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 dystrophy (MD). 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
hormone production.
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.
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.
About the Author - William D. Brink
Will Brink is a columnist, contributing consultant, and writer
for various health/fitness, medical, and bodybuilding publications.
His articles relating to nutrition, supplements, weight loss,
exercise and medicine can be found in such publications as Lets
Live, Muscle Media 2000, MuscleMag International, The Life Extension
Magazine, Muscle n Fitness, Inside Karate, Exercise For Men Only,
Body International, Power, Oxygen, Penthouse, Women’s World
and The Townsend Letter For Doctors.
He is the
author of Priming The Anabolic Environment and Weight Loss Nutrients
Revealed. He is the Consulting Sports Nutrition Editor and a monthly
columnist for Physical magazine and an Editor at Large for Power
magazine. Will graduated from Harvard University with a concentration
in the natural sciences, and is a consultant to major supplement,
dairy, and pharmaceutical companies.
He has been
co author of several studies relating to sports nutrition and
health found in peer reviewed academic journals, as well as having
commentary published in JAMA. He runs the highly popular web site
BrinkZone.com which is strategically positioned to fulfill the
needs and interests of people with diverse backgrounds and knowledge.
The BrinkZone site has a following with many sports nutrition
enthusiasts, athletes, fitness professionals, scientists, medical
doctors, nutritionists, and interested lay people. William has
been invited to lecture on the benefits of weight training and
nutrition at conventions and symposiums around the U.S. and Canada,
and has appeared on numerous radio and television programs.
William has
worked with athletes ranging from professional bodybuilders, golfers,
fitness contestants, to police and military personnel.
See Will's
ebooks online here:
Muscle
Building Nutrition
A complete guide bodybuilding supplements and eating to gain lean
muscle
Diet
Supplements Revealed
A review of diet supplements and guide to eating for maximum fat
loss
He can be contacted at: PO Box 812430
Wellesley MA. 02482.
BrinkZone.com
Email: will@brinkzone.com
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1. Walter MC, et al. Creatine monohydrate in muscular dystrophies:
A double blind, placebo-controlled clinical study. Neurology 2000
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2. Tarnopolsky M, et al. Creatine monohydrate increases strength
in patients with neuromuscular disease. Neurology 1999 Mar 10; 52(4):
854-7.
3. Protective effect of the energy precursor creatine against toxicity
of glutamate and beta-amyloid in rat hippocampal neurons. J Neurochem
1968-1978; 74(5).
4. Malcon C, et al. Neuroprotective effects of creatine administration
against NMDA and malonate toxicity. Brain Res 2000; 860(1-2): 195-8.
5. Matthews RT, et al. Creatine and cyclocreatine attenuate MPTP
neurotoxicity. Exp Neurol 1999; 157(1): 142-9.
6. Balestrino M, et al. Role of creatine and phosphocreatine in
neuronal protection from anoxic and ischemic damage. Amino Acids
Abstract 2002; 23(1-3): 221-229.
7. Matthews RT, et al. Neuroprotective effects of creatine and
cyclocreatine in animal models of Huntington's disease. J Neurosci
1998; 18(1): 156-163.
8. Ferrante RJ, et al. Neuroprotective effects of creatine in a
transgenic mouse model of Huntington's disease. J Neurosci 2000;
20(12): 4389-97.
9. Klivenyi P, et al. Neuroprotective effects of creatine in a
transgenic animal model of amyotrophic lateral sclerosis. Nat Med
1999; 5(3): 347-50.
10. Gordon A, et al. Creatine supplementation in chronic heart
failure increases skeletal muscle creatine phosphate and muscle
performance. Cardiovasc Res 1995 Sep; 30(3): 413-8.
11. Andrews R, et al. The effect of dietary creatine supplementation
on skeletal muscle metabolism in congestive heart failure. Eur Heart
J 1998 Apr; 19(4): 617-22.
12. Broqvist M, et al. Nutritional assessment and muscle energy
metabolism in severe chronic congestive heart failure-effects of
long-term dietary supplementation. Eur Heart J 1994 Dec; 15(12):
1641-50.
13. Park JH, et al. Use of P-31 magnetic resonance spectroscopy
to detect metabolic abnormalities in muscles of patients with fibromyalgia.
Arthritis Rheum 1998 Mar; 41(3): 406-13.
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