Here are a bunch a different articles I found on creatine. Please sticky this (unless something like this already has). I don't know if I need references or not, but I don't have them for some.
Article 1)
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:
Ejection fraction of the heart (blood present in the ventricle at the end of diastole and expelled during the contraction of the heart)
1-legged knee extensor (which tests strength)
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 attent on."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.
Creatine Article 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 pathologie may benefit from higher intakes, in the 5-to-10 grams per day range.
Article 2)

Title: Effects of Long-term Creatine Supplementation on Liver and Kidney Functions in American College Football Players.
Researchers: Mayhew DL, Mayhew JL, Ware JS
Institution: Exercise Science Program at Truman State University, Kirksville, MO 63501 and the Athletic Department at Truman State University, Kirksville, MO.
Summary: The purpose of this study was to determine the effect of long-term Cr supplementation on blood parameters reflecting liver and kidney function.
Methods: Twenty-three members of an NCAA Division II American football team (ages = 19-24 years) with at least 2 years of strength training experience were divided into a Cr monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously ingested creatine, and a control group (n = 13) in which they took no supplements. Individuals in the CrM group averaged regular daily consumption of 5 to 20g for 0.25 to 5.6 years. Venous blood analysis for serum albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine produced no significant differences between groups.
Results: Creatinine clearance was estimated from serum creatinine and was not significantly different between groups. Within the CrM group, correlations between all blood parameters and either daily dosage or duration of supplementation were nonsignificant.
Conclusion: Oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements.
Discussion: Questions about creatine's safety are probably the most frequently brought up by people who don't like (and usually don't understand) supplements. This study by Mayhew and colleagues is a welcome addition to the already growing body of creatine safety research. (1,2,3,4,5,6,7)
Most questions revolve around the effects of creatine supplementation on the liver and kidney. These are the two organs are involved in "processing" creatine once it is ingested. The Liver breaks it down and the kidneys excrete it. From this study, and others before it, we see that long term supplementation with creatine in doses usually taken by bodybuilders (5-20 grams) for extended periods of time do not lead to dysfunction of either organ, nor does it cause abnormalities in the indicators of liver and kidney function.
Considering that fact that creatine supplementation has been shown to enhance anaerobic exercise performance by increasing power output (8), muscular strength and work (9,10,11), and muscle fiber size (12), and to top it off, completely safe even with long term supplementation, its no wonder this is one of my first tier recommendation for effective and safe supplements for putting on muscle size. 
Article 3)
10. Is creatine safe for women, children, the pregnant or the elderly?
Following the example set by traditional sports medicine/physiology, the creatine field has principally concentrated on male subjects between the ages of 18 and 35 years. Scientific studies conducted on this age group have typically demonstrated enhancements in physical performance during repeated bouts of maximal effort, particularly during later repetitions when the accumulation of lactic acid becomes appreciable and contributes significantly to the onset of muscle fatigue. Since one of the major ergogenic contributions of creatine is to lessen the buildup of lactic acid, exercise capacity increases as a result of creatine supplementation. Other contributions of creatine to the total ergogenic package have been discussed previously and have to do with increases in anaerobic energy reserves (ATP and Phosphocreatine; ( see Question #2)), muscle cell proliferation and increases in the production of contractile and metabolic (energy-producing) proteins (see Question #8).
Significantly less is known about the effects of creatine in children, the elderly and women. Although there is no a priori reason to think that creatine’s basic mechanism of action should differ with age or gender, subtle differences may exist and special considerations may apply.
Children: Whether creatine is safe for children is my second most frequently asked question concerning creatine supplementation. Expectedly, the nature of creatine's side effects is my most frequent inquiry. Most experts (at least, those that write on the topic) are of the opinion that it is best to postpone creatine supplementation until after puberty. This is particularly true since the long-term consequences of creatine supplementation are still largely unknown. In other words, if adverse consequences to creatine supplementation do exist, then the younger an athlete starts, the more likely these side effects are to manifest within their lifetime.
A more pertinent question might be, however: “Should children push themselves beyond the normal limits of play?” Remember, creatine supplementation primarily enhances an athlete's ability to generate near maximal force during repetitive bouts of intense exercise. Given that some experts have warned that excessive mechanical stress might have deleterious consequences on a skeletal frame that is rapidly growing, I would advise against creatine supplementation before reaching puberty. This is just my personal opinion, the opinion of other experts may differ.
Adolescents: Creatine studies conducted on adolescents have given both positive and null results creating a bit of confusion in the field. The simple truth is, however, that too few studies exist to objectively state just how great an effective creatine has in the adolescent population. "Nonresponders" are observed even in the most heavily studied age group (18-35 years of age) and, in this respect, the statistical uncertainty may merely reflect the few studies conducted on adolescents (also see Question #6).
