Do antioxidants really blunt hypertrophy? The evidence isn’t as conclusive as you may think.
Free radicals, reactive oxygen species, oxidative stress, oxidative damage, antioxidants, inflammation, carotenoids, polyphenols, flavonoids. This general cluster of terms is often discussed vaguely, sometimes on the label of a “superfood” product, but rarely with sufficient depth or clarity. The conversation typically revolves around issues of long-term health and chronic disease risk, but every now and then it meanders into the realm of lifting. For example, you may have heard that antioxidants enhance performance, or that they impair training adaptations. In this article, we’ll take a look at how antioxidants affect both performance and training adaptations and discuss what this means for your food and supplement intakes.
Before we dive into the research, it’s really important to get some specific definitions sorted out. A lot of these terms tend to get used interchangeably, which can cause a little bit of confusion.
Oxidation is a chemical process that is characterized by the loss of an electron. A free radical is a molecule with one or more unpaired valence electrons, which causes it to be unstable and highly reactive. Free radicals are normal byproducts of metabolic processes in the body, but may also be created in response to radiation exposure, cigarette smoking, air pollution, and some industrial chemicals. When these free radicals interact with other molecules in the body, they steal an electron from them to achieve stability. In many cases, the other molecule becomes a radical, which forms a chain reaction of interactions between unstable molecules. Free radicals consist of both reactive oxygen species (ROS) and reactive nitrogen species (RNS), although there are also some non-radical ROS and RNS that also promote oxidation in the body. This grouping of molecules (free radicals, ROS, and RNS) can collectively be referred to as “reactive species” for the purposes of this article.
Collectively, these oxidation-promoting reactive species have the capacity to damage important components of cells, including proteins, lipids, and DNA. However, they also have important roles in the body. Reactive species are involved in cell signaling, immune responses, gene expression, and ion transport. Under normal circumstances, these compounds are able to carry out their important functions without inducing excessive cell damage because they’re kept in check by antioxidants. Our bodies have endogenous antioxidant systems to deal with reactive species that promote oxidation, and we also consume antioxidants in our diets.
“Antioxidant” is a broad term that summarizes a number of structurally distinct subcategories. As a result, you may see antioxidants being discussed with many different names, which probably adds to the confusion. If you’ve seen articles or advertisements talking about carotenoids, polyphenols, flavonoids, flavanols, or flavones, they were all talking about some type of antioxidant. Trying to evaluate the antioxidant literature can be pretty tricky, as there are a ton of antioxidants. For example, there are over 4,000 known flavonoids, and flavonoids are just one class of polyphenols, and polyphenols are just one class of non-enzymatic antioxidants.
Generally speaking, the antioxidants we most frequently talk about in the health and physiology world are the natural antioxidants, which are further separated into enzymatic and non-enzymatic groups. The non-enzymatic group is broken down further into several subcategories, which contain most of the antioxidants that we tend to see in foods and supplements. Rather than tediously explain the groupings, this information is best summarized as a figure instead of text (Figure 1).
There are a few different ways in which antioxidants can help keep reactive species in check. Antioxidants can directly scavenge reactive species to stabilize them, inhibit the activity or expression of enzymes that generate reactive species, or enhance the activity or expression of enzymes that bolster endogenous antioxidant systems. There are numerous types of antioxidants and multiple potential mechanisms, but the general purpose of antioxidants is to prevent or slow the oxidation of other molecules, thereby limiting the degree of cellular damage caused by reactive species.
Oxidative stress and inflammation
As we’ve discussed, the body is constantly dealing with reactive species. These reactive species are typically kept in check by a combination of endogenous and exogenous antioxidants, but it’s possible for this balance to become lopsided, such that our antioxidant systems are overwhelmed by the production of reactive species. This leads to a state of oxidative stress, which is characterized by excessive oxidative damage. Oxidative stress has been implicated in a wide variety of chronic diseases, including cancer, rheumatoid arthritis, Alzheimer’s, Parkinson’s, diabetes, and a number of diseases affecting the eyes, brain, lungs, and cardiovascular systems.
