties
in the treatment of chronic diseases.
[47,48]
The
antioxidant potential of polyphenols has been
well established and is exhibited through their
chain-breaking and single-electron transfer abil-
ities. However, there is compelling evidence that
the protective actions of polyphenols are not
simply because of their redox properties, but
rather as a result of their ability to modulate
cellular signalling cascades by binding to specific
target proteins.
[46]
a-Lipoic acid is an organosulfur compound de-
rived from octanoic acid. It is an essential co-factor
of the four mitochondrial enzyme complexes,
therefore, is crucially involved in aerobic metabo-
lism. a-Lipoic acid may have potent antioxidant
potential and can recycle vitamin E;
[49]
however, its
accumulation in tissues is limited. Micronutrient
functions of a-lipoic acid may act more as an
effector of cellular stress response pathways.
[50]
N-acetylcysteine is a by-product of an en-
dogenously synthesized antioxidant glutathione.
It is a cysteine derivative and plays a role in
glutathione maintenance and metabolism.
N-acetylcysteine has been proposed to have
1046 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
antioxidant effects and is used as a pharmaceu-
tical drug (mucolytic agent) and a nutritional
supplement.
[51]
Allopurinol, a structural isomer of hypox-
anthine, is an inhibitor of XO. It is a drug primarily
used to treat hyperuricaemia, as it decreases uric
acid formation and purine synthesis.
[52]
Antioxidants are often divided into two
groups: those that act either through stabilizing
ROS or by removing reactive intermediates. The
former, also known as preventative antioxidants,
stabilize free radicals by donating electrons and
become oxidized themselves, forming less active
radicals. The latter, ‘scavengers’, help slow or
stop the damaging chain reaction by removing
free radical intermediates. In addition, transition
metal sequestration and oxidative damage-
repairing mechanisms support the body’s defence
system. Endogenous antioxidant systems re-
spond rapidly to an increased production of
reactive species. Cells can modulate gene expres-
sion and the activity of antioxidant enzymes to
cope with oxidative stress.
[18,53]
2.3 Oxidative Stress
Despite the extensive defence system, an in-
crease in ROS production or diminished anti-
oxidants can lead to progressive cell damage and
a decline in physiological function. When oxidant
capacity exceeds the antioxidant capacity,
homeostatic balance is disturbed and the redox
state becomes more pro-oxidizing. This im-
balance is called oxidative stress.
[54]
As we now
know that individual signalling and control events
occur through discrete redox pathways, rather
than through global balances, the classic defini-
tion of oxidative stress has been refined and also
considers oxidative stress as a disruption of redox
signalling and control.
[55]
Therefore, oxidative
stress may occur without an overall imbalance of
pro-oxidants and antioxidants and can cause
organ-specific and pathway-specific toxicity.
Under usual lifestyle conditions we are ex-
posed to high levels of reactive species from exo-
genous sources (e.g. environmental pollution)
[56]
and oxidative stress has been implicated in a
growing list of human diseases, such as cardio-
vascular, inflammatory, metabolic and neuro-
degenerative diseases, as well as cancer and the
ageing process.
[57]
A diet rich in antioxidants has
been identified as a potentially noninvasive
means of controlling oxidative stress.
[58,59]
Anti-
oxidant supplementation has received much
attention because of its capacity to support the
endogenous defence by scavenging additional
ROS and, therefore, by reducing oxidative
damage.
[60-62]
However, there is little evidence for
the efficacy of antioxidant supplements to treat
ROS-associated diseases. This has led to con-
siderable debate regarding the beneficial health
effects of this kind of supplementation in differ-
ent types of patients and with different types of
antioxidants.
[13,63,64]
Although observational
epidemiological cohort studies with large num-
bers of subjects and diverse populations have
been largely supportive of the health-promoting
effects of antioxidants,
[65-68]
interventional trials
have been controversial, with some positive
findings,
[37,38,69]
many null findings
[70-73]
and some
suggesting a detrimental effect of antioxidant
supplementation, particularly vitamin E, on
morbidity and mortality.
[74-76]
2.4 Beneficial Roles of Reactive Species
Although reactive species are associated with
harmful biological events, they are essential in cel-
lular development and optimal function.
[77,78]
Cells
have evolved strategies to utilize reactive species
as biological stimuli. They act as subcellular mes-
sengers in important molecular signalling processes
and modulate enzyme and gene activation.
[77]
Most
antioxidant enzyme genes contain regulatory
sequences in their promoter and intron regions that
can interact with redox sensitive transcription
factors.
[79]
Reactive species play significant roles in
cellular growth and proliferation.
[77]
It has been
shown recently that physiological levels of ROS are
required to activate DNA repair pathways for
maintaining genomic stability in stem cells.
[80]
Fur-
thermore, ROS are involved in the biosynthesis of
other molecules,
[81]
theimmuneresponseofcells
[26]
and drug detoxification.
[77]
Theyarearequisitefor
vasodilation,
[82]
optimal muscular contraction
[83]
and initiation of apoptosis.
[34]
Antioxidant Supplementation in Exercise Training 1047
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
3. Exercise-Induced Oxidative Stress
3.1 Reactive Species in Skeletal Muscle
During contraction, skeletal muscle is a major
source of ROS, as well as one of the main tar-
gets.
[24]
Exercise increases .
VO
2
by up to 20 times
above resting values.
[84]
In the mitochondria
of exercising muscle cells, this translates to a
200-fold greater oxygen usage.
[84]
Exercise-
induced oxidative stress was first described in the
late 1970s when increased levels of lipid perox-
idation products were found in the expired air of
exercising humans
[35]
and the tissues of exercised
rats.
[85]
In 1982, Davies et al.
[86]
provided the
first direct evidence that high-intensity exercise
significantly increased ROS production in the
muscles and liver of rats, and caused damage to
mitochondrial membranes. It was suggested that
this could, at the same time, deliver a stimulus to
mitochondrial biogenesis. However, the majority
of following studies focused on the damaging
effects of oxidants in muscle and looked for the
potential benefits of antioxidants. Over the last
30 years, an understanding of the sources and
consequences of exercise-produced ROS has
advanced markedly. It is now clear that reactive
species play important roles in skeletal muscle
function and metabolism. Redox signalling in
contracting muscle is considered one of the basic
elements in exercise biology.
[24]
3.2 Adaptation to Exercise-Induced Oxidative
Stress
Cells adapt to increased ROS production to
become more resistant to the adverse effects of
oxidative stress.
[87]
It has to be emphasized,
however, that the effects of a single bout of
exercise and regular exercise are quite different.
Regular physical activity brings about numerous
beneficial effects and the body adapts to elevated
oxidant levels, whilst with acute exercise, the
adaptation is only marginal. Acute adjustment
involves increased vasodilation to enhance blood
flow and fuel transport and a kinetic shift via the
allosteric activity of enzymes, which may not be
sufficient to restore oxidant-antioxidant homeo-
stasis.
[88]
Long-term stimulation of endogenous
defence mechanisms requires the continuous
presence of physiological stimuli that maintain a
certain degree of pro-oxidative milieu, and effec-
tively overload the antioxidant systems.
[89]
With exercise training the body adapts to ex-
ercise-induced oxidative stress and becomes more
resistant to subsequent oxidative challenges. This
is achieved through a number of different mech-
anisms, such as upregulation of redox-sensitive
gene expression and antioxidant enzymes le-
vels,
[90,91]
an increase in enzyme activity,
[92,93]
stimulation of protein turnover,
[94]
improvement
in DNA-repair systems,
[95,96]
and increased mi-
tochondrial biogenesis
[97]
and muscle content of
heat shock proteins (HSPs).
[98,99]
In addition,
adaptation positively affects remodelling of
skeletal muscle after injury and attenuates in-
flammation and apoptosis.
[88,100,101]
Moderate levels of reactive species appear
necessary for various physiological processes,
whereas, an excessive ROS production causes
oxidative damage. This may be described by the
concept of hormesis, a dose-response relationship
in which a low dose of a substance is stimulatory
or beneficial and a high dose is inhibitory or
toxic.
[102]
The adaptive response of mitochondria
to increased formation of ROS is termed
mitochondrial hormesis or mitohormesis.
