Mr. Hyde is perhaps one of the most well-known stimulant-based pre-workouts. Pro Supps has also added several non-stimulant ergogenic ingredients, but some of these are under-dosed…[Skip to the Bottom Line]
Beta Alanine is a non-essential amino acid that serves as a precursor to the amino acid Carnosine, which acts as a lactic acid buffer, effectively reducing muscular fatigue. Like Creatine, Beta Alanine takes time to accumulate, but if taken over a sustained period of time, can also be an extremely effective performance enhancing supplement with a strong safety profile. One study in particular that measured the carnosine levels of sprinters found that individuals with high muscular Carnosine levels exhibited higher power output in the latter half of a 30m sprint. Various studies have shown that Beta Alanine supplementation increases muscular Carnosine, which improves physical performance. In particular, a 2012 study published in “Amino Acids” found that subjects who consumed 1.6 or 3.2 grams of Beta Alanine daily experienced significant increases in muscle carnosine in as little as two weeks, with the higher dose achieving a higher concentration of Carnosine. Mr. Hyde contains 2.5 grams of Beta Alanine, which is an above average dose (compared to similar products) and is certainly effective if consumed daily.
Creatine has the ability to rapidly produce ATP (cellular energy) to support cellular function (in this case exercise). During high intensity exercise, Creatine is used for energy which tends to spare the glycogen that would normally be used. For this reason, Creatine indirectly decreases lactic acid build up because lactic acid is a byproduct formed when glucose is burned for energy. Creatine has consistently been demonstrated to increase power output, as well as muscle size, with maximum benefit being reached at around 8 weeks of consistent supplementation. It is generally recommended to consume 5 grams per day but lower doses (around 3 grams) can still be effective if consumed over a longer period of time. Creatine comes in various forms, the most common of which is Creatine Monohydrate, which is formed by dehydrating a solution of Creatine where a single water molecule remains bound to the Creatine. Mr. Hyde contains an alternative form of Creatine known as Creatine Hydrochloride (HCl) which is created by adding Hydrochloric Acid to a solution of Creatine, forming a salt. Creatine HCl is generally claimed to be more soluble than Monohydrate, though whether that makes any difference in the long run has yet to be determined. While Creatine HCl may indeed be more water-soluble than the monohydrate form, there is no evidence to suggest it is more effective as an ergogenic aid, only theories. That being said, there is no evidence suggesting it is worse either, so it really doesn’t matter much. Unfortunately, in this case the form used is the least of our concern because the 1 gram dose present in the Mr. Hyde formula, which Pro Supps claims is an “efficacious dose”, is short of what has been shown to be effective. Those looking to gain the benefits of Creatine supplementation should consider supplementing with 2-4 grams of additional Creatine.
Leucine is an amino acid that belongs to the group known as Branched Chain Amino Acids (BCAAs). If you have ever purchased a BCAA product, you may have noticed that it contains more Leucine than the other two BCAAs (Isoleucine and Valine). The ratio is generally something along the lines of 2:1:1, but we’ve seen as much as 8:1:1 in favor of Leucine. Mr. Hyde contains only Leucine, likely because Leucine is considered the most important with regards to muscle protein synthesis (hence the heavier weight found in most BCAA supplements). Several studies have confirmed that Leucine is the most important BCAA in regards to muscle protein synthesis. It has been shown to increase protein synthesis in rats as well as humans in dozens of studies. Most recently, a 2012 study found that supplementation with 12 g of Leucine per day resulted in improved protein synthesis in elderly males consuming a low protein diet. This makes Leucine of interest to those who are on a calorie restricted diet (not getting enough protein). Leucine’s primary mechanism of action is via activation of Mammalian Target of Rapamycin (mTOR) which signals the body to synthesize protein. Leucine signals mTOR which in turn stimulates protein synthesis. Overall, efficacy has been demonstrated with 2-5 grams daily, though Mr. Hyde only contains 500mg of Leucine per serving. While there is possibly some marginal benefit at this dose, we can’t say for certain how effective it really is.
