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EricT · 10-26-2006, 09:08 AM

I thought I may as well put up a relevant part of this article I linked in the Creatine FAQ:

http://www.mesomorphosis.com/articles/kreider/creatine.htm#Does%20Creatine%20Enhance%20Exercise% 20Performance?

Clinical Effects of Creatine Supplementation

When someone takes a 5 g dose of creatine, serum creatine levels typically increase for several hours.7,47,72 This is why during the loading phase creatine should be ingested every 4 to 6 hours (4 to 5 times per day). Creatine storage into the muscle primarily occurs during the first several days of creatine supplementation.47,91 Thereafter, excess creatine that is ingested is primarily excreted as creatine in the urine with small amounts converted to creatinine and urea.7,17,47,91 Serum creatinine levels have been reported to be either not affected 2,25 or slightly increased 64,95 following 28-d, 64 56-d 2,25 and 365-d 95 of creatine supplementation. The increased serum and urinary creatinine have been suggested to reflect an increased release and cycling of intramuscular creatine as a consequence of enhanced muscle protein turnover in response to creatine supplementation and not of pathologic origin.7,25,47,59 Yet, these increases have been a source of concern by some physicians in case reports of an athlete68 or a patient with renal disease88 taking creatine. The reason for this is that large elevations in serum and urinary creatinine levels are basic markers of tissue degradation and/or kidney stress. However, these reports have been criticized because intense exercise and dehydration increases serum and urinary creatinine levels.41 Consequently, in people who exercise, these increases reflect a greater breakdown of muscle protein and are completely normal. It makes sense then that if creatine supplementation allows an athlete to train harder, creatinine levels may be slightly elevated as the athlete may experience greater net protein degradation. Some studies which have administered creatine to athletes during training have reported slight increases in serum creatinine (e.g. 1.2 to 1.4 µmol/L).64 Interestingly though, several studies which involved creatine supplementation without training have found no effects on serum or urinary creatinine levels.75 These findings provide some indirect evidence that the elevations in creatinine are related to a greater ability to train harder rather than of pathological origin.

Along these same lines, several studies have evaluated the effects of creatine supplementation on muscle and liver enzyme levels. Muscle and liver enzymes increase in response to exercise training. These enzymes may also be elevated in response to degenerative muscle and/or liver disease. Studies show that creatine supplementation either has no effect 2,95 or may moderately increase creatine kinase (CK), 2,64 lactate dehydrogenase (LDH),64 and/or aspartate amino transferase (AST)64 levels following 28-d and 56-d of supplementation. The increased CK, LDH and AST levels reported following creatine supplementation were within normal limits for athletes engaged in heavy training and may reflect a greater concentration/activity of CK and/or ability to maintain greater training volume.7,59,60,121 Interestingly, in studies in which creatine was administered in subjects not undergoing intense training, creatine supplementation does not appear to affect serum muscle enzyme efflux.2,69,70,75

Creatine supplementation has also been reported to positively affect lipid profiles in middle-aged male and female hypertriglyceremic patients 25 and trained male athletes.64 In this regard, Earnest and colleagues 25 reported that 56-d of creatine supplementation resulted in significant decreases in total cholesterol (-5 and -6% at day 28 and 56, respectively) and triglycerides (-23 and -22% at day 28 and 56, respectively) in mildly hypertriglyceremic patients. A similar response was observed with very low density lipoproteins (VLDL). In addition, Kreider and coworkers 64 reported that 28-d of creatine supplementation increased high density lipoproteins (HDL) by 13%, while decreasing VLDL (-13%) and the ratio of total cholesterol to HDL (-7%). Although additional research is necessary, these findings suggest that creatine supplementation may posses health benefit by improving blood lipid profiles.

An extensive amount of research has been conducted on the potential medical benefits of intravenous PCr administration and oral creatine supplementation. In this regard, intravenous PCr administration has been reported to improve myocardial metabolism and reduced the incidence of ventricular fibrillation in ischemic heart patients.3,19,20,83,93,118,119 The reason for this is that PCr appears to enhance the viability of the ischemic cell membrane thereby minimizing injury cell during ischemia. Consequently, there has been interest in determining the effects of oral creatine supplementation on heart function and exercise capacity in patients with heart disease. Gordon and associates 38 reported that creatine supplementation (20 g/d for 10-d) did not improve ejection fraction in heart failure patients with an ejection fraction less than 40%. However, creatine supplementation significantly increased one legged knee extension exercise performance (21%), peak torque (5%) and cycle ergometry performance (10%).

Creatine supplementation has also been used to treat patients with mitochondrial cytopathies (a condition which reduces exercise capacity) and infants with in-born errors in creatine synthesis. For example, Tarnapolosky et al.107 reported that creatine supplementation (5 g/d for 14-d followed by 2 g/d for 7-d) significantly increased anaerobic and high-intensity aerobic exercise capacity in patients with mitochondrial cytopathy. Moreover, several case reports have been published in the medical literature which indicate that creatine supplementation (4 to 8 g/d for up to 25 months) allows infants with inborn errors in creatine synthesis to develop more mentally and physically normal.4,34,99-103 Collectively, these findings suggest that intravenous PCr administration and/or oral creatine supplementation for up to 25 months in duration is safe and may posses some therapeutic value to certain patient populations.