[103]
The hormetic action of reactive species could
represent a mechanism underlying the health
and performance benefits of regular physical ac-
tivity.
[102]
This can be seen in the role of reactive
species as endogenous regulators of skeletal
muscle function. Indeed, they appear obligatory
for optimal contractile activity. Muscle myofila-
ments, such as myosin and troponin, and proteins
in the sarcoplasmic reticulum are redox-sensitive,
which gives ROS the ability to alter muscle con-
traction.
[104]
Based on Reid’s model for the role
of redox state on muscle force production, reac-
tion to ROS can be described by a bell-shaped
curve.
[104,105]
At baseline, low oxidant levels
appear to be suboptimal for the contraction of
unfatigued muscle. The data from Reid’s studies
suggest modest augmentation in ROS levels cau-
ses muscle force to increase, while antioxidants
deplete oxidant levels and depress force. At
higher ROS concentrations this is reversed and
1048 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
force production decreases in a time- and dose-
dependent manner.
[105-107]
3.3 Oxidative Stress and Muscle Damage
Despite skeletal muscle being relatively resistant
to exercise-induced oxidative damage, it is clear
that intense and/or prolonged muscular activity
can result in harmful outcomes.
[9]
Repetitive ec-
centric contractions, if unaccustomed in particular,
place skeletal muscle under considerable stress that
may cause muscle damage.
[108,109]
Damaging ex-
ercise also induces an inflammatory response,
which further increases ROS formation.
[110]
How-
ever, the studies often lack the information about
the subjects’ redox status and therefore fail to
provideevidenceforthecausalroleofROSin
muscle damage.
The majority of studies have measured indirect
and nonspecific indices of muscle damage,
such as muscle soreness and reduction in the
muscle force production. Eccentric exercise
was shown to cause structural changes of muscle
fibres,
[108,109,111,112]
and has been associated with
muscular soreness,
[110,113,114]
reduced range of
motion
[110]
and loss of torque and force produc-
tion.
[109,111,112,115,116]
This may result in muscle fa-
tigue and development of muscular atrophy.
[117-119]
Extreme fatigue can lead to muscle injury and,
possibly, irreversible cell alterations.
[119,120]
4. Antioxidant Supplementation
and Exercise
4.1 Overview
It is common practice for athletes to use anti-
oxidant supplements with the notion that they
prevent the deleterious effects of exercise-induced
oxidative stress, hasten recovery of muscle func-
tion and improve performance.
[1,121-125]
Indeed,
there is now an enormous range of vitamins, mi-
nerals and extracts marketed as antioxidant sup-
plements. None have undergone adequate test-
ing, and therefore lack scientific evidence
regarding efficacy and long-term safety.
The popularity of antioxidant supplements
with athletes has led to a plethora of small
research studies in this area. As expected, the
studies varied considerably in terms of research
design, exercise protocol, population groups,
supplementation regimen and analysis methods.
Importantly, the studies are also of generally low
quality. As commonly found in sports nutrition
research, the vast majority do not adhere to all
the accepted features of a high-quality trial (e.g.
placebo-controlled, double-blind, randomized
design with an intent-to-treat analysis). Indeed,
most studies fail to provide sufficient detail
regarding inclusion and exclusion criteria, justi-
fication of sample size, adverse events, data
gathering and reporting, randomization, alloca-
tion and concealment methods, and an assess-
ment of blinding success. The poor quality of the
majority of studies in this field increases the
possibility for bias and needs to be always con-
sidered when evaluating the findings.
Supplements used in the studies include vita-
min E, vitamin C, b-carotene, coenzyme Q
10
,a-
lipoic acid, N-acetylcysteine, allopurinol, quercetin,
resveratrol and several other polyphenolic com-
pounds. A number of studies have used combi-
nations of these. The range of dosages across
the supplements was wide and duration of sup-
plemention varied from acute (12 days) to
chronic administration (from 1 week to up to
6 months). Blood, urine, breath and muscle tissue
samples were collected pre-, during and post-
supplementation and exercise. The most common
outcome measure was a marker of oxidative
stress with lipid peroxidation products pre-
dominating, followed by oxidized proteins, DNA
damage markers and alterations in endogenous
antioxidant systems. Direct measurement of
reactive species concentration (e.g. electron spin
resonance spectroscopy) was only performed
in a small number of studies because of the in-
stability of ROS, high costs and extensive work-
up requirements.
4.2 Antioxidant Supplementation and
Exercise-Induced Oxidative Stress
The majority of studies have used measures of
oxidative stress as their main outcome, and most
have demonstrated that antioxidants attenuate
exercise-induced increases in oxidative stress.
Antioxidant Supplementation in Exercise Training 1049
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
Most common antioxidants in these positive
studies were vitamin E
[35,36,62,126-132]
and vitamin
C,
[60,116,133-137]
followed by different combina-
tions of antioxidants
[61,138-147]
and, most recently,
polyphenolic compounds.
[148-156]
Furthermore,
lower levels of oxidative stress markers have been
reported after b-carotene,
[157]
a-lipoic acid,
[158]
N-acetylcysteine
[159]
and selenium
[160]
adminis-
tration. However, there have been many studies
showing no significant effect of antioxidant
supplements on exercise-induced oxidative
stress
[110,161-172]
and several indicating increased
oxidative stress levels following antioxidant ad-
ministration.
[144,173-176]
Although the majority of studies report that
antioxidants can reduce oxidative stress levels,
the physiological implications of these effects
are unknown. In an attempt to determine
the importance of reducing oxidative stress, in-
vestigators have studied the role of antioxidant
supplementation in exercise performance and
muscle damage.
4.3 Antioxidant Supplementation and Muscle
Damage
Strong evidence to support the role of anti-
oxidant supplementation in protecting against
muscle damage is lacking. The majority of
investigations have focused on the effects of
vitamin C and E and looked at oxidative
stress markers and plasma concentrations of in-
tramuscular enzymes, e.g. creatine kinase (CK)
and lactate dehydrogenase, rather than indices of
muscle damage such as force loss, muscle sore-
ness, structural changes of myoproteins and their
plasma concentration.
[6]
As a result of the lack of
direct measurement of specific indices of muscle
damage, it is unclear to what extent muscle
damage was induced in those studies. There are
reports that antioxidant supplementation could
offer some protection from exercise-induced cell
damage,
[127,177-181]
attenuate the inflammatory
response to exercise,
[147,151,182-186]
and reduce
muscle force loss
[154,156,177,187]
and fatigue.
[188-191]
Other investigations, however, found no signif-
icant effect of antioxidants on indices of cell da-
mage,
[111,113,161,192-194]
muscle soreness
[114,195-199]
and inflammation.
[111,114,127,169,194,200,201]
Anum-
ber of studies suggested that antioxidant supple-
mentation may promote muscle damage and
possibly hinder recovery.
[165,175,197,202]
These
studies are the focus of this review and discussed
in section 5.
4.4 Antioxidant Supplements as
Ergogenic Aids
There has been a general inconsistency of
outcomes when investigating the role of anti-
oxidant supplementation in exercise performance
with the majority of the studies reporting no
benefits. In the early 1970s, Sharman and collea-
gues
[203]
showed that supplementation with
vitamin E had no beneficial effect on endurance
performance of adolescent male swimmers.
Moreover, the placebo group demonstrated
greater improvements of cardiorespiratory func-
tion with exercise training compared with the
antioxidant group, which may be the first report
of the unfavourable effect of supplementation. In
the studies that followed, vitamin E proved
ineffective in improving performance in swim-
mers,
[204]
professional cyclists,
[132,205,206]
non-
resistance-trained men,
[202]
athletic students
[167]
and marathon runners.
[207]
Furthermore, vitamin
E supplements had no additive effect beyond that
of aerobic training on indices of physical perfor-
mance in a group of older sedentary adults.
[208]
Supplementation with coenzyme Q
10
did not
exhibit any significant effects on exercise perfor-
mance of men,
[162,209,210]
regardless of their age
and training status. Quercetin supplements also
failed to show any ergogenic effects in sedentary
individuals
[199,211]
or cyclists.