Whenever you hear about oxidative stress, it’s common to hear inflammation discussed simultaneously. The terms are related, but not equivalent. The body has several types of inflammatory cells, such as neutrophils, monocytes, and lymphocytes. These inflammatory cells go to work in response to any number of pro-inflammatory stimuli, such as tissue damage, the presence of toxic substances, pathogens, and many others. Activated inflammatory cells at the site of the stimulus release enzymes, reactive species, and chemical mediators to direct the inflammatory response to the pro-inflammatory insult. The goal of this inflammatory process is to eliminate the pro-inflammatory stimulus (whatever it may be), remove damaged tissue, and initiate the recovery process, for the overall purpose of protecting the organism from infection and injury. The inflammatory response results in the production of reactive species, thereby contributing to oxidative stress. Conversely, chronic oxidative stress can actually trigger low-grade inflammation. So, while “oxidative stress” and “inflammation” are distinct terms that are not interchangeable, they are linked in a bi-directional manner.
Now that we’ve got an understanding of the key terms, let’s take a look at the exercise research.
Relationships between reactive species and exercise
Like many things in physiology, the relationship between reactive species and exercise is a bit complicated and context-dependent. The production of reactive species increases during exercise, with more vigorous bouts causing more substantial increases. This increase appears to be pretty important, as reactive species serve as critical intracellular messengers that are necessary for normal physiological function, and myofibril contractility is reduced when reactive species production is suppressed in vitro. However, too much reactive species production is equally problematic. Elevated levels can damage mitochondrial and myofibrillar proteins, and are associated with fatigue during exercise. Ideally, oxidants and antioxidants are appropriately balanced, such that there is a sufficient reactive species response to exercise, without excessive fatigue or oxidative damage (Figure 2).
Due to the robust increase in reactive species production during exercise, one of the many adaptations to chronic training includes an upregulation of endogenous antioxidant systems. Essentially, due to habitual exposure to reactive species, the body bolsters its built-in antioxidant systems to better accommodate high reactive species production in future exercise bouts. While we’ve known for a while that this effect is observed in response to chronic endurance training, researchers have more recently observed that a similar adaptation occurs with resistance training. For example, Azizbeigi et al put 30 male, untrained participants (with a mean age of 21.7 years) through 8 weeks of endurance training, resistance training, or concurrent training (endurance + resistance). The resistance training consisted of progressive, full-body resistance training with bouts occurring three times per week. Resistance training and endurance training both caused significant improvements in endogenous antioxidant capacity, whether they were done independently or concurrently. Further, this effect does not seem to be intensity-specific; one study compared the effects of two separate training intensities (70% of 1RM versus 85% of 1RM) on markers of endogenous antioxidant status. Training bouts occurred three times per week, with six exercises per bout. After six weeks of training, both groups experienced similar improvements in endogenous antioxidant status.
Obviously, our endogenous antioxidant systems are not the only mechanisms by which we can attenuate oxidative stress; many of the foods we eat have an abundance of antioxidants, and many forms of antioxidant supplements are commercially available. So, let’s take a look at the available research on antioxidant supplementation and exercise.
Effects on blood flow
Several studies have investigated pre-exercise supplementation with a variety of antioxidants, in hopes of identifying exercise-related benefits. Without question, it would appear that pre-exercise antioxidant supplementation can increase blood flow during exercise. A couple of studies have shown pomegranate extract to enhance blood flow parameters, and similar effects have been observed with grape juice, blackcurrant powder, Pycnogenol, and cocoa flavanol supplementation. For example, a single dose of high-flavonol cocoa (701mg) significantly increased flow-mediated vasodilation and altered the blood pressure response to exercise in comparison to a low-flavonol cocoa (22mg) in overweight and obese individuals. A single 1000mg dose of polyphenol-rich pomegranate extract enhanced indices of brachial artery diameter and blood flow before and after high-intensity running in young, healthy individuals, and similar results were observed in healthy subjects performing leg press and bench press repetitions to fatigue in combination with repeated bike sprints. At the microvascular level, polyphenol-rich grape juice (300mL/day for 20 days) improved functional capillary density and red blood cell velocity in male triathletes; while this longitudinal study was not placebo-controlled, it suggests that the more global, centralized parameters of blood flow that are altered in other placebo-controlled trials appear to translate down to the (arguably more important) microvascular level.
