Antioxidants and Exercise Performance: With A Focus On Vitamin E and C Supplementation

International Journal of
Environmental Research
and Public Health
Review
Antioxidants and Exercise Performance: With a Focus
on Vitamin E and C Supplementation
Madalyn Riley Higgins 1 , Azimeh Izadi 2 and Mojtaba Kaviani 1, *
1 Faculty of Pure and Applied Science, School of Nutrition and Dietetics, Acadia University, Wolfville,
NS B4P 2R6, Canada; [email protected]
2 Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of
Medical Sciences, Tabriz 5166/15731, Iran; [email protected]
* Correspondence: [email protected]; Tel.: +1-902-585-1884

Received: 27 September 2020; Accepted: 6 November 2020; Published: 15 November 2020
Abstract: Antioxidant supplementation, including vitamin E and C supplementation, has recently

received recognition among athletes as a possible method for enhancing athletic performance.
Increased oxidative stress during exercise results in the production of free radicals, which leads
to muscle damage, fatigue, and impaired performance. Despite their negative effects on
performance, free radicals may act as signaling molecules enhancing protection against greater
physical stress. Current evidence suggests that antioxidant supplementation may impair these
adaptations. Apart from athletes training at altitude and those looking for an immediate, short-term
performance enhancement, supplementation with vitamin E does not appear to be beneficial.
Moreover, the effectiveness of vitamin E and C alone and/or combined on muscle mass and strength
have been inconsistent. Given that antioxidant supplements (e.g., vitamin E and C) tend to block
anabolic signaling pathways, and thus, impair adaptations to resistance training, special caution
should be taken with these supplements. It is recommended that athletes consume a diet rich in fruits
and vegetables, which provides vitamins, minerals phytochemicals, and other bioactive compounds
to meet the recommended intakes of vitamin E and C.
Keywords: sport performance; altitude training; resistance exercise; dietary supplements; free radicals
1. Introduction
In addition to rigorous training and diet regimes, many high-level athletes still look for an extra
edge to improve their performance, often turning to nutrient supplementation. It has been estimated by
the American College of Sports Medicine that approximately 50% of athletes take vitamin supplements
with the goal of staying fit and improving endurance [1,2]. Recently, antioxidant supplementation has
received attention among athletic populations as a possible method to reduce muscle damage incurred
during exercise [3].
Intakes of vitamin C and E vary widely across the world, with the prevalence of individuals with an
inadequate intake ranging between 34–95% for vitamin E and 5–65% for vitamin C in different groups,
including the general population and athletes [4,5]. The current recommended dietary allowances
(RDA) of vitamin E for adults is 15 mg for both males and females. For vitamin C, the RDA for adults
aged 19 years or older is 75 mg for females and 90 mg for males. It has been reported that most athlete
users of antioxidant supplements already have an adequate intake of vitamin C and E and meet the
RDAs for both vitamins [6]. Over the last decade, the use of antioxidant supplementation has been
questioned, as they seem to inhibit or attenuate the signaling of important adaptations such as muscle
mitochondrial biogenesis and hypertrophy [7]. This paper will review the role of free radicals and
Int. J. Environ. Res. Public Health 2020, 17, 8452; doi:10.3390/ijerph17228452 www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2020, 17, 8452 2 of 26
antioxidants, as well as their effects on athletic performance with a primary focus on vitamin E alone
and in combination with vitamin C.
2. Antioxidants and Sports Performance

Regular exercise has many demonstrated benefits including reducing the risk of diseases such as
type II diabetes, cancer, and dementia, as well as improving the function of our organs, in particular
the skeletal muscle [7]. However, during intense exercise, free radical or reactive oxygen and nitrogen
species (RONS) production increases and may inhibit muscular contractile function leading to muscle
fatigue and performance impairment [8]. Given the role of antioxidants in protection against free
radicals, it has become common practice among athletes to consume antioxidant supplements to
combat muscle damage and fatigue and to enhance performance [7]. Although antioxidants play an
important role in the protection from RONS, evidence suggests that antioxidant supplementation
may impair exercise training adaptations. The concern is that the reactive species generated during
exercise might be implicated in the improvement in aerobic capacity and muscle hypertrophy,
through stimulating molecular pathways via proteins, including peroxisome proliferator-activated
receptor-c coactivator (PGC1-α) and mitogen-activated protein kinases (MAPK) [9–11]. For example,
according to Ristow et al. [12], vitamin E (400 IU/day) and vitamin C (1000 mg/day) consumption
prevents the induction of PGC1-α and mitochondrial biogenesis, as well as key endogenous antioxidant
enzymes in human skeletal muscle. In this sense, increased mitochondrial biogenesis is a major
adaptation to exercise training in skeletal muscle and PGC1-α is considered the master regulator in
mitochondrial biogenesis [13].
Conversely, some authors suggested positive effects of a transient increased level of RONS induced
by exercise. In fact, the RONS is implicated in regulating muscle contractile activity, in addition,
RONS stimulates muscle regeneration [14] and improves vasodilation during exercise [15]. However,
high concentrations of RONS and oxidative stress increase inflammation and damage to cells and
tissues [16].
To sum up, the balance between RONS and antioxidant systems is important. Despite their high
training demands, evidence shows that many endurance athletes have diets which contain insufficient
antioxidants to support their physical activity demands [17]. Given their low intakes of antioxidants,
it is often believed that endurance athletes should take antioxidant supplements. However, given the
many demonstrated health benefits of exercise, it appears to be unlikely that free radical production
via exercise will negatively impact performance in the long term [17].
2.1. Reactive Oxygen and Nitrogen Species

Reactive oxygen and nitrogen species (RONS), also called free radicals, are produced in the
body continually via oxidative metabolism [8]. The terms free radicals and RONS will be used
interchangeably throughout this paper. RONS arise when there is insufficient oxygen to complete a
reduction resulting in the creation of a free radical [18]. Free radicals are highly reactive due to an
unpaired electron in their outer orbital [8]. Due to their reactivity, high concentrations of free radicals
can cause damage to lipids, protein, and DNA [8]. During exercise, increased oxygen consumption
leads to an increase in RONS production [19]. This increase in RONS production during exercise may
contribute to muscle damage, impaired immunity, and fatigue [19]. Muscle damage, including lipid
peroxidation, incurred from RONS during acute exercise has been suggested as a possible cause of
delayed onset muscle soreness (DOMS) and exercise performance impairment [20,21]. Despite the
damage they may cause, free radicals are also essential for proper physiological functioning acting as
intracellular messengers [17].
Although high levels of RONS demonstrate negative effects on exercise performance, more recently,
their role in positive cellular adaptation to stress and athletic training has been investigated [19].
Free radicals may act as signaling molecules for muscle function regulation and adaptation via the
upregulation of protective proteins [22]. This upregulation in protective proteins allows for increased
protection against future stress and free radical exposure [22]. The extent to which these reactive species
are harmful versus beneficial depends on various factors, including exercise duration and intensity,
an athlete’s nutritional and training status, and age [19]. Lower doses of RONS appear to be beneficial
for training adaptations during acute performance [22]. However, increased RONS production in
skeletal muscle is implicated in muscle damage and impaired muscle performance [23]. Regarding the
training status, it has recently been shown [24] that sprinter and endurance master athletes have better
redox balance and inflammatory status, compared to the age-matched control, but worse than the
untrained adults. Regarding the exercise mode, sprinters presented a better antioxidant capacity than
both the controls and endurance runners, whereas the nitric-oxide profile (as a marker of endothelial
function) was better for endurance runners and lower for the controls. Endurance runners have
shown a better nitric-oxide profile, as a marker of endothelial function, whereas sprinters had a better
redox balance and cytokines profile. Therefore, a personalized supplementation with respect to the
type of exercise and training status seems reasonable given the discrepancies existing in the current
literature [25].
2.2. Exogenous and Endogenous Antioxidants

