Some Creatine Info

MrFitness880

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Hey everyone. Both these articles were originally posted by Liftsiron at world class bodybuilding .com:

creatine: More than a sports nutrition supplement

creatine: More than a sports nutrition supplement
By Will Brink, author of:



"Creatine: More than a sports nutrition supplement"


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.


Click Here to Order Creatine Monohydrate Powder and Gain Muscle Now


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."
 

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(continued)

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.


Creatine: A practical guide Teaches how to make the most of creatine with the least adverse consequences.


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.





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Article References:
1. Walter MC, et al. Creatine monohydrate in 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 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.
__________________
 

MrFitness880

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this is something i posted to prompt the second article in case it needs qualification:

This is a really good article.

There have been a few studies that have linked to some degree creatine supplementation and irregular blood glucose levels similar to that by diabetes.

to be fair these were done on rats and i've only read the briefs (there is another term for this that escapes me at the moment) - so its hardly conclusive. do you have any info on that? Im still looking but havent found anything solid.

The thought is that excess creatine - more than the body naturally produces - stresses the islet cells of panceas decreasing insulin sensativity. i dont really buy it but i'm curious.
 

MrFitness880

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also posted by Liftsiron at wcbb:

"I think that if you readthrough this article you may find some of what your looking for."

Using Creatine For More Than Muscles
by Anthony L. Almada


A creatine researcher highlights promising medical applications

Headlines in late 1997 blamed creatine for the deaths of three college wrestlers. Yet, after the dust settled, no evidence linked the supplement to the deaths. Lost in the fray were data supporting creatine's safety and efficacy in improving human performance and body composition. Also overlooked were studies examining the amino acid for various metabolic disorders and diseases.

Creatine is poised to evolve into much more than muscle magic. A variety of published and unpublished research shows creatine may decrease tumor growth, increase body mass, decrease blood glucose, reduce triglycerides and cholesterol, extend exercise endurance in congestive heart failure patients, and even alter metabolism in people with neurodegenerative diseases such as Alzheimer's and Lou Gehrig's diseases.

The history of creatine, a substance that provides energy to muscles, has been documented during nearly 80 years of clinical research. It began in 1926 when two researchers tested it on themselves and found that it changed body weight and urinary markers of protein metabolism.1

In 1981, an article in the New England Journal Of Medicine described the effect 1.5 g of creative daily had on patients with gyrate atrophy of the choroid and retina—a rare, genetically transmitted visual disorder that results in blindness. Patients with gyrate atrophy also have reduced creatine metabolism.2 After a year of daily supplementation, researchers noted no significant progression of the disease and also found an average 10 percent increase in body weight, increased muscle-fiber diameter, and increased strength and physical performance in a few of the subjects. Creatine the muscle supplement was born.

Lead investigator Ilkka Sipila, M.D., continues to follow these patients who take 1.5-3 g/day creatine and has found no adverse effects after 18 years. In fact, muscle atrophy and weakness remain abated with constant creatine use.3

Then, in 1992, a new application for cellular bioenergetics emerged. In short, cell bioenergetics are the events that enable cells to gain, retain and use energy. Because skeletal muscle is the body's predominant creatine reservoir, researcher began investigating if oral doses of creatine could increase muscular levels of creatine. Roger Harris, Ph.D., and colleagues at the Karolinska Institute in Stockholm, Sweden, found muscle levels of creatine increased following supplementation.4 This discovery spawned more than 100 creatine studies in the following six years for a variety of clinical applications.

Tumor Reduction and Weight Gain
The pivotal enzyme in creatine metabolism is creatine kinase, which directs the energy transfer between adenosine triphosphate (ATP) and phosphocreatine (PCr), an energy-liberating compound found in muscles. PCr is produced when creatine is linked with a certain form of phosphorus, a mineral found in food. Creatine kinase works like the fulcrum of a seesaw, fostering the formation of ATP or PCr, depending on metabolic demands. When energy demands are high, ATP is formed at the expense of PCr; when energy demands decline, PCr is reformed at the expense of ATP. This, at a cellular level, is how muscles store and harness energy. Creatine supplementation does not increase ATP but does increase PCr and creatine stores, a bioenergetically favorable alteration.

