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
]. 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
] 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
]. 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
]. 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
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
] 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
]. This vitamin E recycling requires a supply of vitamin C and is often why these nutrients will be consumed simultaneously via supplementation [63
]. More recently, Jungert et al. [64
] investigated the determinants and interrelation between plasma concentrations of vitamin C and E in the elderly. For plasma vitamin C concentrations, the use of supplements, physical activity, fat-free mass, and plasma α-tocopherol were the main determinants. Age, the use of supplements, the use of lipid-modifying drugs, and plasma vitamin C were the main determinants for the α-tocopherol/total cholesterol ratio [64
]. The results emphasize the idea of an interrelation between plasma levels of vitamin C and E, and also suggest an association between physical activity and fat-free mass with vitamin C and E status.
As vitamin E and C work closely together, and this interrelation has been shown previously [65
], therefore, both vitamin C and E will also be explored throughout this paper.
In a study by Morrison et al. [9
], healthy young men were randomly allocated to take a placebo or antioxidant (vitamin C (2 × 500 mg/day) and E (400 IU/day)) for 4 weeks. Following acute exercise, vitamin C and E supplementation did not decrease skeletal muscle oxidative stress or increase gene expression of mitochondrial biogenesis markers. However, supplementation with vitamin C and E mitigated skeletal muscle adaptations indicated by the superoxide dismutase (SOD) activity and mitochondrial transcription factor A (TFAM). Studies investigating the effects of vitamin E with or without vitamin C on exercise performance outcomes in humans and animals are summarized in Table 1
and Table 2
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
], muscle contraction force [10
], 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
]. In particular, antioxidant supplementation has been found in some studies to impair some adaptive responses to resistance [10
] and endurance exercise training [9