Antioxidants are compounds which help protect cellular organs from oxidative damage incurred
via free radicals [26]. There are many different antioxidants which can be classified as endogenous
(produced in the body) or exogenous/dietary (taken in from external sources). Antioxidants can also be
classified as enzymatic (catalytically remove free radicals) or non-enzymatic (remove free radicals in
ways other than a catalytic reaction) [17]. Antioxidants protect against oxidative stress by converting
free radicals into non-radicals thereby reducing their reactivity, or by preventing the conversion of
inactive radicals into more damaging species [17].
Endogenous antioxidants are proteins produced by the body and can be either enzymatic or
non-enzymatic [17]. Endogenous enzymatic antioxidants include superoxide dismutase (SOD),
catalase (CAT), and glutathione peroxide (GPX) [17,22]. The major non-enzymatic endogenous
antioxidant is glutathione (GSH) [17]. Endogenous antioxidants production increases following
exercise and plays a role in protecting cells from oxidative damage [22]. Well-trained athletes possess
higher levels of endogenous antioxidants in their muscles than athletes with less training as a result of
training adaptations [17]. Consequently, those who train irregularly or at lower intensities such as
recreational athletes, will likely have less protection against oxidative stress [18].
Most fruits and vegetables contain a variety of exogenous antioxidants. However, humans can
also acquire exogenous antioxidants though other food sources such as nuts and seeds [17].
Important exogenous antioxidants which play a role in protection from free radicals include vitamin
E, vitamin C, vitamin A, polyphenols, and some minerals (Zinc, Manganese, Cupper, Selenium) [22].
Exogenous antioxidants are obtained in the diet through foods such as fruits and vegetables or through
dietary supplements [17].
The oxidative capacity of antioxidants varies based on the type of free radicals [8].
Exogenous antioxidants, such as vitamin E and C, are non-targeted free radical scavenging
antioxidants, whereas our endogenous antioxidants are more complex and allow for a more controlled,
localized effect [7]. Endogenous antioxidants are our first line of defense against free radicals,
while exogenous antioxidants including vitamin E and C, act as a second line of defense offering further
protection [27]. Recently, supporting endogenous antioxidants through oral ingestion of exogenous
antioxidants has received attention as a possible strategy to reduce oxidative stress and decrease muscle
damage sustained during acute performance [26]. Oxidative stress and muscle damage are thought to
impair performance and recovery, making the promise of antioxidant supplementation to reduce this
effect, of interest to athletes.
2.3. Antioxidants and Impaired Adaptations to Training

Although muscle damage and fatigue are undesirable to athletes and prolonged oxidative stress
may lead to cellular damage, RONS role as signaling molecules may result in favorable adaptations
to exercise training [7]. The physiological stress, including exposure to RONS, which occurs during
acute exercise results in skeletal muscle adaptations enabling muscles to cope with further stressors
in the future [7]. One such training adaptation that may be impaired is the body’s enhanced
endogenous antioxidant production. In response to endurance exercise training, endogenous
antioxidants production is increased and may provide sufficient protection without the need to
increase exogenous antioxidant intake [17].
3. Search Strategy
A systematic literature search was performed up to October 2020 in PubMed, Scopus, and Web of
Sciences based on the following keywords: Vitamin C, ascorbic acid, vitamin E, tocopherol, exercise,
training, exercise performance, aerobic, resistance training, endurance, strength, muscle hypertrophy,
and adaptation. Inclusion criteria were vitamin C or vitamin E supplementation (alone or together)
combined with an exercise training program (both acute and long-term supplementation and training
program). Two investigators (M.R.H. and A.I.) independently screened the abstracts and titles and
retrieved the relevant full texts to assess eligibility based on the inclusion criteria. The full-text articles
included were also searched manually for any additional studies.
4. Vitamin E as An Antioxidant Supplement

There are many different types of exogenous antioxidants athletes may take, although vitamin
E appears to be one of the most widely available [19]. Vitamin E refers to lipid soluble compounds
including four tocopherols and four tocotrienols, with α-tocopherol being the most biologically available
and most well-known form [22]. Tocopherols and tocotrienols act as potent free-radical scavengers in
membranes and lipoproteins, they quench fatty acid peroxyl radicals and yield tocopheroxyl radicals,
the resulting tocopheroxyl radicals may be reduced by an appropriate reducing agent such as ubiquinol
or vitamin C to regenerate vitamin E. Although many antioxidants are found in nature, vitamin E is one
of the most widely distributed [17]. Vitamin E is found in lipid rich structures such as the sarcoplasmic
reticulum, where it scavenges free radicals produced by the mitochondria, thereby reducing lipid
peroxidation and membrane damage [8].
4.1. Food Sources Versus Supplements

