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Pre-Workout Supplements: Benefits, Side Effects, and More

What are Pre-Workout Supplements?

Pre-workout supplements are just what they sound like -- supplements that are taken prior to exercise.  They contain multiple ingredients, usually come in powder form, and are purported to bolster your workout performance in multiple ways.      

Along with whey protein and BCAAs, they’re amongst the most popular supplements currently on the market, with dozens -- if not hundreds -- of different pre-workout products available here in the U.S.  

What Ingredients are in Pre-Workout Supplements?

Just as there are all sorts of different pre-workout supplements though, there are also all sorts of different formulas, meaning that each product ultimately contains a unique blend of ingredients. 

While ingredients can vary significantly from product to products, the types of ingredients used in pre-workouts can be placed into a few broad categories: stimulants, nitric oxide boosters, and muscle enhancers.  

Although there is lots of scientific evidence when it comes to the efficacy of some substances, there is no support for other ingredients commonly found in pre-workout supplements.  On top of that, there are also a number of popular substances with mixed-findings.    

While we’ll be going over a number of different ingredients, the list is by no means exhaustive.  

Caffeine and Other Stimulants

Stimulants are the workhorse of many different pre-workout supplements, with caffeine being by far the most commonly used ingredient.

They primarily function by increasing the activity of your body’s central nervous system -- substances like caffeine have inhibitory effects, helping to block the chemical messenger adenosine form signaling to your body that you’re fatigued.  

Other stimulants that can are commonly found in pre-workouts include: 

  • Yohimbine
  • Theacrine
  • Guarana
  • Synephrine

While stimulants may offer certain benefits, they can also become dangerous at high dosages -- several people have actually died from taking pre-workouts that were too highly dosed. Certain stimulants like DAA -- a once a popular pre-workout ingredient -- have actually been banned by the FDA for this very reason.

Muscle Enhancers

Muscle enhancers are substances that enhance the capacity of your muscles to perform and recover from a workout.  Through multiple pathways, they help to activate and support the underlying physiological processes that take place in your muscles both during and after exercise.  

There are a number of different substances that have been shown to be effective in human trials.  Creatine and beta-alanine are the most well-known, appearing in many different pre-workout supplements, although dosages can vary significantly from product to product.

  • Creatine

    Creatine is an amino acid-like compound that helps to increase your body’s production of adenosine triphosphate (ATP). ATP is an energy-providing chemical centrally involved in both the contraction of your muscles and the function of your brain.

  • Beta-Alanine

    Beta-alanine is a non-essential amino acid used by your body to produce carnosine. Carnosine is a peptide that helps to prevent the build-up of toxic chemical by-products in your muscle tissues.

  • HICA

    Alpha-hydroxy-isocaproic acid (HICA) is naturally metabolized by your body from the amino acid leucine. HICA aids in the activation of the mechanistic target of rapamycin (mTOR) signaling pathways, which play an important role in regulating your body’s muscle mass.

  • HMB

    Β-hydroxy-β-methylbutyrate (HMB) is another leucine that helps to prevent muscle protein breakdown during and following your workout.

  • Phosphatidic Acid

    Phosphatidic acid is a cell signaling lip produced naturally within the body and like the name states, it plays an important role in facilitating communication and coordination between cells. Like HICA, it also helps to promote mTOR signaling, but through different pathways.

  • Nitric Oxide Boosters

    Nitric Oxide (NO) boosters, which are also known as vasodilators, help to boost blood flow to your muscles, which some suggest may help to improve endurance and recovery.  The most common NO boosters include L-arginine and citrulline.  

    Pre-Workout Benefits

    Exercise Performance

    Photo by Pixabay


    There has been a wealth of scientific evidence that creatine supplementation helps to improve exercise performance, which is one of the main reasons it can be found in so many different pre-workout supplements. 

    Research shows that creatine (via ATP) may help to improve muscle contractions -- better muscle contractions ultimately translate to more strength and more reps during your workout.  

    For example, one double-blind, placebo-controlled study investigated the effects of creatine supplementation on elite athletes participating in a weight lifting program.(1) Participants were asked to perform as many reps as they could on the bench press and squat exercises at an intensity level of 60 - 70% of their one-rep max.  

    At the conclusion of the study, the researchers ultimately found that those who supplemented with creatine were able to perform significantly more reps, on average, in comparison to those who were only given a placebo.   

