ArticlePDF AvailableLiterature Review

Abstract and Figures

Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).
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R E V I E W Open Access
International Society of Sports Nutrition
position stand: safety and efficacy of
creatine supplementation in exercise, sport,
and medicine
Richard B. Kreider
1*
, Douglas S. Kalman
2
, Jose Antonio
3
, Tim N. Ziegenfuss
4
, Robert Wildman
5
, Rick Collins
6
,
Darren G. Candow
7
, Susan M. Kleiner
8
, Anthony L. Almada
9
and Hector L. Lopez
4,10
Abstract
Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine
supplementation increases intramuscular creatine concentrations which may help explain the observed improvements
in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise
improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention,
thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical
applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular
dystrophy, Parkinsons, Huntingtons disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia,
adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only
improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing
rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a
number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term
supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient
populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring
habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an
update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine
and to update the position stand of International Society of Sports Nutrition (ISSN).
Keywords: Ergogenic aids, Performance enhancement, Sport nutrition, Athletes, Muscular strength, Muscle power, Clinical
applications, Safety, Children, Adolescents
Background
Creatine is one of the most popular nutritional ergogenic
aids for athletes. Studies have consistently shown that
creatine supplementation increases intramuscular creatine
concentrations, can improve exercise performance, and/or
improve training adaptations. Research has indicated that
creatine supplementation may enhance post-exercise recov-
ery, injury prevention, thermoregulation, rehabilitation, and
concussion and/or spinal cord neuroprotection. A number
of clinical applications of creatine supplementation have
also been studied involving neurodegenerative diseases
(e.g., muscular dystrophy, Parkinsons, Huntingtons
disease), diabetes, osteoarthritis, fibromyalgia, aging, brain
and heart ischemia, adolescent depression, and pregnancy.
The purpose of this review is to provide an update to the
current literature regarding the role and safety of creatine
supplementation in exercise, sport, and medicine and to
update the position stand of International Society of Sports
Nutrition (ISSN) related to creatine supplementation.
* Correspondence: rbkreider@tamu.edu
1
Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department
of Health & Kinesiology, Texas A&M University, College Station, TX
77843-4243, USA
Full list of author information is available at the end of the article
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18
DOI 10.1186/s12970-017-0173-z
Metabolic role
Creatine, a member of the guanidine phosphagen family, is
a naturally occurring non-protein amino acid compound
found primarily in red meat and seafood [14]. The major-
ity of creatine is found in skeletal muscle (~95%) with small
amounts also found in the brain and testes (~5%) [5, 6].
About two thirds of intramuscular creatine is phosphocrea-
tine (PCr) with the remaining being free creatine. The total
creatine pool (PCr + Cr) in the muscle averages about
120 mmol/kg of dry muscle mass for a 70 kg individual [7].
However, the upper limit of creatine storage appears to be
about 160 mmol/kg of dry muscle mass in most individuals
[7, 8]. About 12% of intramuscular creatine is degraded
into creatinine (metabolic byproduct) and excreted in the
urine [7, 9, 10]. Therefore, the body needs to replenish
about 13 g of creatine per day to maintain normal
(unsupplemented) creatine stores depending on muscle
mass. About half of the daily need for creatine is obtained
from the diet [11]. For example, a pound of uncooked beef
and salmon provides about 12 g of creatine [9]. The
remaining amount of creatine is synthesized primarily in
the liver and kidneys from arginine and glycine by the
enzyme arginine:glycine amidinotransferase (AGAT) to
guanidinoacetate (GAA), which is then methylated by
guanidinoacetate N-methyltransferase (GAMT) using
S-adenosyl methionine to form creatine (see Fig. 1) [12].
Some individuals have been found to have creatine
synthesis deficiencies due to inborn errors in AGAT,
GMAT and/or creatine transporter (CRTR) deficiencies
and therefore must depend on dietary creatine intake in
order to maintain normal muscle and brain concentra-
tions of PCr and Cr [1319]. Vegetarians have been
reported to have lower intramuscular creatine stores (90
110 mmol/kg of dry muscle) and therefore may observe
greater gains in muscle creatine content from creatine
supplementation [11, 13, 20, 21]. Conversely, larger ath-
letes engaged in intense training may need to consume 5
10 g/day of creatine to maintain optimal or capacity whole
body creatine stores [22] and clinical populations may
need to consume 1030 g/day throughout their lifespan
to offset creatine synthesis deficiencies and/or provide
therapeutic benefit in various disease states [13, 19, 23].
Phosphagens are prevalent in all species and play an im-
portant role in maintaining energy availability [1, 2, 24, 25].
Theprimarymetabolicroleofcreatineistocombinewith
a phosphoryl group (Pi) to form PCr through the enzym-
atic reaction of creatine kinase (CK). Wallimann and col-
leagues [2628] suggested that the pleiotropic effects of Cr
are mostly related to the functions of CK and PCr (i.e.,
CK/PCr system). As adenosine triphosphate (ATP) is de-
graded into adenosine diphosphate (ADP) and Pi to pro-
vide free energy for metabolic activity, the free energy
released from the hydrolysis of PCr into Cr + Pi can be
used as a buffer to resynthesize ATP [24, 25]. This helps
maintain ATP availability particularly during maximal ef-
fort anaerobic sprint-type exercise. The CK/PCr system
also plays an important role in shuttling intracellular en-
ergy from the mitochondria into the cytosol (see Fig. 2).
The CK/PCr energy shuttle connects sites of ATP produc-
tion (glycolysis and mitochondrial oxidative phosphoryl-
ation) with subcellular sites of ATP utilization (ATPases)
[24, 25, 27]. In this regard, creatine enters the cytosol
through a CRTR [16, 2931]. In the cytosol, creatine and
associated cytosolic and glycolytic CK isoforms help
Fig. 1 Chemical structure and biochemical pathway for creatine synthesis. From Kreider and Jung [6]
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 2 of 18
Fig. 2 Proposed creatine kinase/phosphocreatine (CK/PCr) energy shuttle. CRT = creatine transporter; ANT =adenine nucleotide translocator; ATP =
adenine triphosphate; ADP = adenine diphosphate; OP = oxidative phosphorylation; mtCK = mitochondrial creatine kinase; G = glycolysis; CK-g =
creatine kinase associated with glycolytic enzymes; CK-c =cytosolic creatine kinase; CK-a =creatine kinase associated with subcellular sites of ATP
utilization; 1 4 sites of CK/ATP interaction. From Kreider and Jung [6]
Fig. 3 Role of mitochondrial creatine kinase (mtCK) in high energy metabolite transport and cellular respiration. VDAC = voltage-dependent anion
channel; ROS = reactive oxygen species; RNS = reactive nitrogen species; ANT = adenine nucleotide translocator; ATP = adenine triphosphate; ADP
= adenine diphosphate; Cr = creatine; and, PCr = phosphocreatine. From Kreider and Jung [6]
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 3 of 18
maintain glycolytic ATP levels, the cytosolic ATP/ADP ra-
tio, and cytosolic ATP-consumption [27]. Additionally, cre-
atine diffuses into the mitochondria and couples with ATP
produced from oxidative phosphorylation and the adenine
nucleotide translocator (ANT) via mitochondrial CK (see
Fig. 3). ATP and PCr can then diffuse back into the cytosol
and help buffer energy needs. This coupling also reduces
the formation of reactive oxygen species (ROS) and can
therefore act as a direct and/or indirect antioxidant [32
35]. The CK/PCr energy shuttle thereby connects sites of
ATP production (glycolysis and mitochondrial oxidative
phosphorylation) with subcellular sites of ATP utilization
(ATPases) in order to fuel energy metabolism [24, 25, 27].
In this way, the CK/PCr system thereby serves as an
important regulator of metabolism which may help explain
the ergogenic and potential therapeutic health benefits of
creatine supplementation [4, 27, 33, 3645].
Supplementation protocols
In a normal diet that contains 12 g/day of creatine,
muscle creatine stores are about 6080% saturated.
Therefore, dietary supplementation of creatine serves to
increase muscle creatine and PCr by 2040% (see Fig. 4.)