The mechanism linking antioxidants to blood flow enhancement should effectively span across multiple distinct types of antioxidants; the effect appears to be directly related to their ability to attenuate the activity of reactive species, which enhances the bioactivity of nitric oxide (NO). The activity of NO is severely impaired by its volatility; NO has a half-life of no more than a few seconds and is rapidly degraded or changed almost immediately after forming in the body. Once nitric oxide is formed, it will rapidly be guided toward one of the paths summarized in Figure 3. One fate of NO is to activate guanylyl cyclase (GC), which increases cyclic guanosine monophosphate (cGMP), resulting in vasodilation. It could also become nitrite (NO2–) or nitrate (NO3–), which can be viewed as a form of “short term storage.” Alternatively, NO can also nitrosylate or otherwise modify numerous proteins throughout the body. The final potential path is the least favorable; it may get converted to peroxynitrite (ONOO–), which is essentially a waste of perfectly good NO and causes unfavorable effects like protein damage, DNA damage, and nitric oxide synthase (NOS) uncoupling. Antioxidants inhibit the conversion of NO to peroxynitrite, thereby increasing the bioactivity of NO and promoting blood flow.
As noted in a previous Stronger By Science article, nitric oxide precursor supplements can increase blood flow, but can also influence exercise performance through mechanisms entirely unrelated to blood flow, including direct effects on the contractile function of muscle. As such, it’s reasonable to wonder if these acute effects of antioxidants on endogenous nitric oxide activity and blood flow might acutely improve performance as well.
Effects of short-term antioxidant supplementation on performance
One of the difficulties of summarizing the antioxidant literature is the wide variety of antioxidants that could be studied (see Figure 1). Fortunately, a few solid review articles have summarized much of the literature to date. One review by Braakhuis specifically focused on vitamin C supplementation, both in isolation and in combination with other ingredients, such as vitamin E. The review uncovered 12 studies, with 8 of them conducted in humans. Of the eight human studies, vitamin C dosages ranged from 0.2g/day to 1.5g/day, and the duration of supplementation ranged from a single dose to 16 weeks. While the exact performance outcomes ranged significantly, they utilized endurance exercise modalities (running and cycling) across a variety of exercise intensities. None of the studies reported statistically significant effects in any direction; four of the studies reported small, non-significant impairments, while the other four reported small, non-significant improvements. Obviously, insufficient intake of vitamin C is counterproductive, both for health and for performance. However, the results of this review indicate that there is insufficient evidence to suggest that vitamin C supplementation improves exercise performance. Authors of the review concluded that sufficient doses of vitamin C can be obtained by adhering to common recommendations for fruit and vegetable intake, thereby negating the need to pursue supplementation.
A more recent review by Braakhuis and Hopkins opted to expand upon the previous vitamin C paper by exploring the effects of supplementing with other antioxidants. The review found 14 studies examining the effects of vitamin E, with two of them evaluating acute (one-time) dosing. A human study showed acute vitamin E supplementation to provide pretty trivial effects, whereas a rodent study found an acute vitamin E injection to significantly improve performance. While the divergent outcomes could certainly be attributed to the species tested, it’s also important to note that it’s hard to markedly increase vitamin E levels via acute oral supplementation. The other 12 vitamin E studies utilized chronic vitamin E supplementation over the course of several weeks; the results of these studies did not provide evidence of performance enhancement and were more likely to lean toward modest impairment than improvement. The notable exception is when exercise is performed at altitude; this review identified two studies evaluating the effects of vitamin E supplementation on performance at altitude, with both reporting notable improvements. Altitude exposure increases oxidative stress, which results in reduced red blood cell deformability and increased breakdown of red blood cells. Vitamin E supplementation can help maintain the structural integrity of red blood cells at altitude, thereby attenuating performance impairments. So, while vitamin E might be a good option for individuals training at altitude, it’s not advisable for people training and competing at or near sea level.
N-Acetylcysteine has antioxidant properties, mainly by supporting the synthesis of an endogenous antioxidant called glutathione. Multiple studies have shown that infusion of N-acetylcysteine enhances skeletal muscle function and endurance performance. For example, two separate infusion studies found N-acetylcysteine infusion to significantly improve cycling time to exhaustion at an intensity of 92% of VO2max. In contrast, a separate infusion study found no improvement in time to exhaustion at 130% of VO2max, using an experimental protocol resembling high-intensity interval exercise. These results cannot necessarily be used to make inferences about the effects of oral supplementation, but a few studies evaluating the performance effects of oral N-acetylcysteine supplementation are available. One study found that 1800mg/day for four days enhanced submaximal knee extensor endurance, and another study found that 150mg/kg enhanced submaximal handgrip strength endurance. A third study evaluated the effects of 1200mg/day for nine days, with results showing an improvement in repeated sprint performance during a simulated race on a cycle ergometer. While there is certainly a need for more research, the available evidence suggests that N-acetylcysteine may enhance endurance during submaximal or moderate-intensity exercise, with less promising effects on maximal, high-intensity work. As such, its applications for most lifters would appear to be fairly limited. In addition, relatively high doses have been associated with some unpleasant side effects, including nausea, vomiting, diarrhea, and others.
