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By Robert A. Schinetsky



Pre workout supplements come in all shapes, sizes, and flavors.

Some are micro (under)-dosed proprietary blends that deliver nothing more than a truckload of stimulants (some of which are legal, and some are not).

Others contain serving sizes so massive they rival that of protein powders.

But, if we’re being honest, scoop size isn’t what really matters. It’s the ingredients in that scoop– as well as their quality and dosage– that separate the best pre-workout supplement from the utterly mundane.

For instance, you could make a pre workout that contains 30+ grams of “actives”, but if that same product contains 8 grams of BCAA alongside 2 grams of taurine and 5 grams of’re spending a lot of money on ingredients that aren’t providing much benefit to your workout.

That’s why we say that size isn’t everything.

Today, we review the best pre workout supplements -- which ones work, and which ones don’t, according to the research.

Let’s get started with the ingredient that serves as the “backbone” of all great pre workout supplements…

Best Pre-Workout Supplement Ingredients


Caffeine is an ingredient with which we’re all quite familiar.

It is a powerful central nervous system stimulant naturally occuring in a number of foods, including coffee beans, cocoa beans, and tea leaves. 

Research has shown numerous times that caffeine is an effective performance-enhancing nutrient for high-intensity exercise.[1,2]

It can also enhance upper body strength & power, vigilance during exhaustive exercise, and performance during periods of sustained sleep deprivation.[1,2]

Even when used at doses as low as 32mg, caffeine has been noted to boost mood, performance, vigilance, and reaction time.[3]

Caffeine primarily works by antagonizing adenosine receptors in the body, which promotes increased feelings of alertness, wakefulness, and reactivity.

Additionally, caffeine also is known to stimulate dopamine release as well as increase dopamine receptor availability in the brain.[4]

Dopamine is a highly-important neurotransmitter that affects mood, motivation, motor control, decision-making, and focus.

Perhaps most importantly, caffeine (unlike many conventional pre workout stimulants) has been extensively studied in humans and proven to be safe when consumed at reasonable doses (3-6mg/kg).

AML Pre Workout X-Treme contains a research-supported dose of 400mg caffeine per serving.

Citrulline Malate

Another ingredient that has become a “staple” of sorts in the best pre- workout supplements is citrulline malate.

This combination of L-citrulline and malic acid is known for its ability to help enhance performance, fatigue resistance, stamina, recovery, and muscle pumps!

Citrulline serves as an important player in the urea cycle (along with l-ornithine and l-arginine), which is responsible for removing metabolic waste products generated during intense exercise, including hydrogen (H+ ions) and ammonia.

As these byproducts of muscle contractions accumulate, fatigue begins to set in and eventually results in performance drop off and/or the termination of a working set.

Supplementing with citrulline malate may enhance the body’s ability to buffer these waste products, helping individuals to stave off fatigue for longer, thereby allowing for more total work to be accomplished.

But that’s not all.

Citrulline also increases blood levels of arginine -- the amino acid that serves as the “fuel” for nitric oxide production. In fact, citrulline has actually been shown to be superior to free form (supplemental) l-arginine for increasing blood levels of arginine.[6]

This is due to citrulline’s superior bioavailability as it bypasses metabolism by arginase (the enzyme that degrades arginine), and L-Citrulline is also easier on the GI system than l-arginine.[6]

Citrulline malate supplementation has also been found to help increase the number of repetitions performed while also reducing an individual’s rate of perceived exertion (RPE) and post-workout muscle soreness.[7,8,9]

Creatine Monohydrate

Did you really expect to see a list of the best pre workout supplements that didn’t include creatine monohydrate?

We didn’t think so.

Simply put, if you had to choose one, the best pre-workout supplement you should consider using is creatine monohydrate.

Creatine has stood the test of time, and numerous studies, meta-analyses, systematic reviews, and position stands have stated that creatine supplementation is effective for enhancing energy production, power and strength output as well as supporting lean mass gains.[10,11,12]

Creatine primarily works by increasing the body’s ability to generate ATP (the “currency” of energy production). The more rapidly you can generate ATP, the longer you can sustain a high level of output, thereby accomplishing more total work (lifting heavier weights for more reps).

Creatine also enhances cellular hydrations via is osmolytic qualities, and it promotes muscle growth by activating a variety of cellular mechanisms, including protein synthesis and the stimulation of muscle cell formation.[13,14]

Now, creatine doesn’t have to be taken pre workout necessarily. It is a saturation-driven ingredient, meaning that once your muscles’ creatine stores are fully loaded is when you’ll start to derive benefit. 

