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8/7/2019 Exercise Weight Control
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Jarrad Bard
Michael Wilson
Creatine and its Medical Uses
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Intro
Researchers, having seen creatines effects onthe body when used as a supplement forenhancing athletic performance became aware ofits other possible benefits.
Creatine has been beneficial in treating DuchennesMuscular Dystrophy and other similar diseases.
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Duchennes Muscular
Dystrophy
Is a rapid progression of muscledegeneration.
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Production / Transport Creatine is an amino acid derivative synthesized
by combining arginine, an amino acid andglycine, an organic compound through twoenzyme reactions.
The first enzyme reaction takes place in thekidneys and produces Guanidinoacetate, theintermediate 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 canbe used later for energy production.
Red meats and poultry
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Production / Transport
Creatine acts on the body by crossing the cellmembranes against their concentration gradientsby way of a transporter called CreaT which isNa+/Cl- dependent.
CreaT expression is dependant on the amount ofcreatine and phosphocreatine present in the body.
In patients with myopathies, CreaT is less presentin the skeletal muscles.
Exercise is beneficial to the relocation of CreaT intothe muscle cell membranes.
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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 itsphosphate group to ADP to form ATP This is
known as the creatine kinase (CK) reaction.
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Metabolism
CK is an isozyme which functions in two oppositeways:
Mitochondrial CK
Catalyzes phosphocreatine synthesis from ATP, generatedby oxidative phosphorylation.
Cytosolic CK
Initiates the regeneration of ATP from phosphocreatine atspecific sites of ATP consumption.
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Metabolism
Healthy mice deficient in CK had similarweaknesses found in dystrophic mice such aslower muscular force, power, work, and
contraction of skeletal muscles.
Mice lacking CK relating to the brain had several
factors affecting metabolism such as less weightgain, higher fat metabolism, irregularthermoregulation, and mood swings.
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Exercise and Creatine Studies on creatine used to enhance athletic performance
are inconclusive.
Many of these studies involve only the sudden affects ofcreatine supplementation which are measured by
frequency, duration, and intensity of the exercise beingperformed.
Rawson et al and Volek et al had positive studies on theacute affects of creatine supplements for many bouts ofshort-term resistance training in a controlled double-blind,
placebo study. Using 5g a day for 5-7 days with resistancetraining, increases in fat-free muscle mass and maximalstrength were found by decreasing lactate accumulation.
In healthy men, reports have shown an 8% increase onmuscular strength and a 14% increase in trainingduration.
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Exercise and Creatine
However, Deutekoms et al double-blind, placebocontrolled study using 20g of creatine a day for 6days failed to show any significant increase inathletic performance with acute creatinesupplementation.
Variables studied: Muscle fiber
activation, peak power, maximum
controlled muscle torque, and fatigue/
recovery from intense exercise.
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Exercise and Creatine The effects of long-term creatine supplementation is
in question by many, however, there have beenstudies that show some increases in athleticperformance.
Vandenberghe et al studied the effects in women
who performed resistance training in the leg press,bench press, leg curl, leg extension, squat, shoulderpress, and sit-ups. From these recordings an increasein muscle phosophocreatine is shown, along with anincrease in strength, exercise capacity, and fat-freemass. High creatine intake of (20g/d) for 4 days followed by
(2g/d) for 10 weeks showed an increase in maximumstrength from 20% to 25%, maximum exercise capacityfrom 10% to 25%, and fat-free mass was up 60%.
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Exercise and Creatine
Van Loon et al on the other hand, using creatinesupplementation of 20g a day for 5 days followedby 2g a day for 6 weeks concluded that prolongedcreatine supplementation did not increase oxygencapacity or performance during endurancecycling, but did show an increase in lean musclegain.
There are currently no known health issues withprolonged uses of creatine supplementation.
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Mitochondrial Cytopathies
Scientist have shown that the use of creatine inmedical therapy can help prevent mitochondrialcytopathies which are mechanisms that fail withinthe mitochondria of the cell.
Mitochondria is used for about 90% of energyproduction. Without the main uses ofmitochondria, life threatening diseases can arise.
Huntingtons disease is one example caused by thefailure of mitochondria which results in the loss ofmuscle coordination throughout the body.
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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 inskeletal muscle, and lower phosphocreatine/ATP levels in
the brain. Using a transgenic mouse model, Dedeoglu et al
concluded that creatine introduced before and aftersymptoms of Huntingtons disease are present, extends thequantity of life.
Moderate doses of creatine (5-10g a day for 2-3 weeks) inMC patients show increases in handgrip strength,improved dorsiflexion torque and decreased post-exerciselactate levels.
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Brain Research has shown that creatine
supplementation can help with AmyotrophicLateral Sclerosis also known as Lou Gehrigs
Disease by increasing voluntary muscle
contraction. Lou Gehrigs Disease is a degenerative motor
neuron disease that affects muscle strength andcan ultimately lead to a premature death.