Elderly: Our muscular phosphocreatine levels decline as we age beyond our fifth decade. Such a decline in muscle creatine content may partially explain the decrease in strength and predisposition to fatigue that is observed in the elderly. Creatine supplementation might therefore prove especially worthwhile in the individuals over 50. In support of this notion several recent studies have demonstrated accentuated performance enhancement in healthy individuals in their 50s, 60s and early 70s. That is, creatine supplementation produces relatively greater gains in middle-aged subjects than in younger subjects.
By stark contrast, an effect of creatine supplementation (over physical performance) in individuals in their late 70s and 80s has been somewhat harder to resolve. Age-related decreases in activity-level, anabolic hormones, or type II (fast) muscle mass may underlie the reduced responsiveness of the elderly to creatine supplementation. Recall that type II muscle is the class of muscle fiber that is most responsive to the effects of creatine supplementation and principally mediate explosive bursts of power (also see Question #5). This is not to say, however, that creatine supplementation is a pointless endeavor in later life. Quite the contrary. Many aspects of creatine supplementation may prove particularly beneficial for older athletes. For instance, creatine supplementation may reduce the chances of developing coronary heart disease as well as several neurological disorders that plague us in later life.
The elderly, however, are not without recourse in combating this age-related decline in creatine responsiveness over physical performance. Adopting a more healthful lifestyle, including regular exercise and eating a balanced diet (see next paragraph), can help maintain youthful anabolic hormone levels for longer in life and, hence, preserve one's sensitivity to creatine as well as improve one's overall quality of life. Maintaining an active lifestyle also helps prevent against the loss of existing muscle tissue, which should also translate into greater responses to creatine supplementation. Therefore, exercise and good nutrition should prolong your sensitivity to creatine for longer in life, which should, in turn, slow the normal aging process.
Methylation status is an important contributing factor to the natural decline in strength and mental capacity associated with advanced age. It is now widely accepted that many of the devastating loses in mental and physical capacity that were once thought to be unavoidably linked to the normal aging process are, in fact, now known to be the result of an aged-related decline in methylation capacity. Creatine: A practical guide provides an easy to implement vitamin strategy that together with creatine supplementation will greatly promote your body's methylation status, thereby greatly improving your overall health and increasing your gains in athletic performance. In fact, in a recent study that followed the health indices of 80,000 women for 14 years found that the incidence of heart attack was lowest in those utilizing a similar vitamin regimen (see Coronary Heart Disease below).
If you should opt to supplement with creatine, make sure to use only the highest grade creatine products, an important measure since many of the less expensive brands of creatine contain significant quantities of potentially harmful contaminants. Click here for a free version of the Creatine Products Review explaining the formulations (and myths) behind some of the more popular creatine products currently on the market (pdf format).
Finally, Creatine: A practical guide details other potential benefits of creatine supplementation for the elderly population, including a possible role for creatine in combating osteoporosis.
CORONARY HEART DISEASE (CHD)
Cholesterol: Creatine may provide unexpected benefits for middle-ages to mature athletes. Coronary Heart Disease (CHD) is the leading cause of death in the United States for both men and women. The incidence of CHD increases with age, but can be offset by adopting an active lifestyle and watching your diet. Interestingly, recent evidence now suggests that creatine may also improve serum cholesterol profiles by increasing the ratio of good cholesterol (high-density lipoproteins or HDL) to bad cholesterol (low density lipoproteins or LDL) in the blood (1). Interestingly, this beneficial effect of creatine on blood lipid profiles does not always require a concomitant exercise regimen, which is surprising since exercise also exerts a strong protective over blood lipid profiles and thus was initially given credit for this healthful effect. It is thus that regular exercise in conjunction with moderate creatine use may prove an effective way to combat coronary heart disease from atherosclerosis in later life.
Interestingly, this positive effect of creatine supplementation on blood lipid profiles appears to related to the body's methylation status. Methylation is one of life's most important and ubiquitous forms of biochemical regulation. The scope of this biochemical process is (in all honesty) all encompassing. Methylation is applied at the levels of our genes as well as is responsible for functionalizing many known growth factors, hormones, neurotransmitters, metabolic mediators (including creatine,
adrenaline and carnitine) and structural components of the cell (phospholipids). Indeed, life itself would not be possible without methylation, much less muscle growth. Most importantly, creatine supplementation has been shown in recent scientific studies to improve the body's methylation status and hence mitigate some of the harmful consequences of inadequate methylation capacity.
Homocysteine, Methylation & Coronary Heart Disease
Homocysteine: Imbalances in cellular methylation kinetics increase the levels of an amino acid known as homocysteine in the blood stream, which has very unhealthy repercussions. Homocysteine is a byproduct of methionine consumption during cellular methylation that needs to be removed from the blood stream soon after being produced.
