Journal of the International Society of Sports Nutrition
© 2007 Buford et al., licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
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International Society of Sports
Nutrition position stand:
creatine supplementation and exercise
Thomas W. Buford, Richard B. Kreider*, Jeffrey R. Stout, Mike Greenwood, Bill
Campbell, Marie Spano, Tim Ziegenfuss, Hector Lopez, Jamie Landis, Jose
Antonio
International Society of Sports Nutrition
600 Pembrook Drive
Woodland Park, CO 80863, USA
* Corresponding Author
Email Addresses:
TWB: thomas_buford@baylor.edu
RBK: Richard_Kreider@baylor.edu
JRS: jrstout@ou.edu
MG: Mike_Greenwood@baylor.edu
BC: Campbell@coedu.usf.edu
MS: mariespano@comcast.net
TZ: tim@ohioresearchgroup.com
HL: hlopezmd@gmail.com
JL: jlandis@lakelandcc.edu
A Position Statement and Review of the Literature
Position Statement: The following nine points related to the use of creatine
as a nutritional supplement constitute the Position Statement of the
Society. They have been approved by the Research Committee of the
Society.
1. Creatine monohydrate is the most effective ergogenic nutritional
supplement currently available to athletes in terms of increasing highintensity
exercise capacity and lean body mass during training.
2. Creatine monohydrate supplementation is not only safe, but possibly
beneficial in regard to preventing injury and/or management of select
medical conditions when taken within recommended guidelines.
3. There is no scientific evidence that the short- or long-term use of creatine
monohydrate has any detrimental effects on otherwise healthy individuals.
4. If proper precautions and supervision are provided, supplementation in
young athletes is acceptable and may provide a nutritional alternative to
potentially dangerous anabolic drugs.
5. At present, creatine monohydrate is the most extensively studied and
clinically effective form of creatine for use in nutritional supplements in
terms of muscle uptake and ability to increase high-intensity exercise
capacity.
6. The addition of carbohydrate or carbohydrate and protein to a creatine
supplement appears to increase muscular retention of creatine, although
the effect on performance measures may not be greater than using
creatine monohydrate alone.
7. The quickest method of increasing muscle creatine stores appears to be
to consume ~ 0.3 grams/kg/day of creatine monohydrate for at least 3
days followed by 3-5 g/d thereafter to maintain elevated stores. Ingesting
smaller amounts of creatine monohydrate (e.g., 2-3 g/d) will increase
muscle creatine stores over a 3-4 week period, however, the performance
effects of this method of supplementation are less supported.
8. Creatine products are readily available as a dietary supplement and are
regulated by the U.S. Food and Drug Administration (FDA). Specifically,
in 1994, U.S. President Bill Clinton signed into law the Dietary Supplement
Health and Education Act (DSHEA). DSHEA allows
manufacturers/companies/brands to make structure-function claims;
however, the law strictly prohibits disease claims for dietary supplements.
9. Creatine monohydrate has been reported to have a number of potentially
beneficial uses in several clinical populations, and further research is
warranted in these areas.
The following literature review has been prepared by the authors in support of the
aforementioned position statement.
Creatine Supplementation and Exercise:
A Review of the Literature
Introduction
The use of creatine as a sport supplement has been surrounded by both
controversy and fallacy since it gained widespread popularity in the early 1990’s.
Anecdotal and media reports have often claimed that creatine usage is a
dangerous and unnecessary practice; often linking creatine use to anabolic
steroid abuse [1]. Many athletes and experts in the field have reported that
creatine supplementation is not only beneficial for athletic performance and
various medical conditions but is also clinically safe [2-5]. Although creatine has
recently been accepted as a safe and useful ergogenic aid, several myths have
been purported about creatine supplementation which include:
1. All weight gained during supplementation is due to water retention.
2. Creatine supplementation causes renal distress.
3. Creatine supplementation causes cramping, dehydration, and/or altered
electrolyte status.
4. Long-term effects of creatine supplementation are completely unknown.
5. Newer creatine formulations are more beneficial than creatine
monohydrate (CM) and cause fewer side effects.
6. It’s unethical and/or illegal to use creatine supplements.
While these myths have been refuted through scientific investigation, the general
public is still primarily exposed to the mass media which may or may not have
accurate information. Due to this confounding information, combined with the fact
that creatine has become one of the most popular nutritional supplements on the
market, it is important to examine the primary literature on supplemental creatine
ingestion in humans. The purpose of this review is to determine the present state
of knowledge concerning creatine supplementation, so that reasonable
guidelines may be established and unfounded fears diminished in regard to its
use.
