This should answer most of the questions that come up regarding the use of creatine and it's efficacy.
Of particular note:
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.
and 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.
Enjoy the rest.-CS
-----------------------------------------------------------------------------------
International Society of Sports Nutrition position stand: Creatine
supplementation and exercise
International Society of Sports Nutrition, 600 Pembrook Drive,
Woodland Park, CO 80863, USA
Journal of the International Society of Sports Nutrition 2007,
4:6doi:10.1186/ 1550-2783- 4-6
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
high-intensity 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, short-duration 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 +
β-hydroxy- β-methlybut yrate (HMB), creatine + sodium bicarbonate,
creatine magnesium-chelate, creatine + glycerol, creatine + glutamine,
creatine + β-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 β-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 D-pinitol (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 1 RM 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
[61-64]. 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].
Conclusion
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.
References
1. Metzl JD, Small E, Levine SR, Gershel JC :Creatine use among
young athletes. Pediatrics 2001, 108:421-425. PubMed Abstract |
Publisher Full Text | OpenURL
2. Greenwood M, Kreider RB, Melton C, Rasmussen C, Lancaster S,
Cantler E, Milnor P, Almada A :Creatine supplementation during college
football training does not increase the incidence of cramping or
injury. Mol Cell Biochem 2003, 244:83-88. PubMed Abstract | Publisher
Full Text | OpenURL
3. Kreider RB :Creatine supplementation: analysis of ergogenic
value, medical safety, and concerns. J Exerc Physiol Online 1998., 1:
OpenURL
4. Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S,
Cantler EC, Milnor P, Almada AL :Long-term creatine supplementation
does not significantly affect clinical markers of health in athletes.
Mol Cell Biochem 2003, 244:95-104. PubMed Abstract | Publisher Full
Text | OpenURL
5. Poortmans JR, Francaux M :Long-term oral creatine
supplementation does not impair renal function in healthy athletes.
Med Sci Sports Exerc 1999, 31:1108-1110. PubMed Abstract | Publisher
Full Text | OpenURL
6. Chanutin A :The fate of creatine when administered to man.
J Biol Chem 1926, 67:29-34. OpenURL
7. Hultman E, Bergstrom J, Spreit L, Soderlund K :Energy metabolism
and fatigue. In Biochemistry of Exercise VII. Edited by: Taylor A,
Gollnick PD, Green H. Human Kinetics: Champaign, IL; 1990:73-92. OpenURL
8. Balsom PD, Soderlund K, Ekblom B :Creatine in humans with
special reference to creatine supplementation. Sports Med 1994,
18:268-80. PubMed Abstract | OpenURL
9. Greenhaff P :The nutritional biochemistry of creatine.
J Nutrit Biochem 1997, 11:610-618. Publisher Full Text | OpenURL
10. Greenhaff PL :Muscle creatine loading in humans: Procedures and
functional and metabolic effects. 6th Internationl Conference on
Guanidino Compounds in Biology and Medicine. Cincinatti, OH 2001. OpenURL
11. Greenhaff P, Casey A, Green AL :Creatine supplementation
revisited: An update. Insider 1996, 4:1-2. OpenU
12. Harris RC, Soderlund K, Hultman E :Elevation of creatine in
resting and exercised muscle of normal subjects by creatine
supplementation. Clin Sci (Colch) 1992, 83(3):367-374. OpenURL
13. Brunzel NA :Renal function: Nonprotein nitrogen compounds,
function tests, and renal disease. In Clinical Chemistry. Edited by:
Scardiglia J, Brown M, McCullough K, Davis K. McGraw-Hill: New York,
NY; 2003:373-399. PubMed Abstract | Publisher Full Text | OpenURL
14. Paddon-Jones D, Borsheim E, Wolfe RR :Potential ergogenic
effects of arginine and creatine supplementation. J Nutr 2004,
134:2888S-2894S. PubMed Abstract | Publisher Full Text | OpenURL
15. Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL
:Muscle creatine loading in men. J Appl Physiol 1996, 81:232-237.
