The vast majority of gym attendants use some sort of pre-workout to boost their performance and enhance their workouts. Whether its in the form of a pre-workout supplement, a caffeine pill, or an energy drink. The text below contains detailed information on why each product is relevant and included in pre-workout supplements.

 

Caffeine

(Guaranine)

Of all recorded products, caffeine was in every single product unless identified as a ‘caffeine free’ supplement. Caffeine stimulates the central nervous system (CNS), heart and muscles, as well as controlling blood pressure, and epinephrine release. Because of these effects on the body caffeine is used for mental alertness and improving reaction time. Caffeine is also beneficial for treating migraines, tension headaches, lowering the risk and preventing type 2 diabetes. Caffeine is possibly effective for treating ADHD, asthma, type 1 diabetes, obesity, acute pain and improving memory but more evidence is needed. Because of caffeines ability to improve mental alertness and reaction time, caffeine is commonly used as a stimulant for athletes.

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One of the more common known facts of caffeine is its ability to increase alertness and performance, which has been proven to be true again and again over the years in trials and studies. This includes one very effective double-blind trial directed by Ardith Zwyghuizen-Doorenbos, Timothy Roehrs, Lauren Lipschutz, Victoria Timms and Thomas Roth in March of 1990. This trial consisted of twenty-four males in good health consuming 250mg of caffeine at hours 900 and 1300 for two days, the third day consisting of a placebo intake and the assessment of sleep latency (alertness), divided attention and auditory vigilance. The results showed that caffeine increased sleep latency and auditory vigilance compared to the placebo group. Zwyghuizen-Doorenbos et al. noted that “tolerance to the effects of caffeine on sleep latency developed over four administrations” (1990, para. 1). 

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Caffeine acts as a diuretic, increasing urination and possibly causing dehydration, but regular consumption lessens this effect on the body. Caffeine can also potentially raise blood pressure but with regular consumption of the substance the effect lessens. Caffeine has been shown to cause insomnia, stomach irritation, nausea, increased heart rate, increased respiration, restlessness and nervousness. Caffeine may worsen patients suffering from anxiety and bi-polar. 

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Caffeine is natural in many plants including coffee beans, tea leaves, kola nuts, cacao pods, and is common in soft drinks, energy drinks, energy gums, and pain relief, cold relief and over-the-counter alertness medications. 

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Supplementing caffeine is likely safe in doses up to 400mg per day. Larger doses might cause headaches, anxiety, agitation and chest pain. If the consumption is high enough you can experience harm to the body such as an irregular heartbeat, and possibly lead to death. A caffeine level in the body past a urine concentration over 15mcg/mL is prohibited by the National Collegiate Athletic Association (NCAA). 15mcg/mL is the equivalent to consuming around 800mg of caffeine.

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Why is this beneficial in pre-workout: Caffeine has been identified to improve alertness and sleep latency, but its effects have been shown to potentially diminish with regular consumption.

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Beta-Alanine

(β-alanine)

Beta-Alanine is a non-essential amino acid that is not used in your body to synthesize proteins. It is used to improve athletic performance, leading to the gain of strength and lean muscle mass. Athletic performance is improved by reducing your time-to-exhastion (TTE), resulting in an increase in endurance and performance in training. Beta-alanine has this ability because of what it produces.

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With the help of histidine, beta-alanine produces carnosine. Beta-Alanine and histidine are two of carnosine’s main ingredients. Carnosine is stored in skeletal muscles and reduces lactic acid accumulation in your muscles when training, resulting in the muscles ability to perform for longer periods of time before fatigue sets in. Histidine levels are high compared to your beta-alanine levels naturally, reducing carnosine potential. An increase in beta-alanine levels will result in an increase in carnosine levels in your body, leading to lower fatigue and more energy in your workouts. The downside of increasing beta-alanine in your body is that taurine levels may decrease as beta-alanine and taurine compete against each other for muscle absorption (taurine’s benefits discussed later).

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During high intensity exercise such as anaerobic activity or high intensity weight training, anaerobic glycolysis is the dominant source of energy. Through the glycolysis process lactic acid is produced. Lactic acid then dissociates producing hydrogen ions increasing the pH of the muscles. The lowest pH accumulation is known to occur around four minutes into a high-intensity anaerobic exercise (Osnes and Harmansen, 1972). This accumulation of hydrogen ions is also referred to as acidosis and leads to less exertion in training and higher fatigue rates. Acidosis also “disrupts the resynthesis of phosphorylcreatine […], inhibit glycolysis […], and disrupt the functioning of the muscle contractile machinery directly” (Hobson et al., 2012, para. 3). Carnosine has been shown to reduce the acidity in muscles, by regulating hydrogen ions, limiting fatigue.

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With these qualities, beta-alanine has been used to better athletic performance. Not all evidence shows that supplementing beta-alanine has a benefit to increasing strength, athletic performance and the gain of lean mass directly, but one meta-analysis written by Hobson, Saunders, Ball, Harris, and Sale, identify fifteen trial manuscripts on the subject of beta-alanine and athletic performance that are relevant to our topic of discussion. These fifteen trials consisted of a total of 57 effect sizes calculated, and included males (72.5% of total amount of participants in the 15 trials), females (20.3%) and elderly males and females (55–92 years of age, 7.2%) either in a supplementing group or placebo group doing some form of exercise. The daily dosage of beta-alanine ranged from 2.4–6.4g. The total dosage of beta-alanine ranged from 108.8–448g. 