[7, 8, 10, 4648]. The most effective way to increase
muscle creatine stores is to ingest 5 g of creatine mono-
hydrate (or approximately 0.3 g/kg body weight) four
times daily for 57 days [7, 10]. However, higher levels
of creatine supplementation for longer periods of time
may be needed to increase brain concentrations of creat-
ine, offset creatine synthesis deficiencies, or influence
disease states [13, 19, 23]. Once muscle creatine stores
are fully saturated, creatine stores can generally be main-
tained by ingesting 35 g/day, although some studies
indicate that larger athletes may need to ingest as much
as 510 g/day in order to maintain creatine stores [7, 8, 10,
4648]. Ingesting creatine with carbohydrate or carbohydrate
and protein have been reported to more consistently promote
greater creatine retention [8, 22, 49, 50]. An alternative
supplementation protocol is to ingest 3 g/day of creatine
monohydrate for 28 days [7]. However, this method
would only result in a gradual increase in muscle
creatine content compared to the more rapid loading
method and may therefore have less effect on exercise
performance and/or training adaptations until creatine
stores are fully saturated. Research has shown that
once creatine stores in the muscle are elevated, it
generally takes 46 weeks for creatine stores to re-
turn to baseline [7, 48, 51]. Additionally, it has been
recommended that due to the health benefits of
creatine, individuals should consume about 3 g/day of
creatine in their diet particularly as one ages [27]. No
evidence has suggested that muscle creatine levels fall
below baseline after cessation of creatine supplemen-
tation; therefore, the potential for long-term suppres-
sion of endogenous creatine synthesis does not appear
to occur [22, 52].
Bioavailability
The most commonly studied form of creatine in the
literature is creatine monohydrate [53]. The uptake of
creatine involves the absorption of creatine into the
blood and then uptake by the target tissue [53]. Plasma
levels of creatine typically peak at about 60 min after
oral ingestion of creatine monohydrate [7]. An initial rise
in plasma creatine levels, followed by a reduction in
plasma levels can be used to indirectly suggest increased
uptake into the target tissue [53]. However, the gold
standards for measuring the effects of creatine supple-
mentation on target tissues are through magnetic resonance
spectroscopy (MRS), muscle biopsy, stable isotope tracer
studies, and/or whole body creatine retention assessed by
Fig. 4 Approximate muscle total creatine levels in mmol/kg dry weight muscle reported in the literature for vegetarians, individuals following a
normal diet, and in response to creatine loading with or without carbohydrate (CHO) or CHO and protein (PRO). From Kreider and Jung [6]
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 4 of 18
measuring the difference between creatine intake and urinary
excretion of creatine [53].
Creatine is stable in solid form but not in aqueous so-
lution due to an intramolecular cyclization [54]. Gener-
ally, creatine is converted to creatinine at higher rates
the lower the pH and the higher the temperature. For
example, research has shown that creatine is relatively
stable in solution at neutral pH (7.5 or 6.5). However,
after 3 days of storage at 25 °C, creatine degrades to cre-
atinine (e.g., 4% at pH 5.5; 12% at pH 4.5; and 21% at
pH 3.5) [53, 55]. The degradation of creatine into cre-
atinine over time is the main reason that creatine is sold
in solid form. However, this does not mean that creatine
is degraded into creatinine in vivo through the digestive
process. In this regard, the degradation of creatine to
creatinine can be reduced or halted be either lowering
the pH under 2.5 or increasing the pH [53]. A very low
pH results in the protonation of the amide function of
the creatine molecule, thereby preventing the intra-
molecular cyclization [53]. Therefore, the conversion of
creatine to creatinine in the gastrointestinal tract is min-
imal regardless of transit time; absorption into the blood
is nearly 100% [10, 53, 56, 57].
The vast majority of studies assessing the efficacy of
creatine supplementation on muscle phosphagen levels,
whole body creatine retention, and/or performance have
evaluated creatine monohydrate. Claims that different
forms of creatine are degraded to a lesser degree than
creatine monohydrate in vivo or result in a greater up-
take to muscle are currently unfounded [53]. Clinical
evidence has not demonstrated that different forms of
creatine such as creatine citrate [50], creatine serum
[58], creatine ethyl ester [59], buffered forms of creatine
[60], or creatine nitrate [61] promote greater creatine re-
tention than creatine monohydrate [53].
Ergogenic value
Table 1 presents the reported ergogenic benefits of
creatine supplementation. A large body of evidence
now indicates that creatine supplementation increases
muscle availability of creatine and PCr and can there-
fore enhance acute exercise capacity and training
adaptations in adolescents [6266], younger adults
[61, 6777] and older individuals [5, 40, 43, 7885].
These adaptations would allow an athlete to do more
work over a series of sets or sprints leading to greater
gains in strength, muscle mass, and/or performance
due to an improvement in the quality of training.
Table 2 presents the types of sport events in which
creatine supplementation has been reported to bene-
fit. Creatine supplementation has primarily been rec-
ommended as an ergogenic aid for power/strength
athletes to help them optimize training adaptations or
athletes who need to sprint intermittently and recover
during competition (e.g., American football, soccer,
basketball, tennis, etc.). After creatine loading, per-
formance of high intensity and/or repetitive exercise
is generally increased by 1020% depending on the
magnitudeofincreaseinmusclePCr[46].
Benefits have been reported in men and women, al-
though the majority of studies have been conducted on
men and some studies suggest that women may not
see as much gain in strength and/or muscle mass
during training in response to creatine supplementa-
tion [20, 51, 64, 8690]. However, as will be de-
scribed below, a number of other applications in
Table 1 Potential ergogenic benefits of creatine
supplementation
Increased single and repetitive sprint performance
Increased work performed during sets of maximal effort muscle
contractions
Increased muscle mass & strength adaptations during training
Enhanced glycogen synthesis
Increased anaerobic threshold
Possible enhancement of aerobic capacity via greater shuttling
of ATP from mitochondria
Increased work capacity
Enhanced recovery
Greater training tolerance
Adapted from Kreider and Jung [6]
Table 2 Examples of sport events that may be enhanced by
creatine supplementation
Increased PCr
Track sprints: 60200 m
Swim sprints: 50 m
Pursuit cycling
Increased PCr Resynthesis
Basketball
Field hockey
America Football
Ice hockey
Lacrosse
Volleyball
Reduced Muscle Acidosis
Downhill skiing
Water Sports (e.g., Rowing, Canoe, Kayak, Stand-Up Paddling)
Swim events: 100, 200 m
Track events: 400, 800 m
Combat Sports (e.g., MMA, Wrestling, Boxing, etc.)
Oxidative Metabolism
Basketball
Soccer
Team handball
Tennis
Volleyball
Interval Training in Endurance Athletes
Increased Body Mass/Muscle Mass
American Football
Bodybuilding
Combat Sports (e.g., MMA, Wrestling, Boxing, etc.)
Powerlifting
Rugby
Track/Field events (Shot put; javelin; discus; hammer throw)
Olympic Weightlifting
Adapted from Williams, Kreider, and Branch [269]
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 5 of 18
sport may benefit athletes involved in high intensity
intermittent and endurance events as well. In terms
of performance, the International Society of Sports
Nutrition (ISSN) has previously concluded in its pos-
ition stand on creatine supplementation that creatine
monohydrate is the most effective ergogenic nutri-
tional supplement currently available to athletes in
terms of increasing high-intensity exercise capacity
and lean body mass during training [5, 78]. Recent
position stands by the American Dietetic Association,
Dietitians of Canada, and the American College of
Sports Medicine on nutrition for athletic performance
all drew similar conclusions [91, 92]. Thus, a wide-
spread consensus now exists in the scientific commu-
nity that creatine supplementation can serve as an ef-
fective nutritional ergogenic aid that may benefit
athletes involved in numerous sports as well as indi-
viduals involved in exercise training.
Prevalence of use in sport
Creatine is found in high amounts in the food supply
and therefore its use is not banned by any sport
organization although some organizations prohibit
provision of some types of dietary supplements to ath-
letes by their teams [5, 53, 78, 91, 92]. In these instances,
athletes can purchase and use creatine on their own
without penalty or violation of their banned substance
restrictions. Americans consume over four million kilo-
grams (kg) a year of creatine with worldwide use much
higher [53]. The reported prevalence of creatine use
among athletes and military personnel in survey-based
studies has generally been reported to be about 1540%
[93101], with use more common in male strength/
power athletes. High school athletes have been reported
to have similar prevalence of use of creatine [9597, 102].
In 2014, the NCAA reported that creatine was among the
most popular dietary supplements taken by their male
athletes (e.g., baseball - 28.1%, basketball - 14.6%,
football - 27.5%, golf - 13.0%, ice hockey - 29.4%,
lacrosse - 25.3%, soccer 11.1%, swimming - 19.2%,
tennis - 12.9%, track and field - 16.1%, wrestling - 28.5%)
whilefemaleathletesreportedauserateofonly0.2to
3.8% in various sports [103]. Comparatively, these NCAA
athletes reported relatively high alcohol (83%), tobacco
(1016%), and marijuana (22%) use along with minimal
androgenic anabolic steroid use (0.4%). As will be noted
below, no study has reported any adverse or ergolytic
effect of short- or long-term creatine supplementation
while numerous studies have reported performance
and/or health benefits in athletes and individuals with
various diseases. Therefore, the prevalence of alcohol,
tobacco and drug use among NCAA athletes would
seemingly be a much greater health concern than ath-
letes taking creatine.
