Lean Bodies Logo Top Navigation
Feature Article

Professional Locator
Professional Registry






Fitness Forum
   

Creatine

By
Thomas Incledon, MS, RD, LD/N, CSCS, NSCA-CPT

Introduction

In 1832 a French scientist reported the discovery of a new organic compound extracted from meat [1]. He named this compound creatine. Structurally, creatine contains nitrogen and resembles an amino acid. As __far back as 1926, it was realized that exogenous creatine, obtained from meat or urine, could be given to humans to increase their creatine muscle content [2]. Since then, creatine has been researched in its free form (creatine) and phosphorylated form (phosphocreatine). Both are considered important factors in skeletal muscle metabolism. Creatine is involved temporal energy buffering, spatial energy buffering, proton buffering, and glycolysis regulation - all roles that may influence physical performance. The purpose of this article is to review the current information in the scientific literature on the use of creatine as a dietary supplement. From the information presented in this article, readers should be armed with the necessary facts to determine if creatine use is warranted.

      NH2+
       ||
   NH2-C-N-CH2-C=O-
       |
      CH3
 
      Structure of creatine

Some background on creatine

Most of the creatine in the human body (about 95%) is located in skeletal muscle. Of this total creatine, about 33-40% is in the free form (unbound to phosphate) and the remaining creatine is the phosphocreatine form. Creatine levels vary from individual to individual and are influenced by factors such as diet [3], age [4], muscle fiber type [5, 6], and disease [7-13]. Training [14-16] and gender [5, 6] are not thought to be factors that influence creatine content in skeletal muscle.

Dietary sources of creatine

In the absence of dietary or supplemental creatine, the rate of creatine turnover is estimated to be about 1.6% per day [17]. The reference male has a bodyweight of 70 kilograms and a total creatine pool of 120 grams. A 1.6% turnover represents about 2 grams per day that must be replaced. This creatine is replaced by synthesis in the body or the ingestion of food or supplements. The synthesized creatine is made from the amino acids glycine, arginine, and methionine. The average daily intake of creatine is about 1 gram per day [18]. Food sources of creatine are listed in Table 1. In general, animal flesh products are the highest dietary sources of creatine. Strict vegetarians maintain creatine stores almost entirely by synthesizing creatine [3]. Feedback mechanisms in the body allow creatine synthesis to be regulated by creatine ingestion [19].

Table 1: Food Sources of Creatine [1]

Food Creatine content (g/kg)
Beef 4.5
Cod 3
Cranberries 0.02
Herring 6.5-10
Milk 0.1
Pork 5
Salmon 4.5
Shrimp Trace
Tuna 4

Creatine supplementation theory

The body uses creatine to make creatine phosphate (phosphocreatine). Phosphocreatine functions as a temporal energy buffer, spatial energy buffer, proton buffer, and regulator of glycolysis. As a temporal energy buffer, creatine can be combined with phosphate (PO4) to form phosphocreatine (CP). Phosphocreatine can then combine with adenosine dipshophate (ADP) and a hydrogen ion (H+) to produce adenosine triphosphate (ATP) and creatine (Cr). These reactions are illustrated below.

Cr + PO4 <----> CP
CP + ADP + H+ <-----> ATP + Cr

The reaction can proceed in either direction. At sites such as in the mitochondria, where ADP is removed to produce new ATP, the above reaction proceeds to the left. At sites where ATP is used for energy, the reaction proceeds to the right. By using H+ to make ATP, phosphocreatine serves as a buffer against acidic conditions inside cells. As a spatial energy buffer, creatine and phosphocreatine may diffuse from areas of production to areas of utilization. This has been termed the Phosphocreatine Shuttle [20]. This energy shuttle uses phosphocreatine to carry energy between sites of production and sites of utilization. Another function of phosphocreatine is to modulate glycolysis. As ATP levels are decreased, phosphocreatine is used to resynthesize more ATP. This, in turn, lowers CP levels and serves as a signal to increase glycolysis to produce more ATP [21].

The exact mechanism by which creatine supplementation could enhance performance is not yet clear. Originally it was thought that increased phosphocreatine levels prior to exercise and/or a higher free creatine concentration would enable one to exercise longer before phosphocreatine levels decreased to performance-limiting levels. Additionally it was thought that the restoration of phosphocreatine levels between bouts of intense exercise would occur more rapidly. Recently, it was shown that creatine loading raises skeletal muscle phosphocreatine concentrations and improves performance during rapid and dynamic intermittent muscle contractions [22]. However, creatine loading did not facilitate muscle phosphocreatine resynthesis during intermittent isometric muscle contractions. In another study, higher pre-exercise levels of phosphocreatine at rest compensated for significantly slower recovery rates of phosphocreatine after creatine supplementation [23]. The increased concentration of phosphocreatine in muscle does not affect the muscle ATP cost of contraction [24]. Collectively, these studies argue against the idea of increased phosphocreatine resynthesis and support the idea of higher starting levels of phosphocreatine. These higher levels do not alter the efficiency of ATP utilization.