PubMed Abstract | Publisher Full Text | OpenURL
16. Burke DG, Smith-Palmer T, Holt LE, Head B, Chilibeck PD :The
effect of 7 days of creatine supplementation on 24-hour urinary
creatine excretion. J Strength Cond Res 2001, 15:59-62. PubMed
Abstract | Publisher Full Text | OpenURL
17. Williams MH, Branch JD :Creatine supplementation and exercise
performance: an update. J Am Coll Nutr 1998, 17:216-34. PubMed
Abstract | Publisher Full Text | OpenURL
18. Williams MH, Kreider R, Branch JD :Creatine: The power
supplement. Champaign, IL: Human Kinetics Publishers; 1999:252. OpenURL
19. Kreider RB :Creatine in Sports. In Essentials of Sport Nutrition
& Supplements. Edited by: Antonio J, Kalman D, Stout J, et al. Humana
Press Inc., Totowa, NJ; 2007:in press. OpenURL
20. Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K, Hultman
E :Influence of oral creatine supplementation of muscle torque during
repeated bouts of maximal voluntary exercise in man. Clin Sci (Colch)
1993, 84(5):565-571. OpenURL
21. Greenhaff PL, Bodin K, Soderlund K, Hultman E :Effect of oral
creatine supplementation on skeletal muscle phosphocreatine
resynthesis. Am J Physiol 1994, 266:E725-30. PubMed Abstract |
Publisher Full Text | OpenURL
22. Kreider RB, Leutholtz BC, Greenwood M :Creatine. In Nutritional
Ergogenic Aids. Edited by: Wolinsky I, Driskel J. CRC Press LLC: Boca
Raton, FL; 2004:81-104. OpenURL
23. Steenge GR, Simpson EJ, Greenhaff PL :Protein- and
carbohydrate- induced augmentation of whole body creatine retention in
humans. J Appl Physiol 2000, 89:1165-71. PubMed Abstract | Publisher
Full Text | OpenURL
24. Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL
:Carbohydrate ingestion augments skeletal muscle creatine accumulation
during creatine supplementation in humans. Am J Physiol 1996,
271:E821-6. PubMed Abstract | Publisher Full Text | OpenURL
25. Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D,
Tarnopolsky M :Effect of creatine and weight training on muscle
creatine and performance in vegetarians. Med Sci Sports Exerc 2003,
35:1946-55. PubMed Abstract | Publisher Full Text | OpenURL
26. Willoughby DS, Rosene J :Effects of oral creatine and resistance
training on myosin heavy chain expression. Med Sci Sports Exerc 2001,
33:1674-81. PubMed Abstract | Publisher Full Text | OpenURL
27. Willoughby DS, Rosene JM :Effects of oral creatine and
resistance training on myogenic regulatory factor expression.
Med Sci Sports Exerc 2003, 35:923-929. PubMed Abstract | Publisher
Full Text | OpenURL
28. Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven
L, Hespel P :Long-term creatine intake is beneficial to muscle
performance during resistance training. J Appl Physiol 1997,
83:2055-63. PubMed Abstract | Publisher Full Text | OpenURL
29. Candow DG, Chilibeck PD, Chad KE, Chrusch MJ, Davison KS, Burke
DG :Effect of ceasing creatine supplementation while maintaining
resistance training in older men. J Aging Phys Act 2004, 12:219-31.