Background
Creatine has become one of the most extensively studied and scientifically
validated nutritional ergogenic aids for athletes. Additionally, creatine has been
evaluated as a potential therapeutic agent in a variety of medical conditions such
as Alzheimer’s and Parkinson’s diseases. Biochemically speaking, the energy
supplied to rephosphorylate adenosine diphosphate (ADP) to adenosine
triphosphate (ATP) during and following intense exercise is largely dependent on
the amount of phosphocreatine (PCr) stored in the muscle [6-7]. As PCr stores
become depleted during intense exercise, energy availability diminishes due to
the inability to resynthesize ATP at the rate required to sustained high-intensity
exercise [6-7]. Consequently, the ability to maintain maximal-effort exercise
declines. The availability of PCr in the muscle may significantly influence the
amount of energy generated during brief periods of high-intensity exercise.
Furthermore, it has been hypothesized that increasing muscle creatine content,
via creatine supplementation, may increase the availability of PCr allowing for an
accelerated rate of resynthesis of ATP during and following high-intensity, shortduration
exercise [6-12]. Theoretically, creatine supplementation during training
may lead to greater training adaptations due to an enhanced quality and volume
of work performed. In terms of potential medical applications, creatine is
intimately involved in a number of metabolic pathways. For this reason, medical
researchers have been investigating the potential therapeutic role of creatine
supplementation in a variety of patient populations.
Creatine is chemically known as a non-protein nitrogen; a compound which
contains nitrogen but is not a protein per se [13]. It is synthesized in the liver and
pancreas from the amino acids arginine, glycine, and methionine [9,13-14].
Approximately 95% of the body’s creatine is stored in skeletal muscle.
Additionally, small amounts of creatine are also found in the brain and testes
[8,15]. About two thirds of the creatine found in skeletal muscle is stored as
phosphocreatine (PCr) while the remaining amount of creatine is stored as free
creatine [8]. The total creatine pool (PCr + free creatine) in skeletal muscle
averages about 120 grams for a 70 kg individual. However, the average human
has the capacity to store up to 160 grams of creatine under certain conditions
[7,9]. The body breaks down about 1 – 2% of the creatine pool per day (about 1-
2 grams/day) into creatinine in the skeletal muscle [13]. The creatinine is then
excreted in urine [13,16]. Creatine stores can be replenished by obtaining
creatine in the diet or through endogenous synthesis of creatine from glycine,
arginine, and methionine [17-18]. Dietary sources of creatine include meats and
fish. Large amounts of fish and meat must be consumed in order to obtain gram
quantities of creatine. Whereas dietary supplementation of creatine provides an
inexpensive and efficient means of increasing dietary availability of creatine
without excessive fat and/or protein intake.
Supplementation Protocols and Effects on Muscle Creatine Stores
Various supplementation protocols have been suggested to be efficacious in
increasing muscle stores of creatine. The amount of increase in muscle storage
depends on the levels of creatine in the muscle prior to supplementation. Those
who have lower muscle creatine stores, such as those who eat little meat or fish,
are more likely to experience muscle storage increases of 20-40%, whereas
those with relatively high muscle stores may only increase stores by 10-20% [19].
The magnitude of the increase in skeletal muscle creatine content is important
because studies have reported performance changes to be correlated to this
increase [20-21].
The supplementation protocol most often described in the literature is referred to
as the “loading” protocol. This protocol is characterized by ingesting
approximately 0.3 grams/kg/day of CM for 5 - 7 days (e.g., ~ 5 grams taken four
times per day) and 3-5 grams/day thereafter [18,22]. Research has shown a 10-
40% increase in muscle creatine and PCr stores using this protocol [10,22].
Additional research has reported that the loading protocol may only need to be 2-
3 days in length to be beneficial, particularly if the ingestion coincides with protein
and/or carbohydrate [23-24]. Furthermore, supplementing with 0.25 grams/ kg-fat
free mass/day of CM may be an alternative dosage sufficient to increase muscle
creatine stores [25].
Other suggested supplementation protocols utilized include those with no loading
phase as well as “cycling” strategies. A few studies have reported protocols with
no loading period to be sufficient for increasing muscle creatine (3 g/d for 28
days) [15] as well as muscle size and strength (6 g/d for 12 weeks) [26-27].
These protocols seems to be equally effective in increasing muscular stores of
creatine, but the increase is more gradual and thus the ergogenic effect does not
occur as quickly. Cycling protocols involve the consumption of “loading” doses for
3-5 days every 3 to 4 weeks [18,22]. These cycling protocols appear to be
effective in increasing and maintaining muscle creatine content before a drop to
baseline values, which occurs at about 4-6 weeks [28-29].
