Correspondence

Interstitial Nephritis in a Patient Taking Creatine

N Engl J Med 1999; 340:814-815March 11, 1999

Article

To the Editor:

Creatine is being widely used as a possible performance-enhancing substance. Its safety, however, is being debated in both the scientific community1-3 and in the popular press. We report on a patient who had transient renal insufficiency while taking creatine.

A previously healthy 20-year-old man presented with a four-day history of nausea, vomiting, and bilateral flank pain that began approximately four weeks after he started taking 5 g of creatine (pure creatine monohydrate, ProPerformance Laboratories, Pittsburgh) orally four times a day. He had stopped the creatine and had not taken any medications or other food supplements. His blood pressure was 140/90 mm Hg. Physical examination revealed dehydration and diffuse abdominal tenderness. His serum creatinine concentration was 1.4 mg per deciliter (124 μmol per liter). A complete blood count and measurements of antistreptolysin O, antinuclear antibodies, and plasma complement C3 and C4 concentrations were normal. Urinalysis revealed 4+ protein and 1+ blood; the urine sediment contained dysmorphic red cells and white-cell casts. A spiral computed tomographic scan revealed no abnormalities in the kidneys or the collecting systems.

The patient was hospitalized and treated with intravenous fluid and pain medication. During hospitalization, his blood pressure rose to 160/100 mm Hg and his serum creatinine concentration rose to a peak value of 2.3 mg per deciliter (203 μmol per liter). Urinary protein excretion was 472 mg per day. A renal biopsy revealed acute focal interstitial nephritis and focal tubular injury (Figure 1Figure 1Electron Micrograph of a Renal-Biopsy Specimen Showing Acute Focal Interstitial Nephritis.); electron microscopy revealed effacement of glomerular foot processes and focal thickening of the basement membrane. The patient's blood pressure, serum creatinine concentration, and urinalysis subsequently became normal.

This case of acute interstitial nephritis should serve as a warning that the use of creatine, which is freely available in stores, may be associated with renal injury.

Kevin M. Koshy, M.D.
Elysia Griswold, M.D., M.P.H.
North Shore Medical Center, Salem, MA 01970

Eveline E. Schneeberger, M.D.
Massachusetts General Hospital, Boston, MA 02114

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Author/Editor Response

A spokesperson for General Nutrition Products replies:

To the Editor: General Nutrition Products packages creatine under the ProPerformance label for General Nutrition Centers. The inference that creatine is unsafe for use as a dietary supplement should be tempered in view of the large and growing body of scientific literature on creatine, the wide popularity of creatine as a performance-enhancing dietary supplement among athletes, and the lack of data from controlled studies that would support a causal relation between creatine and renal disease.

Creatine has been studied for many years as a performance-enhancing supplement. A majority of the studies show beneficial effects on performance during intense athletic activity.1-3 These studies, as well as those that did not report a benefit,4,5 are consistent in that they do not report major side effects among the subjects.

In these studies, creatine intake varied, but most subjects used some type of creatine-loading technique, with 20 g of creatine per day for five days a not unusual regimen.3 In none of these studies did the subjects take 20 g per day for 30 days, the regimen described in the case report. The product sold by General Nutrition Centers that was taken by the subject in the case report has clearly written directions for use on the label that read in part, “Mix one heaping teaspoon (5 g) in your favorite beverage daily. For creatine loading, take four heaping teaspoons per day: one heaping teaspoon at four-hour intervals. Continue this process for four days. Do not exceed the loading level of more than four days in any one-month period.”

General Nutrition Centers is committed to offering the public safe food supplements that provide benefits to the consumer. We are also committed to labeling products clearly to assist the consumer in the safe use of such products. We believe that creatine is both safe and beneficial, as demonstrated by the majority of the data on its use in the medical and scientific literature.

Ronald W. Thompson, Ph.D.
General Nutrition Products, Greenville, SC 29607-4197

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