PubMed Abstract | OpenURL
30. Greenwood M, Kreider R, Earnest C, Rassmussen C, Almada A
:Differences in creatine retention among three nutritional
formulations of oral creatine supplements. J Exerc Physiol Online
2003, 6:37-43. OpenURL
31. Stout JR, Cramer JT, Mielke M, O'Kroy J, Torok DJ, Zoeller RF
:Effects of twenty-eight days of beta-alanine and creatine monohydrate
supplementation on the physical working capacity at neuromuscular
fatigue threshold. J Strength Cond Res 2006, 20:938-931. Publisher
Full Text | OpenURL
32. Hoffman J, Ramatess N, Kang J, Mangine G, Faigenbaum A, Stout J
:Effect of creatine and beta-alanine supplementation on performance
and endocrine responses in strength/power athletes. Int J Sport Nutr
Exerc Metab 2006, 16:430-446. PubMed Abstract | OpenURL
33. Falk DJ, Heelan KA, Thyfault JP, Koch AJ :Effects of
effervescent creatine, ribose, and glutamine supplementation on
muscular strength, muscular endurance, and body composition. J
Strength Cond Res 2003, 17:810-816. PubMed Abstract | Publisher Full
Text | OpenURL
34. Kreider RB, Willoughby D, Greenwood M, Parise G, Payne E,
Tarnopolsky M :Effects of serum creatine supplementation on muscle
creatine and phosphagen levels. J Exerc Physio Online 2003, 6:24-33.
OpenURL
35. Selsby JT, DiSilvestro RA, Devor ST :Mg2+-creatine chelate and a
low-dose creatine supplementation regimen improve exercise
performance. J Strength Cond Res 2004, 18:311-315. PubMed Abstract |
Publisher Full Text | OpenURL
36. Peeters BM, Lantz CD, Mayhew JL :Effect of oral creatine
monohydrate and creatine phosphate supplementation on maximal strength
indices, body composition, and blood pressure. J Strength Cond Res
1999, 13:3-9. Publisher Full Text | OpenURL
37. Lehmkuhl M, Malone M, Justice B, Trone G, Pistilli E, Vinci D,
Haff EE, Kilgore JL, Haff GG :The effects of 8 weeks of creatine
monohydrate and glutamine supplementation on body composition and
performance measures. J Strength Cond Res 2003, 17:425-438. PubMed
Abstract | Publisher Full Text | OpenURL
38. Mero AA, Keskinen KL, Malvela MT, Sallinen JM :Combined creatine
and sodium bicarbonate supplementation enhances interval swimming. J
Strength Cond Res 2004, 18:306-310. PubMed Abstract | Publisher Full
Text | OpenURL
39. Jowko E, Ostaszewski P, Jank M, Sacharuk J, Zieniewicz A,
Wilczak J, Nissen S :Creatine and B-hydroxy-B- methylbutyrate (HMB)
additively increase lean body mass and muscle strength during a
weight-training program. Nutrition 2001, 17:558-566. PubMed Abstract |
Publisher Full Text | OpenURL
40. O'Conner DM, Crowe MJ :Effects of β-hydroxy- β-methylbut yrate and
creatine monohydrate supplementation on the aerobic and anaerobic
capacity of highly trained athletes. J Sports Med Phys Fitness 2003,
43:64-68. PubMed Abstract | OpenURL
41. O'Conner DM, Crowe MJ :Effects of six weeks of
beta-hydroxy- beta-methylbutyr ate (HMB) and HMB/creatine
supplementation on strength, power, and anthropometry of highly
trained athletes. J Strength Cond Res 2007, 21:419-423. PubMed
Abstract | Publisher Full Text | OpenURL
42. Easton C, Turner S, Pitsaladis YP :Creatine and glycerol
hyperhydration in trained subjects before exercise in the heat. Int J
Sports Nut Exerc Metab 2007, 17:70-91. OpenURL
43. Greenwood M, Kreider RB, Rasmussen C, Almada AL, Earnest CP
:D-pinitol augments whole body creatine retention in man. J Exerc
Physiol Online 2001, 4:41-47. OpenURL
44. Chromiak JA, Smedley B, Carpenter W, Brown R, Koh YS, Lamberth
JG, Joe LA, Abadie BR, Altorfer G :Effect of a 10-week strength
training program and recovery drink on body composition, muscular
strength and endurance, and anaerobic power and capacity.