What are the facts about creatine supplementation?

Creatine supplementation has the potential to increase performance in dynamic, intermittent, high-intensity type movements/exercises/sports. Creatine supplementation may delay the onset of neuromuscular fatigue [25]. It is known that Type II muscle fibers have higher levels of phosphocreatine and glycogen than Type I muscle fibers [26, 27]. In Type II fibers, phosphocreatine recovery is slower. It has also been reported that high phosphocreatine stores are depleted after 5-7 seconds following sprints from 40-100 m [28, 29]. These facts provide a basis for using creatine as a supplement. Unfortunately, research studies have not consistently reported that creatine supplementation improves performance. Numerous studies have reported increases in body mass after ingestion of 20-30 grams of creatine monohydrate for 5-7 days [2, 30-37]. Body composition was not always measured. Some studies reported an increase in fat-free mass [34, 35]. Some investigators speculated that the increase in body mass was partly due to an increase in total body water content and partly due to an increase in the contractile proteins of Type II muscle fibers [38]. While total body water does increase after creatine supplementation, the percentage of total body water does not change [32, 34]. The gain in body mass that occurs cannot be attributed to water retention and is most likely dry matter growth accompanied with a normal water volume [32]. In 10-12 week long studies, larger increases in Type I, IIA, and IIAB muscle fiber cross-sectional areas [36] and greater gains in strength [35, 36] were reported after weight training and creatine supplementation compared to weight training alone. Creatine supplementation enhances fat-free mass, physical performance, and muscle morphology in response to resistance exercise. These improvements are speculated to be the result of higher quality training sessions, given the greater intensity and workloads performed by the creatine groups.

Creatine was reported to increase muscle protein synthesis in isolated muscle cells [39-42]. However, this work was done primarily using developing chick muscle cells. Research using intact rat skeletal muscles indicates that creatine does not increase muscle size in response to isometric exercise [43]. Preliminary research on humans indicates that creatine may improve net nitrogen status by increasing protein synthesis and/or decreasing protein degradation [44]. With such limited data available, more research with larger numbers of subjects is needed before sufficient conclusions can be drawn.

What are the recommended doses?

Low doses (1 gram of creatine monohydrate or less in water) produce only a modest rise in the plasma creatine concentration [45]. Dosages of 5 grams result in plasma creatine concentrations of about 800 micromoles per liter. Repeated dosing of 5 grams maintains the plasma concentrations around 1000 micromoles per liter. In some people, total creatine stores can be increased as much as 50%. Creatine uptake into the muscle is greatest during the first two days. During the initial ingestion of 30 grams of creatine per day, the kidneys will excrete about 40% on the first day, 61% on the second day, and 68% of the creatine dose on the third day [45]. Several studies have reported that the ingestion of 20-30 grams of creatine per day in divided dosages elevates creatine stores [45-48]. This practice has been termed "loading." Research has also established that ingestion of 20 grams of creatine for 6 days followed by ingestion of 2 grams per day thereafter is sufficient to maintain creatine stores [46]. The researchers estimated that this would equal dosages of .3 grams per kilogram of bodyweight for loading and .03 grams per kilogram per day for maintenance dosages. Another alternative was to simply ingest 3 grams of creatine per day, which would result in similar creatine levels as a loading and maintenance schedule, although at a slower rate [46]. Based on this data it appears that loading is not necessary for long term benefits of creatine. One factor to consider, though, is that it takes longer to experience maximal gains when one does not load. This may not be beneficial for athletes competing in sports with a defined period of time to reach top performance levels. The necessity of loading versus not loading should be considered on an individual basis. Another strategy suggested by Plisk and Kreider is to vary the number of creatine dosages in a zig-zag fashion [49]. While not supported by scientific research, the proposed strategy is in line with current concepts of periodizing nutrition in relationship to training. This area is still largely unexplored by researchers. Assuming a serving contains about 5 grams of creatine, then an athlete could adhere to the following schedule [49]:

  Sun Mon Tues Wed Thurs Fri Sat
   Lower Upper   Lower Upper  
Creatine Servings   Heavy   Explosive  
BM > 100 kg 0 3 2 1 3 2 1
BM < 100 kg 0 2 1 0 2 1 0

It was also reported by other investigators that 93 grams of a simple sugar solution containing glucose along with 5 grams of creatine would augment the skeletal muscle creatine accumulation [50, 51]. More recently it has also been reported that 33 grams of glucose with 5.25 grams of creatine improved bench press strength, vertical jump, 100-yard dash time and fat-free weight in football players better than creatine alone [52].