The review by Braakhuis and Hopkins also summarized the research findings pertaining to a number of additional antioxidant-containing supplements. A flavonoid called quercetin, found in red onion, dill, apples, and capers, has been shown to induce very small positive effects on endurance performance when dosed at around 1g/day, but its effects on resistance exercise are less certain. A polyphenol called resveratrol, most notably found in red wine, has produced some promising findings in active rodents. However, performance effects in inactive rodents tend to be negative, and there’s a glaring lack of human performance data available. Beetroot juice contains polyphenols (more specifically, anthocyanins and flavonoids) and has been shown to enhance performance across a range of exercise intensities and modalities, but the primary ingredient driving performance effects is almost certainly nitrate. Beetroot juice reduces exercise oxygen consumption to a greater degree than a nitrate-matched dose of sodium nitrate, likely due to the presence of antioxidants. However, it’s unclear if this would necessarily translate to a meaningful benefit for endurance exercise performance, and its application to resistance exercise is pretty doubtful. To be clear, beetroot juice itself has some potential promise for resistance training, but it’s mostly due to the direct effect of nitrate, with some assistance provided by the synergistic relationship between nitric oxide and antioxidants.
Braakuis and Hopkins identified 11 other studies on a variety of polyphenol-containing supplements; generally speaking, the results were quite mixed, but there were some polyphenols that showed promising preliminary results, such as epicatechin-rich cocoa. In addition, acute (single-dose) supplementation of pomegranate extract with high polyphenol content has been shown to modestly enhance running time to exhaustion and marginally improve repeated sprint performance, but not leg press or bench press repetitions to fatigue. Similarly, Pycnogenol (a patented pine bark extract formulation) has been shown to enhance both cycling and resistance exercise performance in a couple of isolated studies. Finally, the review by Braakuis and Hopkins also discussed the very limited research pertaining to the performance effects of spirulina supplementation, which contains tocopherols, beta-carotene, polyphenols, and phytocyanins. Of the four studies they found, one was done using rodents, with the other three using human subjects. The rodent study and two of the human studies found statistically significant improvements in performance outcomes including running time and mean isometric quadriceps force over 10 seconds. The fourth study found a small (4%) improvement in running time, which was not statistically significant. Dosages in the human studies ranged from 2-7.5g/day, and study durations ranged from 3-8 weeks.
It’s challenging to give a singular statement that summarizes the entire body of antioxidant literature, as the wide variety and large volume of potential antioxidant-related supplements is pretty staggering, especially when you consider the various combinations you could engineer. It would appear that vitamin E enhances performance at altitude (but not at sea level), quercetin has a small beneficial effect on endurance performance (particularly in untrained folks), and N-acetylcysteine infusion seems to enhance submaximal exercise (with less certain outcomes related to maximal, high-intensity exercise and oral supplementation). Resveratrol may be a promising supplement for endurance performance in trained individuals, but this is entirely based on results from rodent studies. There’s a number of diverse polyphenol-rich supplements available, so the effects of these supplements are quite variable. There are too few studies to draw strong conclusions, but preliminary studies report modestly positive effects of some polyphenol-rich supplements, including beetroot juice, cocoa epicatechins, and grape extract, but not green tea extract or cranberry-grapeseed powder. Finally, it’s important to note that many studies in this research area fail to clearly state when the final supplement dose was provided in relation to the exercise bout. This is important for studies involving multiple weeks of supplementation because it’s hard to tell if the observed effects are due to daily ingestion, an acute effect that lasts a few hours after ingestion, or an interaction between the two. Overall, the data related to acute and short-term antioxidant supplementation suggest that performance effects vary among the wide variety of antioxidants, with some showing pretty negligible effects, and others showing modest positive effects.