    Numerous human trials involving elite athletes like sprinters and football players also found that creatine supplementation significantly improved study participants sprinting performances as well, suggesting that creatine may be particularly effective when it comes to high-intensity exercise in general.(2)(3)


    Positive effects on exercise performance have also been observed with beta-alanine.  Numerous studies have found that beta-alanine supplementation significantly improved study participants’ spriting performances, with those who were given beta-alanine, on average, sustaining greater power outputs for longer durations of time in comparison to those who received only a placebo.(4)(5)(6)(7)

    On top of improving your sprint performance, it may also help to improve your power output in the weight room as well.  For instance, a 2018 randomized, placebo-controlled study examined the effects of beta-alanine supplementation on healthy participants with prior strength training experience.(8)

    Following a 5-week leg-based training program, researchers found that participants who were given a daily dose of beta-alanine, on average, saw significantly greater increases in power output in comparison to individuals who were only given a placebo.   

    Phosphatidic Acid

    While it hasn’t been as extensively researched as creatine or beta-alanine, there is a growing body of evidence that Phosphatidic Acid (PA) may also help to improve your performance on strength-based exercises.  

    Take a 2013 study published by the International Society of Sports Nutrition for example.(9) Over the course of an 8-week weight lifting program involving both strength and hypertrophy training, researchers gave participants a daily dose of either phosphatidic acid or a placebo.  

    At the conclusion of the study, the researchers found that those who supplemented with phosphatidic acid saw significantly greater increases in strength in comparison to those who received only a placebo -- the PA group added nearly 20 more pounds to their one-rep-max, on average, in comparison to the placebo group 


    There is some evidence that L-arginine may be a performance-enhancing substance as well.(10) For instance, a 2006 study published in Nutrition ultimately found that L-arginine supplementation had a significant and positive influence on study participants’ one-rep-max on the bench press over the course of an 8-week training program.(11)

    However, to date, findings have been mixed when it comes to the effectiveness of L-arginine supplementation on exercise performance.  A 2012 review involving 8 different well-designed studies ultimately found that results were split down the middle, with 4 trials demonstrating positive findings, while 4 studies showed no significant effects of L-arginine on exercise performance.(12)


    There have been a number of trials that found positive effects of caffeine on exercise performance, however, like with L-arginine, findings are mixed.  For example, a 2010 systematic review evaluated 29 different studies involving caffeine ingestion and exercise.(13)

    The researchers ultimately found that eleven out of seventeen trials demonstrated significant improvements in athletic performance in elite athletes.  However, these effects were more pronounced in athletes who did not normally take caffeine -- regular caffeine users, on average, were less likely to experience the same type of positive effects.    

    In the same review, only about half of the studies involving caffeine and resistance training (6 out of 11) found positive effects on strength.  Amongst the studies that did not demonstrate positive outcomes, a few actually found a negative effect on exercise performance in instances when caffeine was taken prior to multiple bouts of exercise.  

    Mental Function

    Photo by Bahaa A. Shawqi


    On top of potentially improving your physical performance, caffeine has also been shown to have positive effects on your mental performance as well.  Research shows that it helps to promote the release of serotonin and inhibit the production of adenosine, helping to improve alertness and reduce fatigue. (14)

    One study found that participants reported feeling less tired and having more energy during their workout when they ingested caffeine.(15) On top of that, the researchers found that caffeine may help to improve exercise performance -- particularly in infrequent users -- do to improvements in psychological factors like motivation, mood, and alertness.  


    There is also some evidence that creatine may help to improve mental function as well, which is why it’s sometimes categorized as a nootropic substance.(16)(17)  Because ATP functions as an important energy-providing brain chemical, researchers hypothesize that it may help to improve several mental processes.  

    However, it’s important to point out that most positive findings involving creatine and brain function have involved individuals with various cognitive disorders.  Few studies have explored the effects of creatine on individuals with normal brain function, however, one such trial ultimately failed to find any positive effects on mental processing in healthy, young adults.(18)


    Photo by Jesper Aggergaard

    Prevent Muscle Protein Breakdown

    Amino acid metabolites like HICA and HMB can also help to prevent muscle protein breakdown (MPB) from occurring during your workout -- MPB is the technical term for the damage that occurs in your muscle tissues when you exercise.  

    In general, the more damage that occurs, the more challenging the recovery process -- MPB can ultimately lead to muscle loss in instances when your body isn’t able to adequately repair the damage that’s been done.

    However, research shows that HICA and HMB may help to minimize the amount of muscle protein breakdown that occurs as a result of intense physical exercise. For example, a 2010 double-blind, placebo-controlled study evaluated the efficacy of HICA supplementation in elite soccer players participating in 4 aerobic training sessions, 2 weightlifting sessions, and one game each week.(19)

    The researchers found that compared to the placebo group, who actually lost lean mass over the course of the 4-week study (1% decrease), those who received a daily dose of HICA actually saw increases in muscle mass (2% increase).  Additionally, athletes on average also experienced significantly less Delayed Onset Muscle Soreness (DOMS) with HICA.  