Although exogenous antioxidants can be found in lipid based membranes as well as in aqueous
phase, no endogenous antioxidants exist within lipid based cell membranes, therefore, making it
essential to acquire some antioxidants from the diet [17]. To ensure a variety of exogenous antioxidants,
it is recommended that athletes consume a diet rich in fruits and vegetables [17]. Along with their
high antioxidant content, fruits and vegetables may also provide benefits for athletes given that many
of the additional bioactive compounds they contain are not found in single dose pharmacological
antioxidant supplements [12,28]. It has also been suggested that the different kinds of antioxidants
found in plant foods may act synergistically allowing them to have more positive effects than single,
mega dose antioxidant supplements [27].
Given that vitamin E is a fat soluble vitamin, athletes following lower fat diets may have an
impaired vitamin E intake as well as absorption [29]. Sacheck et al. [30] investigated the dietary intake
of vitamin E among collegiate female rowers following a low fat versus a high fat diet and found that
those in the low fat group consumed significantly less vitamin E (2.9 mg vitamin E/day) than those in
the high fat group (9.8 mg vitamin E/day). In addition to a reduced intake of vitamin E on a lower fat
diet, athletes in the study likely would have an impaired absorption of vitamin E as well. An impaired
absorption of vitamin E as a result of following a low fat diet may result in insufficient levels of vitamin
E, meaning that some athletes may benefit from additional vitamin E through supplementation [29].
Koivisto et al. [28] investigated whether high antioxidant intakes from food affect the adaptive
response to athletic training, as well as whether increasing the antioxidant intake via antioxidant rich
foods would affect adaptive responses in elite athletes following altitude training. Daily antioxidant
rich foods consumed in the study included 50 g of dried berries and fruits, a 750 mL fruit, vegetable,
and berry smoothie, 40 g walnuts, and 40 g dark chocolate (>70% cocoa content) Compared to a
placebo group, no differences were reported in VO2 max, erythropoietin, or hemoglobin mass following
an antioxidant rich diet. The authors concluded that enhancing the antioxidant concentration via
increased consumption of antioxidant rich foods does not impair adaptive responses to training,
thereby contracting results from studies on antioxidant supplementation. This further supports the
idea explaining how antioxidants from foods rather than supplements may help athletes receive
adaptation benefits from oxidative stress while keeping oxidation low enough to avoid harm.
More recently, Koivisto et al. [31] reported that consumption of antioxidant-rich foods increased
antioxidant capacity and decreased some of the altitude-induced inflammatory biomarkers in elite
athletes. Koivisto et al. [31] found that consumption of antioxidant-rich foods had no effect on the
oxidative stress or acute cytokine responses to exercise stress-tests at altitude.
It is reported [32] that a docosahexaenoic acid (DHA) and vitamin E-enriched beverage consumed
at 1 L per day, 5 days/week, for 5 weeks containing 45.7 ± 27.7 mg/L alpha-tocopherol, did not
alter the performance parameters such as blood lactate and fatigue during a maximal exercise test.
The enriched beverage which was provided to both young and senior athletes, protected plasma lipid
oxidative damage, although it enhanced nitrative damage in erythrocytes in the young athletes after
exercise. The gene expression of peripheral blood mononuclear cells (PBCM) antioxidant enzymes
was enhanced after acute exercise only among the young athletes supplemented with the beverage.
Despite beverage supplementation demonstrating a reduction in the plasma oxidative damage and an
enhanced adaptive PBMC antioxidant response in young athletes, no effect was seen among the senior
athletes. In summary, the effects of functional beverage supplementation were age-dependent and
require more studies. In another study by Capó et al. [33], performance (measured as exercise time)
was not affected by enriched beverage supplementation. More recently, Hoene et al. [34] suggested a
cautious use of vitamin E as a dietary supplement, since they observed that a vitamin E-enriched diet
interferes with the adaptation process to exercise in mice. However, Górnicka et al. [35] suggested
that an impaired α-tocopherol status and its adequate intake is required to preserve an optimal status
to prevent the skeletal and cardiac muscles, as well as the testes from damage, since in their study,
α-tocopherol reduced lipid peroxidation in mice subjected to physical effort. Yi et al. [36] investigated
the effects of 75 g of almonds (a good source of vitamin E) consumed as single pre-exercise supplements
over 4 weeks, and observed the improved performance (measured as distance travelled). Similarly,
acute almond supplementation (60 g, 2 h before exercise) is reported to enhance performance in
endurance exercise in the trained subjects [37]. An animal study also [38] reported that tocotrienol-rich
fraction (TRF) increased liver and muscle glycogen and reduced the exercise-induced oxidative stress,
as well as blood lactate forced on swimming rats.
Mega doses of vitamin E via supplementation can result in large increases in body stores of the
vitamin [17]. Receiving too much vitamin E through food alone is nearly impossible, however, a state
of vitamin E toxicity can be met through supplementation resulting in gastric distress and an increased
risk of bleeding due to the role of vitamin E as an anticoagulant [17]. Despite the risk of toxicity,
athletes who do not consume a varied and balanced diet may benefit from antioxidant supplementation
to meet the recommended dietary allowances (RDAs) of antioxidant vitamins including vitamin E [39].
In addition, if reducing oxidative stress and inflammation have priority, adapting a balanced diet with
additional mixed fruit, vegetables, and berries, as well as supplementing with antioxidant-enriched
beverages is indicated.
4.2. Supplementation with Vitamin E Alone and Combined with Vitamin C and Exercise Performance
Vitamin E supplementation, often combined with vitamin C, is common among athletes given their
combined antioxidant effect [40]. Vitamin E is a fat-soluble vitamin which includes four tocopherols
and four tocotrienols with α-tocopherol in the most biologically available and well-studied form [22].
Vitamin E is a powerful antioxidant which is capable of donating hydrogen atoms to free radicals
including superoxide and hydroxyl radicals, converting them to a more stable form, and preventing lipid
peroxidation and membrane damage [8]. Similarly, vitamin C, a hydro soluble vitamin, protects against
free radical production by scavenging free radicals [8]. Vitamin E and C work in conjunction with each
other, with vitamin C helping to recycle vitamin E back to a reduced state and enabling it to continue
to oxidize free radicals [8].
Under most dietary conditions, vitamin E concentrations in the body are relatively low and with
low vitamin E stores shown to increase muscular fatigue; increasing vitamin E concentrations
through supplementation is a promising practice for athletes [17]. In a review of 10 studies
investigating the effects of vitamin E and/or C supplementation on chronic exercise and exercise
adaptation, Nikolaidis et al. (2012) [26] noted mixed results. Of the studies reviewed on antioxidant
supplementation, two of them reported an ergolytic effect, six showed no effect, and a further two
reported an ergogenic effect [7]. Of note, two of the studies reporting a positive effect used rodent
models and cannot be directly applied to humans or exercise performance [26]. One older study by
Akova et al. (2001) [41] tested the effects of vitamin E supplementation on muscular performance
among sedentary females noting no effects following supplementation. Zoppi et al. (2006) [42] also
reported no effect on antioxidant enzymes concentrations or performance following supplementation
with vitamin E and C on elite soccer players. According to Silva et al. [43], vitamin E supplementation
could provide protection from inflammation, exercise-induced muscular and oxidative damage, fatigue,
and muscle force loss induced by exercise.
Current evidence on the effects of vitamin E supplementation on endurance outcomes is equivocal.
Rodent studies [44,45] indicated hindering effects of vitamin E supplementation on exercise-induced
mitochondrial biogenesis and antioxidant enzymes in skeletal muscle. Several human studies reported
no effect on exercise performance outcomes following supplementation with vitamin C and/or E
during endurance exercise training [9,46–48]. However, there are some human studies that have
shown negative effects of combined vitamin C and E on the adaptive responses of skeletal muscle to
endurance training, such as attenuated mRNA responses in mitochondrial proteins and antioxidant
enzymes [9,40]. To sum up, there is convincing evidence that vitamin C and E, taken alone or in
combination blunts some skeletal muscle adaptations to endurance training. There is no evidence that
vitamin C and/or vitamin E supplementation has negative effects on maximum oxygen uptake (VO2max )
as a measure of performance and training adaptations, though. In their 2014 study, Paulson et al. [40]
reported no effect on VO2 maxfollowing supplementation with vitamin E and C despite impaired
cellular adaptations. Paulson et al. [40] also found that following an endurance training protocol,
those in the placebo group showed increased fat oxidation and reduced heart rate while performing
submaximal exercise, whereas those supplementing with vitamin C and E showed no improvements
in fat oxidation or heart rate. In another study on the effects of vitamin E and C supplementation on
endurance performance, Merry and Ristow (2016) [7] noted similar findings reporting no effect of
supplementation on VO2 max. A recent systematic review concluded that vitamin C and/or vitamin E
has no negative effect on VO2 max [49].
More recently, there has been some investigation on the effects of antioxidant supplementation
on muscle hypertrophy. The current evidence suggests that supplementation with vitamin E and C
does not affect hypertrophy in young participants and athletes [19]. However, supplementation of
vitamin C may attenuate lean mass gains in older adults [7]. Bjørnsen et al. [50] observed less increase
in total mass gain following vitamin C (500 mg) and vitamin E (117.5 mg) supplementation compared
with the placebo group. On the contrary, Bobeuf et al. [51] investigated the effects of co-administration
of vitamin C (1000 mg) and E (600 mg) combined with strength training for 6 months in sedentary
healthy elderly participants. Authors observed that only participants who combined strength training
with supplementation gained fat-free mass (+1.5 kg) by the end of study. Authors concluded that
vitamin C and E supplementation might have reduced damage and/or increased protein synthesis
induced by muscle contraction associated with strength training. However, they did not measure
the oxidation or synthesis of protein. Bobeuf et al. subsequently [52] reported that 6 months of
resistance exercise (3 times a week) in healthy elderly participants had no significant effect on lean
mass, while the combination of resistance exercise with antioxidant supplementation (600 mg vitamin
E and 1000 mg vitamin C per day) significantly increased lean mass. The study by Bobeuf et al. likely
has more power due to the larger sample size. In this sense, a short-term high-dose vitamin C and
E supplementation (vitamin C: 2000 mg/day, vitamin E: 1400 IU/day; 4 days) has been effective to
attenuate exercise-induced muscle damage and inflammatory response during and after competitive
Olympic Taekwondo (TKD) matches in elite athletes [53]. However, Cumming et al. [54] reported
that vitamin C and E supplementation did not affect acute stress responses or long-term training
adaptations in the heat shock proteins or endogenous antioxidants among trained adults.
Recently, it is suggested that redox processes might contribute to resistance training adaptations
and muscle hypertrophy [25]. It is worth nothing that although Paulsen et al. [10] showed that in
healthy young adults, subjected to a heavy-load resistance training, vitamin C and E supplementation
did not impair lean body mass gain, or the acute changes in protein synthesis in muscle, the increased
phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and ribosomal protein S6 kinase
(p70S6k), induced by training was blunted. It should be noted that P70S6k and ERK 1/2 are involved
in anabolic cellular transduction pathways leading to muscle hypertrophy [25]. Dutra et al. [55]
investigated the effects of strength training combined with antioxidant supplementation on muscle
performance and thickness among young females. The authors demonstrated that, although vitamin E
in combination with vitamin C did not affect quadriceps muscle thickness, performance measurements
(i.e., peak torque and total work) were negatively affected by supplementation. The authors concluded
that excess vitamin C and E may reduce the phosphorylation of important hypertrophy pathways
mediated by RONS, such as p38, ERK1/2, and p70S6K, which support this explanation. On the other
hand, the study by Bobeuf et al. [52] was carried out in aged populations and reported a beneficial effect
of antioxidant supplementation. Therefore, it is hypothesized that, under pro-oxidative conditions
(ageing), exogenous antioxidants restore redox balance [25] and provide health benefits.
With regard to the importance of achieving and maintaining optimal body weight in many sports,
the necessity for weight loss is a very common situation among athletes [56]. However, this is important
to note that attempting to lose weight/fat might be associated with reduced dietary fat intake, which in
turn is associated with a decreased alpha-tocopherol status [57]. Of note, according to some cohort
studies, there is a positive association between the plasma α:γ-tocopherol ratio and fat-free mass
percentage (FFM%) and BMI [58], and the dietary vitamin E intake is associated with greater fat-free
mass and (FFM)% mass [59].
Regarding the effects of vitamin E alone or combined with vitamin C supplementation (in
conjunction with strength training) on strength gains, five studies [50,52,55,60,61] have been done
and reported neither positive nor negative effects on strength gain. A recent comprehensive
meta-analysis [49] provided evidence that vitamin E supplementation alone or combined with
vitamin C neither enhances nor blunts exercise-induced training adaptations, including changes in
aerobic capacity, muscle strength, or lean mass and endurance performance. However, it is unclear
whether in the state of deficiency or inadequate intake, these supplements would be beneficial for
this purpose.
Although few studies have been conducted on elite athletes, Gillam et al. [62] investigated whether
there is a threshold for the serum and membrane vitamin E level to maintain the integrity of cell
membranes following a bout of intense aerobic exercise. Their study demonstrated that vitamin E levels
are lower in elite male runners compared to untrained individuals. Therefore, to prevent perturbations
in the membrane integrity induced by training, the levels of serum and membrane α-tocopherol should
be higher than 12 and 3 mg/L, respectively, while the reference range for plasma α-tocopherol level
is 8.1–13.0 mg/L. Gillam et al. [62] concluded that supplementation with vitamin E may assist the
recovery in elite athletes.
Many studies investigating the effects of vitamin E supplementation, on both athletes and
nonathletes, also include vitamin C in their supplementation protocol. Vitamin C and E are key
components in an interacting network of the antioxidant defense system [63]. Similar to the function
of vitamin E as an antioxidant, vitamin C has the ability to protect against lipid peroxidation by
scavenging free radicals [63].
The interaction between both vitamins E and C is based on the ‘vitamin E recycling’. With vitamin
E recycling, the vitamin E, tocopherol, reacts with a peroxyl radical to form a tocopheryl radical,
which in turn is regenerated by vitamin C (Figure 1) [8]. This vitamin E recycling requires a supply of
Int. J. Environ.
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26
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Figure 1. Vitamin C acting as a reducing agent to recycle vitamin E to protect against lipid peroxidation.
Figure 1. Vitamin C acting as a reducing agent to recycle vitamin E to protect against lipid peroxidation.
As vitamin E and C work closely together, and this interrelation has been shown previously [65,66],
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As vitamin C and
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therefore, both vitamin C and E will also be explored throughout this paper.randomly allocated to take a placebo or
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for 4 weeks. stress or
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vitamin C and E supplementation did not decrease skeletal muscle oxidative stress or increase gene vitamin C and
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Tables 1vitamin
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Tables 1 and 2, respectively.
Table 1. Effects of vitamin E supplementation, with or without vitamin C, on exercise performance.
Study Participants Exercise Timing Supplementation Result

