Three Supplements Backed by Science to Improve Performance

Top Line 

Creatine Monohydrate, protein, and caffeine are three supplements scientifically proven to increase performance in the gym without adverse side effects. 

Why it Matters 


There are numerous supplements on the market that either don’t work, are a waste of your money, and/or may potentially be dangerous to your health. It’s important to know what you’re putting in your body and which supplements can improve your performance. 


Key Takeaways 


  1. In conjunction with resistance training, creatine monohydrate improves strength, hypertrophy, and power. It is safe, effective, and one of the most highly studied supplements on the market. 
  2. Protein is necessary to build muscle, but supplements should be taken only if the protein requirement cannot be reached through diet alone. 
  3. Caffeine is a highly effective supplement that improves exercise performance. Caffeine with resistance training increases muscular endurance, maximal strength, and power output. Doses of 3-6mg of caffeine per kg of body weight are effective. 

Let’s face it, we all want to be the best version of ourselves - in the gym, in the office, and at home. If there's a magic pill we can take to boost performance, its human nature to seek it out. 


It's no wonder then that the global dietary supplements market was worth an estimated $123.28 billion in 2019 with an estimated compound annual growth rate of 8.2% through 2027 (1). 


What does science say about these supplements? In reality, very few are proven to improve performance while most are snake oil scams marketed by instagram influencers. Let’s take a look at three backed by science that I personally use daily. 


Creatine Monohydrate 

How does it work? 


One energy production system our body uses is called the Phosphagen system. ATP (adenosine triphosphate, the fuel source our cells use) is broken down into ADP (adenosine diphosphate). 


As muscle ATP stores are depleted, performance decreases. Creatine Phosphate binds to ADP and helps regenerate ATP molecules. 


By increasing the amount of creatine stores through oral supplementation, time to exhaustion is decreased during short bouts of intense exercise. 


The body naturally produces 1g of creatine per day in the liver and kidneys and can obtain it exogenously through diet, as creatine is found in meat and fish. 


Approximately 95% of creatine is stored in skeletal muscles with the remaining 5% found in the kidneys, liver, and brain. 


Although a loading phase of creatine is common (taking 15g for 3 days and then 3-5g per day after that), there is no difference in creatine levels over the long term if taken at 3-5g per day without a loading phase. (2). 


Creatine and Resistance Training 

Many studies indicate the benefits of creatine supplementation on improving strength, hypertrophy, and power with resistance training. 


A review of 22 studies found that creatine supplementation in addition to resistance training produced an increase in muscle strength and weightlifting performance compared to resistance training alone, although the response varied individually (3). 


While the exact mechanism by which creatine increases muscle growth/hypertrophy is unknown, it is speculated to impact protein synthesis and myogenesis (growth of new muscle tissue) (4). 


Creatine and Brain Function 


Thanks to continuing research, long gone are the days of creatine being just a supplement for gym bros. 


In fact, creatine has a surprising effect on brain function. 


Several studies have shown benefits of improving depressive symptoms with creatine supplementation (5,6). 


In a study of young, male adults (average age 25 years old), a reduction in mental fatigue was seen when asked to continuously perform unique serial calculations after supplementing 8g of creatine a day for 5 days compared to the placebo (7). 


The exact physiological mechanism for these benefits is unknown; however, it's speculated that an increase in brain creatine stores allows for more energy production in the brain. 


Is it safe? 


Yes. There are numerous studies demonstrating no adverse side effects with creatine supplementation (8). 


Not only is it safe, but it's one of the cheapest supplements on the market as well, averaging 12 cents a serving (5g). 




First off, I recommend obtaining most of your protein from whole-food, nutrient-dense, satiating sources, if possible. 


High-quality meats, wild fish, game, free-range eggs, and dairy sources such as greek yogurt are solid options. 


While most Americans tend to consume more protein than the minimum daily recommended amount (9), the RDA isn’t focused on performance or building muscle mass. 


So in fact, a majority of individuals looking to change their body composition are not eating enough protein. 


How Much Protein is Needed? 


Let’s look at an example to put things in perspective. Joe’s goal is to build muscle. He wakes up in the morning, drinks some coffee, and heads to the gym to workout before work. 


After his workout, he realizes he’s short on time, and grabs an apple quickly from the fruit stand outside his office. 


For lunch, he has a salad with grilled chicken, and meets some co-workers for some sushi after work.


 In this scenario, Joe consumes 70-80g of protein per day tops, which satisfies his RDA of 72g of protein. 


With the current recommendations of 0.7-1.0g of protein per lb of bodyweight during a gaining phase (10), this would mean that a 200lb male should consume at least 140g of protein per day to build muscle. This means Joe falls 70-80g short of his target. 


