A bundle of articles on Creatine can be caught on the Web but let me post just the following to get the point:
The “Strength Supplement” that Improves Brain Power
By Dr. Edward R. Rosick
http://www.health-ma...le-creatine.htm
Some in mainstream medicine believe that anti-aging researchers and physicians are a hedonistic lot, interested only in preserving their young and supple physiques at any cost. In my experience, however, nothing could be further from the truth. I find that a vast majority of anti-aging physicians are proponents not only of keeping their patients looking and feeling their best, but also of keeping their minds sharp and their memories intact.
For those interested in maintaining a sharp mind and a supple figure, creatine is a must-take supplement. Many know creatine only as a popular supplement used by athletes, bodybuilders, and other fitness enthusiasts to maintain muscle mass and improve exercise performance. But exciting new scientific evidence shows that creatine not only can help people with degenerative neurological disorders, but also may help just about everyone maintain a healthy, clear-thinking mind.
Keeping Muscles Strong and Healthy
Creatine, a compound comprising the amino acids methionine, glycine, and arginine, was discovered and isolated from meat extract in 1835. Humans produce creatine in the kidney, liver, and pancreas, but store most of it in muscles, including the heart. While creatine has been known since the early 1800s, not until the end of the 20th century did scientists discover that when taken as a supplement, creatine can be of significant help in adding muscle mass.
More than 500 well-researched studies have been conducted showing that creatine supplements can help everyone—men and women, young and old—maintain muscular fitness and ward off some of the most debilitating effects of aging, such as sarcopenia, the age-related loss of muscle mass and strength. A study published in February 2003 examined the effect of 250 supplements on lean muscle mass and strength gains with resistance exercise. Of all the supplements, creatine was one of the few that consistently augmented lean muscle mass and strength in both the young and old.1 Another study published in 2003, which reviewed over 300 studies on the potential ergonomic value of creatine supplementation, concluded: “the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergonomic aid for a variety of exercise tasks in a number ”2
Essential for Maintaining Energy
Creatine increases exercise capacity and muscle mass through its role in regenerating adenosine triphosphate, or ATP. ATP is the body’s primary “energy molecule” and is used in cells as energy. A useful analogy is to think of ATP as the body’s natural fuel in the same way natural gas is burned in a modern power plant to produce electricity. In the body, ATP is broken down, or “burned,” to produce biochemical energy. During this biochemical process, ATP loses one of its phosphate molecules and is changed to adenosine diphosphate, or ADP, and it is here that creatine becomes so vitally important. Creatine, which is stored in the body as creatine phosphate, or phosphocreatine, recharges ADP by giving up, or donating, a phosphate molecule to ADP, which produces more ATP that can then be used to make more energy. Without creatine to recharge ATP, we literally would be “starved” for energy.
The Brain’s Thirst for Energy
The next time you watch a football game, take a close look at one of the larger players on the offensive or defensive lines. Then try to imagine what part of his body consumes the most energy. Is it his tree-like arms? His barrel-sized chest? Or is it his massive legs, which have to carry that 350-pound frame all over the playing field?
The surprising answer is none of the above. The part of the human body that needs the most energy is the small, three-pound mass of gray matter residing in the skull—the brain. While the human brain makes up only 1-3% of a person’s total body weight, its billions of neurons (the brain’s active nerve cells) use 15-20% of the body’s total ATP-derived energy.
Energy derived from ATP is used by the brain for neuronal repair, to produce, package, and secrete neurotransmitters, and to power the bioelectrical discharges that occur when neurons communicate with one another. This bioelectrical process, which is active every second of every day, occurs via the rapid, continuous exchange of sodium and potassium ions across neuronal membranes, a process that depends on biochemical “pumps” inside the membrane to move the sodium and potassium ions back and forth. It has been estimated that as much as 45% of a neuron’s ATP may be used to power these all-important sodium-potassium pumps.