VO2 peak and W max
were significantly increased
Ten, 4 min intervals at 90% Vitamin C (2 × 500 mg/day) with no effect of
Healthy, young men
Morrison et al. 2015 [9] VO2 peak interspersed by 2 Once per day for 4 weeks and vitamin E (400 IU/day) supplementation. Rate of
(n = 11)
min active rest at 50 W (placebo added) perceived exertion was
reduced independent of
supplementation
Supplementation did not
Recreationally 4 × 10 RM leg press and knee
Vitamin C (1000 mg/day) and blunt muscle hypertrophy,
strength trained men extension with 1 min rest 1–3 h before training and 1
Paulsen et al. 2014 [10] vitamin E (235 mg/day) but measurements of muscle
(n = 21) and women between sets and 3 min rest h following training
(placebo added) strength were lower
(n = 11) between exercises
following supplementation
Previously untrained Exercise increased parameters
Vitamin C (1000 mg/day) and
(n = 19) and Four-week physical of insulin sensitivity in both
Ristow et al. 2009 [12] Once per day for 4 weeks vitamin E (400 IU/day)
pretrained (n = 20) exercise intervention groups only in absence
(placebo added)
healthy, young males of antioxidants
Although antioxidant
supplementation reduced
A protocol consisting of After 7 days of oxidative stress, it did not
Football athletes plyometric jumping and supplementation, athletes vitamin C (500 mg/d) and E attenuate elevated markers of
de Oliveira et al. 2019 [21]
(n = 21) strength resistance sets were submitted to (400 UI/d) for 15 days muscle damage or muscle
to exhaustion training protocol soreness do not exert any
ergogenic effect on
football performance
1–3 h before every
Recreationally
training session and 1 h
endurance trained VO2 max treadmill test at Ascorbic acid (1000 mg/day) VO2 max and shuttle test
after on training days,
Paulsen et al. 2014 [40] (n = 45) and untrained 5.3% elevation, and 20 shuttle and DL α-tocopherol acetate performance was increased in
and in the morning and
(n = 14) men run beep test (235 mg/day) (placebo added) both groups
evening on
and women
non-training days
Table 1. Cont.

Submaximal cycling (50%)
followed by maximal
Once per day across the
Sedentary, healthy concentric-eccentric Alpha-tocopherol No effect of vitamin E on
Akova et al. 2001 [41] duration of two
women (n = 18) combined contractions to (300 mg/day) (placebo added) muscle performance
menstrual cycles
measure maximal work force
of the dominant knee
Lactate maximum speed
protocol, one rep max Ascorbic acid (1000 mg/day)
Young male soccer Four equal doses every No effect on aerobic capacity,
Zoppi et al. 2006 [42] two-legged knee extension, and α-tocopherol (800
players (n = 5) day for 90 days strength, or speed
and a 30 m maximal mg/day) (placebo added)
sprint test
Incremental exercise test on a Once per day at breakfast
Healthy, physically cadence-independent cycle for 4 weeks prior to
Yfanti et al. 2010 [48] vitamin E (400 IU/day) No effect on Pmax or VO2 max
active males (n = 21) ergometer for VO2 max training then for 12 weeks
(placebo added)
and Pmax during cycling training
500 mg vitamin C and
Vitamin C (1000 mg/day) and Supplementation blunted
One repetition max (1 RM) 117.5 mg vitamin E before
Bjørnsen et al. 2016 [50] Elderly men (n = 34) vitamin E (235 mg/day) muscular some adaptations
leg extension and after training 3 times
(placebo added) (lean mass gains)
per week for 3 weeks
Sedentary older men Vitamin C (1000 mg/day) and
Resistance training 3 days per
Bobeuf et al. 2011 [52] (n = 27) and women Daily for 6 months vitamin E (400 IU/day) No effect on strength gains
week for 6 months
(n = 30) (placebo added)
Supplementation attenuated
circulating creatine kinase
Twice daily 3 days before Vitamin C (2000 mg/day) and and myoglobin. Antioxidant
Elite male taekwondo Four TKD matches against
Chou et al. 2018 [53] and the day vitamin E (1400 IU/day) supplementation suppressed
(TKD) athletes (n = 18) weight matched competitors
of competition (placebo added) exercise provided RBC
hemolysis and
systemic inflammation
A 4x10 RM leg press and knee
Physically active male Two pills 1–3 h before Vitamin C (1000 mg/day) and
extension with 1 min rest No effect on acute
Cumming et al. 2017 [54] (n = 18) and female training and 2 pills in the vitamin E (235 mg/day)
between sets and 3 min rest stress responses
(n = 10) first hour after training (placebo added)
between exercises
Table 1. Cont.

