The supplement industry is saturated with pre-workout supplements: C4, No-Xplode, PreJYM. I would venture to guess its a 9 figure market. Interestingly, very few of these pre-workout supplements have been thoroughly investigated in the scientific literature. However, there have been investigations into some of the individual ingredients in these supplements. In this article we are going to discuss 4 of the most popular: Arginine, Beta-Alanine, Caffeine, and BCAAs
The pre-workout ingredient Arginine (also written as L-arginine) is an amino acid that is converted into nitric oxide in the human body. It is used as a pre-workout supplement under the premise that it increases nitric oxide and thus blood flow during training.
What is Arginine
Arginine is a conditionally-essential amino acid, meaning the body is able to manufacture it, but under certain states it is unable to make enough to meet the demand for it. It is directly involved in the production of nitric oxide. Nitric oxide causes vasodilation and increases blood flow which ought to improve training performance. Additionally, arginine is one of the amino acids that makes up creatine.
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What Does the Science Say?
Interestingly, the results from L-arginine studies are equivocal. One has shown that arginine supplementation increases levels of arginine in the blood but does not increase levels of nitric oxide or muscular blood flow, nor does it enhance muscle protein synthesis (1). Yet, another shows that it increases blood volume but not strength performance (cite). More studies have shown no meaningful or significant increase in training capacity (2, 3)
Doses between 2-5 g/day are shown to be effective. If you experience paresthesia at high, bolus doses, you can take it several times per day at lower doses (i.e. 4 doses at 750-1000 mg).
Currently, the evidence suggests that L-arginine may increase circulatory blood flow, but does not consistently or meaningfully increase training performance.
Caffeine is touted as one of the most efficacious pre-workout supplements for increasing energy, focus, and training capacity. It is also thought to elicit the following: increased anaerobic running capacity, power output, adrenaline, aerobic exercise, blood glucose and fat oxidation, as well as decreased insulin sensitivity.
What is Caffeine?
Caffeine primarily works by antagonizing (essentially blocking) adenosine receptors. Adenosine normally binds to these receptors, causing drowsiness. By antagonizing these receptors, caffeine can increase alertness and combat drowsiness. Caffeine is also distributed throughout the body and interacts with receptors on the surfaces of other cells to elicit different physiological processes including the release of adrenaline and cortisol.
What Does the Science Say?
Several studies have shown that caffeine pre-workout can increase power output (4, 5, 6); however, it appears to not be related to improvements in 1 repetition maximums but in “sustain power,” e.g. 3-5 RM and Wingate. It may be due to a reduction in pain perception, and mobilization of intramuscular calcium (the stuff that lets your muscles actually contract).
Increased Aerobic capacity
There have been documented increases in aerobic capacity from caffeine supplementation (7, 8, 9). This is potentially mediated by increased free fatty acid (FFA) release; however, contradictory evidence shows that adrenaline increased FFA release, thus decreasing FFA oxidation (cite).
Dosing of caffeine is highly variable. Your genetics and habitual use of caffeine play a large role in how much is needed to elicit an effect. The more you consume on a daily basis, the more you will need to consume in order to see any training benefit. Additionally, there appears to be a “saturation” limit where you only receive an anti-fatigue benefit and no additional effects from higher levels of caffeine intake.
The recommendations for dosing are to start with 100mg and see how you tolerate it. Most studies use doses around 5mg/kg with ~3mg/kg being the point where you see ergogenic effects.
Beta-Alanine is purported to increase your training capacity by improving the body’s ability to buffer exercise-induced decreases in pH.
What is Beta-Alanine?
Beta-alanine is the beta form of the amino acid alanine (meaning the amino group is in the beta position). It is the rate limiting* precursor to a chemical called carnosine which acts as a buffer to prevent reductions in pH. In essence, Beta-alanine isn’t doing the work; it is providing your body with the ability to make more carnosine
* “Rate limiting” means it is essentially the bottleneck of the reaction. You can only make carnosine if you have Beta alanine present.