[212]
Polyphenol res-
veratrol did not improve muscle force output
and muscle fatigability in mice subjected to elec-
trically stimulated isometric contractions.
[213]
In
a study by Marshall et al.,
[214]
vitamin C was
shown to slow racing greyhounds.
Despite the presumption that antioxidants
work synergistically and may therefore be more
efficient in combating oxidative stress, combina-
tions of vitamins E, C, coenzyme Q
10
and other
vitamins and minerals failed to improve the
exercise performance of competitive male
1050 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
runners,
[215]
cyclists,
[144,216]
triathletes,
[217,218]
soccer players,
[146,219]
resistance-trained men,
[220]
ultraendurance runners,
[221]
moderately trained
men,
[222]
and trained and untrained males and
females.
[166]
Nonetheless, there have been a number of
studies showing positive, albeit, modest effects of
antioxidant supplementation on physical perfor-
mance. Coenzyme Q
10
was associated with im-
proved maximal .
VO
2
(.
VO
2max
)and aerobic and
anaerobic threshold of professional cross-
country skiers that resulted in an increased
exercise capacity and a faster recovery rate.
[223]
Similarly, supplementation with coenzyme Q
10
indicated beneficial effects on performance,
fatigue sensation and recovery during fatigue-
inducing workload trials in a group of healthy
volunteers.
[189]
Furthermore, results from sup-
plementation studies that involved male cy-
clists,
[224]
trained and untrained individuals
[225]
and sedentary men
[226]
supported the perfor-
mance-enhancing effect of coenzyme Q
10
. Vita-
min E supplementation was proposed to have a
beneficial effect on the performance of climbers
at high altitude
[128]
and endurance performance
of mice,
[227]
rats
[228]
and sled dogs.
[229]
In two
early studies, supplementation with vitamin C
was associated with an improved exercise capa-
city of untrained male students
[230]
and ath-
letes.
[231]
In a study by Aguilo et al.,
[232]
male
athletes supplemented with a combination of vita-
min E, C and b-carotene exhibited lower blood
lactate levels after a maximal exercise test and ex-
hibited a more significant increase more in .
VO
2max
after 3 months of exercise training than the placebo
group. Supplementation with different combina-
tions of antioxidants also positively affected
the exercise performance of students,
[233]
elderly
endurance-trained athletes
[234]
and aged rats.
[139]
Medved and colleagues
[235]
have studied the
effect of N-acetylcysteine on muscle fatigue
and performance in untrained and trained men.
Although N-acetylcysteine was shown to mod-
ulate blood redox status during high-intensity
intermittent exercise, it did not affect time to
fatigue in a group of untrained men. Similarly,
N-acetylcysteine infusion during prolonged sub-
maximal exercise had no effect on time to fatigue
in a group of team-sport athletes and endurance-
trained cyclists. Nonetheless, the antioxidant
improved regulation of plasma K
+
concentra-
tion and it was suggested the ergogenic effect of
N-acetylcysteine depends on an individual’s train-
ing status.
[236]
Finally, N-acetylcysteine infusion
during prolonged submaximal exercise was re-
ported to augment time to fatigue in a group of
well trained individuals, possibly by increasing
muscle cysteine and glutathione availability.
[237]
Recently, there have been a number of in-
vestigations showing the performance enhancing
effects of polyphenols, including quercetin,
[201,238-240]
resveratrol,
[241]
and polyphenolic compounds
from grape extract,
[152]
beetroot juice,
[242-245]
Rhodiola rosea plant
[246]
and Ecklonia cava
algae.
[247]
Emerging evidence suggests that the
antioxidant potential of phenolic compounds is
unlikely to be the sole mechanism responsible
for their protective action, which could also be
mediated by their interaction with various key
proteins in the cell-signalling cascades.
[248]
As mentioned above in section 4.1, many of
the studies evaluating the effects of antioxidants
on exercise performance have been of low quality
with small subject numbers. In addition, most
have had important methodological details left
out of the articles (e.g. recruitment, randomiza-
tion, allocation and concealment methods)
leading to the assumption that they were not
considered. This creates a potentially dangerous
bias in regards to subject selection and the
assessment of performance effects.
5. Antioxidant Supplementation
Interferes with the Beneficial
Effects of Exercise Training
Recent studies have indicated that antioxidant
supplements have a detrimental effect on the
health and performance benefits of exercise
training. Considering the multifunctional bene-
ficial roles of ROS in living organisms discussed
above in section 2.4, reports of unfavourable ef-
fects of antioxidant supplementation should not
come as a surprise. The studies reporting negative
outcomes are discussed in sections 5.15.3 with
more details presented in table I.
Antioxidant Supplementation in Exercise Training 1051
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Table I. Studies with negative outcomes using antioxidant supplementation during exercise training
Study (y) Subjects Supplements (daily dose) Duration Study design Findings
Malm et al.
[249]
(1996)
15 M Coenzyme Q
10
(120 mg) 20 d Placebo-controlled trial: Exercise tests:
anaerobic test (Wingate test, 5 min
recovery, 10 ·10 sec all-out cycling), .
VO
2
submax and max test. Exercise training: 9
sessions (15 ·10 sec all-out cycling
sprints). Samples: plasma CK activity
After exercise, CK levels only in the
supplemented group. Subjects taking
supplements showed smaller training-
induced improvements in physical
performance than the placebo group
Malm et al.
[250]
(1997)
18 M Coenzyme Q
10
(120 mg) 22 d Placebo-controlled double-blind trial:
Exercise tests: anaerobic test (30 sec
all-out cycling, 5 min recovery, 10 ·10 sec
all-out cycling), submax and peak cycling
.
VO
2
test, .
VO
2max
running test. Exercise
training: 7 sessions (15 ·10 sec all-out
cycling sprints). Samples: plasma lactate
There was a greater increase in anaerobic
performance in the placebo group
compared with the supplemented group.
Moreover, supplementation was
associated with reduced exercise training-
induced increase in power output and
recovery rate between cycling sprints.
Coenzyme Q
10
had no effect on submax
and peak cycling .
VO
2
, running .
VO
2max
and
lactate levels
Childs et al.
[175]
(2001)
14 M Vitamin C (12.5 mg/kg BW)
+NAC (10 mg/kg BW)
1 wk (post-
exercise)
Double-blind placebo-controlled trial:
Exercise protocol: eccentric arm exercise
(3 ·10 repetitions, 80%of 1RM). Samples:
serum free iron levels, plasma lipid
hydroperoxides, F2-isoprostanes,
myeloperoxidase and IL-6, plasma CK and
LDH activities, serum SOD and GPX
Exercise inflammatory indicators, free
iron concentration and the levels of
oxidative stress and muscle damage
markers. The amount of iron, levels of lipid
hydroperoxides and isoprostanes and LDH
and CK activities were higher in the
supplemented group than in the placebo
group
Coombes et al.
[251]
(2001)
28 F rats Vitamin E (10 000 IU/kg
diet) +a-lipoic acid
(1.65 g/kg diet)
8d In situ experiment: Contractile
measurements (tibialis anterior): P
o
,P
t
and
force-frequency curve, 60 min fatigue
protocol. Samples: muscle MDA and lipid
hydroperoxide
Contracted muscles of supplemented
animals had lower levels of oxidative stress
than the muscles from the control group.
Vitamin E and a-lipoic acid supplemen-
tation had no effect on muscle fatigue but
was associated with decreased muscle
force production at low stimulation
frequencies (in situ). In vitro experiments
indicated that vitamin E depressed force
production at low stimulation frequencies
32 F rats Vitamin E: 100, 200,
400 mM/DHLA;
100 mM/vitamin E;
400 mM+DHLA; 100 mM
In vitro experiment: contractile measure-
ments (costal diaphragm): P
o,
P
t
and force-
frequency curve, 30 min fatigue protocol
Marshall et al.
[214]
(2002)
5 F racing
greyhounds
Vitamin C (1 g) 4 wk (each
treatment)
Crossover controlled trial: Treatments: no
supplementation; supplementation after
racing; supplementation 1 h before racing.
Exercise training: 2 ·500 m races/wk.