The first clinical condition involving elevated homocysteine levels (homocysteinemia) was described nearly half a century ago by Carson and Neill (2). Patients presenting with this metabolic disorder displayed severe developmental abnormalities including mental retardation, skeletal disorders and invasive vascular disease at an early day. Noteworthy, the vascular manifestation of this disease includes widespread arterial and venous thrombosis, usually resulting in the death of afflicted individuals while still within their first decade of life. It is now understood that homocysteine, among its other harmful effects, is a principal cause of vascular disease among the general population (3, 4). Only a 5 micoMolar increase in plasma homocysteine level results in a 60% and 80% increased risk of developing coronary heart disease in males and females, respectively. Be absolutely clear on this point, your homocysteine levels need to be kept in check at all cost or your health is at risk and the best way to do this is to optimize your methylation status (see next for details).
Creatine Combats Coronary Heart Disease
Now the good news... Recent evidence now indicates that creatine supplementation decreases blood homocysteine levels, an effect downstream of its positive effect of cellular methylation status (5, 6, 7). In this respect, creatine supplementation should protect against the development of heart and vascular disease. It is hence becoming increasingly clear that creatine use is heart-smart.
Click here for the benefits of combining creatine with essential B-vitamins (B12, B6 & Folic Acid) over nervous system functioning.
This potential benefit of creatine supplementation has not gone unnoticed by some members of the sports medicine community. One organization, The European Health and Fitness Group, is currently formulating supplements with the goal of extracting creatine's the full range of healthful benefits by optimizing an athlete's methylation status. Learn more about this innovative and safe approach to supplementation at the following link:
http://www.ehf-group.com
Selected Scientific References:
1. Earnest, C. et al. (1998) High performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clinical Science, Volume 91 (1), pages 113-118.
2. Carson N. A. and Neill D. W. (1962) Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Archives of Disease in Childhood, Volume 37, pages 505-513.
3. Nehler, M. R. et al. (1997) Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovascular Surgery, Volume 5 (6), pages 559-567.
4. Malinow, M. R. et al. (1999) Homocyst(e)ine, diet, and cardiovascular diseases: A statement for healthcare professionals from the nutrition committee, American Heart Association. Circulation, Volume 99, pages 178-182.
5. McCarty, M. F. (2001) Supplemental creatine may decrease serum homocysteine and abolish the homocysteine 'gender gap' by suppressing endogenous creatine synthesis. Medical Hypotheses, Volume 56 (1), pages 5-7.
6. Stead, L. M. et al. (2001) Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. American Journal of Physiology and Endocrinological Metabolism, Volume 281, pages E1095-E1100.
7. Taes, Y. E. C. et al. (2003) Creatine supplementation decreases homocysteine in an animal model of uremia. Kidney International, Volume 64, pages 1331–1337.
Click here for a summary of the devastating effects of homocysteine on central nervous system functioning.
Women: Several recent studies have examined the effects of creatine supplementation in women of diverse fitness levels. And, although creatine clearly enhanced exercise performance in women, the documented effects were less pronounced than those observed in males countyerparts of the study. Apparent differences were observed at the level of muscle protein turnover. Specifically, creatine supplementation appears to have a greater anti-catabolic action in males. Differences in the anabolic-androgenic sex hormone, namely the predominance of testosterone in males, may underlie this distinct response to creatine in females.
Pregnancy: It is not known whether the levels of creatine in breast milk increases in response to creatine supplementation. Since it is simply not known how serum creatine levels might influence neonateal development, women nursing infants are advised to abstain from using creatine. This recommendation is intended to avoid inadvertently exposing the infant to abnormally elevated levels of creatine that might alter child development.
A red flag, however, was raised by studies examining rat fetal development. A region of the placenta known as the decidua was found in rodents to express very high levels of an enzyme known as AGAT (L-Arginine:GlycineAmidinoTransferase). AGAT is first of two enzymes used in the synthesis of creatine from amino acids. AGAT catalyzes the reaction involving the combining of arginine and methionine to form GuanidinoAcetic Acid (GAA) and ornithine in the liver. GAA is then transported in the blood stream to the liver where it is activated with the addition of a methyl group (from methionine) to produce creatine. This second step is one of the principal methylation reactions undertaken by the body (also see Coronary Heart Disease).
Click here to see the creatine synthetic reaction in full detail.
Most importantly, the expression of AGAT has been shown to be suppressed (downregulated) by the presence of elevated creatine in the blood stream. Supplementing during pregnancy may, therefore, interfere with the endogenous role of AGAT in fetal development, whatever it may be. Although provocative, this result needs to be expanded upon and corroborated in the placenta of pregnant human females.
A similar concern arose from the finding that creatine transporter expression changes dramatically during the first few weeks of life in certain animal species. For instance, in rabbit pups the levels of creatine transporter expressed on neurons within the brain drops by 60% between days 5 and 15 post-birth. Although remaining to be demonstrated in humans, given the fact that creatine levels influence the expression of the creatine transporter (also see Question #4), the possibility thus exists that exogenous creatine supplementation may upset an inherent developmental program based on natural changes in serum creatine levels.