Creatine and Neurodegenerative Disorders
When you realize how important ATP and thus creatine is to brain function, it should come as no surprise that certain genetic disorders characterized by inborn errors in brain creatine metabolism can cause significant neurological defects. The first inborn error of brain creatine metabolism, GAMT (guanidinoacetate methyltransferase) deficiency, was clinically described in 1994.3
GMAT deficiency is an autosomal recessive disorder in which creatine levels in the brain are almost undetectable. This genetic deficiency manifests early in life as developmental delay, mental retardation, speech disabilities, and muscular weakness. Studies have shown that oral creatine supplementation by patients with this disorder can help slow or even reverse some of its most debilitating symptoms. AGAT (arginine: glycine amidinotransferase) deficiency is another autosomal genetic disorder in which minimal or no creatine metabolism in the brain results in mental retardation, language disorders, and poor fine motor skills.3 In a study of two sisters aged four and six years with AGAT deficiency, creatine supplementation caused rapid progress in fine motor skills and an increase in general cognitive development.
Three Deadly Neurological Diseases
Recent studies have shown that creatine can help not only in genetic disorders of creatine metabolism but also in nongenetic disorders of the central nervous system. It is now postulated by many brain researchers that devastating neurological disorders such as Parkinson’s, Huntington’s, and Alzheimer’s diseases share fundamental biochemical processes in their pathogenesis, such as oxidative stress and the impairment of creatine-powered ATP energy metabolism. To support this theory, varieties of animal models and, in some cases, human studies have shown that creatine supplementation can significantly ameliorate various common symptoms of many neurological diseases. It is believed that creatine may accomplish this by acting as a “booster” to the ATP energy system and also as a direct antioxidant.4
Parkinson’s is a chronic neurological disease that was first described in 1817 by Dr. James Parkinson, a London physician. Since that time, some limited medical therapies have been developed to treat this progressive disease, yet scientists still do not know what causes Park-inson’s disease. What is known is that neurons in the area of the brain known as the substania nigra degenerate and die, causing reduced levels of dopamine, a vital brain neurochemical. Common symptoms of Park-inson’s include resting tremors, rigidity, balance problems, and depression.
While scientists continue to search for the cause of Parkinson’s, some medical researchers are postulating that impairment of the ATP energy-generated system and oxidative damage to neurons may play key roles in the pathogenesis of this disease affecting 1.5 million Americans.5 Supplements such as creatine, which can help boost ATP levels and work as antioxidants, are being examined as possibly safe and effective fighters of Parkinson’s disease. Recent animal studies are quite promising and show that creatine supplementation can protect against both the dopamine depletion and neuronal loss seen in Parkinson’s.5,6 While no human studies have been published, it makes sense to think that supplements such as creatine, which can act as a potent brain antioxidant and boost ATP function, may prove to be valuable tools in combating Parkinson’s.
Creatine supplementation also may prove to be a valuable weapon in the fight against Huntington’s disease. This devastating, irreversible neurological and genetic disorder affects a quarter of a million Americans and robs them of the ability to walk, think, talk and reason. At present, no effective cure exists for Huntington’s disease. Yet here again, creatine supplementation may prove to be useful in ameliorating some of the disease’s most debilitating effects. A 1998 study found creatine supplementation offered significant protection against Huntington’s-like brain damage in rats.7 The study’s authors concluded, “oral administration of either creatine or cyclocreatine can buffer cellular ATP concentrations and can attenuate cell death in animal models that mimic the neuropathological and clinical phenotype of Huntington’s disease.” More good news emerged from a study published in July 2003 that examined the effects of 10 grams a day of creatine on patients with Huntington’s disease.8 After one year, patients who took supplemental creatine showed no measurable change in their mental condition, a sign that creatine was able to stop the neurological degeneration associated with Huntington’s disease.
Some researchers believe that creatine may even be useful in combating the debilitating mental effects of Alzheimer’s disease. In cultured rat neurons, creatine has been shown to prevent the toxic effects of b-amyloid, a significant component of Alzheimer’s disease. With this in mind, the authors of a recent study that examined elderly patients who have the ApoE genotype (known to be a genetic risk factor for Alzheimer’s) stated: “… the potentially therapeutic effects of creatine in cognitive impairment and AD [Alzheimer’s disease] might merit further inquiry and should perhaps best not be overlooked.”9
Keeping Mind and Memory Strong
While creatine may prove useful in combating some of our most debilitating neurological diseases, recently published research highlights how creatine can help people without neurological disorders maintain optimal brain function and even improve memory.
Several well-researched studies have conclusively demonstrated that brain creatine levels are tied to optimal memory ability and retention. One study published in 2000 examined working memory ability—defined as the brain’s capacity to “hold” information for future use without the use of external cues—in children using magnetic resonance spectroscopy to measure various brain neurochemicals.10 The researchers found that children with the highest levels of creatine had the most robust working memory, and concluded: “… we speculate that higher resting creatine levels may allow for greater in-task activation [and] facilitate processing.”