Other applications in sport and training
Recent research demonstrates a number of other appli-
cations of creatine supplementation that may benefit
athletes involved in intense training and individuals who
want to enhance training adaptations. For example, use
of creatine during training may enhance recovery, re-
duce the risk of injury and/or help individuals recover
from injuries at a faster rate. The following describes
some applications of creatine in addition to serving as
an ergogenic aid.
Enhanced recovery
Creatine supplementation can help athletes recover from
intense training. For example, Green and coworkers [8]
reported that co-ingesting creatine (5 g) with large
amounts of glucose (95 g) enhanced creatine and carbo-
hydrate storage in muscle. Additionally, Steenge et al.
[49] reported that co-ingesting creatine (5 g) with 47
97 g of carbohydrate and 50 g of protein enhanced creat-
ine retention. Nelson and colleagues [104] reported that
creatine loading prior to performing an exhaustive exer-
cise bout and glycogen loading promoted greater glyco-
gen restoration than just carbohydrate loading alone.
Since glycogen replenishment is important to promoting
recovery and preventing overtraining during intensified
training periods [78], creatine supplementation may help
athletes who deplete large amounts of glycogen during
training and/or performance to maintain optimal glyco-
gen levels.
Evidence also suggests that creatine supplementation
may reduce muscle damage and/or enhance recovery
from intense exercise. For example, Cooke and associ-
ates [105] evaluated the effects of creatine supplementa-
tion on muscle force recovery and muscle damage
following intense exercise. They reported that partici-
pants supplemented with creatine had significantly
greater isokinetic (+10%) and isometric (+21%) knee ex-
tension strength during recovery from exercise-induced
muscle damage. Additionally, plasma CK levels were sig-
nificantly lower (84%) after 2, 3, 4, and 7 days of recov-
ery in the creatine supplemented group compared to
controls. The authors concluded that creatine improved
the rate of recovery of knee extensor muscle function
after injury. Santos and coworkers [106] evaluated the
effects of creatine loading in experienced marathon run-
ners prior to performing a 30 km race on inflammatory
markers and muscle soreness. The researchers reported
that creatine loading attenuated the changes in CK
(19%), prostaglandin E2 (61%), and tumor necrosis
factor (TNF) alpha (34%) and abolished the increase in
lactate dehydrogenase (LDH) compared to controls.
Similar findings were reported by Demince et al. [107]
who reported that creatine supplementation inhibited
the increase of inflammatory markers (TNF-alpha and
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 6 of 18
C-reactive protein) in response to intermittent anaerobic
sprint exercise. Finally, Volek and colleagues [77] eval-
uated the effects of creatine supplementation (0.3 g/
kg/d) for 4 weeks during an intensified overreaching
period followed by a 2 weeks taper. The researchers
found that creatine supplementation was effective in
maintaining muscular performance during the initial
phase of high-volume resistance training overreaching
that otherwise results in small performance decre-
ments. These findings suggest that creatine supple-
mentation can help athletes tolerate heavy increases
in training volume. Therefore, there is strong evi-
dence that creatine supplementation can help athletes
enhance glycogen loading; experience less inflamma-
tion and/or muscle enzyme efflux following intense
exercise; and tolerate high volumes of training and/or
overreaching to a greater degree thereby promoting
recovery.
Injury prevention
Several studies have reported that creatine supplementa-
tion during training and/or competition either has no ef-
fect or reduces the incidence of musculoskeletal injury,
dehydration, and/or muscle cramping. For example, sev-
eral initial studies on creatine supplementation provided
1525 g/day of creatine monohydrate for 4 12 weeks
in athletes engaged in heavy training with no reported
side effects [67, 77, 108110]. Kreider and colleagues
[109] reported that American collegiate football players
ingesting 20 or 25 g/day of creatine monohydrate with a
carbohydrate/protein supplement for 12 weeks during
off season conditioning and spring football practice ex-
perienced greater gains in strength and muscle mass
with no evidence of any adverse side effects. Addition-
ally, in a study specifically designed to assess the safety
of creatine supplementation, American collegiate foot-
ball players ingesting about 16 g/day of creatine for 5
days and 510 g/day for 21 months had no clinically sig-
nificant differences among creatine users and controls in
markers of renal function, muscle and liver enzymes,
markers of catabolism, electrolytes, blood lipids, red cell
status, lymphocytes, urine volume, clinical urinalysis, or
urine specific gravity [22]. Meanwhile, creatine users
experienced less incidence of cramping, heat illness/de-
hydration, muscle tightness, muscle strains/pulls, non-
contact injuries, and total injuries/missed practices than
those not taking creatine [111].
Similar findings were reported by Greenwood and co-
workers [112] who examined injury rates during a 4
months American collegiate football season among cre-
atine users (0.3 g/kg/day for 5 days, 0.03 g/kg/day for 4
months) and non-users. The researchers reported that
creatine users experienced significantly less incidence of
muscle cramping, heat illness/dehydration, muscle
tightness, muscle strains, and total injuries compared to
athletes who did not supplement their diet with creatine.
Likewise, Cancela and associates [113] reported that cre-
atine supplementation (15 g/day x 7-d, 3 g/day x 49-d)
during soccer training promoted weight gain but that
those taking creating had no negative effects on blood
and urinary clinical health markers. Finally, Schroder et
al. [114] evaluated the effects of ingesting creatine (5 g/
day) for three competitive seasons in professional bas-
ketball players. The researchers found that long-term
low-dose creatine monohydrate supplementation did not
promote clinically significant changes in health markers
or side effects. Thus, contrary to unsubstantiated re-
ports, the peer-reviewed literature demonstrates that
there is no evidence that: 1) creatine supplementation in-
creases the anecdotally reported incidence of musculo-
skeletal injuries, dehydration, muscle cramping,
gastrointestinal upset, renal dysfunction, etc.; or that 2)
long-term creatine supplementation results in any clinic-
ally significant side effects among athletes during train-
ing or competition for up to 3 years. If anything,
evidence reveals that athletes who take creatine during
training and competition experience a lower incidence
of injuries compared to athletes who do not supplement
their diet with creatine.
Enhanced tolerance to exercise in the heat
Like carbohydrate, creatine monohydrate has osmotic
properties that help retain a small amount of water. For
example, initial studies reported that creatine loading
promoted a short-term fluid retention (e.g., about 0.5
1.0 L) that was generally proportional to the acute
weight gain observed [22, 46]. For this reason, there was
interest in determining if creatine supplementation may
help hyper-hydrate an athlete and/or improve exercise
tolerance when exercising in the heat [76, 115126]. For
example, Volek and colleagues [76] evaluated the effects
of creatine supplementation (0.3 g/kg/day for 7 days) on
acute cardiovascular, renal, temperature, and fluid-
regulatory hormonal responses to exercise for 35 min in
the heat. The researchers reported that creatine supple-
mentation augmented repeated sprint cycle performance
in the heat without altering thermoregulatory responses.
Kilduff and associates [123] evaluated the effects of cre-
atine supplementation (20 g/day for 7 days) prior to per-
forming exercise to exhaustion at 63% of peak oxygen
uptake in the heat (30.3 °C). The researchers reported
that creatine supplementation increased intracellular
water and reduced thermoregulatory and cardiovascu-
lar responses to prolonged exercise (e.g., heart rate,
rectal temperature, sweat rate) thereby promoting
hyper-hydration and a more efficient thermoregulatory
response during prolonged exercise in the heat. Wat-
son and colleagues [117] reported that short-term
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 7 of 18
creatine supplementation (21.6 g/day for 7 days) did
not increase the incidence of symptoms or comprom-
ise hydration status or thermoregulation in dehy-
drated (2%), trained men exercising in the heat.
Similar findings were observed by several other
groups [118, 119, 127, 128] leading researchers to add
creatine to glycerol as a highly effective hyper-
hydrating strategy to help athletes better tolerate ex-
ercise in the heat [116, 120122, 125, 126]. These
findings provide strong evidence that creatine supplemen-
tation (with or without glycerol) may serve as an effective
nutritional hyper-hydration strategy for athletes engaged
in intense exercise in hot and humid environments
thereby reducing risk to heat related-illness [5, 129].