Nutrition 2004, 20:420-427. PubMed Abstract | Publisher Full Text |
OpenURL
45. Carter JM, Bemben DA, Knehans AW, Bemben MG, Witten MS :Does
nutritional supplementation influence adaptability of muscle to
resistance training in men aged 48 to 72 years? J Geriatric Phys
Therapy 2005, 28(2):40-47. OpenURL
46 Theodorou AS, Havenetidis K, Zanker CL, O'Hara JP, King RF, Hood
C, Paradisis G, Cooke CB :Effects of acute creatine loading with or
without CHO on repeated bouts of maximal swimming in high-performance
swimmers. J Strength Cond Res 2005, 19:265-269. PubMed Abstract |
Publisher Full Text | OpenURL
47. Beck TW, Housh TJ, Johnson GO, Coburn DW, Malek MH, Cramer JT
:Effects of a drink containing creatine, amino acids, and protein,
combined with ten weeks of resistance training on body composition,
strength, and anaerobic performance. J Strength Cond Res 2007,
21:100-104. PubMed Abstract | Publisher Full Text | OpenURL
48. Cribb PJ, Williams AD, Stathis CG, Carey MF, Hayes A :Effects of
Whey Isolate, Creatine, and Resistance Training on Muscle Hypertrophy.
Med Sci Sports Exer 2007, 39:298-307. Publisher Full Text | OpenURL
49. Kreider RB :Effects of creatine supplementation on performance
and training adaptations. Mol Cell Biochem 2003, 244:89-94. PubMed
Abstract | Publisher Full Text | OpenURL
50. Volek JS, Kraemer WJ, Bush JA, Boetes M, Incledon T, Clark KL,
Lynch JM :Creatine supplementation enhances muscular performance
during high-intensity resistance exercise. J Am Diet Assoc 1997,
97:765-70. PubMed Abstract | Publisher Full Text | OpenURL
51. Tarnopolsky MA, MacLennan DP :Creatine monohydrate
supplementation enhances high-intensity exercise performance in males
and females. Int J Sport Nutr Exerc Metab 2000, 10:452-63. PubMed
Abstract | OpenURL
52. Wiroth JB, Bermon S, Andrei S, Dalloz E, Heberturne X, Dolisi C
:Effects of oral creatine supplementation on maximal pedalling
performance in older adults. Eur J Appl Physiol 2001, 84:533-9. PubMed
Abstract | Publisher Full Text | OpenURL
53. Skare OC, Skadberg , Wisnes AR :Creatine supplementation
improves sprint performance in male sprinters. Scand J Med Sci Sports
2001, 11:96-102. PubMed Abstract | Publisher Full Text | OpenURL
54. Mujika I, Padilla S, Ibanez J, Izquierdo M, Gorostiaga E
:Creatine supplementation and sprint performance in soccer players.
Med Sci Sports Exerc 2000, 32:518-25. PubMed Abstract | Publisher
Full Text | OpenURL
55. Ostojic SM :Creatine supplementation in young soccer players.
Int J Sport Nutr Exerc Metab 2004, 14:95-103. PubMed Abstract | OpenURL
56. Theodorou AS, Cooke CB, King RF, Hood C, Denison T, Wainwright
BG, Havenitidis K :The effect of longer-term creatine supplementation
on elite swimming performance after an acute creatine loading. J
Sports Sci 1999, 17:853-9. PubMed Abstract | Publisher Full Text | OpenURL
57. Preen D, Dawson B, Goodman C, Lawrence S, Beilby J, Ching S
:Effect of creatine loading on long-term sprint exercise performance
and metabolism. Med Sci Sports Exerc 2001, 33:814-21. PubMed Abstract
| Publisher Full Text | OpenURL
58. Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven
L, Hespel P :Long-term creatine intake is beneficial to muscle
performance during resistance training. J Appl Physiol 1997,
83:2055-63. PubMed Abstract | Publisher Full Text | OpenURL
59. Kreider RB, Ferreira M, Wilson M, Grindstaff P, Plisk S,
Reinardy J, Cantler E, Almada AL :Effects of creatine supplementation
on body composition, strength, and sprint performance. Med Sci Sports
Exerc 1998, 30:73-82. PubMed Abstract | Publisher Full Text | OpenURL
60. Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez
AL, Pearson DR, Fink WJ, Kraemer WJ :Performance and muscle fiber
adaptations to creatine supplementation and heavy resistance training.
