Citrulline is a non-essential, non-protein amino acid that forms during the urea cycle and forms ornithine when combined with carbon dioxide. Citrulline is also a critical source of endogenous (natural) arginine, as it is rapidly and efficiently converted to arginine in the vascular endothelium and other tissues.
Citrulline’s benefits have been shown to be greater than its parent compound. While arginine undergoes direct hepatic (liver) metabolism through the enzyme arginase, citrulline bypasses hepatic metabolism entirely and it is delivered straight to the bloodstream. The result is that gut absorption and plasma (blood) bioavailability studies comparing citrulline and arginine have shown two things. First, that citrulline is less readily destroyed and has greater absorption than arginine. Second, that citrulline supplementation increases arginine levels more effectively than arginine supplementation itself.
This translates to promising results. For example, animal studies show a significant increase in anaerobic performance at a 250mg/kg/day serving of citrulline, while studies in humans implicate citrulline in both aerobic and anaerobic performance increases. As a critical part of the urea cycle, citrulline’s performance benefits are thought to be a result of its role in ammonia clearance. Citrulline is implicated in reducing the oxygen cost of muscle processes, along with increasing the rate of post-exercise ATP and phosphocreatine replenishment. As ATP and phosphocreatine are the body’s ‘exercise fuel,’ this may result in citrulline delaying time to exhaustion in aerobic and anaerobic exercise.
Sometimes called the “grandfather” of dietary supplements, creatine is, along with caffeine, one of the most extensively studied dietary compounds. Certainly, it is the most well-studied ergogenic aid. Generally speaking, the extensive amount of data on creatine demonstrates that it positively contributes to dilation of the vasculature, plasma-nutrient mobilization, post-workout nitrogen retention and protein synthesis, along with dose-dependently increasing contractile force through ATP (adenosine triphosphate) provision (i.e., it helps support increased strength).
If the human body could be considered a bank account, then ATP would be the currency, and every cellular process would be like spending a little money from that account. Without making a deposit, the account runs dry (fatigue). Unfortunately, making a direct deposit to that account in the form of exogenous adenosine triphosphate is impossible, given that ATP itself is incredibly unstable. The use of supplemental creatine, however, is analogous to making a deposit in the body’s energy bank, given that creatine is eventually metabolized to ATP via several steps. In skeletal muscle, creatine is first phosphorylated into its primary derivative, known as phosphocreatine (PCr), by the muscle-specific creatine kinase, creatine kinase-MB (muscle-brain). Following the phosphorylation of creatine, phosphocreatine may then anaerobically donate a phosphate molecule to adenosine diphosphate (ADP) to form the ATP required during the initial stages of intense muscular contraction. The result is not only an increase in contractile force, but also an increase in potential type IIx (‘fast-twitch’) muscle recruitment – the type of muscle fibers which are not only traditionally associated with speed, strength, and impressive physiques, but which are also unsurprisingly the most energy-demanding fiber types. Literally speaking, creatine contributes to the building of muscle.
Both through the ATP provision just described, as well as effects on nutrient mobilization, protein-sparing, and fluid dynamics, creatine has been consistently demonstrated to increase both lean mass and muscle mass in clinical data. In the short-term, these effects are most likely the result of extra-cellular fluid retention normally associated with exogenous creatine use. In the long term, these effects are likely attributable to creatine’s collective effect on muscle metabolism. The most recent research on creatine suggests it exerts direct effects on muscle metabolism, including altering the expression of genes responsible for ribosomal assembly, attenuating the breakdown of leucine, and most famously, by expanding cell volume. Cutting through the jargon, let us just say that the amount of creatine monohydrate contained in Core FURY Xsimply works: these servings have been shown time and again to significantly increase lean body mass and muscle volume, lower fatigue, and improve performance (measured in several ways).
HydroMax® (65% Glycerol)
Glycerol is a fascinating and highly useful compound that has achieved a somewhat cult status in the fitness community – while both peer-reviewed research and anecdotal reports centered on the endurance functions of glycerol are plentiful, its bodybuilding applications are not as widely lauded. Those who do use glycerol, however, are persistent in their belief that it provides some of the most noticeable, and effective, engorging (“pump”) effects possible.
Glycerol has been well-established as a so-called, “hyperhydrating agent” because of its ability to potently and positively affect plasma (blood) osmolality. As an incredibly powerful osmotic agent, and when combined with large quantities of water, glycerol induces the intracellular retention of fluid (not the extracellular kind, you do not want) that would otherwise be renally excreted. Various research has shown that glycerol’s capacity to positively affect osmolality and expand fluid volume (an increase in total body water) has beneficial effects on performance and physiologic function.