Enhanced rehabilitation from injury
Since creatine supplementation has been reported to
promote gains in muscle mass and improved strength,
there has been interest in examining the effects of creat-
ine supplementation on muscle atrophy rates as a result
of limb immobilization and/or during rehabilitation
[130]. For example, Hespel and coworkers [131] exam-
ined the effects of creatine supplementation (20 g/day
down to 5 g/day) on atrophy rates and rehabilitation
outcomes in individuals who had their right leg casted
for 2 weeks. During the 10 week rehabilitation phase,
participants performed three sessions a week of knee ex-
tension rehabilitation. The researchers reported that in-
dividuals in the creatine group experienced greater
changes in the cross-sectional area of muscle fiber
(+10%) and peak strength (+25%) during the rehabilita-
tion period. These changes were associated with greater
changes in myogenic regulating factor 4 (MRF4) and
myogenic protein expression. In a companion paper to
this study, Opt Eijnde et al. [132] reported that creatine
supplementation offset the decline in muscle GLUT4
protein content that occurs during immobilization and
increased GLUT4 protein content during subsequent re-
habilitation training in healthy subjects. Collectively,
these findings suggest that creatine supplementation
lessened the amount of muscle atrophy and detrimental
effects on muscle associated with immobilization while
promoting greater gains in strength during rehabilita-
tion. Similarly, Jacobs and associates [133] examined the
effects of creatine supplementation (20 g/d for 7 days)
on upper extremity work capacity in individuals with
cervical-level spinal cord injury (SCI). Results revealed
that peak oxygen uptake and ventilatory anaerobic
threshold were increased following creatine supplemen-
tation. Conversely, Tyler et al. [134] reported that creat-
ine supplementation (20 g/day for 7 days, and 5 g/day
thereafter) did not significantly affect strength or func-
tional capacity in patients recovering from anterior cru-
ciate ligament (ACL) surgery. Moreover, Perret and
colleagues [135] reported that creatine supplementation
(20 g/day for 6 days) did not enhance 800 m wheelchair
performance in trained SCI wheelchair athletes. While
not all studies show benefit, there is evidence that creat-
ine supplementation may help lessen muscle atrophy fol-
lowing immobilization and promote recovery during
exercise-related rehabilitation in some populations.
Thus, creatine supplementation may help athletes and
individuals with clinical conditions recover from injuries.
Brain and spinal cord neuroprotection
The risk of concussions and/or SCI in athletes involved
in contact sports has become an international concern
among sports organizations and the public. It has been
known for a long time that creatine supplementation
possesses neuroprotective benefits [29, 38, 40, 136]. For
this reason, a number of studies have examined the ef-
fects of creatine supplementation on traumatic brain in-
jury (TBI), cerebral ischemia, and SCI. For example,
Sullivan et al. [137] examined the effects of 5 days of
creatine administration prior to a controlled TBI in rats
and mice. The researchers found that creatine monohy-
drate ameliorated the extent of cortical damage by 36 to
50%. The protection appeared to be related to creatine-
induced maintenance of neuronal mitochondrial bio-
energetics. Therefore, the researchers concluded that
creatine supplementation may be useful as a neuropro-
tective agent against acute and chronic neurodegenera-
tive processes. In a similar study, Haussmann and
associates [138] investigated the effects of rats fed creat-
ine (5 g/100 g dry food) before and after a moderate
SCI. The researchers reported that creatine ingestion im-
proved locomotor function tests and reduced the size of
scar tissue after the SCI. The authors suggested that pre-
treatment of patients with creatine may provide neuro-
protection in patients undergoing spinal surgery who are
at risk to SCI. Similarly, Prass and colleagues [139] re-
ported findings that creatine administration reduced
brain infarct size following an ischemic event by 40%.
Adcock et al. [140] reported that neonatal rats fed 3 g/
kg of creatine for 3 days observed a significant increase
in the ratio of brain PCr to Pi and a 25% reduction in
the volume of edemic brain tissue following cerebral
hypoxic ischemia. The authors concluded that creatine
supplementation appears to improve brain bioenergetics
thereby helping minimize the impact of brain ischemia.
Similarly, Zhu and colleagues [141] reported that oral
creatine administration resulted in a marked reduction
in ischemic brain infarction size, neuronal cell death,
and provided neuroprotection after cerebral ischemia in
mice. The authors suggested that given the safety record
of creatine, creatine might be considered as a novel
therapeutic agent for inhibition of ischemic brain injury
in humans. Allah et al. [142] reported that creatine
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 8 of 18
monohydrate supplementation for 10 weeks reduced the
infarction size and improved learning/memory following
neonatal hypoxia ischemia encephalopathy in female
mice. The authors concluded that creatine supplementa-
tion has the potential to improve the neuro-function fol-
lowing neonatal brain damage. Finally, Rabchevsky and
associates [143] examined the efficacy of creatine-
supplemented diets on hind limb functional recovery
and tissue sparing in adult rats. Rats were fed a control
diet or 2% creatine-supplemented chow for 45 weeks
prior to and following SCI. Results revealed that creatine
feeding significantly reduced loss of gray matter after
SCI. These findings provide strong evidence that creat-
ine supplementation may limit damage from concus-
sions, TBI, and/or SCI [33, 144].
Potential medical uses of creatine
Given the role of creatine in metabolism, performance,
and training adaptations; a number of researchers have
been investigating the potential therapeutic benefits of
creatine supplementation in various clinical populations.
The following highlights some of these applications.
Creatine synthesis deficiencies
Creatine deficiency syndromes are a group of inborn er-
rors (e.g., AGAT deficiency, GAMT deficiency, and
CRTR deficiency) that reduce or eliminate the ability to
endogenously synthesize or effect transcellular creatine
transport [17]. Individuals with creatine synthesis defi-
ciencies have low levels of creatine and PCr in the
muscle and the brain. As a result, they often have clin-
ical manifestations of muscle myopathies, gyrate atrophy,
movement disorders, speech delay, autism, mental
retardation, epilepsy, and/or developmental problems
[13, 17, 145]. For this reason, a number of studies have in-
vestigated the use of relatively high doses of creatine mono-
hydrate supplementation (e.g., 0.3 0.8 g/kg/day equivalent
to 21 56g/dayofcreatinefora70kgperson,or12.7
times greater than the adult loading dose) throughout the
lifespan as a means of treating children and adults with cre-
atine synthesis deficiencies [13, 17, 145149]. These studies
generally show some improvement in clinical outcomes
particularly for AGAT and GAMT with less consistent ef-
fects on CRTR deficiencies [145].
For example, Battini et al. [150] reported that a patient
diagnosed at birth with AGAT deficiency who was
treated with creatine supplementation beginning at 4
months of age experienced normal psychomotor devel-
opment at 18 months compared to siblings who did not
have the deficiency. Stockler-Ipsiroglu and coworkers
[151] evaluated the effects of creatine monohydrate sup-
plementation (0.3 0.8 g/kg/day) in 48 children with
GMAT deficiency with clinical manifestations of global
developmental delay/intellectual disability (DD/ID) with
speech/language delay and behavioral problems (n= 44),
epilepsy (n= 35), or movement disorder (n= 13). The
median age at treatment was 25.5 months, 39 months,
and 11 years in patients with mild, moderate, and severe
DD/ID, respectively. The researchers found that creatine
supplementation increased brain creatine levels and im-
proved or stabilized clinical symptoms. Moreover, four
patients treated younger than 9 months had normal or
almost normal developmental outcomes. Long-term cre-
atine supplementation has also been used to treat pa-
tients with creatine deficiency-related gyrate atrophy
[152156]. These findings and others provide promise
that high-dose creatine monohydrate supplementation
may be an effective adjunctive therapy for children and
adults with creatine synthesis deficiencies [18, 145, 157
159]. Additionally, these reports provide strong evidence
regarding the long-term safety and tolerability of high-
dose creatine supplementation in pediatric populations
with creatine synthesis deficiencies, including infants less
than 1 year of age [157].
Neurodegenerative diseases
A number of studies have investigated the short and long-
term therapeutic benefit of creatine supplementation in
children and adults with various neuromuscular diseases
like muscular dystrophies [160165], Huntingtons disease
[23, 166171]; Parkinson disease [23, 40, 166, 172174];
mitochondria-related diseases [29, 175177]; and,
amyotrophic lateral sclerosis or Lou GehrigsDisease
[166, 178184]. These studies have provided some
evidence that creatine supplementation may improve
exercise capacity and/or clinical outcomes in these
patient populations. However, Bender and colleagues
[23] recently reported results of several large clinical
trials evaluating the effects of creatine supplementa-
tion in patients with Parkinsons disease (PD),
Huntingtons disease (HD), and amyotrophic lateral
sclerosis (ALS). A total of 1,687 patients took an
averageof9.5g/dayofcreatineforatotalof5,480
patient years. Results revealed no clinical benefit on
patient outcomes in patients with PD or ALS. How-
ever, there was some evidence that creatine supple-
mentation slowed down progression of brain atrophy
in patients with HD (although clinical markers were
unaffected). Whether creatine supplementation may
have a role in mediating other clinical markers in
these patient populations and/or whether individual
patients may respond more positively to creatine sup-
plementation than others, remain to be determined.