Does creatine use have to be cycled?

Twenty-eight days without creatine supplementation is a sufficient time to return intramuscular creatine stores to their starting levels [35, 47]. So __far no studies on humans have examined the effects of creatine cycling. Various anecdotal recommendations have been made to cycle creatine using different strategies, yet without research to compare these different strategies, the effectiveness of one over the other is debatable. Research on rats examining the effect of creatine on creatine transport proteins has led the authors to recommend creatine use to be limited to three months or less, followed by a one month lay-off from creatine [53]. Until more applicable research becomes available, this advice (based on animal data) is the best information available.

Are all creatine supplements the same?

Presently there are numerous creatine products on the market. Supplement companies make incredible claims that are mostly unsubstantiated. Creatine monohydrate in a powder form is the supplement used in most research studies. Supplement companies have made claims that creatine citrate, creatine phosphate, and creatine combined with other agents (ie ribose) enhances performance better than creatine monohydrate. This is unsupported by research thus __far . Only simple sugars such as dextrose, or mixtures containing dextrose, have been reported to increase the effects of creatine. One study indicates that caffeine may decrease the effects of creatine [54]. While this remains to be verified by additional research, it may seem prudent at this point to avoid ingestion of caffeine products and creatine in combination.

Effervescent creatine, creatine suspensions, and liquid creatine are other forms of creatine being marketed to consumers. There is no published evidence at this time that effervescent creatine works better than creatine monohydrate powder. Creatine suspension and liquid creatine manufacturers claim to have stabilized creatine in a liquid medium, yet this has not been verified by any published research. Claims in supplement ads for these products state that most of the creatine is rapidly converted into creatinine in the gut, yet recent evidence does not support this [55]. In fact, the conversion of creatine to creatinine in humans is considered negligible following the first 6 hours of ingestion, although additional research is required to examine longer time periods of creatine on creatinine metabolism. When one considers the cost of these products versus the costs of creatine monohydrate powder, it would seem unnecessary to spend additional money for products not proven any more effective.

Does it benefit all populations?

Several reviews have been published which address the types of conditions that creatine supplementation may benefit [1, 56-63]. The reader is referred to these reviews for additional information. In general, research indicates that men and women should respond in a similar fashion to creatine ingestion. Research indicates that creatine monohydrate supplementation augments gains in resistance exercise in men [36] and women [35]. Research on adults over 60 years of age indicates that creatine supplementation may delay fatigue, but does not affect body composition or strength alone [64], or in conjunction with resistance exercise [65]. These studies administered creatine with 7-8 grams of dextrose/glucose per serving. Other research using younger individuals indicates that 33 grams of dextrose per serving [52] or 93 grams of simple sugars [50, 51] may augment the effects of creatine. The difference in calorie intakes between these studies of older and younger adults range from 400 to 1376 kilocalories per day. The younger adults received 2000-6880 more kilocalories over 5 days [50-52] than the older adults [64, 65]. It is conceivable that if either extra sugars and/or calories were administered with the creatine, the older subjects would have experienced similar improvements.

Research on other populations includes various athletic groups. Creatine supplementation was reported to increase multiple sprint performance in ice hockey players [66], increase fat-free mass, vertical jump, strength, and sprint speed in football players [34, 52, 67], and increase lean body mass, vertical jump, power output, and work capacity in track and field athletes [68]. Creatine supplementation for five days in rowers improved whole body creatine stores, resulting in improvements in performance that were not statistically significant [69]. One would expect that with a longer training period, the interaction between creatine and row-training would produce results superior to row-training alone.

In contrast to studies reporting positive results for some athletic groups, research on swimmers indicates that creatine supplementation may decrease or not affect performance, presumably by increasing body mass [70-77]. Creatine supplementation was also shown to decrease 6 km run times, presumably by increasing body mass [31]. One strategy considered was the effects of 6 grams of creatine on anaerobic performance in triathletes [78]. The idea is that the lower dose may not increase body mass as rapidly, while at the same time allow the athletes to train at higher intensity levels. Over time this may lead to improved performance if body mass does not increase substantially. Creatine did improve anaerobic performance with this strategy, but it is not known if this transfers to improved performance in the triathlon.

Are there any side-effects or known health risks?

