Can creatine supplementation prolong lifespan and quality of life in subjects with Amyotrophic Lateral
Sclerosis (ALS) through decreasing the degenerative process of motor control, decreasing muscle
atrophy, and decreasing muscle weakness?
A magazine article for patients with ALS and their family members
Holly Hanzel
Fall 2005
An article for an information packet for ALS patients
(Packet is printed for offices of ALS neurologists)
**Parentheses[] will be definition boxes in magazine article**
When my father-in-law was diagnosed with a neurodegenerative disease, he was not ready or
willing to through in the towel on life. Even though he has a non-curable disease, he has taken every
possible step to educate himself and our family regarding the medical aspects and the available
research concerning his disease. This has enabled him to effectively communicate with the doctors,
and enabled him to critically analyze all possible data and information on the disease. He has tried a
plethora of drugs and supplementations. Five years ago he was told he had five years to live and
would be in a wheelchair in three. Today he is not in a wheelchair; furthermore, his motor
performance degeneration has only progressed to the estimated point of one year after his diagnosis.
Having a family member with a terminal illness, of which symptoms have been reduced by
supplements, is my motive for writing this review article.
My purpose is to analyze the available literature on the treatment of ALS symptoms with
creatine monohydrate, which will provide you, patients with ALS and their family members, with
insight into the impact of creatine in the treatment of ALS. This easily obtainable over-the-counter
supplement could provide an affordable treatment for you, by possibly prolonging your quality of life.
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Introduction to Analysis
Following is my analysis about the muscular and neurological symptoms of ALS. I need to
assess both because motor neurons control the movement of voluntary muscles, and evidence shows
creatine has neuroprotective effects in addition to helping muscular symptoms. Therefore, my analysis
is based on one review article assessing the long-term efficacy of creatine supplementation in health
and disease, and seven research studies that used creatine supplementation to determine its efficacy in
treating the degenerative muscular symptoms of ALS. My review is also based on one research study
that analyzed the efficacy of creatine supplementation on the muscular symptoms of ALS and
Huntington’s disease, which has similar neurodegenerative symptoms. In addition, my review is based
on six studies that discuss the neuroprotective properties of creatine in relation to the neurological
symptoms of ALS. These studies will not be analyzed in detail like the muscular studies because my
primary concern is your muscular symptoms. I am using them to strengthen my claim that creatine can
help you. These sources date from 1994 through 2003, and were obtained by computerized searches of
PubMed, Science Direct, Sport Discus and Web of Science databases, using key search terms such as
‘amyotrophic lateral sclerosis’, ‘creatine’ and ‘neurological disease’.
Definition of ALS
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, usually effects
males and has an incidence rate between 1 and 5 out of every 100,000 people, which typically strikes
during mid to late life (Cluskey and Ramsden, 2001). ALS is a progressive neuromuscular disease that
causes degeneration of some of the largest of all nerve cells, called motor neurons (Rowland and
Shneider, 2001). Motor neurons control the movement of voluntary muscles. Motor neurons extend
from the brain to the spinal cord [the upper motor neurons] and from the spinal cord to the muscles
throughout the body [the lower motor neurons]. The disease causes the motor neurons to degenerate
and eventually die. As the motor neurons die, the muscle cells are paralyzed and eventually
deteriorate. The ongoing loss of motor neurons leads to progressive weakness and atrophy of skeletal
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muscles [loss of muscle fiber volume characterized by a visible decrease in muscle size] along with
impaired control of those muscles (Cluskey and Ramsden, 2001). In the beginning of the disease, the
person starts out with fatigue and becomes progressively weaker, eventually becoming paralyzed. In
most cases, ALS results in fatality within two to five years from the first appearance of the symptoms.
Definition of Creatine Monohydrate
α-Methylguanidino-acetic acid, known as creatine monohydrate, is consumed in a typical
western diet of about 1 g per day from protein foods (Persky and Brazeau, 2001). Creatine is also
synthesized by the body primarily in the liver, kidneys and pancreas (Persky and Brazeau, 2001).
Most creatine is not stored in the tissue in which it is synthesized. Actually, 95% is found in skeletal
muscle, with the remainder found in the brain, liver and kidneys (Persky and Brazeau, 2001). Creatine
is actively transported (uses energy) from the synthesized tissue into the target tissue by a transporter
protein called CreaT (Persky and Brazeau, 2001). Once inside the cell, creatine becomes
phosphocreatine (PCr), which constitutes 60-70% of stored creatine in muscle cells. Once creatine has
been used by the muscle tissue, it is eliminated by the kidneys (Persky and Brazeau, 2001).
