Pre-Workout Supplements and Nutrition: The Autonomic Nervous System, Caffeine, and NO Boosters

Pre-workout nutrition has been a fun topic for me. Individual opinions are all over the place: we’ve got hard-gainers shoving pre-workout powder into their mouths sans water, athletes fasting hours beforehand and scoffing at those very same gym rats, and unknowing fitness newcomers gently sipping coffee during their warm-ups. We see an incredible variability of offerings even within the realm of pre-workout supplements; however, the two main claims of these pre-workout supplements is to provide a necessary boost of energy for and to induce a muscle-popping pump during your workout. As such, I will focus on these two aspects of pre-workout nutrition: boosting training performance by stimulating fight-or-flight neurology, and improving both performance and outcomes (i.e. gains) by vasodilation and nitric oxide effects, known as the “muscle pump.”

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Look at how aggressive those labels are!


Of course, what is “correct” when it comes to pre-workout supplementation and nutrition is highly dependent on one’s own goals, metabolism, and, as I’ll go into later, neurology. Instead of simply saying “it depends,” we’re going to take an in-depth look at some of the concepts underlying pre-workout supplementation, and hopefully you can derive your own plan for pre-workout nutrition based on these ideas.


Since these concepts are fairly heavy in biology, I’ve split this article into nice little bite-sized chunks. First, we will take an in-depth look at our Autonomic Nervous System and its subcomponents to understand the role of stimulants and the dangers of sympathetic dominance. Next, we will investigate the power of caffeine as a pre-workout supplement as well as its role outside of pre-workout nutrition. Lastly, we will consider the existing knowledge surrounding NO-inducing supplementation and some foods that may be excellent substitutes for tradition pre-workout powders. So read on, fitness friends!


Part I – A Quick Bio Lesson on the Sympathetic and Parasympathetic Systems


To start things off, we are going to take a look at the big picture; specifically we will look at the underlying neurological systems that dominate our lives and performance in the macro scale. When we talk about neurology, it is important to remember that no system in the human body operates in isolation. The Autonomic Nervous System (ANS) is perhaps the least isolated of these systems, responsible for all unconscious functions of the human body, including heart rate, metabolic processes, blood pressure, cell repair, and many hormonal responses. In contrast, the Somatic Nervous System (SNS) is the analogous system for voluntary neurology such as movement and sensation, mostly via the triggering of skeletal (voluntary) muscle tissue. When we talk about building a mind-muscle connection, perfecting movement patterns for a compound lift, or correctly activating a muscle group during an exercise, we are talking about improving our SNS.


While the activities for which the ANS is responsible seems largely isolated to bodily functions that occur outside of sport, ignoring the ANS can be detrimental to athletes. For strength athletes (and anyone concerned with fitness), the ANS directly corresponds to the ways in which our body prepares for, recovers from, and performs during workouts or any other important physical or mental event. Moreover, disfunction within one’s ANS is surprisingly common, largely corroborated by common symptoms such as mental fogginess, feeling “off” during a workout, or being over-stimulated early or even after a workout. As such, the ANS is a vital component of human health that we must investigate before we learn more about stimulants and their effect on our overall performance.


The Sympathetic and Parasympathetic Systems


Two subsystems compose one’s ANS: the sympathetic and the parasympathetic nervous systems. The sympathetic system is known as the “fight or flight” system, and we can think of it as the part of the ANS that prepares us to perform at optimal levels based on stress stimuli. On the other end of the spectrum is the parasympathetic system, which is known as the “rest and digest” or “feed and breed” system. The parasympathetic system dominates when there are a lack of stressors, restoring the body to homeostasis.


These two subsystems are constantly battling one another for dominance based on the presence of stressful stimuli that are relayed via perception that is processed by the brain. Looking at the characteristics of each subsystem, the parasympathetic system seems to be associated with all of the “good” qualities that we desire from training: muscle growth, cell repair, digestive improvements, fat breakdown (lipolysis), a bolstered immune system, and even better memory formation, as well as a lowered heart and pulmonary (breath) rate. On the other hand, the sympathetic system is associated with an almost complete end to digestion and immune system function (via diminished circulation and hydration in the lymphatic system), shutdown of cell and muscle repair processes, activated sweat glands, deactivated pain receptors, vasodilation within our muscles and vasoconstriction basically everywhere else (more on this later when we talk about NO), and an increased heart rate.