    The researchers ultimately concluded that these positive gains in muscle mass were primarily due to the preventive effects of HICA on muscle protein breakdown, helping to protect the athletes against muscle catabolism during physically intensive exercise.  

    Promote Muscle Protein Synthesis

    On the flipside of muscle protein breakdown is muscle protein synthesis (MPS), which is the process through which your body repairs and replaces broken down muscle proteins.  In order to maintain your lean body mass, the number of new muscle proteins that are synthesized in your body must be equal to the number that are broken down -- to build muscle, MPS must eclipse MPB.  

    Leucine metabolites like HICA and HMB have been shown to keep your levels of MPS elevate, not only helping your muscles to adequately recover, but also putting them in an excellent position to grow bigger and stronger.  

    For example, a systematic review evaluated the findings of seven studies involving HMB supplementation and resistance training. The researchers ultimately found that across the included studies, those who were given HMB gained 50 to 200 percent more lean muscle mass in comparison to those who went unsupplemented.(20)

    Pre-Workout Ingredients With No Proven Efficacy

    While there is evidence for the efficacy of a number of different substances -- although the findings surrounding some compounds are mixed -- there are also other common pre-workout ingredients that have no proven efficacy.  

    So while they may not be harmful, researchers have failed to find any significant effect on exercise performance for the following substances:

    • Agmatine sulfate
    • Taurine
    • Alpha-ketoglutarate
    • Glutamine
    • Vanadyl sulfate
    • L-carnitine
    • ZMA

    Pre-Workout Side Effects and Downsides

    While a number of different substances may offer certain benefits, there are also some potential downsides to some pre-workout ingredients. Caffeine, in particular, can cause a number of unwanted side effects, especially at high dosages.      


    One of the most common side effects associated with pre-workout supplements is the jitters.  At high dosages, stimulants like caffeine can overtax your central nervous system making you feel nervous and jumpy.  Some people even report feeling like their heart is beating out of their chest.  

    While it’s only a temporary side effect, the jitter can certainly impinge on your ability to perform at your best during your workout, which is the exact opposite of what you want from a pre-workout.  

    Skin Irritation (beta-alanine)

    Another common side effect associated with pre-workout supplements -- particularly beta-alanine -- is paraesthesia, which is generally described as tingling sensation beneath the skin.  

    While it may cause discomfort to some users, paraesthesia is only a minor and temporary side effect.  There doesn’t appear to be any long-term safety concerns associated with beta-alanine supplementation.

    Digestive Issues

    Certain pre-workout ingredients may also cause gastrointestinal problems.  Substances, like caffeine, create and L-arginine have been shown to cause stomach pain and digestive issues in some people.

    Energy Crash

    Some pre-workouts are also loaded with added sugars.  While this might provide you with an initial burst of energy, it can lead to an energy crash well before your workout is over, impinging on your ability to perform at your best.   


    Certain supplements also contain excessive amounts of caffeine, which in addition to causing the jitters and gastrointestinal problems, can also lead to poor sleep quality and even insomnia in some individuals.  

    Should You Take a Pre-Workout Supplement?

    Most pre-workouts are meant to overcharge the central nervous system with stimulants to amp you up -- in fact, many users specifically look for this.  It’s true that amping up the CNS does allow you to do more in the gym but it comes at a cost.  

    Overstimulation of the CNS will eventually downregulate it, meaning that with regular use, you become less and less sensitive to the stimulant.  This requires you to take more and more to continue feeling effects, which can lead to a number of different negative health outcomes, including death.  

    Ultimately, that’s why many people who take stimulant-based supplements find that themselves going on and of the pre-workout to allow their systems to reset.  

    Also, taking stimulant-based pre-workout does not take advantage of what it is you are trying to do when you take a pre-workout:  to make the muscles work better. So ingredients that actually work at the muscle biochemistry level work better at improving performance in comparison to stimulants.

    But you need to take a product with the right ingredients at the right dosages in order to experience the effects you’re after.  Unfortunately, many products contain inferior ingredients and/or less than ideal dosages.

    Wrap Up

    One of the easiest ways to limit the side effects and maximize your workout performance is to take a stimulant-free pre-workout.

    Substances like creatine, beta-alanine, and phosphatidic acid can all help to improve your performance in the gym and unlike caffeine (and other stimulants), you don’t have to keep taking more and more in order to continue feeling the effects.   

    Although to find a product the gives you positive results, you have to do your research.  Know what ingredients actually work and make sure you’re taking them at the appropriate dosages.

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