What’s the bottom line? If you take creatine your serum and urinary creatine levels will increase for several hours after supplementation. Without training, there appears to be little if any impact on serum and urinary creatinine, muscle and liver enzymes, or blood pressure.75,84 However, if you take creatine during training you may observe an increase in serum creatinine, CK, LDH and possibly AST. These elevations appear to be related to excess creatine being excreted and/or due to a greater ability to train harder following creatine supplementation. You may also experience some positive effects on your blood lipid profiles. Although additional research is necessary to evaluate the long-term effects of creatine supplementation on medical status, available studies suggest that creatine supplementation for up to 2 years is medically safe and may provide health benefit for various populations when taken at dosages described in the literature.

Side Effects

The only side effect reported from clinical studies investigating dosages of 1.5 to 25 g/d for 3- to 365-days in preoperative and post-operative patients, untrained subjects, and elite athletes has been weight gain.7,59,60,121 However, a number of concerns about possible side effects of creatine supplementation have been mentioned in lay publications, supplement advertisements, and on Internet mailing lists. It should be noted that these concerns emanate from unsubstantiated anecdotal reports and may be unrelated to creatine supplementation. There is no evidence from any well-controlled clinical study indicating that creatine supplementation causes any of these side effects. However, one must also consider that although researchers are required to report side effects in scientific publications, few long-term studies on creatine supplementation have been conducted. Consequently, discussion about possible side effects is warranted.

Some concern has been raised whether creatine supplementation may suppress endogenous creatine synthesis. Studies have reported that it takes about four weeks after cessation of creatine supplementation for muscle creatine 32 and phosphocreatine 115 levels to return to normal. While it is unclear whether muscle creatine or phosphocreatine content falls below normal thereafter, there is no evidence that creatine supplementation causes a long-term suppression of creatine synthesis.7,50

Since creatine is an amino acid, it has been suggested that creatine supplementation may increase renal stress or cause liver damage. However, no studies have reported clinically significant elevations in liver enzymes in response to creatine supplementation.2,64 Further, Poortmans and colleagues 86 reported that short-term creatine supplementation (20 g/d for 5-d) does not affect markers of renal stress. Moreover, preliminary results reported at the 1998 American College of Sports Medicine annual meeting from this group indicate that longer term creatine supplementation (9 weeks) does not affect markers of renal stress. Consequently, there is no evidence that creatine supplementation increases renal stress when taken at recommended dosages.

There have also been some anecdotal claims that athletes training hard in hot or humid conditions may experience a greater incidence of severe muscle cramps and/or muscle injury when taking creatine. However, no study has reported that creatine supplementation causes cramping, dehydration, changes in electrolyte concentrations, or increases susceptibility to muscle strains/pulls even though some of these studies have evaluated highly trained athletes undergoing intense training 14,36,45,48,57,61,63-66,73,78,91,104,110,116 in hot/humid environments. 36,61,63,65,104 For example, data that we recently presented at the 1998 National Strength and Conditioning Association indicated no reports of muscle cramping or injury in athletes involved in our previous creatine studies.67 Most creatine researchers feel that these observations are overblown.

Finally, concern has been expressed regarding unknown long-term side effects. While long-term (> 1 year) well-controlled clinical trials have yet to be performed, it should be noted that athletes have been using creatine as a nutritional supplement since the mid 1960s. Yet, this author is not aware of any significant medical complications that have been directly linked to creatine supplementation. Additionally, preliminary data presented at the 1998 American College of Sports Medicine Annual Meeting from Dr. Mike Stone’s laboratory indicate that long-term creatine supplementation (up to 2 years) does not result in any abnormal clinical outcome in comparison to controls. Consequently, from the literature currently available, creatine supplementation appears to be medically safe when taken at dosages described in the literature.

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Summary and Conclusions

Based on available research, short-term creatine supplementation may improve maximal strength/power by 5 to 15%, work performed during sets of maximal effort muscle contractions by 5 to 15%, single-effort sprint performance by 1 to 5%, and work performed during repetitive sprint performance by 5 to 15%. Moreover, long-term supplementation of creatine or creatine containing supplements (15 to 25 g/d for 5 to 7-d and 2 to 25 g/d thereafter for 7 to 140-d) may promote significantly greater gains in strength, sprint performance, and fat free mass during training in comparison to matched-paired controls. However, not all studies have reported ergogenic benefit possibly due to differences in subject response to creatine supplementation, length of supplementation, exercise criterion evaluated, and/or the amount of recovery observed during repeated bouts of exercise. The only side effect from creatine supplementation reported in the scientific literature from studies lasting up to two years in non-athletes, athletes, and patient populations has been weight gain. Consequently, creatine supplementation appears to be a safe and effective nutritional strategy to enhance exercise performance and promote muscle hypertrophy.

Please send us your feedback on this article.

Richard B. Kreider, PhD, FACSM
rkreider@memphis.edu