Creatine Research Update
Chester J. Zelasko, Ph.D. | October 25, 2006

Anabolic steroids and human growth hormone (HGH) have been in the news since professional athletes have been caught using these drugs to enhance performance. Journalists and healthcare professionals seem to have lumped creatine into that group in their published discussions and recommendations, and as a result, we’ve been getting numerous questions about the safety of creatine. It’s time to update the information in our last Newsletter about the subject, Creatine: Not Just for Weight Training (September 16, 2003), with the research that’s been done since then.

Defining Anabolic
The primary difference between performance enhancing drugs and creatine is that they are anabolic and creatine is not. Anabolic means to build up--as it relates to athletics, it means to build up muscle mass. Both steroids and HGH are anabolic in nature. Creatine, on the other hand, is not anabolic--its primary role in muscle is to produce energy as part of the immediate-energy system. In fact, 94% of all creatine is found in muscle tissue.

While not anabolic in itself, creatine can indirectly contribute to increasing muscle mass. When an athlete uses creatine, it increases the water content of the muscle. The cross-sectional area of the muscle is increased as well and the muscle is stronger, albeit temporarily. That allows the athlete to life heavier weights, and it’s the weight training that builds muscle mass--no weight training, no increase in permanent muscle mass.

The Safety Issue
Healthcare professionals are worried about the chronic use of creatine, with three areas generally identified as cause for concern. The first is the potential negative effects on the kidneys; the previous Newsletter discussed the effects of creatine on the kidneys of healthy intercollegiate athletes. Since then, creatine supplementation has been used with patients with chronic obstructive pulmonary disease (1), congestive heart failure (2), and many other serious health issues with no negative effects on the renal system or any other system, for that matter. Further, even elderly subjects have used creatine safely as part of fitness and weight-training research programs (3,4). If there were harmful effects, they would have been even more pronounced in these populations, but there were none. In a study specifically designed to examine renal function and metabolites (breakdown products) of creatine use, no negative effects were found on kidney function in spite of high levels of metabolites excreted through the kidneys (5).

The second area is cardiovascular health. There have been case reports on the potential association between arrhythmias and creatine supplementation (6). Case reports can reveal a lot about an individual but little about the generalizability of the results. With millions of doses of creatine used by people of all ages and health conditions, if arrhythmias were caused by creatine, it certainly would be more prevalent.

The final area of concern is the production of carcinogenic substances called nitrosamines with creatine use. In a thorough review of the literature on creatine metabolism, the authors reported that while certain carcinogenic metabolites of creatine can be manufactured in test-tube conditions, it’s very unlikely that this could be duplicated in the body due to the highly acidic conditions in the stomach (7). This observation was recently supported in a clinical trial (8); researchers examined a group of subjects who followed a typical pattern of creatine use for 21 weeks. Measures taken before and after the trial period did not produce an increase in N-nitrososarcosine, a carcinogen produced by nitrosylation of creatine.

While the definitive study on the safety of creatine hasn’t been done--and probably won’t be done--the numerous studies that have examined its use as a dietary supplement would have produced a significant number of problems if it caused them. The fact that it hasn’t speaks volumes. While creatine supplementation isn’t for everybody, no specific profile of someone who would have a negative effect has emerged.

What’s New?
Here are brief reports on clinical trials that have used creatine supplementation. Keep in mind that most of these studies were small, but the results give an indication of the potential for creatine supplementation in the future.

Timing: In a recent study, researchers examined the effect of timing on changes in strength and body mass of a group of male body builders ingesting a creatine, protein, and carbohydrate supplement (9). After a 10-week supervised weight-training program, those athletes who consumed the supplement immediately before and after training gained significantly more muscle mass and strength than those who took it in the morning and before bed. If you’re using creatine, it would be best if you took it together with protein and carbohydrates in the 30 minutes before lifting weights and again in the 30 minutes after lifting for maximal benefits.

Sleep Deprivation: Researchers examined the effect of creatine supplementation on a group of subjects forced to stay up for 24 hours (10). Performance of physical tasks-- balance, reaction time, and movement patterns--as well as mood state were better in those who supplemented with creatine when compared to those taking a placebo. There’s no substitute for sleep, but if you’re burning the candle at both ends, creatine may help you physically perform better--and be happy about it!

Memory: In a double-blind, placebo-controlled study of young vegetarian subjects, researchers tested the hypothesis that creatine supplementation would improve memory and intelligence, both of which require high-speed processing in the brain (11). After six weeks of supplementing with five grams of creatine per day, those who took creatine had a significant improvement in both areas. While creatine supplementation may not benefit those who eat meat (a dietary source of creatine), it may benefit vegetarians and is probably worth a try in anyone who has problems with memory.

COPD: Many disease states cause muscle wasting due to lack of use. Chronic obstructive pulmonary disease (COPD) is a degenerative lung disease that restricts an individual’s physical capacity. Researchers examined the benefit of creatine supplementation during a COPD rehabilitation program (1). While exercise capacity did not improve, muscular strength and endurance did improve in those who supplemented with creatine over those taking a placebo. In effect, while it didn’t improve their ability to use oxygen, it did improve their ability to move and therefore presumably improved the patients’ quality of life.

There are many more research studies examining the use of creatine in a variety of conditions. If someone has a disease or condition that affects muscle strength and endurance or causes fatigue, it would benefit the individual to discuss the use of creatine with a physician. While it won’t cure any diseases, it may improve the quality of life.

  1. Fuld JP, et al. Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease. Thorax. 2005. 60(7):531-7.

  2. Kuethe F, et al. Creatine supplementation improves muscle strength in patients with congestive heart failure. Pharmazie. 2006. 61(3):218-22.

  3. Chilibeck PD, et al. Creatine monohydrate and resistance training increase bone mineral content and density in older men. J Nutr Health Aging. 2005. 9(5):352-3.

  4. Canete S, et al. Does creatine supplementation improve functional capacity in elderly women? J Strength Cond Res. 2006. 20(1):22-8.

  5. Poortmans JR, et al. Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc. 2005. 37(10):1717-20.

  6. Kammer RT. Lone atrial fibrillation associated with creatine monohydrate supplementation. Pharmacotherapy. 2005. 25(5):762-4.

  7. Wyss, M and Rima Kaddurah-Daouk. Creatine and Creatinine Metabolism. Physiol Rev 80: 1107–1213, 2000.

  8. Derave W, et al. Oral creatine supplementation in humans does not elevate urinary excretion of the carcinogen N-nitrososarcosine. Nutrition. 2006. 22(3):332-3.

  9. Cribb, P. and Hayes, A. Effects of Supplement-Timing and Resistance Exercise on Skeletal Muscle Hypertrophy. Med Sci Sports Exer. 2006.

  10. Rae C, et al. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003. 270(1529):2147-50.

  11. McMorris T, et al. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology (Berl). 2006. 185(1):93-103.
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