NW Spine - Library

© 2000

Originally published online at Peak Health (www.peakhealth.com) and in Exercise Protocol Annual 2001, pp. 65-66.

Perhaps more so than any other contemporary dietary supplement, creatine finds itself amidst a flurry of never-ending controversy. While there is debate regarding the ethics of allowing this performance-enhancing supplement to be used by competitive athletes (1,2), this article will focus on alleged safety issues related to creatine supplementation.

The safety of creatine usage has been addressed in several forums and has been lampooned predominately in the lay press. A prime example is the premature blame of three collegiate wrestlers’ deaths on creatine usage, an accusation dismissed following an investigation by the Centers for Disease Control and Prevention (3). As we shall see, some misconstrued scientific reports of creatine-related side effects have also fueled the fire among creatine’s critics.

Let’s begin with some fundamental examples of what has led to the monumental misunderstanding surrounding creatinine supplementation. Stop!!! Hold it right there! Did you catch the mistake? Look again at the first sentence of this paragraph, which improperly used the term "creatinine" instead of "creatine." Indeed, the striking similarity of the words "creatine" and "creatinine" makes the terms easily confused.

Miscommunications of these nearly identical terms are certainly not limited to the average Joe, for I have personally noted in passing many physicians who mistakenly refer to fictional substances such as "creatinine monohydrate," "creatinine phosphate" and "creatinine kinase." (The correct terms are "creatine monohydrate," "creatine phosphate" and "creatine kinase.")

This terminology has been confused even in scientific communications, from which knowledge is to trickle down to the masses through the (mis)informed health care professional or researcher. I have found at least two such examples in the scientific literature (4,5), and I’m sure there are plenty more. I mean no disrespect to these authors, as none of us is infallible, but it does underscore how easily this mistake occurs.

Equally sneaky as mistaken terminology is the incorrect reporting of creatine dosage. The problem is that creatine’s dosage is measured in grams (g) as opposed to the dosages of most other dietary supplements or drugs that are measured in milligrams (mg) or micrograms (ug). It is not uncommon for respected publications to misreport the dosage of creatine in milligrams. Take for example an unfavorable blurb about creatine safety in The Physician and Sportsmedicine that on three occasions misreported the dosage units as milligrams (6). The result, of course, is that the quantity of creatine discussed in the article was off by a factor of 1000! Thus, for the relatively uninformed physician who may have read that blurb and taken it at its word, you can imagine how prejudicial such an article can be.

You know that reporting accurate dosage of creatine must be problematic if the folks who conducted the research sometimes don’t get it right. Yes, some original research in scientific journals has misreported units of measure as well (7), and I suspect there are more errors in the scientific literature of which I am unaware. Readers should be aware that creatine dosage is virtually always reported in grams. And, on those rare occasions when it is reported in milligrams, dosage should be expressed as thousands of milligrams (e.g., 5 g = 5000 mg).

So, you may wonder exactly what creatinine is. Creatinine is an inactive breakdown product of creatine. As my friend and colleague Dr. Jeff Stout likes to say, "Creatinine forms when creatine bites itself on the tail." In other words, creatinine’s molecular structure is ring-shaped. Creatinine has no function in the body and is simply excreted in urine, which is why it is monitored clinically as a marker of kidney function (8). There is much confusion regarding creatinine measurements in people using creatine supplements. The incorrect interpretation of creatinine levels in creatine users has greatly contributed to this confusion and its perpetuation.

The majority of evidence does not support the contention of kidney damage from normal creatine supplementation in persons without preexisting kidney disease. Of the hundreds of volunteers who have participated in scientific studies and the tens of thousands of individuals who regularly consume creatine supplements in real-life situations, only three cases allegedly linking creatine supplements to kidney insufficiency have appeared in the scientific literature as brief reports (9,10,11).

In one report of creatine toxicity (9), the authors used a method to assess kidney function that they themselves later criticized (12). In another case, the patient who developed kidney inflammation consumed nearly three times the suggested dose of the creatine supplement during a month (10). A third case involved a man with an 8 year history of kidney disease who began taking creatine (11). These isolated reports have been embraced by alarmists and ultraconservative nutritionists who frown upon any dietary supplement. This is hardly compelling evidence of toxicity. These reports have been met with some criticism by other scientists (13-15).

Under normal circumstances without creatine supplementation, increased levels of blood creatinine indicate a decrease in kidney filtration rate (16), which is indeed a sign of kidney dysfunction. However, some clinicians have viewed blood creatinine values with tunnel vision. Because creatine supplementation increases body creatine stores, it would be expected that more creatinine would be produced within the muscle and then released into the blood stream where it could inflate blood creatinine concentration in the absence of kidney problems. Another source of creatinine is from the conversion in the gut of unstable creatine to creatinine which is then taken up into the bloodstream. Several studies--though not all--have shown increased blood creatinine during periods of creatine supplementation (17-19). Also, individuals with greater lean body mass, like many users of creatine, naturally produce greater creatinine (8). Furthermore, physical activity, which typically has accompanied creatine ingestion, also increases blood creatinine levels (8). For these reasons, it is unlikely that isolated elevated creatinine in creatine users indicates pathological changes in the kidney. Aside from the three previously mentioned cases, seven studies with many participants consuming creatine for periods of 5 days to 5 years have found no negative effects of loading or maintenance dosages (roughly 20 g daily or 5 g daily, respectively) of creatine supplementation on kidney function (14,18,20-25).