Med Sci Sports Exerc 1999, 31:1147-56. PubMed Abstract | Publisher
Full Text | OpenURL
61. Stone MH, Sanborn K, Smith LL, O'Bryant HS, Hoke T, Utter AC,
Johnson RL, Boros R, Hruby J, Pierce KC, Stone ME, Garner B :Effects
of in-season (5 weeks) creatine and pyruvate supplementation on
anaerobic performance and body composition in American football
players. Int J Sport Nutr 1999, 9:146-65. PubMed Abstract | OpenURL
62. Noonan D, Berg K, Latin RW, Wagner JC, Reimers K :Effects of
varying dosages of oral creatine relative to fat free body mass on
strength and body composition. J Strength Cond Res 1998, 12:104-108.
Publisher Full Text | OpenURL
63. Kirksey KB, Stone MH, Warren BJ, Johnson RL, Stone M, Haff GG,
Williams FE, Proulx C :The effects of 6 weeks of creatine monohydrate
supplementation on performance measures and body composition in
collegiate track and field athletes. J Strength Cond Res 1999,
13:148-156. Publisher Full Text | OpenURL
64. Jones AM, Atter T, Georg KP :Oral creatine supplementation
improves multiple sprint performance in elite ice-hockey players. J
Sports Med Phys Fitness 1999, 39:189-96. PubMed Abstract | OpenURL
65. Kreider RB, Almada AL, Antonio J, Broeder C, Earnest C,
Greenwood M, Incledon T, Kalman DS, Kleiner SM, Leutholtz B, Lowery
LM, Mendel R, Stout JR, Willoughby DS, Ziegenfuss TN :ISSN exercise &
sport nutrition review: research and recommendations. Sport Nutr Rev J
2004, 1:1-44. OpenURL
66. Greenwood M, Kreider RB, Greenwood L, Byars A :Cramping and
injury incidence in collegiate football players are reduced by
creatine supplementation. J Athl Train 2003, 38:216-219. PubMed
Abstract | PubMed Central Full Text | OpenURL
67. Greenwood M, Kreider RB, Greenwood L, Byars A :The effects of
creatine supplementation on cramping and injury occurrence during
college baseball training and competition. J Exerc Physiol Online
2003, 6:16-23. OpenURL
68. Poortmans JR, Francaux M :Adverse effects of creatine
supplementation: fact or fiction? Sports Med 2000, 30:155-170. PubMed
Abstract | Publisher Full Text | OpenURL
69. Pritchard NR, Kalra PA :Renal dysfunction accompanying oral
creatine supplements. Lancet 1998, 351:1252-1253. PubMed Abstract |
Publisher Full Text | OpenURL
70. La creatine dangereuse? L'Equipe10. Open URL 1998, April 10
71. Koshy KM, Giswold E, Scheenberger EE :Interstitial nephritis in
a patient taking creatine. N Engl J Med 1999, 340:814-5. PubMed
Abstract | Publisher Full Text | OpenURL
72. Thorsteinsdottir B, Grande JP, Garovic VD :Acute renal failure
in a young weight lifter taking multiple food supplements including
creatine monohydrate. J Renal Nutr 2006, 16(4):341-345. OpenURL
73. Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson
GR :Effect of short-term creatine supplementation on renal responses
in men. Eur J Appl Physiol 1997, 76:566-567. Publisher Full Text | OpenURL
74. Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux
M :Effect of oral creatine supplementation on urinary methylamine,
formaldehyde, and formate. Med Sci Sports Exerc 2005, 37:1717-1720.
