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Effects of Pre-Workout Supplements on the Body
Working out and body building has become an extremely popular past time, as the
amount of gym time increases so does the amount of pre-workout supplements that are being
utilized. Pre-workout ingredients are put together to give the user the advantages of increased
energy, endurance, and strength. There are many different types of pre-workout supplements;
one of the more popular types would be energy drinks and multi-vitamins in the young adult
population (Spradley, Crowley, Tai, Esposito, Fukuda, Kendall, S. Moon, & J. Moon 2012).
Research shows that some of the most common pre-workout nutrients include arginine, betaine,
branched-chain amino acids, creatine, taurine, and caffeine. Each different pre-workout
supplement uses different combinations of nutrients to provide the most effective supplement
and to give the best results. This lit review will be used to go into greater detail on the
ingredients of supplements and how they affect the body individually and an example of how
they are all put together to form an energy drink and how that can cause different effects.
NUTRIENTS
Branched Chain Amino Acids (BCAAs) include the three amino acids Leucine,
Isoleucine, and Valine. BCAAs also affect brain function by altering large, neutral amino acid
(LNAAs) transport at the blood-brain barrier. Transport is shared by several LNAAs, the BCAAs
and the aromatic amino acids, and is competitive with one another. “Consequently, when plasma
BCAA concentrations rise, which can occur in response to food ingestion or BCAA
administration, or with the onset of certain metabolic diseases, brain BCAA concentrations rise,
and aromatic amino acid concentrations decline (Fernstrom, 2005).” The effects of the
neurochemical changes in the body include altered hormonal function, blood pressure, and
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affective state. The BCAAs leucine, isoleucine, and valine all participate directly and indirectly
in different biochemical functions of the brain. “These include protein synthesis, the production
of energy, the compartmentalization of glutamate, and the synthesis of the amine
neurotransmitters serotonin and the catecholamines, dopamine and norepinephrine (Fernstrom,
2005).” A major fraction of ingested BCAAs are not metabolized by the liver and pass into the
systemic circulation after a meal, which results in plasma concentrations to rise appreciably and
in proportion to the protein content that is a part of the meal (Fernstrom, 2005). BCAAs are used
in humans to help with the athletic ability and mental performance. When the body is unable to
process certain amino acids properly a disorder called Maple Syrup Urine Disease can occur.
MSUD is able to be diagnosed specifically by the sweet smell of the urine like maple syrup. It
can be treated effectively with a diet that is restricted with respect to the branched-chain amino
acids. “As the amino acid levels decline, brain edema resolves, and neurologic status improves
(Charrow, 2005).” If the disease is treated right away, then there is a better chance of full
recovery.
Betaine is a methylamine, being in the human body by choline. Betaine is used to lower
plasma homocysteine concentrations (Schwab, Alfthan, Aro, & Uusitupa, 2011). A high plasma
concentration of homocysteine, fasting homocysteine, and the increase in homocysteine
concentrations after a methionine loading test are predictors of cardiovascular disease risk
(Olthof, Trinette, Boelsma, & Verhoef, 2003). In obese people, betaine decreases significantly
plasma homocysteine concentration, but in healthy individuals betaine has resulted in a
significant acute decrease in homocysteine concentration. “In some studies, betaine
supplementation has been shown to increase serum LDL-cholesterol concentrations in healthy
subjects, subjects on a weight-loss diet, and also in subjects with chronic renal failure (Schwab et
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al., 2011).” Only doses of betaine >6 g/d lower plasma homocysteine in hyperhomocysteinemic
patients with genetic defects in homocysteine metabolism therefore lower doses of betaine have
been kept out of clinical settings(Olthof et al., 2003). Other than pre-workout supplements
betaine is found in foods that are eaten every day. Some foods that contain sources of betaine
include spinach, beets, and wheat products (Olthof et al., 2003). “Betaine is a component found
at relatively high concentration in wheat gram, particularly in the bran and aleurone fractions,
and although its potential role in the health benefits of whole grains has been proposed, it largely
has been neglected (Price, Keaveney, Hamill, Wallace, M. W., Ward, Ueland, . . . Welch,
2010).” Betaine can also act as a lipotrope and can play a role as a therapeutic agent for
nonalcoholic fatty liver disease. “Betaine supplementation has also been shown to increase
plasma total and LDL cholesterol, possibly through the increased synthesis and availability of
phosphatidycholine, which promotes VLDL production, leading to clearance of triacylglycerol
from the liver (Price et al., 2010).”