Once per day at breakfast
for 5 weeks prior to Vitamin C (1 g/day) and Peak torque increased in both
Isometric knee extensor peak
Yfanti et al. 2017 [60] Healthy men (n = 16) training and for 4 weeks vitamin E (400 IU/day) groups with no significant
at 90◦ knee flexion
during eccentric (placebo added) difference between groups
exercise training
Five sets of 15 eccentric No significant supplement
Vitamin C (1 g/day) and
Recreationally trained maximal contractions with Once daily for 11 weeks and time effect on muscle
Theodorou et al. 2011 [61] vitamin E (400 IU/day)
healthy men (n = 28) each leg on an at breakfast function, redox status, or
(placebo added)
isokinetic dynamometer hemolysis observed
Supplementation reduced the
Vitamin C (500 mg/day) and deficit in muscle function
Moderately active Thirty sets of 10 eccentric
Shafat et al. 2004 [67] Once per day for 37 days vitamin E (1200 IU/day) experienced during and after
males (n = 12) knee extensions
(placebo added) bouts of eccentric
muscle contractions
Exercise alone or combined
with vitamin E
three sessions of walking
Nalbant et al. 2009 [68] Older adults (n = 57) Six months Vitamin E (900 IU/day) supplementation improved
exercise per week
6-min walk, chair stand, arm
curl tests.
Moderately trained VO2 max cadence dependent Daily supplementation for No effect on VO2 max or
Yfanti et al. 2010 [69] vitamin E (400 IU/day)
young men (n = 21) cycle test 16 weeks maximum power output
(placebo added)
Supplementation does not
Healthy, physically One hour at 65% max power Once per day at breakfast further decrease interlukin-6
Yfanti et al. 2012 [70] vitamin E (400 IU/day)
active males (n = 21) on a cycle ergometer for 16 weeks levels following
(placebo added)
endurance training
Supplementation enhanced
repeated bout effect as
Moderately trained 40 min downhill run at Vitamin C (1000 mg/day) and evidenced by attenuation of
He et al. 2015 [71] Daily for 2 weeks
males (n = 22) 65–70% VO2 max vitamin E (400 IU/day) biomarkers of muscle damage
and greater
antioxidant capacity
Table 1. Cont.

VO2 max treadmill test to
A reduction was seen in
Healthy, physically exhaustion under normal Vitamin E (250 mg)
Santos et al. 2018 [72] One hour before exercise creatine kinase (CK) and
active males (n = 9) conditions and hypoxia (placebo added)
lactate dehydrogenase levels.
conditions
vitamin C (1 g daily) and Supplementation with
On the training days,
Recreationally active vitamin E (235 mg daily), antioxidants vitamin C and E
nine sessions (three tablets were taken at least
Wyckelsma et al. 2020 [73] elderly (mean age 65, treatments were initiated 7 blunts SIT-induced cellular
sessions/week for 3 weeks) 1 h before the
n = 18) days before the first sprint signaling in skeletal muscle of
training session
interval training (SIT) session elderly individuals
Table 2. Effects of vitamin E supplementation, with or without vitamin C, on exercise performance and oxidative stress markers in animals.
Study Participants Exercise Supplementation Result

The increase in circulatory free fatty acids 1-h
Diet supplemented with 100 mg/kg
post exercise was blunted vitamin E.
Hoene et al. 2018 [34] Male mice One hour of treadmill running vitamin C and 2000 IU/kg vitamin E
Upregulation of several exercise-responsive
(as _-tocopheryl acetate) for 4 weeks
transcripts was attenuated by vitamin E.
Vitamin E supplementation significantly
Fifteen minutes of treadmill Two mg/day of vitamin E as α-tocopherol
Górnicka et al. 2019 [35] Male Wistar rats reduced thiobarbituric acid reactive substance
running/day acetate for 14 days
(TBARS) in the muscles and heart.
25 or 50 mg/kg of tocotrienol-rich fraction TRF improved endurance capacity indicated
Forced swimming 10 h after the
Lee et al. 2009 [38] Male Wistar rats (TRF), or 25 mg/kg D-α-tocopherol (T-25) by longer duration of swimming and reduce
last treatment
for 28 days the exercise-induced oxidative stress.
No effect on the changes of exercise induced
Treadmill running 4 days/week for Vitamin E (1000 mg/kg) and α-lipoic acid
Strobel et al. 2011 [44] Male Wistar rats markers of mitochondrial biogenesis and
14 weeks (1.6 g/kg) fortified feed
mitochondrial proteins
Swimming 5 days/week for Vitamin E supplementation attenuated training
Venditti et al. 2014 [45] Male Wistar rats Vitamin E (700 mg/kg) fortified food
10 weeks induced declines in mitochondrial respiration.
10,000 IU vitamin E/kg diet and 1.65 g/kg A decline in skeletal muscle force production
Coombes et al. 2001 [74] Antiox rats A fatigue protocol (30 min)
and α-lipoic acid for 8 weeks at low stimulation frequencies
Table 2. Cont.
Study Participants Exercise Supplementation Result

Three times weekly for 4.5 weeks Diet supplemented with Vitamin E
Supplementing with vitamin E and C reduced
Young and aged using 80 maximal (DL-alpha tocopheryl acetate;
Ryan et al. 2010 [75] oxidative damage markers
Male rats stretch–shortening contractions 30,000 mg/kg) and Vitamin C (Lascorbic
(e.g., malondialdehyde) associated with aging.
per session acid; 2% by weight)
Vitamin E supplementation resulted in a
Vitamin E was administered by
higher soleus muscle single-twitch tension
90 min of daily intraperitoneal
immediately post-exercise compared to the
Kyparos et al. 2011 [76] Male Wistar rats intermittent downhill running on a injections of 100 mg/kg body mass of
placebo condition.
motor-driven treadmill DL-α-tocopheryl acetate for 5
No effect of vitamin E supplementation on
consecutive days prior to exercise
eccentric exercise-induced muscle damage.
Co-ingestion of vitamin E and C
Acute forced exhaustive swimming
A single dose of 25 mg/kg of vitamin E resulted in lower activities of SOD and catalase
stress for a duration of 2.5 h in glass
Al-Hashem 2012 [77] Male rats and 20 mg/kg of vitamin C 1 h before the in the lungs under high and low
tanks (in both low and
experimental procedure altitude conditions.
high altitude)
measured at both altitudes
No difference in insulin area under curve was
found between the conditions. Exercise
Dietary supplementation with vitamin E
Running 5days/week for 12 weeks combined with vitamin C and vitamin E
Picklo et al. 2015 [78] Male obese rats (0.4 g α-tocopherol acetate/kg) and
on a motorized wheel resulted in a higher mitochondrial DNA
vitamin C (0.5 g/kg) during a high fat diet
content versus exercise alone or high fat diet
alone conditions.
Two equal daily doses of vitamin E (first Vitamin E in a dose-dependent manner
The rats were
half of the total dose, i.e., 10, 20, and blocked some of the immune changes such as,
exposed to simulated conditions of
Goswami and 30 mg/kg of vitamin E) was given orally phagocytic activity of white blood cell,
Male Albino rats hypobaric hypoxia (HH) for
Ghosh. 2019 [79] 5–6 min before the exposure to HH and cytotoxic activity of splenic mononuclear cell.
8 h daily
the second half was given Also, corticosterone levels was reduced by
for 6 consecutive days
immediately after vitamin E.
Horses divided to three groups and fed
the control diet plus (1) 1000 IU/day
Vitamin E improved some oxidative
synthetic α [44] tocopherol, (2)
Fagan et al. 2020 [80] horses Six-week conditioning program and inflammatory
4000 IU/day synthetic α-tocopherol, or (3)
responses.
4000 IU/day RRR-α-tocopherol
(natural source)
4.3. Acute Versus Chronic Supplementation with Vitamin E