How to best combine creatine, exercise, diet and nutritional supplements in order to optimize your anabolic hormone levels and preserve existing muscle mass is clearly explained in my creatine guide.
11. Side effects?
Understandably, "What are creatine's side effects?" is my most frequently asked question. While several classes of side effects have unequivocally been linked to creatine consumption, others have not. I will begin this section by describing those side effects which have been clearly linked to creatine use and end with a discussion of the side effects often attributed to creatine consumption, but largely unexplained based on our current knowledge of creatine's accepted mechanisms of action, and give some possible explanations.
Most of the substantiated side effects arising from creatine use involve the propensity for creatine to draw water into the body compartments where it has accumulated. Scientifically speaking, creatine is osmotically active. This may not sound too serious, but if NOT compensated for with adequate fluid intake, other body tissues may be deprived of much needed fluids, especially during strenuous exercise (see Dehydration). It is thus very important that you remain well hydrated while supplementing. Drink at least 1-2 ounces of water daily per kilogram of body weight while supplementing. Other possible side effects have to do with the body's ability, or rather inability, to clear creatine and its associated by-products from the body.
Volumizing: An increase in body weight is the most widely accepted side effect attributed to creatine use. As much as 3 kilograms (6.6 pounds) of added body weight have been reported during the first weeks of supplementation. This rapid increase in body mass is almost exclusively due to the movement of water from the blood stream into skeletal muscle. Such an increase in body mass is simply too rapid to be due to an increase in "dry" muscle mass (proteins). This form of muscle growth is known as Muscle Volumizing because our muscles increase in volume as they inflate with water. Some types of athlete (bodybuilders, for example) may not consider this side effect a negative, and, in fact, may find it a desirable characteristic. By contrast, other athletes (endurance athletes, for example), may find that muscle volumizing interferes with their athletic performance. It is easy to imagine how a few extra "kilos" may hinder one's performance in a marathon. In any case, creatine-based energy production bestows little benefit during endurance events (see Question #5).
Later stages of muscle growth, on the other hand, do involve the acquisition of new muscle proteins, but will be smaller in magnitude and more protracted in time when compared to the increase in body mass attributed to Muscle Volumizing. The proportion of gains that persist, moreover, will increase by combining creatine with essential B vitamins and other important nutrients (also see Question #8).
The contributions that B vitamins can make to the benefits of creatine supplementation are discussed in Issue 30 of the Creatine Newsletter.
Dehydration: Again, it's imperative that you remain well-hydrated while supplementing. Adequate hydration is important since much of our body water follows creatine into skeletal muscle, possibly depriving our remaining tissues of much needed fluid, especially when exercising in hot and humid environments. Down the road this may lead to impaired thermoregulation and subsequent heat exhaustion. This precaution is especially valid in combative sports (wrestling, etc) where athletes strive to make weight before competition. Weight loss under these circumstances is often achieved through fluid restriction, which, in combination with creatine use, could lead to excessive dehydration.
1997 Wrestlers Death Controversy
Hyperthermia and Dehydration
Highlighting this concerns was the controversy over the deaths of three college wrestlers. The deaths occurred independently, at three separate college campuses, on three separate occasions. From the available evidence, it appeared that dehydration, elevated body temperature and excessive weight loss all contributed to their demise. To what degree, however, creatine may have participated in their unfortunate deaths was then hotly debated in the popular press. Later, it was revealed that two of the athletes might not have used creatine after all. USA Today later retracted its original allegation that creatine was implicated in these deaths. Nonetheless, it is imperative to remain well hydrated while supplementing and undertaking extreme measures to lose weight and/or participating in strenuous exercise in hot and humid environments. These incidents have contributed to the National Collegiate Athletic Association (NCAA) imposing stronger restrictions on weight loss protocols among college athletes.
Click here for the US Government's Department of Health and Human Resource's Center for Disease Control and Prevention (CDC) official synopsis of the event.
Gastrointestinal Distress: Gastrointestinal distress is the secondly most common side effect reported. Incidences of stomach cramps, nausea, flatulence, and diarrhea are more commonly reported during the loading phase when greater amounts of creatine are consumed each day. These side effects are principally due to the presence of large quantities of undissolved creatine particles residing within the intestinal compartment. Remember, creatine has the propensity to draw water into the body compartment where it is found (see above). If the body compartment in question is the large intestine, then excessive water absorption may lead to diarrhea and intestinal cramps. These side effects can often be largely circumvented by making sure that creatine is completely dissolved in at least 16 ounces of water (or juice) and never consuming more than the recommended dosing amount (see Question #7).
To circumvent incidences of gastrointestinal distress, micronized and effervescent forms of creatine have been developed. These forms of creatine are more easily absorbed into the blood stream and, hence, have less of a tendency to collect within the intestinal compartment. Downstream the increased solubility of these products this will help evade gastrointestinal complications. You can find out more about the different forms of creatine by reading my Creatine Products Review. Learn the theory behind the formulations of the most popular creatine products on the market. After reading this review, anyone will be able to determine which additives are truly enhancing the properties of a given creatine product, or are merely added to inflate the price and to give a false sense of innovation. This review is normally included as a bonus to those purchasing Creatine: A practical guide. However, you can download an abbreviated version of the Creatine Products Review for free.