Some studies show tumors can be identified by their much higher creatine kinase activity.5 Although this suggests creatine kinase directly influences tumor formation and progression, no cause and effect relationship has been described. Indeed, creatine and its chemical cousin, cyclocreatine, both of which can increase creatine kinase activity, decrease the growth rate of several animal and human tumors implanted in animals.6,7 Recent research shows tumor concentrations of creatine and cyclocreatine correlate with tumor inhibition in immune-deficient mice implanted with human colon-cancer cells.7 These data suggest that increasing creatine levels within tumors inhibits them. However, no human studies have been conducted.

Frequent companions of cancerous tumors and immunodeficiency diseases are muscle wasting and general weight loss. HIV/AIDS is probably the most common disease characterized by wasting. The severe and often unremitting weight reductions are not unlike those noted in starvation. One popular strategy to retard this is to increase body mass before the patient advances to a wasting state. With this in mind, I designed a study with Allan Hollister, M.D., Ph.D., of the University of Colorado Health Sciences Center in Denver to assess the impact of creatine supplementation on body composition in the pre-wasting, HIV-infected state. We conducted a double-blind, exploratory study on 30 HIV-positive males without wasting symptoms. For eight-weeks, participants were given either 10 or 15 g creatine/day. The men in both groups significantly increased their lean-body mass and modestly increased fat mass; the increase in lean mass lasted at least four weeks after supplementation ended. As a side benefit, both groups also increased their strength.8,9
 

MrFitness880

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(continued)

Carbohydrate and Lipid Modulator
If we examine the chemistry of the creatine molecule (see above) we find one portion harbors a nitrogen-rich component called a guanidine group. Metformin, a recently introduced prescription drug for diabetes, contains two guanidine groups and thus is called a biguanide. One of its principal actions is improving tissue sensitivity to insulin, thereby facilitating the disposal of glucose into tissues.

From a chemist's perspective, it is not improbable to suggest creatine would modify glucose disposal since it also contains guanidine. Indeed, preliminary data from animal studies published in 1928 indicate high doses of creatine cause low blood sugar.10 Recent studies performed in fasting insulin-dependent (Type I) diabetics found a single 3-g dose of creatine produces significant reductions in blood glucose without changing blood insulin.11,12 Recent studies presented at the 1999 American Diabetes Association annual meeting describe a similar effect in noninsulin dependent (Type II) diabetics. Researchers from the University of Zagreb in Croatia found one 3-g dose of creatine reduced blood glucose in such cases. They also found the effects of creatine equaled those produced by a drug that increases insulin output, but the effects were greatest when the drug and creatine were taken together.13

Occasionally in clinical research you look for one thing but find another. In a study conducted with Conrad Earnest, Ph.D., and colleagues at Texas Women's University, in Denton, and the University of Texas Southwestern Medical School, Dallas, we researched the effects of creatine on body composition and strength (see sidebar below). In the process we saw a considerable reduction in blood cholesterol concentrations in a few subjects.14 Eight subjects were asked to maintain their usual diet and training regimen throughout the 28-day study. Although analysis of three-day diet diaries revealed the creatine group ate fewer total calories and had lower carbohydrate and fat intakes, these differences were not statistically significant.

In light of the unexpected results from this study, we undertook a systematic double-blind, placebo-controlled investigation of 34 mildly hyperlipidemic (blood fasting total cholesterol levels between 220 and 250 mg/dL) patients at the Cooper Clinic in Dallas. We found 10_20 g creatine/day for eight weeks reduced triglycerides by 22 to 23 percent and total cholesterol by 5 to 6 percent in both men and women aged 32 to 70.15 There was no effect on high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol. Surprisingly, we also found these effects persisted at least four weeks after discontinuing creatine supplementation. The men in the study tended to have greater blood lipid-lowering effects and reductions in fasting blood glucose levels than the women. Unfortunately, we did not measure fasting insulin concentrations, which would have provided more data to evaluate whether creatine decreases insulin resistance or improves insulin sensitivity.