The best known function of creatine is its role in the support of energy production inside the
cell. The biological form of energy is called ATP. Creatine provides nearly half the energy for the
first 10 seconds of muscle contraction. (Bogdanis, Nevill and Boobis, 1996) This increase in energy is
why some athletes believe creatine supplementation enhances high-intensity performance. In fact,
some studies have shown that ingestion of 20g of creatine per day for 2-5 days, increases creatine in
the muscle by about 20% (Bogdanis, Nevill and Boobis, 1996).
Creatine also has neuroprotective properties. These properties include direct antioxidant
activity, stabilization of mitochondrial [produce energy for the cell through cellular respiration]
membranes, stimulation of glutamate [produced by the body, plays an essential role in initiating and
transmitting nerve impulses, and in human metabolism] uptake into synaptic vesicles and increased
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delivery of ATP to sarcoplasmic reticulum [membrane structures in muscle involved in the control of
calcium concentration and hence muscle contraction] (Persky and Brazeau, 2001).
Introduction to Scientific Studies
The eight studies, which are based on muscular symptoms, I have investigated aimed to answer
the question of whether creatine supplementation can prolong quality of life in ALS patients by
decreasing the progression of the degenerative symptoms, such as decreased motor control, increased
muscle atrophy, and decreased muscle weakness. Two of these studies also aimed to investigate
whether creatine can increase the lifespan of mice (Andreassen et al., 2001 and Klivenyi et al., 1999).
Of the eight studies, four used animals and four used humans for their subject populations (Table 1and
2). The population sizes of the animal studies do not vary much, ranging from 10 to 12 mice per
investigation. On the other hand, the population sizes of the clinical trials vary greatly, ranging from
14 to 175 ALS patients. Creatine concentrations range from 1% to 3% (equivalent to 5g and 20g in
humans) of daily food intake for three of the animal studies, with one study using 50 mg/kg (mg per kg
of body weight) daily. The clinical trials use a variety of creatine dosage, ranging from 5g/day to
20g/day. The study durations for the humans range from 5 and 7 days with a six month follow-up to
16 months. These eight studies assessed an assortment of findings, such as maximum voluntary
isometric contraction [example is pushing down on a table with your hand and forearm as hard as you
can], muscle atrophy and muscle weight for the animals, motor performance, muscle weakness by
measuring fatigability, grip strength, and vital capacity. The results indicate major differences in the
findings with creatine supplementation, in helping with the symptoms of ALS, in three animal studies
and one clinical trial. In contrast, three clinical trials and one animal study found no major difference
in the findings.
Scientific Evidence of Creatine in the Treatment of ALS
Table 1: Supporting evidence to date on the efficacy of creatine supplementation for treatment of ALS.
Study
Population
Duration
Creatine
Results
4
Andreassen et al. (2001)
(N)
12 ALS
mice
150 days
Monohydrate
1, 2 and 3% daily
food intake
Klivenyi et al. (1999)
10 ALS
mice
Up to 200 days
1% or 2% daily
food intake
Mazzini et al. (2001)
28 ALS
7 days and six
20 g/day for 7
days, 3 g/day for 6
months
Ikeda et al. (2000)
10 ALS
mice
Four weeks
50 mg/kg daily
1. Lifespan increased by
14.6% with 2% creatine
2. Delayed onset motor
performance decline
increased by 15 days
3. Weight loss
significantly delayed
with 2% creatine from
110-150 days
4. Concentrations of
glutamate significantly
decreased with 2%
creatine at 80 days from
0.62 to 0.27 %
glutamate
1. Rotorod performance
significantly better from
116 to 136 days
2. No significant
difference in motor
performance
3. Lifespan increased 13
days with 1% and 26
days with 2%
4. No difference with
1%, significant
reduction in neuron loss
with 2%
5. No significant
difference in body
weight
1. Increase MVIC after
7 days, 70% increase
knee extensors in 20,
53% increase elbow
flexors in 15
2. Significant decrease
fatigue elbow flexors
39% in 11, decrease in
knee flexors but not
significant
1. Grip strength
significantly increased
(p<0.01)
2. Biceps muscle weight
significantly increased
(p<0.01)
3. Number motor
neurons significantly
increased (p<0.01)
Table 2: Non-supporting evidence to date on the efficacy of creatine supplementation for treatment of ALS.