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Out of all fifteen studies, twelve studies saw an increase in the ability or effect or effects being recorded. The overall effect size of the beta-alanine groups was 0.374, whereas the overall effect size of the placebo groups was 0.108.  When comparing exercise performance and exercise capacity, beta-alanine had a larger effect on exercise capacity than exercise performance. The averages for trials that tested exercise performance were 0.150 in the placebo group and 0.326 in the beta-alanine group, where trials testing for exercise capacity performance had an average of 0.156 in the placebo group and 0.591 in the beta alanine group. It should be known that beta-alanine does not improve performance-based measures, but instead improves exercise capacity — the maximum amount of physical exertion that a patient can sustain. The authors note in the literature that, “Analysis indicates that supplementation with a total of 179g of β-alanine (the median dose across all studies) would result in a median improvement of 2.85% compared with a placebo. Assuming a linear relationship between running speed and percentage effect, if this improvement was extrapolated and applied to a sporting event lasting around 4 min, such as a 1500 m run, performance time would have been improved by ~ 6 s. This improvement would be sufficient to move the last place finalist in the mens 1500 m at the Beijing 2008 Olympic games to a bronze medal position" (Hobson et al., 2012, para. 22).

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In regards to exercise duration, the meta-analysis broke the trials down into three sections; under 60 seconds, 60–240 seconds, and over 240 seconds. Hobson et al. concluded that “for the 14 measures lasting <60 s there was no significant difference between the effect sizes in BA and Pla groups”, meaning that there was no distinct difference between the placebo and beta-alanine groups when practicing exercises that lasted under 60 seconds. The nine measures lasting between 60 and 240 seconds saw a significant difference between the beta-alanine groups (0.665) and the placebo groups (0.121). The same outcome occurred with trials consisting over 240 seconds as the trials being tested in the range between 60 and 240 seconds, the beta-alanine groups being 0.665 and the placebo group being 0.121. 

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With the increase in time-to-fatigue and athletic performance, strength gain and muscle mass will benefit in the long run.

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Doses of beta-alanine supplementation are listed at around 2.4–6.4g daily for athletic performance. when taking too much beta-alanine you may experience paraesthesia, a skin sensation that can be described as ‘tingling’ or ‘strong pins and needles’. Paraesthesia is usually felt in the face, neck, forearms and the back of hands. There is no evidence that paraesthesia is harmful.

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Why is this beneficial in pre-workout: Beta-alanine increases your time-to-fatigue, resulting in an increase in energy during training leading to more training volume per workout, but has not been seen to be effective in anaerobic exercise lasting under 60 seconds.

 

Creatine

(Creatine Monohydrate)

Creatine monohydrate is one of the most research-backed supplements on the market today, and for good reason. Create can bring many benefits to the table including:

• An increase in overall strength and power.

• Reduced recovery time between workouts and sets.

• Muscle morphology when regularly practicing heavy resistance training.

• Improved neuromuscular performance.

• Improved reaction time.

• Improved muscle endurance.

• An increase in lean muscle mass. 

Synthesis occurs in the liver, kidneys, and the pancreas. Many have agreed on creatine’s mechanisms, but there is some controversy on the topic of how beneficial it is to aerobic exercise.

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ATP (adenosine triphosphate) is the source of energy inside your body. When working out ATP is the reason for your muscle contractions. Creatine promotes a faster regeneration of ATP between training sessions by combining ADP (adenosine diphosphate) to generate more ATP. Because of this process your body’s needed recovery time is decreased and you will be able to train harder and for longer periods of time before fatigue sets in compared to if you were not supplementing creatine. You will also be able to add extra sessions now that your recovery time has shortened, bringing fourth more volume per week.

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A paper published by Cooper et al. broke down many studies on the subject of creatine and exercise/sports performance, and listed multiple studies of creatine in regards to physical performance, literature included was from 1999 (1), 2000 (2), 2000 (3), 2001 (4), 2003 (5), 2003 (6), 2003 (7), 2004 (8), and 2010 (9). The literature from 1, 2, 4, 5 , 6, 7, and 8 all saw benefits in athletic performance when supplementing creatine compared athletic performance increases with no supplementation. Studies 3 and 9 found no effects or benefits from supplementing creatine, although study 3 did not identify if creatine supplementation was concurrent with resistance training. For study 9, Cooper et al. stated that, “These conflicting results can be explained by the possibility that the supplemented groups were formed by a greater amount of non-responders or even because creatine supplementation was administered on training days only” (2012, para. 8). The subjects only trained three times a week. 

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With the evidence provided over the years most scientists agree that creatine supplemented daily with resistance training will result in an increase in strength and hypertrophy in lifters and trainers. Now that scientists have come to this conclusion more recent literature has provided more information on creatine and its performance enhancing capabilities. a 2007 paper written by Hespel et al., a 2008 study written by Safdar et al., and a 2010 study written by Hickner et al provided evidence that creatine’s mechanics may be due to satellite cell proliferation, myogenic transcription factors, and insulin-like growth factor-1 signalling. Another 2010 study, this one written by Saremi et al saw a change in myogenic transcription factors during creatine supplementation and concurrent resistance training. Saremi et al found levels of the muscle growth inhibitor myostatin were lowered in the creatine group compared to the placebo group.

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Creatine is for those who frequently do high intensity training including hypertrophy, weightlifting, powerlifting, and stop-and-go sports such as football, hockey and basketball to name a few. Creatine provides benefits to neuromuscular performance for short duration exercises. A meta-analysis from 2003 written by J. David Branch saw an overall creatine supplementation effect size of 0.22–0.26 for high intensity exercise lasting under 30 seconds. During the trials the creatine supplementation group saw an increase range between 6.8% to 8.2% whereas the placebo group saw an increase of only 3.7% to 4.9%. One individual paper included in the meta-analysis included one test of repititions. The creatine supplementation group found an increase in the repitions of 38.2% to 52.6%, where the placebo group resulted in a 15.6% to 30.2% increase. Another piece of literature was tested on weight lifted, with an 20.8-28.6% increase observed for the supplementation group and a 10.7–16.1% increase for the placebo group observed. Cooper et al states that “Other measures improved by creatine with a mean ES [effect size] greater than 0 were from the amount of work accomplished, weight lifted, time, force production, cycle ergometer revolutions/min and power (2012, para. 11).” 

