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Creatine Monohydrate

Creatine supplementation and exercise performance : recent findings.

Bemben MG, Lamont HS.

Neuromuscular Research Laboratory, Department of Health and Sport Sciences, University of Oklahoma, Norman, Oklahoma, USA.

Creatine monohydrate (Cr) is perhaps one of the most widely used supplements taken in an attempt to improve athletic performance. The aim of this review is to update, summarise and evaluate the findings associated with Cr ingestion and sport and exercise performance with the most recent research available. Because of the large volume of scientific literature dealing with Cr supplementation and the recent efforts to delineate sport-specific effects, this paper focuses on research articles that have been published since 1999.Cr is produced endogenously by the liver or ingested from exogenous sources such as meat and fish. Almost all the Cr in the body is located in skeletal muscle in either the free (Cr: ~40%) or phosphorylated (PCr: ~60%) form and represents an average Cr pool of about 120-140g for an average 70kg person.It is hypothesised that Cr can act though a number of possible mechanisms as a potential ergogenic aid but it appears to be most effective for activities that involve repeated short bouts of high-intensity physical activity. Additionally, investigators have studied a number of different Cr loading programmes; the most common programme involves an initial loading phase of 20 g/day for 5-7 days, followed by a maintenance phase of 3-5 g/day for differing periods of time (1 week to 6 months). When maximal force or strength (dynamic or isotonic contractions) is the outcome measure following Cr ingestion, it generally appears that Cr does significantly impact force production regardless of sport, sex or age. The evidence is much more equivocal when investigating isokinetic force production and little evidence exists to support the use of Cr for isometric muscular performance. There is little benefit from Cr ingestion for the prevention or suppression of muscle damage or soreness following muscular activity.When performance is assessed based on intensity and duration of the exercises, there is contradictory evidence relative to both continuous and intermittent endurance activities. However, activities that involve jumping, sprinting or cycling generally show improved sport performance following Cr ingestion. With these concepts in mind, the focus of this paper is to summarise the effectiveness of Cr on specific performance outcomes rather than on proposed mechanisms of action.The last brief section of this review deals with the potential adverse effects of Cr supplementation. There appears to be no strong scientific evidence to support any adverse effects but it should be noted that there have been no studies to date that address the issue of long-term Cr usage.

Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs. nonresponders.

Syrotuik DG, Bell GJ.

Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Canada. Syrotuik@ualberta.ca

The purpose of this study was to describe the physiological profile of responders (>20 mmol.kg(-1) dry weight [dw] increase in total intramuscular creatine monohydrate [Cr] + phosphorylated creatine [PCr]) versus nonresponders (<10 mmol.kg(-1) dw increase) to a 5-day Cr load (0.3 g.kg(-1).d(-1)) in 11 healthy men (mean age = 22.7 years). Pre-post 5-day cellular measures included total resting Cr content (Cr + PCr), fiber type composition, and fiber type cross-sectional area (CSA) determined from muscle biopsies of the vastus lateralis. Body mass, daily dietary intake, 24-hour urine outputs, urinary Cr and creatinine (CrN), and strength performance measures (1 repetition maximum [1RM] bench and leg press) were also assessed before and after the 5-day loading period. Results indicated that there were 3 levels of response to the 5-day supplementation: responders (R), quasi responders (QR), and nonresponders (NR) with mean changes in resting Cr + PCr of 29.5 mmol.kg(-1) dw (n = 3), 14.9 mmol.kg(-1) dw (n = 5), and 5.1 mmol.kg(-1) dw (n = 3), respectively. The results support a person-by-treatment interaction to acute Cr supplementation with R possessing a biological profile of lowest initial levels of Cr + PCr, greatest percentage of type II fibers, and greatest preload muscle fiber CSA and fat-free mass. Responders also showed improvement in 1RM leg press scores following the 5-day loading period. NR had higher preload levels of Cr + PCr, less type II muscle fibers, small preload muscle CSA, and lower fat-free mass and displayed no improvements in 1RM strength scores. The results suggest that to be considered a responder to acute oral supplementation, a favorable preexisting biological profile may determine the final extent to which an individual responds to supplementation. Physiologic profiles of nonresponders appear to be different and may limit their ability to uptake Cr. This may help partially explain the reported equivocal performance findings in the Cr supplementation literature.
J Strength Cond Res. 2004 Aug;18(3):610-7



R.B. Kreider, C. Rasmussen, J. Ransom, and A.L. Almada. Exercise and Sport Nutrition Laboratory, Department of HMSE, The University of Memphis, Memphis, TN 38152.