Creatine is an amino acid which represents one of the most important nitrogen containing
compounds playing a role in energetic metabolism. “About 90-95% of the body’s creatine is
found in the skeletal muscle and approximately one-third of this is free creatine, whereas twothirds exists as phosphocreatine (PCr). When energy demands increase, PCr donates its
phosphate to ADP to produce ATP. The ATP-PCr system can provide energy at high rates for
about 10-15 seconds before it is empty. Thus, creatine is involved in temporal energy buffering,
and also in spatial energy buffering, proton buffering, and glycolysis regulation (Paddon-Jones,
Borsheim, & Wolfe, 2004).” Creatine is normally included as a part of food because it is formed
naturally within the body (Navrátil, Kohlíkova, Petr, Pelclová, Heyrovský, & Pristoupilová,
2010). Creatine is found in the heart muscle, the brain, testes, and other organs along with the
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skeletal muscles (Juhn, O’Kane, & Vinci, 1999). Creatine increases strength, power and fat free
mass, enhances fatigue resistance, and improves functional performance in older adults (Stec,
M.J., & Rawson, 2010). “In normal healthy men the turnover of creatine is about 1-2 g daily,
which is covered by its endogenous synthesis from amino acids in liver and kidneys, and by food
intake (Navratil et al, 2010).”
The table lists the side effects experienced from subjects of an experiment conducted with
athletes who voluntarily took creatine supplements. Diarrhea was the side effect that was
reported to be experienced the most, followed by muscle cramping. Seven athletes considered
the weight gain to be a “negative” side effect, and 7 athletes experienced dehydration. Fourteen
subjects reported no perceived side effects (Juhn et al., 1999). Because of the possible ergogenic
effect of creatine there has been a wide-spread use of supplementation in sport. Many athletes
ingest creatine for extended periods of time to increase strength and body mass (Paddon-Jones et
al., 2004). Reported benefits of creatine supplementation in older adults are related to improved
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muscle function and increased fat free mass, but it may also improve bone health and cognitive
processing, which may be able to reduce morbidity in older adults (Stec & Rawson, 2010).
Arginine is a conditionally essential amino acid. In healthy adults, arginine can be
produced in sufficient quantities to meet most normal physiological demands with the rate of de
novo synthesis remaining unaffected by several days of not having an arginine. “Exogenous
arginine provided parenterally or as a dietary supplement has been shown to facilitate the
maintenance of lean body mass and improve functional capacity, benefits consistent with
arginine’s well documented vasodilatory properties and effect of growth hormone secretion.
Endogenous arginine is synthesized primarily in the kidney from L-ornithine and L-citrulline
precursors (Paddon-Jones et al., 2004).” After being ingested, a small amount of arginine is
metabolized by the enterocytes and the liver, with the remainder reaching the systemic
circulation. The most widely explored metabolic fate of arginine is its conversion to nitric oxide
via nitric oxide synthase, chronic exposure to nitric oxide also acts to slow a number of the
processes associated with the onset of atherosclerosis. Nutritional supplements that enhance
exercise capacity are considered to have an ergogenic effect. Arginine is thought to have
ergogenic effects that fall into 2 different categories: acute effects with results of enhanced
exercise capacity after ingestion, and a long-lasting effect from the stimulation of muscle protein
synthesis and thus anabolism of muscle protein (Paddon-Jones et al., 2004). “Under normal
conditions sufficient arginine is produced endogenously to enable the exogenous ingestion of a
mixture of essential amino acids to effectively stimulate muscle protein synthesis (Paddon-Jones
et al., 2004).” The fact that increased arginine availability neither causes an anabolic response in
muscle nor is needed for the acute anabolic action of essential amino acids means that any effect
of arginine on muscle protein synthesis is likely caused from an indirect action. If sufficient
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arginine is ingested to increase muscle blood flow as a consequence of accelerated nitric oxide
(NO) production, then just from ingestion of arginine alone may not motivate muscle protein
synthesis, but if arginine is taken in conjunction with other amino acids, a specific effect of
arginine may be expected to happen(Paddon-Jones et al., 2004). “In addition to its role as a
precursor for NO production and protein synthesis, in some instances exogenous arginine can act
as a secretagogue, promoting growth hormone release via an inhibition of somatostatin secretion
(Paddon-Jones et al., 2004).”