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When looking at anaerobic exercise lasting longer than 30s (30–150s), Branch observed an 3.4–6.4% improvement from the creatine supplementation group, and -2.6% to -1.4% improvment in the placebo group. To draw a conclusion, anaerobic exercise lasting under 30 seconds appears to receive a larger affect when supplementing creatine compared to anaerobic exercise lasting 30–150 seconds. It is important to know that anaerobic exercise lasting 30 seconds primarily uses the ATP-phosphocreatine energy system, whereas longer anaerobic exercise lasting closer to 150 seconds consists of anaerobic glycolysis energy system being the main energy system.

Those who practice a more aerobic-type of exercising such as long distance running, cycling and swimming are not going to see as good of results when supplementing creatine as “it appears that the effects of creatine diminish as the length of time spent exercising increases” (Cooper et al., 2012, para. 1), but there are still benefits that come to aerobic trainers. The oxidative phosphorylation energy system is most dominant during aerobic training. It is known that as the time of exercise continues, the performance effects of creatine diminish but creatine has been seen in trials causing a change in substrate utilization, resulting to a possible increase in steady state endurance performance, a decrease in blood lactate accumulation and an increase in lactate threshold. To these seen improvements there is also literature to go the other way. Graef et al. examined the effects of creatine during high intensity interval training (HIIT) and noticed a greater ventilatory threshold, but both the creatine supplementation group and the placebo group had the same amount of oxygen consumption. Another study by Thompson et al. saw no effects of creatine supplementation on aerobic performance in female swimmers. When analyzing this paper Cooper et al. notes “In addition of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization.” (2012, para. 20) Thompson et al also saw no effects on anaerobic performance.

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With all the benefits that come with supplementing creatine there are also issues that may arise in the body. These issues include possible liver damage, kidney stones, kidney damage and digestive issues. Although there are some negative aspects, the ISSN (International Society of Sports Nutrition) labels creatine as an extremely safe supplement, and one of the most beneficial sports supplements available.

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The universal known dosage is 5g daily, but some sources preach to consume larger quantities to attain full muscle saturation quicker (as taking creatine will need consistent supplementation for a few weeks until its effect begins to emerge).  Once introduced to the body, creatine needs around 7 days to show results in the body if practicing a loading phase of 20g/day. If only consuming 5g a day at the beginning of consumption it might take as long as three to four weeks. Creatine and last for as long as 4–6 weeks without daily intake, and could last even longer if consuming many foods high in creatine. Although most lifters consume ~5g of creatine daily, Cooper, Naclerio, Allgrove and Jimenez note that, “More recent research suggests that creatine supplementation in amounts of 0.1g/kg of bodyweight combined with resistance training improves training adaptations at a cellular and sub-cellular level.” (2012, para. 1). 

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Creatine is mainly found in meat, so a vegetarian diet may result in lower creatine levels. The average omnivorous diet contains about 1g of creatine a day. 95% of creatine storage is in skeletal muscles. The other 5% of creatine in the body is distributed in the brain, liver, kidneys, and testes. When taking creatine with a meal high in carbs or protein absorption might slightly be increased due to the spike in insulin.

 

Why is this beneficial in pre-workout: Creatine promotes faster regeneration of ATP, lowering recovery in and out of the gym resulting in an increase in strength and hypertrophy.

 

Citrulline

(Citrulline Malate, L-Citrulline, L-Citrulina)

 

L-Citrulline is a non-essential amino acid that vasodialates (widens) blood vessels, allowing for an increase flow of nutrients and oxygen in the body, as well as the removal of waste and toxins in the body. Because of this vasodialation, citrulline is commonly used for improving and increasing athletic performance, endurance and recovery. Citrulline is also used to treat heart failure, high blood pressure, cardiovascular problems. Citrulline may be a beneficial treatment for sickle cell disease, a lysinuriyc protein intolerance, muscular dystrophy, and diabetes, but more evidence is needed.

 

In the body L-Citrulline is turned into another amino acids called L-arginine, as well as a chemical called nitric oxide. Data shows that taking a citrulline supplement will increase arginine levels more than an arginine supplement alone. Citrulline is also better absorbed than arginine.

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One study written by Wax, Kavazis, Weldon, and Sperlak observed citrulline in regards to exercise performance, blood lactate, heart rate and blood pressure in a randomized, counterbalanced, double-blind trial. Twelve advanced resistance training athletes performed 5 sets of 60% of their one-rep max till failure on leg press, hack squat, and leg extension machine. It was reported that the citrulline supplementation group (8g) performed significantly higher numbers of repetitions in all three exercises than the placebo group. No differences in blood pressure were recognized between the two groups.

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There are mixed findings about if exercise and citrulline supplementation together result in higher or lower heart rate. The study above reported that "Blood lactate and heart rate were significantly increased (p < 0.05) after exercise compared with before exercise but were not significantly different between citrulline malate and PL [placebo group]" (Wax et al., 2015, para. 1). Another piece of literature written by Cunniffe et al. found different results. They observed a higher heart rate in the citrulline group compared to their placebo group.