In a recent study conducted in collaboration with Richard Kreider, Ph.D., and colleagues at the University of Memphis, Tenn., we duplicated the hypolipidemic effects in a group of university football players during off-season training.16 However, another study by Jeff Volek, Ph.D., and colleagues at Penn State University, University Park, did not corroborate the findings after three months of creatine supplementation in young male weight lifters (see sidebar).17

Because elevated triglycerides are a risk factor for cardiovascular disease, especially coronary heart disease, creatine's triglyceride-lowering effect is significant.18,19 The Stockholm Ischemic Heart Disease Prevention Study conducted on 555 people in the 1980s showed that patients whose triglyceride levels dropped 30 percent halved their risk of dying from a secondary coronary heart disease event. This was related to reductions of triglycerides, not total cholesterol.20 No pharmaceuticals have hypolipidemic effects limited to the triglyceride fraction. Certainly a larger trial of creatine's triglyceride-lowering effects must be completed to better understand this important potential application.

Flexing the Heart Muscle
Congestive heart failure (CHF) patients have greatly compromised exercise tolerance. It seems logical that defects in cardiac metabolism are the cause, but this may not be the case. Since the heart is a collection of smooth and skeletal muscles, it is likely that impaired use of PCr in skeletal muscle also contributes to reduced endurance.21 In support of this theory, creatine supplementation has been shown to extend exercise endurance in CHF patients22—probably a result of creatine's ability to prolong cellular energy production in skeletal muscle under periods of metabolic demand, rather than a direct effect on cardiac function. In addition, studies show that muscle creatine and PCr concentrations increase following supplementation in CHF patients, suggesting improved skeletal muscle performance.

Creatine and Clinical Neurology
Most creatine is stored in skeletal muscle cells, but the brain and nerves also store it. Investigations by Rima Kaddurah-Daouk, Ph.D., of Avicena Group, Cambridge, Mass., and Flint Beal, Ph.D., of Harvard Medical School, Cambridge, and Massachusetts General Hospital, Boston, have uncovered some novel applications for creatine in several neurodegenerative diseases. Recent studies in an animal model of Lou Gehrig's disease show creatine is equal or superior to riluzole, the current drug of choice, in extending survival time.23

A common element in Alzheimer's, Huntington's, Lou Gehrig's and Parkinson's diseases may be impaired energy production in the brain that ultimately leads to increased cell damage.24 For example, the genetic mutation present in Huntington's disease may impair nerve cell energy production. To test this theory, rats with a chemically induced condition mimicking the lesions found in Huntington's disease were given an oral dose of creatine and cyclocreatine totaling 0.25 to 3 percent of their diet, by weight, for two to three weeks. Following supplementation they showed significant neuroprotection (decreased lesion volume and preservation of PCr and ATP) and reduced oxidative stress.25 Kaddurah-Daouk and Beal have begun intervention trials with Lou Gehrig's disease patients and other studies with Parkinson's and Alzheimer's patients.

Duchenne's muscular dystrophy (DMD), a gender-specific genetic neuromuscular disease affecting only young boys, may be characterized by elevated intracellular calcium concentrations. A recent report from Swiss scientists suggests creatine supplementation may enable affected muscle cells to regulate calcium concentration within the cell, increase phosphocreatine concentrations, and increase the survivability of DMD mouse muscle cells.26 A preliminary investigation to assess creatine's effect in DMD boys is being planned. Creatine supplementation for children appears safe based on studies of infants with an enzymatic defect in creatine synthesis who took 400 to 500 mg/kg/day—almost double the adult loading dose—for more than two years.27,28

Creatine's potential usefulness has been building through nearly eight decades of research. After entering the laboratory as a "steroid substitute" with questionable efficacy and safety, creatine is now moving into a position of prominence in clinical medicine. Given the role of creatine and phosphocreatine in cellular metabolism, it is easy to imagine other metabolic avenues that may be influenced by creatine. The next century will undoubtedly reveal more about creatine's potential in both health maintenance and disease treatment.

Sidebars:
Maxing Muscle Performance
The Bioavailability Issue

Anthony L. Almada, M.Sc., a nutritional/exercise biochemist, co-founded Experimental and Applied Sciences Inc. (EAS) in Golden, Colo. He now leads IMAGINutrition and MetaResponse Sciences in Aptos, Calif.
 