Samples: plasma TBARS and antioxidant
capacity
Vitamin C showed no effect on oxidative
stress and antioxidant capacity. The dogs
ran slower when supplemented
Continued next page
1052 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
Table I. Contd
Study (y) Subjects Supplements (daily dose) Duration Study design Findings
Avery et al.
[202]
(2003)
18 untrained M Vitamin E (1200 IU) 3 wk Randomized placebo-controlled double-
blind trial: Exercise Protocol: 3 resistance
exercise sessions separated by 3 days of
recovery. Measurements: muscle
soreness, muscle strength and power
assessment. Samples: plasma MDA and
CK activity
There was no effect of supplementation on
muscle soreness, performance indices and
MDA levels. CK levels were greater in the
supplemented group than in the placebo
group
Bryant et al.
[144]
(2003)
7 M cyclists Vitamin C (1 g)/vitamin C
(1 g) +vitamin E
(200 IU/kg)/vitamin E
(400 IU/kg)
3 wk (each
treatment)
Controlled crossover single-blind trial:
Treatments: placebo; vitamin C;
vitamin C +vitamin E; vitamin E. Exercise
tests: 60 min steady state ride
(70%.
VO
2max
) and 30 min performance ride
(70%.
VO
2max
). Samples: plasma MDA and
lactic acid
Supplementation had no effect on exercise
performance. Vitamin E MDA levels, the
combination of vitamins E and C had no
effect, vitamin C alone MDA levels
Khassaf et al.
[98]
(2003)
16 untrained M Vitamin C (500 mg) 8 wk Randomized controlled trial:
Muscle samples (exercise protocol: 45 min
single leg cycling, 70%.
VO
2max
, vastus
lateralis): HSP60 and HSP70 content.
Lymphocytes (treated with H
2
O
2
for
30 min): SOD and CAT activity, HSP60 and
HSP70 content
Supplementation with vitamin C was
associated with attenuated exercise-
induced increase in HSP content and SOD
and CAT activity
Nieman et al.
[176]
(2004)
36 triathletes
(26 M, 10 F)
Vitamin E (800 IU) 2 mo Randomized placebo-controlled
double-blind trial: Ironman Triathlon
race samples: plasma and urinary
F
2
-isoprostanes, urinary 8-OHdG and
8-oxoG, plasma lipid hydroperoxides
and cytokines
Post-race concentrations of isoprostanes,
lipid hydroperoxides, IL-6, IL-1ra and IL-8
increased more in the vitamin E group than
in the placebo group. Supplementation had
no effect on race time
Gomez-Cabrera
et al.
[252]
(2005)
20 M rats Allopurinol (32 mg /kg) Admin prior
to exercise
Randomized controlled trial:
Exercise protocol: progressive intensity
treadmill test, exercise to exhaustion.
Samples: plasma lactate and XO activity,
muscle GSH, GSSG, carbonylated
proteins, p38, ERK1 and ERK2, NF-kb
DNA-binding activity and Mn-SOD, iNOS
and eNOS
Allopurinol treated rats exhibited
oxidative stress levels and exercise-
mediated increase in XO activity and
induction of MAPKs. This was associated
with DNA binding of NF-kB and blunted
upregulation of Mn-SOD,eNOS and iNOS
gene expression
Gomez-Cabrera
et al.
[253]
(2006)
25 marathon
runners
Allopurinol (300 mg) 2 h prior to
marathon
race
Randomized placebo-controlled trial:
Marathon race - samples: lymphocyte
NF-kb p50 activation, plasma MDA and
XO activity
Allopurinol prevented XO activation and
lipid peroxidation. Inhibiton of XO-derived
ROS formation prevented NF-kB activa-
tion. Allopurinol had no effect on race time
Continued next page
Antioxidant Supplementation in Exercise Training 1053
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Table I. Contd
Study (y) Subjects Supplements (daily dose) Duration Study design Findings
Close et al.
[197]
(2006)
20 M Vitamin C (1 g) 2 h prior to
and for
2 wk post-
exercise
Randomized placebo-controlled
double-blind trial: Exercise protocol:
downhill running test (30 min, 60%.
VO
2max
).
Measurements: pain assessment (visual
analogue scale, pressure algometry) and
muscle function (quadriceps torque
assessment). Samples: serum MDA
Supplementation with vitamin C
exercise-induced increase in MDA levels
but had no effect on DOMS. Delayed
recovery of muscle function was noted in
the supplemented group
Fischer et al.
[99]
(2006)
21 M a-Tocopherol
(400 IU) +vitamin C
(500 mg)
4 wk Randomized placebo-controlled single-
blind trial: Exercise protocol: 3 h, 2-legged
dynamic knee extensor exercise. Samples:
muscle HSP72 mRNA and protein, plasma
HSP72 and F
2
-isoprostanes
a-Tocopherol +vitamin C treatment
attenuated in lipid peroxidation post-
exercise. Exercise-induced increase in
HSP72 levels in skeletal muscle and
circulation was abolished in a-tocopherol +
g-tocopherol +vitamin C group
a-Tocopherol (290 IU)
+g-tocopherol
(130 IU) +vitamin C
(500 mg)
Knez et al.
[93]
(2007)
16 half-
Ironman
triathletes
(13 M, 3 F)
Vitamin C
(1095 447 mg) +vitamin E
(314 128 mg)
Vitamin C:
4.9 4.7 y;
vitamin E:
5.6 5.2 y
Observational study: subjects recruited 4 wk
before the race, controls active <3h/wk:
Triathletes: training and competing for
4.7 2.4 y, 14.5 3.4 h/wk, 10 taking
supplements; race: 1.9 km swim, 90.1 km
cycle, 21.1 km run. Samples: plasma MDA
and erythrocyte SOD, GPX and CAT
activities
Dose-response relationship between
adaptations of antioxidant enzymes and
responses to ultraendurance exercise.
Ultraendurance training upregulated
endogenous antioxidant system (GPX and
CAT activity). Triathletes taking
supplements had elevated post-race MDA
levels compared with nonsupplementers
29 Ironman
triathletes (23
M, 6 F)
Vitamin C
(558 350 mg) +vitamin E
(702 756 mg)
Vitamin C:
0.8 0.6 y;
vitamin E:
1.6 0.8 y
Triathletes: training and competing for
6.9 6.4 y, 17.19 3.4 h/wk, 8 taking
supplements; race: 3.8 km swim, 180km
cycle, 42.2 km run. Samples: plasma MDA
and erythrocyte SOD, GPX and CAT activities
Richardson
et al.
[254]
(2007)
25 M Dose: a-lipoic acid
(300 mg) +vitamin C
(500 mg) +vitamin E
(200 IU)
2 h and
1.5 h prior
to exercise
Randomized placebo-controlled crossover
double-blind trial: Exercise protocol:
forearm handgrip exercise at low-intensity
workload (3, 6 and 9 kg at 0.5Hz) for 3 min.
Measurements: plasma FR, vasodilation.
Antioxidant administration total
antioxidant capacity and exercise-
induced oxidative stress but brachial
artery vasodilation during submaximal
exercise.
Dose: a-lipoic acid
(300 mg) +vitamin C
(500 mg) +vitamin E
(400 IU)
Gomez-Cabrera
et al.
[97]
(2008)
14 sedentary M Vitamin C (1 g) 8 wk Randomized double-blind controlled trial:
Exercise test: .
VO
2max
test (bicycle
ergometer). Exercise training: 40 min
cycling 3 d/wk (65%-80%.
VO
2max
)
Continued next page
1054 Peternelj & Coombes
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Table I. Contd
Study (y) Subjects Supplements (daily dose) Duration Study design Findings
36 M rats Vitamin C: 0.24 mg/cm
2
body surface area
3 wk; 6 wk Untrained group, trained group,
trained +supplemented group:
RT-PCR experiment: 3 wk training.
Western blotting and performance
experiments: 6 wk training. Exercise
training: 5 d/wk, treadmill (75%.
VO
2max
,
25-85 min/d). Endurance test (run to
exhaustion), .
VO
2max
test (treadmill run).
