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Why supplement with creatine?
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The energy that fuels most metabolic functions
comes from the splitting of high-energy
phosphate compounds.
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ATP is the major source of fuel for metabolism.
ATP is constantly resynthesized so that there is a
continual source of ATP for biologic work.
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The major energy sources for ATP resynthesis
are fats and carbohydrates. However,
phosphocreatine (PCr) is another high-energy
phosphate that can be hydrolyzed to provide the
energy to form ATP from ADP+P (it is often called
an “energy reservoir”).
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Creatine is found in meat, poultry, and fish. Until recently,
scientists believed that vegetarians had normal levels of
muscle creatine because the body synthesizes creatine
from amino acids in the diet.
However, a study
published in 2003
offers the first
evidence that
vegetarians
have lower muscle
creatine.
Tarnopolsky et al MSSE 2003
amino acid
excreted in the urine
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About 95% of the body’s total creatine is
contained in skeletal muscle as one of two forms.
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PCr (~60%) and free creatine (~40%).
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CK stimulated to hydrolyze PCr to Cr by buildup
of ADP. This makes sense since a large amount
of ADP is indicative of low energy in the cell and
PCr is used to create more ATP.
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PCr is referred to as “buffering” the ATP levels in
the cell - meaning the presence of PCr keeps
ATP levels from falling.
Creatine Metabolism
H 2N
NH2
ATP
CH
ADP
PO3
CH
H 3C N
H3C N
CH2
HN
H 2N
Creatine Kinase (CK)
+ H+
CH2
COO
COO
Creatine
Phosphocreatine
Pi
H 2O
H
N
HN
H 2O
O
N
H 3C
Creatinine
• PCr is used as an energy source for quick, intense
bouts of work.
H+ + PCr + ADP  ATP + Cr
enzyme is creatine kinase (CK)
• The idea behind creatine supplementation is that
increasing the body’s stores of PCr will provide an
advantage for high power, short-duration work.
• The key was thought to be an increase in PCr.
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As the data below show, PCr is the predominant
energy source for ATP synthesis for very short
duration, high intensity muscle contraction.
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Rate of ATP production (mmol/sec/kg) during
maximal contraction in human muscle
Duration
0-1.3 sec
1.4-2.5 sec
2.6-5 sec
5-10 sec
10-20 sec
20-30 sec
PCr
9.0
7.5
5.3
4.2
2.2
0.2
glycolysis
2.0
4.3
4.4
4.5
4.5
2.1 Greenhaff, Int. J. Sport Nutr. 1995
• PCr may also shuttle intramuscular phosphate between the
mitochondria and muscle filament cross-bridge sites (the
actual sites of muscle contraction).
• Theoretically, high levels of PCr should also lessen the
reliance on anaerobic glycolysis. Remember that H+ ions
are produced during glycolysis which are buffered by
pyruvate which reduces to lactate.
• The rate controlling step of glycolysis is catalyzed by an
enzyme called phosphofructose kinase (PFK). PCr levels
exert some control over the activity of this enzyme. As PCr
levels decrease the activity of PFK goes up, increasing the
rate of glycolysis.
ATP  ADP


ATP  ADP
Cr  CrP




mitochondria
Potential mechanism
Cr  CrP
ATP  ADP
Actin and myosin
Summary: Role of PCr in Muscle
1. Fast production of ATP (maximal work?)
2. Buffers change in ATP/ADP (maintain high rate of
work?)
3. Faster high energy phosphate diffusion (faster
recovery?)
4. Buffers intracellular hydrogen ions (less fatigue?)
5. Reduced PCr, increased Pi may activate glycolysis
(less reliance on glycolysis – less glycogen use?
Cr Supplementation Era
1993 - 2000 ??? human studies
Major focus
– Exercise performance
– Body composition
– Optimizing uptake
Recent Studies
– Clinical - elderly, muscle disease, CHF,
COPD, Arthritis, Gyrate Atrophy & other
diseases
Cr Supp & Performance
Exercise performance
involving short periods of
extremely powerful
activity can be enhanced,
especially during
repeated bouts.
….enhanced accrual of
strength in strengthtraining programs.
Terjung et al. ACSM Creatine
Roundtable. MSSE, 2000
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N = 8 fit men/group
Randomized, double-blind
30 g Cr/d for 6 d
4 familiarization trials
10 x 6s maximal cycling;
30s rest intervals
Target rpm = 140/min
Pedaling Rate
Creatine and Performance
145
140
135
130
Creatine
Placebo
125
Balsom et al., Scand. J. Med. Sci.
Sports 3:143-149, 1993
120
0 1 2 3 4 5 6 7 8 9 10
Number of Cycling Bouts
Kreider et al (1998) “Effects of creatine supplementation on body composition,
strength, and sprint performance”.