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(continued)

References

1. Chanutin A. The fate of creatine when administered to man. J Biol Chem 1926;67:29-41.

2. Sipila I, et al. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. N Engl J Med 1981;304:867-70.

3. Sipila I. Personal communication. 1998, fall.

4. Harris R, et al. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992;82:367-74.

5. Shatton JB, et al. Creatine kinase activity and isozyme composition in normal tissues and neoplasms of rats and mice. Cancer Res 1979;39:492-501.

6. Miller EE, et al. Inhibition of rate of tumor growth by creatine and cyclocreatine. Proc Nat Acad Sci USA 1993;90:3304-8.

7. Kristensen CA, et al. Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies. Br J Cancer 1998;79:278-85.

8. Daniel V, et al. Tolerability and effects of a biochemical/nutritional supplement in HIV positive males. XI International Conference on AIDS, Vancouver, BC, 1996 July 7-12.

9. Hollister AS, Almada AL. Effects of a creatine-containing supplement on body composition, strength, and immune parameters in HIV positive, non-wasting males. Manuscript in preparation.

10. Hill RM. The effect of the administration of creatine on the blood sugar. J Biol Chem 1928;78:iv.

11. Rocic B, et al. Effect of creatine on glycation of albumin in vitro. Horm Metab Res 1995;27:511-2.

12. Beisswenger PJ, et al. Metformin reduces systemic methylglyoxal levels in type II diabetes. Diabetes 1999;48:198-202.

13. Rocic B, et al. The effect of creatine on glycemic control in NIDDM patients on sulfonylurea therapy. Diabetes 1999;48(Suppl. 1):A359.

14. Earnest CP, et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995;153:207-9.

15. Earnest CP, et al. High-performance capillary electrophoresis pure creatine monohydrate reduces blood lipids in men and women. Clin Sci 1996;91:113-8.

16. Kreider RB, et al. Effects of creatine supplementation on body composition, strength and sprint performance. Med Sci Sports Ex 1998;30:73-82.

17. Volek JS, et al. Effects of long term creatine supplementation in strength training athletes. Presented at the National Strength and Conditioning Association annual meeting, 1998 June 24-27, Nashville, Tenn. Med Sci Sports Ex 1999; in press.

18. Criqui MH, et al. Plasma triglyceride level and mortality from coronary heart disease. N Engl J Med 1993;328:1220-5.

19. Hokanson JE, Austin MA. Plasma triglyceride is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996;3:213-9.

20. Carlson LA, Rosenhamer G. Reduction of mortality in the Stockholm Ischemic Heart Disease Prevention Study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand 1988;223:405-18.

21. Okita K, et al. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure. Circulation 1998;98:1886-91.

22. Gordon A, et al. Creatine supplementation in heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995;30:413-8.

23. Klivenyi P, et al. Neuroprotective effects of creatine in a transgenic model of amyotrophic lateral sclerosis. Nature Med 1999;5:347-50.

24. Beal MF. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 1992;31:119-30.

25. Matthews RT, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J Neurosci 1998;18:156-63.

26. Pulido SM, et al. Creatine supplementation improves intracellular Ca+2 handling and survival in mdx skeletal muscle cells. FEBS Lett 1998;439:357-62.

27. Stockler S, et al. Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 1996;348:789-90.

28. Schulze A, et al. Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: Diagnostic tools for a new inborn error of metabolism. J Pediatr 1997;131:626-31.
 

MrFitness880

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LOL - now there is no way you read all that that fast !

its good info, trust me its worth taking the time to read it, or copy it to word and print it out for later.
 

TyTe`EyEs

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LOL, I read the first page though. ;)

I'll read the rest later.
 

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oh. my. god.

We need to find all the good suppliments posts and attatch it to this, cause this is a stunning amount of info.

thanks fitness :eek:
 

Kidquick

Don Juan
Joined
Mar 18, 2004
Messages
101
Reaction score
3
Age
47
I was on Creatine for several months a few years ago, and I became significantly stronger and bigger - added about 30lbs to my bench press if I recall. I'm thinkin about goin back on it!
 
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