Samples: muscle mTFA and NRF-1 mRNA
and protein, cyt c and PGC-1 protein, Mn-
SOD and GPX mRNA
Moderate intensity exercise enhanced
endogenous antioxidant defence (
expression of Mn-SOD and GPX) and
mitochondrial biogenesis (upregulation of
PGC-1 -NRF-1 -mTFA -cyt c
pathway) and increased endurance
capacity. Vitamin C prevented these
training induced adaptations
Copp et al.
[255]
(2009)
19 M rats Vitamin C
(76 mg/kg) +tempol
(52 mg/kg)
Acute
infusion
(after first
exercise
protocol)
Exercise protocol (right spinotrapezius
muscle): 1 Hz twitch contractions for
180 sec (2 sessions: pre- and post-
antioxidant administration);13 rats: blood
flow and PO2mv measurements; 6 rats:
muscle force measurements
Antioxidant administration serum
antioxidant capacity but blood flow,
baseline PO2mv, muscle oxygen utilization
and muscle force production
Lamprecht
et al.
[174]
(2009)
8 trained M
cyclists
Vitamin E (107 IU) +
vitamin C (450 mg) +
b-carotene (36 mg) +Se
(100 mg)
2 wk Randomized double-blind placebo-
controlled crossover trial:
Exercise test: cycle ergometer, 90 min
cycling (45%.
VO
2max
)+30 min cycling (75%
.
VO
2
max). Samples: plasma MDA and GPX
MDA concentrations were and GPX
levels after antioxidant treatment (pre-
and post-exercise)
Ristow et al.
[91]
(2009)
20 untrained
M(<2h of
exercise/wk),
20 pretrained
M(>6h of
exercise/wk)
Vitamin C (1 g) +vitamin E
(400 IU)
4 wk Controlled trial, 2 part-study open-label
study; double blind placebo-controlled
study: 4 groups: untrained nonsupplemented,
trained nonsupplemented, untrained
supplemented, trained supplemented.
Exercise training 5d/wk, session: 20 min
biking/running, 45 min circuit training.
Measurements: GIR. Samples: plasma
adiponectin, muscle PGC-1a,PGC-1b,
PPARg,SOD1 and SOD2, and GPX gene
levels
Exercise training insulin sensitivity,
fasting plasma insulin levels, gene
expression of PGC-1a,PGC-1b,PPARg,
SOD1 and SOD2,GPX (irrespective of
training status). Supplementation with
vitamins E and C was shown to prevent
these health promoting effects
Teixeira et al.
[165]
(2009)
20 competitive
kayakers
(14 M, 6 F)
a-Tocopherol
(272 mg) +vitamin C
(400 mg) +b-carotene
(30 mg) +lutein (2 mg) +Se
(400 mg) +Zn (30 mg) +mg
(600 mg)
4 wk Randomized double-blind placebo-
controlled trial: Exercise test: maximal
flat-water kayaking trial (1000 m).
Samples: plasma antioxidants, TBARS,
IL-6 and CK, SOD, GR, GPX activities
Antioxidant supplementation antioxidant
capacity but had no effect on oxidative
stress and inflammation markers.
Supplemented athletes showed a blunted
decrease in CK activity post-exercise
Continued next page
Antioxidant Supplementation in Exercise Training 1055
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Table I. Contd
Study (y) Subjects Supplements (daily dose) Duration Study design Findings
Wray et al.
[256]
(2009)
6 older, mildly
hypertensive M
Dose: a-lipoic acid
(300 mg), vitamin C
(500 mg), vitamin E
(200 IU)
Prior to and
after 6 wk
of training:
2 h before
exercise
protocol
Double-blind placebo-controlled
crossover trial: Exercise protocol d1,
2: antioxidant efficacy test; d 36: FMD
procedure followed by knee extensor
exercise, subjects crossed over, returned
after 24 h. Exercise training: 3 ·wk-single
leg knee-extensorexercise. Measurements:
plasma FR, BP and FMD
Antioxidant administration reduced FR
levels pre- and post-exercise. Exercise
training reduced BP and improved
vasodilation, supplementation after training
negated these effects
Dose: a-lipoic acid
(300 mg), vitamin C
(500 mg), vitamin E
(400 IU)
Prior to and
after 6 wk
of training:
30 min
after 1
Bailey et al.
[110]
(2010)
38 M Vitamin C
(800 mg) +vitamin E
(536 mg) +vitamin B6
(4 mg) +vitamin B
9
(400 mg) +zinc sulphate
monohydrate
(10 mg) +vitamin B
12
(2 mg)
6wk
(including.
2 d post-
exercise)
Randomized placebo-controlled double-
blind trial: Exercise test (d 40): 90 min
intermittent high-intensity shuttle-running.
Measurements: pre- and post-exercise
ratings of perceived muscle soreness and
assessment of muscle function (peak
isometric torque of the knee flexors and
extensors, range of motion at the knee
joint). Samples: urine F2-isoprostanes,
serum IL-6 and cortisol
Antioxidant supplementation was
associated with attenuated exercise-
induced in cortisol concentration but
post-exercise IL-6 and F2-isoprostane
levels (compared with the placebo).
Treatment had no effect on indices of
muscle damage, muscle function
measures and perception of muscle
soreness
Matsumoto
et al.
[257]
(2011)
48 M rats a-Tocopherol (1000 IU/kg
diet) +a-lipoic acid
(1.6 g/kg diet)
14 wk Controlled trial: 4 groups: untrained
nonsupplemented, trained
nonsupplemented, untrained
supplemented, trained supplemented.
Exercise training: 90 min treadmill run
4d/wk. Samples: left ventricular and
coronary artery endothelial cells (gene
analysis)
IL-6 gene levels were by all treatments.
RhoA gene expression was by exercise
training, by antioxidant supplementation.
The combination of exercise and
supplementation resulted in a blunted of
RhoA gene levels (compared with the
exercise training effect)
1RM =repetition maximum; 8-OHdG =8-hydroxy-2-deoxyguanosine; 8-oxoG =7,8-dihydro-8-oxoguanosine; BP =blood pressure; BW =bodyweight; CAT =catalase; CK =creatine
kinase; cyt c =cytochrome c; DOMS =delayed onset muscle soreness; DHLA =dihydrolipoic acid; ERK =extracellular signal-regulated protein kinases; F=female; FMD =flow-
mediated vasodilation; FR =free radical; GIR =glucose infusion rate; GPX =glutathione peroxidase; GR =glutathione reductase; GSH =reduced glutathione; GSSG =oxidized
glutathione; H
2
O
2
=hydrogen peroxide; HSP =heath shock protein; IL-1ra =interleukin 1 receptor antagonist; IL-6(8) =interleukin-6(8); LDH =lactate dehydrogense; M=male;
MAPK =mitogen activated protein kinase; max =maximal; MDA =malondialdehyde; mRNA =messenger RNA; mTFA =mitochondrial transcription factor A; NAC =N-acetyl
cysteine; NF-jB=nuclear factor kappa-light chain-enhancer of activated B cells; NOS =nitric oxide synthase; NRF-1 =nuclear respiratory factor 1; p38 =a member of MAPKs; p50 =a
subunit of NF-kb complex; PGC-1 =peroxisome proliferator-activated receptor gamma coactivator 1; PPARc=peroxisome proliferator-activated receptor gamma; PO2mv =
microvascular O
2
partial pressure; P
o
=max specific tension; P
t
=twitch tension; RhoA =Ras homolog gene family member A; RT-PCR =real-time reverse transcriptase-polymerase
chain reaction; Se =selenium; SOD =superoxide dismutase; submax =submaximal; TBARS =thiobarbituric acid reactive substances; .
VO
2
=oxygen uptake; .
VO
2
max =maximal
.
VO
2
;XO =xanthine oxidase; Zn =zinc; indicates increase; indicates decrease; -indicates ‘leads to’/outcome.
1056 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
5.1 Antioxidant Supplements Promote
Exercise-Induced Oxidative Stress
Antioxidants, especially when present in high
amounts, have been shown to increase markers of
exercise-induced oxidative stress. After high-
intensity exercise, coenzyme Q
10
supplementa-
tion was associated with an increase in a marker
of cell damage (CK)
[249]
and a decrease in
exercise-training induced improvements in phy-
sical performance.