Many factors including the type of antioxidant, duration of supplementation, and type of training
determine the effect of antioxidant supplementation on exercise performance [7]. The duration
of antioxidant supplementation may vary greatly among athletes with some choosing to only the
supplement acutely during periods of intense exercise, while others may continually supplement
throughout their training phases.
Acute or single dose antioxidant supplementation during high intensity, short recovery intervals,
has been shown to improve performance by reducing oxidative stress and speeding up recovery [7].
Merry and Ristow (2016) [7] suggested that antioxidant supplementation may only benefit athletic
performance acutely and when an immediate performance enhancement is desired, and adaptation
is less important such as during a championship game or performance. Supporting the argument
that only acute supplementation appears beneficial, Bentley et al. [8] stated that following a chronic
antioxidant supplementation regimen, training adaptations and future exercise performance may
be impaired.
An animal study also reported that acute vitamin E supplementation enhanced the endurance
of exercise-induced vasodilation in response to acetylcholine [29]. However, chronic vitamin E
supplementation had no further effects on vascular function compared to exercise training alone [81].
A possible exception where chronic supplementation, or supplementation which occurs more than
once in succession, may provide additional benefits is a tournament style situation where several bouts
of high-intensity exercise are endured within a short period of time. To explain the differences between
acute and chronic antioxidant supplementation, Bentley et al. explained that likely a dose dependent
relationship exists for antioxidant supplements suggesting that an optimal amount of antioxidants
depends on the type and duration of exercise undertaken.
In a review on chronic vitamin E consumption among athletes, Braakhuis and Hopkins [19] reported
a trend towards performance impairment rather than enhancement. In contrast, Roberts et al. [81]
reported performance enhancement following antioxidant supplementation and stated that high doses
(1600 IU) of vitamin E for 16 weeks was the minimum dose required to demonstrate beneficial effects.
Although this study also did not investigate the effects of vitamin E on athletes, Roberts et al. [82]
suggested that after supplementing vitamin E at 1600 IU each day for 6 weeks, a reduction in
oxidative stress can be seen, which reduces the risk of diseases associated with high levels of
oxidative stress. As being physically active has many demonstrated health benefits and no physical
activity was administered as part of this study, care should be taken before applying these results to
athletic populations.
Redox-signaling pathways are involved in both acute and chronic responses of skeletal muscle to
exercise, including muscle insulin sensitivity and glucose uptake [83], mitochondrial biogenesis [40,44],
muscle contraction force [10,84], and muscle hypertrophy [50]. In addition, both acute and chronic
exercise modulate endogenous antioxidant enzyme levels, therefore, enhancing the capacity of skeletal
muscle to neutralize RONS [85]. Moreover, the common antioxidant supplementation may also
improve the capacity to decrease deleterious effects of increased RONS generation during exercise [84].
Benefits might relate to an ameliorating effect of antioxidant supplementation on exercise-induced
muscle damage and delayed onset of muscle soreness (DOMS) [71]. RONS are also implicated
in premature muscular fatigue during sustained submaximal muscle contraction and exercise [86].
According to Mason et al., antioxidant supplementation might help delay muscular fatigue and
improve exercise performance [84].
Although there are potential benefits of antioxidant supplementation in exercising humans,

according to some evidence, supplementation with vitamin C and E might impair rather
than improve some acute and chronic adaptive responses to exercise [9,10,40]. In particular,
antioxidant supplementation has been found in some studies to impair some adaptive responses to
resistance [10,50] and endurance exercise training [9,40].
5. Supplementation with Vitamin C and Exercise Performance

The effects of vitamin C on muscle strength and function have been investigated in several
studies, however, results so far have been inconsistent. For example, Gomez-Cabrera et al. [11]
reported that vitamin C supplementation decreased endurance capacity (running time) and suppressed
the exercise-induced increase in mitochondrial biogenesis (PGC-1α). Furthermore, in the human
experiment, vitamin C supplementation suppressed the exercise-induced in VO2 max. However,
according to Evans et al. [87], vitamin C supplementation is capable of increasing a peak muscular
pushing force (PMF) in untrained individuals.
In our review, we concluded that muscle strength and function are not influenced by vitamin
C supplementation. However, individuals with a poor vitamin C status appear to benefit most
from supplementation [88], as vitamin C has already been reported to be beneficial in increasing
exercise performance in individuals with low baseline levels of vitamin C [89]. Paschalis et al. [89]
investigated whether baseline concentrations of vitamin C determine the efficacy of supplementation
in enhancing physical performance. A summary of studies investigating the effects of vitamin C on
exercise performance outcomes and oxidative stress markers is presented in Table 3.
Table 3. Effects of vitamin C supplementation on exercise performance outcomes.

Vitamin C reduced factors are PGC-1,
For humans: 1 g/day nuclear respiratory factor 1, and
For humans: Static bicycle on 3
Gomez-Cabrera et al. Human (15 men) and vitamin C and for rats mitochondrial transcription factor A.
days/week for 8 weeks; for animals For 8 weeks
2008 [11] male Wistar rats 0.24 mg/cm2 body The exercise-induced expression of
5 days/week on an animal treadmill
surface area cytochrome C, SD, and glutathione
peroxidase were blocked by vitamin C.
Training-induced improvements of
Roberts et al. Recreationally active high-intensity interval running
For 4 weeks 1 g/day VO2max, 10 km time trial, and running
2011 [47] males (n = 15) protocol, 4 times per week
economy were not affected by vitamin C.
One RE bout was performed
pre-supplementation and one was
performed post-supplementation;
RE bouts consisted of a warmup set Vitamin C supplementation increased
Nine persons naive to of bodyweight pushups, three peak muscular pushing force (PMF) and
Evans et al. 2017 [87] For 28 days 250 mg every 12 h
resistance exercise (RE) working sets (WS) of 10 isokinetic reduced exercise-induced
contracting push-pull repetitions, oxidative stress.
and one maximal effort set (ME) of
five isokinetic contracting
push-pull repetitions
The low vitamin C group had lower VO2
three vitamin C
max values than the high vitamin C
Paschalis et al. recreationally trained tablets/day (each
aerobic exercise to exhaustion For 30 days group. Vitamin C supplementation in
2016 [89] healthy males (n = 20) tablet contained
this group marginally increased
333 mg of vitamin C)
VO2 max.
Vitamin C supplementation had modest
Thompson et al. Aerobic: A prolonged intermittent
Active men (n = 16) For 14 days 400 mg/day beneficial effects on muscle soreness and
2001 [90] shuttle-running test for 90 min
muscle function
for 2 weeks prior Vitamin C reduced muscle soreness and
Bryer and Goldfarb Seventy eccentric elbow extensions
healthy men (n = 18) and 4 days after 3 g/day delayed CK increase. Muscle force and
2006 [91] with their non-dominant arm
eccentric exercise range of motion were not affected.
For 2 h pre-, and Vitamin C attenuated RONS production
Physically active male Aerobic: Downhill running
close et al. 2006 [92] for 14 days after 1 g/day following downhill running. No effect
subjects (n = 20) for 30 min at 60% VO2 max
exercise on DOMS was seen.
Table 3. Cont.