Anecdotal reports have suggested that creatine supplementation during training may increase the incidence of cramping, muscle strains/pulls, and/or gastrointestinal (GI) distress. This study evaluated the incidence of side effects reported in subjects who participated in one of five placebo, double-blind, and randomized studies which investigated the effects of ingesting creatine or creatine- containing supplements during training. One hundred sixty- four post-study questionnaires were evaluated in which 84 subjects ingested placebos and 80 subjects ingested supplements containing creatine during training. Training and supplementation protocols included: 1.) 9 d of ingesting a carbohydrate placebo (n=9) or 21 g/d of creatine (n=9) in male and female elite junior swimmers during training (20.5 � 2 hr/wk); 2.) 14 d of ingesting a carbohydrate placebo (n=7), 16.5 g/d of creatine (n=8), or Phosphagen HP� containing 15.75 g/d of creatine (n=9) in untrained and competitively trained male and female endurance athletes; 3.) 28 d of ingesting a carbohydrate placebo (n=11), Gainers Fuel 1000� (n=10), or Phosphagain� containing 20 g/d of creatine (n=7) during resistance-training (7.6 � 2 hr/wk); 4.) 28 d of ingesting a carbohydrate placebo (n=22) or Phoshagen HP containing 15.75 g/d of creatine (n=23) in college football players undergoing resistance/agility training (8 hr/wk); or, 5.) 84 d of ingesting a carbohydrate placebo (n=13), MetRx� (n=12), Phosphagain� containing 20 g/d of creatine (n=11), or Phosphagain II� containing 25 g/d of creatine (n=13) in college football players undergoing resistance/agility training and spring football practice. Results revealed no reports of muscle cramping or injury in subjects taking placebos or creatine-containing supplements during training. Further, a significantly greater incidence (p<0.05) of GI distress was reported in subjects ingesting placebos compared to creatine-containing supplements. These findings indicate that creatine supplementation during various exercise training conditions does not increase the incidence of muscle cramping, muscle strains/pulls, or GI distress. Presented at the National Strength and Conditioning Association Convention, Nashville, TN, June 24-28, 1998.

Creatine Monohydrate May Improve Blood Lipid Profiles

C.P. Earnest, A.L. Almada, and T.L. Mitchell, High- Performance Capillary Electrophoresis-Pure Creatine Monohydrate Reduces Blood Lipids in Men and Women,Clin. Sci. 91 (1996): 113-118.

Just when you thought the news about creatine monohydrate couldn't get any better, we're finding that creatine may, in addition to its well-documented positive effects on body composition and athletic performance, reduce blood lipids. A team of researchers in Dallas, Texas, including EAS researcher Anthony Almada, B.Sc., M.Sc., examined the effects of creatine monohydrate (5 grams) combined with glucose (1 gram) on the blood chemistry of 34 male and female subjects, ages 32-70 years. Scientists measured creatine's effects against those of a placebo containing 6 grams of glucose for a total of 56 days, with dosages of both creatine and the placebo given orally 4 times a day for 5 days, then twice a day for 51 days.

Results indicated significant reductions in plasma total cholesterol, triglycerides, and very low-density lipoproteins (VLDL) in the creatine monohydrate group. High levels of these substances in the blood can lead to heart disease, a problem that killed over 740,000 Americans in 1993 alone. Researchers also noted a trend towards a reduction in blood glucose for subjects ingesting creatine monohydrate.

Additionally, the trend for lower blood glucose in subjects receiving creatine monohydrate indicates the possibility that creatine enhances insulin sensitivity, which could prove helpful for some diabetics. This result could also mean that glucose moves from the bloodstream into muscle cells more quickly with creatine use. Again, further research is necessary to determine whether or not these results can be repeated and strengthened, but there is a strong possibility that creatine monohydrate can actually lower blood lipids and improve glucose metabolism.