Study
Shefner et al. (2003)
Population
(N)
104 ALS
patients
Duration
5 days and six
months
Creatine
Monohydrate
20 g/day for 5
days, 5 g/day for 6
Results
1. No significant
difference in MIVC
5
months
Groeneveld et al.
(2003),
175 ALS
patients
16 months
10 g/day
Drory and Gross
(2002),
14 ALS
patients
1 mo.(10 subjects),
2 mo. (8), 3 mo.
(5) and 4 mo. (5)
5g/ day
Derave et al. (2003)
10 ALS
mice
120 days
2 % daily food
intake
2. No significant
difference in grip
strength
1. No significant
difference in MVIC
2. No significant
difference in vital
capacity (found
difference but not
significant p=0.12)
3. No significant
difference in quality of
life
No significant
difference in all 4
outcomes: forced vital
capacity, forced
expiratory volume, peak
expiratory flow rate and
maximum voluntary
ventilation
1. No difference in
MVIC, fatigue or
rotorod performance
2. Significant increase
in soleus muscle weight
from 0.31 mg/ g to 4.2
mg/g (P<0.05)
Animal Studies
By looking at the data in Table 1, you can see the majority of studies examining creatine
supplementation in ALS mice support creatine’s efficacy. In one study, oral administration of 1%
creatine resulted in a significant 13-day increase in lifespan. An even greater increase in lifespan by 26
days was shown with 2 % creatine. Creatine was also associated with improvements in motor
performance and protection against loss of motor neurons (Klivenyi et al., 1999). In addition, a study
performed by Ikeda, Iwasaki, and Kinoshita, (2000) found a daily dose of 50 mg/ kg for four weeks
considerably improved all three findings of grip strength, bicep muscle weight and number of motor
neurons.
You can see in Table 2 one study by Derave, Bosch, Lemmens, Eijnde, Robberecht and Hespel
(2003), implementing 2% creatine in ALS mice failed to show major effects on grip strength, body
weight or rotorod (exercise wheel for mice) performance; however, a separate study in Table 1 found
that 2% creatine supplementation considerably improved motor performance, delayed onset of motor
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deficits by an average of 15 days, and deferred weight loss (Andreassen et al, 2001). Creatine was also
shown to increase glutamate [produced by the body and plays an essential role in human metabolism
and in initiating and transmitting nerve impulses] at 80, but not 110 days. In this study, all doses of
creatine administered considerably improved survival.
Human Studies
You can also see in Table 1 and 2 the clinical trials of the efficacy of creatine supplementation
in ALS that are available. Of these only one indicates a major potential benefit with creatine
supplementation (Mazzini et al., 2001). In this study, 28 ALS patients received creatine 20 g/day for 7
days, then 3 g/day for 3-6 months. Maximal voluntary isometric muscle contraction (MVIC) was
tested at the beginning, after 7 days, 3 months and 6 months. Major improvement was seen in MVIC
for knee extensors and elbow flexors after 7 days. A trend for increased body max index (BMI) was
also observed. All variables tested showed a linear progressive decline during the 6 months of followup. The researchers concluded that creatine supplementation increased high-intensity, isometric
[muscle contraction without movement at the joint] power in ALS patients, which may indicate an
effect to prolong your quality of life (Mazzini et al., 2001).
You can see in Table 2 that three clinical trials failed to find major differences with creatine
supplementation. The most recent clinical trial enrolled 104 ALS patients from 14 different sites in the
US (Shefner, Cudkowiez, and Colombo, 2003). Patients were randomly assigned to receive either
creatine or placebo (sugar pill) at a heavy dose of 20g for 5 days, followed by a maintenance dose of
5g for 6 months. This study failed to show a major difference between treatment and control groups
for MVIC and grip strength. A study of ALS patients in the Netherlands failed to show benefits of
creatine supplementation (Groeneveld et al., 2003). In a double-blind [a study in which neither the
subject(s) nor the investigator(s) know which treatment a subject is receiving], placebo-controlled [an
inactive substance or mock therapy (sugar pill) is given to one group while the treatment being tested
is given to another] trial, 175 ALS patients ingested either creatine 10 g/day or placebo for 16 months.