Effects on muscle damage and recovery
As discussed previously, exercise induces an acute increase in oxidative stress. Given that antioxidants can counteract the cell-damaging effects of reactive species, some athletes consume antioxidant supplements in hopes of attenuating muscle damage, reducing soreness, and expediting recovery. As reviewed by Sousa et al, there are some isolated studies suggesting that vitamin C and E, alone or combined, may favorably affect outcomes related to oxidative stress, inflammation, muscle damage, or soreness. However, the totality of the evidence available fails to show consistent positive effects. For carotenoids, there are far fewer studies available, but there is some evidence to suggest that carotenoid supplementation attenuates post-exercise muscle damage. Similarly, studies have indicated that a number of polyphenols can also reduce the magnitude of post-exercise responses related to muscle damage and can improve markers of recovery. However, it’s important to note that you need not exclusively rely on pills or powders to observe such an effect. For example, tart cherry juice has been shown to have favorable effects on inflammation, muscle soreness, and performance recovery following prolonged exercise, and it has also been shown to reduce post-exercise pain levels. Similarly, two studies have reported that pomegranate juice facilitates performance recovery and reduces soreness following eccentric exercise, and reductions in perceived soreness have also been reported in watermelon juice interventions.
Taken together, the studies looking at antioxidant-rich supplements derived from fruits and/or vegetables appear to report neutral to positive effects on acute performance, and neutral to positive effects on acute recovery. So, what’s the catch?
Effects on training adaptations
The idea of using antioxidant supplements as training aids is pretty appealing at the surface level; you might possibly get a modest boost in training capacity or blood flow (depending on the choice of antioxidant source), and you might expedite recovery, thereby allowing you to pack more high-quality training into a given training cycle. Unfortunately, there is reason to second-guess the merits of this nutritional strategy as a means of promoting greater gains over time.
In 2005, Gomez-Cabrera et al reported that experimentally decreasing reactive species formation in rats altered multiple signaling pathways associated with endurance training adaptations. The authors speculated that these findings might translate to blunted adaptations to endurance exercise, and that avoidance of high-dose antioxidant supplementation in close proximity to exercise may be warranted. As reviewed by Merry and Ristow, a number of studies in the past 15 years have followed up on their work. Collectively, these studies have indicated that pre-exercise antioxidant supplementation does interfere with signaling pathways related to mitochondrial biogenesis, which is a key adaptation by which training enhances endurance capacity. While this would seem to pretty conclusively extinguish any existing optimism regarding antioxidant supplementation, the matter isn’t quite that simple. Despite the evidence showing an impairment in various signaling pathways, the evidence directly assessing training-induced changes in mitochondrial biogenesis is mixed; some studies report impairment, whereas others report no effect of antioxidants. While it may seem a bit paradoxical that the relationship between impaired signaling and impaired mitochondrial biogenesis is a bit tenuous, this lack of a consistent effect matches the results we’ve seen for the ultimate outcomes: aerobic capacity, and performance on endurance tasks. When it comes to endurance training adaptations, there doesn’t appear to be a consistent negative impact in trials lasting multiple weeks.
For example, studies by Gomez-Cabrera et al, Roberts et al, Yfanti et al, and Paulsen et al found that vitamin C supplementation, with or without vitamin E, did not significantly impair VO2 max improvements over 4-12 weeks of endurance training, and studies by Roberts et al, Braakhuis et al, Abadi et al, and Meier et al failed to identify significant impairments in endurance performance following training with antioxidant supplementation. In addition, a recent meta-analysis found that vitamin C and E studies have collectively failed to consistently find negative effects on maximal aerobic capacity (VO2max) or endurance performance. With regards to the apparent discrepancy between cellular signaling findings and actual endurance training adaptations, Merry and Ristow speculate that there may be physiological redundancies present, such that partial perturbation of the acute mitochondrial biogenesis signaling response fails to consistently and meaningfully blunt improvements in endurance capacity.
Generally speaking, Stronger By Science readers tend to be more focused on strength and hypertrophy outcomes than endurance performance. While the last couple of paragraphs have focused on endurance outcomes, lifters might justifiably have similar concerns. Just as Gomez-Cabrera et al reported that antioxidant supplementation altered signaling related to endurance training adaptations, multiple studies have found antioxidant supplementation to inhibit anabolic signaling pathways related to muscle hypertrophy, resulting in reduced phosphorylation of ERK1/2, p38 MAPK, and p70S6 kinase. Additional work by Ito et al suggests that nitric oxide could potentially be a contributing factor that explains at least part of the interference between antioxidants and anabolic signaling. Ito and colleagues found that nitric oxide production increases in response to mechanical loading, and under normal circumstances, peroxynitrite is also formed when the nitric oxide reacts with superoxide. Peroxynitrite activates transient receptor potential cation channel subfamily V member 1 (TRPV1, also known as the capsaicin receptor), which causes an increase in intracellular calcium concentrations, which triggers the activation of mTOR, the key regulator of muscle protein synthesis. As demonstrated in Figure 3, antioxidants prevent the conversion of nitric oxide to peroxynitrite, which may therefore reduce the magnitude of mTOR activation in response to mechanical loading, if we extrapolate the findings of Ito and colleagues.
