Creatine and its Medical Uses

Jarrad Bard
Michael Wilson
Intro

 Researchers, having seen creatine’s effects on

the body when used as a supplement for
enhancing athletic performance became aware of
its other possible benefits.
 Creatine has been beneficial in treating Duchenne’s
Muscular Dystrophy and other similar diseases.
Duchenne’s Muscular
Dystrophy
 Is a rapid progression of muscle
degeneration.
Production / Transport
 Creatine is an amino acid derivative synthesized
by combining arginine, an amino acid and
glycine, an organic compound through two
enzyme reactions.
 The first enzyme reaction takes place in the
kidneys and produces Guanidinoacetate, the
intermediate biosynthesis in creatine formation.
Guanidinoacetate is then moved to the liver where
methyl groups are added to form creatine.
 Creatine can also be absorbed through the diet
where it is stored in the skeletal muscles, and can
be used later for energy production.
 Red meats and poultry
Production / Transport

 Creatine acts on the body by crossing the cell

membranes against their concentration gradients
by way of a transporter called CreaT which is
Na+/Cl- dependent.
 CreaT expression is dependant on the amount of
creatine and phosphocreatine present in the body.
 In patients with myopathies, CreaT is less present
in the skeletal muscles.
 Exercise is beneficial to the relocation of CreaT into
the muscle cell membranes.
Metabolism

 Creatine exerts its effects on the metabolism by:

 The formation of ATP

 When energy demands of a body increase:

 The ready form of Phosphocreatine donates its
phosphate group to ADP to form ATP – This is
known as the creatine kinase (CK) reaction.
Metabolism

 CK is an isozyme which functions in two opposite

ways:
 Mitochondrial CK
 Catalyzes phosphocreatine synthesis from ATP, generated
by oxidative phosphorylation.

 Cytosolic CK
 Initiates the regeneration of ATP from phosphocreatine at
specific sites of ATP consumption.
Metabolism

 Healthy mice deficient in CK had similar

weaknesses found in dystrophic mice such as
lower muscular force, power, work, and
contraction of skeletal muscles.

 Mice lacking CK relating to the brain had several

factors affecting metabolism such as less weight
gain, higher fat metabolism, irregular
thermoregulation, and mood swings.
Exercise and Creatine
 Studies on creatine used to enhance athletic performance
are inconclusive.
 Many of these studies involve only the sudden affects of
creatine supplementation which are measured by
frequency, duration, and intensity of the exercise being
performed.
 Rawson et al and Volek et al had positive studies on the
acute affects of creatine supplements for many bouts of
short-term resistance training in a controlled double-blind,
placebo study. Using 5g a day for 5-7 days with resistance
training, increases in fat-free muscle mass and maximal
strength were found by decreasing lactate accumulation.
 In healthy men, reports have shown an 8% increase on
muscular strength and a 14% increase in training
duration.
Exercise and Creatine

 However, Deutekom’s et al double-blind, placebo

controlled study using 20g of creatine a day for 6
days failed to show any significant increase in
athletic performance with acute creatine
supplementation.
 Variables studied: Muscle fiber
activation, peak power, maximum
controlled muscle torque, and fatigue/
recovery from intense exercise.
Exercise and Creatine
 The effects of long-term creatine supplementation is
in question by many, however, there have been
studies that show some increases in athletic
performance.
 Vandenberghe et al studied the effects in women
who performed resistance training in the leg press,
bench press, leg curl, leg extension, squat, shoulder
press, and sit-ups. From these recordings an increase
in muscle phosophocreatine is shown, along with an
increase in strength, exercise capacity, and fat-free
mass.
 High creatine intake of (20g/d) for 4 days followed by
(2g/d) for 10 weeks showed an increase in maximum
strength from 20% to 25%, maximum exercise capacity
from 10% to 25%, and fat-free mass was up 60%.
Exercise and Creatine

 Van Loon et al on the other hand, using creatine

supplementation of 20g a day for 5 days followed
by 2g a day for 6 weeks concluded that prolonged
creatine supplementation did not increase oxygen
capacity or performance during endurance
cycling, but did show an increase in lean muscle
gain.