Very little is known about Agmatine, although it possesses a variety of implications. The proposed benefits include: Increased growth hormone production, anti-oxidant properties, increased Nitric Oxide (NO), and fat loss, though none of these claims have been completely substantiated. Recently, Agmatine has become quite pervasive in pre-workout supplements because of its alleged ability to inhibit Nitric Oxide Synthase (an enzyme that breaks down excess NO). However, lack of sufficient evidence makes us skeptical of this claim. In fact, Agmatine has been shown to do the opposite. A 2000 study, published in the “Journal of Brain Research”, found that Agmatine actually suppressed NO production in microglia (glial cells in the brain which mainly protect neurons). It should be noted that NO can be harmful to neurons, and the conclusion of the study was that Agmatine may support cognitive function. Furthermore, it is possible that Agmatine suppresses NO in microglia but not elsewhere. However, these findings certainly do not lend credibility to the notion that it increases NO. Further research should shed some light on the proposed benefits of Agmatine, but for now there is just not enough evidence for us to get behind it as a vasodilator (though cognitive benefits seem more likely).
Citrulline is a precursor to the amino acid Arginine, which is a precursor to Nitric Oxide (NO). Citrulline has recently gained recognition in the supplement community for its ability to increase plasma (blood) Arginine levels better than supplemental Arginine itself. A 2009 study, published in the “Journal of Free Radical Research”, found that 6 grams of Citrulline Mallate given to male cyclists before a race increased “plasma Arginine availability for NO synthesis and PMNs priming for oxidative burst without oxidative damage”. You may be wondering: How can Citrulline be more effective at increasing Arginine than Arginine itself? The problem with supplemental Arginine is that it is metabolized in the intestines and liver into other substances such as Ornithine and Urea. The intestines and liver contain relatively high levels of Arginase, the enzyme that converts Arginine to Ornithine and Urea. As a result, very little goes on to be involved with the synthesis of NO because it is being diverted. Citrulline, on the other hand, is able to bypass the liver and is metabolized into Arginine elsewhere, where not as much Arginase is present. Thus, more of the Arginine is able to convert into NO. A 2002 study, published in the “British Journal of Sports Medicine” found that Citrulline supplementation (6g/day for 15 days) significantly increased ATP production during exercise in healthy adult males. A 2011 study, the subjects of which were rats, found that supplemental Citrulline increased muscular contraction efficiency (less ATP was required for the same amount of power), in-line with the findings of the above-mentioned human study. While Citrulline has demonstrated significant ergogenic effects in animals and humans (in multiple studies), most pre-workout supplements do not use anywhere near a scientifically validated dose, and Mr. Hyde is no exception. The 500mg of L-Citrulline found in the Mr. Hyde formula cannot be considered an effective dose because no studies have ever been conducted using doses this low in humans.
Caffeine is the most widely consumed psychoactive substance in the world, and is a well-established ergogenic aid. Caffeine consumption causes an increase in Catecholamines (Adrenaline, Noradrenaline, and Dopamine), which tend to increase focus, concentration, and perceived energy while simultaneously promoting fat oxidation. However, the weight loss effects of caffeine tend to fade with prolonged use, so it does not appear as though caffeine is a long-term effective fat burner. While caffeine’s weight loss potential is negligible, it increases focus and perceived energy in most people, which generally leads to more intense workouts (thus burning more fat), and may act as a mild appetite suppressant in some.
INFINEGY (DICAFFEINE MALATE):
Dicaffeine Malate is simply a combination of Caffeine and Malic Acid. While Creative Compounds, the manufacturer of Infinergy, claims a variety of additional benefits over what can be achieved with regular caffeine, there are no scientific studies to support these claims. Malic Acid plays a role in energy production, but supplementation has never been shown to increase energy in healthy individuals, so for now we would consider Dicaffeine Malate just another form of Caffeine.
As with Dicaffeine Malate, there is no evidence to suggest that Caffeine Citrate (Caffeine combined with Citric Acid) is any more beneficial than Caffeine alone. Generally, Caffeine Citrate is about 67% Caffeine, bringing the total amount of Caffeine present in the Mr. Hyde formula upwards of 350mg, more than enough to provide the average individual with a noticeable increase in focus and perceived energy.