The main function that has been found of taurine in humans is conjugation of bile acids in
the liver to form bile salts that are instrumental in micellar formation and fat absorption. Taurine
has not really been found to be an essential amino acid in humans due to the several
demonstrable biosynthetic pathways (Paauw & Davis, 1994). “The major route of taurine
biosynthesis involves conversion of cysteine to cysteine sulfinic acid decarboxylase (Paauw &
Davis, 1994).” “Taurine is involved in neuronal modulation, osmoregulation, and protection
against oxidative stress. Its plasma levels are maintained within a normal range through protein
intake, and de novo synthesis is limited by the activity of hepatic cysteinesulphinic acid
decarboxylase, which is low in humans. Taurine depletion can occur rapidly, possibly leading to
retinal, cardiac, neural, immune, and hemostatic dysfunction (Merheb, Daher, Nasrallah, &
Sabra, 2007).” Specifically in diabetics, intestinal absorption of taurine is reduced while urinary
taurine excretion is enhanced. Ingested taurine is absorbed in the small intestine by its receptor
and is then spread to many organs against a concentration gradient by active uptake. Taurine is
then conjugated in the liver to bile salts or eliminated by the kidneys. “The final outcome of
taurine homeostasis is through fecal excretion after deconjugation by the bacterial flora or renal
excretion as intact molecules (Merheb et al., 2007).” There have not been very many studies
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conducted with taurine and how it affects the human body, but it has been closely related to that
of rats. Taurine is the most abundant free amino acid in the body and is seen the most at high
concentrations during development. Taurine has a number of physiological properties including
membrane stabilization, osmoregulation, neuromodulation, regulation of calcium homeostasis,
antioxidation, modulation of ion flux, and serves as a neurotransmitter or neuromodulator.
Taurine can be found in parietal cells and smooth muscle (Haung, Chang, Ho, Lu, Tsai & L.H.,
2011). Taurine has an important role in the stomach. In the stomach of the rat, the taurine first
markedly increases gastric acid secretion. “Long-term administration of taurine in drinking water
results in increased susceptibility to seizures and a decreased latency for clonic seizures in
kaininc acid-induced seizure models in rats (Dikici, Saritas, Besir, Tasci, Kandis, 2013).”
“Taurine stimulates acid secretion that abolished by TTX, atropine, and bicuculline but not by
cimetidine, proglumide, or strychnine. Taurine potently increases the level of cAMP. Taurine
stored in the mucosal glands may protect cells from self-destruction during oxidation.
Taurinergic neurons in the muscle layer of the gastrointestinal tract might be involved in motility
of the GI tract and the function of endocrine cells as well (Haung et al., 2011).”
Caffeine is one of the most widely consumed supplements in the world. It is found in
many different types of foods, drinks, pills, and powders. Caffeine is rapidly absorbed in the
digestive tract and given to all tissues and easily crosses the blood-brain barrier. Caffeine appears
to block the action of endogenous adenosine at the adenosine Al receptor subtype by occupying
those sites (Leiberman, 2001).” Effects on certain aspects of cognitive function are generally
consistent with the lay perception of caffeine as a compound that increases mental and physical
energy (Leiberman, 2001). “Caffeine has the same affects that amphetamines and cocaine have,
just to a lesser degree. It can exert effects on the central nervous system and the peripheral
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tissues that result in physiological effect (McDaniel, McIntire, Streitz, Jackson, & Gaudet,
2010).” Caffeine is an adenosine antagonist and blocks the adenosine receptor, so it increases the
effect of dopamine of the D2 receptor. Adenosine blockade through caffeine allows for a less
sleepy person that shows more focus through enhanced dopamine and decreased adenosine
availability (McGuinness & Fogger, 2011). Caffeine has been said to be a powerful ergogenic
aid that is beneficial in athletic training and performance. Caffeine has been found to increase
speed and power, improve the length of training, and helps the user no not become fatigued as
quickly. Caffeine has been found to stimulate the brain, causing clearer thinking and ability to
concentrate more intensely on the task that is present (McDaniel et al., 2010). The American
Alliance for Health stated that there are three ways that caffeine may provide ergogenic effects,
“First, the metabolic theory suggests that caffeine provides improved endurance due to an
increased utilization of fat as fuel and a sparing effect on carbohydrate utilization. Secondly,
caffeine may increase the calcium content of the skeletal muscle and enhance the strength of
muscle contraction. Lastly, caffeine has a direct effect on the central nervous system as a
stimulant, which can help with fatigue, increased alertness, and increased muscle recruitment”
(Powers, 2004). Dependence, tolerance, drug craving, and withdrawal symptoms can occur when
caffeine is used chronically (McDaniel et al., 2010).
