The Safety of Creatine Monohydrate Use in Young Athletes Aged 16-21

Nick Esmail, Karleigh Huber, Justin Marrie, Ariana Ormiston

Centofanti School Of Nursing

NURS 3749

Dr. Danielle Class

April 9, 2023
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The Safety of Creatine Monohydrate Use in Young Athletes Aged 16-21

Creatine is a popular supplement used by athletes to enhance their performance.

However, with the increasing use of the supplement, its use in young athletes has raised concerns

about potential adverse effects. Possible side effects of creatine include dehydration, muscle

cramps, and gastrointestinal distress. In addition to these effects, there is also suspicion of kidney

damage and liver dysfunction through the use of the workout supplement. Therefore, to fully

understand the safety of creatine usage in young athletes ages 16-21, it is essential to identify

how creatine works in the body, its enhancement on athletic performances, and its history of

adversities with its increased use within the last decade. While discussing the effects of

supplemental creatine in this review, supplemental creatine refers to the use of Creatine

Monohydrate, the most common supplement available for purchase.

Creatine is most recognizable as a workout supplement and a naturally occurring amino

acid in the human body. While supplemental creatine has become increasingly popular, many are

unaware that naturally occurring amounts of the amino acid are present in the body. Thus, it is a

primary indication for many studies to understand what supplemental creatine does to enhance

what naturally occurring creatine already achieves within the body.

Athletes may choose creatine supplementation primarily to increase muscle mass and

enhance athletic performance. However, a supplemental form of creatine is one of many ways

young athletes can increase their intake. Natural creatine is located chiefly in the body's skeletal

muscles and brain. In these areas, the natural form of creatine exists in two types, phosphorylated

and free, which help supply the body with energy. Natural creatine may also be obtained from

dietary sources, as it is found in many common foods, such as seafood and red meat (Hall et al.,

2021). Therefore, for the athlete looking to increase their intake through their diet, they should be
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instructed to include foods in their diet that are of animal origin, as creatine is not present in

vegetables. In addition, studies have identified that subjects who consumed low amounts of meat

and fish, in turn, have low amounts of creatine, which is not optimal for athletic performance.

(Balestrino, 2021). Obtaining additional creatine in one's diet was less effective than artificial

supplementation. In comparing whether creatine intake through one's diet or supplemental

Creatine Monohydrate is more beneficial, creatine levels in food are far below the effects of what

synthetically made creatine can provide.

The body can make approximately one gram of creatine daily from the liver, pancreas,

and kidneys. Skeletal muscle contains ninety-five percent of the body's creatine stores, which

plays a crucial role in ATP production via the phosphocreatine shuttle. The remaining five

percent of creatine stores disperses among one's nervous, hepatic, and renal systems (Balestrino,

2021). A study has shown that endogenous synthesis of creatine occurs in the kidney, liver, and

pancreas from the amino acids glycine, arginine, and methionine. The endogenous synthesis of

creatine includes the decomposition of creatine to creatinine, which leads to a stable reduction of

the body's creatinine store. The creatinine store reloads itself partially from endogenous synthesis

and by consuming creatine with meals (Balestrino, 2021).

The kidneys complete the first step of creatine synthesis by forming guanidino acetic acid

from arginine and glycine. Next, Guanidino acetic acid converts to creatine with the involvement

of the methyl donor S-adenosyl-methionine as guanidino acetic acid travels to the liver. The

hepatic and nervous systems can also synthesize creatine for their consumption. Regarding the

human cardiac system, studies have also indicated that cardiomyocytes, cells responsible for the

heart's contraction, may synthesize creatine just as the other body systems can (Balestrino, 2021).

The body's natural synthesis of creatine and additive effects provided by supplemental creatine
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enhance the body's natural energy storage for optimal athletic performance. These effects on the

body are why creatine monohydrate is becoming a supplement of choice among younger

athletes.