 There are currently no known health issues with

prolonged uses of creatine supplementation.
Mitochondrial Cytopathies

 Scientist have shown that the use of creatine in

medical therapy can help prevent mitochondrial
cytopathies which are mechanisms that fail within
the mitochondria of the cell.
 Mitochondria is used for about 90% of energy
production. Without the main uses of
mitochondria, life threatening diseases can arise.
 Huntingtons disease is one example caused by the
failure of mitochondria which results in the loss of
muscle coordination throughout the body.
Mitochondrial Cytopathies
 MC disorders cause defects in aerobic energy production.
As a result ATP production becomes dysfunctional.
 MC patients display lower resting phosphocreatine levels,
delayed recovery of phosphocreatine after workouts in
skeletal muscle, and lower phosphocreatine/ATP levels in
the brain.
 Using a transgenic mouse model, Dedeoglu et al
concluded that creatine introduced before and after
symptoms of Huntingtons disease are present, extends the
quantity of life.
 Moderate doses of creatine (5-10g a day for 2-3 weeks) in
MC patients show increases in handgrip strength,
improved dorsiflexion torque and decreased post-exercise
lactate levels.
Brain
 Research has shown that creatine
supplementation can help with Amyotrophic
Lateral Sclerosis also known as Lou Gehrig’s
Disease by increasing voluntary muscle
contraction.
 Lou Gehrig’s Disease is a degenerative motor
neuron disease that affects muscle strength and
can ultimately lead to a premature death.

 Two significant studies researched by

Andreassen and Berger provide evidence that
creatine could have positive neuro-protective
effects.
Brain
 Andreassen et al concluded that creatine increased
quantity of life, motor performances, and decreased
cortical glutamate concentrations.
 During Andreassen’s study it was found that creatine can
pass through the placental barrier preventing ischemia
(brain hypoxia) in newborns which results in brain
damage, spinal, and neural cell damages.
 Berger et al, testing guinea pigs had an increase in
the recovery of protein production in the
hippocampus after being deprived of oxygen-
glucose for 2 hours. He also showed a decrease in
ATP depletion and a delay in anoxic depolarization
along with an improvement in post-synaptic potential.
Skeletal Muscle Disease

 Creatine supplementation is being used to focus

on patients with Duchenne’s Muscular Dystrophy
resulting from mutations in the protein Dystrophin.
 Without the normal function of dystrophin, calcium
levels within the cells become unstable and
eventually lead to high calcium concentration
levels in the cytosol of the cell.
 High amounts of Ca+ in the cytosol inevitably
leads to the disuse of one voluntarily contracting
their muscles.
Creatine and Muscular
Dystrophy

 Researchers have learned through studies:

 Creatine supplementation increases phosphocreatine
levels and improves the regulation of Ca2+ in MDX
myotubes exposed to stress.
 Creatine can reduce skeletal muscle degeneration and
enhance mitochondrial function in MDX mice.
Creatine and Muscular
Dystrophy

 There have been very few studies on human

responses to creatine.
 Of the studies which have been done, outcomes
are debatable.
 Walter et al showed little to know benefit of
creatine in patients with myotonic and muscular
dystrophy. Where as Louis et al documented
increased maximal voluntary contraction in DMD
and BMD patients by 25% and almost doubled
their energy capacity by using 3g/d for 3 months.
Creatine and Muscular
Dystrophy

 Tarnopolsky et al is another researcher who

performed the first long-term study on creatine
supplementation in patients with DMD relating to
improvements in motor function and muscle
strength.
 Tarnopolsky’s study examined the use of creatine
alongside corticosteroid therapy to see if
corticosteroids would affect the outcome of
creatine supplementation as well as the safety of
using creatine in conjunction with corticosteroid
therapy.
Creatine and Muscular
Dystrophy
 Tarnopolsky’s research involved a controlled
double-blind, placebo, cross-over study which
involved 30 participants that were randomly split
in two groups.
 One of the groups was given creatine
supplementation where the other group was
given corticosteroids.
 In the group assigned corticosteroids:
 13 of these patients were given Deflazacort
 2 of these patients were given Prednisone
 Both supplementations were given in the form of
a chewable tablet.
Creatine and Muscular
Dystrophy
 After 4 months of creatine/corticosteroid
supplementation all participants were to
discontinue use for 6 weeks and then switch to
the opposite supplementation for another 4
months.