Studies that administered glycerol before both moderate and high endurance fitness tests found that glycerol reduced increases to core temperature, caused athletes to exercise significantly longer before fatigue, reduced urinary elimination of water and increased total body water content, and, in several studies, significantly improved intramuscular water expansion. In less complex terms, this means glycerol has been demonstrated to keep your muscles hydrated, significantly increase the ever-desired, “pump effect” of muscle engorgement, and, maybe most importantly when it comes to a supplement formulation, deliver and keep more nutrients where they are needed (inside the muscle).
Until recently, however, most of these studies noted a significant drawback: the low glycerol concentration of market-available glycerol products forced researchers to test glycerol loads that were significantly higher than average use cases. Core FURY X uses HydroMax® to overcome precisely this problem.
HydroMax® is a highly-concentrated (65%) form of glycerol that offers greater water stability, and therefore potency, as compared to standard GMS (glycerol monostearate). Of particular interest to bodybuilders, HydroMax®’s greater potency translates to even greater levels of intramuscular water retention – keyword, intramuscular, and therefore no bloat – over GMS.
Overall, supplementation with HydroMax® has been shown to:
- Keep athletes hyperhydrated for extended periods of time.
- Reduce post-workout urine volume (more efficient fluid use).
- Lower heart rate and improve endurance time.
- Enhance plasma and intramuscular volume expansion.
Betaine Nitrate (as N03-T®)
Betaine (trimethylglycine) is found naturally in most living organisms. It is well known to protect non-mammalian animal life in conditions of osmotic stress (a rapid change in the amount of solute surrounding a cell), in addition to functioning as an osmolyte in mammalian (including human) tissues\. Betaine is formed in cells as an oxidation product of choline and can be obtained in the diet from foods such as spinach and beets.
Though data on betaine is limited, and recent, the available literature suggests that this compound may have effects in a number of areas. Studies on betaine using servings as little as 1.25g/day and up to 5g/day for up to 14 days have shown promising results. In one study, a 2.5g/day serving was found to enhance endurance and total repetition volume for the squat, bench press, and jump squat in in healthy-exercised trained adults. A similar study using the same serving found that betaine use increased peak power and maximum peak power, along with force and the maintenance of both force and power in healthy, exercise-trained subjects.
Perhaps more interesting, however, is a study which examined betaine’s effect on the endocrine system. This study revealed that betaine may exert an effect on several endocrine processes given the proper conditions, causing the authors to hypothesize that long(er) term betaine supplementation may increase the hypertrophic response to resistance training.
Pairing betaine with the patented nitrate (N03-T®) enhances nitric oxide production via the nitrate-nitrite pathway. Organic nitrate esters have a direct relaxant effect on vascular smooth muscles through non-nitric oxide synthase pathways, being directly converted first to nitrites and then to nitric oxide itself. (With attendant increases to guanylyl cyclase and then cyclic guanosine monophosphate (cGMP), which relax the vasculature.) Pairing both nitric oxide synthase and non-nitric oxide synthase-dependent mechanisms of actions theoretically enhances total NO production, given that rate-limiting enzymatic pathways in either mechanisms do not determine total NO production.
In an absolute sense, both inorganic and organic nitrates also possess benefits beyond a secondary NO-production pathway. Studies in athletes have demonstrated that nitrate ingestion prior to both aerobic and anaerobic exercise meaningfully increases both delay to fatigue and total work capacity – likely a consequence of nitrate’s activation in hypoxic (oxygen-deprived tissues). Nitrate effectively reduces the oxygen cost of muscular activity, making contractions more efficient.
Tyrosine is amongst a class of amino acids known as ‘non-essential’ amino acids, so called because the body can produce them endogenously, and it is therefore not essential to consume dietary tyrosine. That said, tyrosine is also what is known as a conditionally-essential amino acid; conditionally-essential because, along with glucose and ammonia, the synthesis of tyrosine additionally requires adequate levels of phenylalanine. Once synthesized, tyrosine is one of the most critical amino acids, given its prominent role as a substrate in the synthesis of the catecholamines dopamine, norepinephrine, and epinephrine, in addition to both T3 (triiodothyronine) and T4 (thyroxine) thyroid hormones.
In studies on stress modulation, tyrosine has been demonstrated to reverse stress-induced norepinephrine depletion and the depressant-behavioral effects normally associated with it. In simpler terms, tyrosine may, in certain conditions, dampen the extent to which norepinephrine is removed from the bloodstream during a stress event. In simpler terms still, tyrosine may help to mitigate the sense of depletion and fatigue felt at the end of a workout.