While the characteristics of the sympathetic system seem objectively worse than those of the parasympathetic system, I like to think of each system and having their own benefits during the correct times. From a strength standpoint, the sympathetic system does a fantastic job of making our body and mind perform at peak levels during a workout; however, once that workout is over, we must be able to transition our neurological dominance back over to the parasympathetic system. I try to preach this as much as possible, but fat loss and muscle growth occur outside of the gym. If your parasympathetic system cannot take over after a workout, then proper digestion, cell repair, fat loss (via glycogen or energy-store regeneration), and hypertrophy will never happen! Say goodbye to your gains (and overall health) if that’s the case.


Unfortunately, sympathetic dominance is fairly widespread, and it comes from a variety of sources. For college students, these sources can be the never-ending cycle of stress from classes, homework assignments, exams, and other obligations. It is important to remember that psychological stress is in this context nearly identical to physical stress; both raise cortisol and adrenaline levels that trigger sympathetic dominance. For athletes, constantly barraging oneself with stimulants and training modalities (such as running to the gym, working out, doing a prolonged ab session, running home, listening to hype-up music in the shower, throwing in a couple sets of push-ups afterwards, etc.) will have the very same effect, never allowing the parasympathetic system to take over.


As a little aside, the parasympathetic system is responsible for sexual stimulation, providing excitatory input to the sexual organs of both biological men and women. The sympathetic system, on the other hand, actively prevents tumescence, which is a fancy word for when blood rushes to the sexual organs, a marker for sexual excitation. What I’m trying to get at here is problems achieving or maintaining an erection for men, or painful intercourse or penetration for women, as well as general problems with arousal, can be signs that your sympathetic system is overactive.


For those who are interested in strengthening their recovery modalities, I can go into greater detail about recovery tools and the role of soft-tissue work, stretching, and breathing patterns for parasympathetic activation, but for the purposes of this article, I won’t go much further. When it comes to pre-workout nutrition, many people have trouble entering a mindspace that allows for sympathetic dominance, and stimulants such as caffeine can be a helpful tool. Where we need to be cautious, however, is when these stimulants are not isolated to workouts, are not properly cycled, and fuel a pattern of dependence. Throughout this article, remind yourself of the importance of the parasympathetic system and take into account your own predilection towards or away from relaxation. As is the case with most questions, when it comes to pre-workout supplementation, the answer is “it depends,” but if you have trouble reaching a relaxed state, then you must be weary of stimulants.


Heart Rate Variability as a Tool for SNS Health Measurement


Let’s say you are (1) serious about your fitness, (2) have a little extra spending money, and (3) are concerned about your recovery, particularly in the context of sympathetic dominance. In this case, it is a good idea to track your heart rate variability (HRV). As I mentioned before, the sympathetic part of one’s SNS tries to drive one’s heart rate up while the parasympathetic part does the opposite; we can think of this as a tug-of-war battle. If the parasympathetic system is strong, then the tug-of-war battle will be an exciting contest, with the parasympathetic constantly trying to drive down heart rate in the absence of stressors. In this case, one’s heart rate variability would be high, with micro-scale changes in heart rate from beat to beat indicating a healthy battle between the two sides of the SNS. In contrast, a low HRV (or very steady heartbeat) generally means that the sympathetic system is dominating while the parasympathetic system is unable to put up much of a fight.

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Ooooh those heart beats sure have some variability in their rate! [1]

Why is this important? For all of the reasons above. Basically, we can measure sympathetic dominance in a non-invasive way, and that’s pretty cool. Unfortunately, most heart rate trackers lack the millisecond-level accuracy necessary to calculate HRV, so there is only a small, relatively expensive group of niche wearables targeted towards athletes concerned with HRV. For those who have recently looked at my right wrist, I have a WHOOP strap that is able to measure my daily recovery, strain, and sleep performance. The key metric in the recovery measurement is HRV. For me, this provides an excellent way to track which specific activities are responsible for poor sleep and HRV readings so that I can actively adjust my lifestyle to best accommodate the necessary recovery after hard workouts − in the biz we call this autoregulation. I am able to use this information to make decisions about whether I should drink alcohol or perform mentally stressful activities (both of which significantly reduce HRV) after a strenuous workout.