Nevertheless, these studies show that creatine supple-
mentation has been used to treat children and adults
with neurodegenerative conditions and is apparently
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 9 of 18
safe and well-tolerated when taking up to 30 g/day
for 5 years in these populations.
Ischemic heart disease
Creatine and phosphocreatine play an important role in
maintaining myocardial bioenergetics during ischemic
events [33]. For this reason, there has been interest in
assessing the role of creatine or phosphocreatine in re-
ducing arrhythmias and/or improving heart function
during ischemia [185194]. In a recent review, Bales-
trino and colleagues [33] concluded that phosphocrea-
tine administration, primarily as an addition to
cardioplegic solutions, has been used to treat myocardial
ischemia and prevent ischemia-induced arrhythmia and
improve cardiac function with some success. They sug-
gested that creatine supplementation may protect the
heart during an ischemic event. Thus, prophylactic cre-
atine supplementation may be beneficial for patients at
risk for myocardial ischemia and/or stroke.
Aging
A growing collection of evidence supports that creatine
supplementation may improve health status as individ-
uals age [41, 4345, 195]. In this regard, creatine supple-
mentation has been reported to help lower cholesterol
and triglyceride levels [67, 196]; reduce fat accumulation
in the liver [197]; reduce homocysteine levels [198];
serve as an antioxidant [199202]; enhance glycemic
control [132, 203205]; slow tumor growth in some
types of cancers [32, 198, 206, 207]; increase strength
and/or muscle mass [37, 41, 44, 45, 82, 208212];
minimize bone loss [211, 212]; improve functional cap-
acity in patients with knee osteoarthritis [213] and fibro-
myalgia [214]; positively influence cognitive function
[43, 83, 195]; and in some instances, serve as an anti-
depressant [215217].
For example, Gualano and associates supplemented
patients with type II diabetes with a placebo or creatine
(5 g/day) for 12 weeks during training. Creatine supple-
mentation significantly decreased HbA1c and glycemic
response to standardized meal as well as increased
GLUT-4 translocation. These findings suggest that creat-
ine supplementation combined with an exercise program
improves glycemic control and glucose disposal in type
2 diabetic patients. Candow and others [211] reported
that low-dose creatine (0.1 g/kg/day) combined with
protein supplementation (0.3 g/kg/day) increased lean
tissue mass and upper body strength while decreasing
markers of muscle protein degradation and bone resorp-
tion in older men (5977 years). Similarly, Chilibeck et
al. [212] reported that 12 months of creatine supplemen-
tation (0.1 g/kg/day) during resistance training increased
strength and preserved femoral neck bone mineral dens-
ity and increased femoral shaft subperiosteal width in
postmenopausal women. A recent meta-analysis [80] of
357 elderly individuals (64 years) participating in an aver-
age of 12.6 weeks of resistance training found that partici-
pants supplementing their diet with creatine experienced
greater gains in muscle mass, strength, and functional
capacity. These findings were corroborated in a meta-
analysis of 405 elderly participants (64 years) who experi-
enced greater gains in muscle mass and upper body
strength with creatine supplementation during resistance-
training compared to training alone [37]. These findings
suggest that creatine supplementation can help prevent
sarcopenia and bone loss in older individuals.
Finally, a number of studies have shown that creatine
supplementation can increase brain creatine content
generally by 5 15% [218220]. Moreover, creatine sup-
plementation can reduce mental fatigue [221] and/or im-
prove cognitive function [83, 222225]. For example,
Watanabe et al. [221] reported that creatine supplemen-
tation (8 g/day for 5 days) reduced mental fatigue when
subjects repeatedly performed a simple mathematical
calculation as well as increased oxygen utilization in the
brain. Rae and colleagues [222] reported that creatine
supplementation (5 g/day for 6 weeks) significantly
improved working memory and intelligence tests re-
quiring speed of processing. McMorris and co-
workers [224] found that creatine supplementation
(20 g/day for 7 days) after sleep deprivation demon-
strated significantly less decrement in performance in
random movement generation, choice reaction time,
balance and mood state suggesting that creatine im-
proves cognitive function in response to sleep
deprivation. This research group also examined the
effects of creatine supplementation (20 g/day for 7
days) on cognitive function in elderly participants
and found that creatine supplementation significantly
improved performance on random number gener-
ation, forward spatial recall, and long-term memory
tasks. Ling and associates [225] reported that creat-
ine supplementation (5 g/day for 15 days) improved
cognition on some tasks. Since creatine uptake by
the brain is slow and limited, current research is in-
vestigating whether dietary supplementation of creat-
ine precursors like GAA may promote greater
increases in brain creatine [226, 227]. One recent
study suggested that GAA supplementation (3 g/day)
increased brain creatine content to a greater degree
than creatine monohydrate [227].
Pregnancy
Since creatine supplementation has been shown to
improve brain and heart bioenergetics during ische-
mic conditions and possess neuroprotective proper-
ties, there has been recent interest in use of creatine
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 10 of 18
during pregnancy to promote neural development and
reduce complications resulting from birth asphyxia
[228237]. The rationale for creatine supplementation
during pregnancy is that the fetus relies upon placental
transfer of maternal creatine until late in pregnancy and
significant changes in creatine synthesis and excretion
occur as pregnancy progresses [230, 232]. Consequently,
there is an increased demand for and utilization of
creatine during pregnancy. Maternal creatine supple-
mentation has been reported to improve neonatal sur-
vival and organ function following birth asphyxia in
animals [228, 229, 231, 233235, 237]. Human studies
show changes in the maternal urine and plasma creat-
ine levels across pregnancy and association to mater-
nal diet [230, 232]. Consequently, it has been
postulated that there may be benefit to creatine sup-
plementation during pregnancy on fetal growth, devel-
opment, and health [230, 232]. This area of research
may have broad implications for fetal and child devel-
opment and health.
Safety
Since creatine monohydrate became a popular dietary sup-
plement in the early 1990s, over 1,000 studies have been
conducted and billions of servings of creatine have been
ingested. The only consistently reported side effect from
creatine supplementation that has been described in the lit-
erature has been weight gain [5, 22, 46, 78, 91, 92, 112].
Available short and long-term studies in healthy and dis-
eased populations, from infants to the elderly, at dosages
ranging from 0.3 to 0.8 g/kg/day for up to 5 years have con-
sistently shown that creatine supplementation poses no ad-
verse health risks and may provide a number of health and
performance benefits. Additionally, assessments of adverse
event reports related to dietary supplementation, including
in pediatric populations, have revealed that creatine was
rarely mentioned and was not associated with any signifi-
cant number or any consistent pattern of adverse events
[238240]. Unsubstantiated anecdotal claims described in
thepopularmediaaswellasrarecasereportsdescribedin
the literature without rigorous, systematic causality assess-
ments have been refuted in numerous well-controlled clin-
ical studies showing that creatine supplementation does not
increase the incidence of musculoskeletal injuries [22, 111,
112, 241], dehydration [111, 112, 117, 122, 127129, 242],
muscle cramping [76, 106, 111, 112, 117], or gastrointes-
tinal upset [22, 111, 112, 241]. Nor has the literature pro-
vided any support that creatine promotes renal dysfunction
[22, 51, 85, 114, 156, 172, 243248] or has long-term detri-
mental effects [22, 23, 53, 155, 172]. Rather, as noted above,
creatine monohydrate supplementation has been found to
reduce the incidence of many of these anecdotally reported
side effects.
With regard to the question of whether creatine has
effect on renal function, a few case studies [249252] re-
ported that individuals purportedly taking creatine with
or without other supplements presented with high cre-
atinine levels and/or renal dysfunction [249251]. Add-
itionally, one study suggested that feeding rats with renal
cystic disease 2 g/kg/d of creatine for 1 week (equivalent
to 140 g/day for a 70 kg individual) and 0.4 g/kg/d
(equivalent to 28 g/day for a 70 kg individual) for 4
weeks exacerbated disease progression. These reports
prompted some concern that creatine supplementation
may impair renal function [253256] and prompted a
number of researchers to examine the impact of creatine
supplementation on renal function [22, 51, 85, 114, 156,
172, 243248, 257259]. For example, Ferreira and asso-
ciates [260] reported that creatine feeding (2 g/kg/d for
10 weeks equivalent to 140 g/kg/d in a 70 kg person)
had no effects on glomerular filtration rate and renal
plasma flow in Wistar rats. Likewise, Baracho and col-
leagues [261] reported that Wistar rats fed 0, 0.5, 1, or
2 g/kg/d of creatine did not result in renal and/or hep-
atic toxicity. Poortmans and coworkers reported that
ingesting 20 g/day of creatine for 5 days [243], and up to
10 g/day from 10 months to 5 years [257] had no effect
on creatine clearance, glomerular filtration rate, tubular
resorption, or glomerular membrane permeability com-
pared to controls. Kreider et al. [22] reported that creat-
ine supplementation (510 g/day for 21 months) had no
significant effects on creatinine or creatinine clearance
in American football players. Gualono and associates
[262] reported that 12 weeks of creatine supplementa-
tion had no effects on kidney function in type 2 diabetic
patients. Finally, creatine supplement has been used as a
means of reducing homocysteine levels and/or improv-
ing patient outcomes in patients with renal disease
[263265] as well as ameliorating birth asphyxia related
renal dysfunction in mice [228]. Moreover, long-term,
high dose ingestion of creatine (up to 30 g/d for up
to 5 years) in patient populations has not been asso-
ciated with an increased incidence of renal dysfunc-
tion [23, 155, 156, 172]. While some have suggested
that individuals with pre-existing renal disease consult
with their physician prior to creatine supplementation
in an abundance of caution, these studies and others
have led researchers to conclude that there is no
compelling evidence that creatine supplementation
negatively affects renal function in healthy or clinical
populations [5, 6, 22, 53, 259, 266, 267].
