Creatine: The Power Supplement?

By
Jeremy Cunningham

Abstract
The purpose of this paper is to comprise many studies together to give a basic
understanding of what creatine is, how creatine works and what it effects. This paper
should not be conclusive as there are many more experiments and findings that are
being discovered. This paper just intends to end the common myths that the creatine
supplement carries. The topics covered will be based on cell function, its location and
the athletic benefits of creatine.
Overview of Creatine
Creatine is composed of 3 naturally occurring amino acids and is found in the
pancreas, liver and kidneys of most vertebrates. Natural intake from of creatine is very
low, it is found mostly in red meat and fish. Herring has the highest gram per pound at
3-4.5 g/lb. Although creatine is synthesized in the body, dietary intake plays a large role
in creatine synthesis. Vegetarians have virtually no net intake of creatine as plant life
contains very little creatine. According to building-muscle101.com, a large majority of
this creatine is stored in skeletal muscle (building-muscle.com) . Which is true,
phosphocreatine, which is creatine with an added phosphate, is stored in reserves in
the mitochondria of skeletal muscles awaiting use for extreme energy demands. It helps
to provide muscle cells with quick burning energy in 3 main steps, creatine is taken and
converted into phosphocreatine, the phosphocreatine then loses its phosphate to ADP
to create ATP increasing production of adenosine triphosphate (ATP). (See image)
PCr + ADP

ATP + Cr

The only issue is that creatine when converted and stored in mitochondrial
skeletal muscles can be used and depleted in seconds of quick energy demands.
Creatine is often used as an athletic supplement to gain muscle mass and increase
performance. Creatine supplements research has been the subject of scrutiny and
rumors for years, rumors of quick muscle mass gains and better endurance have been
put to rest due to extensive research of what creatine actually does to muscle cells .
Creatine is produced in the liver and kidneys, the amino acid is non-essential but
is comprised of arginine, glycine, and methionine (aminoacidstudies.com) . (See photo
below)

This amino acid gets a phosphocreatine added and is stored in the muscle cells until it
is needed. Once the muscle cells under-go high intensity, short term strain the
phosphocreatine is converted into extra ATP which helps power the cell . In short
creatine stores allow for a quick boost of energy.

ATP-PC system
The main function of the ATP-PC system (ATP-Phosphocreatine system) is to
provide homeostasis of cells during high energy demands. This provides a quick but
limited energy source for the cell as well. This system works by taking processed
creatine and binding a phosphate to it, when the ATP becomes quickly depleted the
phosphocreatine loses its phosphate to ADP to correct the equilibrium by creating ATP.
The ATP-PC system is what is controlling the initial ATP synthesis (Greenhaff, 2001) .
This process is anaerobic, it doesnt require any oxygen so the delivery of energy is
very quick but limited. Reents during his research finds that, Even with the assistance
of phosphocreatine (PCr), the ATP stores can meet the anaerobic energy demands of
intense exercise for the initial 15 seconds (Reents. 2000. p. 187). This process is to
provide the immediate burst of energy is very quick. The site of energy transportation in

this pathway has led to many studies and discoveries, the most common thought is that
the cellular energy translocation for ATP and ADP were located at the energy production
and output sites of the cell. But studies have shown that phosphocreatine and ATP can
be looked at like energy carriers due to the fact that creatine kinases form in the cell,
which leads to the thought that they have different metabolic roles. Other studies show
that that creatine kinase and phosphocreatine also have a function of energy transport.
The phosphocreatine will actually act as a transport molecule between the sites of ATP
production and hydrolysis sites. This makes sense because the re-synthesis of
phosphocreatine once the phosphate is stripped off should be the critical factor for
sustained cell energy. Due to creatine being able to help with ATP regeneration through
phosphocreatine, creatine will sometimes be referred to as a metabolic buffer.
PCr + ADP

ATP + Cr

Walker (1979) concludes, that PCr and creatine can serve as auxiliary energy
messengers between mitochondria and the cytosolic sites of ATP utilization (As cited in
Creatine. Williams, Kreider, Branch. 1999. p 23). But creatine kinases are the
responsible for the transportation of energy from the skeletal mitochondria to the

sarcoplasm resulting in contraction. (See figure below)

Creatine Kinase

Creatine kinase is the enzyme responsible for stripping the phosphate from
phosphocreatine to create ATP + creatine. This kinase catalyzes with the reversible
transfer of a phosphate between phosphocreatine (PCr) and ATP. Creatine kinase is
really the responsible enzyme that keeps the cell in correct equilibrium between ATP
and PCr. So without the enzymatic reaction that creatine kinase initiates there would be
no phosphate to give to the ADP. Creatine Kinase has also been linked to serve as a
limiting enzyme for oxygen uptake in tissue. Fluctuation in the concentration of creatine
and PCr may control cellular metabolic activity to a greater degree than alteration in the
concentrations of ATP and ADP. (Williams, Kreider, Branch. 1999. P 26.) So creatine
kinases can serve as a metabolic rate limiter and controls the phosphorylation of
phosphocreatine into creatine. There is also an added benefit to increased creatine, it
increases the oxidative phosphorylation because it is bonded to mitochondrial creatine
kinases just outside of the inner mitochondrial membrane. This increases mitochondrial
respiration because of the elevated membrane space. Creatine kinases can also be
found in specific forms known as an isoenzyme relative to the brain, cardiac muscles
and skeletal muscles. There is supporting evidence that creatine kinases can also help
with the formation of neuronal dendrites. A study was conducted on the homeostasis on
dendritic mitochondria in growing neuronal dendrites found that creatine kinase helps
with the growth of Purkinje cells. Purkinje cells are large neuron with many branching
extensions that is found in the cortex of the cerebellum of the brain and that plays a
fundamental role in controlling motor movement (Brittanica. 2015). The experiment
exposed cultured Purkinje cells to a creatine kinase inhibitor which hindered cell growth
greatly. Then the Purkinje cells were subjected to a glycolysis inhibitor to see if growth