Creatine monohydrate is a supplemental version of creatine in the body. Instructions for

creatine use include taking five grams three to five times daily before and after working out.

Whether short duration or high intensity, athletes utilize supplemental creatine to increase the

muscles' strength and performance. In addition, as creatine is a critical component in the body's

natural supply of creatine, supplementation using creatine monohydrate further enhances the

athlete's energy supply for exertion during weightlifting activity. The extensive research on

creatine monohydrate studies its bioavailability, mechanisms of action, supplementation

strategies, ergogenic effects, safety and efficacy in different sports, and clinical applications. In

survey-based studies, the frequent use of creatine monohydrate among recreational and elite

athletes and military personnel have demonstrated 9% to 46%, with a common similarity seen in

high school athletes. In addition, total muscle creatine concentrations also increased significantly

with high doses of supplemental creatine. (Hall et al., 2021). Moreover, various factors play a

role in tissue responsiveness to creatine supplementation, including initial intramuscular creatine

levels, muscle fiber properties, or habitual dietary creatine intake (Hall et al., 2021).

The purpose of various studies surrounding the effectiveness and safety of creatine use

included investigating various dosing strategies to determine the degree of effect on creatine

stores and subsequent per-performance benefits. The most standard effective dosing strategy

utilizes a loading phase of twenty grams divided into four equal doses for five days to seven

days, followed by a more extended maintenance period of three to five grams a day. Without a

loading phase, creatine stores accumulate more slowly, so training benefits may appear more
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gradually. In addition, the body's production of creatine slows down and decreases the amount

made during exogenous creatine supplementation; however, the body's production will return to

baseline after supplementation is discontinued (Hall et al., 2021).

The effects of naturally made creatine and supplemental creatine and the benefits of

having an adequate supply of these stores during periods of exertion are the primary reason

creatine is widely used today by professional and amateur bodybuilders. Many athletes choose to

use this supplement due to its muscle-building effect. Nevertheless, it also has a potentially

negative harmful effect on the kidneys. Creatine ingested as a supplement helps increase the

body's storage of creatine in the muscles. However, the body also needs to excrete all the excess

creatine, and it does this through the kidneys and then the urine.

The kidneys are the organ solely responsible for excretion. Therefore, they filter all the

creatine ingested throughout supplementation. Glomerular filtration rate, plasma urea levels, and

serum creatinine levels are critical indicators of kidney function. The glomerular filtration rate

shows how much blood passes through the kidneys each minute, whereas plasma urea and

creatinine are waste products in the blood that the kidneys filter out. A study that assessed

creatine usage on renal function included a creatine group that ingested anywhere from four to

20 grams daily and a control group that took the placebo solution made of 500 milliliters of

carbohydrates, dextrose, maltodextrin, glucose polymer, and Gatorade powder (Pertille et al.,

2019). The study lasted for 132 weeks. As expected, the placebo group showed no renal function

impairment over 132 weeks. No renal impairment was an anticipated finding as without the

creatine supplement, and the placebo group has no way to impair renal functioning; subjects

were not ingesting anything supplemental that would need to be excreted by the kidneys. As the
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placebo group findings were as expected, the group provided supplemental creatine did not

reveal the anticipated results.

With 136 subjects being placebos and no effects seen, 246 subjects within the creatine

group demonstrated slightly different results. An athlete may administer creatine

supplementation in two ways: as a consistent, steady dose for the entire supplementation or with

loading and sequential maintenance doses. The loading dose is significantly higher than the

maintenance dose as it loads the body with creatine for results to take effect more rapidly. The

study observed both methods of administration within the group receiving creatine

supplementation. Subjects instructed to ingest creatine through the use of a loading dose were

instructed to ingest 20 grams of creatine daily, split into four doses for 12 days. After 12 days,

subjects decreased their dosing to the maintenance dose of five grams daily for 112 weeks. Only

a slight difference in kidney function was noted when this amount of creatine was ingested over

the 112 weeks. The difference was so minute that researchers concluded that the alteration in

kidney function could not be related to creatine supplementation. (Kreider et al., 2019). Although

a relationship was not established between Creatine Monohydrate and impaired kidney function,

a relationship has been between creatine and several post-workout benefits, such as aiding

muscle recovery.