In my opinion, these wearables are a little expensive to be a good deal for the average fitness enthusiast (the WHOOP strap is something like $28/month for 12 months). Luckily, more mainstream brands such as Fitbit are currently exploring HRV tracking, so hopefully future generations of their products will provide cheaper HRV tracking options. If you are very interested in your SNS health and are willing to dish out the necessary dough, let me know and we can together take a look at the different products out there.


In any case, now that we have a fundamental understanding of the Somatic Nervous System, its constituent subsystems, and the ramifications and markers of sympathetic dominance, we can look more closely at pre-workout stimulants, including everyone’s favorite drug: caffeine.



Part II – Caffeine


Caffeine is perhaps the most widely consumed drug on the planet, used by 90% of all adults in the US daily. Yes, it is a drug. Yes, it can be (on a relatively small scale) physically addictive, slowing the rate of dopamine reabsorption so that we artificially obtain high dopamine levels. There are loads of studies surrounding caffeine and coffee, but for the purposes of this article, we are going to look at how caffeine affects strength-based performance, the best ways to use caffeine supplementation, and important concerns or precautions that one should have before declaring “caffeine is healthy!”


How does it do?


First, I think it is always helpful to take a look at the biological mechanism behind an activity or drug. For caffeine, the exact mechanism is not fully understood, but we can get a good picture of how it works by looking at a simplified model of its hormonal effects. In general, human tissue is a lot less passive than most people think. Our tissue releases hormones or proteins that signal or trigger processes that directly correspond to the state of that tissue. For example, muscles actively release trigger proteins such as histamines that are responsible for stimulating muscle protein synthesis (MPS = gains). As an aside, these same chemicals that trigger MPS in part cause DOMS (Delayed Onset Muscle Soreness).


Adenosine is a hormone that is responsible for drowsiness; basically, it is the way that the tissue in our brains signal to our ANS that we need to repair the brain via sleep or parasympathetic-dominant recovery. Caffeine has a very similar chemical structure to adenosine, so when we consume caffeine, it binds to adenosine receptors. With these receptors taken up, any adenosine that the brain produces has no binding sites and thus cannot instill drowsiness. No adenosine binding means no drowsiness, but more specifically, it speeds up the pace of neuron firing, giving us that mentally sharp feeling that we associate with caffeine. It is for this reason that caffeine can be used as a “study drug,” although it is actually hilarious how little consensus there is in the scientific community about caffeine’s effect on memory.


For a little glimpse into that controversy, there are studies that show positive, negative, and insignificant relationships between caffeine and memory recall and formation. In one study, habitual caffeine use of ~700 mg/week boosted word and list recall in comparison to low habitual caffeine intake of ~150 mg/week, which could have been a result of lifestyle changes due to increased energy levels; we know that exercise boosts cognitive output both short and long term. On the other hand, we know that long-term consumption of low-dose caffeine reduces neurogenesis (brain repair) in the hippocampus, which makes sense if sleep is impaired by caffeine use. Furthermore, the hippocampus is responsible for emotion, memory, and the autonomic nervous system (!!!). The ANS is hard to study, but reduced neurogenesis in the hippocampus is definitely a bad look in terms of the effects of prolonged caffeine use and symptoms of sympathetic dominance. Also, the increase in adenosine receptors that occurs due to prolonged caffeine use can result in a breakdown in the reactivity of the ANS in response to chemicals released by the brain; in a word, this is a dangerous breakdown in the balance between the sympathetic and parasympathetic ANS.


Regardless of the effect of caffeine on memory, we know that our neurons fire faster after caffeine consumption. This signals to our pituitary glands that we are in a state of emergency, making it produce more adrenaline, which is the “fight or flight” hormone. Just like that, the sympathetic nervous system is primed to take over, which is a good thing if you need to perform and a bad thing if you need to recover. In this sense, we need to be careful to consume caffeine in a way that still allows us to enter a relaxed, parasympathetic state post workout.