Including it in a pre workout at the research-backed 5,000mg dose, like AML PreWorkout X-Treme, simplifies things so that you don’t have to worry about taking (or forgetting to take it) at other times during the day.

Beta Alanine

What creatine is to muscle growth, beta alanine is to endurance and stamina.

Beta alanine is an amino acid that binds to L-Histidine to form carnosine, a powerful intracellular pH buffer.[15] 

Why is this important?

When muscles repeatedly contract during intense physical activity, various metabolites, including hydrogen ions (H+), accumulate

As these ions continue to build up, the muscle’s pH becomes more acidic, which eventually prevents the muscle from continuing to contract.

Some other data suggests that carnosine may act as an antioxidant, thereby counteracting reactive oxygen species (ROS), which are produced at an increased rate during exercise. Higher levels of ROS may contribute to muscle fatigue and exercise-induced muscle damage under certain circumstances.[16,17] 

Supplementing with beta alanine effectively increases carnosine concentrations in skeletal muscle tissue, thereby improving its ability to buffer H+ ions and delay the onset of fatigue.

Ultimately, this helps athletes complete more repetitions and more total work before succumbing to fatigue, which supports muscle gain.

Similar to creatine, beta alanine is a saturation-based nutrient, so while it doesn’t “need” to be taken in the pre workout setting, doing so helps simplify your daily supplement intake.

Additionally, combining the two gives a “best of both worlds” in regards to performance as creatine augments performance during short-duration high-intensity work (typically efforts lasting effect <30 s)[18] while beta alanine improves performance during activities lasting between 60-240 seconds.

Betaine Anhydrous

Betaine is a natural osmolyte found in a number of foods, including shellfish, sugar beets, spinach, and assorted whole grains.[19]

It is involved in a number of critical processes including methylation reactions and homocysteine detoxification.

In case you weren’t aware, research indicates that high levels of homocysteine can be a risk factor for heart disease.[20]

Additional studies suggest that diets high in betaine may also reduce the risk for certain diseases.[20]

Betaine’s other primary role is as an osmolyte, which helps protect cells, proteins, and enzymes from environmental stress.

As an osmolyte, betaine also helps maintain cell volume and fluid balance, which may help protect against the dehydration effects of intense exercise.

It also increases intracellular water content, causing cellular swelling, which has been identified as a contributor to muscle growth via stimulation of muscle protein synthesis.

Essentially, cellular expansion is perceived as a threat to the cell’s survival. As a result, the cell upregulates protein synthesis as a means to “batten down the hatches” and ensure the cell is stable.

So, what does this have to do with resistance training and pre workout supplements?

Well, a number of human studies have found that betaine supplementation may significantly increase anaerobic power, muscle protein synthesis, and body composition.[21,22,23,24,25]

Most recently, a study noted that higher dietary intakes of betaine were associated with less loss of skeletal muscle mass in middle-aged adults.[26]


When discussing caffeine above, we mentioned how it stimulates the release of the “motivation and reward molecule”, dopamine.

L-Tyrosine is an amino acid that serves the “raw material” for the production of dopamine, as well as two other highly important neurotransmitters/hormones in epinephrine (adrenaline), and norepinephrine (noradrenaline).

Deficiencies in dopamine are known to impact motivation, performance, mood, and cognition.[30]

Prolonged stress (such as intense physical activity) can deplete dopamine stores in the brain, leading to increased fatigue as well as decrements in performance.[27]

Assorted human studies indicate that supplementing with 2,000mg L-Tyrosine may help alleviate stress, leading to improvements in mental and physical performance as well as memory.[27,28,29]

Dopamine Synthesis Support Agents (Folic Acid + Mucuna Pruriens)

L-Tyrosine is but one part (albeit a very important part) of dopamine production in the body.

The body takes tyrosine and converts it to L-Dopa -- the direct precursor to dopamine.[31]

In cases where the conversion of tyrosine to L-dopa is blocked, dopamine production declines.

However, L-Dopa can cross the blood-brain barrier and undergo conversion to dopamine, restoring neurotransmission as well as offering anti-inflammatory and neuroprotective effects.[31]

Mucuna Pruriens (aka velvet bean) is a plant that has long been used in traditional Ayurvedic Indian medicine which contains L-Dopa.