ENERGY DRINKS
Because all of the nutrients are different from one another whenever they are separated, it
is important to look deeper at how they affect the body when they are all combined together. The
most common supplement used by people that are going to participate in any kind of physical
activity or workout is the energy drink. According to Jay Hoffman, more than 30% of all
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American male and female adolescents use these supplements on a regular basis (2010). It is
most commonly used because it is easily accessed and depending on which brand you drink, sold
at a reasonable price. Unlike other caffeinated products, current FDA regulations do not require
energy drinks to display comprehensive ingredient and warning labels, therefore consumers do
not really understand what they are inputting into their bodies. Energy drinks are known for
improving attention and/or reaction times and alertness, mixing caffeine and glucose can upgrade
deficits in cognitive performance and subjective fatigue during extended periods of cognitive
demand. Energy drinks have stimulating properties that can boost heart rate and blood pressure,
dehydrate the body; they may mess with the effects of other stimulants when they are mixed.
The amount of caffeine that is in most energy drinks may lead to insomnia, nervousness,
headache, tachycardia, and seizures (Attila & Cakir, 2011). Orimoloye, Hurlock, Ferguson, and
Lee say that “effects included nausea, tachycardia, high blood pressure,
jitteriness/agitation/tremors dizziness, chest pain, and numbness” (2013). There have also been
instances of seizures, liver problems, and complete kidney failure due to the consumption of
energy drinks (Orimoloye, 2013). The quantities of caffeine within one serving of an energy
drink is not normally high enough to cause severe symptoms, but whenever multiple energy
drinks are taken at the same time or throughout the day is when the body starts to react. Due to
drinking so many energy drinks and the amount of caffeine that is taken in, there is something
called caffeine toxicity. Central nervous system toxicity may start with irritability and
continually progress to lethargy and coma. Myoclonic jerks, clonus, hallucinations, and
opisthotonos have all been described with acute caffeine toxicity (Babu, Church, & Lewander,
2008). “One case series of 4 adults with new-onset seizures questioned an association with heavy
energy drink use. Each of these patients reported no further seizure activity after abstinence from
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energy drink use (Babu et al., 2008).” Rhabdomyolysis is an irregular complication of caffeine
toxicity that has been discovered, but only after an extreme overdose. One mechanism for muscle
injury is the tetanic contraction of skeletal muscle, and that results from seizing of intracellular
calcium. Caffeine-induced Rhabdomyolysis produces serum creatine phosphokinase levels that
are higher than 28000 IU/L and extended renal impairment. There have been cases of
hypokalemic paralysis with the excessive use of caffeine as well (Babu et al., 2008).
CONCLUSION
When people use workout supplements, most of the time they are unaware of what is all
included with the ingredients and how they can affect the body. According to bodybuilding.com,
about Cellucor C4 Extreme pre-workout supplement, “Possessing the power to ignite your mind,
muscles, and workout regimen” or “You will have more energy. You will have help getting that
extra rep, complete that last set” is enough to purchase and use this product. There is very little
information of the ingredients that are included and how they can affect the body after extended
use or overuse. When taken in moderation and with the recommended serving sizes, pre-workout
supplements can positively affect the body, but if the supplement can result in life-altering
consequences it may not be worth the risk. As seen in this literature review, the ingredients
included in the pre-workout supplements can cause liver damage, kidney failure, possible
seizures, high blood pressure, and cause problems with the heart. Even though the positive
outcomes that come with taking a pre-workout supplement may be enough for someone to take
the risk, it is important for people to first confirm the safety and efficacy. There are better and
more natural ways to get the effects that can be given from the pre-workout supplements.
Allowing the body to naturally produce the nutrients needed and taking other supplements that
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may have smaller amount of the nutrients would be another way in which the body may not be
affected so intensely. Any kind of activity or athletic workout comes with its potential risks to
the body, taking pre-workout supplements is just another way to increase the dangerous effects
that could happen to the human body.
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