Safety Report on Creatine

T. Mitchell, A. Almada, and C. Earnest, Creatine Reduces Blood Lipid Concentrations in Men and Women, Influence of Chronic Creatine Supplementation on Hepatorenal Function, Impact of Chronic Creatine Supplementation on Serum Enzyme Concentrations, FASEB J. 10.3 (1996): A251, A791, A790.

A group of scientists from Texas Woman's University and the Cooper Clinic in Dallas, Texas, presented results of the longest creatine supplementation study to date. These studies were designed to assess the influence of eight weeks of creatine ingestion on various markers of metabolism and organ function. Although a large number of creatine supplementation studies have been conducted, virtually all of them focused on muscular performance and muscle metabolism after short-term supplementation.

Thirty-four men and women (ages 32-70) participated in this double-blind, placebo-controlled study. Twenty subjects received creatine (20 grams per day for 5 days, then 10 grams a day for 51 days, followed by a 4- week washout /non-supplemented period), while the remaining 14 received a glucose placebo. Few changes in the blood profiles were noted in the creatine group: a slight increase in blood urea nitrogen (BUN) in only the women at week eight was seen (BUN is a marker of liver and kidney function and protein metabolism), and among the men, at week three, a mild elevation in creatine phosphokinase (CPK) was seen. Both returned to baseline after week 12. CPK is an enzyme critical to creatine and energy metabolism. It's continuously released from various cells including skeletal muscle and is a crude marker of muscle cell membrane integrity.

Interestingly, recent university studies with creatine HP noted similar effects in a group of young, resistance- trained males, with CPK going up in the HP group but not in the placebo group. Increases in CPK suggest either an increase in muscular force or tension production, consequent decreases in the stability of muscle-cell membranes (leading to increased CPK leak), decreases in muscle-cell membrane integrity (more holes), and/or an increase in the activity/concentration of this enzyme due to increased concentrations of one of the substrates for this enzyme, which may induce creatine-loaded cells to synthesize more CPK. Why women didn't show an increase in CPK may be due to the protective effect of estrogens on cell membranes. (The majority of the women had moderate circulating concentrations of estrogens, either naturally or from oral estrogens.)

Liver enzymes didn't increase nor did blood creatinine, the irreversible breakdown product of creatine, commonly mistaken for creatine and incorrectly believed to be toxic to the kidneys.

Comments: The most fascinating observation from these studies was a drop in blood triglycerides, total cholesterol, and VLDL cholesterol, a blood lipoprotein enriched in triglycerides, in the creatine group (these findings were published in full, peer-review form in the July 1996 issue of Clinical Science). As all of the subjects began with moderately elevated blood cholesterol and triglycerides, these findings suggest creatine may prove to be a useful nutritional supplement in the management of high blood lipids. The mechanism of creatine's action is suggested by the reduction of blood glucose in the males who received creatine. As insulin regulates both carbohydrate and triglyceride/VLDL metabolism, and creatine and fourth-generation diabetes drugs (like metformin) are classified as guanidine- containing compounds with glucoregulatory actions, this raises the likelihood that, at least in this group of individuals, creatine may be capable of potentiating the action of insulin. Similar to the persistence of vanadyl sulfate's effects in diabetic individuals, four weeks after going off Phosphagen, triglycerides and VLDL remained reduced. The fact that EAS funded these studies underscores the company's commitment to extending the science of creatine supplementation by continuing to examine the safety and biological effects of this fascinating nutrient.

Creatine and its application as an ergogenic aid.

Greenhaff PL. Department of Physiology and Pharmacology, University Medical School, Queens Medical Centre, Nottingham, U.K. Int J Sport Nutr, 5 Suppl():S100-10 1995 Jun

Phosphocreatine (PCr) availability is likely to limit performance in brief, high-power exercise because the depletion of PCr results in an inability to maintain adenosine triphosphate (ATP) resynthesis at the rate required. It is now known that the daily ingestion of four 5-g doses of creatine for 5 days will significantly increase intramuscular creatine and PCr concentrations prior to exercise and will facilitate PCr resynthesis during recovery from exercise, particularly in those individuals with relatively low creatine concentrations prior to feeding. As a consequence of creatine ingestion, work output during repeated bouts of high-power exercise has been increased under a variety of experimental conditions. The reduced accumulation of ammonia and hypoxanthine in plasma and the attenuation of muscle ATP degradation after creatine feeding suggest that the ergogenic effect of creatine is achieved by better maintaining ATP turnover during contraction.