Two significant studies researched byAndreassen and Berger provide evidence thatcreatine could have positive neuro-protective
effects.
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Brain Andreassen et al concluded that creatine increased
quantity of life, motor performances, and decreasedcortical glutamate concentrations.
During Andreassens study it was found that creatine can
pass through the placental barrier preventing ischemia(brain hypoxia) in newborns which results in braindamage, spinal, and neural cell damages.
Berger et al, testing guinea pigs had an increase inthe recovery of protein production in thehippocampus after being deprived of oxygen-glucose for 2 hours. He also showed a decrease inATP depletion and a delay in anoxic depolarizationalong with an improvement in post-synaptic potential.
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Skeletal Muscle Disease
Creatine supplementation is being used to focuson patients with Duchennes Muscular Dystrophy
resulting from mutations in the protein Dystrophin.
Without the normal function of dystrophin, calciumlevels within the cells become unstable andeventually lead to high calcium concentrationlevels in the cytosol of the cell.
High amounts of Ca+ in the cytosol inevitablyleads to the disuse of one voluntarily contractingtheir muscles.
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Creatine and Muscular
Dystrophy
Researchers have learned through studies:
Creatine supplementation increases phosphocreatinelevels 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.
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Creatine and Muscular
Dystrophy
There have been very few studies on humanresponses to creatine.
Of the studies which have been done, outcomesare debatable.
Walter et al showed little to know benefit ofcreatine in patients with myotonic and muscular
dystrophy. Where as Louis et al documentedincreased maximal voluntary contraction in DMDand BMD patients by 25% and almost doubledtheir energy capacity by using 3g/d for 3 months.
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Creatine and Muscular
Dystrophy
Tarnopolsky et al is another researcher whoperformed the first long-term study on creatinesupplementation in patients with DMD relating to
improvements in motor function and musclestrength.
Tarnopolskys study examined the use of creatinealongside corticosteroid therapy to see ifcorticosteroids would affect the outcome ofcreatine supplementation as well as the safety ofusing creatine in conjunction with corticosteroidtherapy.
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Creatine and Muscular
Dystrophy Tarnopolskys research involved a controlled
double-blind, placebo, cross-over study whichinvolved 30 participants that were randomly splitin two groups.
One of the groups was given creatinesupplementation where the other group wasgiven 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 ofa chewable tablet.
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Creatine and Muscular
Dystrophy
After 4 months of creatine/corticosteroidsupplementation all participants were todiscontinue use for 6 weeks and then switch to
the opposite supplementation for another 4months.
Creatine tablet doses ranged from .102 -
.027g/kg/d Corticosteroid doses were identical to the creatine dose
which varied day to day.
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Creatine and Muscular
Dystrophy From Tarnopolskys study, strength data was
recorded over 3 trials in maximal manual handstrength using a dynamometer and a custommade force transducer for both the dominant and
non-dominant hands.
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Creatine and Muscular
Dystrophy Results from the strength data and functional test
showed creatine having positive benefits without theco-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 inhandgrip 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, andpulmonary function were insignificant.
Lean mass while it increased during the creatine phasewas still insignificant when compared to the
corticosteroid phase.
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Creatine and Muscular
Dystrophy
Certain biomechanical markers located in theblood and urine were also monitored for theeffects of creatine and corticosteroid
supplementation.
Blood samples were used to determine activity of:
CK y-glutamyl activity
Creatine concentrations
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Creatine and Muscular
Dystrophy
Urine specimens were then collected for 24 hoursafter 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
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Creatine and Muscular
Dystrophy Niether creatine nor corticosteroid treatmentaffected the serum creatinine, creatine kinase, or
y-glutamyl. 8-hydroxy-2-deoxyguianosine and N-
telopeptide/creatinine showed decreases with
corticosteroids when compared to pure creatinesupplementation. Ironically, N-telopeptide/creatinineshowed decreases with creatine when compared tocorticosteroid 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 studiedin the N-telopeptide response.
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Conclusions
Creatine used alongside corticosteroids canprevent catabolic symptoms from progressing.
Creatine can also be used safely for DMDpatients without the use of corticosteroids.
The anabolic effects of corticosteroids assist withmuscular dystrophy, but the many side affectstied to steroids are not found from creatinesupplementation.
If patients gain strength from corticosteroidswhich last from months to years, creatine willcertainly benefit those strength gains.
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Conclusions
Tarnopolsky et al stated two important finds fromhis research:
Creatine as an alternative therapy to
corticosteroids.
Long-term users of corticosteroids may findadditional benefits by using creatine.
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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
http://www.mondofacto.com/http://www.umdf.org/http://www.scienceblogs.com/http://www.topendsports.com/http://www.muscleextreme.co.uk/http://www.msmdhelp.com/http://www.msmdhelp.com/http://www.muscleextreme.co.uk/http://www.topendsports.com/http://www.scienceblogs.com/http://www.umdf.org/http://www.mondofacto.com/