This is where the protein shake comes in handy. One scoop of whey contains on average 25g of protein. 


Adding one shake before/after his workout, one with lunch, and perhaps even another before bed, would allow Joe to hit his target with ease. 


If Joe was vegan or dairy-free, there are a multitude of other protein powders such as egg, soy, and pea that he could supplement with. 


When to Consume 


Don’t fall for the marketing gurus - protein powder isn’t some magic supplement that is absolutely necessary to pack on muscle. The idea that you need to consume protein immediately after your workout or you will miss the “anabolic window” has been disproven (11). 


Unless training fasted, as long as you reach your protein target throughout the day, there will be an adequate supply of amino acids through your bloodstream to start the repair process post-training. 


Is it safe? 


The National Institute of Health’s Office of Dietary Supplements reports no safety concerns or adverse side effects at daily recommended intakes for athletes up to 2.0g/kg body weight. 


The idea that a high protein diet is bad for your kidneys is no longer mainstream. Take this study, for example, which demonstrates high protein diets (2.51-3.32 g/kg/d) are not harmful on kidney function in healthy resistance-trained males (12). 


Bottom line - if you’re having difficulty reaching your protein targets through diet, go ahead and supplement with some protein powder, it's safe for your kidneys and your wallet. 




While coffee consumption has numerous health benefits ranging from reductions in DNA damage to reducing all cause mortality risk (13,14), just to name a few - let’s focus on the performance enhancing benefits of caffeine here. 


How does it Work?


Caffeine is the most widely consumed drug in the world. 


It acts as a central nervous system stimulant by blocking the activity of the neurotransmitter adenosine, which has a sedative like effect. 


Caffeine helps prevent the onset of tiredness, increases blood pressure by causing vasoconstriction, and improves alertness/mood. 


Effect on Performance 


A 2019 systematic review of caffeine’s effect on resistance exercise demonstrates that caffeine supplementation increases muscular endurance, maximal strength, and power output (15). 


Caffeine has been shown to reduce perceived pain and exhaustion, similar to RPE used in resistance training, which may be part of the reason it improves exercise performance (15,16). 


A systematic review of 26 studies containing 33 trials total of endurance performance shows an average improvement of 2.3% ± 3.2% in performance when caffeine ingested before exercise and 4.3% ± 5.3% mean improvement in performance when caffeine ingested before and during exercise. 


It is speculated to be due to an increase in glycogen sparing during the first 15 minutes of exercise and increased muscle triglyceride use during the first 30 minutes of exercise. Doses of 3-6mg/kg seem to be effective enough to improve performance (17). 


Tolerance to caffeine can occur over time with repeated, habitual use. Research shows that this diminishing effect from repeated use occurs more in endurance training rather than resistance training. 


A good rule of thumb is to save caffeine for the more intense workouts or when it’s truly needed, rather than getting in a habit of taking it everyday. 


Aim for the minimum effective dose to get the desired effect.


 It’s important to note that individual’s responses to caffeine consumption in the research vary, and your experience with the drug might be different than another’s. 


Is it Safe? 


The FDA marks caffeine as GRAS (generally regarded as safe), with the National Institute of Health noting its safety at up to 400-500mg/day for adults. 


Some adverse side effects include insomnia, restlessness, nausea, vomiting, tachycardia, and arrhythmia, although these are generally reported at much higher doses. 


Risk of death occurs at an acute oral dose of 10-14g of pure caffeine, the equivalent of 106 cups of coffee at once (the average caffeine in an 8oz cup of coffee is 95mg). 


The idea that coffee causes dehydration has been disproven, as coffee provides similar hydrating qualities to water (18). 


It’s a good idea to avoid caffeine before bedtime in order to preserve sleep quality, as caffeine intake near sleep can affect your body’s natural internal clock, or circadian rhythm (19). 


Bottom Line 


It's important to keep in mind that the supplement industry is not regulated by the FDA, so make sure to buy from a credible source. Some supplements are verified by independent labs, such as those marked with a USP seal of approval. 


Supplementation should be just that - a supplement to your diet. A well balanced diet should be suited to fit your physiological and behavioral state.


 Focus on eating mono- and poly-unsaturated fats, a variation of protein sources, whole, nutrient dense fruits and vegetables, as well as fueling your workouts with carb sources like quinoa, oats, and sweet potato. 


For optimal function, your body needs proper macronutrients (carbs, proteins, and fats) as well as micronutrients (vitamins and minerals). Micronutrients like potassium, iron, magnesium, and yes, even salt, are all crucial to performance. So if your diet isn’t in check, fix that first and then worry about supplements. 