Brain creatine levels also have been found to correlate with memory ability in older adults. A study published in February 2003 examined via magnetic resonance spectroscopy changes in the brain in 20 older adults (average age of 70) during memory training tasks.11 The researchers found that brain creatine levels rose during memory training. Another article published recently in Neuroscience Research examined the effects of supplemental creatine on mental fatigue in 24 adult men and women.12 In this double-blind, placebo-controlled trial, subjects who took 8 grams of creatine daily over a five-day period showed significantly less mental fatigue while performing simple mathematical calculations compared to the subjects who did not take creatine. The authors noted that while they did not know the specific mechanism of action, creatine appeared to help increase oxygen utilization in the brain.
Maintaining Optimal Brain Health
A study published in October 2003 sheds additional light on creatine’s ability to increase memory and even intelligence.13 The researchers used vegetarians as their subjects, postulating that creatine supplementation might be more effective in vegans because they do not derive much creatine from their diet (creatine is found mainly in meat). Forty-five subjects (12 men and 33 women) aged 19 to 37 were enrolled in a double-blind, placebo-controlled, cross-over study for a period of six weeks, during which some subjects were supplemented with 5 grams per day of creatine while the others received placebo. Both groups then took a battery of tests examining their memory and analytical skills. This was followed by a six-week “washout” period, during which no creatine or placebo was given, and then another six-week trial during which subjects who received creatine in the first trial were given placebo, and vice versa. Following this, another battery of tests for memory and intelligence was administered.
As in earlier studies, subjects who took creatine scored significantly higher on tests for both memory and analytical skills compared to those who took placebo. The study’s authors concluded: “creatine supplementation had a significant positive effect on both working memory and intelligence, both tasks that require [mental] speed of processing. These findings underline a dynamic and significant role of brain energy capacity [and creatine] in influencing brain performance.”
However begrudgingly and slow, mainstream medicine appears to be coming to the acceptance that the brain and body are one. Many have long held the notion that one has to forsake the brain to develop the body, and vice versa. Creatine, however, has been shown in multiple studies to be a safe, effective supplement that nourishes both the mind and body, helping each to achieve greater levels of functioning.
References
1. Nissen SL, Sharp RL. Effect of dietary sup- plements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol. 2003 Feb;94(2):651-9. Epub 2002 Oct 25.
2. Kreider RB. Effects of creatine supplemen- tation on performance and training adapta- tions. Mol Cell Biochem. 2003 Feb;244(1-2): 89-94.
3. Wyss M, Schulze A. Health implications of creatine: can oral creatine supplementation protect against neurological and atheroscle- rotic disease? Neuroscience. 2002;112(2):243-60.
4. Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun. 2002 Jan;290(1):47-52.
5. Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann N Y Acad Sci. 2003 Jun;991:120-31.
6. Tarnopolsky MA, Beal MF. Potential for cre- atine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol. 2001 May;49(5):561-74.
7. Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci. 1998 Jan 1;18(1):156-63.
8. Tabrizi SJ, Blamire AM, Manners DN, et al. Creatine therapy for Huntington’s disease: Clinical and MRS findings in a 1-year pilot study. Neurology. 2003 Jul 8;61(1):141-2.
9. Laakso MP, Hiltunen Y, Kononen M, et al. Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers. J Neural Transm. 2003 Mar;110(3):267-75.
10. Yeo RA, Hill D, Campbell R, Vigil J, Brooks WM. Developmental instability and working memory ability in children: a mag- netic resonance spectroscopy investigation. Dev Neuropsychol. 2000;17(2):143-59.
11. Valenzuela MJ, Jones M, Wen W, et al. Memory training alters hippocampal neuro- chemistry in healthy elderly. Neuroreport. 2003 Jul 18;14(10):1333-7.
12. Watanabe A, Kato N, Kato T. Effects of cre- atine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res.
2002 Apr;42(4):279-85.
13. Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc R Soc Lond B Biol Sci. 2003 Oct 22;270(1529):2147-50.
Creatine supplementation and neuroprotection
Arch Dis Child Fetal Neonatal Ed. 2000 May;82(3):F224-7.