Performance-related studies in adolescents, younger
individuals, and older populations have consistently re-
ported ergogenic benefits with no clinically significant
side effects [5, 6, 22, 23, 53, 113, 129, 244, 245, 268].
The breadth and repetition of these findings provide
compelling evidence that creatine monohydrate is well-
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 11 of 18
tolerated and is safe to consume in healthy untrained
and trained individuals regardless of age. Moreover, as
noted above, the number of potential medical uses of
creatine supplementation that can improve health and
well-being as one ages and/or may provide therapeutic
benefit in clinical populations ranging from infants to
senior adults has continued to grow without identifying
significant risks or adverse events even in these diseased
or compromised special populations. It is no wonder
that Wallimann and colleagues [27] recommended that
individuals should consume 3 g/day of creatine through-
out the lifespan to promote general health.
Some critics of creatine supplementation have pointed
to warnings listed on some product labels that individ-
uals younger than 18 years of age should not take creat-
ine as evidence that creatine supplementation is unsafe
in younger populations. Its important to understand that
this is a legal precaution and that there is no scientific
evidence that children and/or adolescents should not
take creatine. As noted above, a number of short- and
long-term studies using relatively high doses of creatine
have been conducted in infants, toddlers and adolescents
with some health and/or ergogenic benefit observed.
These studies provide no evidence that use of creatine at
recommended doses pose a health risk to individuals less
than 18 years of age. Creatine supplementation may, how-
ever, improve training adaptations and/or reduce risk to
injury, including in younger athletes. For this reason, it is
our view that creatine supplementation is an acceptable
nutritional strategy for younger athletes who: a.) are in-
volved in serious/competitive supervised training; b.) are
consuming a well-balanced and performance enhancing
diet; c.) are knowledgeable about appropriate use of creat-
ine; and d.) do not exceed recommended dosages.
Position of the internationals society of sports
nutrition (ISSN)
After reviewing the scientific and medical literature in
this area, the International Society of Sports Nutrition
concludes the following in terms of creatine supplemen-
tation as the official Position of the Society:
1. Creatine monohydrate is the most effective
ergogenic nutritional supplement currently available
to athletes with the intent of increasing high-
intensity exercise capacity and lean body mass dur-
ing training.
2. Creatine monohydrate supplementation is not only
safe, but has been reported to have a number of
therapeutic benefits in healthy and diseased
populations ranging from infants to the elderly.
There is no compelling scientific evidence that the
short- or long-term use of creatine monohydrate (up
to 30 g/day for 5 years) has any detrimental effects
on otherwise healthy individuals or among clinical
populations who may benefit from creatine
supplementation.
3. If proper precautions and supervision are provided,
creatine monohydrate supplementation in children
and adolescent athletes is acceptable and may
provide a nutritional alternative with a favorable
safety profile to potentially dangerous anabolic
androgenic drugs. However, we recommend that
creatine supplementation only be considered for use
by younger athletes who: a.) are involved in serious/
competitive supervised training; b.) are consuming a
well-balanced and performance enhancing diet; c.)
are knowledgeable about appropriate use of creatine;
and d.) do not exceed recommended dosages.
4. Label advisories on creatine products that caution
against usage by those under 18 years old, while
perhaps intended to insulate their manufacturers
from legal liability, are likely unnecessary given the
science supporting creatines safety, including in
children and adolescents.
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 uptake 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 may be to consume ~0.3 g/kg/day of creatine
monohydrate for 57-days followed by 35 g/day
thereafter to maintain elevated stores. Initially,
ingesting smaller amounts of creatine monohydrate
(e.g., 35 g/day) will increase muscle creatine stores
over a 34 week period, however, the initial
performance effects of this method of
supplementation are less supported.
8. Clinical populations have been supplemented with
high levels of creatine monohydrate (0.3 0.8 g/kg/
day equivalent to 2156 g/day for a 70 kg individual)
for years with no clinically significant or serious
adverse events.
9. Further research is warranted to examine the
potential medical benefits of creatine monohydrate
and precursors like guanidinoacetic acid on sport,
health and medicine.
Conclusion
Creatine monohydrate remains one of the few nutritional
supplements for which research has consistently shown
Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 12 of 18
has ergogenic benefits. Additionally, a number of potential
health benefits have been reported from creatine supple-
mentation. Comments and public policy related to
creatine supplementation should be based on careful as-
sessment of the scientific evidence from well-controlled
clinical trials; not unsubstantiated anecdotal reports,
misinformation published on the Internet, and/or poorly
designed surveys that only perpetuate myths about
creatine supplementation. Given all the known benefits
and favorable safety profile of creatine supplementation
reported in the scientific and medical literature, it is the
view of ISSN that government legislatures and sport orga-
nizations who restrict and/or discourage use of creatine
may be placing athletes at greater riskparticularly in
contact sports that have risk of head trauma and/or
neurological injury thereby opening themselves up to legal
liability. This includes children and adolescent athletes
engaged in sport events that place them at risk for head
and/or spinal cord injury.
Acknowledgements
We would like to thank all of the participants and researchers who
contributed to the research studies and reviews described in this position
stand. Your dedication to conducing groundbreaking research has improved
the health and well-being of countless athletes and patients.
Prepared as a Position Stand on behalf of the International Society of Sport
Nutrition with approval of Editors-In-Chief, Founders, and Research
Committee Members.
Funding
Support to prepare this manuscript was provided by the Council for
Responsible Nutrition.
Availability of data and materials
Not applicable.
Authorscontributions
RBK prepared the manuscript. Remaining coauthors reviewed, edited, and
approved the final manuscript. The manuscript was then approved by the
Research Committee and Editors-In Chief to represent the official position of
the International Society of Sports Nutrition.
Competing interests
RBK is a co-founder of the International Society of Sports Nutrition (ISSN) and
has received externally-funded grants from industry to conduct research on
creatine, serves as a scientific and legal consultant, and is a university approved
scientific advisor for Nutrabolt. He prepared this position stand update at the
request of the Council for Responsible Nutrition and ISSN. DSK is a co-founder
of the ISSN who works for a contract research organization (QPS). QPS has
received research grants from companies who sell creatine. DSK sits in an
advisory board (Post Holdings) to Dymatize that sells creatine. DSK declares no
other conflicts of interest. JA is the CEO and co-founder of the ISSN; has
consulted in the past for various sports nutrition brands. TNZ has received
grants and contracts to conduct research on dietary supplements; has
served as a paid consultant for industry; has received honoraria for
speaking at conferences and writing lay articles about sports nutrition
ingredients; receives royalties from the sale of several sports nutrition
products; and has served as an expert witness on behalf of the plaintiff
and defense in cases involving dietary supplements. TNZ is also co-inventor on
multiple patent applications within the field of dietary supplements, applied
nutrition and bioactive compounds. RW is the Chief Science Officer for Post
Active Nutrition. ALA is CEO of Vitargo Global Sciences, Inc., a company that
markets and sells a high insulinemic, starch-based carbohydrate. HLL has
received research grants from companies who sell creatine and do business in
the dietary supplement, natural products and medical foods industry. HLL is co-
founder of Supplement Safety Solutions, LLC, serving as an independent
consultant for regulatory compliance, safety surveillance and Nutravigilance to
companies who sell creatine. Dr. Lopez is also co-inventor on multiple patent
applications within the field of dietary supplements, applied nutrition
and bioactive compounds. Remaining investigators have no competing
interests to declare. The comments and positions taken in this paper do
not constitute an endorsement by institutions the authors are affiliated.
Consent for publication
Not applicable.