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Cunniffe et al. studied citrulline's role in time-to-exhaustion (TTE) and acid-base balance during high intensity cycling in a double-blind, placebo controlled, crossover study. The trials consisted of ten trained males practicing ten 15 second cycle sprints with thirty second rest intervals. Following this was a time-to-exhaustion cycle test after five minutes of rest. They saw no results in performance variables such as time-to-exhaustion, peak power, mean power, subjective rating of perceived exertion, or acid-base balance measures. One reason behind their findings is that citrulline has been proven to have greater effects with chronic supplementation compared to acute supplementation. Individuals were only given their citrulline or placebo intake that day an hour prior to their training and testing. Patients were only tested one a week for a span of three weeks. The citrulline group did experience an increase in plasma concentration of ornithine and glutamine.  Even with acute supplementation of citrulline there are some benefits still.

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Taking L-citrulline does not increase muscle size and strength directly, but with its capabilities of improving performance in lifters and increase in muscle size and strength will be a possibility. Citrulline has been shown to have a larger effect in chronic supplementation rather than acute supplementation. 

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There are very few foods that contain high levels of citrulline. One of the most know food to contain high amounts of citrulline is watermelon, as well as other fruits and vegetables. 

 

Dosing of L-citrulline supplementation include: 6000–8000 miligrams daily pre workout (about an hour before) for athletic performance, and reduced fatigue. It is important to take note that “1.76g of citrulline malate is needed to about 1g of citrulline” (Patel, 2021, para. 5). Some rare side effect of taking L-citrulline include: upset stomach, heartburn, swelling, changes in urination, and coughing.

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Why is this beneficial in pre-workout: Citrulline vasodialates blood vessels allowing more transportation of nutrients and oxygen to the muscles quicker, as well as the removal of toxins.

 

Arginine

(L-Arginine)

When ingested into the body L-arginine is converted into L-citrulline and nitric oxide through the process of Citrullination in the intestines. Citrulline later runs into the kidneys and converts back into arginine. Arginine has the same reaction on the body as citrulline does. Why people choose to consume citrulline over arginine are because of two reasons:

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1. it has been shown that citrulline is more effective at vasodilation than arginine.

2. Supplementing arginine has been shown to cause more common irritations and issues in the body.

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Foods high in arginine include read meat, poultry, fish, dairy products, and nuts. When ingested as a a supplement, arginine has been seen to cause abdominal pain, bloating, worsening of asthma and lower blood pressure. Dosage of arginine is listed around 8g/day.

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Why is this beneficial in pre-workout: Arginine provides nitric oxide and citrulline malate, vasodialating blood vessels allowing faster transportation of oxygen and nutrients to muscles, as well as removing toxins faster.

 

Tyrosine

(L-Tyrosine)

Tyrosine is a non-essential amino acid that is mentally beneficial when in stressful times. Naturally produced from phenylalanine, tyrosine is present in all tissues of the human body and assists in the adrenal, thyroid and pituitary glands to develop and regulate hormones.

Tyrosine assists in the production of:

• dopamine — a type of neurotransmitter which regulates your pleasure centres and is plays an important role in memory and motor mechanics.

• Epinephrine — also known as adrenaline.

• Norepinephrine — a chemical in your body which acts as both a neurotransmitter and a stress hormone.

• adrenaline and noradrenaline — oversee fight-or-flight responses.

• Thyroid hormones — oversees metabolism regulation.

• Melanin — A pigment in your skin, hair and eyes responsible for your colour. The more melanin inside your cells, the darker your skin.

Tyrosine has been seen restricting some symptoms of Phenylketonuria (PKU), a rare genetic condition, and potentially act as an antidepressant, but more evidence is needed.

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Tyrosine is important because of all the hormones and substances it controls and regulates. Supplementation of tyrosine can elevate mood as well with its ability to increase dopamine, adrenaline or noradrenaline levels.

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It has been thought that tyrosine can improve mental performance in stressful environments, and that stress decreases neurotransmitter levels, more importantly, epinephrine and norepinephrine (stress neurotransmitters). reducing your memory, attention and reasoning. However this may sound reliable, many pieces of literature have disagreed with this statement, including one paper from May of 2007 (Young) and a meta analysis published in 2015 (Attipoe et al.).

 

Supplementing tyrosine has been preached to help individuals stay alert when sleep deprived. One double-blind trials by Neri et al.  analyzed the effects of tyrosine when awake for over 24 hours. Neri et al. states that the tyrosine supplementation group (comsuming 150mg kg^-1) saw a significant benefit on the psychomotor task given as well as the vigilance tasks given compared to the placebo group. Neri et al. states that effects of tyrosine lasted for three hours , and that the dosage of tyrosine as quite gentle.

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Tyrosine is found in cheeses and diary products, soy products, nuts and seeds, some fruits, and most foods containing high levels of protein including chicken and fish.Typical dosage is around 150mg per day. Taking vitamin B6, vitamin B9, and copper may aid in the intake of tyrosine.

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With all the benefits tyrosine brings to the table, there may also be some side effects. Individuals with hyperthyroidism, graves disease or individuals prone to migraines should possibly avoid tyrosine supplementation. Tyrosine can cause an upset stomach. People who are being treated with the following medications: Monoamine Oxidase Inhibitors (MAOIs), Levodopa (L-dopa), or Thyroid hormones should not take added tyrosine.

 

Why is this beneficial in pre-workout: Tyrosine controls many hormones in the body, controlling your mood and holding the ability to stay awake when sleep deprived.

 

Taurine

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Taurine is one of the most abundant natural occurring amino acids which is important for overall health in the body. Taurine

• Stimulates metabolism and digestion.

• Supports the nervous system.

• Promotes heathy metabolism and digestive system.