A common side effect of weight lifting is muscle soreness on the days following

extensive amounts of exercise, specifically weightlifting. This soreness is known as exercise-

induced muscle damage from muscular contractions, particularly with unfamiliar activities,

eccentric contractions, or those under heavy loads (Boullosa et al., 2022). There are a few ways

to test the damage to the muscle using serum muscle proteins such as creatine kinase,

interleukin-6, oxidative stress, and delayed onset muscle soreness (Boullosa et al., 2022). This
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study tested the amount of muscle damage markers 24-36 hours post-workout and 48-90 hours

post-workout to see the difference between creatine and placebo effects. The idea is that creatine

in the muscle could help reduce soreness and indirect muscle damage markers. The 240

participants in the creatine group showed lower indirect muscle damage markers in the 48-90

hour period; however, the damage markers were more significant in the creatine group 24-36

hours post-exercise (Boullosa et al., 2022). The amount of muscle damage differs between the

placebo and the creatine groups because creatine helps tear down more muscle during the

workout and repair them quicker post-workout than the placebo group. In addition, the creatine

group showed lower inflammation and oxidative stress in short-term and long-term post-exercise

effects. This difference, again, is the effect of creatine accelerating muscle repair faster than the

placebo group (Boullosa et al., 2022). The most significant finding is the delayed onset of muscle

soreness (DOMS). The placebo group had a high soreness rating post-workout, meaning it would

take longer to recover than the creatine group (Boullosa et al., 2022).

With no real difference in the placebo and creatine groups, it is safe to take and will not

negatively affect the kidneys. Thus, creatine supplementation is safe for short- and long-term

therapy, up to five grams a day, including the administration by a loading dose. In addition to

safety, supplementation also decreases inflammatory response and muscle soreness for 90 hours

after the workout, significantly benefiting the athlete's post-workout recovery. The research

study "Muscle glycogen supercompensation is enhanced by prior creatine supplementation" was

conducted to investigate the effects creatine has on glycogen restoration when loaded

simultaneously with glycogen before exercise. Twelve men participated in this study in which

they "performed two standard glycogen loading protocols interspersed with a standard creatine

load of 20 grams per day for five days" (Nelson et al., 2001). The results of this study found that
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there was a slight increase in glycogen following the first glycogen load. However, after the

creatine and final glycogen loads, there was "a significant 53% increase in muscle glycogen"

(Nelson et al., 2001). Thus, total glycogen content in muscle post-creatine load compared to pre-

creatine load was significantly greater.

Ergogenic aids have been used by athletes for a long time to improve performance. An

ergogenic aid is "a technique or substance used to enhance performance" (Thein et al., 1995).

These aids can be physical, nutritional, and psychological. The scope of ergogenic aids is

extensive and includes dietary shifts such as carb loading and anabolic steroids. Creatine has an

extensive array of ergogenic effects. It is one of many nutritional supplements with consistent

research to support this claim. For example, in the study "International Society of Sports

Nutrition position stand safety and efficacy of creatine supplementation in exercise, sport, and

medicine," researchers found "that creatine supplementation increases muscle availability of

creatine and PCr and can therefore enhance acute exercise capacity" (Kreider et al., 2017).

This allows athletes to compete at higher levels of performance by approximately ten to 20

percent, based on how much the level of phosphocreatine increases (Kreider et al., 2017). Some

potential benefits are "increased single and repetitive sprint performance, increased muscle mass

& strength adaptations during training, and enhanced glycogen synthesis" (Kreider et al., 2017).