Ethics approval and consent to participate
This paper was reviewed by the International Society of Sports Nutrition
Research Committee and represents the official position of the Society.
PublishersNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department
of Health & Kinesiology, Texas A&M University, College Station, TX
77843-4243, USA.
2
Nutrition Research Unit, QPS, 6141 Sunset Drive Suite 301,
Miami, FL 33143, USA.
3
Department of Health and Human Performance,
Nova Southeastern University, Davie, FL 33328, USA.
4
The Center for Applied
Health Sciences, 4302 Allen Road, STE 120, Stow, OH 44224, USA.
5
Post
Active Nutrition, 111 Leslie St, Dallas, TX 75208, USA.
6
Collins Gann
McCloskey & Barry, PLLC, 138 Mineola Blvd., Mineola, NY 11501, USA.
7
Faculty
of Kinesiology and Health Studies, University of Regina, Regina, SK S4S 0A2,
Canada.
8
High Performance Nutrition, LLC, Mercer Island, WA 98040, USA.
9
Vitargo Global Sciences, Inc., Dana Point, CA 92629, USA.
10
Supplement
Safety Solutions, LLC, Bedford, MA 01730, USA.
Received: 27 April 2017 Accepted: 30 May 2017
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Kreider et al. Journal of the International Society of Sports Nutrition (2017) 14:18 Page 18 of 18
... Creatine, a nitrogen containing compound, is derived from three amino acids (arginine, glycine, and methionine) endogenously primarily in the liver and kidneys [6] and can also be synthesized in the brain [7]. It is well established that Cr supplementation elevates intramuscular phosphocreatine (PCr) and free Cr stores in skeletal muscle by~20% [8] and~5-10% in the brain [7]. This increases the capacity to re-phosphorylate adenosine triphosphate (ATP) during short-term intense physical exercise or during times of stress [9]. ...
... Further, PCr hydrolysis consumes H + and therefore acts to buffer acidosis [12]. Cr also shuttles ATP from mitochondria to sites of ATP utilization, which may reduce oxidative stress [8]. In addition, creatine alters calcium handling which enhances myofibrillar cross-bridge formation and force production [8]. ...
... Cr also shuttles ATP from mitochondria to sites of ATP utilization, which may reduce oxidative stress [8]. In addition, creatine alters calcium handling which enhances myofibrillar cross-bridge formation and force production [8]. Overall, there is strong evidence that Cr supplementation can enhance exercise performance [8] and there is a growing body of literature showing beneficial effects on cognitive performance [7]. ...
Article
Full-text available
The purpose was to investigate the effects of a 7-day creatine (Cr) loading protocol at the end of four weeks of β-alanine supplementation (BA) on physical performance, blood lactate, cognitive performance, and resting hormonal concentrations compared to BA alone. Twenty male military personnel (age: 21.5 ± 1.5 yrs; height: 1.78 ± 0.05 m; body mass: 78.5 ± 7.0 kg; BMI: 23.7 ± 1.64 kg/m2 ) were recruited and randomized into two groups: BA + Cr or BA + placebo (PL). Participants in each group (n = 10 per group) were supplemented with 6.4 g/day of BA for 28 days. After the third week, the BA + Cr group participants were also supplemented with Cr (0.3 g/kg/day), while the BA + PL group ingested an isocaloric placebo for 7 days. Before and after supplementation, each participant performed a battery of physical and cognitive tests and provided a venous blood sample to determine resting testosterone, cortisol, and IGF-1. Furthermore, immediately after the last physical test, blood lactate was assessed. There was a significant improvement in physical performance and mathematical processing in the BA + Cr group over time (p < 0.05), while there was no change in the BA + PL group. Vertical jump performance and testosterone were significantly higher in the BA + Cr group compared to BA + PL. These results indicate that Cr loading during the final week of BA supplementation (28 days) enhanced muscular power and appears to be superior for muscular strength and cognitive performance compared to BA supplementation alone.
... Recent reviews, including the ISSN Position Stand on creatine monohydrate, have outlined the ergogenic potential of creatine supplementation [116,117]. These reviews highlight creatine's documented potential to increase high-intensity exercise capacity, peak power, maximal strength, repetitions completed before fatigue, and fat-free mass while undergoing physical training. ...
... Long-term highdose creatine monohydrate supplementation (e.g., 20-25 g/day for 12 weeks and 5-10 g/ day for up to 21 months) has been studied in athletic populations and have been shown to be safe and lower the incidence and severity of an injury [119,120,131,132]. Additionally, clinical populations have been studied with doses 10-30 g/day for up to 5 years [69,116,133]. The interested reader is highly encouraged to read the following reviews to further understand the potential health and performance implications of creatine monohydrate supplementation, including data that summarizes any potential safety concerns for its use [116,117,127,134]. ...
... Additionally, clinical populations have been studied with doses 10-30 g/day for up to 5 years [69,116,133]. The interested reader is highly encouraged to read the following reviews to further understand the potential health and performance implications of creatine monohydrate supplementation, including data that summarizes any potential safety concerns for its use [116,117,127,134]. ...
Article
Full-text available
This position stand aims to provide an evidence-based summary of the energy and nutritional demands of tactical athletes to promote optimal health and performance while keeping in mind the unique challenges faced due to work schedules, job demands, and austere environments. After a critical analysis of the literature, the following nutritional guidelines represent the position of the International Society of Sports Nutrition (ISSN). GENERAL RECOMMENDATIONS Nutritional considerations should include the provision and timing of adequate calories, macronutrients, and fluid to meet daily needs as well as strategic nutritional supplementation to improve physical, cognitive, and occupational performance outcomes; reduce risk of injury, obesity, and cardiometabolic disease; reduce the potential for a fatal mistake; and promote occupational readiness. MILITARY RECOMMENDATIONS Energy demands should be met by utilizing the Military Dietary Reference Intakes (MDRIs) established and codified in Army Regulation 40-25. Although research is somewhat limited, military personnel may also benefit from caffeine, creatine monohydrate, essential amino acids, protein, omega-3-fatty acids, beta-alanine, and L-tyrosine supplementation, especially during high-stress conditions. FIRST RESPONDER RECOMMENDATIONS Specific energy needs are unknown and may vary depending on occupation-specific tasks. It is likely the general caloric intake and macronutrient guidelines for recreational athletes or the Acceptable Macronutrient Distribution Ranges for the general healthy adult population may benefit first responders. Strategies such as implementing wellness policies, setting up supportive food environments, encouraging healthier food systems, and using community resources to offer evidence-based nutrition classes are inexpensive and potentially meaningful ways to improve physical activity and diet habits. The following provides a more detailed overview of the literature and recommendations for these populations.
... Several studies have found some positive performance benefits from the acute ingestion of pre-workout supplements (Bird et al., 2013;Kedia et al., 2014). Further, the use of creatine as a performance-enhancing dietary supplement is well established (see review Kreider et al., 2017). Thus, it is tempting to conclude that acute creatine ingestion may impart beneficial effects on exercise performance. ...
... Indeed, plasma creatine rises after ingestion, followed by a reduction in plasma levels, indirectly suggesting increased uptake into the target tissue. However, data from the "gold standard" instruments for measuring the effects of creatine supplementation on target tissues, magnetic resonance spectroscopy (MRS), muscle biopsy, or stable isotope tracer studies are scanty (Harris et al., 2002;Jäger et al., 2007;Kreider et al., 2017) Pharmacokinetics of creatine absorption, half-life, and transport show that the time elapsed between plasma creatine's rise and fall can be up to 60 min (Deldicque et al., 2008;Harris et al., 2002;Persky et al., 2003), in addition, it appears that higher doses of orally consumed creatine result in lower bioavailability (Alraddadi et al., 2018). Also, the bioavailability of creatine appears to vary depending on the type of supplement (lower in creatine monohydrate vs. creatine pyruvate; Jäger et al., 2007). ...
... No studies have yet traced the time between serum creatine increases and intracellular increases. Furthermore, it is uncertain whether a unique orally consumed creatine dose within an hour prior to exercise could meaningfully contribute to performance enhancement in a resistance training session via the energy buffer system (Kreider et al., 2017). ...