Clearly, the topic of creatine supplementation safety has suffered primarily due to what may best be categorized as a comedy of errors. Creatine is commonly confused with creatinine, and creatine dosage is sometimes misreported. Even health care providers may not understand how to interpret creatinine concentration as it relates to kidney function in creatine users because markedly increased blood creatinine levels indicate kidney dysfunction in non-creatine users. Hopefully, this article has emphasized the importance of attention to detail in reporting and discussing dosages and laboratory findings.

Dr. Greg Bradley-Popovich holds dual master's degrees in Exercise Physiology and Human Nutrition from West Virginia University as well as a doctorate in Physical Therapy from Creighton University. He is the Director of Clinical Research at Northwest Spine Management, Rehabilitation, and Sports Conditioning in Portland, Oregon.

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Benzi G. Is there a rationale for the use of creatine either as nutritional supplementation or drug administration in humans participating in a sport? Pharmacol Res. 2000;41:255-264.

Williams MH, Kreider RB, Branch JD. Creatine: The Power Supplement. Champaign, Ill: Human Kinetics; 1999.

Schnirring L. Creatine supplements face scrutiny [News Briefs]. Phys Sportsmed. 1998;26:15,16,22,23.

Poortmans JR, Francaux M. Renal dysfunction accompanying oral creatine supplements [correspondence]. Lancet. 1998;352:234.

Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements [letter]. Lancet. 1998;351:1252-1253.

Kidney disorder linked to creatine use? [Field Notes]. Phys Sportsmed. 1999;27:21.

Koehler S, Kuehl K, Dulacki K, Goldberg L, Elliot D. Adverse and mood altering effects of oral creatine supplementation [abstract]. Med Sci Sports Exerc. 2000;32(suppl):S135. Abstract 555.

Baines AD. Disorders of the kidney and urinary tract. In: Gornall AG, ed. Applied Biochemistry of Clinical Disorders. 2nd ed. Philadelphia, Pa: JB Lippincott; 1986:139-171.

Kuehl K, Goldberg L, Elliot D. Renal insufficiency after creatine supplementation in a college football athlete [abstract]. Med Sci Sports Exerc. 1998;30(suppl):S235. Abstract 1337.

Koshy KM, Griswold E, Schneeberger EE. Interstitial nephritis in a patient taking creatine [letter]. New Engl J Med. 1999;340:814-815.

Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements [letter]. Lancet. 1998;351:1252-1253.

Kuehl K, Goldberg L, Elliot D. Re: long-term oral creatine supplementation does not impair renal function in healthy athletes [letter]. Med Sci Sports Exerc. 2000;32:248.

Greenhaff P. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998;352:233.

Poortmans JR, Francaux M. Renal dysfunction accompanying oral creatine supplements [correspondence]. Lancet. 1998;352:234.

Poortmans JR, Francaux M. Re: long-term oral creatine supplementation does not impair renal function in healthy athletes [reply]. Med Sci Sports Exerc. 2000;32:248-249.

Guyton AC, Hall JE. Textbook of Medical Physiology. 9th ed. Philadelphia, Pa: WB Saunders; 1996.

Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H. Creatine supplementation--part I: performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc. 1999;31:1763-1769.

Kuehl K, Koehler S, Dulacki K, Goldberg L, Elliot D, Bennett W, Haddock B. Effects of oral creatine monohydrate supplementation on renal function in adults [abstract]. Med Sci Sports Exerc. 2000;32(suppl):S168. Abstract 747.

Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L, Hespel P. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol. 1997;83:2055-2063.

Gotshalk LA, Kraemer WJ. The effects of creatine supplementation on the muscular performance of older men [abstract]. Med Sci Sports Exerc. 2000;32(suppl):S137. Abstract 569.

Mayhew DL, Satterly TF III, Ware JS, Mayhew JL. Effect of long-term creatine supplementation on liver and kidney function in college football players [abstract]. Med Sci Sports Exerc. 2000;32(suppl):S135. Abstract 558.

Millard-Stafford ML, Snow TK, Rosskopf LB. Limited side effects associated with creatine supplementation [abstract]. Med Sci Sports Exerc. 2000;32(suppl):S133. Abstract 545.

Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol. 1997;76:566-567.

Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999;31:1108-1110.

Sugiura K, Takasaki M, Ohta A. Creatine supplementation increases the requirement of nutrients (ntrogen [sic] and minerals) in rats with spontaneous exercise [abstract]. Med Sci Sports Exerc. 2000;32(suppl):S136. Abstract 563.

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