What Does the Science Say?
Beta-Alanine is a well-researched supplement with some actual evidence to support its use. However, their appears to be no real timing component and it does not necessarily have to be taken as a pre-workout
Briefly, Beta-Alanine helps you avoid “hitting the wall” a little bit longer, essentially increasing your workload by 1-2 additional reps in the 8-15 rep range (10, 11, 12). The consistent finding throughout the research is that it can increase your muscle endurance by about 2.5%. It has also been shown to improve interval-type training, where individuals have improved performance in repeated bouts of sprint intervals.
In addition to Beta-Alanine increasing muscle endurance, there have been some small improvements in fat reduction reported in the literature (13). One important facet of this finding is that the research is unable to determine if it was directly due to supplementation, or if the increased fat loss was a result of the increased work during training.
Synergies with Creatine
There have been conjectures that beta-alanine works separately and synergistically with creatine supplementation. This is based upon the notion that there are two anaerobic energy systems, the phosphagen and glycolytic systems. Creatine augments the phosphagen system, while beta-alanine augments the capacity of the glycolytic system.
As such, beta-alanine and creatine are often stacked together and sold as an excellent combination for individuals looking to increase performance in their anaerobic training. Unfortunately, there is no good evidence to show measurable and consistent synergies from stacking them (14). However, as they do have separate mechanisms and are both shown to be efficacious, it is reasonable to take both.
Although it is marketed as a pre-workout supplement, there is little evidence to support a specific time-domain. You can take it at any time and you will receive the benefit as the goal is to increase your intramuscular carnosine levels.
The typical dose for beta-alanine is 2-5g/day. There have been reports of users getting a tingling feeling when consuming large doses of beta-alanine (aka paresthesia). Splitting your daily dose into two smaller doses can alleviate this. This has been shown to be as effective as a larger, once-daily dose.
Like creatine, beta alanine has well documented benefits for increasing training capacity in certain training modalities. If you are looking for an extra few percent in your training, beta-alanine might be a useful tool.
Branched chain amino acids (BCAAs) are often sold as pre-workout supplements to improve training capacity, increase alertness, and to augment muscle protein synthesis.
What are BCAAs
BCAAs are essential amino acids (meaning our body does not create them) which contain an aliphatic (branched) side-chain. These amino acids are key players in the regulation of muscle mass and must be consumed through your diet. There are three BCAAs: leucine, isoleucine, and valine.
What Does the Science Say?
Alertness and Fatigue
Studies in humans exploring whether BCAAs improve alertness and fatigue are equivocal (cite, cite, cite, cite). It is likely that any benefit for alertness and fatigue is minimal, and a supplement like caffeine has greater and more robust effects for alertness.
There are plausible mechanisms and some evidence to suggest that BCAA supplementation prior to exercise may attenuate glycogen depletion, and enhance fatty acid oxidation (15, 16, 17). This may be due to interacting with the Krebs cycle, whereby BCAAs increase levels of Acetyl-CoA.
Muscle Protein Synthesis
The main reason people use BCAAs is to optimize muscle building, and in the land of BCAAs leucine is the main promoter of muscle protein synthesis. When we think of the science behind muscle protein synthesis we think of two proteins, mTOR and S6K.
Interestingly, leucine is able to activate the mTOR pathway independently of other growth signals, like insulin.
A large amount of research has shown that protein supplementation can activate the mTOR pathway, and it is likely that leucine is a major contributor to the anabolic capabilities of protein supplementation. For example, 5g of leucine elicits a greater muscle protein synthesis signal than 5g of a mixture of BCAAs.
From the current basis of literature, it appears that, as a pre-workout, BCAAs are not going to give you large increases in performance. It may, however, improve your muscle protein synthesis and reduce soreness. Currently, there is some debate that acute increases in muscle protein synthesis are not well correlated with increases in muscle size; nevertheless, it still may be a good marker for long-term muscle growth (18, 19).