What do the data say?


When it comes to training performance, sports scientists have often found that the human body is far too complex to rely on just a biological model to make conclusions about the best methods for performance optimization. I personally believe in abstracting from biological phenomena to derive a general understanding of how to optimize performance, but this rule can be broken when the data say otherwise. In the world of supplements, I have found that there is a sliding scale of efficacy as corroborated by data-based findings, ranging from the most effective (creatine, the holy grail of supplements) to the least effective (“natural testosterone boosters”). Where does caffeine reside, according to the data? Somewhere in the upper quartile when used correctly on high-volume workouts, and somewhere in the lower quartile when used incorrectly or on relatively low-volume workouts.


Of course, we can find a far-ranging set of conclusions regarding caffeine usage for athletic performance, with a few negative, many inconclusive or insignificant, and some positive effects. After perusing an almost endless stream of journal articles with different test setups and results, it seems that caffeine is most effective in increasing muscular strength and power (i.e. how much weight and with how much bar speed you can perform a lift) for upper body movements such as bench press and less effective for lower body movements such as squat. Also, caffeine seems to provide the largest benefit for untrained individuals, whereas more experienced lifters get less of a benefit, which I account mostly to the fact that new lifters are less likely to have existing methods for entering sympathetic dominance before a workout. Reaction times have been shown to improve with caffeine use, which could be particularly helpful for skill- or form-based movements such as olympic lifts or other sports. Importantly, the positive effects of caffeine supplementation on strength athletes is most significant towards the end of a workout, particularly when the rate of perceived exertion (RPE) is high and the number of sets is high (five or more on a given movement). Caffeine can also reduce the perception of DOMS after a hard workout. Lastly, caffeine is a proven exergonic, burning about 50 extra calories per day when used; the idea that caffeine more readily burns through fats rather than stored glycogen stores, however, is incomplete at the best and the exact reverse of the truth at the worst.


Since that was a big block of information, here is a list of the situations where caffeine is most effective:

  • Upper body workouts (compared to lower body)
  • Untrained individuals (compared to trained athletes)
  • Skill-based movements or sports
  • High-volume and high-RPE workouts
  • Workouts where soreness is a large concern
  • Whenever small calorie differences are important (e.g. competition prep)


So, given these regimes, caffeine may help you with performance during a workout. Why does that matter? Well, one general idea that a lot of beginner lifters do not fully comprehend is the power of training volume. For an intermediate or advanced lifter, that extra 2 reps on a final top set makes a world of difference. While maintaining form is paramount, putting more weight on the bar at the same perceived level of exertion will result in better training outcomes (i.e. gains), ceteris paribus. If you are still at the stage where your workouts are centered around building a mind-muscle connection and thus do not really push your strength endurance levels, then it is likely that caffeine supplementation before a workout is simply not worth it.


How do I do this safely?


So you’ve read about the power of caffeine and you are sufficiently convinced that it can either improve or worsen your overall health. You could super-power your workout volume, but just as easily you can fall into sympathetic dominance or become addicted. How do you proceed?


The science gives us some clues as to what to do, and thus I give to you the commandments of caffeine use:


