The Five Best Pre-Workout Supplement Ingredients Backed by Science (Updated 2021)

by Elliot Reimers, M.S.(C), CISSN, CNC | Reviewed by Advisory Board

Best pre-workout supplement 2021

Best Pre-Workout Supplements 2021: 5 Ingredients for Optimal Athletic Performance

Pre-workout supplements are among the most popular sports supplements on the market. There are thousands of products to choose from in this niche, which is a gift and a curse. Some pre-workouts contain stimulants to provide energy before training, while others are stimulant-free for those who are sensitive to ingredients like caffeine and theobromine.  Unfortunately, it can be hard to decipher what products work and which are pretty much bunk (or even harmful). 

For example, many companies formulate their pre-workout products with supplement ingredients that lack scientific credibility; instead, their formulas rely on egregious doses of harsh stimulants that"feel" great the first few times you take them. But after a week or two, the "benefits" wane and the side effects take over. Moreover, quality control is often lacking in the supplement industry, leaving consumers with the onus of distinguishing truthful and untrustworthy brands.

But fear not!

As part of the R&D team at Transparent Labs, we are continually researching the most effective and safe ingredients to include in our growing lineup of pre-workouts that cater to athletes, fitness enthusiasts, and gym-goers alike. Read on to learn more about the five best pre-workout supplement ingredients backed by science as well as the ingredients you should avoid before hitting the gym.

The Five Best Pre-Workout Ingredients Backed by Science

Pre-workout supplements are a staple for many gym-goers thanks to their ergogenic (performance-enhancing) properties. In other words, taking a pre-workout before exercising can bolster strength and power, support endurance, improve focus, facilitate muscle building and enhance nitric oxide production (i.e. increase blood flow and muscle pumps).

Sounds pretty awesome, right? Well, it certainly can be if you know which pre-workout supplements are effective (and safe). After perusing the current body of scientific literature, we curated the list below of the five best pre-workout supplement ingredients to take for exercise performance.

Caffeine

Caffeine is a naturally occurring methylxanthine that stimulates the central nervous system predominately by blocking adenosine receptors and inhibiting phosphodiesterase activity [1]. In so doing, caffeine enhances focus, energy levels, and fat-oxidation ("burning") during exercise while also reducing the rate of perceived exertion [2].

More simply, taking caffeine pre-workout allows you to train harder, longer, and more effectively. Hence, caffeine anhydrous is one of the best pre-workout ingredients you can find.

By stimulating lipolysis and preserving muscle glycogen, caffeine is suggested to facilitate the use of fatty acids for energy [3]. Thus, supplementing with caffeine before exercise may favorably impact the body composition of active individuals and support weight loss.

A range of studies also show that a moderate pre-workout dose of caffeine (e.g. 200 mg of caffeine per serving) significantly improves both physical and mental performance aspects of aerobic and anaerobic exercise [4]. ("Moderate dose" meaning 2-4 mg of caffeine per kg of body weight.)

Research also suggests that caffeine has synergistic effects with L-theanine, another one of the best pre-workout ingredients that we will discuss below [5]. However, those sensitive to stimulants may fare better with caffeine-free pre-workouts.

L-Citrulline

L-Citrulline is a non-proteinogenic amino acid that was first discovered in the rind of watermelon (Citrullus lanatus). Hence, "citrulline" is an eponym of the scientific name for "watermelon." Instead of being used for protein synthesis like branched-chain amino acids (BCAAs), L-citrulline has a well-established role in the urea cycle and nitric oxide (NO) cycle. It serves as both a precursor and metabolite of L-arginine [6].

As part of the nitric oxide cycle, arginine is converted to citrulline, releasing NO and promoting better blood flow in the process. Interestingly, L-citrulline appears to be more effective than L-arginine itself for increasing NO production [7].

Essentially, citrulline acts like a reservoir of arginine and therefore, NO. As such, citrulline is arguably the best pre-workout ingredient to amplify the esteemed "muscle pump" that bodybuilders crave.

Numerous studies have also shown that taking 4 - 6 grams of L-citrulline before exercise can significantly increase oxygen uptake (VO2 max) and reduce blood lactate levels, both of which are conducive to athletic performance, recovery, and muscle cell volumization [8, 9, 10]. In contrast to citrulline malate — the citrulline salt of malic acid — pure L-citrulline is the native free-form amino acid (the most researched form of L-citrulline). However, citrulline and citrulline malate are both effective pre-workout ingredients for exercise performance and blood flow since malic acid appears to have ergogenic properties of its own [11].