Article
The purpose of this study was to test whether believed versus actual acute creatine ingestion impacted resistance exercise performance. Fifteen men (21.9 ± 2.7 years old) completed four bouts of three sets each of squat and bench press to volitional fatigue at a 10RM load with 1-min between-sets rest interval. Thirty minutes prior to each exercise bout, they received the following treatments in a randomized order: 1) nothing (CON); 2) 0.3 g·kg−1 dextrose placebo (PLC); 3) 0.3 g·kg−1 dextrose, identified as creatine (Cr-False); 4) 0.3 g·kg 20 −1 creatine, identified as creatine (CrTrue). Between-treatments comparisons included the total repetitions completed and the rate of perceived exertion. Results revealed (p < 0.05) higher repetitions performed for all treatments versus CON for both squat and bench press. In the squat, more repetitions were performed with Cr-True (p < 0.001) and CrFalse (p < 0.001) than with either CON or PLC. Bayes Factor analyses revealed strong (PLC to Cr-True BF = 19.1) and very strong (PLC to CrFalse BF = 45.3) posterior probability favouring positive effects for both "creatine" conditions over PLC for the squat. In conclusion, in acute measures, belief versus ingestion of creatine yields similar exercise performance. ARTICLE HISTORY
... However, we suggest that creatine-based MIPS positively affected performance fatigability (CV slopes) and TtT after REP, while no effects were observed on central factors (FD slopes). Even though MIPS was unable to significantly affect maximal force production (MVC) or performance outcomes (WRPM or BCRs), the positive effect on CV slopes and TtT registered in MIPS, but not in CC and PLA, may relate to the acute positive action of the supplement on peripheral components of performance fatigability, independently from the protons buffering function of creatine (38) and its ergogenic contribution (34). The observed results after MIPS may be linked to two possible additional mechanisms, which involve other components of the mixture, able to synergistically produce benefits to different levels of muscle work intensities, as we observed through the measure of CV slopes at 20 and 60% of MVC: (1) an acute role of β-alanine on the buffer capacity of the muscle during the fatiguing task as previously hypothesized by Invernizzi et al. (7), although we were not able to provide biochemical evidence of this assertion by measuring differences of blood pH, and (2) an overall "antifatigue" effect due to the presence of molecules able to regulate recognized mechanisms involved in the onset of high-intensity resistance exercise-induced fatigue (39)(40)(41), such as glutamine, arginine, and taurine. ...
... We discovered that neither MIPS nor CC affected MVC after REP. This result is not surprising considering that all the available studies on creatine and β-alanine supplementation suggest that 5-7 days and 4 weeks of administration are required, respectively, to increase muscle stores of their active metabolites (i.e., phosphocreatine and carnosine) and effectively increase the acute exercise capacity (34,45). At present, only one study by Invernizzi et al. (7) provided evidence that a single bolus of β-alanine (2 g of β-alanine combined with 2 g of L-carnosine) in physically active young males was able to promote a positive effect on MVC compared with PLA, during isometric and dynamic tests performed 4 h after the supplement ingestion. ...
... CITROGEN and CITROFOS are commercially available products containing the same amount of creatine per dose. The creatine content in each product agrees with those suggested in studies that underline as a minimum dose of 3 g is required in an MIPS to exert an ergogenic effect(2,34). To guarantee the blindness during each step of the experimental design, MIPS, CC, and PLA powder were undistinguishable for flavor, color, and odor, and all the sachets, packaged by Akela S.r.l. ...
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Background This study aims to investigate the acute effects of a single oral administration of a creatine-based multi-ingredient pre-workout supplement (MIPS) on performance fatigability and maximal force production after a resistance exercise protocol (REP).Methods Eighteen adult males (age: 23 ± 1 years; body mass: 76.4 ± 1.5 kg; height: 1.77 ± 0.01 m) were enrolled in a randomized, double-blind, crossover design study. Subjects received a single dose of a MIPS (3 g of creatine, 2 g of arginine, 1 g of glutamine, 1 g of taurine, and 800 mg of β-alanine) or creatine citrate (CC) (3 g of creatine) or a placebo (PLA) in three successive trials 1 week apart. In a randomized order, participants consumed either MIPS, CC, or PLA and performed a REP 2 h later. Before ingestion and immediately after REP, subjects performed isometric contractions of the dominant biceps brachii: two maximal voluntary contractions (MVCs), followed by a 20% MVC for 90 s and a 60% MVC until exhaustion. Surface electromyographic indices of performance fatigability, conduction velocity (CV), and fractal dimension (FD) were obtained from the surface electromyographic signal (sEMG). Time to perform the task (TtT), basal blood lactate (BL), and BL after REP were also measured.ResultsFollowing REP, statistically significant (P < 0.05) pre–post mean for ΔTtT between MIPS (−7.06 s) and PLA (+0.222 s), ΔCV slopes (20% MVC) between MIPS (0.0082%) and PLA (−0.0519%) and for ΔCV slopes (60% MVC) between MIPS (0.199%) and PLA (−0.154%) were found. A pairwise comparison analysis showed no statistically significant differences in other variables between groups and condition vs. condition.Conclusion After REP, a creatine-enriched MIPS resulted in greater improvement of sEMG descriptors of performance fatigability and TtT compared with PLA. Conversely, no statistically significant differences in outcomes measured were observed between CC and PLA or MIPS and CC.
... These supplements, known as ergogenic aids, are defined as substances used to improve endurance, total fitness level and sports performance (5). Some of them, as creatine, caffeine, bicarbonate, protein and amino acids, have been used for different purposes: to increase energy intake, to maintain strength, to recover muscular mass or to prevent nutritional deficiencies, among others (6)(7)(8)(9). Two of the most marketed supplements in sports nutrition are proteins and amino acids. ...
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Nutrition and sport play an important role in achieving a healthy lifestyle. In addition to the intake of nutrients derived from the normal diet, some sport disciplines require the consumption of supplements that contribute positively to improved athletic performance. Protein intake is important for many aspects related to health, and current evidence suggests that some athletes require increased amounts of this nutrient. On the other hand, society's demand for more environmentally friendly products, focus on the search for alternative food sources more sustainable. This review aims to summarize the latest research on novel strategies and sources for greener and functional supplementation in sport nutrition. Alternative protein sources such as insects, plants or mycoproteins have proven to be an interesting substrate due to their high added value in terms of bioactivity and sustainability. Protein hydrolysis has proven to be a very useful technology to revalue by-products, such as collagen, by producing bioactive peptides beneficial on athletes performance and sport-related complications. In addition, it has been observed that certain amino acids from plant sources, as citrulline or theanine, can have an ergogenic effect for this target population. Finally, the future perspectives of protein supplementation in sports nutrition are discussed. In summary, protein supplementation in sports nutrition is a very promising field of research, whose future perspective lies with the search for alternatives with greater bioactive potential and more sustainable than conventional sources.
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Traumatic brain injury and the susceptibility to secondary injury pose a public health problem with a substantial financial burden on the society. Current researches suggest that consumption of certain diets or their associated physiologically active constituents may be linked to disease risk reduction. This chapter reviews some of the extensively explored dietary supplements like eicosapentaenoic acid, docosahexaenoic acid, creatine, vitamins, zinc, magnesium, and their clinical interventions for the treatment of TBI and recovery from the tissue damage. On the brighter side, there appear to be no adverse effects to any of these dietary supplements, when used appropriately. The major challenges of the future are performing well-designed clinical studies in patients to confirm anticipated effects, to define the optimal doses, to compare single vs multiple dietary components, and to assess possible side effects.
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Background: Athletic performance can be substantially enhanced with supplements and functional food which are considered by scientists as efficient, safe and legal, such as protein, carbohydrate and protein-carbohydrate supplements, isotonic sports drinks, carbohydrate-protein bars, carbohydrate bars, creatine and caffeine. Objective: The study is aimed at an analysis and evaluation of the prevalence of using effective ergogenic aids (creatine, caffeine, isotonic drinks, carbohydrates, and proteins) in a group of Polish professional athletes. Material and methods: The research was conducted on 600 athletes (216 women, 384 men) practicing various sports disciplines; the younger group (18-23 years old) consisted of 307 people, while the older one (24-35 years old) was comprised of 293 subjects. A questionnaire was used with questions concerning the frequency and types of consumed supplements. Results: Nearly half of the athletes (48,2%) admitted to taking supplementation, of which 36.7% consumed the supplements occasionally and 11.5% continually. The majority of the group (75.4%) claimed to be consuming isotonic drinks, which were the most commonly chosen nutritional aid enhancing physical performance, most frequently supplementing the diet in a continuous manner (41.2%). The least frequently used supplement was creatine, chosen by only one in three interviewees (34,5%). The ergogenic aids were used more often by men than women (50.5% vs. 44.1%), and so were nutrients based on proteins (51.8% vs. 32.0%), carbohydrates (60.7% vs. 46.8%), protein-carbohydrates (45.6% vs. 32.9%), as well as creatine (39.8% vs. 25.0%). The studies showed the inessential difference in the frequency of taking supplementation based on the interviewees' age (0.4%). Conclusions: Competitors who use supplements over those who choose not to, seems to reflect the continuous lack of the athletes' sufficient awareness of the effectiveness, safety, and health benefits of dietary supplementation that enhances physical performance. Key words: supplements, dietary supplementation, sport, performance-enhancing substances, athletes.
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