The only consistent side-effect of creatine supplementation is weight gain. Numerous studies and reviews have reported no harmful side-effects [33-37, 79, 80]. Critics against creatine supplementation cite the possibility of renal dysfunction and muscle cramps. Several studies and abstracts have investigated the effects of creatine on renal function [34, 35, 45, 46, 69, 80-82]. None of the aforementioned studies reported any effects of creatine monohydrate supplementation on renal function. The highest dosage reported in these studies under controlled conditions was 15.75 grams per day for 28 days [34]. The highest reported dosage in these studies for athletes self-administering creatine was 10 grams per day for 5 years and 30 grams per day for one year [80]. In contrast with these studies, case reports have been made implicating creatine in renal dysfunction [83-85]. In one case, an existing renal dysfunction existed prior to creatine use [85] and in the other two cases, dosages of 20 grams per day for 4 weeks were ingested [83, 84]. These reports raise the possibility of a dose response effect to creatine in some individuals. As a safety precaution, creatine users may consider either loading for five days followed by a maintenance dosage or ingesting dosages less than 10 grams per day. In other research, 20 grams per day for five days did not affect hematocrit or any of the liver enzymes measured (ASAT, ALAT, GT, CK, LDH) [33]. For individuals concerned with renal side effects from taking creatine monohydrate, the consistent monitoring of creatinine clearance and albumin excretion will provide information on renal function. These tests, while not perfect, are not invasive or expensive and could be used to estimate potential early renal impairment. It should be noted that no reports have been made for renal impairment at dosages less than or equal to 15.75 grams of creatine monohydrate per day. Another area of filled with anecdotal reports is creatine-induced muscle cramps. Preliminary evidence indicates that creatine monohydrate supplementation of 20 grams per day for five days does not affect plasma volume or serum electrolyte and mineral balance during acute dehydration [86]. Under similar conditions, 3 out of 7 subjects receiving creatine reported muscle cramping or excessive muscle tightness versus 1 out of 9 placebo subjects [87]. The low subject number of this report makes it difficult to interpret this data. In other preliminary research using a much larger sample size (53 subjects) involving college football players during pre-season conditioning, creatine supplementation did not affect markers of fluid or electrolyte status [88]. Research using much larger sample sizes during field conditions (as opposed to laboratory conditions) appears warranted to investigate the possibility of cramping. To date no peer-reviewed studies have reported an increase in cramping after creatine ingestion and the information thus __far is anecdotal or preliminary.

One other area of concern focuses on the quality of supplements in general. With so many different products on the market, many times the consumer is faced with difficult decisions. Exaggerated marketing claims and product endorsements further cloud the issues. Consumers need to be cautious in general when purchasing dietary supplements because of the lack of regulatory control over product quality. To date, only carbohydrate ingestion has been shown to increase creatine uptake [50, 51]. Alpha lipoic acid, vanadyl sulfate, Kreb's cycle intermediates, chromium picolinate, and other supplements marketed with creatine have not been reported in peer-reviewed studies to increase creatine uptake.

Creatine and diseases

Since creatine impacts the phosphocreatine energy system, it has the potential to positively affect a number of diseases where energy metabolism is impaired. Several papers have been published detailing the effects of creatine supplementation for individuals afflicted with inborn errors of creatine synthesis [89-94]. Creatine supplementation of patients with gyrate atrophy of the choroid and retina reported promising preliminary results [95]. Longer term studies indicated that creatine supplementation may slow down the progression of gyrate atrophy in some individuals with an arginine restricted diet [96, 97] and normalize muscle concentrations of creatine [98].

Other research has shown that creatine supplementation can improve strength and endurance in individuals with chronic heart failure by increasing creatine phosphate stores in skeletal muscle [99, 100]. Creatine may also have some value in controlling blood lipids in hyperlipidemia [101] and increasing strength in individuals with mitochondrial cytopathies [102] and neuromuscular disease [103]. These studies are very promising, but should be interpreted as preliminary information until more research is available. individuals with the above conditions should discuss creatine use with their physician prior to ingestion.

Other research has indicated that creatine supplementation increases brain concentrations of creatine [104]. The increases vary by region of the brain. This is certainly expected, as creatine ingestion elevates blood concentrations, which in turn elevate tissue concentrations. Based on animal data, this may provide some protection to the brain during periods of reduced blood flow, such as during a stroke [105]. Research in humans is needed to confirm this possible protective role of creatine.

Where can I go for more information?

Numerous reviews have appeared on creatine supplementation [1, 56-63]. These reviews provide an overall view of the research and point out limitations in the present body of knowledge. Several organizations have been involved in publishing creatine-related research and may provide additional information at their web sites:
  1. The American College of Sports Medicine (ACSM)
  2. The National Strength & Conditioning Association (NSCA)
  3. The American Dietetic Association (ADA)

For databases containing research information:

  1. Internet Grateful Med
  2. Office of Dietary Supplements
   Researchers that have published studies accessible on these sites include: Almada, Earnest, Greenhaff, Kreider, Stout, and Volek.