Another important player in the production of dopamine is Folic Acid (vitamin B9), a nutrient which is used to combat feelings of sluggishness or depression.

Folic acid is required for the production of an important cofactor needed for the synthesis of dopamine, BH4.[32]

Research has noted an association between low folic acid levels and reduced dopamine levels, which themselves are linked to depression. It stands to reason then that by increasing folic acid intake, more of the “supporting cast” nutrients required for dopamine synthesis are present, supporting optimal neurotransmitter synthesis.

Peak ATP®

ATP, as you know, is the “currency” of energy production within cells.

The more ATP available, the more work that can ultimately be accomplished.

Over the years, researchers have attempted to develop exogenous forms of ATP salts, all of which have failed (in human testing at least) even when using large doses, due to poor bioavailability.

Peak ATP® is a clinically-researched, patented form of adenosine 5’-triphosphate (ATP) disodium that is identical in structure to human ATP.

Human studies indicate that supplementation with Peak ATP® may improve athletic performance and body composition by increasing blood flow, muscular excitability, and recovery.

These effects have been observed after just a single dose, too!

Additionally, Peak ATP supplementation has also been found to boost the ratio of muscle activation and power output during high-intensity exercise as well as help reduce protein breakdown and attenuate performance drop-off as an individual gets deeper into their workout.[33,34,35,36]

p-Synephrine (Advantra Z)

p-synephrine is an alkaloid present in Citrus Aurantium (Bitter orange) that is structurally similar to ephedrine but significantly weaker (which is a good thing).

Studies indicate that supplementation with p-synephrine may increase energy expenditure, post exercise oxygen uptake, and fat oxidation, which lead to improvements in repetition performance and volume load during training.[33,34]

Advantra Z® is a patented extract of Citrus Aurantium (a.k.a. Bitter Orange) that is backed by multiple human efficacy clinical studies and safety data.

Not only has p-synephrine been found to improve performance on its own, it’s also been shown to work even better alongside caffeine.[37,38]

Specifically, when participants consumed caffeine with 100mg p-synephrine (the same dose included in AML PreWorkout X-Treme), they were able to complete faster, more powerful repetitions with no additional perceived exertion or lactate accumulation![38]

Note that p-synephrine is not to be confused with m-synephrine (or ephedrine), both of which are banned substances in dietary supplements.

Grape Skin Extract

Grape skin extract contains a variety of polyphenols known to support blood flow, nitric oxide production, and athletic performance by stimulating endothelial nitric oxide synthase (eNOS) -- the enzyme that catalyzes NO production in the body.

Research indicates that supplementing with polyphenol-rich extracts may help significantly  increase maximal peak power output (3.7%), average power (5%), total power output (5%).[39]

Additional research notes that supplementation with grape skin extract can reduce muscle damage after high intensity strength training.[40,41]


As you’ve likely experienced for yourself, intense exercise very often results in intense sweating.

In addition to losing water, your body also loses valuable electrolytes -- charged minerals in the body that affect everything from hydration to muscle contraction/relaxation to neurotransmission.

Depletion of electrolyte stores can lead to performance decline, cramping, fatigue, increased risk of injury, and cognitive impairment.

Supplementing with electrolytes helps ensure there are ample stores of these key minerals in the body, which helps guard against the dehydrating effects of exercise and supports better performance and fatigue resistance.

Furthermore, magnesium and potassium are also known to support cardiovascular health and athletic performance.

More specifically, magnesium increases nitric oxide synthase activity, promoting vasodilation and greater blood flow while potassium can soften the endothelium and increase nitric oxide production.[42,43]


There are a lot of pre workout supplements on the market, many of which are good quality and many that aren’t…so what is the best pre-workout supplement?

But, few (if any) are formulated using the principles that Advanced Molecular Labs implements when creating its premium-quality products.

AML Pre Workout X-Treme was engineered with the singular goal of cultivating the best pre workout supplements (backed by science) and assembling them into one comprehensive product.

Click here to learn more about AML Pre Workout X-Treme and how it can help you push harder and last longer in your training sessions!