Beta-Alanine

Similar to L-citrulline, beta-alanine (not to be confused with betaine anhydrous) is another non-proteinogenic amino acid. It bonds to histidine in the body, thereby creating the dipeptide carnosine. In fact, beta-alanine is the rate-limiting factor for muscle carnosine synthesis.

Carnosine is crucial in muscles for retaining optimal pH during a workout. A drop in skeletal muscle pH reduces contractile force (i.e. your muscles feel fatigued and weaker). By "soaking up" free hydrogen ions (H+), carnosine buffers muscle pH and increases your capacity to train at a high intensity [12]. Thus, beta-alanine is one of the best pre-workout ingredients for athletes and gym-goers looking to increase anaerobic and aerobic performance.

Research has demonstrated that muscle carnosine can increase as much as 58% after just four weeks, of supplementing with 2,500 mg of beta-alanine daily [13].

You may be wondering, "Wouldn't it be more effective to just take carnosine pre-workout?" Well, not really. Carnosine is rapidly hydrolyzed (broken down) into beta-alanine and histidine after ingestion. Since histidine weighs about twice as much beta-alanine, the dose of carnosine would have to be considerably greater than the recommended 2, 400 - 4,500 mg of pure beta-alanine. Normally, that wouldn't be a big deal, but high doses of histidine (from carnosine) can increase histamine production, thereby triggering an inflammatory response and various side effects like nausea and upset stomach.

Therefore, the best pre-workout supplements contain at least 2, 400 mg of beta-alanine per serving.

Creapure® Creatine Monohydrate

TL Creatine HMB

Creatine is naturally produced by the body in small amounts to help maintain the availability of cellular energy (ATP) for vital biological processes. During high-intensity workouts, however, muscles are constantly using ATP to perform work (i.e. contract). Creatine monohydrate bolsters the ATP regeneration process, and it is unequivocally effective for increasing strength and building muscle [14]. Importantly, creatine monohydrate also has an exceptional safety profile in healthy adults [15].

Moreover, creatine monohydrate has consistently been shown to improve athletic performance, especially during high-intensity training like weight lifting and running sprints.

Over time, taking creatine can boost muscle strength, increase muscle growth, and help reduce recovery time between workouts [16].

The problem is many supplement companies cut corners and use bulk-sourced creatine monohydrate that's adulterated and rife with impurities like heavy metals and organic contaminants [17]. Transparent Labs does the opposite with Creatine HMB. Every serving of Creatine HMB packs 5,000 mg of patented Creapure®, the gold-standard for creatine monohydrate quality and purity, plus 1,500 mg of synergistic hydroxymethyl butyrate (HMB) and vitamin D for enhanced muscle growth.

Note that creatine monohydrate works great as either a pre-workout supplement or post-workout supplement. You can easily add it to your favorite pre-workout supplements if it's not already in them. The key is taking creatine monohydrate consistently — 3,000 - 5,000 mg per day — to saturate muscle creatine stores.

L-Theanine

L-theanine is an amino acid found in green tea. Chemically, it is similar in structure to glutamate, glutamine, and gamma-aminobutyric acid (GABA). However, L-theanine has the advantage of being able to readily traverse the blood-brain barrier, which confers a variety of nootropic effects.

Research suggests that L-theanine is absorbed into the brain where it modulates alpha brainwave activity [18]. Thus, L-theanine helps you feel more at ease while remaining attentive. Clinical trials have also shown that patients who take L-theanine feel less anxious than those taking a placebo [19].

Arguably one of the best properties of L-theanine is its synergy with caffeine, with studies finding it can effectively extend the positive effects of caffeine in the body and attenuate the negative side effects (e.g. jitters and restlessness) [20]. Ideally, look for pre-workouts that provide a 2:1 ratio of theanine to caffeine.

Worst Pre-Workout Ingredients: Why You Should Avoid These

Now that you have an idea of what ingredients to look for in the best pre-workout supplements, let's shift gears a bit. The list below details the worst pre-workout ingredients and why you should avoid them (especially if you're an athlete).

1,3-DMAA (Dimethylamylamine)

1,3-DMAA has a similar chemical structure (and effect) as ephedrine — a popular weight-loss ingredient that was banned by the FDA in the early 2000s [21]. The use of 1,3-DMAA began as a party drug throughout Europe; eventually, 1,3-DMAA made it’s way into dietary supplements throughout the U.S. after more people became aware of its potent stimulating properties (and euphoric effects in high enough doses).

A case study from 2012 reported that two active-duty soldiers died from cardiac arrest after consuming pre-workout supplements with 1,3-DMAA [22]. Thereafter, in a similar fate as ephedrine, the FDA banned 1,3-DMAA for use in dietary supplements and companies slowly phased it out of their pre-workouts.