PubMed Abstract | Publisher Full Text | OpenURL
75. Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M,
Coglianese R, Smith L, O'Bryant HS, Fry AC, Starks M, Keith R, Stone
ME :Creatine supplementation and health variables: a retrospective
study. Med Sci Sports Exerc 2001, 33:183-188. PubMed Abstract |
Publisher Full Text | OpenURL
76. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL
:Dietary creatine supplementation does not affect some haematological
indices, or indices of muscle damage and hepatic and renal function.
Br J Sports Med 2000, 34:284-8. PubMed Abstract | Publisher Full Text
| OpenURL
77. Sipila I, Rapola J, Simell O, Vannas A :Supplementary creatine
as a treatment for gyrate atrophy of the choroid and retina. New Engl
J Med 1981, 304:867-870. PubMed Abstract | OpenURL
78. Vannas-Sulonen K, Sipila I, Vannas A, Simell O, Rapola J :Gyrate
atrophy of the choroid and retina. A five-year follow-up of creatine
supplementation. Ophthalmology 1985, 92:1719-27. PubMed Abstract | OpenURL
79. Ensenauer R, Thiel T, Schwab KO, Tacke U, Stockler-Ipsiroglu S,
Schulze A, Hennig J, Lehnert W :Guanidinoacetate methyltransferase
deficiency: differences of creatine uptake in human brain and muscle.
Mol Genet Metab 2004, 82:208-13. PubMed Abstract | Publisher Full Text
| OpenURL
80. Schulze A, Ebinger F, Rating D, Mayatepek E :Improving treatment
of guanidinoacetate methyltransferase deficiency: reduction of
guanidinoacetic acid in body fluids by arginine restriction and
ornithine supplementation. Mol Genet Metab 2001, 74:413-419. PubMed
Abstract | Publisher Full Text | OpenURL
81. Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA
:Guanidinoacetate methyltransferase deficiency: new clinical features.
Pediatr Neurol 1997, 17:155-157. PubMed Abstract | Publisher Full
Text | OpenURL
82. Zhu S, Li M, Figueroa BE, Liu A, Stavrovskaya IG, Pasinelli P,
Beal MF, Brown RH Jr, Kristal BS, Ferrante RJ, Friedlander RM
:Prophylactic creatine administration mediates neuroprotection in
cerebral ischemia in mice. J Neurosci 2004, 24:5909-12. PubMed
Abstract | Publisher Full Text | OpenURL
83. Hausmann ON, Fouad K, Wallimann T, Schwab ME :Protective effects
of oral creatine supplementation on spinal cord injury in rats. Spinal
Cord 2002, 40:449-56. PubMed Abstract | Publisher Full Text | OpenURL
84. Brustovetsky N, Brustovetsky T, Dubinsky JM :On the mechanisms
of neuroprotection by creatine and phosphocreatine. J Neurochem 2001,
76:425-34. PubMed Abstract | Publisher Full Text | OpenURL
85. Sullivan PG, Geiger JD, Mattson MP, Scheff SW :Dietary
supplement creatine protects against traumatic brain injury. Ann
Neurol 2000, 48:723-9. PubMed Abstract | Publisher Full Text | OpenURL
86. Jacobs PL, Mahoney ET, Cohn KA, Sheradsky LF, Green BA :Oral
creatine supplementation enhances upper extremity work capacity in
persons with cervical-level spinal cord injury. Arch Phys Med Rehabil
2002, 83:19-23. PubMed Abstract | Publisher Full Text | OpenURL
87. Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W :Oral
creatine supplementation in Duchenne muscular dystrophy: a clinical
and 31P magnetic resonance spectroscopy study. Neurol Res 2000,
22:145-50. PubMed Abstract | OpenURL
88. Tarnopolsky MA, Mahoney DJ, Vajsar J, Rodriguez C, Doherty TJ,
Roy BD, Biggar D :Creatine monohydrate enhances strength and body
composition in Duchenne muscular dystrophy. Neurology 2004,
62:1771-1777. PubMed Abstract | Publisher Full Text | OpenURL
89. Pearlman JP, Fielding RA :Creatine Monohydrate as a therapeutic
aid in muscular dystrophy. Nutr Reviews 2006, 64:80-88. Publisher Full
Text | OpenURL
90. Matsumura T :A clinical trial of creatine monohydrate in
muscular dystrophy patients. Clin Neurol (Japan) 2004, 44(10):661-666.