• Protects against neurological conditions and diabetes.

• Regulates calcium levels.

• Assists liver with bile salt development.

• Balances electrolytes.

• Protects brain and maintains long term memory.

• Protects eyes from retinal degeneration. 

 

Early research also shows that taurine may provide protection to immune systems. Taurine also provides protection for many organs in the body. Low levels of taurine have been linked to cardiomyopathy, a condition where the heart works harder than it should, which can lead to congestive heart failure. Reduced amounts of taurine have been shown to contribute to glaucoma, and diabetic retinopathy. Taurine has also been linked to alleviating symptoms of some forms of brain injuries or defects.

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Taurine protects against muscle damage and maintains muscle function. Early research shows that taurine may play a role in muscular dystrophy. A paper written by Spriet et al. states that, "There is clear evidence that a normal taurine level is important for the normal functioning of skeletal muscle. Taurine is believed to be involved in many cellular functions, but in skeletal muscle its main roles are to facilitate Ca2+ dependent excitation–contraction processes, contribute to the regulation of cellular volume, and aid in antioxidant defence from stress responses."

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Taurine is naturally found in meat and fish. A deficit in taurine can lead to developmental disorders, kidney disfunction, damage to eye tissues, cardiomyopathy, which may increase the risk of heart failure. 

 

Why is this beneficial in pre-workout: taurine protects agains muscle damage and maintains muscle function, as well as proving numerous health benefits.

 

Theanine

(L-Theanine)

Theanine is an amino acid not produced in the body although it is not essential for humans. L-Theanine improves mental focus and performance, relaxation, and sleep quality. Theanine also promotes weight loss, boosts your immune system, reduces blood pressure as it reduces stress and an increase in relaxation, as well as supports certain drugs for cancer.

 

Attention and reaction times are also improved with theanine supplementation. Cognitive Performance [Study]

Because of theanine’s affect on the brain chemicals serotonin and dopamine, it is known to give people the ability relax before bed, allowing to get to sleep quicker and sleep deeper. supplementing theanine reduces your resting heart rate as well, resulting in a more relaxed feeling.

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Weight loss has been connected to theanine, more specifically green tea, as green tea contains what is known as a umami flavor. Umami flavours reduce appetite, helping with weight loss.

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Naturally in green tea, black tea, and certain types of muschrooms. An overdose of L-theanine is highly unlikely and is usually available in 200mg tablets. The FDA has classified as “generally recognized as safe”. There are some exceptions to this statement. Theanine May interact with some medications including medication used to treat high blood pressure and ADHD.

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Why is this beneficial in pre-workout: Theanine provides a relaxed can focused state of mind when training, as well as reducing appetite leading to weight loss.

 

Vitamin B3

(Niacin)

Vitamin B3, otherwise known as Niacin is known to improve cholesterol levels

Niacin has also been known to imporve HDL cholesterol levels and lower triglycerides as well as LDL cholesterol. Because of these factors, vitamin B3 can be included in a prescription for statins and cholesterol control.

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Mechanics that require proper niacin levels include:

• The tryptophan-kyneurenic acid pathway - 

• The poly (ADP-ribose) polymerase (PARP) pathway - Poly (ADP-ribose and polymerase (PARP) are two enzymes which catalyze and transfer ADP-ribose to target proteins.

• The genetic consequences of niacin deficiency - A severe deficiency in the vitamin can lead to dermatitis, dementia, pellagra, and even possibly death

• The mitochondrial ATP generation related abnormality - Without Sufficient Vitamin B3, your body's ATP potential is limited.

• BDNF-TRKB Axis abnormalities - Brain-Derived Neurotrophic Factor. provided 'information' instruction for construction of a protein found in the brain and spinal cord. Signals through the Tromomyosin receptor kinase B

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Vitamin B3 also has relations to nicotinamide adenine dinucleotide (NAD) function. NAD serves for three major function in the body: NAD is an essential coenzymes in redox reactions. on important redox reaction they take part in is energy metabolism. NAD is also a signalling molecule and a substrate for enzymes regulating cellular energy metabolism and stress responses. Garten describes this process: "Sirtuins are NAD-dependent enzymes that, together with AMPK [AMP kinase - enhances glucose transportation and fatty acid oxidation], activate the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) during prolonged exercise, which leads to enhanced mitochondrial biogenesis in skeletal muscle and gearing of whole-body energy metabolism towards energy production" (2020, para. 6). NAD lastly assists in the protection against oxidative stress. Vitamin B3 refuels depleted NAD to meet the increased stress on the body when exercising.

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Niacin occurs naturally in meat, poultry, fish, eggs, greens, and fortified foods. side effects of niacin include, flushing (discussed below), upset stomach and diarrhea. The recommended doses of Niacin are between 14–18mg a day for an adult.

 

If supplementing vitamin B3, food intake with supplementation can prevent an upset stomach. If redness and warmth in the face and neck (flushing) occur after supplementation, takin one aspirin tablet along with the dose can reduce that. Avoiding alcohol and spicy foods can also reduce the chance of flushing from occurring. A niacin deficiency can result in the development of diarrhea, dermatitis, dementia, pellagra, and death. The higher the deficiency the worse the symptoms. High doses of Vitamin B3 can lead to risks such as liver damage, stomach ulcers, muscle damage, low blood pressure and other cardiac changes. The maximum daily intake of Niacin is 35mg, anything past this will put u at risk for these side effects. Ones with liver and kidney diseases, diabetes, high blood pressure or cardiovascular problems should be cautious with vitamin B3 supplementation. Vitamin B3 can interact with drugs for diabetes, blood thinners, anticonvulsants, blood pressure, thyroid hormones antibiotics and antioxidants.