Anaerobic: 40 (2 × 20) For 8 days (3 days
Connolly et al. 24 subjects (male maximal eccentric prior to an exercise Vitamin C had no effect on muscle
3 g/day
2006 [93] and female) contractions of the elbow bouts and soreness and muscle strength
flexors 5 days after)
Adults with T2D (n = 31) Peak oxygen uptake was
Scalzo et al. IV infusion of Acute vitamin C infusion did not change
and healthy adults determined via graded exercise Single dose
2018 [94] vitamin C (7.5 g) VO2 peak
(n = 21) to exhaustion
6. Effects Vitamin E and C Supplementation: Environment and Physiological Factors
6.1. Altitude Training

Altitude training increases RONS production and oxidative stress making antioxidant
supplementation of interest to athletes training at altitude [28]. Within the past decade, there
has been a dramatic increase in antioxidant supplementation among athletes particularly among
endurance athletes training at altitude [28]. The primary characteristic of high altitude is decreased
oxygen availability, which can impair physical and mental performance among those living and/or
training at high altitudes [18]. To account for the decreased oxygen availability, our body increases
important oxygen carrying components of our blood including hemoglobin and hematocrit [18].
As a result of its role in the maintenance of red blood cell (RBC) structure, vitamin E may provide
performance enhancing benefits to athletes training at altitude [19]. Braakhuis and Hopkins (2015) [19]
suggested that when training at altitude, RBC lysis may occur which may be prevented by vitamin E
supplementation. In their review of studies investigating the effects of vitamin E supplementation on
athletic performance, Takanami et al. (2000) [29] noted that at sea level, vitamin E appears to be of little
ergogenic aid to athletic individuals, however, at altitude it may benefit physical performance. As the
altitude increases, ultraviolet (UV) radiation, both UV-A and UV-B, are simultaneously increased [18].
This increase in UV-B radiation has been postulated as a major reason for increased oxidative stress,
particularly lipid peroxidation, at high altitudes [18]. Vitamin E levels are increased in those whose
skin receives chronic sun exposure suggesting that vitamin E may help protect against the oxidative
damage, which occurs via UV-B radiation at an increased rate at high elevations [18].
Although nutrient deficiencies may be of concern for athletes even at low altitudes, at high
altitudes they are most certainly of concern given the increased stress incurred on the body [18].
In an investigation of two different high altitude mountaineer expeditions, Simon-Schnass [18] found
that nutrient intake, including vitamin E, was below the recommended intakes. Although these
studies were not focused on high performance athletes, the results suggest that there is a higher
risk of insufficient nutrient intake at high altitudes as a result of many factors including price and
weight of food, availability of fresh produce, as well as reduced appetite [18]. Due to low intakes,
and increased oxidative stress at altitude, Simon-Schnass [18] stated that it may be advisable for athletes
to supplement with vitamin E when training at an increased elevation.
Additionally, early studies [95,96] provided evidence on the beneficial effects of vitamin E on
performance at altitude. However, Subudhi et al. [97] reported that supplementation with vitamin E
(400 IU per day), had no significant effect on markers of oxidative stress induced by increased energy
expenditure at high altitudes. An animal study [77] investigated the effects of vitamin E and C in
protecting against lung damage caused by acute swimming at different altitudes. While acute forced
swimming significantly increased thiobarbituric acid reactive substances (TBARS) levels and resulted
in a significant decrease in activities of SOD, and CAT, combined vitamin E and C supplementation was
effective to ameliorate exhaustive swimming and high altitude-associated lung injury. More recently,
Santos et al. [72] investigated the effects of vitamin E (250 mg) supplementation on muscle damage and
inflammation after moderate exercise in hypoxia simulating an altitude of 4200 m, and reported that
supplementation with vitamin E at 1 h before exercise decreases cell damage markers after exercise in
hypoxia and reduces the concentration of inflammatory cytokines, suggesting a potential protective
effect against inflammation caused by exercise at altitude.
A recent animal study [79] investigated the effects of vitamin E on the immune changes caused by
oxidative stress in hypobaric hypoxia (HH) at high altitudes. The results indicate that vitamin E, by its
reactive oxygen species quenching effects, blocks the immune changes mediated by free-radicals at high
altitudes in a dose-dependent manner. In this regard, vitamin E is the most important lipid-soluble
antioxidant that assists in the membranes integrity maintenance and has a direct effect on the functions
of immune cells [98]. Moreover, it should be reminded that the reduction in oxygen availability
in the mitochondrial electron transport chain in a hypobaric hypoxia state, such as a high altitude,
increases the production of free radicals, which are damaging to the cell membrane [99,100].
6.2. Mitochondrial Biogenesis and Antioxidant Induction

With regards to the antioxidant effects of vitamin C and E in humans, Yfanti et al. have reported
that supplementation with vitamin C (500 mg/day) and vitamin E (400 IU/day) does not interfere
with the training-induced adaptations, such as increased mitochondrial proteins and antioxidant
enzymes [48,60,69,70]. In contrast, several studies have observed the blunting effects of combined
vitamin C and E skeletal muscle adaptations to endurance training [9,12,40]. Ristow et al. [12] have
shown that the combined vitamin C (1 g/day) and vitamin E (400 IU/day) supplementation decreased
mRNA expression in antioxidant enzymes and several biomarkers of mitochondrial biogenesis
following endurance training. Paulsen et al. [40] reported that supplementation with 1 g/day vitamin C
and 260 IU/day vitamin E attenuated the increase in COX IV protein abundance and the cytosolic (but
not whole cell) levels of PGC-1α in response to training. It is also reported that the combined vitamin
C (1 g/day) and vitamin E (400 IU/day) supplementation attenuates the increase in skeletal muscle
mitochondrial TFAM protein abundance and SOD enzyme activity [9]. However, the increased citrate
synthase activity indicates mitochondrial content levels [101], and its involvement in skeletal muscle
adaptations was not attenuated. Thus, collectively, there is now evidence that 1 g/day of vitamin C in
combination with vitamin E (400 IU/day) in humans hinders some, but not all of the skeletal muscle
adaptations to exercise. However, much of this hampering effect has been attributed to the higher
dose of 1 g/day of vitamin C, rather than any effect of vitamin E [84]. Therefore, further studies are
needed to investigate if this blunting of some training adaptations is also observed with 1 g/day of
vitamin C alone.
More importantly, despite the potential impairment of some cellular adaptations involved in
mitochondrial biogenesis and antioxidant defenses, there are no data available that the combined
1 g/day of vitamin C and 400 IU/day vitamin E supplementation have a negative effect on VO2 max
or endurance performance. Wyckelsma et al. [73] investigated effects of a 4-week supplementation
of vitamin E (235 mg/day) in combination with vitamin C (1 g/day) on several markers of training
adaptations and exercise performance in elderly adults following a 3-week sprint interval training
on a cycle ergometer. The results showed blunted changes in mRNA expression of ROS-related,
inflammatory, and mitochondria proteins in the vitamin groups versus placebo while no significant
differences were found in VO2max and maximal power out. From mechanistical point of view,
authors suggested that some of the RONS-dependent gene and protein expressions of sarcoplasmic
Ca2+ handling proteins which play key roles in mitochondrial biogenesis signaling pathways were
blunted by the vitamin supplementation. It was also noted that no performance enhancement in both
groups might be attributed to the training period (i.e., 3 weeks), age, and fitness status of participants.
It is noteworthy to mentioned that there are several factors including RONS concentration,
duration of exposure, and training status of individuals determining to what extent RONS exerts
positive or negative effects. Gene polymorphisms are another important factor determining the
impact of elevated RONS on muscle damage [102]. Approximately 165 autosomal genes, five on the ×
chromosome, and 17 mitochondrial genes have been identified to contribute to exercise performance.
Given the presence of polymorphisms within antioxidant genes which is linked to cellular damage
and may result in muscle damage, further studies are needed in this area [103].
6.3. Skeletal Muscle Contraction Force

