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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
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
(10%, 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

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.

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.

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