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The primary endpoint, survival, did not considerably differ between the creatine and placebo groups.
However, the study was terminated early due to an unexplained rate of death in the two groups.
Creatine supplementation also had no major effect on secondary variables of functional decline and
forced vital capacity [the amount of air in a full breath]. Another study that investigated forced vital
capacity as the primary finding also found no effect of creatine supplementation on respiratory
function (Drory and Gross, 2002). After 4 months of follow-up, ALS patients supplemented with
creatine 5 g/day showed no major differences in forced vital capacity and other incidences of
respiratory decline compared to controls.
Long Term Safety of Creatine
Finally, the review by Derave, Eijnde and Hespel, 2003, aimed to evaluate the long-term safety
and efficacy of creatine in health and disease. They investigated several studies and found ingestion of
creatine to be safe and well tolerated, with weight gain of up to 20% being the only confirmed side
effect. Since ALS is characterized by weight loss and muscle atrophy, this side effect may indeed be
beneficial for you.
Now that you have a clear understanding of the varying findings of creatine, you should
appreciate that there is definitely an unresolved issue regarding its effect on ALS. Therefore, you can
appreciate why I conclude that creatine does help ALS.
Assessment of the Study Designs for Muscular Symptoms
An assessment of the study designs is needed to clarify these confusing and different findings.
This can be a challenging and puzzling process, but you are in luck because I have assessed several of
these findings in great detail: the population type, the population numbers, the duration of the studies
and the doses of creatine. These features of the different studies are considered limitations, which are
aspects of a study that may influence the results or the extent to which the findings are generalizable.
Therefore, you need to evaluate these limitations of the studies in order to read between the lines of
their findings.
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1. Population Type (Animal or Human)
The first limitation you need to evaluate is the population type. This leads to the question of
why do most of the animal studies demonstrate that creatine helps ALS, and the majority of clinical
trials exhibit that creatine does not help ALS? One reason why so many scientific studies are
performed on animals is because the researchers can control for more of the variables than in clinical
trials. For instance, diet, exercise, environmental factors, timing and assurance/ compliance of doses
and population size can be controlled with animals. However, with clinical trials, humans drop out of
studies for various reasons, do not obey one hundred percent with the timing and compliance of doses,
and have varying diets and exercise routines. Another reason is that researchers can perform
experiments on animals that would be unethical on humans. For instance, researchers take actual
measurements of muscle size by taking the muscle tissue out of the animal body. Hence, you can
understand that there is less room for differences in the findings of animal studies, making their
findings more straightforward. This is a very important factor to consider when analyzing the
limitations of the study designs.
2. Population Number
Another important factor to examine is population size. By looking at Table 1 and 2, you can
see that the population size of the animal studies ranges from 10-12 mice per investigation. This factor
allows for a clear cut comparison of the animal population sizes. However, you can see the population
sizes for the clinical trials range from 14-175 ALS patients. This poses a problem for comparing the
findings of the clinical trials because larger populations indicate more powerful studies, which means
the findings are more convincing. For your understanding, the clinical trials with the larger
populations indicate creatine not to have an effect on ALS (Drory and Gross, 2002, Groeneveld,
Veldink, and Tweel, 2003 and Shefner, Cudkowiez, and Colombo, 2003). The clinical trail by
Mazzini et al. (2001) illustrates a benefit to creatine supplementation, but at the end of the trial their
population was only 28 patients due to a high number of dropouts. Due to the population numbers
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being different in the human studies, our analysis of these studies is difficult. Therefore, other
important factors need to be examined, such as study duration and size of creatine doses.
3. Study Duration and Creatine Doses
The last limitations you need to compare are the duration and the doses of the studies. The
animal studies by Andreassen et al., 2001, Derave et al., 2003, and Klivenyi et al., 1999, all used
similar durations and doses ranging from 120 to 200 days and from 1% to 3% creatine (equivalent to
5g and 20g in humans) of daily food intake respectively. Ikeda et al., 2000, used four weeks for their
duration with a dose of 50mg/kg. Andreassen et al., 2001, and Ikeda et al., 2000, of whom used
varying duration and doses, found major differences in all findings with creatine. However, Klivenyi
et al., 1999, found major differences in two findings of rotorod (exercise wheel for mice) performance
and lifespan, but found no major difference in motor performance and muscle weight. In addition,
Derave et al., 2003, who used 2% creatine, found no major difference in three findings of MVIC,
fatigue and rotorod performance, but found a difference in muscle weight. The differences in findings
between these highly controlled animal studies are hard to assess because they are confusing for a
nonscientist. For your purpose, the designs are similar and three out of four of the animal studies give
a good indication that creatine can help decrease your symptoms.