Creatine depletion elicits structural, biochemical, and physiological adaptations in rat costal diaphragm.

Levine S; Tikunov B; Henson D; LaManca J; Sweeney HL Pulmonary and Critical Care Section, Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. Am J Physiol, 271(5 Pt 1):C1480-6 1996 Nov

To elucidate adaptations elicited by creatine (Cr) depletion in the costal diaphragm (Dia), 16 12-wk-old male Fisher 344 rats had 2% beta-guanidinopropionic acid (beta- GPA), a competitive inhibitor of Cr transport into muscle, added to their food; a control group (Con) of 16 rats ate normal rat chow. After 18 wk, beta-GPA and Con Dia did not differ histochemically with respect to fiber-type distribution; however, the cross-sectional area of type II (b + x) fibers was 33% less in beta-GPA than Con Dia. Biochemically, the proportion of myosin heavy chain IIb in beta-GPA Dia was decreased 42% from Con Dia, whereas the proportions of myosin heavy chains I and IIa were increased. Physiologically, both peak twitch tension and tetanic tension in beta-GPA Dia were decreased 40% from Con. To assess fatigability, we used the protocol of Kelsen and Nochomovitz (J. Appl. Physiol. 53; 440-447, 1982) for 2-6 min duration; the percentage of initial force exhibited by beta-GPA Dia was approximately twice that of Con Dia. We conclude that these structural, biochemical, and physiological adaptations elicited by Cr depletion can all be explained by selective atrophy of IIb muscle fibers in the Dia.

Creatine kinase of rat heart mitochondria. The demonstration of functional coupling to oxidative phosphorylation in an inner membrane-matrix preparation.

Saks VA; Kuznetsov AV; Kupriyanov VV; Miceli MV; Jacobus WE J Biol Chem, 260(12): 7757-64 1985 Jun 25

To define more clearly the interactions between mitochondrial creatine kinase and the adenine nucleotide translocase, the outer membrane of rat heart mitochondria was removed by digitonin, producing an inner membrane- matrix (mitoplast) preparation. This mitoplast fracton was well-coupled and contained a high specific activity of mitochondrial creatine kinase. Outer membrane permeabilization was documented by the loss of adenylate kinase, a soluble intermembrane enzyme, and by direct antibody inhibition of mitochondrial creatine kinase activity. With this preparation, we documented four important aspects of functional coupling. Kinetic studies showed that oxidative phosphorylation decreased the value of the ternary enzyme-substrate complex dissociation constant for MgATP from 140 to 16 microM. Two approaches were used to document the adenine nucleotide translocase specificity for ADP generated by mitochondrial creatine kinase. Exogenous pyruvate kinase (20 IU/ml) could not readily phosphorylate ADP produced by creatine kinase, since added pyruvate kinase did not markedly inhibit creatine + ATP-stimulated respiration. Additionally, when ADP was produced by mitochondrial creatine kinase, the inhibition of the translocase required 2 nmol of atractyloside/mg of mitoplast protein, while only 1 nmol/mg was necessary when exogenous ADP was added. Finally, the mass action ratio of the mitochondrial creatine kinase reaction exceeded the apparent equilibrium constant when ATP was supplied to the creatine kinase reaction by oxidative phosphorylation. Overall, these results are consistent with much data from intact rat heart mitochondria, and suggest that the outer membrane plays a minor role in the compartmentation of adenine nucleotides. Furthermore, since the removal of the outer membrane does not alter the unique coupling between oxidative phosphorylation and mitochondrial creatine kinase, we suggest that this cooperation is the result of protein-protein proximity at the inner membrane surface

13/08/03 - Taking supplements of creatine, a compound found in muscle tissue, can significantly boost both working memory and general intelligence, according to researchers in Australia.

The work, to be published in the Proceedings B journal published by the UK�s Royal Society, found that young adult vegetarians who took 5g of creatine had better recall under pressure than the control group.

"The level of creatine supplementation chosen was 5g per day as this is a level that has previously been shown to increase brain creatine levels. This level is comparable to that taken to boost sports fitness," explained Dr Caroline Rae from the University of Sydney.

