The 2017 Introduction Creatine monohydrate has been gaining



The physiological effects of Creatine on muscle size and

Clayton Harms

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Biology L403
Senior Seminar Paper

December 15, 2017
























Creatine monohydrate
has been gaining popularity among athletes and fitness enthusiasts. Creatine is
used primarily to increase performance under aerobic and anaerobic conditions
relating to maximal effort exercise. No other supplement has been researched as
much or as in depth as Creatine. This review paper is designed to explore the
question of the efficacy of Creatine. This will be done in 5 parts: Part 1 will
define how Creatine works by laying out the physiological mechanisms involved
in Creatine. This will be done with an introduction into the theory of how
Creatine benefits athletic performance through increasing ATP synthesis. Part 2
will explore the topic of increasing muscular strength. Creatine is taken to
increase muscle size and strength in the hopes to increase athletic performance
in sport. Part 3 will cover the topic of high intensity exercise and
benefits to general athleticism. Creatine is also known for its benefits in
sport-specific conditions such as sprinting and Rugby. Part 4 will be a
reflection of articles disputing the efficacy of Creatine. Some research shows
variation in efficacy among individuals, where some see no benefits to
supplementing Creatine. What are the implications of these findings as they
relate to the research in favor of Creatine? And finally, Part 5 will cover the
safety, public concern and possible side effects of Creatine.


1) How Creatine works

Creatine was discovered
in 1832 by a scientist named Michel Chevreul (Williams et al., 1999). Creatine
is produced in the body from glycine and arginine. It is found primarily in
muscle cells; it is chemically similar to amino acids and serves to help skeletal
muscle produce energy during anaerobic and aerobic exercise. The average person
is turning over 2g of Creatine in a 24-hour period. (Wyss and Kaddurah-Daouk,
2000). Creatine is involved in the adenosine triphosphate-phosphocreatine
system (ATP-PC). This system has the greatest potential for power output in the
body and is thus an important system to consider when studying power output
potential in athletes. The ATP-PC system consists of adenosine triphosphate
(ATP) and phosphocreatine (PC). This system is responsible for providing immediate
short-term energy by breaking down high energy phosphates. This short energy
store lasts between 5 and 15 seconds before it is exhausted. (Williams and
Branch 1998). Fatigue is attributed to the decreasing PC. Therefore,
supplementing PC could be used as a means to regenerate ATP for replenished
energy stores (Williams and Branch 1998). Therefore, an athlete supplementing
Creatine would be able to increase the rate of ATP synthesis during
short-duration exercise. Creatine supplementation would also increase the rate
of PC synthesis when the athlete is recovering, meaning the athlete could exercise
more frequently than an athlete not supplementing Creatine because he is
recovering faster. The research of Kurosawa et al. (2003) helps support this
claim. Kurosawa evaluated the rate of ATP synthesis using PC hydrolysis and
mean power output.  The subjects
participated in a maximal output grip exercise by utilizing magnetic resonance
spectroscopy. The test was done before and after supplementing Creatine at
30g/day for 14 days. The rate of ATP synthesis during PC hydrolysis increased
with mean power output during the grip exercise for all subjects after
ingesting the Creatine. The authors of this study were able to conclude that
30g of Creatine for 14 days lead to an improvement of ATP synthesis, thus supporting
the general claim that supplementing Creatine has a physiologically and
logically sound basis. Finally, Creatine may be dependent on the intensity and
duration of exercise. In other words, when an exercise reaches a level of
intensity that exceeds the available power of the aerobic system the muscle
will then switch to the anaerobic system. This switch taps into phosphocreatine
and glycogen stores and uses them as fuels. Therefore, during peak exercise the
muscle will utilize the PC stores with priority. This could lead to performance
gains in both weight lifting style sports as well as high intensity sports,
which will be discussed further in this paper.

2) Increasing Muscular Strength

            Athletes rely on
muscular strength to perform sport-specific tasks under some kind of
competitive or otherwise physically demanding context. This section will
explore research articles that test the idea that Creatine will increase
muscular strength as measured through resistance exercise. Vandenburghe et al.

(1997) researched the effects of supplementing Creatine on muscle phosphocreatine
concentration and muscular strength. As discussed earlier, Creatine should be
able to replenish ATP faster and lead to performance gains.  Researchers used nineteen female volunteers placed
in two groups receiving either a placebo or Creatine. Subjects were then
instructed to perform resistance training for ten weeks. The Creatine group was
given 20g/day of Creatine for the initial 4 days followed by 5g/day for the
remainder of the ten weeks. When compared to the placebo group, the muscle strength
for those on Creatine increased by 20-25%. Fat-free mass increased by 60%. This
research is able to demonstrate that long-term Creatine supplementation is
effective in increasing muscle strength in the context of resistance training;
something very important for competitive athletes (Kurosawa et al. 2003).