Ergogenic effects are reported in men, women, and young and elderly populations. However,

most of these studies have been conducted on men (Kreider et al., 2017).

Creatine has not only been studied for its ergogenic effects and ability to assist athletes in

increasing high performance or adapting to training schedules. Researchers Richard B. Kreider

and Jeffery R. Stout investigated the potential health benefits of creatine for the general

population, not just high-performing athletes. Researchers reported that creatine supplementation
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had been shown to help enhance glycemic control, diminish the build-up of fat in the liver, and

in some cases, even make antidepressants more effective (Thein et al., 1995).

Creatine has also been studied for its psychological effects on athletes throughout their

training periods. In the study "Psychological effect of acute creatine pre-workout

supplementation induces performance improvement in resistance exercise," researchers analyzed

data collected over six lab visits. The participants of this study were young men with recreational

weightlifting experience who did not previously use dietary or nutritional supplements (Kreider

& Stout, 2021). During the first two sessions, the participants performed ten repetition

maximums for squat and bench presses. Then, throughout the subsequent four visits, participants

were randomly provided no creatine, dextrose, creatine, or dextrose they believed to be creatine

(placebo) (Kreider & Stout, 2021). They were then asked to perform three sets of their repetition

maximum load with a minute of rest between sets. Researchers recorded the participants' level of

fatigue during these rest periods (Kreider & Stout, 2021). Once all the data had been recorded,

they used an ANOVA test to analyze their data and test for statistical significance. The results of

this study showed that the exercise performance yield of participants taking creatine compared to

participants taking what they believed to be creatine was similar (Kreider & Stout, 2021).

The long-term effects of creatine on young athletes still need to be fully understood. In addition,

there is a need for further research to determine the potential risks associated with its use in this

population.

In conclusion, creatine offers short-term benefits for athletic performance when young

athletes approach its use as intended. When used as intended, minimal adverse effects arise on

health in development. Before use, users interested in beginning creatine supplementation should

prioritize safe and healthy training methods over quick fixes that may have long-lasting
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consequences, such as misusing supplementation. In turn, creatine is a safe and highly researched

supplement to be utilized by young adults aged 16-21. However, more research is needed to

unveil any adversities that would be specific to this demographic.

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References

Aguiar, M., Pereira, R., Koch., A., & Machado, M. (5, April 2022) Psychological effect of acute

creatine pre-workout supplementation induces performance improvement in resistance

exercise. Research in Sports Medicine, DOI: 10.1080/15438627.2022.2090253

Boullosa, D., Doma, K., Ramachandran, A.K., (2, January 2022) The Paradoxical Effect of

Creatine Monohydrate on Muscle Damage Markers. A Systematic Review and Meta-

Analysis. Sports Med 52, 1623–1645 https://doi.org/10.1007/s40279-022-01640-z

Jagim, A. R., Stecker, R. A., Harty, P. S., Erickson, J. L., & Kerksick, C. M. (2018). Safety of

Creatine Supplementation in Active Adolescents and Youth: A Brief Review. Frontiers

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Hall, M., Manetta, E., & Tupper, K. (2021). Creatine Supplementation: An Update. Current

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Kreider, R., Kalman, D., Antonio, J., Ziegenfuss, T., Wildman, R., Collins, R., Candow, D.,

Kleiner, S., Almada, A., & Lopez, C.(13, June 2017)International Society of Sports

Nutrition position stand: safety and efficacy of creatine supplementation in exercise,

sport, and medicine. J Int Soc Sports Nutr 14, 18 https://doi.org/10.1186/s12970-017-

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Nelson, Arnold G., Arnall, David A., Kokkonen, J., Day, R.; Evans, J. (July 2001). Muscle

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and Science in Sports and Exercise. 33(7), 1096–1100.

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Pertille, A., Reis Barbosa, C., Aparecida de Oliveira Silva, J., de Jesus, D., Ribeiro, A., Baganha,

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