What's the simple story on creatine?

The simple story on creatine is that people can either take 5 grams, 4 times per day for 5 days and then maintain with 2 grams per day, or take 3 grams per day. A lack of information exists on cycling, so 3 months on creatine and 1 month off creatine is the most prudent advice at this point. Individuals supplementing with creatine can expect gains in strength when combined with resistance exercise. Improvements in jumping and short-term sprint abilities should also be expected. Simple sugars like dextrose/glucose will increase the effects of creatine. Since these are fairly high glycemic agents, the optimal time to ingest a creatine/sugar drink is immediately after a training session.

References

  1. Balsom, P.D., K. Soderlund, and B. Ekblom, Creatine in humans with special reference to creatine supplementation. Sports Med, 1994. 18(4): p. 268-280.
  2. Chanutin, A. and L. Guy, The fate of creatine when administered to man. J Biol Chem, 1926. 67: p. 29-41.
  3. Delanghe, J., et al., Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians [letter]. Clin Chem, 1989. 35(8): p. 1802-1803.
  4. Moller, P., et al., Effect of aging on energy-rich phosphagens in human skeletal muscles. Clin Sci, 1980. 58(6): p. 553-555.
  5. Rehunen, S. and M. Harkonen, High-energy phosphate compounds in human slow-twitch and fast-twitch muscle fibres. Scand J Clin Lab Invest, 1980. 40(1): p. 45-54.
  6. Rehunen, S., et al., High-energy phosphate compounds during exercise in human slow-twitch and fast-twitch muscle fibres. Scand J Clin Lab Invest, 1982. 42(6): p. 499-506.
  7. Bergstrom, J., et al., Preliminary studies of energy-rich phosphagens in muscle from severely ill patients. Crit Care Med, 1976. 4(4): p. 197-204.
  8. Gertz, I., et al., Muscle metabolism in patients with chronic obstructive lung disease and acute respiratory failure. Clin Sci Mol Med, 1977. 52(4): p. 396-403.
  9. Jakobsson, P., L. Jorfeldt, and A. Brundin, Skeletal muscle metabolites and fibre types in patients with advanced chronic obstructive pulmonary disease (COPD), with and without chronic respiratory failure. Eur Respir J, 1990. 3(2): p. 192-196.
  10. Karlsson, J., et al., Skeletal muscle metabolites in patients with cardiogenic shock or severe congestive heart failure. Scand J Clin Lab Invest, 1975. 35(1): p. 73-79.
  11. Moller, P., et al., Energy-rich phosphagens, electrolytes and free amino acids in leg skeletal muscle of patients with chronic obstructive lung disease. Acta Med Scand, 1982. 211(3): p. 187-193.
  12. Nordemar, R., et al., Muscle ATP content in rheumatoid arthritis--a biopsy study. Scand J Clin Lab Invest, 1974. 34(2): p. 185-191.
  13. Tarnopolsky, M.A. and G. Parise, Direct measurement of high-energy phosphate compounds in patients with neuromuscular disease. Muscle Nerve, 1999. 22(9): p. 1228-1233.
  14. Grimby, G., et al., Metabolic effects of isometric training. Scand J Clin Lab Invest, 1973. 31(3): p. 301-305.
  15. Houston, M.E. and J.A. Thomson, The response of endurance-adapted adults to intense anaerobic training. Eur J Appl Physiol, 1977. 36(3): p. 207-213.
  16. Karlsson, J., et al., Muscle lactate, ATP, and CP levels during exercise after physical training in man. J Appl Physiol, 1972. 33(2): p. 199-203.
  17. Hoberman, H., E. Sims, and J. Peters, Creatine and creatinine metabolism studied in the normal male adult studied with the aid of isotopic nitrogen. J Biol Chem, 1948. 172: p. 45-58.
  18. Hoogwerf, B.J., D.C. Laine, and E. Greene, Urine C-peptide and creatinine (Jaffe method) excretion in healthy young adults on varied diets: sustained effects of varied carbohydrate, protein, and meat content. Am J Clin Nutr, 1986. 43(3): p. 350-360.
  19. Crim, M.C., D.H. Calloway, and S. Margen, Creatine metabolism in men: urinary creatine and creatinine excretions with creatine feeding. J Nutr, 1975. 105(4): p. 428-438.
  20. Meyer, R.A., H.L. Sweeney, and M.J. Kushmerick, A simple analysis of the "phosphocreatine shuttle". Am J Physiol, 1984. 246(5 Pt 1): p. C365-C377.
  21. Storey, K.B. and P.W. Hochachka, Activation of muscle glycolysis: a role for creatine phosphate in phosphofructokinase regulation. FEBS Lett, 1974. 46(1): p. 337-339.