The presence of additives or contaminants may also be a source of gastrointestinal discomfort. These days, it seems as if every creatine manufacturer is trying to distinguish their particular product from the rest of the crowd. Each day new marketing twists are appearing with the main objective of making their particular products appear superior to all the rest. As a result more and more extraneous agents are being added to the growing list of creatine products (see above). People who experience gastrointestinal discomfort from creatine may merely be sensitive to these additives and not to the creatine per se. If your particular brand of creatine gives you an upset stomach, switch to a source of pure creatine monohydrate. It's thus important that you purchase your creatine from a reputable creatine provider.
Flatulence: The large amounts of sugars often consumed with creatine may lead to flatulence, complicate gastric emptying and lead to cramps (see Question #4). Certain sugars, particularly when consumed in large quantities, may pass undigested through the small intestine and ultimately collect (nearly intact) in the large intestine. Here, intestinal bacteria decompose the sugar, releasing gas. If sufficiently large amounts of gas are produced to exert pressure within the intestinal compartment, then cramps may ensue. Flatulence, obviously, is the expelling of the gas produced by the bacteria.
Fructose and sorbitol are especially notorious in this respect. Therefore, avoid mixing your creatine in juices containing mainly fructose.
Muscle strains, cramps and tears: These side effects are sometimes reported in chat rooms and in the popular press. As a result, these incidences are sometimes dismissed as anecdotal and unfounded. Similar incidences, although rare, have also been reported during controlled scientific studies. Nevertheless, the validity of these side effects is still being debated in the creatine scientific community. This is due, in great part, to appearance of scientific studies showing no, or even a positive, effect of creatine over the incidence of muscle injury. The problem may be that most of the before mentioned studies used highly-trained college-aged athletes. The body's of such individuals have adapted quite well to a demanding exercise load.
Muscle cramping might result from an electrolyte imbalance downstream of possible creatine-induced dehydration. Alternatively, muscle lesions might result from one over-reaching their physical capacity. In other words, during creatine supplementation the amount of force we are able to generate may increase faster than our muscle's (ligaments, tendons, etc) ability to adapt to the increased load; a weakest link phenomena. Again, drink plenty of fluids while taking creatine!
Renal Stress: Sensible creatine use doesn't appear to adversely influence kidney function in healthy individuals. There is some concern, however, that "creatine abuse" may place undue stress on the kidneys, particularly during the loading phase when large quantities of creatine are being ingested on a daily basis. During loading the kidneys must work harder to clear unabsorbed creatine from the blood stream. Persons with pre-existing kidney disorders, or predisposed to renal dysfunction, such as diabetics or the elderly, should minimally omit the loading phase of supplementation, or abstain from creatine use altogether. These individuals, should they choose to supplement, should also be checked by their doctors on a regular basis.
Blood Pressure: There was some concern that creatine-induced fluid retention could reduce blood pressure. This was the topic of a recent scientific study demonstrating that acute creatine use does not alter blood pressure. Importantly, some blood pressure medications may negatively interact with creatine-induced muscle fluid retention.
Cholesterol & Protein Synthesis: Not all of creatine's reputed side effects are detrimental. For example, recent research has shownt that creatine supplementation may improve our serum cholesterol levels. In addition, muscle volumizing may directly stimulate the production of new muscle proteins. There are also indications that creatine may possess antioxidant properties on its own (see box for details). Finally, and most importantly for overall health, creatine supplementation may reduce serum homocysteine levels by sparring the body's methyl reserves. Reducing serum homocysteine levels, in turn, will greatly improve physical and mental health.
Antioxidant Properties of Creatine & B-Vitamins
Energy metabolism liberates electrons (each electron is accompanied by one proton, H+), which then need to be removed from the cell soon after being produced. Oxygen is the final acceptor of these protons to produce water (oxygen is the “O” in H2O). This is one of the principal reasons that our breathing rate increases in response to heavy exercise. This process is not perfect, however, and a small amount of oxygen is inevitably converted into Reactive Oxygen Species (ROS), a class of molecule known as “free radical”. Most importantly, the rate at which ROS are produced increases in parallel with exercise intensity, i.e. with increasing consumption of oxygen. ROS are notorious at destabilizing cellular membranes, ultimately causing muscle damage and possibly muscle cell death, especially after strenuous exercise.
