Creatine: More than a sports nutrition supplement
Copyright 2005 Internet Publications
Although creatine offers an array of benefits, most people
think of it simply as a supplement that bodybuilders and
other athletes use to gain strength and muscle mass.
Nothing could be further from the truth.
A substantial body of research has found that creatine may
have a wide variety of uses. In fact, creatine is being
studied as a supplement that may help with diseases
affecting the neuromuscular system, such as muscular
Recent studies suggest creatine may have therapeutic
applications in aging populations for wasting syndromes,
muscle atrophy, fatigue, gyrate atrophy, Parkinson’s
disease, Huntington’s disease and other brain pathologies.
Several studies have shown creatine can reduce cholesterol
by up to 15% and it has been used to correct certain inborn
errors of metabolism, such as in people born without the
enzyme(s) responsible for making creatine.
Some studies have found that creatine may increase growth
What is creatine?
Creatine is formed in the human body from the amino acids
methionine, glycine and arginine. The average person’s body
contains approximately 120 grams of creatine stored as
creatine phosphate. Certain foods such as beef, herring and
salmon, are fairly high in creatine.
However, a person would have to eat pounds of these foods
daily to equal what can be obtained in one teaspoon of
Creatine is directly related to adenosine triphosphate
(ATP). ATP is formed in the powerhouses of the cell, the
mitochondria. ATP is often referred to as the “universal
energy molecule” used by every cell in our bodies. An
increase in oxidative stress coupled with a cell’s
inability to produce essential energy molecules such as
ATP, is a hallmark of the aging cell and is found in many
Key factors in maintaining health are the ability to: (a)
prevent mitochondrial damage to DNA caused by reactive
oxygen species (ROS) and (b) prevent the decline in ATP
synthesis, which reduces whole body ATP levels. It would
appear that maintaining antioxidant status (in particular
intra-cellular glutathione) and ATP levels are essential in
fighting the aging process.
It is interesting to note that many of the most promising
anti-aging nutrients such as CoQ10, NAD, acetyl-l-carnitine
and lipoic acid are all taken to maintain the ability of
the mitochondria to produce high energy compounds such as
ATP and reduce oxidative stress.
The ability of a cell to do work is directly related to its
ATP status and the health of the mitochondria. Heart
tissue, neurons in the brain and other highly active
tissues are very sensitive to this system. Even small
changes in ATP can have profound effects on the tissues’
ability to function properly.
Of all the nutritional supplements available to us
currently, creatine appears to be the most effective for
maintaining or raising ATP levels.
How does creatine work?
In a nutshell, creatine works to help generate energy. When
ATP loses a phosphate molecule and becomes adenosine
diphosphate (ADP), it must be converted back to ATP to
produce energy. Creatine is stored in the human body as
creatine phosphate (CP) also called phosphocreatine.
When ATP is depleted, it can be recharged by CP. That is,
CP donates a phosphate molecule to the ADP, making it ATP
again. An increased pool of CP means faster and greater
recharging of ATP, which means more work can be performed.
This is why creatine has been so successful for athletes.
For short-duration explosive sports, such as sprinting,
weight lifting and other anaerobic endeavors, ATP is the
energy system used.
To date, research has shown that ingesting creatine can
increase the total body pool of CP which leads to greater
generation of energy for anaerobic forms of exercise, such
as weight training and sprinting. Other effects of creatine
may be increases in protein synthesis and increased cell
Creatine has had spotty results in affecting performance in
endurance sports such as swimming, rowing and long distance
running, with some studies showing no positive effects on
performance in endurance athletes.
Whether or not the failure of creatine to improve
performance in endurance athletes was due to the nature of
the sport or the design of the studies is still being
Creatine can be found in the form of creatine monohydrate,
creatine citrate, creatine phosphate, creatine-magnesium
chelate and even liquid versions.
However, the vast majority of research to date showing
creatine to have positive effects on pathologies, muscle
mass and performance used the monohydrate form. Creatine
monohydrate is over 90% absorbable. What follows is a
review of some of the more interesting and promising
research studies with creatine.
Creatine and neuromuscular diseases
One of the most promising areas of research with creatine
is its effect on neuromuscular diseases such as MD. One
study looked at the safety and efficacy of creatine
monohydrate in various types of muscular dystrophies using
a double blind, crossover trial.
Thirty-six patients (12 patients with facioscapulohumeral
dystrophy, 10 patients with Becker dystrophy, eight
patients with Duchenne dystrophy and six patients with
sarcoglycan-deficient limb girdle muscular dystrophy) were
randomized to receive creatine or placebo for eight weeks.
The researchers found there was a “mild but significant
improvement” in muscle strength in all groups. The study
also found a general improvement in the patients’
daily-life activities as demonstrated by improved scores in
the Medical Research Council scales and the Neuromuscular
Symptom scale. Creatine was well tolerated throughout the
study period, according to the researchers.1
Another group of researchers fed creatine monohydrate to
people with neuromuscular disease at 10 grams per day for
five days, then reduced the dose to 5 grams per day for
The first study used 81 people and was followed by a
single-blinded study of 21 people.
In both studies, body weight, handgrip, dorsiflexion and
knee extensor strength were measured before and after
treatment. The researchers found “Creatine administration
increased all measured indices in both studies.” Short-term
creatine monohydrate increased high-intensity strength
significantly in patients with neuromuscular disease.2
There have also been many clinical observations by
physicians that creatine improves the strength,
functionality and symptomology of people with various
diseases of the neuromuscular system.
Creatine and neurological protection/brain injury
If there is one place creatine really shines, it’s in
protecting the brain from various forms of neurological
injury and stress. A growing number of studies have found
that creatine can protect the brain from neurotoxic agents,
certain forms of injury and other insults.