An animal study reported that co-administration of vitamin E and α-lipoic acid impaired muscle
contractile force in unfatigued, but not fatigued skeletal muscle. Further experiments revealed that
the impairment in force production was mostly mediated by vitamin E [74]. It is suggested [85] that
since in an unfatigued muscle the redox state is more reduced following antioxidant supplementation,
submaximal force production would have been impaired.
Combined vitamin C (500 mg/day) and vitamin E (1200 IU/day) supplementation enhanced the
rate of recovery of the maximal knee extensor voluntary isometric contraction force following intense
eccentric knee extension exercises [67]. However, another study reported that co-supplementation with
vitamin C (1 g/day) and vitamin E (260 IU/day) did not improve the maximal voluntary knee extensor
force recovery after an acute exercise bout [10]. The combination of vitamin C and E supplementation
impaired maximal strength development during resistance training in the biceps muscle group
and mitigated exercise-induced activation of ERK1/2, MAP kinases p38 MAPK, and p70S6k in the
skeletal muscle [10]. Other recent studies investigating the effects of combined vitamin C and E
supplementation and resistance training over 3–6 months, have reported no impairment in strength
performance following supplementation [52,61]. Overall, the effects of vitamin C and E supplementation
on the skeletal muscle contractile function and force production are inconsistent and require future
studies. It should be noted that some studies have evaluated the effects of vitamin E on the recovery of
muscle contraction force following exercise. Overall, the available evidence on the effects of vitamin E
alone or combined with vitamin C against exercise-induced muscle damage are not conclusive [3].
6.4. Skeletal Muscle Hypertrophy

Bjørnsen et al. [50] reported that combined vitamin C (500 mg/day) and vitamin E (175 IU/day)
supplementation during 12 weeks of resistance training attenuated the gains in leg lean mass and rectus
femoris thickness. As well as total lean mass, no significant between-group difference was observed for
other body segment masses and muscle thicknesses after training [50]. In contrast, another study [52]
reported a significant gain in lean mass only when resistance training was combined with vitamin
C (1 g/day) and vitamin E (400 IU/day) supplementation. However, it should be noted that the
aforementioned studies were conducted among the elderly and the interpretation of findings related to
RONS/antioxidants in this population may not be representative of an athletic population, and therefore,
drawing a conclusion for athletes is difficult. Paulsen et al. [10] observed that supplementation with
vitamin C (1 g/day) and vitamin E (350 IU/day) during 10 weeks of resistance exercise training had no
significant improving effect on lean body mass accretion or muscle group cross-sectional areas in young
adults. Although the fractional protein synthetic rate was also unaltered, the acute exercise-induced
activation of p70S6k 842 and MAP kinases p38 MAPK and ERK1/2 was attenuated. Interestingly,
the antioxidant supplementation attenuated protein degradation as indicated by the attenuation of the
post-exercise increase in activation of the ubiquitin proteasome pathway. This latter finding needs
future investigation. The contradictory evidence on the effects of vitamin E alone or combined with
vitamin C on the overload-induced activation of kinases involved in protein synthesis and protein
degradation implies that redox-related signaling pathways in human skeletal muscle hypertrophy
remains to be clearly investigated in future studies. More studies are needed to investigate the effects
of vitamin E on muscle hypertrophy and strength performance.
7. Conclusions
Drawing clear conclusions on the effects of antioxidant supplementation, including vitamin
E with or without vitamin C, is difficult due to variations in the fitness status of the participants,
supplementation protocol (type, dosage, duration, timing), type of exercise used, and gender [22].
With very few studies investigating the effects of vitamin E on female participants, more research
is needed on the effects of vitamin E on female athletes before any conclusions can be made [26].
As vitamin E supplementation is often combined with additional antioxidants, namely vitamin C,
conclusions on the effects of vitamin E alone cannot be made and additional research is warranted.
Growing evidence suggests that antioxidant supplementation may impair muscle mitochondrial
biogenesis and muscle hypertrophy [7]. Chronic supplementation with vitamin E has been shown to
impair athletic performance and is not currently recommended for athletes [19]. Current research fails
to show any consistent, positive effect of vitamin E supplementation on health or athletic performance
for most athletes [104].
Vitamin E supplementation does show promise in two areas of athletic performance. The first
area which vitamin E supplementation shows potential benefits, is for athletes participating in altitude
training. Supplementation with vitamin E has demonstrated positive effects on athletes training at
altitude via a reduction in RBC deformation, however, results still remain inconclusive and further
research is warranted [19]. The second area of interest is acute supplementation. Acute antioxidant
supplementation has been shown to improve performance during high intensity exercise with short
recovery intervals [7]. Supplementation with antioxidants has been suggested to benefit athletes when
performance adaptations are not the main focus and immediate enhanced performance is desired.
Although acute antioxidant supplementation research appears positive, little research has focused
exclusively on acute vitamin E supplementation.
Based on current evidence, with the possible exception of athletes partaking in altitude training
or acute, high stakes performances, vitamin E supplementation, with or without vitamin C, may not
provide additional benefits for athletes. To ensure antioxidants needs are met, athletes should instead
focus on consuming a diet high in fruits, vegetables, and other plant foods which are rich in antioxidants,
as well as other potentially beneficial compounds not found in high dose antioxidant supplements.
Overall, the effects of vitamin C and E on muscle mass and strength have been inconsistent.
As antioxidant supplements (e.g., vitamin E and C) tend to block anabolic signaling pathways,
and thus, impair adaptations to resistance training, special caution should be taken with these
supplements. Nonetheless, the effects of antioxidants on muscle mass/strength might also depend on
the oxidative stress/antioxidants balance of the subject [105].Moreover, among the mechanisms involved
in regulating the redox balance, some polymorphisms in genes of antioxidants are associated with
cellular damage [102]. While determining the role of the oxidative state and the effects of antioxidants
in different types of exercise such as resistance or endurance training, as well as in different categories
of athletes such as recreationally active or elite remains to be fully elucidated. Thus, a personalized
supplementation approach would be highly recommended.
Author Contributions: Conceptualization, M.K.; methodology, M.K., M.R.H., and A.I.; resources, M.K., M.R.H.,
and A.I.; writing—original draft preparation, M.K. and M.R.H.; writing—review and editing, M.K. and M.R.H.;
supervision, M.K.; project administration, M.K. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflict of interest.
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Antioxidants and Exercise Performance: With A Focus On Vitamin E and C Supplementation

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Antioxidants and Exercise Performance: With A Focus On Vitamin E and C Supplementation

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International Journal of

Abstract: Antioxidant supplementation, including vitamin E and C supplementation, has recently

2. Antioxidants and Sports Performance

2.1. Reactive Oxygen and Nitrogen Species

2.2. Exogenous and Endogenous Antioxidants

2.3. Antioxidants and Impaired Adaptations to Training

4. Vitamin E as An Antioxidant Supplement

4.1. Food Sources Versus Supplements

Ascorbate Reduced form of Vitamin E

Table 1. Effects of vitamin E supplementation, with or without vitamin C, on exercise performance.

Study Participants Exercise Timing Supplementation Result

Study Participants Exercise Timing Supplementation Result

Study Participants Exercise Timing Supplementation Result

Study Participants Exercise Timing Supplementation Result

Study Participants Exercise Supplementation Result

Study Participants Exercise Supplementation Result

4.3. Acute Versus Chronic Supplementation with Vitamin E

Although there are potential benefits of antioxidant supplementation in exercising humans,

5. Supplementation with Vitamin C and Exercise Performance

Table 3. Effects of vitamin C supplementation on exercise performance outcomes.

Study Participants Exercise Timing Supplementation Result

Study Participants Exercise Timing Supplementation Result

6. Effects Vitamin E and C Supplementation: Environment and Physiological Factors

6.1. Altitude Training

6.2. Mitochondrial Biogenesis and Antioxidant Induction

6.3. Skeletal Muscle Contraction Force

6.4. Skeletal Muscle Hypertrophy

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