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 powdered creatine.
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 disease
states. 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
hydration.
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 debated.
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
five days. 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 stressors."
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 energy
production. 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 the brain. 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 <40
were supplemented with 20 grams of creatine daily for 10
days. Before and after creatine supplementation, the researchers
looked at:
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
endurance)
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 < 0.05) and endurance
(10%, P < 0.05). Both peak torque and 1-legged performance
increased linearly with increased skeletal muscle phosphocreatine
(P < 0.05). After just one week of creatine supplementation,
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 endurance. 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 fatigue. 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.12
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 Conclusion
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 nutrients. 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 body. 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 range.
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