Creatine Formulations and Combinations
Many forms of creatine exist in the marketplace, and these choices can be very
confusing for the consumer. Some of these formulations and combinations
include creatine phosphate, creatine + -hydroxy--methlybutyrate (HMB),
creatine + sodium bicarbonate, creatine magnesium-chelate, creatine + glycerol,
creatine + glutamine, creatine + -alanine, creatine ethyl ester, creatine with
cinnulin extract, as well as “effervescent” and “serum formulations”. Most of
these forms of creatine have been reported to be no better than traditional CM in
terms of increasing strength or performance [30-38]. Reliable studies are yet to
be published for creatine ethyl ester and creatine with cinnulin extract. Recent
studies do suggest, however, that adding -alanine to CM may produce greater
effects than CM alone. These investigations indicate that the combination may
have greater effects on strength, lean mass, and body fat percentage; in addition
to delaying neuromuscular fatigue [31-32].
Three alternative creatine formulations have shown promise, but at present do
not have sufficient evidence to warrant recommendation in lieu of CM. For
example, creatine phosphate has been reported to be as effective as CM at
improving LBM and strength, [36] yet this has only been reported in one study. In
addition, creatine phosphate is currently more difficult and expensive to produce
than CM. Combining CM with sodium phosphate, which has been reported to
enhance high-intensity endurance exercise, may be a more affordable alternative
to creatine phosphate. Secondly, a creatine/HMB combination was reported to be
more effective at improving LBM and strength than either supplement alone [39],
but other data has reported the combination offers no benefit in terms of
increasing aerobic or anaerobic capacity [40-41]. The conflicting data therefore
do not warrant recommendation of the creatine/HMB combination in lieu of CM.
Lastly, creatine + glycerol has been reported to increase total body water as a
hyper-hydration method prior to exercise in the heat, but this is also the first
study of its kind. In addition, this combination failed to improve thermal and
cardiovascular responses to a greater extent than CM alone [42].
The addition of nutrients that increase insulin levels and/or improve insulin
sensitivity has been a major source of interest in the last few years by scientists
looking to optimize the ergogenic effects of creatine. The addition of certain
macronutrients appears to significantly augment muscle retention of creatine.
Green et al. [24] reported that adding 93 g of carbohydrate to 5 g of CM
increased total muscle creatine by 60%. Likewise, Steenge et al. [23] reported
that adding 47 g of carbohydrate and 50 g of protein to CM was as effective at
promoting muscle retention of creatine as adding 96 g of carbohydrate.
Additional investigations by Greenwood and colleagues [30,43] have reported
increased creatine retention from the addition of dextrose or low levels of Dpinitol
(a plant extract with insulin-like properties). While the addition of these
nutrients has proved to increase muscle retention, several recent investigations
have reported these combinations to be no more effective at improving muscle
strength and endurance or athletic performance [44-46]. Other recent studies,
however, have indicated a potential benefit on anaerobic power, muscle
hypertrophy, and 1RM muscle strength when combining protein with creatine
[47-48]. It appears that combining CM with carbohydrate or carbohydrate and
protein produces optimal results. Studies suggest that increasing skeletal muscle
creatine uptake may enhance the benefits of training.
Effects of Supplementation on Exercise Performance and Training
Adaptations
CM appears to be the most effective nutritional supplement currently available in
terms of improving lean body mass and anaerobic capacity. To date, several
hundred peer-reviewed research studies have been conducted to evaluate the
efficacy of CM supplementation in improving exercise performance. Nearly 70%
of these studies have reported a significant improvement in exercise capacity,
while the others have generally reported non-significant gains in performance
[49]. No studies have reported an ergolytic effect on performance although some
have suggested that weight gain associated with CM supplementation could be
detrimental in sports such as running or swimming. The average gain in
performance from these studies typically ranges between 10 to 15% depending
on the variable of interest. For example, short-term CM supplementation has
been reported to improve maximal power/strength (5-15%), work performed
during sets of maximal effort muscle contractions (5-15%), single-effort sprint
performance (1-5%), and work performed during repetitive sprint performance (5-
15%) [49]. Long-term CM supplementation appears to enhance the overall
quality of training, leading to 5 to 15% greater gains in strength and performance
[49]. Nearly all studies indicate that “proper” CM supplementation increases body
mass by about 1 to 2 kg in the first week of loading [19].