  1. Do not use it late in the day. Remember, the effect that supplements can have on your performance and health is a game of inches, but large-scale factors such as sleep are meters long. Caffeine negatively affects sleep if used close to bedtime (let’s say within 5-6 hours of sleep). Also, its efficacy diminishes the more adenosine your body has built up over the course of the day, so that cup of coffee at 8PM simply won’t do as much for you as the one earlier in the day will.
  2. Do not overuse it. Your body will build up a tolerance to it, and the negative effects will grow with quantity while the positive effects will not. The hormonal and hippocampal effects of caffeine overuse mean irritability and jitteriness is a likely outcome. Furthermore, if you need caffeine in order to study, I would try to reserve the caffeinated studying to before a workout rather than after it. Taking caffeine after a workout will prevent your parasympathetic system to do its job and give you those hard-earned gains!
  3. Cycle off of it. This is vital to prevent tolerance buildup and addiction; one’s neurology adapts to adenosine blocking, creating more and more receptors, thoroughly mucking up the brain’s ability to control your ANS. Also, prolonged high dopamine levels and simple habitual patterning will give you a good old-fashioned dosage of addiction. A good rule of thumb is to take 5-8 days off (yes, completely off, which means no tea, coffee, energy drinks, absurd doses of dark chocolate, or even kombucha for you people made of money) for every 30-50 days on caffeine. Longer durations require longer off-cycles, so if you need all 50 of those days on caffeine, try to stick to a 6-8 day off-cycle.
  4. Keep your doses to a reasonable size. A lot of pre-workout supplements will throw over 300mg of caffeine at you in a single dose, which will shock the systems of unacclimated athletes. I do not have much of a tolerance, so I try to keep my pre-workout dosages in the 100-200mg range. Remember, a very small dose might not be enough to properly superpower your workout, but it can be part of your own repertoire of sympathetic ANS-inducing tools.
  5. Hydrate! Caffeine is a diuretic, and coffee is extremely acidic and hard to digest. Simply put, you are about to shed your water in both #1 and #2 form, and that needs to be replenished in order to properly perform and recover. When I talk about large-scale factors, hydration joins sleep in the meter-long club.


In general, listen to your body. If you feel too jittery from caffeine to perform, then stop taking it. If you find yourself pooping your brains out because of coffee, then stop drinking it. If you find your tolerance reaching crazy levels, then stop taking it or cycle off of it briefly. If you find yourself in a cycle of dependency, then stop taking it or cycle off of it briefly. Really, if a week-long break from coffee seems too daunting, then it’s probably a good sign that you need to make a lifestyle change. Cliché as it may sound, caffeine is a drug, and we have to treat it as such.


Part III – Nitric Oxide Boosters


The “pump” is a frankly wonderful sensation; bodybuilders are incredibly obsessed with the feeling and look of inflated muscle tissue, so much so that their lord and savior, Arnold Schwarzenegger, has likened it to the feeling orgasm. The biological cause of the pump is increased vasodilation, where blood vessels dilate in skeletal muscle and blood flow to these affected muscles increase, making the muscle swell up and giving our skin that tight feeling. As I’ve mentioned before, the human body uses signaling molecules to induce short-term physiological changes that usually are caused by external stimulus or activity, such as the release of melatonin and serotonin as the day drags on to prepare your body for sleep.


In the cause of the muscle pump, the signaling molecule is actually a gas by the name of nitric oxide (NO). NO came onto the fitness and science scene with a bang, being declared the “Molecule of the Year” in 1992 and quickly being featured on exercise supplements everywhere, complete with associated pictures of bodybuilders with the most enviable pumps you’ve ever seen. Of course, these supplements didn’t actually have NO in them, as NO is a gas with a half-life in the 2-5 second range. Effectively this means that the body must produce its own NO locally, where it can do a whole slew of things by modifying proteins in the body (called nitrosylation for those of you who like to learn new long words for fun). NO can also activate a fancy protein by the name of guanylyl cyclase, which in turn increases levels of another fancy molecule called cGMP, which results in vasodilation.


For supplements, since NO can’t be packed in a powder or pill and swallowed, we instead must concern ourselves NO precursors, or the chemicals from which our body can produce NO. To make things fun, there are approximately three options for these precursors: arginine, citrulline, and nitrates. While most supplements don’t really try to give a real explanation of the effect of their pump-inducing ingredients on hypertrophy (muscle growth) or performance and instead focus heavily on emphasizing how ridiculous your pump will be after ingesting their proprietary formula, most strength athletes agree that the increased blood flow would increase these two factors by increasing the availability of oxygen, energy substrates, and protein molecules to the trained muscles. This way, more energy means better performance, more available protein means better muscle protein synthesis, and a harder training session (in conjunction with these other two factors) means better adaptations to the training, and thus more gains! There are some other, more complicated explanations that are thrown around, such as NO’s effect on energy efficiency and intramuscular calcium handling, but for the purpose of this article we are going to pretend that my above explanation is just about the only one that matters.


So, let’s say you enjoy the feeling a nice muscle pump, you read my explanation for why it might help your training outcomes, and are down to dish out a little dough for a shiny new supplement or food to consume preworkout. Which of those three ingredients, arginine, citrulline, or nitrates, should you be looking for? Let’s take a closer look.