[249,250]
A number of important
methodological details were omitted from the
articles, indicating low quality. A study by Childs
et al.
[175]
found that vitamin C and N-acetyl-
cysteine following eccentric arm exercise in-
creased oxidative stress and cell damage above
levels induced by muscle injury alone. The effects
of vitamins E and C alone and in combination
were investigated in seven male cyclists.
[144]
Vitamin E decreased malondialdehyde, an oxi-
dative stress marker, whereas the combination of
both had no effect and vitamin C increased mal-
ondialdehyde. This indicates that the type of anti-
oxidant (e.g. water vs lipid soluble) is likely to be
an important factor. In another study, an in-
crease in the serum CK levels following a 3-day
resistance exercise was greater after the use of
vitamin E supplements compared with a placebo
group.
[202]
However, the increase was both
modest and transient with no effect of supple-
mentation on muscle soreness and exercise
performance. Furthermore, variability in the
baseline CK levels between groups and the large
interindividual variability of the measure need to
be considered.
Two months of supplementation with high
doses of vitamin E had no effect on the race time
of Ironman Triathlon participants but was asso-
ciated with increased lipid peroxidation and in-
flammation.
[176]
Knez et al.
[93]
demonstrated that
ultraendurance training upregulated the resting
activity of several antioxidant enzymes and re-
duced resting levels of oxidative stress, whilst
supplementation with vitamins C and E had no ef-
fect on these values. Moreover, athletes taking sup-
plements had elevated post-race malondialdehyde
levels compared with nonsupplementers. It is im-
portant to recognize that this was only an observa-
tional study; although, when a randomized control-
led crossover design was used, similar findings were
reported with 2 weeks of supplementation with an
antioxidant concentrate (vitamins E, C, b-carotene
and selenium) associated with increased lipid
peroxidation and decreased plasma glutathione
peroxidase concentration pre- and post-exercise.
[174]
Finally, in a recent study by Bailey et.al.,
[110]
young
men were supplemented with a combination of
vitamins C and E for 6 weeks before and 2 days after
a 90-minute intermittent shuttle run. The supple-
mented subjects had increased markers of oxidative
stress and inflammation compared with the placebo
group. However, although the overall change
in isoprostane levels (baseline vs post-exercise) ap-
proached significance, the tendency for slightly
higher isoprostane levels in the placebo group at
baseline precluded establishment of any significant
differences at the final recovery timepoint. The
authors noted that a large inter-individual variability
in the responses of isoprostanes and interleukin (IL)-
6 after supplementation could have impacted on the
findings. Indeed, in all of the above mentioned
studies there were no attempts to provide sample size
or power calculations to assess the likelihood that
the findings were real.
5.2 Antioxidant Supplementation Hinders
Cell Adaptation to Exercise-Induced
Oxidative Stress
Cells adapt to increased exposure to oxidation,
thereby reducing the risk of tissue damage.
[90,98,258]
Five small studies now show that antioxidant
supplements hinder the beneficial cell adaptations
to exercise.
[97-99,252,253]
In a group of untrained
males, supplementation with vitamin C resulted in
the inactivation of redox-sensitive transcription
factors responsible for the expression of cytopro-
tective proteins, including HSPs.
[98]
Such suppres-
sion of cell adaptation may negatively impact cell
viability over the longer term. Similarly, supple-
mentation with g-tocopherol inhibited an exercise-
induced increase of HSP levels in skeletal muscle
and the circulation.
[99]
A research group at the University of Va-
lencia, Valencia, Spain has published a number of
important studies on this topic. In one of their
Antioxidant Supplementation in Exercise Training 1057
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
first studies they used allopurinol in rats and
found it attenuated the exercise-induced increase
of XO activity and ROS formation.
[252]
This was
associated with a decreased activation of mito-
gen-activated protein kinases (MAPKs) and
blunted DNA-binding of nuclear factor kappa B
(NF-kB). MAPKs respond to extracellular sti-
muli, including oxidative stress, and regulate cell
development and survival. Transcription factor
NF-kB mediates gene expression of enzymes such
as Mn-SOD,eNOS and iNOS. Therefore, im-
pairing the exercise training effects on MAPKs
and NF-kB would likely impact on these positive
benefits. Indeed, in humans, administration of
allopurinol prior to a marathon race did suppress
the exercise-induced increase of antioxidant en-
zyme expression.
[253]
In another study, Gomez-
Cabrera et al.
[97]
showed that chronic supple-
mentation with vitamin C impacted on exercise
performance by decreasing exercise training effi-
ciency. This was shown in both humans and rats.
Analysis of animal muscles showed that the anti-
oxidant supplementation inhibited upregulation
of Mn-SOD and GPX gene expression. More-
over, attenuated mitochondrial biogenesis in the
supplemented rats was indicated by reduced
protein levels of cytochrome c (cyt c) and
transcription factors peroxisome proliferator-
activated receptor co-activator 1 (PGC-1), nuclear
respiratory factor 1 (NRF-1) and mitochondrial
transcription factor A (mTFA). Cyt c, a protein
in the inner membrane of mitochondria, is an
essential component of the electron transport
chain and serves as a marker of mitochondrial
content. PGC-1 is a transcriptional coactivator of
the genes involved in cellular energy metabolism.
It induces messenger RNA expression of NRF-1
and mTFA and provides a link between ex-
ternal physiological signals and mitochondrial
biogenesis.
In a recent study from our laboratory,
[257]
the
effects of 14 weeks of antioxidant supplementa-
tion (a-tocopherol and a-lipoic acid) and tread-
mill exercise on myocardial and vascular endo-
thelium gene expression were investigated in rats.
Both antioxidant therapy and exercise training
downregulated IL-6 gene expression, while the
expression of the RAS homolog gene family
member A (RhoA), a gene involved in cardio-
vascular disease progression, was upregulated by
antioxidant supplementation and downregulated by
exercise. The combination of supplementation and
exercise resulted in a blunted downregulation of
RhoA expression. These findings confirmed an un-
favourable effect of antioxidants on exercise-
induced cardiovascular protection.
5.3 Reactive Oxygen Species Elimination
and Physiological Processes
Given that reactive species play an important
role in the regulation of muscle contractile ac-
tivity, their elimination with high doses of anti-
oxidants may result in negative effects on muscle
function. We have shown that supplementation
of rats with vitamin E and a-lipoic acid decreased
lipid peroxidation after a fatigue protocol but
had no effect on fatigue resistance.
[251]
Moreover,
high levels of vitamin E depressed muscle force
production at low stimulation frequencies. Acute
supplementation of rats with vitamin C and
tempol, a radical scavenger, reduced skeletal
muscle blood flow, oxygen utilization and force
production at rest and during electrically stimu-
lated contractions.
[255]
Close and colleagues
[197]
found consumption
of high doses of vitamin C in the days post-
exercise delayed the recovery of muscle function
in humans. Chronic supplementation of compe-
titive kayakers with a mixture of vitamins and
minerals failed to protect from exercise-induced
oxidative stress and inflammation, and hindered
the recovery of muscle damage after a 1000 m
race.
[165]
Together, these findings suggest that
ROS produced post-exercise play a role in muscle
regeneration.
Physical activity is known to improve insulin
sensitivity as the transient rise in ROS production
efficiently counteracts insulin resistance.
[91]
In
one of the most interesting studies on this topic,
Ristow et al.
[91]
reported that supplementation
with vitamins E and C inhibited the insulin sen-
sitizing effects of exercise training, regardless of
previous training status. They found that ex-
ercise-induced oxidative stress increased expres-
sion of ROS-sensitive transcriptional regulators
1058 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
of insulin sensitivity PGC-1a, PGC-1band per-
oxisome proliferator-activated receptor-g, a nu-
clear receptor protein involved in fatty acid sto-
rage and glucose metabolism. Exercise training
also decreased fasting plasma insulin levels
and caused an adaptive response promoting
endogenous antioxidant defence capacity by up-
regulation of SOD1,SOD2 and GPX gene
expression. Supplementation with antioxidants
precluded these health promoting effects of
exercise in both pre-trained and untrained men.