Despite the FDA ban of 1,3-DMAA, it's still found in “black market” pre-workout products. Some supplement labels simply hide 1,3-DMAA under the guise of “geranium extract,” which is quite misleading.  Regardless, this stimulant has no place in your pre-workout supplements.

Picamilon

Picamilon is a synthetic prodrug of gamma-aminobutyric acid (GABA) originally created by researchers in the now-dissolved Soviet Union. GABA is the chief inhibitory neurotransmitter in humans that plays a versatile role in alleviating stress and anxiety [23]. In fact, anti-anxiety medications like benzodiazepines (e.g. Xanax) typically work by modulating GABA receptors.

Picamilon is an intriguing nootropic because, unlike GABA itself, it permeates the blood-brain barrier and is broken down to niacin (vitamin B3) and GABA [24]. In turn, GABA transmission increases, and niacin relaxes blood vessels in the brain.

Sounds pretty great, right? 

While picamilon is generally a beneficial nootropic for relaxation, it produces effects that directly counteract the "kick" you want from a pre-workout. Moreover, picamilon does not meet the statutory definition of a dietary ingredient, nor is it approved for over-the-counter use by the United States Food and Drug Administration (FDA) [25]. As such, picamilon is banned for use in dietary supplements sold in the U.S. and you should be skeptical if you see it in a pre-workout formula.

Higenamine

Higenamine is a plant-derived compound that activates adrenoreceptors in the body. Much like caffeine, higenamine increases cellular levels of cyclic adenosine monophosphate (cAMP), which confers stimulatory effects and enables a stronger response to adrenaline [26].

That may sound beneficial before a workout, but a recent peer-reviewed study from Harvard University warns that supplements containing this compound should be avoided due to the unpredictable nature of it and inaccurate product labeling [27]. Many of the sports supplements that were analyzed in the study had more than twice as much higenamine as the labels claimed.

With a volatile stimulant like higenamine, the seemingly inconsequential difference between taking 100 mg instead of 50 mg could be the deciding factor for a trip to the hospital instead of the gym. Steer clear of pre-workout supplements with this ingredient.

Artificial Food Coloring

Many pre-workout powders come in a variety of colors depending on the flavor that's used. If you see ingredients like "FD&C Blue Lake 2" or "Sunset Yellow" in a pre-workout, it has artificial food coloring.

While artificial food colorings aren't necessarily "bad," their ubiquity in foods, beverages, and supplements remains controversial. A growing body of evidence suggests synthetic/artificial food coloring may be harmful in doses relevant to everyday consumption [28]. Researchers note that various synthetic food dyes increase inflammatory response and inhibit enzymes responsible for metabolizing noxious substances [29].

The simple workaround is to look for pre-workout products that use natural food coloring, like beetroot powder and spirulina, instead of synthetic dyes.

Choosing the Best Pre-Workout SupplementTL Stim-Free Pre-Workout

Pre-workout supplements are always evolving, meaning so is the hype behind them. While it's certainly exciting to try new formulas and experiment a bit, remember that effective pre-workout ingredients are few and far between. You don't need to get too fancy, and "new" ingredients aren't necessarily any better for muscle building and weight loss than those that have stood the test of time, like creatine monohydrate, caffeine, and beta-alanine.  

Also, consider that supplement brands will often “label dress” their pre-workout products by sprinkling in negligible doses of ingredients per serving. Needless to say, those products are garbage.

For optimal exercise performance and training results, stick to the basics and find a pre-workout that includes tried-and-true ergogenic ingredients in proper doses. This is why Transparent Labs BULK Pre-Workout is so dependable and highly rated — it's formulated based on science and clinical research instead of anecdotes and conjecture. For those who want a caffeine-free performance enhancer, opt for Transparent Labs Stim-Free Pre-Workout.




Elliot Reimers, M.S.(C), CISSN, CNC
Elliot Reimers, M.S.(C), CISSN, CNC

Author

Elliot holds a B.S. in Biological Sciences from the University of Minnesota, as well as being a Certified Sports Nutritionist (CISSN) and Certified Nutrition Coach (CNC). He is currently pursuing a Master's of Science in Molecular Pharmacology and Toxicology at Michigan State University. Elliot began freelance writing circa 2012 and has since written 100s of articles and several eBooks pertaining to nutritional science, dietary supplements, exercise physiology, and health/wellness. Being a “science whiz,” he has a passion for helping people understand how nutrients (and other chemicals) and exercise work on a cellular and molecular level so they can make smarter choices about what they put in, and do with, their bodies. When Elliot is not busy writing or studying, you can find him pumping iron, hiking the mountains of beautiful Colorado, or perusing nutraceutical research.



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