Arginine – Probably the Worst Option

Let’s start with the bad news. Arginine is probably the worst NO precursor to consume in a preworkout. This is a little confusing, however, because it is directly converted to NO by some enzymes in the body, so really the goal of any of these NO boosters is to increase arginine levels in the bloodstream. However, arginine has pretty miserable bioavailability, which just means that a very small proportion of the arginine that you consume will actually enter circulation and thus have a real effect on your physiology. In other words, you need a heck ton of arginine to do any real good. For that reason, we are going to skip over everything related to arginine, say “hey, don’t get a preworkout that emphasizes arginine levels because we know that’s silly,” and move on to our next ingredient!



And now for the good news! Citrulline has very good bioavailability, so much so that ingesting a given quantity of citrulline creates higher blood arginine levels than the same quantity of ingested arginine, by quite a lot. Whether it is L-Citrulline or Citrulline Malate does not really matter, but citrulline malate may be best because malate is a part of something called the tricarboxylic acid cycle, and as such it could contribute to increased ATP levels during aerobic work and decreased fatigue-causing chemicals during anaerobic work. As another fun aside, citrulline is also a part of the urea cycle, helping to clear ammonia and thus decreasing fatigue through that mechanism as well. For a quick sneak-peek into the future of this article, the main comparison here is going to be between citrulline malate and nitrates (found in foods such as beets, pomegranates, and dark chocolate), so the contributions of citrulline and malate to the urea and TCA cycles, respectively, will be a big plus for citrulline malate during that comparison.


So, we have a pretty good conceptual understanding of how citrulline malate boosts NO: arginine levels shoot up, and as a result so does NO, resulting in a delectable pump. But does citrulline increase performance?


To answer this question, we will look both at evidence-based research and the details of the biological mechanism through which citrulline works. On the research end, we need to look both at citrulline’s effects on training outcomes (i.e. did the participant get stronger or increase muscle power output by the end of the study) and its effects on hypertrophy (i.e. did the participant’s muscles grow). Looking at training outcomes, the results sum up to a “it probably helps a little” type of conclusion, which by supplement standards, is actually very good.


For those who have not heard me talk about supplements before, it is important to understand that supplements do not provide anything near the bulk of your training progress; in fact, the best supplements can give you is a sort of (+/-)1-5% gains margin. What I mean by this is that even the gold standard of supplements, creatine, will not make you significantly bigger, stronger, or more powerful at the same order of magnitude as simple training frequency, intensity, eating habits, sleeping habits, and recovery methodologies. For some of us, we will do anything and everything to make gains as much as one percent, and as such, supplements provide us value. However, if your training or recovery regimen is significantly suboptimal, then I would encourage you to focus on that before pumping your money into supplements.


Anyways, we know that citrulline does increase arginine blood levels, which in turn boosts NO levels. Citrulline requires one extra step beyond what nitrates require to be converted into NO, and that is the help of nitric oxide synthase (NOS) enzymes. Importantly, this process requires both time and oxygen, of which the latter is incredibly important when regarding performance effects. If citrulline’s conversion to NO is dependent on available oxygen, then we should not expect muscle power output to increase significantly in low-rep, high-weight lifting scenarios. It therefore should not be surprising to find that the studies that cited training benefits to citrulline supplementation found these benefits in the later sets as a sort of fatigue-preventing agent. Practically, this means that citrulline might not be the best supplement during a 1RM test or low-rep strength-building days, but very well could be helpful in endurance or long, strenuous hypertrophy training.


Overall Grade: B+ (Good when used correctly)



I generally try to keep my opinions out of my articles, but I will always advocate for utilizing natural sources over supplemental ingredients if the data say that performance outcomes are similar. Nitrates are a perfect example of this, and anyone who has seen my Instagram stories (hey follow me @thegainsmanifesto) knows that I love my beets and dark chocolate. The cold hard truth is that real foods are generally safer and more effective than a supplement, all while providing benefits that you may not have been seeking out. For example, you can use beets for their NO-boosting properties, but at the same time you are going to hit yourself with incredibly potent antioxidant, anti-inflammatory, and cellular detoxification effects. Heck, you will even get a solid dose of betaine from beets, which is another common pre-workout ingredient that may improve hormonal training responses, training performance, and body composition. The fun thing about nutrition science is that it is constantly growing, and with this growth we find new compounds, benefits, and ingredient interactions from natural foods that can’t be replicated by single-ingredient supplementation.