The body normally defends itself from free radical damage with the help of antioxidants that are typically able to neutralize ROS as soon as they are produced. During strenuous exercise, however, the levels of ROS rise to the point where they actually overrun the body’s normal antioxidant defenses, giving rise to a degenerative scenario known as oxidative stress. To combat oxidative stress the body produces its own battalion of antioxidants as well as obtains antioxidants from the diet. Glutathione is one of the most potent antioxidants produced by the body. On the other side of the issue, the superoxide radical is one of the most insidious of ROS produced by heavy exercise, disease or injury. Oxidative stress resulting from the production of free radicals will prolong the times it takes for your muscle to recover following intense exercise in preparation of muscle growth. Therefore, consuming dietary antioxidants is necessary to combat the development of OverTraining Syndrome (OTS).
Antioxidants are Superoxide Scavengers
Creatine: A recent report has shown that creatine may act as an antioxidant in its own right (1). In fact, creatine is nearly as effective as glutathione in neutralizing the superoxide radical. This raises the intriguing possibility that part of creatine’s ergogenic benefit arises from its capacity to act as an antioxidant.
Folate: Vitamin B supplementation is effective at reducing oxidative damage (2). For instance, folic acid supplementation has been shown to reduce the production of the superoxide radical (3). The ability of folic acid to act as an superoxide scavenger will effectively reduce an athlete's chances of developing OverTraining Syndrome (OTS).
Vitamin B6: Homocysteine is converted into glutathione with the assistance of vitamin B6. The importance of this antioxidant-sustaining pathway is best exemplified by the finding that rats deprived of dietary vitamin B6 exhibit severely attenuated antioxidant defenses and are more sensitive to oxidative stress (4). It is thus not surprising that another report demonstrated that supplementation with vitamin B6 reduces markers of oxidant stress under conditions where homocysteine levels were exaggeratedly elevated by depriving animals of folic acid (5). Therefore, vitamin B6 represents yet another important way to reduce the harmful effects of oxidative stress following intense exercise.
Creatine, Folic Acid, Vitamin B6 & Nitric Oxide (NO)
One study demonstrated that folic acid increases the production of NO (Nitric Oxide) from the endothelial cells lining the inside of arteries (3). NO is a very important vasodilator and is essential for maintaining overall health. In fact, the name originally given to NO (before it was discovered to be a simple gas) was Endothelium-Derived Relaxing Factor, or EDRF; arteries in a healthy individual are soft and relaxed largely due to the presence of NO. Accordingly, the increased degradation of NO by superoxide is a key step in the development of atherosclerosis (arteriosclerosis - hardening of the arteries). Superoxide's NO-neutralizing effects have earned it the name Endothelium-Derived Constricting Factor, or EDCF. Certainly, creatine, folic acid and vitamin B6, by scavenging superoxide radicals, are essential for cardiovascular health.
Macrophages are specialized cells of our immune systems that literally eat (phagocytize) foreign invaders. Macrophages use NO to combat the growth of tumors. Accordingly, inhibition of NO production reduces the microbiocidal and tumouricidal activities of macrophages. In fact, the long-standing practice of curing meat with nitrite is an extension of NO's antibacterial properties. Therefore, folic acid will increase your resistance to invading foreign pathogens by potentiating the effects of NO.
Previous studies have shown that NO is also a stimulator of insulin release. Insulin, growth hormone and testosterone are key players in the anabolic hormone response to exercise. Insulin also
activates the transport of creatine into the cells of our body. Therefore, folic acid should improve your anabolic status.
NO also detoxifies homocysteine by chemically combining with it, thereby interfering its ability to produce superoxide. On the other hand, the fact that homocysteine itself is a prooxidant and produces superoxide radicals (that deplete cellular NO levels) counteracts this positive effect of NO (6). It now appears that homocysteine exerts its prooxidant effect by inducing the expression of a tumor promoting factor (Tumor Necrosis Factor-alpha, or TNF-alpha) that then stimulates the production of superoxide radicals via the actions of an enzyme known as NADH oxidase. These enzymatically produces superoxide radicals then interfere with the relaxation of blood vessels in response to NO, commencing the biochemical cascade of events that ultimately lead to atherosclerosis (7). The plot thickens... Regardless of downstream biochemical ramifications..., creatine and essential B-vitamins, by reducing serum homocysteine levels and scavenging superoxide radicals, will extend the healthful benefits of NO.
Click here for a discussion of the other detrimental effects of homocysteine.
In 1992 Science magazine named NO "Molecule of the Year" for its life-sustaining properties.
Surely, since creatine, folic acid and vitamin B6 help preserve our cellular levels of NO (by neutralizing superoxide), they are a worthwhile addition to any fitness regimen!
Antioxidant Supplementing Regimen: As demonstrated by numerous scientific studies, uniting creatine and specific B-vitamin supplementation will greatly improve your antioxidant status, accelerate muscle recovery following intense exercise and accentuate muscle anabolism. It is for these reasons that I strongly recommend that an athlete combine creatine and vitamin B supplementation during periods of intense training to assist in muscle recovery and growth.
Click here for more information about a new B-vitamin supplement specifically designed to accompany creatine for greatest anabolic effect.