�Vegetarians or vegans were chosen as carnivores and omnivores obtain a variable level of creatine depending on the amount and type of meat they eat - although to reach the level of supplementation in this experiment would involve eating around 2kg of meat a day!" she added.

Creatine supplements are widely used by athletes and fitness fanatics to increase sports performance. It is manufactured by the body, but also found in dietary sources such as meat. A close relative of the amino acids, it has also been trialed successfully in the treatment of neurological, neuromuscular and atherosclerotic disease.

"We know that creatine plays a pivotal role in maintaining energy levels in the brain," said Dr Rae. "It was a reasonable hypothesis that supplementing a diet with creatine could assist brain function."

The experiment tested this hypothesis by giving a group of 45 subjects a creatine supplement and a second group a placebo for six weeks, followed by a six week period with no intake and a final six week period when the control and placebo group were swapped. Intelligence and memory were tested at four points: the start of the trial; the end of the first six week period; and the start and endpoint of the final six week period.

The effect on working memory was tested using a backward digit span test in which the subject has to repeat in reverse order progressively longer verbal random number sequences. Intelligence was tested using Ravens Advanced Progressive Matrices - a methodology commonly used for IQ assessment involving completion of pattern sequences. The test is a well validated measure of general ability with minimal dependence on cultural factors.

"Both of these tests require fast brain power and the Ravens task was conducted under time pressure," said Dr Rae. "The results were clear with both our experimental groups and in both test scenarios: creatine supplementation gave a significant measurable boost to brain power. For example in the digit span test, subjects� ability to remember long numbers, like telephone numbers, improved from a number length of about 7 to an average of 8.5 digits."

The study shows that increased creatine intake results in improved brain function, similar to effects shown previously in muscle and heart. The results also appear to back previous observations showing that brain creatine levels correlate with improved recognition memory and reduced mental fatigue.

"These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance," said Dr Rae. "Increasing the energy available for computation increases the power of the brain and this is reflected directly in improved general ability."

Long-term supplementation with creatine has yet to be declared fully safe as there have been reported effects on glucose homeostasis (the regulation of blood sugar levels) and potential subjects with a medical history of diabetes were excluded from the experiment. In addition taking the supplement can have some antisocial effects, �[it] can make you a considerably less 'fragrant' person�, according to Dr Rae.

But she added that creatine supplementation may be of use to those requiring boosted mental performance in the short-term, such as university students.

Source: Proceedings of the Royal Society: Biological Sciences, Vol. 270, No. 1529, (22 October 2003)

Researchers have now been able to stretch creatine�s usefulness beyond the realm of professional sports. In the newest issue of the Royal Society Proceedings of Biological Sciences, Australian researchers have found creatine supplementation in vegetarians to enhance cognitive skills. Forty-five vegetarians college students were selected (meat eaters get abundant amounts of creatine in their diets), with one group taking five grams of creatine daily for six weeks and another group taking a placebo. After the initial six weeks, the subjects went six weeks without any supplementation. During the final six weeks, the subjects then switched supplements. The creatine significantly enhanced the subjects� cognitive performance.

When searching for an explanation, the researchers deduced that the increase in brain energy provided by creatine influenced brain performance. Even though Japanese researchers have found creatine helpful in preventing mental fatigue during mathematical problem-solving tests, creatine has also found usefulness in treating neuromuscular disease, such as amyotropic lateral sclerosis (Lou Gehrig�s Disease) (1). One area of creatine metabolism that is receiving attention is the effect of creatine metabolism on the kidneys. While some studies report both short-term (4) and long-term (3) use of creatine to be benign to the kidneys, all agree that more research still needs to be done.


1. Tarnopolsky M. Creatine monohydrate increases strength in patients

with neuromuscular disease. Neurology 1999; 52: 854.

2. Casey A. Does dietary creatine supplementation play a role in

skeletal muscle metabolism and performance? American Journal of

Clinical Nutrition 2000; 72: 607S � 617

3. Poortmans JR. Long-term oral creatine supplementation does not

impair renal function in healthy athletes. Medical Science and Sports

Exercise 2000; 32(1): 248-249

4. Farquhar WB. Effects of creatine use on the athlete's kidney.

Current Sports Medicine Reports 2002; 1(2): 103-6

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