Reactive species act as potent vasodilators and
may be an important part of the vasodilatory
response during exercise. Administration of an
antioxidant cocktail (vitamins C, E and a-lipoic
acid) augmented plasma antioxidant capacity
and reduced circulating levels of free radicals in a
group of healthy young males.
[254]
Importantly,
brachial artery vasodilation was decreased during
a submaximal handgrip exercise in the supple-
mented group. The direct measurement of oxi-
dative stress is a strength of this study. Wray
et al.
[256]
from the same research group, showed
that 6 weeks of single leg knee-extensor exercise
lowered blood pressure at rest and during ex-
ercise in a group of mildly hypertensive older
men. Acute administration of a-lipoic acid, vita-
min C and vitamin E after the training period
returned blood pressure to pre-training values.
Furthermore, with exercise training, vasodilation
improved significantly, but the effect was blunted
after consuming antioxidants. It was concluded
that antioxidant administration negated the
health benefits of exercise training in older in-
dividuals. Although the study only included six
subjects, the authors state they had sufficient
statistical power.
Negative outcomes following the combination
of two potentially beneficial interventions em-
phasize the complex nature of oxidative stress.
Reactive species in skeletal muscle are generated
in response to physiological and pathophysio-
logical stimuli and are not solely by-products of
aerobic metabolism. Attempts to decrease their
levels, such as, for example, through antioxidant
supplementation, may lead to a blunting of po-
sitive effects of exercise and even deleterious
health effects.
6. Limitations of the Studies and Future
Directions
An obvious limitation of the current body of
research on this topic is the lack of studies
investigating antioxidants other than vitamin E,
vitamin C and coenzyme Q
10
. Despite the vast
range of antioxidant supplements commercially
available, many of these compounds have not been
studied based on our systematic search. Therefore,
generalizing the results to all antioxidant supple-
ments may be problematic. Furthermore, numer-
ous methodological issues interfere with the ability
to interpret the effects of antioxidant supple-
mentation on exercise. These include differences in
exercise protocols, subject population, dosage and
form of supplements, duration and timing of sup-
plementation, and the methodology used to assess
oxidative stress. It should be made clear that de-
tection of differences between treatment and con-
trol groups in measured indices does not imply
cause and effect of antioxidant supplements. Most
studies investigated the effect of supplementation
in small groups of subjects and did not employ a
crossover design that could easily lead to type I and
type II errors.
[99,202,249,250,259]
Null findings in supplementation studies could
be partially explained by insufficient dosages or
treatment durations and the lack of sensitive de-
tection techniques. Most studies lacked informa-
tion on the redox state of the subjects to confirm
whether their endogenous defence system was
actually overwhelmed by increased ROS forma-
tion. For instance, highly trained individuals may
experience an attenuated oxidative stress res-
ponse, especially with long-duration, low-
intensity exercise protocols. This is likely due to
an enhanced endogenous antioxidant defence
that is sufficient to combat an increased free
radical production, thus masking any potential
effect of supplementation. However, prolonged
vigorous exercise can lead to a very large increase
in ROS production, overwhelming antioxidant
systems. In such conditions, additional doses of
antioxidants may not exert any significant effect
on oxidative stress levels.
Furthermore, detection depends, to a large
degree, on the tissue/biofluid sampled, the timing
Antioxidant Supplementation in Exercise Training 1059
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
of sampling and the sensitivity and specificity of
the chosen biomarker. For example, in some
studies, oxidative stress may have occurred pre-
ceding or following the sample collection and
was therefore not detected. Importantly, nearly
all of the studies included in the review did not
determine the actual levels of ROS but, rather,
measured indirect markers of oxidative stress,
such as by-products of lipid, protein and DNA
damage.
[93,144,174,175,197,202,259]
In addition, in the
majority of the studies, a single assay analysis of
oxidative stress was used. Indeed, investigating
only a particular oxidative stress marker does not
represent universal oxidative stress status. Given
the complexity of oxidative stress, a number of
markers should be chosen (e.g. lipid peroxidation
and protein oxidation measures). Moreover,
changes in redox status within cells may be
compartmentalized and regulated via specific
signalling pathways. It seems highly unlikely that
various potential targets in cells would show an
equivalent sensitivity to specific ROS. In addi-
tion, ROS are present in low concentrations in
biological systems, have short half-lives and are
highly reactive. Thus, direct measurement is dif-
ficult and as reactive species cannot be targeted
easily exogenous antioxidants may not scavenge
the relevant ROS.
Difficulty in quantifying oxidative stress and
understanding the health implications of oxida-
tive stress measures are important issues when
establishing appropriate intervention strategies.
Despite the increasing awareness of the im-
portance of reactive species, screening and mon-
itoring of oxidative stress has not yet become
routinely available. Individuals are often recom-
mended antioxidant therapy, although there is no
test that advises whether to assess if they are
exposed to increased levels of free radicals or
have depleted antioxidant capacities.
Careful reassessment of the existing evidence is
warranted to better understand the conflicting
data and design future studies appropriately.
There is a need for more rigorous clinical trial
designs with populations under high levels of
oxidative stress and carefully chosen outcomes.
Large randomized controlled trials with exercis-
ing individuals consuming a variety of anti-
oxidant supplements and using hard endpoints,
such as onset of disease, would need to be con-
ducted to adequately address the question of the
impact of antioxidant supplementation on ex-
ercise-induced oxidative stress. Bioavailability
and pharmacokinetics of antioxidants should be
examined closely to establish the dosage, timing
and duration of supplementation that would
significantly reduce oxidative stress levels in the
study participants. In addition, nutrigenomic is-
sues might be considered as people respond dif-
ferently to particular antioxidants based on their
genetic profile. Further research, supported by
improved techniques to measure oxidative stress
and target specific ROS, will help to clarify
the potential roles of antioxidant supplements in
exercise-training.
7. Optimizing Nutrition
7.1 Summary
Studies included in this review have demon-
strated disparate results with regards to the ef-
fects of antioxidant supplementation on exercise-
induced oxidative stress. In summary, there is
insufficient evidence to recommend antioxidant
supplements for exercising individuals who con-
sume the recommended amounts of dietary anti-
oxidants through food. Antioxidant supplements
generally do not improve physical performance.
There is little proof to support their role in pre-
vention of exercise-induced muscle damage and
enhancement of recovery. Although ingesting
supplemental antioxidants can decrease exercise-
induced oxidative stress, there is no evidence that
this confers health benefits. Further work is
warranted to illuminate the interactive effects of
exercise training and antioxidant supplementation.
7.2 Current Recommendations
The outcomes of supplementation studies
have important implications for nutritionists,
physicians, practitioners, exercise trainers and
athletes, as well as for the general population.
Reports that high doses of antioxidants preclude
health-promoting effects of exercise training and
interfere with ROS-mediated physiological pro-
1060 Peternelj & Coombes
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
cesses suggest caution in the use of antioxidant
supplements. Physically active individuals need
to optimize their nutrition rather than use sup-
plements. Diets rich in antioxidants should
be attained by consuming a variety of fruits, ve-
getables, whole grains and nuts. Whole foods,
rather than capsules, contain antioxidants pre-
sented in beneficial ratios and numerous phyto-
chemicals that may act in synergy with the former
to optimize the antioxidant effect. Antioxidant
supplementation may be warranted when in-
dividuals are exposed to high levels of oxidative
stress and struggle to meet the dietary antioxidant
requirements. Athletes, who restrict their energy
intake, use severe weight loss practices and elim-
inate one or more food groups from their diet
or consume unbalanced diets with low micro-
nutrient density, are at risk of suboptimal anti-
oxidant status. A qualified sports dietitian would
need to provide individualized nutrition direction
and advice subsequent to blood analysis and
comprehensive nutritional assessment. Careful
product evaluation is required prior to adopting
an antioxidant regimen, which should be
clinically supervised and should only represent a
short-term solution while dietary changes are
being implemented.