Selected Scientific References:
1. Lawler J. M. et al. (2002) Direct antioxidant properties of creatine. Biochemical and Biophysical Research Communications, Volume 290 (1), pages 47-52.
2. Ullegaddi R. et al. (2004) B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke. Clinical Science, Volume 107, pages 477–484.
3. Stroes E. S. G. et al. (2000) Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circulation Research, Volume 86, pages 1129-1134.
4. Taysi. S. (2005) Oxidant / antioxidant status in liver tissue of v itamin B6 deficient rats. Clinical Nutrition, Volume 24, pages 385– 389.
5. Mahfouz M. M. and F. A. Kummerow (2004) Vitamin C or Vitamin B6 supplementation prevent the oxidative stress and decrease of prostacyclin generation in homocysteinemic rats. The International Journal of Biochemistry and Cell Biology, Volume 36 (10), pages 1919-1932.
6. Stamler J. S. et al. (1993) Adverse vascular effects of homocysteine are modulated by endothelium derived relaxing factor and related oxides of nitrogen. Journal of Clinical Investigation, Volume 91, pages 308-318.
7. Ungvari Z. et al. (2003) Increased superoxide production in coronary arteries in hyperhomocysteinemia: role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase. Arteriosclerosis, Thrombosis, and Vascular Biology, Volume 23 (3), pages 418-424.
Contaminants: Pure creatine monohydrate is not toxic. Certain impurities, however, may be potentially harmful. Creatine monohydrate is produced commercially by mixing sodium sarcosine and cyanamide in a heated water bath. Although seemingly straightforward certain chemical by-products may be formed, especially if inferior quality starting materials are used or sufficient care isn't exercised during synthesis. These contaminants are particularly evident for cheaper brands of creatine. Moreover, some of the impurities present in poorer quality brands of creatine are potentially toxic and may give rise to adverse side effects.
The presence of contaminants is particularly worrisome during the loading phase when much greater amounts of creatine are consumed each day. A person loading with a poorer quality creatine product may actually be taking in grams of potentially toxic impurities each week.
Finally, some cheaper (or less scrupulous) creatine products have been shown to contain trace amounts of certain anabolic steroids. The presence of steroids in some cheaper creatine products may account for incidences of false-positives in some creatine users. Importantly, under the new Anabolic Steroid Control Act of 2005 (USA), ignorance is no excuse. If you test positive for any banned agent you may be barred from receiving federal financial aid as well as be declared ineligible for further athletic competition. This is no joking matter. In essence, cheaper brands of creatine literally dilute the amount of "real creatine" with contaminants making them pointless, potentially harmful, possibly illegal and a huge waste of money.
Given these caveats, it's important that you purchase only quality creatine products. Full descriptions of creatine's possible contaminants as well as the best producers of high quality creatine internationally are discussed in Creatine: A practical guide.
Click here for an official list of drugs banned by the NCAA.
Rumors & Unexplained Side Effects: Side effects that cannot be explained from what is scientifically known about creatine are sometimes reported. Whether these side effects represent fact or fiction is still a matter of controversy. Some unexplained side effects may be merely rumor and arise from creatine being mistakenly associated with anabolic steroids. On the other hand, other incidences of unexplained side effects may be real and stem from contaminants or additives present in cheaper brands of creatine. This second set of unexplained side effects may have previously escaped detection owing to the fact that most scientific studies use only the highest-grade creatine products, WITHOUT unstudied additives that could confound the analysis of the data.
Unsubstantiated side effects reported include breast formation in men (gynecomastia), a reduction in penis size, hair loss (men), hair growth (women) and stunted growth in children. Unexplained incidences of aggression and acne have also been linked to creatine use.
Examples of personal accounts of some unexplained side effects attributed to creatine use can be found here.
Unexplained Effects of Creatine?
Having raised these concerns about certain "unexplained dangers" of creatine supplementation (above), it is now important to stress that certain "unexplained BENEFITS" of creatine supplementation have also been recently uncovered.
Fortunately, the majority of the negative attributes sometimes linked to creatine supplementation can be easily circumvented by purchasing only quality creatine products; that is, most negative side effects are not the result of the creatine per se. Equally fortunate, the positive benefits of creatine supplementation can be fortified with a simple nutritional intervention.
It is my personal belief that many of these “mysterious benefits” now being attributed to creatine supplementation, but lacking full explanations, have to do with creatine's ability to increase the body’s capacity to methylate important cellular targets, including our genes and essential anabolic modulators. Exactly how creatine supplementation spars the body's methyl reserves is discussed in a recent issue of the Creatine Newsletter. Click here to view this issue.
A new (safe & legal) product has very recently emerged that was specifically designed to make the most of this special aspect of creatine supplementation. Click here for information about this novel approach to creatine supplementation.
Misconceptions: Oh, Fat is Fat and Muscle is Muscle, "and never the twain shall meet"...