et al 2003. published a paper titled “Effects of Creatine supplementation and
resistance training on muscle strength and weightlifting performance.” These
researchers were able to prove that Creatine supplementation when combined with
some form of resistance training, most commonly weight lifting, produced
strength increases 8% greater than those taking a placebo. These strength
increases are measured using the maximal amount of weight a subject can move
for one repetition. Another measure of increased performance is maximal repetition
at a set percentage of maximal strength. For example, 80% of a one rep max for repetitions
can be described as a measure of weight lifting performance, rather than
maximal strength. In this case, using Creatine lead to a 14% increase in muscular
performance when compared to a placebo. Several peer-reviewed articles show
similar findings. Volek et al. 1999 recruited 19 subjects put into either a
Creatine or placebo group. Subjects in the Creatine group received 25g/day for
one week followed by 5g/day. Each group received instructions to complete weight
lifting for 12 weeks. The Creatine group experienced a 6.3% increase in
fat-free mass over the placebo, an indicator of muscle hypertrophy that can be
attributed to Creatine supplementation. Furthermore, the Creatine group also
saw significant strength increases in the back squat and bench press. Muscle
size also increased in the Creatine group by 24% over the placebo group. The
researchers were able to conclude that Creatine was increasing fat-free mass
and improving strength (Volek et al. 1999). Therefore, these papers demonstrate
ample evidence that supplementing Creatine is effective at improving muscular
strength and performance.



3) High Intensity Interval Training

is also thought to help improve High Intensity Interval Training (HIIT) performance.

This type of training can be described as high intensity effort followed by low
intensity rest periods meant to allow the athlete time to recover. Sprints are
an example of HIIT.  Research shows that
Creatine supplementation can improve an athlete’s performance during a sprint. Dawson
et al. (1995) discovered that 20g/day of Creatine supplementation for five days
increased performance during six second sprints with 30 second recovery
periods. The group supplementing Creatine showed significantly greater scores in
kJ of work completed in six bouts of sprints, as well as peak power output when
compared to the group receiving a placebo. Essentially, Dawson et al were able
to conclude that Creatine can significantly improve an athlete’s ability to
perform high intensity exercise. Schneider et al. (1997) further demonstrates
this concept. Subjects in Schneider’s study ingested 5g/day Creatine and then performed
15 second bouts of maximal cycling with 60 second rest periods. The group
ingesting Creatine performed 50.6 kJ of total work as compared to just 47.5 kJ in
the placebo group. Meir R 1995 performed a case study on rugby players that
were supplementing Creatine. Rugby can be considered a high intensity sport.

Meir sent a questionnaire to the players after they completed ingesting 20g/day
of Creatine for one month. The author was able to conclude that Creatine could
be considered effective in improving performance in HIIT style exercise, such
as Rugby (Meir R 1995).

These two papers are able to show that
Creatine is able to improve performance during HIIT protocols.



4) Studies showing no benefit to Creatine

the interest of providing a fair and balanced review of Creatine, this section
will explore studies that show no benefit to supplementing Creatine. Table 1
shows a summary of three papers along with their protocol, Creatine Dose and




Creatine Dose


Biwer et al. 2001

Treadmill intervals

0.3 g/kg /day

No effect on sub-maximal treadmill

Wilder et al. 2001

Progressive weight training
10 weeks

5 g/day

No effect on 1-RM squat strength.

Odland et al. 1997


20 g/day

No effect on any recorded exercise measures


Table 1. Three papers showing Creatine as
being ineffective for increased performance.


The reasoning behind
these conclusions mentioned in Table 1 could be explained through individual
variance in responding to Creatine supplementation. Greenhaff (1997) was able
to demonstrate that individual variance can account for as many as 30% of subjects
showing little to no change in muscle size or performance when supplementing
Creatine. This large variance should be studied further with subject-specific
dosing where certain individuals may require larger dosing to achieve the
desired outcome (Greenhaff 1997). Delecluse et al. (2003) used trained
sprinters taking 0.35g/kg Creatine for seven days or were given a placebo. These
subjects were then measured on a 40-meter sprint. Performance did not improve
in these subjects. There was no change between groups in maximal speed. The
authors concluded that Creatine had no effect on these subjects. Odland et al.

(1997) had subjects consume 20g/day and perform maximal effort cycling for 30
second bouts. The results showed that Creatine did not affect performance. Odland
speculates that it is possible conditioned athletes do not respond well to
Creatine as it relates specifically to a maximal sprint (Odland et al. 1997).

Finally, Finn et al. (2001) discovered comparable results. Finn also prescribed
Creatine taken at 20g/day and had subjects perform a maximal sprint on a
cycling machine. The researchers concluded that Creatine did not improve
performance better than a placebo. These papers seem to demonstrate
questionable results for Creatine use only in very well-conditioned athletes. That
is to say the average fitness enthusiast seems to benefit most of all from
supplementing Creatine.


5) Safety Concerns

Creatine being a popular supplement, many casual fitness enthusiasts are potentially
concerned about side-effects or drawbacks form taking Creatine. A study was
done to investigate possible side effects. Kreider et al (2003) studied 98
athletes and measured Creatine use that lasted as long as 21 months. Testing
was thorough with full blood work and urinary tests being taken and compared
against several health markers.  The
researchers were able to show that there is no evidence that Creatine use is
causing any change to these health markers when compared to athletes that do
not take Creatine.

6) Conclusion

is the most popular supplement on the market and for good reason, it works. Through
the available research it can be demonstrated that Creatine is able to increase
muscular size, strength and performance. There does seem to be a degree of
variance between individuals when it comes to the effectiveness of Creatine.

For those that do respond well to Creatine, it can be said to be a safe and
effective supplement. Furhter research is needed to fully understand the



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