Andrew Malkiel, MSc






  1. “Dietary Supplements Market Size: Industry Analysis Report, 2020-2027.” Dietary Supplements Market Size | Industry Analysis Report, 2020-2027, Feb. 2020,
  2. Clinical pharmacology of the dietary supplement creatine monohydrate (Presky and Brazeau, 2001) Kreider, Richard B., Douglas S. Kalman, Jose Antonio, Tim N. Ziegenfuss, Robert Wildman, Rick Collins, Darren G. Candow, Susan M. Kleiner, Anthony L. Almada, and Hector L. Lopez.
  3. Rawson, Eric S., and Jeff S. Volek. “Effects of Creatine Supplementation and Resistance Training on Muscle Strength and Weightlifting Performance.” Journal of Strength and Conditioning Research, vol. 17, no. 4, 2003, pp. 822–831., doi:10.1519/00124278-200311000-00031.
  4. Farshidfar, Farnaz, et al. “Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.” Current Protein & Peptide Science, vol. 18, no. 12, 2017, doi:10.2174/1389203718666170606105108.
  5.  Lyoo, In Kyoon, Sujung Yoon, Tae-Suk Kim, Jaeuk Hwang, Jieun E. Kim, Wangyoun Won, Sujin Bae, and Perry F. Renshaw. A Randomized, Double-Blind Placebo-Controlled Trial of Oral Creatine Monohydrate Augmentation for Enhanced Response to a Selective Serotonin Reuptake Inhibitor in Women With Major Depressive Disorder American Journal of Psychiatry 169, no. 9 (September 2012): 937–45. 
  6.  Kondo, Douglas G., Young-Hoon Sung, Tracy L. Hellem, Kristen K. Fiedler, Xianfeng Shi, Eun-Kee Jeong, and Perry F. Renshaw. Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: A 31-phosphorus magnetic resonance spectroscopy study Journal of Affective Disorders 135, no. 1-3 (December 2011): 354–61. 
  7. Watanabe, Airi, Nobumasa Kato, and Tadafumi Kato. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation Neuroscience Research 42, no. 4 (April 2002): 279–85. 
  8.  International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine Journal of the International Society of Sports Nutrition 14, no. 1 (June 2017). 
  9.  Berryman, Claire E, et al. “Protein Intake Trends and Conformity with the Dietary Reference Intakes in the United States: Analysis of the National Health and Nutrition Examination Survey, 2001–2014.” The American Journal of Clinical Nutrition, vol. 108, no. 2, 2018, pp. 405–413., doi:10.1093/ajcn/nqy088.
  10. Morton, R.W., et al., A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. BR J Sports Med, 2018. 52(6): p.376 
  11.  Schoenfeld, B.J., A.A Aragon, and J.W. Krieger.The effect of protein timing on muscle strength and hypertrophy: a meta-analysis. J Int Soc Sports Nutr, 2013. 10 (1): p.53. J Nutr Metab. 2016;2016:9104792. Epub 2016 Oct 11.
  12. Antonio, Jose, et al. “A High Protein Diet Has No Harmful Effects: A One-Year Crossover Study in Resistance-Trained Males.” Journal of Nutrition and Metabolism, vol. 2016, 2016, pp. 1–5., doi:10.1155/2016/9104792.
  13. European Society of Cardiology. "Higher coffee consumption associated with lower risk of early death." ScienceDaily. ScienceDaily, 27 August 2017.
  14. Schipp, D., Tulinska, J., Sustrova, M. et al. Consumption of a dark roast coffee blend reduces DNA damage in humans: results from a 4-week randomised controlled study. Eur J Nutr 58, 3199–3206 (2019).
  15. Grgic, J., Mikulic, P., Schoenfeld, B.J. et al. The Influence of Caffeine Supplementation on Resistance Exercise: A Review. Sports Med 49, 17–30 (2019).
  16.  Goldstein ER, Ziegenfuss T, Kalman D, Kreider R, Campbell B, Wilborn C, Taylor L, Willoughby D, Stout J, Graves BS, Wildman R, Ivy JL, Spano M, Smith AE, Antonio J. International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr 2010;7:5.
  17. Ganio, Matthew S, et al. “Effect of Caffeine on Sport-Specific Endurance Performance: A Systematic Review.” Journal of Strength and Conditioning Research, vol. 23, no. 1, 2009, pp. 315–324., doi:10.1519/jsc.0b013e31818b979a
  18.  Killer, Sophie C., et al. “No Evidence of Dehydration with Moderate Daily Coffee Intake: A Counterbalanced Cross-Over Study in a Free-Living Population.” PLoS ONE, vol. 9, no. 1, 2014, doi:10.1371/journal.pone.0084154.
  19. Burke TM, Markwald RR, McHill AW, et al. Effects of caffeine on the human circadian clock in vivo and in vitro. Sci Transl Med 2015; 7(305): 305ra146.