Muscle will not convert to fat after stopping creatine supplementation. It simply can't. Muscle and fat are two completely different tissue types.
Our muscles initally grow in response to creatine use as a result of increased hydration (aka, muscle volumizing) and later on because of an increase in muscle protein content (aka, protein synthesis). After stopping creatine supplementation any gains in muscle size that were attributed to muscle volumizing will be lost (see Question #9). This is unavoidable. Remember, however, that this is only muscle water that is being lost, not muscle proteins. On the other hand, any gains you made as a result of increased muscle protein content will be more enduring.
The only way you can create body fat is to consume more calories than you burn with physical activity. Therefore, if your activity level decreases significantly after stopping creatine supplementation, while your caloric intake remains the same (or increases), you will gain fat.
Article 4
The following is a compilation of various articles on creatine.
What is Creatine?
Creatine is an amino acid derivitive found naturally in animal muscle tissue (fish, meat) that enables the body's muscles to produce high-energy compounds (ATP) quickly. It's also created by the human liver and kidneys, formed by the breakdown of amino acids. Used by muscle cells to store energy for sprinting and explosive exercise, creatine supplementation is believed to boost muscle performance during intense workouts by allowing the muscles to recover more rapidly. Usually, muscle creatine is used up within 10 seconds of exercise.
Is Creatine Safe?
Absolutely! Creatine is a
substance that is naturally found in our bodies. No negative side effects have ever been noted in the research.
Creatine Shows New Health Benefits
While creatine supplementation has been studied for over 80 years, widespread use of this substance has only gained popularity in the past decade. With numerous investigations demonstrating unprecedented effects of creatine on strength, power, and muscle mass, scientists studying various muscular and neurological disorders have taken notice and begun experimenting with creatine as a possible therapeutic agent. A recent report in the journal Neurology (1999) found that individuals with differing neuromuscular disorders, including muscular dystrophy, improved muscle strength and increased muscle mass following 15 to 17 days of creatine monohydrate supplementation. Another study, appearing in the journal Nature Medicine (1999), found positive neuroprotective effects of creatine on the degenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The research was performed on mice rather than humans, but creatine provided about twice the benefits of the standard prescription medication.
Creatine Still on Top!
The abundance of creatine research presented at the American College of Sports Medicine conference shows creatine's popularity and benefits continue to rise. Proper maintenance dose following a loading phase has been a subject of controversy among sport scientists. New research had found that following a five-day loading phase (25g/day), elevated creatine levels and enhanced performance can be maintained for as long as two months on 5 g/day. Studies were also presented demonstrating that not only did creatine not increase the incidence of muscle cramping, but it may be beneficial in reducing the risk of injury during training. These findings were further supported by evidence that creatine does not cause alterations in fluid or electrolyte balance. Creatine isn't just for gaining strength and muscle either. Creatine was found to reduce the loss of muscle mass and improve anaerobic performance during a weight loss program combined with weight training.
Creatine Should Not Cause Cramping
Recently the Penn State Sports Medicine Newsletter asked Jeff Volek, M.S., R.D., a research assistant at Penn State, to update their readers regarding the effect of creatine on performance. "We do know that creatine supplementation has been shown to enhance short-term, high-intensity, intermittent performance." Adds Volek: "Some athletes are not using creatine because they have heard that is causes cramps. There are no data to support those claims. The mechanism of cramping is not even understood aside from the creatine issue."
EFFECTIVE CREATINE PLAN
How To Gain 8 to 10 Pounds Of Muscle Within The Next Eight Weeks!
By Dan Gallapoo
Some people have noticed that they have some gastric upset and diarreah when they start their creatine cycle with a 20 to 25 gram "loading cycle". And I've found that the commonly recommended maintenance dosage of 5 grams a day is just not enough for many people to get maximum benefits.
Here's a plan that should help you get the maximum cell volumizing and muscle building effects from creatine without much (if any) gastric distress:
WEEK # DAILY DOSAGE (grams)
1 10
2 20
3 30
4 40
5 40
6 30
7 20
8 10
This cycle is a fairly long one which allows you to
retain the cell volumizing effect for a longer period of time. This provides more opportunity to gain the benefits associated with creatine usage (strength increase, increased rate of hypertrophy, etc.)
You may not start seeing and feeling benefits until the third week of the cycle. The third week is usually about the optimal dosage for most people.
Editors Note:
All I can say is that this special creatine muscle volumizing plan has exceeded all expectations! I am only in my fourth week of the eight week cycle and...
"I’ve already gained a solid 7 pounds of bodyweight and have increased my squat forty pounds!"
Almost all of my other lifts have gone up, too.
I've had moderate success with creatine supplementation in the past, but nothing like I'm experiencing now. Every time I go into the gym I'm stronger. And the pumps are incredible...almost as good as a steroid pump!
For great prices on creatine go to Discount Supplements
P.S. This creatine cycle works great while stacking it with "Andro-Shock".