Regardless of the benefits of natural ingredients, let’s look closer at the mechanisms of NO production and evidence-based research on nitrate consumption. The nitrate pathway is fairly simple, where nitrates are converted to nitrites, which are then immediate precursors to NO. Importantly, this pathway does not require NOS enzymes and therefore does not require the presence of oxygen. Interestingly, this pathway is actually boosted by acidosis (carbon dioxide buildup) and hypoxia (oxygen depletion), making it even more effective in taxing, anaerobic workouts. For further proof, rodent testing found NO boosters to be most helpful in increasing performance of Type 2 (fast-twitch) muscle fibers. If you’re a heavy lifter, this should be great news!


As a quick aside, I think the fact that nitrates are more effective in anaerobic settings whereas citrulline malate is more effective in aerobic settings is pretty funny. Most people using proprietary pre-workout blends from their favorite supplement company are of the hard-gainer variety, putting themselves under heavy weight and expecting results whereas those who look towards natural ingredients for performance-boosting effects seem much more likely to pursue cardiovascular or endurance-style workouts. And both groups would probably benefit from utilizing the opposite NO-boosting ingredients! Just a funny little thing that made me giggle – moving on.


Other benefits of utilizing the nitrate pathway is that the conversion of nitrates to nitrites seems to autoregulate nitrite and NO levels to a safe, non-toxic level (whereas nitrite consumption has some unpleasant reported side effects). Also, by being found in high-antioxidant foods such as beets, pomegranates, greens, and dark chocolate, the half-life and bioactivity (i.e. efficacy) of NO within the human body is increased. In short, nitrates provide a safe means of increasing NO while providing further health benefits and making the NO do even more work, particularly in anaerobic situations.


There are far fewer studies into the effect of nitrates, usually beetroot juice, on strength performance than there are on citrulline. This is largely because of the endurance-sports community’s obsession with beetroot juice, making most studies focused on biking or running. However, the few studies that we do have on nitrates have shown increased knee extension velocities at the extremes of range of motion and increased reps to failure on the bench press (at 60% of 1RM).


Overall Grade: A (it works, plus it has plenty of other benefits)


Hypertrophy Effects:

When it comes to hypertrophy, there are not a lot of studies on the effect of citrulline or nitrates on muscle tissue size since most studies annoyingly focus on laundry-list pre-workout blends (called Multi-Ingredient Pre-workout Supplements, or MIPS). However, we know that increased training volume is a sure-fire way to increase muscle growth, and NO’s ability to increase reps to failure seems to point to an obvious hypertrophic benefit. While these other effects are hardly confirmed, studies have shown that cell swelling (which probably promotes hypertrophy) and satellite cell differentiation (where new muscle cells form and proliferate) are increased by NO. In any case, we can say “yeah, probably” if someone asks us if NO boosters increase hypertrophy.


How do I use these ingredients?

  1. Arginine: don’t. 
  2. Citrulline Malate:
    Citrulline malate 2:1. It tastes pretty good and is very cheap. Unfortunately the 2:1 ratio of citrulline to malate is generally a lie (as is the case with many supplement claims), but it shouldn’t matter too much. L-citrulline is also an okay option, but citrulline malate is a better bet since it is better studied and has the added benefit of the malate.

    Somewhere in the 1-2 hours pre-workout would be great. Peak arginine levels are reached in the 1.4-2.3 hours after your ingestion window, so use that as your guide, remembering that the hardest parts of your workouts probably are not right at the beginning. 

    How much?
    Research generally uses 8 grams, and that’s about what I would recommend. It seems that many MIPS provide far fewer grams than that, and they also generally are wrong when it comes to exact dosing. As such, I would recommend finding citrulline malate as a separate product and adding it in the 8-10g quantity.