Anoxic ATP depletion in neonatal mice brainstem is prevented by
creatine supplementation.
Wilken B, Ramirez JM, Probst I, Richter DW, Hanefeld F.
Klinik fur Padiatrie und Neuropadiatrie, Universitat Gottingen, 37075
Gottingen, Germany.
Background
Sufficient ATP concentrations maintain physiological
processes and protect tissue from hypoxic damage. With decreasing
oxygen concentration, ATP synthesis relies increasingly on the presence
of phosphocreatine.
Aim
The effect of exogenously applied creatine on
phosphocreatine and ATP concentrations was studied under control and
anoxic conditions.
Methods
Pregnant mice were fed orally with creatine
monohydrate (2 g/kg body weight/day). Brainstem slices from these mice
pups were compared with those from pups of non-creatine supplemented
pregnant mice. Measurements were performed under normoxic and anoxic
conditions. In addition, brainstem slices from non-creatine treated
mice pups were incubated for 3 hours in control artificial
cerebrospinal fluid (CSF) (n = 10) or in artificial CSF containing 200
microM creatine (n = 10). ATP and phosphocreatine contents were
determined enzymatically in single brainstem slices.
Results
ATP concentrations were in the same range in all preparations. However,
there was a significant increase of phosphocreatine in the brainstems
from pups of creatine fed mice when compared with the brainstems of
pups from non-creatine treated mice or in non-incubated brainstems of
control animals. After 30 minutes anoxia, ATP as well as
phosphocreatine concentrations remained significantly higher in
creatine pretreated slices compared with controls.
Conclusion
The data indicate that exogenous application of creatine is effective in
neuroprotection.
PMID: 10794791 [PubMed - indexed for MEDLINE]
FULL TEXT
http://fn.bmjjournal.../full/82/3/F224
http://www.ncbi.nlm....5&dopt=Abstract
http://www.ncbi.nlm....6&dopt=Abstract
http://www.ncbi.nlm....6&dopt=Abstract
http://www.ncbi.nlm....5&dopt=Abstract
http://www.ncbi.nlm....8&dopt=Abstract
Neuroprotective mechanisms of creatine occur in the absence of
mitochondrial creatine kinase.
Neurobiol Dis. 2004 Apr;15(3):610-7.
Klivenyi P, Calingasan NY, Starkov A, Stavrovskaya IG, Kristal BS, Yang
L, Wieringa B, Beal MF.
Department of Neurology and Neuroscience, New York-Presbyterian
Hospital, Weill Medical College of Cornell University, New York, NY
10021, USA.
There is substantial evidence that creatine administration exerts
neuroprotective effects both in vitro and in vivo. The precise
mechanisms for these neuroprotective effects however are as yet
unclear. We investigated whether creatine administration could exert
neuroprotective effects in mice deficient in ubiquitous mitochondrial
creatine kinase (UbMi-CK). UbMi-CK-deficient mice showed increased
sensitivity to 1-methyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced
dopamine depletion and loss of tyrosine hydroxylase (TH) stained
neurons. Isolated mitochondria from these mice showed no alterations in
calcium retention, oxygen utilization, membrane potential, or swelling
in response to a calcium challenge. Creatine administration
significantly increased brain concentrations of both creatine and PCr
in the UbMi-CK knockout mice. Creatine administration to the
UbMi-CK-deficient mice exerted significant neuroprotective effects
against MPTP toxicity that were comparable in magnitude to those seen
in wild-type mice. These results suggest that the neuroprotective
effects of creatine... are not mediated by an effect on UbMi-CK to inhibit
the mitochondrial permeability transition, and ...are more likely to be
mediated by maintenance of appropriate ATP/ADP and PCr/Cr levels.
PCr/Cr: PhosphoCreatine/Creatine.
PMID: 15056469 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm....7&dopt=Abstract
http://www.ncbi.nlm....5&dopt=Abstract
http://www.ncbi.nlm....0&dopt=Abstract
http://www.ncbi.nlm....3&dopt=Abstract
*** Enlightening MIT article to follow ***
Role of mitochondria in synaptic function; benefit of creatine
http://www.sciencedaily.com/releases/2004/12/041219165906.htm
Source: Massachusetts Institute Of Technology.
Date: 2004-12-22
Cell's Tiny Power Source Critical For Synapse Function
Mitochondria, the tiny power plants inside all plant and animal cells,
play a critical role in the health and well-being of synapses,
neuroscientists at MIT's Picower Center for Learning and Memory report
in the Dec. 17 issue of the journal Cell.