On the other hand, the duration and doses for the clinical trials vary. The durations range from
5 and 7 days, with a six month follow-up, to 16 months. These differences are important and need to
be addressed. The two studies by Shefner, Cudkowiez, and Colombo, 2003, and Mazzini et al, 2001,
are easy to compare because both used a duration of six months with a high dose of 20g for 5 or 7days
respectively, followed by a maintenance dose of 5g for six months. These two studies used a couple of
different variables, but both used MVIC. Shefner, Cudkowiez, and Colombo, 2003, found no
difference in MVIC and Mazzini et al, 2001, found a major difference in MVIC. These different
findings with the same duration and doses leads you back to the population sizes. Therefore, you need
to look at the different population sizes to determine the more legitimate study. Shefner, Cudkowiez,
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and Colombo, 2003, used 104 ALS patients and Mazzini et al, 2001, used 28 ALS patients. Therefore,
the more legitimate study by Shefner, Cudkowiez, and Colombo, 2003, indicates creatine to not have
an effect on ALS.
As you can see, it is very important to look at as many factors as you can in order to effectively
analyze the results of scientific studies. For your purpose, all but one of the clinical trials indicate
creatine to be ineffective for treating symptoms of ALS, but it is not as legitimate due to the population
size. Now, you are directed to my counterargument because the majority of the human studies found
creatine to not be effective in treating ALS.
Counterargument
The strongest counterargument to my claim is that the majority of the clinical trials did not find
creatine to be effective in treating symptoms of ALS (Table 2). Furthermore, the clinical trial showing
efficacy of creatine only used 28 patients (Mazzini et al, 2001), which causes their findings to be
weaker than the studies with higher populations. Just because animal studies show a major difference,
does not mean the same will be seen in humans. There are many important findings in animal studies,
but when they are applied to humans, the findings are not there. This means that animal data cannot be
directly applied to humans. It can be extrapolated and considered, but cannot be taken as a direct
indication. This is very important to this analysis and indicates the need for further investigation on
this subject. This being noted, I still conclude that creatine can help you. This is because it also has
neuroprotective properties that are directly linked to the neurodegenerative symptoms of your disease.
The support to this claim will be discussed next when you look at how ALS begins: the origin of motor
neuron loss in ALS.
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Refutation to Counterargument Based on the Origin of Motor Neuron Loss in ALS
Table 3 Neuroprotective Properties of
Creatine
Origin of motor neuron loss in ALS
Damage by reactive oxygen species
Mitochondrial dysfunction
Imbalance of calcium homeostasis
inside the cell
Glutamate excitotoxicity
Neuroprotective properties of creatine
Direct antioxidant activity
Energy buffering and stabilization of mitochondrial
membranes
Increased delivery of ATP by creatine kinase/
phosphocreatine
Stimulation of glutamate uptake into synaptic vesicles
Table 3: Recent data suggests that creatine also has neuroprotective effects. Even though recent studies indicate conflicting
results on the efficacy of creatine, the properties of creatine indicate a potential benefit for treating this neurodegenerative
disease.
My refutation to the counterargument for creatine’s effect on ALS is based on the fact that I
have also researched the origin of motor neuron loss in your disease and the neuroprotective properties
of creatine. There appears to be a connection, which can be seen in Table 3, between ALS and creatine
that further supports my claim. I conclude that creatine can help you based on my study of this
literature. Following are four indirect connections to the benefit of creatine for ALS. They are indirect
because they were not tested on ALS; however, they where discovered by various scientific
experiments with strong study designs, which makes their findings acceptable to discuss.
First, oxidative damage from reactive oxygen species [called free radicals, which have been
implicated in aging, cancer, cardiovascular disease and other kinds of oxidative damage to the body]
appears to play a role in the destruction of motor neurons in ALS. This is because motor neurons have
high metabolic activity (use a lot of energy); therefore, they are particularly sensitive to oxidative
damage. Approximately 25% of ALS patients possess a defect in a gene called SOD-1, which acts as
an antioxidant against the free radicals that form in the body from toxic exposures (Rowland and
Shneider, 2001). Furthermore, it is believed that this defect actually increases oxidative damage to
cells. A recent study found creatine to have major antioxidant-scavenging activity, indicating it to
have direct antioxidant properties (Lawler, Barnes and Wu, 2002). This indicates that creatine can
12
protect motor neurons from damage by free radicals, which is one way it can help reduce the
progression of your decreasing muscle control.