  22. Vandenberghe, K., et al., Phosphocreatine resynthesis is not affected by creatine loading. Med Sci Sports Exerc, 1999. 31(2): p. 236-242.
  23. Kreis, R., et al., Creatine supplementation--part II: in vivo magnetic resonance spectroscopy. Med Sci Sports Exerc, 1999. 31(12): p. 1770-1777.
  24. Smith, S.A., et al., Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study. J Appl Physiol, 1999. 87(1): p. 116-123.
  25. Stout, J., et al., Effect of creatine loading on neuromuscular fatigue threshold [In Process Citation]. J Appl Physiol, 2000. 88(1): p. 109-112.
  26. Tesch, P.A., A. Thorsson, and N. Fujitsuka, Creatine phosphate in fiber types of skeletal muscle before and after exhaustive exercise. J Appl Physiol, 1989. 66(4): p. 1756-1759.
  27. Soderlund, K., P.L. Greenhaff, and E. Hultman, Energy metabolism in type I and type II human muscle fibres during short term electrical stimulation at different frequencies. Acta Physiol Scand, 1992. 144(1): p. 15-22.
  28. Hirvonen, J., et al., Breakdown of high-energy phosphate compounds and lactate accumulation during short supramaximal exercise. Eur J Appl Physiol, 1987. 56(3): p. 253-259.
  29. Hirvonen, J., et al., Fatigue and changes of ATP, creatine phosphate, and lactate during the 400-m sprint. Can J Sport Sci, 1992. 17(2): p. 141-144.
  30. Earnest, C.P., et al., The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand, 1995. 153(2): p. 207-209.
  31. Balsom, P.D., et al., Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand, 1993. 149(4): p. 521-523.
  32. Francaux, M. and J.R. Poortmans, Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol, 1999. 80(2): p. 165-168.
  33. Kamber, M., et al., Creatine supplementation--part I: performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc, 1999. 31(12): p. 1763-1769.
  34. Kreider, R.B., et al., Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc, 1998. 30(1): p. 73-82.
  35. Vandenberghe, K., et al., Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol, 1997. 83(6): p. 2055-2063.
  36. Volek, J.S., et al., Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc, 1999. 31(8): p. 1147-1156.
  37. Volek, J.S., et al., Creatine supplementation enhances muscular performance during high- intensity resistance exercise. J Am Diet Assoc, 1997. 97(7): p. 765-770.
  38. Balsom, P., et al., Creatine supplementation and dynamic high intensity intermittent exercise. Scand J Med Sci Sports, 1993. 3: p. 143-149.
  39. Ingwall, J.S., M.F. Morales, and F.E. Stockdale, Creatine and the control of myosin synthesis in differentiating skeletal muscle. Proc Natl Acad Sci U S A, 1972. 69(8): p. 2250-2253.
  40. Ingwall, J.S., et al., Specificity of creatine in the control of muscle protein synthesis. J Cell Biol, 1974. 62(1): p. 145-151.
  41. Ingwall, J.S., Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res, 1976. 38(5 Suppl 1): p. I115-I123.
  42. Ingwall, J.S. and K. Wildenthal, Role of creatine in the regulation of cardiac protein synthesis. J Cell Biol, 1976. 68(1): p. 159-163.
  43. Hofmann, W.W., J. Butte, and H.A. Leon, Relationship of intracellular creatine concentration and uptake to muscle mass in vivo. Am J Physiol, 1978. 235(5): p. C199-C203.
  44. Ziegenfuss, T., et al., Acute creatine ingestion: Effects on muscle volume, anaerobic power, fluid volumes, and protein turnover. Med Sci Sports Exerc, 1997. 29: p. S127.
  45. Harris, R.C., K. Soderlund, and E. Hultman, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Colch), 1992. 83(3): p. 367-374.
  46. Hultman, E., et al., Muscle creatine loading in men. J Appl Physiol, 1996. 81(1): p. 232-237.
  47. Febbraio, M.A., et al., Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans. Acta Physiol Scand, 1995. 155(4): p. 387-395.
  48. Greenhaff, P.L., et al., Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol, 1994. 266: E725-E730.
  49. Plisk, S. and R. Kreider, Creatine controversy? Strength Cond J, 1999. 21(1): p. 14-23.
  50. Green, A.L., et al., Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am J Physiol, 1996. 271(5 Pt 1): p. E821-E826.
  51. Green, A.L., et al., Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand, 1996. 158(2): p. 195-202.