 

Why is this beneficial in pre-workout: Provides assistance to many mechanisms in the body, including NAD function, ATP function, cholesterol levels, and prevention of many mental disorders.

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Vitamin B6

(Pyridoxine, pyridoxal, pyridoxamine, PLP, PMP)

Vitamin B6 is a water soluble vitamin which is involved in over 100 enzyme reactions in the body. It is important for:

• Protein, fat and carbohydrate metabolism.

• The creation of haemoglobin in red blood cells.

• Development of neurotransmitters.

• Regulation of the amino acid homocysteine. 

• Gluconeogenesis and glycogenolysis.

• Immune function.

• the conversion of tryptophan into niacin 

Vitamin B6 may also help treat nausea during pregnancies, can prevent and may also be able to treat Anemia and age-related macular degeneration, reduce the potential for heart disease, decreasing inflammation in rheumatoid arthritis,  and decreasing the risk of Alzheimers disease (evidence is inconclusive). Vitamin B6 must be attained through foods as the body cannot produce vitamin B6 alone.

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Vitamin B6 coenzymes function in the metabolism of protein carbohydrates and fats. Vitamin B6 functions as a coenzyme for glycogen phosphorylase, an enzyme the directs the release of glucose stored in muscle as glycogen. Vitamin B6 coenzymes play a crucial role in metabolizing amino acids, participating in reactions which allow a cell to synthesize the amino acid.

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With vitamin B6’s assist in the development of neurotransmitters, specifically neurotransmitters that regulatre emotions such as dopamine, serotonin and gamma-aminobutyric acid (GABA), it can possibly reduce symptoms of depression, improve mood. High homocysteine levels have been linked to mental issues and depression. An increase in vitamin B6 increases the regulation and lowering of homocysteine levels, improving mood and mental ability.

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Foods rich in vitamin B6 include fish, beef, poultry, organ meats, salmon, tuna, fortified cereals, bananas and potatoes. The recommended daily amount of vitamin B6 is 1.3–1.7mg for adults. A deficiency in vitamin B6 is rare. Too much vitamin B6 intake a day can lead to vitamin B6 toxicity and nerve damage. An intake of 1000mg or more has the potential to cause pain or numbness in the hands or feet and nerve damage. although 1000mg is significantly over the daily amount recommended and a challenge to consume that much in a day, these side effects have also been shown in some cases with just as little as 300–400mg a day. 

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Why is this beneficial in pre-workout: Vitamin B6 plays an important role in protein, carb and fat metabolism, and neurotransmitter development and regulation.

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Vitamin B9

(Folate, Folic Acid)

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Folate otherwise known as vitamin B9 has many functions in the body. Folate assists with the central nervous system, the formation of blood cells, the develop and repair of genetic material, cell division, and is vital in prenatal health. Folate also helps in reducing the risk of depression, as depression has been linked to low levels of folate and supplementing folate can make depression medication more effective. Folate protects against anemia (folate deficiency anemia). Half of folic acid is absorbed in the upper portion of the small intestine and the liver stores the largest portion of B9. 

 

Vitamin B9 acts as a coenzyme for the synthesis of methionine. Methionine regulates immune function, digestive function and metabolic processes. B9 also acts as a coenzyme for tetrahydroforic acid, which assists in the metabolism of proteins. Low levels of folate will result in low amino acid metabolism.

 

Folate is a factor in DNA synthesis and RNA synthesis. Low levels of Folate will result in low RNA synthesis and impaired DNA synthesis, leading to inadequate red blood cell production, leading to metabolic anemia, fatigue, and weakness.

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Vitamin B9, along with other B vitamins 6 and 12, are important vitamins to keep in check because they play a role in the conversion of creatine into phosphocreatine. Phosphocreatine is what acts as a temporary energy buffer.

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Vitamin B9 might possibly be able to lengthen time-to-exhaustion in athletes  but more evidence is needed before a conclusion can be made.

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Folic acid is the synthetic version of folate, which is most common in manufactured foods such as fortified cereals, pastas, bread, cereals, and vitamins. The body absorbs folate better through vitamins and fortified foods that foods naturally containing folate. Among the fortified foods, folate is naturally in beef liver, spinach, asparagus, broccoli, green peas, kidney peas, lettuce, avocado, bananas, grape fruit, and oranges. Although folate deficiencies are rare, symptoms include depression, fatigue, weakness, issues with concentration, headache, heart palpitations, changes in colour of hair, skin and fingernails, and sores on the tongue and inside of mouth. People with an increased chance of folate deficiency are pregnant women, people with achohol use disorders, people with conditions that affect nutrient absorption, and people with MTHFR polymorphism. It is recommended to supplement folate if you are pregnant or planning to be, as folate is crucial for fetus development. An upset stomach can be the result of too much folate, but there are no serious side effects for ingesting too much folate as it is water soluble and passed through urine. 

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Why is this beneficial in pre-workout: Vitamin B9 assists in multiple processes in the body as well as the synthesis of many substances. Vitamin B9 also provides an energy boost.

 

Vitamin B12

(Cobalamin)

An essential vitamin that the body is unable to produce itself alone. Vitamin B12 has many benefits to the body including:

• supporting nerve cell function.

• red blood cell formation and function, and the prevention of anemia.

• Heart health and  macular degeneration (managing homocysteine levels).

• Supporting bone health, preventing osteoporosis.

• DNA synthesis. 

• Boost in energy (when deficient)

• Improve memory and brain function (when deficient)

• Improving mood (via serotonin), and lessening depressed mood and MDD if in a deficit to B12

• Prevent heart disease. 