The vast expanse of literature confirming the effectiveness of CM
supplementation is far beyond the scope of this review. Briefly, short-term
adaptations reported from CM supplementation include increased cycling power,
total work performed on the bench press and jump squat, as well as improved
sport performance in sprinting, swimming, and soccer [38,50-57]. Long-term
adaptations when combining CM supplementation with training include increased
muscle creatine and PCr content, lean body mass, strength, sprint performance,
power, rate of force development, and muscle diameter [39,54-60]. In long-term
studies, subjects taking CM typically gain about twice as much body mass and/or
fat free mass (i.e., an extra 2 to 4 pounds of muscle mass during 4 to 12 weeks
of training) than subjects taking a placebo. The gains in muscle mass appear to
be a result of an improved ability to perform high-intensity exercise via increased
PCr availability and enhanced ATP synthesis, thereby enabling an athlete to train
harder and promote greater muscular hypertrophy via increased myosin heavy
chain expression possibly due to an increase in myogenic regulatory factors
myogenin and MRF-4 [26-27,65]. The tremendous numbers of investigations
conducted with positive results from CM supplementation lead us to conclude
that it is the most effective nutritional supplement available today for increasing
high-intensity exercise capacity and building lean mass.
Medical Safety of Creatine Supplementation
While the only clinically significant side effect reported in the research literature is
that of weight gain [4,18,22], many anecdotal claims of side effects including
dehydration, cramping, kidney and liver damage, musculoskeletal injury,
gastrointestinal distress, and anterior (leg) compartment syndrome still exist in
the media and popular literature. While athletes who are taking CM may
experience these symptoms, the scientific literature suggests that these athletes
have no greater, and a possibly lower, risk of these symptoms than those not
supplementing with CM [2,4,66-67].
Many of these fears have been generated by the media and data taken from
case studies (n=1). Poortmans and Francaux reported that the claims of
deleterious effects of creatine supplements on renal function began in 1998 [68].
These claims followed a report that creatine supplementation was detrimental to
renal glomerular filtration rate (GFR) in a 25-year-old man who had previously
presented with kidney disease (glomerulosclerosis and corticosteroid-responsive
nephritic syndrome) [69]. Three days later, a French sports newspaper, L’Equipe,
reported that supplemental creatine is dangerous for the kidneys in any condition
[70]. Several European newspapers then picked up the “news” and reported the
same. Since that time, other individual case studies have been published posing
that CM supplementation caused deleterious effects on renal function [71-72].
Much of the concern about CM supplementation and renal function has centered
around concerns over increased serum creatinine levels. While creatinine does
make up a portion of GFR and must be excreted by the kidneys, there is no
evidence to support the notion that normal creatine intakes (< 25 g/d) in healthy
adults cause renal dysfunction. In fact, Poortmans et al. have shown no
detrimental effects of short- (5 days), medium- (14 days), or long-term (10
months to 5 years) CM supplementation on renal function [5,73-74]. Interestingly,
Kreider et al. [4] observed no significant difference in creatinine levels between
CM users and controls, yet most athletes (regardless of whether taking CM or
not) had elevated creatinine levels along with proper clearance during intense
training. The authors noted that if serum creatinine was examined as the sole
measure of renal function, it would appear that nearly all of the athletes
(regardless of CM usage) were experiencing renal distress. Although case
studies have reported problems, these large-scale, controlled studies have
shown no evidence indicating that CM supplementation in healthy individuals is a
detriment to kidney functioning.
Another anecdotal complaint about supplemental creatine is that the long-term
effects are not known. Widespread use of CM began in the 1990’s. Over the last
few years a number of researchers have begun to release results of long-term
safety trials. So far, no long-term side effects have been observed in athletes (up
to 5 years), infants with creatine synthesis deficiency (up to 3 years), or in clinical
patient populations (up to 5 years) [4-5,18,75-76]. One cohort of patients taking
1.5 – 3 grams/day of CM has been monitored since 1981 with no significant side
effects [77-78]. In addition, research has demonstrated a number of potentially
helpful clinical uses of CM in heart patients, infants and patients with creatine
synthesis deficiency, patients suffering orthopedic injury, and patients with
various neuromuscular diseases. Potential medical uses of supplemental
creatine have been investigated since the mid 1970s. Initially, research focused
on the role of CM and/or creatine phosphate in reducing heart arrhythmias and/or
improving heart function during ischemic events [18]. Interest in medical uses of
creatine supplements has expanded to include those with creatine deficiencies
[79-81], brain and/or spinal cord injuries [82-86], muscular dystrophy [87-90],
diabetes [91], high cholesterol/triglyceride levels [92], and pulmonary disease
[93] among others. Although more research is needed to determine the extent of
the clinical utility, some promising results have been reported in a number of
studies suggesting that creatine supplements may have therapeutic benefit in
certain patient populations. In conjunction with short- and long-term studies in
healthy populations, this evidence suggests that creatine supplementation
appears to be safe when taken within recommended usage guidelines.