  52. Stout, J., et al., Effects of 8 weeks of creatine supplementation on exercise performance and fat-free weight in football players during training. Nutr Res, 1999. 19(2): p. 217-225.
  53. Guerrero-Ontiveros, M.L. and T. Wallimann, Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle. Mol Cell Biochem, 1998. 184(1-2): p. 427-437.
  54. Vandenberghe, K., et al., Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol, 1996. 80(2): p. 452-457.
  55. Schedel, J.M., et al., Acute creatine ingestion in human: consequences on serum creatine and creatinine concentrations. Life Sci, 1999. 65(23): p. 2463-2470.
  56. Kraemer, W.J. and J.S. Volek, Creatine supplementation. Its role in human performance. Clin Sports Med, 1999. 18(3): p. 651-666.
  57. Jacobs, I., Dietary creatine monohydrate supplementation. Can J Appl Physiol, 1999. 24(6): p. 503-514.
  58. Graham, A.S. and R.C. Hatton, Creatine: a review of efficacy and safety. J Am Pharm Assoc (Wash), 1999. 39(6): p. 803-810; quiz 875-877.
  59. Demant, T.W. and E.C. Rhodes, Effects of creatine supplementation on exercise performance. Sports Med, 1999. 28(1): p. 49-60.
  60. Williams, M.H. and J.D. Branch, Creatine supplementation and exercise performance: an update [see comments]. J Am Coll Nutr, 1998. 17(3): p. 216-234.
  61. Juhn, M.S. and M. Tarnopolsky, Oral creatine supplementation and athletic performance: a critical review [published erratum appears in Clin J Sport Med 1999 Apr;9(2):62]. Clin J Sport Med, 1998. 8(4): p. 286-297.
  62. Volek, J. and W. Kraemer, Creatine supplementation: Its effect on human muscular performance and body composition. J Strength and Cond Res, 1996. 10: p. 200-210.
  63. Kreider, R., Creatine supplement: analysis of ergogenic value, medical safety, and concerns. Journal of Exercise Physiology, JEP online, 1998. 1(1): p. 1-11; http:
  64. Rawson, E.S., M.L. Wehnert, and P.M. Clarkson, Effects of 30 days of creatine ingestion in older men. Eur J Appl Physiol, 1999. 80(2): p. 139-144.
  65. Bermon, S., et al., Effects of creatine monohydrate ingestion in sedentary and weight- trained older adults. Acta Physiol Scand, 1998. 164(2): p. 147-155.
  66. Jones, A.M., T. Atter, and K.P. Georg, Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players. J Sports Med Phys Fitness, 1999. 39(3): p. 189-196.
  67. Stone, M.H., et al., Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr, 1999. 9(2): p. 146-165.
  68. Kirksey, B., et al., The effects of 6 weeks of creatine monohydrate supplementation on performance measures and body composition in collegiate track and field athletes. J Strength Cond Re, 1999. 13: p. 148-156.
  69. Rossiter, H.B., E.R. Cannell, and P.M. Jakeman, The effect of oral creatine supplementation on the 1000-m performance of competitive rowers. J Sports Sci, 1996. 14(2): p. 175-179.
  70. Theodorou, A.S., et al., The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading. J Sports Sci, 1999. 17(11): p. 853-859.
  71. Peyrebrune, M.C., et al., The effects of oral creatine supplementation on performance in single and repeated sprint swimming. J Sports Sci, 1998. 16(3): p. 271-279.
  72. Grindstaff, P.D., et al., Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int J Sport Nutr, 1997. 7(4): p. 330-346.
  73. Mujika, I., et al., Creatine supplementation does not improve sprint performance in competitive swimmers. Med Sci Sports Exerc, 1996. 28(11): p. 1435-1441.
  74. Thompson, C.H., et al., Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers. Br J Sports Med, 1996. 30(3): p. 222-225.
  75. Burke, L.M., D.B. Pyne, and R.D. Telford, Effect of oral creatine supplementation on single-effort sprint performance in elite swimmers. Int J Sport Nutr, 1996. 6(3): p. 222-233.
  76. Oopik, V., et al., Effect of creatine administration on blood urea level and postexercise glycogen repletion in liver and skeletal muscle in rats. Ann Nutr Metab, 1996. 40(6): p. 359-363.
  77. Leenders, N.M., D.R. Lamb, and T.E. Nelson, Creatine supplementation and swimming performance. Int J Sport Nutr, 1999. 9(3): p. 251-262.
  78. Engelhardt, M., et al., Creatine supplementation in endurance sports. Med Sci Sports Exerc, 1998. 30(7): p. 1123-1129.
  79. Maughan, R.J., Creatine supplementation and exercise performance. Int J Sport Nutr, 1995. 5(2): p. 94-101.
