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Effect of Oral Creatine Supplementation on Urinary Methylamine, Formaldehyde, and Formate


Medicine & Science in Sports & Exercise: October 2005 - Volume 37 - Issue 10 - p 1717-1720
doi: 10.1249/01.mss.0000176398.64189.e6
Basic Sciences: Original Investigations

Purpose: It has been claimed that oral creatine supplementation might have potential cytotoxic effects on healthy consumers by increasing the production of methylamine and formaldehyde. Despite this allegation, there has been no scientific evidence obtained in humans to sustain or disprove such a detrimental effect of this widely used ergogenic substance.

Methods: Twenty young healthy men ingested 21 g of creatine monohydrate daily for 14 consecutive days. Venous blood samples and 24-h urine were collected before and after the 14th day of supplementation. Creatine and creatinine were analyzed in plasma and urine, and methylamine, formaldehyde, and formate were determined in 24-h urine samples.

Results: Oral creatine supplementation increased plasma creatine content 7.2-fold (P < 0.001) and urine output 141-fold (P < 0.001) with no effect on creatinine levels. Twenty-four-hour urine excretion of methylamine and formaldehyde increased, respectively, 9.2-fold (P = 0.001) and 4.5-fold (P = 0.002) after creatine feeding, with no increase in urinary albumin output (9.78 ± 1.93 mg·24 h−1 before, 6.97 ± 1.15 mg·24 h−1 creatine feeding).

Conclusion: This investigation shows that short-term, high-dose oral creatine supplementation enhances the excretion of potential cytotoxic compounds, but does not have any detrimental effects on kidney permeability. This provides indirect evidence of the absence of microangiopathy in renal glomeruli.

1Higher Institute of Physical Education and Physical Therapy and 2Medical Biochemistry, Institute of Pharmacy, Free University of Brussels, Brussels, BELGIUM; and 3Institute of Physical Education and Rehabilitation, Catholic University of Louvain-la-Neuve, Louvain-la-Neuve, BELGIUM

Address for correspondence: Jacques R. Poortmans, Ph.D., FACSM, Higher Institute of Physical Education and Physical Therapy, C.P. 168, Free University of Brussels, 28 Avenue P. Héger, B-1000 Brussels, Belgium; E-mail:

Submitted for publication March 2005.

Accepted for publication June 2005.

We thank F. Louppe-Reding and J. Genin-Ramakers for their skillful technical help as well as Flamma-Italy for their kind gift of pure creatine monohydrate. We are also indebted to M. Cabaset, A. M. Cebolla, and A. Grethen for their help with the subjects. The authors acknowledge Lindy Castell (University of Oxford, England) for reading our manuscript.

©2005The American College of Sports Medicine