• Benefits to fetuses (B12 is very important in the early stages of pregnancy)

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along with the many health benefits vitamin B12 bring to the table. Athletes supplement vitamin B12 for its effects of boosting energy and improving mood and memory.

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Supplementing Vitamin B12 may give you some extra energy if you are deficient in the vitamin already. All B vitamins play a role in energy production. One of the more common signs of a deficiency in vitamin B12 is fatigue.

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Vitamin B12 helps in synthesizing and metabolizing serotonin affecting your mood. A decrease in Vitamin B12 from your body can lower serotonin production, causing a depressed mood.

 

Supplementing vitamin B12 can better the outcome of patientients suffering from major depressive disorder (MDD).

 

Although vitamin B12 can improve your mood when in a B12 deficit, Berkheiser from healthline states that “research does not currently suggest that they [supplementing B12] have the same effect in those with normal B12 levels.” (June, 2018, para. 41)

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Loss of neurones leading to memory loss can also be prevented with proper vitamin B12 levels. 

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People of the age of 60 or older have a higher risk of a vitamin B12 disorder as the secretion of hydrochloric acid in the stomach is reduced, reducing absorption. People on a vegan diet, some gastrointestinal disorders, people who have had gastrointestinal surgeries, or ones who take metformin for blood sugar control or proton pump inhibitors for chronic heartburn may also be at a rick for vitamin B12 deficiency.

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Although it doesn't bring many benefits when B12 levels are high, many reactions affecting mood and energy will occur if in a deficiency.

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Why is this beneficial in pre-workout: vitamin B12 promotes serotonin, boosting your mood and confidence when working out. B12 may boost your energy and is overall good for maintaining health.

 

Vitamin C

(Ascorbic Acid)

Ascorbic Acid, otherwise known as vitamin C is an essential vitamin that assists in the maintenance of all bodily tissues. Vitamin C helps in immune system function, the absorption of iron, and the maintenance of collagen (cartilage, bones and teeth) health. Ascorbic acid provides protection against immune system deficiencies, cardiovascular disease, certain types of cancer, strokes, stress, prenatal health problems, macular degeneration, skin aging, and toxic chemicals such as cigarette smoke.

 

Although vitamin C does not provide direct protection towards colds and flu, studies have concluded that vitamin C can help prevent further complications that arise from the flu and colds, such as pneumonia and lung infections.

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Vitamin C plays a role in the production of energy, as vitamin C is needed for two diexygenase enzymes involved in carintine synthesis. Carintine assists in the transport of fatty acids, specifically into the mitochondria. Low levels of vitamin C will result in insufficient levels of carintine, leading to weakness and muscle aching

 

Vitamin C is an antioxidant, protecting against free radicals. Free radicals are unstable atoms in constant search to bind with another atom to become stable. This reaction in the body can effect DNA causing damage to it and cells. When free radicals build up they contribute to the development of heart conditions including heart diseases, cancer, and arthritis.

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Foods high in vitamin C include fruits and vegetables including: oranges, strawberries, tomatoes, peppers, broccoli and potatoes. Because the average person does not meet their daily recommended amount of fruits and vegetables. 

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Supplementing vitamin C may be a good option, although a vitamin C deficiency is quite rare. A vitamin C deficiency leads to scurvy: weakness, anemia, bruising, bleeding and the loss of teeth. As vitamin C is one of the first nutrient depleted in alcoholics, smokers and obese individuals, maintaining vitamin C levels needs to be monitored more closely. There is also speculation that the current daily recommended intake of vitamin C (75–90mg for adults) is in fact too low. Excess vitamin C is easily excreted from the body, so an overdose is not a large concern, but doses above 2000mg can lead to stomach irritation. Some forms of the supplement cause stomach irritation because of the high acidity.

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Why is this beneficial in pre-workout: Vitamin C plays a role in production of energy and provides many general health benefits.

 

Betaine Anhydrous

(Beatine)

A naturally occurring chemical in the body, betaine is another chemical which controls homocysteine metabolism in the body. Homocysteine is involved in the functioning of blood, heart, bones, eyes, muscles, nerves and the brain. High homocysteine levels contribute to heart disease, eye issues, osteoporosis and other skeletal issues.

 

Betaine’s functions to regulate blood homocysteine levels and improve athletic performance. One piece of literature written by Cholera et al. investigated the long term effects of betaine anhydrous supplementation in men with experience in strength training. The double-blind trial consisted of 11 men in the betaine supplementation group consuming 2.5g/day, and 12 men in the placebo group. Groups performed three two-week micro cycles (six weeks of training total). Bench and squat volume were recorded and assessed at each micro cycle. Urine samples were obtained at baseline, and weeks 2, 4, and 6. Bench press one rep max, squat one rep max, vertical jump,  arm cross sectional area, thigh cross sectional area, body fat percentage, fat mass, and lean body mass were all  analyzed and recorded during the six weeks.

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Cholera et al. came to the conclusion that “Six-weeks of betaine supplementation improved body composition, arm size, bench press work capacity, attenuated the rise in urinary HCTL, and tended to improve power (p= .07) but not strength”. Arm cross sectional area was significantly increased in the betaine group but not in the placebo group. there were no differences in thigh cross sectional area. Body composition (body fat percentage  fat mass, lean body mass) was significantly improved un the betaine group compared to the placebo group. Back squat development was consistent with both the betaine group and the placebo group, however bench press volume was better developed in the betaine group in micro cycles one and three. No differences were found between the betaine group and placebo group in regards to squat one rep max, bench one rep max, and vertical jump. However Cholera et al. notes that "there was a trend (p=.07) for increased VJ [vertical jump] power in BET [betaine group]  versus PL [placebo group]".