Pikamilon (alternatively spelled ‘Picamilon’) is formed by combining Niacin (vitamin B3) and GABA (the primary inhibitory neurotransmitter in mammals). Pikamilon is able to effectively cross the blood-brain-barrier where it is converted into GABA. Since GABA is an inhibitory neurotransmitter (as opposed to excitatory) it may produce anxiolytic effects when levels are increased beyond normal. For this reason, Pikamilon is touted as an anxiolytic. However, it has also been demonstrated to increase cerebral blood flow in animals, due to its niacin component (niacin is a vasodilator). Despite a fair amount of efficacy demonstrated in animal studies for both cerebral vasodilation and as an anxiolytic, human studies remain scarce. This is likely because there are better (pharmaceutical grade) anxiolytic compounds as well as cerebral vasodilators. As far as a direct effect on exercise capacity, there are no studies but the theoretical mechanisms of action exist.
Tyramine is a derivative of the amino acid Tyrosine, and has the ability to increase the level of the catecholamine neurotransmitters Norepinephrine, Epinephrine, and Dopamine. Tyramine is thought to act as a Monoamine Oxidase Inhibitor (MAOI), meaning it blocks the enzyme (Monoamine Oxidase) responsible for oxidizing the above mentioned neurotransmitters. The result is an elevation in levels of these neurotransmitters which generally results in increased focus, mood, and perceived energy. For this reason, it is recommended that people currently taking prescription MAOIs be careful not to consume too much dietary (or supplemental) Tyramine. While studies on Tyramine are scarce, Adrenaline and Noradrenaline induce lipolysis in humans, which may result in increased fat loss during workouts.
Hordenine (chemical name N, N-dimethyltyramine) is chemically related to the above mentioned Tyramine, and likewise, is used in dietary supplements as a fat-burner as well as for increased energy. Hordenine has been shown in animals to augment adrenaline induced muscle contraction while not directly inducing contractions itself, which indicates it works as a catecholamine (Adrenaline) reuptake inhibitor (similar to Tyramine). However, we’d like to be very clear that there is very little research published on the use of Hordenine in humans, especially as it relates to physical performance and exercise.
The primary active component of Yohimbe (Pausinystalia Yohimbe) is Yohimbine, which acts as an alpha-2 receptor antagonist, meaning it inhibits the receptor responsible for blocking lipolysis (fat burning). By blocking the action of this receptor Yohimbine essentially “leaves the gates open” for lipolysis to occur. A 2006 study showed that while there were no increases in strength, supplementation induced fat loss in athletes (soccer players). As previously stated, Yohimbine directly acts on alpha-2 receptor, but it’s fat loss capabilities may also be magnified by its ability to increase the catecholamine neurotransmitters adrenaline and noradrenaline which in turn induce lipolysis. As mentioned above, an increase in these neurotransmitters may result in increased focus and workout intensity.
Rauwolscine (also known as alpha-yohimbine) is what is known as a ‘stereoisomer’ of yohimbine, meaning it is chemically similar in structure. Because of this similarity, Rauwolscine produces similar effects, although perhaps to a milder degree. It is common for supplement companies to include both Rauwolscine and Yohimbine together since both compounds are naturally present in certain plants.
THE BOTTOM LINE:
Mr. Hyde contains several standard pre-workout ingredients (Beta-Alanine, Citrulline, Creatine, etc.) as well as several stimulants (including a hefty dose of Caffeine) aimed at increasing focus and intensity via increasing the action of certain neurotransmitters (Adrenaline, Noradrenaline, Dopamine). These stimulants may very well result in a sensation of focus and perceived energy, leading to more intense (or longer) workouts. While the level of Beta-Alanine (2.5g) is certainly adequate, the amount of Citrulline (500mg), Leucine(500mg), and Creatine (1g) fall short of what can be considered truly effective in the eyes of science.
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