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 has over 15 years experience as a respected author, columnist and
consultant, to the supplement, fitness, bodybuilding, and weight loss industry
and has been extensively published.Will graduated from Harvard University with
a concentration in the natural sciences, and is a consultant to major supplement,
dairy, and pharmaceutical companies.
His often ground breaking articles can be found in publications such 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.
Will was a former high level trainer with a rep for getting Olympic athletes, bodybuilders and fitness stars into shape and has gained a reputation for being a no "BS" industry insider who's not afraid to reveal the lies and hype found in the fat loss , muscle building & supplement industry.
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. 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 and now runs seminars for tactical law enforcement (SWAT).
He is the author, of Bodybuilding Revealed which teaches you how to gain solid muscle mass drug free and Fat Loss Revealed. which reveals exactly how to get lean , ripped and healthy completely naturally. Both e-books come with access to his private forums and numerous tools to aid you in either endevour.
Find out more at Bodybuilding Revealed or Fat Loss Revealed.
>Article References:
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muscular dystrophies: A double blind, placebo-controlled clinical study.
Neurology 2000 May 9; 54(9): 1848-50.
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
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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
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