Of course, as we learned from mitochondrial biogenesis signaling and endurance adaptations, we shouldn’t assume that these mechanistic findings necessarily translate to blunted strength and muscle gains. For the current article, I’m going to focus on the studies that include hypertrophy assessments, rather than all studies including a strength outcome of any type. Frankly, aside from blunting hypertrophy, it’s difficult to hypothesize a mechanism by which antioxidants would impair strength performance. In addition, some of the strength-focused studies utilized testing outcomes or training interventions with limited ecological validity, and a recent meta-analysis summarizing the available literature provided minimal reason for concern, as vitamin C and E supplementation resulted in an effect size for muscle strength that actually favored the antioxidant group in comparison to placebo (effect size = 0.15, which was not statistically significant). That same meta-analysis summarized the available studies evaluating the effects of antioxidant supplementation on hypertrophy in response to resistance training; for a long-form discussion on its findings, Greg and I discussed some preliminary thoughts on the paper on the Stronger By Science Podcast shortly after its publication. The meta-analysis found that vitamin C or E supplementation did not significantly impact lean mass gains in response to resistance training. However, as Greg noted, not all of the studies included in the analysis are equally informative. It’s quite possible that three of the studies included were actually one study reported three times and used whole-body DXA to assess lean mass rather than a direct assessment of muscle size. In contrast, the other three studies included more direct and precise assessments of muscle hypertrophy, such as muscle thickness or fiber cross-sectional area.
In the first of these three studies, Paulsen et al evaluated the effects of vitamin C (1000mg) and E (400 IU) on acute and chronic responses to resistance training in 32 recreationally trained men and women (mean age around 25-26 years old). Participants completed three resistance training sessions per week for 10 weeks, and acute training responses were also assessed during a single workout in a subset of subjects. Acutely, antioxidant supplementation interfered with anabolic signaling, but also reduced total ubiquitination levels (which are associated with protein degradation), with no significant impact on muscle protein fractional synthetic rate. Antioxidants did not significantly alter changes in lean mass, whole muscle cross-sectional area, or muscle fiber cross-sectional area. The study also reported a handful of strength-related outcomes; the placebo group improved biceps curl strength significantly more than the antioxidant group (+17.1 ± 17.0% versus +7.6 ± 5.0%), with non-significant results reported for the rest of the strength outcomes. While the placebo group tended to have slightly (and non-significantly) better gains than the antioxidant group, the overall differences were not large enough or consistent enough to get particularly concerned over.
In the second study, Bjornsen et al evaluated the effects of vitamin C (1000mg) and E (400 IU) on adaptations to a 12-week training program with three resistance training sessions per week in 34 untrained elderly males. They measured muscle thickness of the rectus femoris, vastus lateralis, and arm flexors at 4, 8, and 12 weeks. There were no between-group differences at any time point for the vastus lateralis or arm flexors. For the rectus femoris, the groups had statistically similar values at weeks 4 and 8, but the placebo group achieved significantly more growth by week 12 (+3.4mm for the placebo group versus +1.9mm for the antioxidant group). After 12 weeks, the placebo group experienced larger gains in total lean mass (2191g versus 867g) and lean mass of the legs (727g versus 343g). Changes in the placebo group were also larger for arm lean mass and trunk lean mass, but these differences were not statistically significant. The study also evaluated changes in biceps curl, leg extension, and leg press one-rep max (1RM); both groups increased all three lifts, with no differences between them.