Each living cell is a miniature breathing, eating, waste-expelling
organism. Hundreds or thousands of little footprint-shaped mitochondria
generate energy for cell functions from sugar and oxygen. They are
particularly important in brain cells, where they perform additional
jobs related to signaling and programmed cell death, but little is known
about how their distribution and movement relates to the synaptic
activity crucial for learning and memory, said Morgan Sheng, the Menicon
Professor of Neuroscience at MIT and an investigator with the Howard
Hughes Medical Institute.
Compared with most cells, neurons are more elongated and complex.
Neurons are divided into different sections: the long, thin axon and the
branching, tree-like dendrites that receive signals from other neurons
via the suction cup-shaped synapses. Synapses, tiny gaps separating
neurons, consist of a presynaptic ending at the very tip of an axon that
contains neurotransmitters, a postsynaptic ending that contains
neurotransmitter receptor sites, and the space between the two endings.
Both presynaptic and postsynaptic endings require the energy generated
by mitochondria.
Critical functions, such as synapses' transmission of information and
ability to change rapidly in response to stimuli, are managed by distant
cellular compartments that can become isolated from their nearest
mitochondria. Sheng and postdoctoral fellow Zheng Li explored whether
having the power source far away, like a too-distant room heater, would
affect synaptic function.
The researchers looked at mitochrondria in living hippocampal neurons.
The hippocampus, a seahorse-shaped brain region in the temporal lobe, is
known to play a critical role in memory.
When synapses were stimulated, the researchers found, mitochrondria in
the dendrites changed from being long and thin to more aggregated,
collecting in globules near the enlarged dendritic spines, as if the
mitochondria were reporting for duty at the active part of the neuron.
"Our studies reveal that mitochrondria dynamically redistribute into
dendritic protrusions in response to synaptic excitation S The dendritic
distribution of mitochondria appears to be an essential and limiting
factor for synaptic density and plasticity," the authors wrote. If
mitochondria don't migrate into the distant reaches of the
dendrites--where most synapses are present--the synapses become less
numerous and lose some of their ability to respond to external input.
Enhancing mitochondria with the nutrient creatine also promoted synaptic
density, the study showed.
These findings on mitochondrial function correlate with the fact that
neurodegenerative diseases such as Alzheimer's and Parkinson's are
associated with abnormal mitochondria. The synapse loss characteristic
of these diseases may stem in part from mitochondrial dysfunction, the
authors write.
In addition to Li and Sheng, authors include Picower Center researchers
Yasunori Hayashi, assistant professor of brain and cognitive sciences,
and postdoctoral associate Ken-Ichi Okamoto.
This work is funded by the Howard Hughes Medical Institute.
This story has been adapted from a news release issued by Massachusetts
Institute Of Technology.
Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation
http://www.ncbi.nlm....0&dopt=Abstract
Watanabe A, Kato N, Kato T.
Department of Neuropsychiatry, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan.
While the role of creatine in preventing muscle (peripheral) fatigue for high performance athletes is well understood, its biochemical role in prevention of mental (central) fatigue is not. Creatine is abundant in muscles and the brain and after phosphorylation used as an energy source for adenosine triphosphate synthesis. Using double-blind placebo-controlled paradigm, we demonstrated that dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when subjects repeatedly perform a simple mathematical calculation. After taking the creatine supplement, task-evoked increase of cerebral oxygenated hemoglobin in the brains of subjects measured by near infrared spectroscopy was significantly reduced, which is compatible with increased oxygen utilization in the brain.
Publication Types:
Clinical Trial
PMID: 11985880 [PubMed - indexed for MEDLINE]
Creatine is naturally rich in meat (beef) and fish (herring, salmon, tuna…).
Large amount of these foods must be supplied to get the benefits achieved with Creatine supplementation.
Carnitine, Cysteine, Taurine, Idebenone, COQ10, Niacin/Niacinamide, Alpha Lipoic Acid would synergize nicely with Creatine. EDTA (Ethylene Diamine Tetraacetic Acid) may also stabilize the mitochondrial membrane (that’s another story).
I wouldn't though ingest 8g/day, I think 0.5 - 2 g daily ought to be enough for healthy adults on long-term supplementation.