  3. Nitrates:
    This is a harder question that I’d hoped it to be. Beets are my go-to, and beet juice, while a little expensive, provides the most reliable source of nitrates in the books. Others, such as my personal hero Eugene Teo, rely more on pomegranates or pomegranate juice, which provides a similar combination of sugars, antioxidants, and nitrates. Leafy greens, such as arugula and spinach, technically have more nitrates per gram than these fruit, but 200 grams is actually a pretty big serving of greens, which could be a little taxing on your digestive system before a workout. Dark chocolate is an excellent ingredient to mix with a diet heavy in nitrate-containing produce, as it utilizes a slightly different pathway that utilizes cocoa’s rich flavonol content to increase the bioavailability of NO without necessarily contributing directly to nitrate or nitrite levels.

    Nitrates take a good deal of time until they affect athletic performance, due to the fact that they need to be absorbed and then your oral bacteria needs to convert it to nitrate. Most research has shown that 2-3 hours before a workout allows enough time for this absorption and conversion. More interestingly, studies looking at chronic supplementation seem to have even stronger significance than those looking at acute supplementation; in other words, the ergogenic (performance-boosting) effects of nitrates might be more of a result of prolonged exposure than single-dose effects. Some have conjectured that mitochondria and muscle function may be boosted via altered protein expression as a result of long-term exposure to nitrates. In fewer words, take your nitrates 2-3 hours before a workout and do it as often as possible (which here just means eating more nitrate-heavy produce) to get long term and perhaps more significant ergogenic effects.

    How Much?
    Annoyingly, studies seem to happily switch between mg and mmol (millimoles) of nitrate, where a mmol is about 60mg of nitrate. Since mg has a slightly more intuitive meaning, we will stick with that measurement. Most studies use somewhere in the 400-800mg range of nitrates, with some dose dependence. I would shoot for 500mg of nitrates since it seems that performance is not further enhanced by doses beyond that level. Of course, 500mg of nitrates does not mean 500mg of nitrate-containing produce, which is where we hit the issue of variation of nitrate concentrations. In a study comparing nitrate contents of vegetables throughout major US cities, it was found that the lowest nitrate content in spinach was 65ppm in NYC and the highest was 8000ppm in LA, which is frankly hilarious. The best source I could find on specific nitrate contents of different produce can be found here, with an important caveat being that what you consume could be significantly different from these approximate values. If you’re a beet juice drinker, having a cup of the stuff will probably do the trick. Otherwise, you’re on your own to do the math. Personally, I think having a nitrate-rich diet is the best way to go about this, perhaps with greens, dark chocolate, and other fun produce in your pre-workout meal several hours beforehand.



A Conclusion of Sorts

While this article started as an attempt to cover pre-workout nutrition as a whole, it turns out that I spent so much time going down the rabbit-hole of science that I was only able to dig into a couple interesting phenomena. Nonetheless, I think that taking deep, critical looks at the biological mechanisms for caffeine and NO boosters is essential for anyone seeking a deeper understanding of their own body or performance, particularly for strength athletes and college students who likely abuse or misunderstand these chemicals.


I also understand that many have looked at my thoughts on caffeine, shrugged their shoulders, called me an alarmist, and moved on unchanged. I am not against the use of caffeine, in fact, I think it has the ability to improve anyone’s life if used correctly. You love your caffeine, and me telling you to take a 5-day hiatus from the stuff apparently offends many of you to a hilarious degree, but the truth is that you will likely rediscover exactly how amazing the stuff is if and only if you take a break from it. Furthermore, the inability to take a break from your morning cuppa presents what I believe to be an excellent opportunity to prove to yourself that you do in fact have the self-discipline to do something mildly difficult. I will write more about the role that fitness can have in one’s pursuit of mindfulness, discipline, and personal growth down the road, but this particular topic really makes me realize how unwilling some of us are to take difficult steps to improve their own wellbeing.


Okay, sorry about the caffeine rant. What I really wanted to say in this conclusion is that I hope you all found the information interesting and clear, and if you didn’t, then I really hope you reach out for clarification! As always, there is a solid chance I made some small errors in the biology lessons above, so please let me know if I messed something up. Stay tuned for more on the other ingredients that people take pre-workout in a separate article – until then, happy lifting!




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