Finally, Dutra et al evaluated the effects of vitamin C (1000mg) and E (400 IU) on adaptations to 10 weeks of resistance training, with two training sessions per week. The study recruited 42 women, who were assigned to one of three groups: an antioxidant group (n = 15, age = 23.7), a placebo group (n = 12, age = 24.0), and a control group (n = 15, age = 23.6). Hypertrophy was assessed via quadriceps muscle thickness; both the antioxidant group and placebo group increased thickness, with no significant difference between them. They also assessed leg extension peak torque, total work, and fatigue using an isokinetic dynamometer. The researchers concluded that the placebo group experienced significantly larger peak torque and total work improvements than the antioxidant group, but I respectfully disagree with their interpretation of the data. A superficial glance at the study figures would indicate that the placebo and antioxidant groups experienced quite similar changes, which were very divergent from the lack of changes observed in the control group. A closer look at the statistical approach appears to indicate that the researchers tested for group main effects, but have interpreted these main effects as interaction effects that would be representative of divergent responses. Perhaps no example is more clear than the interpretation of the peak torque values: while the authors concluded that “chronic antioxidant supplementation may attenuate peak torque and total work improvement,” the antioxidant and placebo groups increased peak torque by 24.1 Newton meters (Nm) and 23.8 Nm, respectively. For a measurement with a standard deviation of roughly 25-30 Nm, these responses differing by only 0.3 Nm represent a virtually identical response. The total work results are a less glaring example, but the same concept applies.
The same lab group published another study more recently in 2019, but it lacked a direct measurement of hypertrophy and relied instead on DXA. They used the same three-group approach and the same doses of vitamins C and E, with 33 women completing 10 weeks of resistance training. After the 10-week program, estimated 1RM for deadlift and dumbbell lunges increased to a similar degree in the placebo and antioxidant groups. The authors concluded that the placebo group increased fat-free mass to a greater degree than the antioxidant group, but I respectfully disagree with their interpretation again. The increase from pre-testing to post-testing was significant in the placebo group, and not significant in the antioxidant group, but this is not synonymous with suggesting that the groups were significantly different from each other. Furthermore, the results give no clear indication that any significant interaction effects were present; these are necessary prerequisites that make it permissible to perform the follow-up tests that would determine if one group significantly increased and another group did not. I don’t mean to get overly technical with the stats, and I certainly don’t support the concept of being rigidly bound to p values for all of our decisions, but I find it important to note when the conclusions do not match the calculations upon which they are based. For a more practical look at the results, the placebo group increased fat-free mass by 1.4kg, and the antioxidant group increased by 0.7kg. Given the (lack of) precision associated with DXA and the sample size of 10-12 subjects per group, that magnitude of difference is, in my opinion, not particularly notable.
Taken together, the evidence linking antioxidant supplementation to impaired muscle growth is characterized by a small body of inconsistent findings. It would seem premature to conclude that antioxidant supplementation unequivocally and substantially impairs hypertrophy or strength gains. However, it’s also worth noting that the results, despite being modest in magnitude and relatively inconsistent, generally tend to show either no effect, or a negative effect, of high-dose supplementation with vitamins C and E. As noted in a very recent review by Ismaeel et al, the studies that do tend to report modest impairments related to muscle growth tend to be carried out in younger subjects, whereas the limited number of studies using older subjects (generally above 60 years of age) tend to show either no effect or a modest beneficial effect of vitamin C and E supplementation. We should be cautious of over-interpreting a trend with so few data points, but it would at least make sense that elderly individuals, who typically have elevated baseline oxidative stress levels, might have more favorable responses to training with antioxidants in comparison to younger individuals with lower baseline oxidative stress.
Ismaeel et al also point out that the findings for previous studies on vitamin C and E may not necessarily apply to all antioxidants. Given the highly diverse compounds that fall under the “antioxidant” umbrella, it’s quite illogical to assume that they all exert the same effects with the same magnitudes. For example, Furlong et al studied a dietary supplement containing a proprietary blend of herbal antioxidant compounds. Throughout the course of a 12-week resistance training program, 24 young untrained participants (mean age = 20.5 years) were randomly assigned to consume the antioxidant blend or a placebo. Supplementation did not significantly impact bench press 1RM, leg press 1RM, vertical jump, perceived recovery, or a variety of isokinetic strength outcomes. Similarly, Beyer et al evaluated the effects of a proprietary polyphenol blend on adaptations to a six-week resistance training program in untrained men between the ages of 18-31. Squat, leg press, and leg extension strength increased in response to training, but supplementation did not significantly impact the magnitude of improvement. It’s possible that vitamins C and E may operate quite differently than other types of plant-derived phytonutrient antioxidant compounds, such as polyphenols, flavonols, and anthocyanins. Ismaeel et al suggest that oral polyphenol supplementation has a comparatively limited ability to increase plasma polyphenol concentrations in vivo, and that polyphenols and other phytonutrient antioxidants are unlikely to act directly as potent reactive species scavengers like high doses of vitamin C and E. Rather, these phytonutrients may exert their effects by activating nuclear factor erythroid 2–related factor 2 (Nrf2), which could induce antioxidant effects by increasing the activation of antioxidant enzymes. This is an important distinction, as polyphenols, flavonols, anthocyanins, and other plant-derived antioxidant compounds may therefore act in a manner that could modestly facilitate recovery while carrying less likelihood of unfavorably impacting key anabolic signaling pathways (Figure 4). Of course, this body of literature is in its infancy, and we have much more to learn about which antioxidants may affect training adaptations, which specific adaptations are affected, and the relative magnitude and importance of any such effects.