Several in vitro studies found that neurons exposed to
either glutamate or beta-amyloid (both highly toxic to
neurons and involved in various neurological diseases) were
protected when exposed to creatine.3 The researchers
hypothesized that “? cells supplemented with the precursor
creatine make more phosphocreatine (PCr) and create larger
energy reserves with consequent neuroprotection against
More recent studies, in vitro and in vivo in animals, have
found creatine to be highly neuroprotective against other
neurotoxic agents such as N-methyl-D-aspartate (NMDA) and
malonate.4 Another study found that feeding rats creatine
helped protect them against tetrahydropyridine (MPTP),
which produces parkinsonism in animals through impaired
The results were impressive enough for these researchers to
conclude, “These results further implicate metabolic
dysfunction in MPTP neurotoxicity and suggest a novel
therapeutic approach, which may have applicability in
Parkinson’s disease.”5 Other studies have found creatine
protected neurons from ischemic (low oxygen) damage as is
often seen after strokes or injuries.6
Yet more studies have found creatine may play a therapeutic
and or protective role in Huntington’s disease7, 8 as well
as ALS (amyotrophic lateral sclerosis).9 This study found
that “? oral administration of creatine produced a
dose-dependent improvement in motor performance and
extended survival in G93A transgenic mice, and it protected
mice from loss of both motor neurons and substantia nigra
neurons at 120 days of age.
Creatine administration protected G93A transgenic mice from
increases in biochemical indices of oxidative damage.
Therefore, creatine administration may be a new therapeutic
strategy for ALS.” Amazingly, this is only the tip of the
iceberg showing creatine may have therapeutic uses for a
wide range of neurological disease as well as injuries to
One researcher who has looked at the effects of creatine
commented, “This food supplement may provide clues to the
mechanisms responsible for neuronal loss after traumatic
brain injury and may find use as a neuroprotective agent
against acute and delayed neurodegenerative processes.”
Creatine and heart function
Because it is known that heart cells are dependent on
adequate levels of ATP to function properly, and that
cardiac creatine levels are depressed in chronic heart
failure, researchers have looked at supplemental creatine
to improve heart function and overall symptomology in
certain forms of heart disease.
It is well known that people suffering from chronic heart
failure have limited endurance, strength and tire easily,
which greatly limits their ability to function in everyday
life. Using a double blind, placebo-controlled design, 17
patients aged 43 to 70 years with an ejection fraction
were supplemented with 20 grams of creatine daily for 10
Before and after creatine supplementation, the researchers
1) Ejection fraction of the heart (blood present in the
ventricle at the end of diastole and expelled during the
contraction of the heart)
2) 1-legged knee extensor (which tests strength)
3) Exercise performance on the cycle ergometer (which tests
Biopsies were also taken from muscle to determine if there
was an increase in energy-producing compounds (i.e.,
creatine and creatine phosphate). Interestingly, but not
surprisingly, the ejection fraction at rest and during the
exercise phase did not increase.
However, the biopsies revealed a considerable increase in
tissue levels of creatine and creatine phosphate in the
patients getting the supplemental creatine. More
importantly, patients getting the creatine had increases in
strength and peak torque (21%, P
Both peak torque and 1-legged performance increased
linearly with increased skeletal muscle phosphocreatine (P
the researchers concluded: “Supplementation to patients
with chronic heart failure did not increase ejection
fraction but increased skeletal muscle energy-rich
phosphagens and performance as regards both strength and
This new therapeutic approach merits further attention.”10
Another study looked at the effects of creatine
supplementation on endurance and muscle metabolism in
people with congestive heart failure.11 In particular the
researchers looked at levels of ammonia and lactate, two
important indicators of muscle performance under stress.
Lactate and ammonia levels rise as intensity increases
during exercise and higher levels are associated with
High-level athletes have lower levels of lactate and
ammonia during a given exercise than non-athletes, as the
athletes’ metabolism is better at dealing with these
metabolites of exertion, allowing them to perform better.
This study found that patients with congestive heart
failure given 20 grams of creatine per day had greater
strength and endurance (measured as handgrip exercise at
25%, 50% and 75% of maximum voluntary contraction or until
exhaustion) and had lower levels of lactate and ammonia
than the placebo group.
This shows that creatine supplementation in chronic heart
failure augments skeletal muscle endurance and attenuates
the abnormal skeletal muscle metabolic response to exercise.
It is important to note that the whole-body lack of
essential high energy compounds (e.g. ATP, creatine,
creatine phosphate, etc.) in people with chronic congestive
heart failure is not a matter of simple malnutrition, but
appears to be a metabolic derangement in skeletal muscle
and other tissues.
Supplementing with high energy precursors such as creatine
monohydrate appears to be a highly effective, low cost
approach to helping these patients live more functional
lives, and perhaps extend their life spans.
Creatine is quickly becoming one of the most well
researched and promising supplements for a wide range of
diseases. It may have additional uses for pathologies where
a lack of high energy compounds and general muscle weakness
exist, such as fibromyalgia.
People with fibromyalgia have lower levels of creatine
phosphate and ATP levels compared to controls.13 Some
studies also suggest it helps with the strength and
endurance of healthy but aging people as well.
Though additional research is needed, there is a
substantial body of research showing creatine is an
effective and safe supplement for a wide range of
pathologies and may be the next big find in anti-aging
Although the doses used in some studies were quite high,
recent studies suggest lower doses are just as effective
for increasing the overall creatine phosphate pool in the
Two to three grams per day appears adequate for healthy
people to increase their tissue levels of creatine
phosphate. People with the aforementioned pathologies may
benefit from higher intakes, in the 5-to-10 grams per day
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