was stunted by stopping glycolysis, which in turn had no effect on the Purkinje cell,
which was stated, had little or no effect on dendrite development and dendritic
distribution of mitochondria, consistent with the fact that we observe very little glycogen
in these dendrites by electron microscopy (Fukumitsu, Fujishima, Yoshimura, Wu,
Heuser, Kengaku. 2015). Research proved that the main source for energy in dendrite
growth relied on the CK-Mitochondria system.
There is also a downfall to having too high of a creatine kinase system in your
body. High serum levels of creatine kinase is usually a signal of diseases such as
muscular dystrophy and other cerebral diseases. It is an indicator of damaged cells as
creatine kinase leaked from the damaged cell and enters the bloodstream. This can
stem from anything from a good workout, which is less damaging to cells but still causes
creatine to flow to the blood. Or it can stem from muscular dystrophy and internal
trauma to cells.
Creatine in the Brain
It has been thought that supplemented creatine levels may increase brain
function. A double blind test created by Rea, Digney, McEwan and Bates (2006) proves
this theory. Phosphocreatine is converted into ATP which is greatly stored in the brain.
During brain function or activation the ATP levels stay relatively stable while
phosphocreatine levels decline. Since the PCr-ATP system is exhausted very quickly it
would make sense that the more available the phosphocreatine is, the more of a
sustained workload the brain could handle. Since creatine levels are relatively low in
meats, oral supplementation would be the answer. During creatine loading cycles, some
creatine is excreted through urine. One test in example had a load cycle of 10 grams

per day for 5 days, with 50 grams total urinalysis revealed that around 35% of the
ingested creatine was excreted through urine (As stated by Williams, Kreider, Branch. in
Creatine Maganaris and Maughn. 1998.) So if a brain retained any of the remaining
65% of the absorbed creatine, how would the brain function increase? So a doubleblind, placebo controlled, cross over design was created utilizing 45 vegan subjects.
Each subject was given a cognitive test prior to dosage, then creatine or a placebo was
given in a dosage of 5g for 6 weeks. The ending results were conclusive, mental fatigue
was reduced and memory recall was increased, results stating The mean RAPMs raw
score under placebo was 9.7 (s.d. = 3.8) items correct in 10 min versus 13.7 (s.d.= 4.1)
items correct under the experimental treatment. (Rea, Digney, McEwan and Bates.
2006.) The reasoning behind this is that the increased phosphocreatine levels are
working to smooth out fluctuating blood oxygen levels that result from brain activation.
(Gjedde. 1999).
Creatine in Exercise
It has been known that different individuals respond differently to creatine
dosage. Things like health, how much their body naturally produces creatine, etc. can
affect the gains that someone receives upon taking creatine. Many studies have been
conducted with performance and creatine in conjunction. One study tested if D-Pinitol
when taken with creatine will increase the uptake of creatine, therefor leading to a better
workout. D-Pinitol is a methylated isomer that has insulin like properties, it increases
glucose uptake and promotes the synthesis for glycogen. Utilizing 24 males in a double
blind test, they concluded that there was an increase in body mass over 4 weeks but
only for the group that did not take the D-Pintol with the supplement. This group also

had a lower lean body mass that the group that ingested the D-Pinitol. (Kersick,
Wilborn, Campbell, Harvey, Marcello, Roberts, Parker, Byars, Greenwood, Almada,
Kreider, Greenwood. 2009.) Another subject that has been intensely studied is how
endurance is effected by creatine, since phosphocreatine stores are usually expended
in a couple of seconds how much is regenerated and used in endurance sports?
Williams, Abt, and Kilding (2014) created a simulated soccer performance to test how
creatine supplementation affected running endurance. Soccer is mostly an aerobic
sport, it requires running endurance with little high intensity short time frame needs. The
subjects were instructed to run a high intensity course before and after supplements
were taken, the result concluded no significant increase in performance in the athletes
that took creatine or a placebo (Williams, Abt, and Kilding. 2014.) So does this mean
that creatine only shows its performance best when partaking in anaerobic sports such
as lifting? Reents (2000) reviewed many different studies and discovered that the
benefits of creatine are diverse. Supplementation varies per the individual. The only
group that ever showed a large benefit were those who were not trained professional
athletes. Reents states, In general, roughly half of the laboratory based studies of
activities thought to rely most heavily on the anaerobic system have documented an
ergogenic effect of creatine supplementation. (p 196-197). He later points out that
dietary factors could explain why different results were given for almost every test
subject.
Conclusion
Creatine supplements and athletic performance results may vary drastically for
the individual. Things such as amount of training, diet or even how much creatine is

consumed meat could affect the performance and muscle gains for individuals.
Vegetarians might experience more positive results from creatine for the reason that
their diet alone does not get the daily recommended dosage of creatine. Results for
growing brain cells and metal endurance have shown a positive, daily creatine
supplements can increase dendrite growth and improve memory recall and even lessen
mental fatigue. Many more studies need to be conducted to discover why there is a
huge variance of positive results for various test subjects and no results for other
individuals.

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