Have you committed an unnatural act today?

Morgan Freeman’s character in the movie Million Dollar Baby (2004) says “boxing is an unnatural act.” Believe it not, I frequently say the same about lifting weights, tongue in cheek of course, when asked why more people don’t exercise regularly. (Actually, the question is usually more along the lines of “why don’t people get off their lazy asses?”)

Exercise adherence issues aside, anything—a brutal training session, a “natural disaster,” a Frankensteinian creation of genetic engineering—that actually happens could be considered de facto “natural.” As far as weight training goes, unless you’re routinely arranging furniture per the whim of a highly indecisive interior decorator, the act of repeatedly picking up and putting down the very same object in the very same place over and over isn’t exactly an “activity of daily living,” at least for most people.

Is vitamin C an unnatural supplement?

Pondering many exercise-related activities from this semi-evolutionary, teleological viewpoint might lead one to think they are a bit “unnatural.” Drinking iced, calorically-laden recovery supplements during a workout is a bit counterintuitive but nonetheless a potentially effective bodybuilding strategy. (I cover this in my first set of articles.) In sporting competition, the delineation of what constitutes “natural” generally revolves more around what enhances performance versus what is man-made or not “natural” in that sense.

My focus here, though, is specifically on antioxidant supplementation and vitamin C in particular. The daily consumption of vitamin C in amounts equivalent to that of several dozen oranges (1g/day or more) is permitted in many naturally sporting organizations and fairly common despite dubious health(1–5) and performance benefits(6–8). Is that level of vitamin supplementation more “natural” than medically supervised restoration of blood testosterone to normal levels (for the purposes of health and well-being), a practice typically prohibited by overseeing sporting bodies that test for performance enhancing drugs (9–11)?

Semantics aside, let’s investigate whether megadosing vitamin C (otherwise known as ascorbic acid) is indeed an “unnatural act” from a biological perspective or simply a crafty application of sports nutritional technology.

A bit about vitamin C and free radicals

Ascorbic acid is both an antioxidant (quencher of free radicals) as well as a vitamin, at least for humans. A free radical is simply a reactive atom or molecule with one or more unpaired electrons that is highly likely to oxidize other molecules and thus create what’s called oxidative stress (12). As an antioxidant, vitamin C has the ability to counter the damaging effects of free radicals (13) implicated in a host of diseases (14) ranging from gastrointestinal disorders (15, 16) to cancer (17, 18) and even neurodegenerative conditions like Alzheimer’s (19). Free radicals may originate from unwanted sources such as radiation or toxins as well as normal biochemical processes within the body (17, 19). Of particular interest to you and me is that exercise actually generates free radicals and oxidative stress, in particular superoxide radicals (20, 21). However, as you’ll see below, this is the kind of stress we can maybe live with.

 

For humans, ascorbic acid is also a vitamin, meaning that it can't be produced endogenously (22)—we have to obtain it in our diets. The few mammals that lack this ability generally compensate with higher levels of an enzyme with similar antioxidant roles (superoxide dismutase). However, vitamin C is still needed because it does such a good job at protecting against oxidative damage to lipids and proteins and is particularly important for protecting the collagenous protein (23) found in structures like tendons, cartilage, and the skin (24).

How much “C” do I need to get an A?

Despite the role of oxidative stress in disease (5), research generally doesn’t support vitamin C supplementation for living a longer life (1, 2), although it may have a modest effect against some cancers (3). Some of this paradox is probably a matter of dose and the fact that vitamin C can act as a pro-oxidant (increasing oxidative stress), particularly if one consumes more than about 500mg/day(25–27). You see, the highest RDA for vitamin C (for lactating mothers) is a mere 120mg/day. (RDA for men 19 years old and above is just 90 mg (28).) A miniscule daily intake of only 10 mg of vitamin C is enough to prevent scurvy, which manifests in the skin due to collagen breakdown (29).

The rationale that we need or could make use of more vitamin C (in megadoses far beyond the RDA) largely ignores our bodies’ own ability to adjust free radical defenses (see below) and instead presumes that other animals’ ability to upregulate vitamin C biosynthesis should set our standard for vitamin C supplementation. Healthy, unstressed rats produce about 2 mg of vitamin C per 100 mg of body weight daily (or about 2 g/day for a 220-pound human sized “rat”) but can increase vitamin C production fivefold under toxic stress (30). However, when this baseline, unstressed vitamin C production is appropriately scaled from rat to human, based on the metabolic rate (31, 32), the equivalent is only about 300 mg per day, comfortably below the 500 mg/day level that some have suggested may lead to pro-oxidant effects (26).

Naturally, it’s possible that some individuals might need more antioxidant protection due to the oxidant stresses they encounter (5). If you’re thinking ahead, you might even suspect that there is even a time when providing antioxidant support could be especially beneficial, such as during a workout when one is producing more free radicals.

Stress is good?

If you’ve read my articles on nutrient timing during exercise in the form of a peri-workout recovery supplement, I may be about to throw you for a loop. Just as rats and most other animals can increase vitamin C in response to a free radical or toxic threat (23, 30), humans do so with the plethora of other components of our antioxidant defense system. Indeed, there is a common response element (an “on” switch) associated with a multitude of the genes involved in generating a counter-response to oxidative stress (33). This means that a single oxidative threat can quickly trigger a multifaceted and coordinated effort to quench free radicals (34). Mother ature didn’t leave us out in the cold when we lost the ability to synthesize vitamin C (35).