Addition of creatine to the
glucose/taurine/electrolyte
supplement promoted
greater gains in fat/bonefree mass, isotonic lifting
volume, and sprint
performance during intense
resistance/agility training.
CHANGE AFTER 28 d
Creatine (16 g/d): 11 football players
Placebo:
14 “ “ (matched on body weight)
Resistance training: 4 d/wk monitored
Sprint/agility training: 3 d/wk; Diets: monitored
2.5
2
Placebo
1.5
Creatine
1
0.5
0
-0.5
-1
Body Mass
Fat Mass
Fat-and-BoneFree Mass
Body Water
Becque et al. ”Effects of oral creatine supplementation on muscular
strength and body composition”. MSSE, 2000
Biceps training for 6 weeks with either Cr (20g/d for 5
days and then 2g/d) or placebo.
After 6 weeks: increase of 2.0 kg in Cr group (+0.4 with
placebo) with FFM increasing 1.6 kg. Upper arm area
incr. 8 cm3 with Cr and 2.5 cm3 with placebo.
1 RM incr. 2x more with Cr than with training alone.
Authors conclude “creatine supplementation during arm
flexor strength training lead to greater increases in arm
flexor muscular strength, upper arm muscle area, and fatfree mass than strength training alone”
Cr Supp & Body Mass
Consistent  in body mass (1
- 3 kg)
Acute - Most likely water
retention
–  urine vol. during Cr supp
(Hultman et al. 1996)
Water retention 1st?
Protein synthesis 2nd?
Both together?
Cr & Protein Synthesis
 synthesis of myosin, actin, & CK in vitro & in
vivo (Ingwall et al. 1972 -1976)
Rat Studies
–  protein content (Flisinska - Bojanowska 1996)
– Ø in CK or myosin (Brannon et al. 1997)
–  satellite cell activity (Dangott et al. 2000)
How to use creatine effectively...
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Remember, the benefits of creatine are related to
an athlete’s ability to train harder.
–
This means that creatine alone (without training) likely
won’t increase strength.
Most common creatine supplementation regime:
1.
2.
LOADING PHASE: 5-10 days (20-25g/day)
MAINTENANCE PHASE: (2-5g/day)
- Goal of maintenance phase is maintain muscle
saturation.
Creatine absorption appears to be enhanced when the
supplement is taken with a high CHO drink (ex: juice)
- Tarnopolsky et al., 2001
Cr uptake and Glucose ingestion
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Creatine and Body Mass Conclusions
1. Body mass does tend to increase with creatine
supplementation.
2. The increase is almost exclusively fat free mass
3. Although there may be some retention water in the
short-term, there is some evidence that longerterm use (>6-8 weeks) may increase myofibrillar
protein?
4. Do size and strength gains result because creatine
allows faster recovery between bouts so that
people can train at a higher intensity/longer
duration?
Creatine and Caffeine
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Vandenberghe et al. (1996) looked at whether
combining Cr and caffeine would increase Cr
uptake by muscle.
–
–
0.5g/kg BW of Cr
0.5mg/kg BW of caffiene (equivalent to about 3 cups of
coffee for 70kg male)
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Expected additive effect but Cr in muscle was
same with or w/o caffeine.
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Unexpectedly, addition of caffeine eliminated
ergogenic effects of creatine on knee extensor
force.
This recent work suggests that caffeine ingestion
disrupts the mechanism through which creatine
ingestion increases muscle creatine levels.
May be due to muscle contraction relaxation time
being prolonged (Hepsel et al 2002) thereby
interrupting recovery of PCr?
Based on these and other studies, athletes who
use creatine are often told to abstain from caffeine
during the loading phase of creatine
supplementation when loading the muscle
Caffiene known to enhance prolonged bouts of
exercise, not necessarily high intensity exercise
Side Effects
Anecdotally reported:
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Gastrointestinal distress
Nausea
Dehydration
Muscle cramping
Not reported in
scientific literature
Long term effects of creatine supplementation have not been
documented in healthy individuals but no adverse events
have been linked to creatine use > 5yrs.
Individuals with pre-existing kidney or liver dynsfunction often
not recommended to ingestion Cr supplementation
Conclusions from a host of different studies
1. Creatine supplementation increases total Cr, but
not necessarily CR-P in skeletal muscle
2. Size of the increase is related to initial Cr levels
(start low = bigger response) and individual
responses vary a lot
3. In many people, Cr supplementation enhances
performance of repeated, high-intensity exercise
4. Caffeine use (and probably hard training)
probably reduce the size of the creatine effect
Conclusions from a host of different studies
5. Supplementation results in an initial increase in
body mass (likely due to water retention)
6. May have an age related effect. Older
individuals may show greater improvement
compared to younger individuals. Not clearly
shown.
7. Seems that there is no clear effect of training
status or gender on performance outcomes after
creatine supplementation. (Due to large variance
among individuals taking creatine)