  1. Grgic, J., Trexler, E.T., Lazinica, B. et al. Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr 15, 11 (2018) doi:10.1186/s12970-018-0216-0
  2. Goldstein, E.R., Ziegenfuss, T., Kalman, D. et al. International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr 7, 5 (2010) doi:10.1186/1550-2783-7-5
  3. Lieberman, H. R., Wurtman, R. J., Emde, G. G., Roberts, C., & Coviella, I. L. (1987). The effects of low doses of caffeine on human performance and mood. Psychopharmacology, 92(3), 308–312.
  4. Volkow ND, Wang G-J, Logan J, et al. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain. Translational Psychiatry. 2015;5(4):e549-. doi:10.1038/tp.2015.46.
  5. Bahri, S., Zerrouk, N., Aussel, C., Moinard, C., Crenn, P., Curis, E., Sfar, S. (2013). Citrulline: from metabolism to therapeutic use. Nutrition (Burbank, Los Angeles County, Calif.), 29(3), 479–484.
  6. Curis E., et. al; “Citrulline and the gut;”; Current Opinion in Clinical Nutrition and Metabolic Care; September 2007
  7. Wax, B., Kavazis, A. N., Weldon, K., & Sperlak, J. (2015). Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. Journal of Strength and Conditioning Research, 29(3), 786–792.
  8. Glenn, J. M., Gray, M., Wethington, L. N., Stone, M. S., Stewart, R. W. J., & Moyen, N. E. (2017). Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. European Journal of Nutrition, 56(2), 775–784.
  9. Perez-Guisado, J., & Jakeman, P. M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research, 24(5), 1215–1222.
  10. Kreider, R.B., Kalman, D.S., Antonio, J. et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 14, 18 (2017).
  11. Mielgo-ayuso, J., Calleja-gonzalez, J., & Marqu, D. (n.d.). Effects of Creatine Supplementation on Athletic Performance in Soccer Players : A Systematic Review, 1–17.
  12. Mills, S.; Candow, D.G.; Forbes, S.C.; Neary, J.P.; Ormsbee, M.J.; Antonio, J. Effects of Creatine Supplementation during Resistance Training Sessions in Physically Active Young Adults. Nutrients 2020, 12, 1880.
  13. Bemben MG and Lamont HS. Creatine supplementation and exercise performance: recent findings. Sports Med 2005;35, 107-125.
  14. Carnac G, Vernus B, Bonnieu A. Myostatin in the pathophysiology of skeletal muscle. Curr Genomics. 2007;8(7):415-22.
  15. Trexler, E.T., Smith-Ryan, A.E., Stout, J.R. et al. International society of sports nutrition position stand: Beta-Alanine. J Int Soc Sports Nutr 12, 30 (2015).
  16. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243–76. doi:10.1152/physrev.00031.2007
  17. Bailey DM, Davies B, Young IS, Hullin DA, Seddon PS. A potential role for free radical-mediated skeletal muscle soreness in the pathophysiology of acute mountain sickness. Aviat Space Environ Med. 2001;72(6):513–21
  18. Wang CC, Yang MT, Lu KH, Chan KH. The Effects of Creatine Supplementation on Explosive Performance and Optimal Individual Postactivation Potentiation Time. Nutrients. 2016;8(3):143. Published 2016 Mar 4. doi:10.3390/nu8030143
  19. Stuart AS Craig, Betaine in human nutrition, The American Journal of Clinical Nutrition, Volume 80, Issue 3, November 2004, Pages 539–549,
  20. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. Published 2015 Jan 10. doi:10.1186/1475-2891-14-6
  21. Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD. Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr. 2009;6:7. Published 2009 Feb 27. doi:10.1186/1550-2783-6-7
  22. Cholewa, J.M., Hudson, A., Cicholski, T. et al. The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial. J Int Soc Sports Nutr 15, 37 (2018).
  23. Cholewa, J. M., Wyszczelska-Rokiel, M., Glowacki, R., Jakubowski, H., Matthews, T., Wood, R., Paolone, V. (2013). Effects of betaine on body composition, performance, and homocysteine thiolactone. Journal of the International Society of Sports Nutrition, 10(1), 39.
  24. Gao, X., Zhang, H., Guo, X., Li, K., Li, S., & Li, D. (2019). Effect of betaine on reducing body fat—A systematic review and meta-analysis of randomized controlled trials. Nutrients, 11(10), 2480.