Tyrosine may also play important metabolic functions, mostly related to its role in synthesizing compounds which stimulate the nervous system. While not traditionally considered a sympathomimetic amine, studies which have coadministered tyrosine and stimulants demonstrate a synergistic effect. These studies suggest that tyrosine may potentiate the effects of both endogenous and supplemental norepinephrine and its mimetics (in the case of exogenous use) with respect to lipolysis, thermogenesis, and energy expenditure. Meaning that tyrosine may play a role in assisting norepinephrine to break up triglycerides and increase body heat transiently.
Choline is an essential nutrient involved in numerous metabolic pathways, including DNA regulation and repair, protein function, and metabolism. Perhaps most importantly, the critical neurotransmitter acetylcholine is produced directly from free choline via cholinergic neurons. Acetylcholine is then responsible for a number of functions itself, most crucially as the compound which induces muscular contraction, and as the neuromodulator partially responsible for modulating risk/reward, arousal, and enhancing memory.
Choline’s essential role as a substrate for acetylcholine, and therefore brain development, is well documented in animal models. These studies demonstrate that levels of free maternal choline have a direct and fundamental impact on prenatal brain development, with the enhancements or deficits lasting into adulthood. Choline’s enhancing effect is particularly prominent in the hippocampus. In humans, the hippocampus is primarily involved in the consolidation of memory (taking short, episodic memory and translating it into long-term memory) and the learning of new information. Acetylcholine is a critical component in these processes, as mentioned above, and choline may therefore play a potential role in these processes as well by providing the substrate for acetylcholine synthesis.
Tartaric acid occurs naturally in the food source, while its salt derivatives (tartrate, for example) have been used as acidulants, antioxidant synergists, buffers and sequestrants. As free base choline is rapidly destroyed in metabolism, attaching a salt to enhance absorption is necessary. The bitartrate salt addition preserves choline from being destroyed during metabolism.
Caffeine is one of the most widely consumed, and perhaps one of the most reviewed, psychoactive compounds. Its physiological effects in a range of areas have been well-documented, including exercise performance, information processing, alertness and mood enhancement, attention, and awareness, along with its anti-lipogenic and lipolytic abilities.
Most importantly to Core FURY X, caffeine has been shown to have significant effects on exercise performance, even with ingestion in servings as small 3 to 9mg/kg/bw/day (the equivalent of 2 cups of standard coffee, for a 170lb male). In endurance training, possible explanations for caffeine’s performance-enhancing effects lie in its metabolic effects on both lean and fat tissue. It is suggested that caffeine’s potent lipolytic (the breakdown of fat tissue into fatty acids) and oxidative (the actual ‘burning’ of fat) action allow the body to utilize these sources during prolonged submaximal exercise. As a consequence, muscle glycogen is spared and available for use later in the training session. Practically speaking, this means caffeine is forcing your body to preferentially use fat tissue as a fuel source, while sparing the glycogen which gives you the full-bodied look!
In short-term exercise, caffeine’sdemonstrated role in the inhibition of cyclic AMP- phosphodiesterases (PDE), adenosine receptor antagonism, and adrenoreceptor agonism come into play. These three pathways collectively stimulate lipolytic activity, boost fat metabolism, increase metabolic rate and energy expenditure, and regulate the body’s thermogenic activity. The practical results of activating these pathways are increases to the contractile force of both cardiac and skeletal muscle (harder flexion), an increase in energy expenditure (freeing up more caloric energy to be used in contraction), dilation of vasculature (better blood flow), and improvements to both nitrogen retention and skeletal muscle protein synthesis (key components to muscle building).
In Core FURY X, we have included a per-serving amount of caffeine that is neither excessive, nor arbitrary, but that instead reflects the servings used in clinical research.
Methylliberine (as Dynamine 40%) and Theacrine (as TeaCrine® 40%)
Camellia kucha is a tea plant endemic to the wild woods of Yunnan, where it grows above 1000m altitude. C. kucha has been consumed as a tea in the region for centuries, and has been found to contain two molecularly similar purine alkaloids: theacrine and, more recently, dynamine. C. kucha’s principal bioactives, theacrineand dynamine, are structurally similar to caffeine but exhibit important physiological differences – namely, that pharmacological studies in laboratory animals have demonstrated that they act on the central nervous system causing sedation at lower servings. In larger servings, however, theacrineand dynamineproduce stimulation (as an adenosine agonist). The stimulant component of theacrine was demonstrated in clinical trials using healthy, normal adults, who reported increased feelings of (subjective) psychometric enhancement.
Dynamine, while being structurally similar toteacrine, is a perfect additive agent due to its distinct pharmacology. As seen in the graph below, dynamine’s AUC (area under curve) deviates from theacrine’s in that it possesses a shorter delay to onset and duration time:
Using dynamine in addition to theacrine thus produces a dual peak stimulation effect, where the user experiences the initial increase to mood and alertness with dynamine; and then a second peak with theacrine.