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Betaine Anhydrous can be found in spinach, beets, and seafood. Supplementing betaine has caused side effects of nausea, stomach upset and diarrea. Ones with high cholesterol levels should be cautious when consuming betaine as cholesterol levels may be raised with supplementation

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Why is this beneficial in pre-workout: Betaine Anhydrous controls homocysteine levels has been scientifically proven to benefit athletic performance in regards to strength and body composition.

 

Huperzine A

(Selagine, HupA, Huperzina A)

Huperzine A has been known as the  'godfather of nootropics', benefiting the brain by improving mental function and memory. Originating from the plant named Chinese club moss and developed synthetically, huperzine A is a substance that some even label to be a drug. Huperzine A works to increase acetylcholine levels, a chemical that is essential to nerve communication in the brain, muscles and other areas around the body. Because of huperzine A’s ability to improve one’s memory, other than used in athletic sports , it has been used in the past and present to treat Alzheimer’s disease and dementia. Huperzine A is also used to treat the disorder myasthenia gravis, where antibodies destroy nerve and muscle communication resulting in weakness of skeletal muscles. A successful treating of myasthenia gravis will result in an increase in alertness and readiness and protection against nerve damaging agents.

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Dosage for huperzine A is around 0.2-0.4mg/day. Some side effects of supplementing huperzine A include: nausea, vomiting, dry mouth, excessive sweating, dizziness, fainting, blurred vision, slurred speech, slowed heart rate, high blood pressure, lost of appetite, contraction and twitching of muscle fibres, cramping, and restlessness. Because one of huperzine’s possible side effects is slowed heart rate, it might not be beneficial for people with heart problems. Patients who suffer from epilepsy may want to avoid huperzine A as well because of its effect on brain chemicals. Others who are in concern with supplementing huperzine A are patients with lung conditions, gastrointestinal tract blockage, stomach ulcers, urinary tract or reproductive system blockage.

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Why is this beneficial in pre-workout: Huperzine A improves mental function and cognitive performance when training, as well as brings benefits for memory and bodily communications.

 

Kanna

(Sceletium tortuosum, channa, kougoed)

Sceletium tortuosum otherwise known as kanna, is a herb consumed in South America for thousands of years because of its reactions on the mind and body, relieving stress, anxiety, depression, and a boost in mood.

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Terberg et al. shares that "extract of the plant (Zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition" (2013, para. 1). PDE4 (phosphodiesterase-4) is responsible for the hydrolysis of the cyclic adenosine monophosphate in the energy system. 5-HT refers to the 5-Hydroxytriptamine receptors, otherwise known as serotonin receptors.

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Kanna contains the chemical compounds mesembrine, mesembrenone, mesembrenol, mesembranol, epimesembranol, and tortuosamine. These compounds are alkaloids which are serotonin reuptake inhibitors, acting as an antidepressant. 

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Kanna is a non-hallucinogenic but nausea has been a reaction in the past from consuming kanna. dosage ranges between 50-400mg.

 

Why is this beneficial in pre-workout: Sceletium tortuosum contains alkaloids that act as an antidepressant, reliving stress and anxiety.

 

Theacrine

(Tetramethyluric Acid)

Theacrine is a chemical that affects the brain similar to caffeine, Theacrine reduces fatigue, and benefits cognitive function and memory. Theacrine also can benefit Aging, the common cold, and fatigue.

 

Found in tea and coffee theacrine is generally known as a safe chemical. Dosing of Theacrine is usually around 300mg daily.

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Why is this beneficial in pre-workout: Tetramethyluric Acid reduces fatigue and increases memory and cognitive performance.

 

N-Phenethyl Dimethylamine Citrate

(Eria Jarensis Extract)

The controversy of finding an excessive stimulant has been going on since Ephedrine was banned in 2004. The next big stimulant was DMAA which was later banned as well. Then AMP-Citrate was discovered which was once again banned by the FDA. The newest stimulant is N-Phenethyl Dimethylamine Citrate, more commonly know as Eria Jarensis extract. Eria Jarensis extract is similar to Ephendrine, DMAA, and AMP-Citrate and is still legal by the FDA, but has been recently banned in Australia. 

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The stimulant also has a similar structure to PEA (phenethylamine). PEA functions as a neuromodulator in the CNS, and contains mood boosting effects, boosting dopamine. The issue with PEA is that it lasts for only 5–10 minutes. Some manufacturers combine PEA with MAO inhibitors to generate longer lasting effects. What seperates N-Phenethyl Dimethylamine Citrate from PEA is its ability to block monoamine oxidase, which eliminates effects. This resulting in longer lasting effects. 

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N-Phenethyl Dimethylamine Citrate increases levels of dopamine and noradrenaline, enhancing concentration alertness and focus, and reducing anxiety. The stimulant also reduces appetite, acts as a fat burner, and acts as a bronchodilator. Eria Jarensis extract also contains a specific alkyl group which allows it to pass though the blood brain barrier, leading to a larger impact on neurotransmitters.

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As Eria Jarensis extract is a relatively new substance, not much information is known on the substance. So most scientists and analysts go to the chemical make-up of the substance and compare it to other known substances.

 

N-Phenethyl Dimethylamine Citrate is extracted from the orchid species Eria Jarenis, local to China and South East Asia. The average known dosage for N-Phenethyl Dimethylamine Citrate is currently 125–200mg before training. Effects of the substance begin to occur right as the substance reaches your bloodstream.

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Why is this beneficial in pre-workout: N-Phenethyl Dimethylamine Citrate increases dopamine and noradrenaline levels, reducing anxiety and enhancing concentration, alertness and focus.

 

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