Second, motor neuron degeneration involves mitochondrial dysfunction. As already
mentioned, the primary function of mitochondria is the production of ATP (biological energy);
therefore, mitochondrial damage results in energy deficiency that can result in cell death. Increased
creatine levels means increased reserves of ATP. In addition, the mitochondrial creatine promotes the
transport of ATP from the mitochondria to the cytosol (fluid inside the cell) where it can be used
(Wyss and Wallimann, 1994). This increase in energy reserves inside the cell may help to offset the
high energy demands of motor neurons, thereby reducing your cell death.
Third, according to Klivenyi (1999), abnormal calcium handling inside the cell is also part of
the development of ALS symptoms. Studies have shown a direct link between the creatine system and
calcium regulation inside the cell. In one animal study with mutations for creatine, its absence
disrupted both calcium release and uptake by the sarcoplasmic reticulum (Steeghs, Benders and
Oerlemans, 1997). Again, the sarcoplasmic reticulum is the membrane structure in muscle that is
involved in the control of calcium concentration and hence muscle contraction. Another animal study
demonstrated the importance of creatine in the delivery of ATP to the sarcoplasmic reticulum (de
Groof, Fransen and Errington, 2002). Thus, the neuroprotective property of creatine to increase
delivery of ATP to the sarcoplasmic reticulum helps amend the imbalance of calcium homeostasis for
muscle contraction.
Finally, glutamate is produced by the body and plays an essential role in human metabolism
and in initiating and transmitting nerve impulses (Persky and Brazeau, 2001). As previously noted in
the study by Andreassen et al (2001), glutamate excitotoxicity, which is over stimulation of nerve cells
by nerve impulses that often leads to cell death, is another factor involved in the development of ALS
symptoms. Because removal of glutamate from the nerve cell requires energy, creatine may aid this
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process by increasing energy reserves in the cell. Therefore, creatine can increase your muscle
contraction and give you more strength by removing excess glutamate from muscle cells.
Now that you have an understanding of the connection between the origin of motor neuron loss
in ALS and the neuroprotective properties of creatine, you should appreciate the possible benefit of
creatine for you.
Conclusion: Creatine Can Help You!
Supplementation with oral creatine appears safe and effective in improving exercise
performance and lean mass in healthy populations. The increase in energy due to creatine along with
associated increases in lean muscle mass also hold promise for the treatment of neurodegenerative
diseases, like ALS, which are characterized by muscle weakness and muscle atrophy. Creatine also
possess neuroprotective properties that could improve mitochondrial stabilization, calcium handling in
side the cell, glutamate reuptake into synaptic vesicles and antioxidant properties, all of which are
potentially beneficial in the treatment of ALS.
Creatine has been shown to be effective in neurodegenerative diseases other than ALS, such as
Huntington’s disease, which has similar neurodegenerative symptoms. Evidence for the efficacy in
animals appears promising. This is because these highly controlled studies indicate creatine to be
effective in decreasing the degenerative process of motor control, decreasing muscle atrophy, and
decreasing muscle weakness. However, this is not the end all be all of the effect of creatine on ALS.
You can not live in a box like an animal. Therefore, it is necessary to make sure you take creatine
daily as recommended by your neurologist so that you can comply with the timing of doses. In
addition, it is necessary that your neurologist recommend a healthy diet and a light exercise routine.
This will give you the power to control for these variables (compliance and timing of doses, diet, and
exercise) that the human studies were unable to control. Limited evidence from the clinical trials in
ALS has shown little benefit (Drory and Gross, 2002, Groeneveld, Veldink, and Tweel, 2003 and
Shefner, Cudkowiez, and Colombo, 2003). Therefore, it is evident that future clinical trial research is
14
still needed with highly controlled study designs using large subject populations and longer treatment
durations.
In conclusion, I believe you should consider creatine supplementation to help delay the
symptoms of this neurodegenerative disease especially since studies indicate it to be safe and well
tolerated by the body.
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