What’s the solution?
The body’s balance between oxidative stress and antioxidants needs to be sufficiently regulated, and dietary consumption of antioxidants plays a role in that regulation. In addition, some antioxidants happen to be essential micronutrients that we need to obtain from our diet. As a result, “antioxidant” has become a bit of a buzzword in the health and fitness industries, and tends to be a key selling point for many of the foods that have been arbitrarily designated as “superfoods.” However, as we seem to learn time and time again from physiology, more is not always better. It seems reasonable to suggest that we probably ought to shoot for a reasonably high intake of antioxidants, but not an intake that is higher than one could feasibly achieve from consuming antioxidant-rich foods (rather than supplements). If you’re looking for a helpful resource to assist in the process, a 2010 paper by Carsen et al lists the total antioxidant content of more than 3,100 common foods, beverages, herbs, spices, and dietary supplements. One fringe benefit of seeking out antioxidant-rich food sources is that it indirectly increases the likelihood that you’ll end up with a diet that checks all the typical “healthy” boxes – plenty of fruits, vegetables, and fiber, with tons of food and beverage options that offer relatively high micronutrient density and low energy density. Seeking out these antioxidant-rich foods won’t acutely increase plasma antioxidant levels anywhere close to the same magnitude you’d see with high-dose vitamin C and E supplementation, but should bring an appealing mixture of phytonutrients to generally promote good health and performance, with the capacity to curb excess oxidative stress within reasonable limits.
You’ve probably heard that antioxidant supplementation blunts hypertrophy, and there is some evidence to support this contention. However, the evidence is probably not as strong as you might have thought. Personally, as I dug into my literature search for this article, I was surprised to find just how limited the evidence truly is. At this point in time, we are left with a fairly small body of literature that reports inconsistent findings, but we can still make some tentative conclusions to guide our decision making until more evidence becomes available.
Generally speaking, high-dose supplementation with vitamin C or E doesn’t seem to be an advisable strategy. It doesn’t appear to consistently lead to any particularly terrible outcomes in terms of performance, recovery, or training adaptations, but the evidence suggesting meaningful benefits from high-dose supplementation with vitamin C or E is weak, and there is at least some evidence pointing toward a modest impairment of select training adaptations. Conversely, the story for polyphenols and other phytonutrients with antioxidant properties is a bit more promising. I wouldn’t heavily lean on any of them for enormous performance improvements, but there is some promising evidence reporting modest benefits for acute performance and recovery, and there is reason to believe that they would be less likely to impair training adaptations in comparison to high-dose vitamin C or E supplementation. However, for individuals with relatively high baseline levels of oxidative stress (such as the elderly), the likelihood of vitamin C or E blunting hypertrophy is reduced, and the likelihood of a modest beneficial effect is increased.
I feel pretty confident suggesting that consuming a diet rich in antioxidants is a good idea, and that high-dose antioxidant supplementation (particularly with vitamin C and E) is generally inadvisable based on the lack of meaningful benefit and small risk of detriment. Any enthusiastic calls for the avoidance of high-dose vitamin C and E supplements are probably more forceful than the evidence warrants, but in my opinion, the potential upside is too limited to justify the gamble. The justification for using polyphenols and other phytonutrients with antioxidant properties is a bit more compelling, with some degree of evidence supporting enhancements in blood flow, performance, and recovery, with limited reason to believe that impairment of training adaptations is likely.
Obviously, this body of literature is very, very challenging to interpret; it’s characterized by heterogeneity, it requires you to pretend that completely distinct compounds are similar enough to classify as the same general “thing,” and it requires you to pretend that the food matrices wrapped around each of these singular phytonutrients don’t contain countless other bioactive compounds. Notably, you can get plenty of these phytonutrients without purchasing a single dietary supplement; I would speculate that simply seeking out antioxidant-rich foods is a practical strategy with likely upsides and virtually no downsides.