OpenURL
91. Op't Eijnde B, Urso B, Richter EA, Greenhaff PL, Hespel P
:Effect of oral creatine supplementation on human muscle GLUT4 protein
content after immobilization. Diabetes 2001, 50:18-23. PubMed Abstract
| Publisher Full Text | OpenURL
92. Earnest CP, Almada A, Mitchell TL :High-performance capillary
electrophoresis- pure creatine monohydrate reduced blood lipids in men
and women. Clinical Science 1996, 91:113-118. PubMed Abstract | OpenURL
93. Fuld JP, Kilduff LP, Neder JA, Pitsiladis Y, Lean MEJ, Ward SA,
Cotton MM :Creatine supplementation during pulmonary rehabilitation in
chronic obstructive pulmonary disease. Thorax 2005, 60:531-7. PubMed
Abstract | Publisher Full Text | OpenURL
94. Tyler TF, Nicholas SJ, Hershman EB, Glace BW, Mullaney MJ,
McHugh MP :The effect of creatine supplementation on strength recovery
after anterior cruciate ligament (ACL) reconstruction: a randomized,
placebo-controlled, double-blind trial. Am J Sports Med 2004,
32:383-8. PubMed Abstract | Publisher Full Text | OpenURL
95. Kilduff LP, Georgiades E, James N, Minnion RH, Mitchell M,
Kingsmore D, Hadjicharlambous M, Pitsiladis YP :The effects of
creatine supplementation on cardiovascular, metabolic, and
thermoregulatory responses during exercise in the heat in
endurance-trained humans. Int J Sport Nutr Exerc Metab 2004,
14:443-60. PubMed Abstract | OpenURL
96. Volek JS, Mazzetti SA, Farquhar WB, Barnes BR, Gomez AL, Kraemer
WJ :Physiological responses to short-term exercise in the heat after
creatine loading. Med Sci Sports Exerc 2001, 33:1101-8. PubMed
Abstract | Publisher Full Text | OpenURL
97. Wyss M, Schulze A :Health implications of creatine: can oral
creatine supplementation protect against neurological and
atherosclerotic disease? Neuroscience 2002, 112:243-60. PubMed
Abstract | Publisher Full Text | OpenURL
98. Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S,
Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF :Neuroprotective
effects of creatine in a transgenic mouse model of Huntington's
disease. J Neurosci 2000, 20:4389-97. PubMed Abstract | Publisher Full
Text | OpenURL
99. Tarnopolsky MA :Potential benefits of creatine monohydrate
supplementation in the elderly. Curr Opin Clin Nutr Metab Care 2000,
3:497-502. PubMed Abstract | Publisher Full Text | OpenURL
100. Hespel P, Op't Eijnde B, Van Leemputte M, Urso B, Greenhaff PL,
Labarque V, Dymarkowski S, Van Hecke P, Richter EA :Oral creatine
supplementation facilitates the rehabilitation of disuse atrophy and
alters the expression of muscle myogenic factors in humans. J Physiol
2001, 536:625-33. PubMed Abstract | Publisher Full Text | OpenURL