 Creatine tablet doses ranged from .102 -

.027g/kg/d
 Corticosteroid doses were identical to the creatine dose
which varied day to day.
Creatine and Muscular
Dystrophy
 From Tarnopolsky’s study, strength data was
recorded over 3 trials in maximal manual hand
strength using a dynamometer and a custom
made force transducer for both the dominant and
non-dominant hands.
Creatine and Muscular
Dystrophy
 Results from the strength data and functional test
showed creatine having positive benefits without the
co-use of corticosteroids on patients with DMD.
 There was an increase of less than .05 in both dominant
and non-dominant hands but not a significant increase in
handgrip strength.
 Muscle strength reduced in the placebo group by a 3.7%
loss vs. the creatine group with a strength loss of 2.8%.
These results were also not significant.
 Changes in daily living, functional testing, and
pulmonary function were insignificant.
 Lean mass while it increased during the creatine phase
was still insignificant when compared to the
corticosteroid phase.
Creatine and Muscular
Dystrophy

 Certain biomechanical markers located in the

blood and urine were also monitored for the
effects of creatine and corticosteroid
supplementation.

 Blood samples were used to determine activity of:

 CK
 y-glutamyl activity
 Creatine concentrations
Creatine and Muscular
Dystrophy

 Urine specimens were then collected for 24 hours

after each 4 month period to test for:
 8-hydroxy-2-deoxyguianosine
 a marker of DNA oxidative damage
 N-teopeptide
 a marker of bone breakdown
 3-methylhistidine
 a marker for myofibrillar protein catabolism
Creatine and Muscular
Dystrophy
 Niether creatine nor corticosteroid treatment
affected the serum creatinine, creatine kinase, or
y-glutamyl.
 8-hydroxy-2-deoxyguianosine and N-
telopeptide/creatinine showed decreases with
corticosteroids when compared to pure creatine
supplementation. Ironically, N-telopeptide/creatinine
showed decreases with creatine when compared to
corticosteroid supplementation.
 The 3-methylhistidine content was not affected by
creatine or corticosteroid supplementation.
 It has been concluded from this data that creatine
has the potential to reverse bone damage studied
in the N-telopeptide response.
Conclusions
 Creatine used alongside corticosteroids can
prevent catabolic symptoms from progressing.
 Creatine can also be used safely for DMD
patients without the use of corticosteroids.
 The anabolic effects of corticosteroids assist with
muscular dystrophy, but the many side affects
tied to steroids are not found from creatine
supplementation.
 If patients gain strength from corticosteroids
which last from months to years, creatine will
certainly benefit those strength gains.
Conclusions

 Tarnopolsky et al stated two important finds from

his research:
 Creatine as an alternative therapy to
corticosteroids.
 Long-term users of corticosteroids may find
additional benefits by using creatine.
Resources
 Creatine Monohydrate as a Therapeutic Aid in Muscular
Dystrophy, Jared P. Pearlman BS and Roger A. Fielding,
Nutrition Reviews®, Vol. 64, No. 2, February 2006.
 Creatine as a Therapeutic Strategy for Myopathies, Tarnopolsky,
M, Amino Acids, Vol. 40 Issue 5, p1397-1407, May 2011
 www.Mondofacto.com
 www.Umdf.org
 www.Scienceblogs.com
 www.Topendsports.com
 www.muscleextreme.co.uk
 www.msmdhelp.com