  80. Poortmans, J.R. and M. Francaux, Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc, 1999. 31(8): p. 1108-1110.
  81. Earnest, C., A. Almada, and T. Mitchell, Influence of chronic creatine supplementation on hepatorenal function. FASEB J, 1996. 10: p. A790.
  82. Poortmans, J.R., et al., Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol, 1997. 76(6): p. 566-567.
  83. Koshy, K.M., E. Griswold, and E.E. Schneeberger, Interstitial nephritis in a patient taking creatine [letter]. N Engl J Med, 1999. 340(10): p. 814-815.
  84. Kuehl, K., L. Goldberg, and D. Elliot, Renal insufficiency after creatine supplementation in a college football athlete. Med Sci Sports Exer, 1998. 30: p. S235.
  85. Pritchard, N.R. and P.A. Kalra, Renal dysfunction accompanying oral creatine supplements [letter] [see comments]. Lancet, 1998. 351(9111): p. 1252-1253.
  86. McArthur, P., et al., Creatine supplementation and acute dehydration. Med Sci Sports Exerc, 1999. 31: p. S263.
  87. Webster, M., et al., Creatine supplementation: Effect on exercise performance at two levels of acute dehydration. Med Sci Sports Exerc, 1999. 31: p. S265.
  88. Rasmussen, C., et al., Creatine supplementation during pre-season football training does not affect fluid or electrolyte status. Med Sci Sports Exerc, 1999. 31: p. S299.
  89. Stockler, S., et al., Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res, 1994. 36(3): p. 409-413.
  90. Stockler, S., F. Hanefeld, and J. Frahm, Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet, 1996. 348(9030): p. 789-790.
  91. Stockler, S., et al., Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet, 1996. 58(5): p. 914-922.
  92. Stockler, S., et al., Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism, 1997. 46(10): p. 1189-1193.
  93. Stockler, S. and F. Hanefeld, Guanidinoacetate methyltransferase deficiency: a newly recognized inborn error of creatine biosynthesis. Wien Klin Wochenschr, 1997. 109(3): p. 86-88.
  94. Stockler-Ipsiroglu, S., Creatine deficiency syndromes: a new perspective on metabolic disorders and a diagnostic challenge [editorial; comment]. J Pediatr, 1997. 131(4): p. 510-511.
  95. Sipila, I., et al., Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. N Engl J Med, 1981. 304(15): p. 867-870.
  96. Vannas-Sulonen, K., et al., Gyrate atrophy of the choroid and retina. A five-year follow-up of creatine supplementation. Ophthalmology, 1985. 92(12): p. 1719-1727.
  97. Nanto-Salonen, K., et al., Reduced brain creatine in gyrate atrophy of the choroid and retina with hyperornithinemia [see comments]. Neurology, 1999. 53(2): p. 303-307.
  98. Heinanen, K., et al., Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia. Eur J Clin Invest, 1999. 29(12): p. 1060-1065.
  99. Andrews, R., et al., The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure [see comments]. Eur Heart J, 1998. 19(4): p. 617-622.
  100. Gordon, A., et al., Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance [see comments]. Cardiovasc Res, 1995. 30(3): p. 413-418.
  101. Earnest, C.P., A.L. Almada, and T.L. Mitchell, High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci (Colch), 1996. 91(1): p. 113-118.
  102. Tarnopolsky, M.A., B.D. Roy, and J.R. MacDonald, A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies [see comments]. Muscle Nerve, 1997. 20(12): p. 1502-1509.
  103. Tarnopolsky, M. and J. Martin, Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology, 1999. 52(4): p. 854-857.
  104. Dechent, P., et al., Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol, 1999. 277(3 Pt 2): p. R698-R704.
  105. Wick, M., et al., Brain water diffusion in normal and creatine-supplemented rats during transient global ischemia. Magn Reson Med, 1999. 42(4): p. 798-802.

Copyright ©2000 by Lean Bodies, Inc. All rights reserved.

    

Lean Bodies
Phone 908-688-9392
E-Mail info@leanbodies.net

Customized Fitness Programs | Personal Training New Jersey | Pro Shop

Home | Search Engine | Professional Registry | About Lean Bodies
Tips | Fitness Forum | FAQ | Disclaimer
Testimonials | Before & After | Professional Locator | Add Url

Copyright © 2000 Lean Bodies, Inc. All Rights Reserved