8. Conclusions
The multifunctional role of reactive species in
living organisms, and the beneficial and deleterious
effects of antioxidant supplementation demon-
strate the complexity of exercise-induced oxidative
stress. Interactions of antioxidants and reactive
species should be carefully considered as the redox
state will dictate cell functioning. More detailed
research and critical appraisal of the situations that
may warrant antioxidant supplementation in
exercise training are required. A balanced diet in-
cluding a variety of fruits and vegetables remains
the best nutritional approach to maintain optimal
antioxidant status.
Acknowledgements
The authors wish to declare no conflicts of interest or
funding that are directly relevant to the content of this review.
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Correspondence: Tina-Tinkara Peternelj, School of Human
Movement Studies, University of Queensland, St Lucia,
Brisbane, QLD, 4072, Australia.
E-mail: tpeternelj@hms.uq.edu.au
Antioxidant Supplementation in Exercise Training 1069
ª2011 Adis Data Information BV. All rights reserved. Sports Med 2011; 41 (12)
... Our rats were subjected to increasing levels of physical activity (Table 2), and it is likely that the oxidative stress induced by the intense activity of the last weeks cannot be compensated by the concomitant catechin administration. This is in line with several experimental results showing that the administration of exogenous antioxidants (catechins included) to human subjects performing physical activity does not have positive effects on various physiological parameters 63,64 . It has even been suggested that high doses of antioxidants have adverse effects on the performance of athletes, outweighing their potential beneficial effects 65 . ...
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Hypertension represents the main risk factor for the onset of cardiovascular diseases. Pharmacological treatments to control hypertension have been associated with new treatments involving physical activity and/or the intake of natural components (nutraceuticals). We here report the effects produced by a combination of a natural component (catechins) and a moderate exercise program on the development of hypertension in spontaneous hypertensive rats compared with those of each individual treatment. Arterial blood pressure and heart rate were measured with a non-invasive method in 28 rats randomly assigned to four groups: rats subjected to moderate physical exercise; rats with a catechins-enriched diet; rats subjected to moderate physical exercise combined with a catechins-enriched diet; control, untreated-rats left to age. All treatments were applied for 6 weeks. The statistical analysis revealed that the three treatments significantly reduced the weekly increase in arterial blood pressure observed in control rats (SBP, P < 0.0001; DBP, P = 0.005). However, the reduction of arterial blood pressure induced by combined treatments was not higher than that induced by the single treatment, but more prolonged. All treatments showed strong antioxidative properties. Our data show that physical activity and a diet enriched with catechins individually have an important hypotensive effect, while the association did not produce a higher hypotensive effect than the single treatment, even if it was able to decrease blood pressure for a longer time. These findings have important implications for developing a protocol to apply in novel hypertension prevention procedures.
... It is necessary to supply these compounds from food sources through adequate consumption of raw fruits, vegetables, spices, and vegetable oils. The use and duration of supplementation during the training period should be determined by a physician and nutritionist [48]. ...
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It is said that football matches are the second most important thing in the world. Football is currently one of the most popular sports and brings record numbers of people together in stadiums and in front of TV sets. For many years, players were allowed to consume the products they preferred at the times they subjectively deemed appropriate. However, today's soccer has evolved due to self-improvement and players following elite athletes. This change in approach to the sport has coincided with an increase in the pace and intensity of top soccer games over the past two decades. In addition, the commercialization of the sport has resulted in increasing demands and continually increasing the level of sportsmanship. Nutrition is an important part of the sports training program. International guidelines, based on scientific research, recommend amounts, types and timing of food intake to ensure excellent training while reducing injuries and trauma. In order to achieve metabolic optimization, there must be a balance between nutrition, training, and recovery. Energy should be provided from optimal sources, and maintaining an adequate energy balance is critical for those who engage in physical activity, especially professional athletes. Supplements and foodstuffs for special nutritional purposes are widely used, so knowledge of the indications for their use, as well as the risks posed by inappropriate use, is essential.
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Effective nutritional-metabolic support strategies are of interest to athletes, coaches, and physicians prescribing various supplements. Dietary deficiencies in macronutrients, vitamins, and minerals of the right type can interfere with training adaptation, while in athletes who eat a balanced diet, physiological training adaptation can be enhanced. Therefore, in the event of a lack of specific nutrients, athletes are forced to use various supplements, but will individual combinations of them be safe for the body as a whole and effective for improving athletic performance? The paper analyzes and summarizes studies on the compatibility of some supplements and the safety and efficacy of such combinations in sports, in particular: the compatibility of vitamins E and C, vitamin D and calcium, creatine and caffeine, branched chain amino acids (isoleucine, leucine and valine).
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The purpose of this study was to determine the effects of antioxidant therapy on indirect markers of muscle damage following eccentric exercise (EE). Eighteen women were randomized to an antioxidant supplement or a placebo before a bout of EE. Plasma creatine kinase (CK) activity, muscle soreness (MS), maximal isometric force (MIF), and range of motion (ROM) were assessed before and through 14 d postexercise. Eccentric exercise resulted in an increase in CK activity and MS, and a drop in MIF and ROM during the days following EE, which returned to baseline values 14 d after EE in both groups. Antioxidants attenuated the CK activity and MS response to the EE, while little difference was noted between groups in MIF or ROM. These fndings suggest that antioxidant supplementation was helpful in reducing the elevations in plasma CK activity and MS, with little impact on MIF and ROM loss.
Article
Initial experiments were conducted using an in situ rat tibialis anterior (TA) muscle preparation to assess the influence of dietary antioxidants on muscle contractile properties. Adult Sprague-Dawley rats were divided into two dietary groups: 1) control diet (Con) and 2) supplemented with vitamin E (VE) and alpha -lipoic acid (alpha -LA) (Antiox). Antiox rats were fed the Con rats' diet (AIN-93M) with an additional 10,000 IU VE/kg diet and 1.65 g/kg alpha -LA. After an 8-wk feeding period, no differences existed (P > 0.05) between the two dietary groups in maximum specific tension before or after a fatigue protocol or in force production during the fatigue protocol. However, in unfatigued muscle, maximal twitch tension and tetanic force production at stimulation frequencies less than or equal to 40 Hz were less (P < 0.05) in Antiox animals compared with Con. To investigate which antioxidant was responsible for the depressed force production, a second experiment was conducted using an in vitro rat diaphragm preparation. Varying concentrations of VE and dihydrolipoic acid, the reduced form of -LA, were added either individually or in combination to baths containing diaphragm muscle strips. The results from these experiments indicate that high levels of VE depress skeletal muscle force production at low stimulation frequencies.
Article
Carotenoids are natural pigments which are synthesized by plants and are responsible for the bright colors of various fruits and vegetables. There are several dozen carotenoids in the foods that we eat, and most of these carotenoids have antioxidant activity. beta-carotene has been best studied since, in most countries it is the most common carotenoid in fruits and vegetables. However, in the U.S., lycopene from tomatoes now is consumed in approximately the same amount as beta-carotene. Antioxidants (including carotenoids) have been studied for their ability to prevent chronic disease, beta-carotene and others carotenoids have antioxidant properties in vitro and in animal models. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. The use of animals models for studying carotenoids is limited since most of the animals do not absorb or metabolize carotenoids similarly to humans. Epidemiologic studies have shown an inverse relationship between presence of various cancers and dietary carotenoids or blood carotenoid levels. However, three out of four intervention trials using high dose beta-carotene supplements did not show protective effects against cancer or cardiovascular disease. Rather, the high risk population (smokers and asbestos workers) in these intervention trials showed an increase in cancer and angina cases. It appears that carotenoids (including beta-carotene) can promote health when taken at dietary levels, but may have adverse effects when taken in high dose by subjects who smoke or who have been exposed to asbestos. It will be the task of ongoing and future studies to define the populations that can benefit from carotenoids and to define the proper doses, lengths of treatment, and whether mixtures, lather than single carotenoids (e.g. beta-carotene) are more advantageous.
Article
It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. METHODS: 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. FINDINGS: There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. INTERPRETATION: Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.
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IntroductionInflammatory DiseasesNeurodegenerative DiseasesDiseases of the EyeBlood DisordersAtherosclerosis and Cardiovascular DiseaseInfections and Parasitic DiseasesCancerProteins of the Peroxiredoxin-Based System as Diagnostic and Prognostic Tools, and Potential Drug TargetsConclusions References