In fact, it seems as if oxidative stress is actually an essential part of engaging and coordinating intracellular free radical quenching. This kind of stress reactivity, termed hormesis (36, 37), is the body’s way of fine tuning its antioxidant army. The critical issue lies with what the appropriate amount of oxidative signaling is to improve antioxidant defenses without falling prey to the ill effects of oxidative damage.

Here’s the kicker

When it comes to exercise, oxidative stress is also crucial for eliciting training adaptation. In other words, by limiting oxidative stress during exercise, high dose antioxidant supplementation (with vitamin C or some other antioxidants) may put the kibosh on your training efforts. By analogy, excessively quenching free radicals during exercise may be like adding 200 pounds of upward band assistance to a bar only loaded to 200 pounds. It defeats the purpose. If you minimize training stress, you minimize adaptation.

Vitamin C, along with vitamin E, is the most studied culprit in this regard (20, 38-40). A daily dose of 1000 mg of vitamin C has been shown to prevent the normal increase in muscle mitochondria from endurance exercise (41). Add 400 IU of vitamin E to that dose of vitamin C and you may completely block the induction of the body’s antioxidant defense systems and even prevent the training-induced improvements in insulin sensitivity (42). However, more conservative daily dosing of vitamin C (500 mg) with E (400 IU) may not be enough to impact improvements in VO2 max (aerobic power) or mitochondrial density (43).

Where’s the kicker?

There is some disagreement in the literature regarding the effects of vitamin C and vitamin E on exercise training adaptation. In addition to dose, species differences (rat versus human), the possible pro-oxidant effects of high dosing (see above), subject training status, and even ineffectiveness of some supplement regimes to actually improve antioxidant status (redox homeostasis) are likely candidates for the mixed results in the research literature (40, 44). However, at very least, when it comes to exercise training adaptation, high dose vitamin C and vitamin E supplementation present long-term negatives that don’t seem to be balanced by tangible benefits (45).

Not all antioxidants are created equal

Because free radicals are both a signal for stress and adaptation, one might correctly suspect that they are also a potential source of muscle fatigue (46, 47). This may be partly because free radicals initiate oxidative damage during exercise itself (48, 49). Quenching free radicals with an antioxidant like coenzyme-Q10 may indeed be ergogenic during a single bout (50), but by limiting the training signal, doing so also impairs adaptation to repeated bouts (51). Similarly, n-acetylcysteine has been found to improve performance (52) but also blunt the adaptive processes after exercise (53). In one study, 14 days of vitamin C dosing (1g/day) did not reduce post-exercise muscle soreness (after a single damaging bout of downhill running) but impaired the full recovery muscle strength, which manifested after the first week of supplementation (54).

Luckily for you and me, not all antioxidants are created equal. Some, in fact, are known to exert their effects by calling into action our cells’ own antioxidant defenses. Quercetin has this effect (55) and has been shown to improve aerobic exercise performance and stimulate mitochondrial biogenesis (1000mg/day) after only two weeks of supplementation (56).

Whey protein, if undenatured (57), is truly impressive in this regard, as it has powerful intrinsic antioxidant activity, making it ergogenic (58, 59) in both rodents (60, 61) and humans(62). More importantly though, undenatured whey consumption increases activity of the body’s own free radical scavenging enzymes in animals (58) and people (63–65).

Nature has provided us with a multitude of other substances like quercetin and undenatured whey that upregulate cells’ ability to quench free radicals. This property has also been demonstrated in plant extracts (e.g., from white willow bark (66) to several food components and spices (67) including cinnamon (68–70), garlic (71–73), curcumin (found in tumeric), carnosol (rosemary), sulforaphane (cruciferous vegetables like broccoli), and polyphenols such as resveratrol (Japanese knotweed), quercetin (various fruits and vegetables) and EGCG (green tea) (18, 55)).

Go natural with super supplements

It’s unknown just where the tipping point lies (5) between free radical stress that encourages adaptive defenses (40) and free radical quenching that prevents oxidative stress and its correlates of disease and aging (37). Perhaps ergogenic antioxidants could be strategically and only periodically used, thus avoiding interfering with training adaptation. (For example, one might use them to prevent overtraining during high volume or high intensity training phases.) A better option, from a mechanistic standpoint as well as from the limited existing data, is to employ antioxidant “super supplements” such as those listed above to encourage expression of the body’s own endogenous antioxidant activity, thus truly “supplementing” and reinforcing the natural cellular adaptation to oxidative stress.

When it comes to vitamin C and E (and the same may hold true for coenzyme-Q10, N-acetylcysteine, and other similar antioxidants), some researchers have gone so far as to say that these “antioxidant supplements are, at the least, useless" (45).

In other words, you could even say that megadosing of antioxidant vitamins like C and E is an “unnatural act.” Regardless of terminology, the bottom line is that regularly doing so may very well run counter to getting the results from your training that you so rightly deserve.

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