  25. Apicella, Jenna M., "The Effect of Betaine Supplementation on Performance and Muscle Mechanisms" (2011). Master's Theses. 109.
  26. Long JA, Zhong RH, Chen S, Wang F, Luo Y, Lu XT, Yishake D, Chen YM, Fang AP, Zhu HL. Dietary betaine intake is associated with skeletal muscle mass change over 3 years in middle-aged adults: the Guangzhou Nutrition and Health Study. Br J Nutr. 2020 Jul 3:1-8. doi: 10.1017/S0007114520002433. Epub ahead of print. PMID: 32616104.
  27. Selasi Attipoe, Stacey A. Zeno, Courtney Lee, Cindy Crawford, Raheleh Khorsan, Avi R. Walter, Patricia A. Deuster, Tyrosine for Mitigating Stress and Enhancing Performance in Healthy Adult Humans, a Rapid Evidence Assessment of the Literature, Military Medicine, Volume 180, Issue 7, July 2015, Pages 754–765,
  28. Steenbergen, L., Sellaro, R., Hommel, B., & Colzato, L. S. (2015). Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive control during task switching performance. Neuropsychologia, 69, 50–55.
  29. Jongkees, B. J., Hommel, B., Kuhn, S., & Colzato, L. S. (2015). Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review. Journal of Psychiatric Research, 70, 50–57.
  30. Nieoullon A. Dopamine and the regulation of cognition and attention. Prog Neurobiol. 2002 May;67(1):53-83. doi: 10.1016/s0301-0082(02)00011-4. PMID: 12126656.
  31. Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The Magic Velvet Bean of Mucuna pruriens. Journal of Traditional and Complementary Medicine. 2012;2(4):331-339.
  32. Homma, D., Katoh, S., Tokuoka, H., & Ichinose, H. (2013). The role of tetrahydrobiopterin and catecholamines in the developmental regulation of tyrosine hydroxylase level in the brain. Journal of Neurochemistry, 126(1), 70–81.
  33. Wilson JM, et al. Effects of oral adenosine-5’-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutrition and Metabolism. 2013, 10:57.
  34. Lowery RP, et al. Oral ATP administration improves blood flow responses to exercise in both animal and human training models. Presented at 10th Annual ISSN Conference. Colorado Springs, CO. June 2013.
  35. Rathmacher JA, et al. Adenosine-5’-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. Journal of the International Society of Sports Nutrition. 2012, 9:48.
  36. Martin Purpura PhD, John A. Rathmacher PhD, Matthew H. Sharp MS, Ryan P. Lowery MS, Kevin A. Shields MS, Jeremy M. Partl MS, Jacob M. Wilson PhD & Ralf Jäger PhD, MBA (2017): Oral Adenosine-5′-triphosphate (ATP) Administration Increases Postexercise ATP Levels, Muscle Excitability, and Athletic Performance Following a Repeated Sprint Bout, Journal of the American College of Nutrition, DOI: 10.1080/07315724.2016.1246989
  37. Ratamess NA, Bush JA, Kang J, et al. The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance. Journal of the International Society of Sports Nutrition. 2015;12:35. doi:10.1186/s12970-015-0096-5.
  38. Ratamess NA, Bush JA, Kang J, et al. The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise. J Am Coll Nutr. 2016;35(8):657-669. doi:10.1080/07315724.2016.1150223.
  39. Cases J, Romain C, Marín-Pagán C, et al. Supplementation with a Polyphenol-Rich Extract, PerfLoad®, Improves Physical Performance during High-Intensity Exercise: A Randomized, Double Blind, Crossover Trial. Nutrients. 2017;9(4):421. doi:10.3390/nu9040421.
  40. Kim J, So WY. Effects of acute grape seed extract supplementation on muscle damage after eccentric exercise: A randomized, controlled clinical trial. J Exerc Sci Fit. 2019;17(2):77-79. doi:10.1016/j.jesf.2019.01.001
  41. Kim, J., & Stebbins, C. L. (2018). Effects of Grape Seed Extract Supplementation on Exercise Performance in Athletes, 2(2017), 2017–2018.
  42. Oberleithner H, Callies C, Kusche-Vihrog K, et al. Potassium softens vascular endothelium and increases nitric oxide release. Proc Natl Acad Sci U S A. 2009;106(8):2829–2834. doi:10.1073/pnas.0813069106
  43. Howard, A. B., Alexander, R. W., & Taylor, W. R. (1995). Effects of magnesium on nitric oxide synthase activity in endothelial cells. The American Journal of Physiology, 269(3 Pt 1), C612-8.