Creatine Use in Children and Adolescents
Opponents of creatine supplementation have claimed that it is not safe for
children and adolescents [1]. While fewer investigations have been conducted in
using younger participants, no study has shown CM to have adverse effects in
children. In fact, long-term CM supplementation (e.g., 4 – 8 grams/day for up to 3
years) has been used as an adjunctive therapy for a number of creatine
synthesis deficiencies and neuromuscular disorders in children. Clinical trials are
also being conducted in children with Duschenne muscular dystrophy [87-88].
However, as less is known about the effects of supplemental creatine on children
and adolescents, it is the view of the ISSN that younger athletes should consider
a creatine supplement only if the following conditions are met [19]:
1. The athlete is past puberty and is involved in serious/competitive training
that may benefit from creatine supplementation;
2. The athlete is eating a well-balanced, performance-enhancing diet;
3. The athlete and his/her parents understand the truth concerning the
effects of creatine supplementation;
4. The athlete’s parents approve that their child takes supplemental creatine;
5. Creatine supplementation can be supervised by the athletes parents,
trainers, coaches, and/or physician;
6. Quality supplements are used; and,
7. The athlete does not exceed recommended dosages.
If these conditions are met, then it would seem reasonable that high school
athletes should be able to take a creatine supplement. Doing so may actually
provide a safe nutritional alternative to illegal anabolic steroids or other
potentially harmful drugs. Conversely, if the above conditions are not met, then
creatine supplementation may not be appropriate. It appears that this is no
different than teaching young athletes’ proper training and dietary strategies to
optimize performance. Creatine is not a panacea or short cut to athletic success.
It can, however, offer some benefits to optimize training of athletes involved in
intense exercise in a similar manner that ingesting a high-carbohydrate diet,
sports drinks, and/or carbohydrate loading can optimize performance of an
endurance athlete.
The Ethics of Creatine
Several athletic governing bodies and special interest groups have questioned
whether it is ethical for athletes to take creatine supplements as a method of
enhancing performance. Since research indicates that CM can improve
performance, and it would be difficult to ingest enough creatine from food in the
diet, they rationalize that it is unethical to do so. In this age of steroid suspicion in
sports, some argue that if you allow athletes to take creatine, they may be more
predisposed to try other dangerous supplements and/or drugs. Still others have
attempted to directly lump creatine in with anabolic steroids and/or banned
stimulants and have called for a ban on the use of CM and other supplements
among athletes. Finally, fresh off of the ban of dietary supplements containing
ephedra, some have called for a ban on the sale of CM citing safety concerns.
Creatine supplementation is not currently banned by any athletic organization
although the NCAA does not allow institutions to provide CM or other “muscle
building” supplements to their athletes (e.g., protein, amino acids, HMB, etc). In
this case, athletes must purchase creatine containing supplements on their own.
The International Olympic Committee considered these arguments and ruled that
there was no need to ban creatine supplements since creatine is readily found in
meat and fish and there is no valid test to determine whether athletes are taking
it. In light of the research that has been conducted with CM, it appears that those
who call for a ban on it are merely familiar with the anecdotal myths surrounding
the supplement, and not the actual facts. We see no difference between creatine
supplementation and ethical methods of gaining athletic advantage such as using
advanced training techniques and proper nutritional methods. Carbohydrate
loading is a nutritional technique used to enhance performance by enhancing
glycogen stores. We see no difference between such a practice and
supplementing with creatine to enhance skeletal muscle creatine and PCr stores.
If anything, it could be argued that banning the use of creatine would be unethical
as it has been reported to decrease the incidence of musculoskeletal injuries
[2,66,75,94], heat stress [2,95-96], provide neuroprotective effects [82-83,85,97-
98], and expedite rehabilitation from injury [86,99-100].
Conclusions
It is the position of the International Society of Sports Nutrition that the use of
creatine as a nutritional supplement within established guidelines is safe,
effective, and ethical. Despite lingering myths concerning creatine
supplementation in conjunction with exercise, CM remains one of the most
extensively studied, as well as effective, nutritional aids available to athletes.
Hundreds of studies have shown the effectiveness of CM supplementation in
improving anaerobic capacity, strength, and lean body mass in conjunction with
training. In addition, CM has repeatedly been reported to be safe, as well as
possibly beneficial in preventing injury. Finally, the future of creatine research
looks bright in regard to the areas of transport mechanisms, improved muscle
retention, as well as treatment of numerous clinical maladies via
supplementation.
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