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Aug 11, 2010
These researchers studied the in vivo effect of dietary creatine as well as 3-GPA (a creatine analog that is a competitive inhibitor of creatine entry) on the expression of the creatine transporter (creatine T). Long term feeding of rats with 3-GPA has been previously shown to decrease creatine levels in skeletal muscles without effecting creatine T expression. In this study, the expression of the creatine T was examined in rats chronically fed either 4% creatine or 2.5% GPA. Dietary creatine administered for 3-6 months, significantly lowered the expression of creatine T polypeptides. The rats fed the creatine analog GPA showed virtually no change (perhaps even a slight increase) in creatine T polypeptide expression.


The wide spread use of creatine among athletes and bodybuilders has raised concerns about possible negative side effects. Of course most of the nay sayers are looking to control its availability with little real concern for the well being of those who use it. This study has answered a question that has rested on the minds of many, which is, "Is there any reason to cycle creatine?" From the study above we see that the abundance and activity of the creatine transporter is negatively effected by long term creatine ingestion. The creatine transporter is down regulated with continued exposure to extracellular creatine.

Human skeletal muscle has an upper limit of creatine that can, or will, be contained within the cell. This limit is around 150-160 mmol/kg of dry muscle. As the intracellular concentration of creatine approaches this level, the synthesis of creatine transporters declines and even stops depending on the amount of creatine ingested over time. In the study above, it was shown that the creatine transporter is regulated by the content of creatine in the cell rather than by the interaction of creatine, or it’s analog 3-GPA, with the transporter.

All the arguments about creatine absorption being a limiting factor in creatine content within the cell are bogus. Creatine does not need to be "micronized" or "effervesent" to lead to an increase in creatine content within your muscles. The activity of the creatine transporter is the limiting factor. Any trick increase in creatine absorption will only hasten creatine transporter down regulation. It only requires about 5 grams per day for 30 days to increase the content of creatine within muscle tissue to the same extent as 30 grams per day for 6 days. The sooner you reach the upper limit the sooner your muscles become unable to take up creatine. It is better to maintain sufficient levels of creatine transporters in order not to cause a rapid decline in creatine content once creatine supplementation is discontinued. Clearly there appears to be good reason to cycle creatine supplementation.

The authors of this study recommend not using creatine for over 3 months at a time. To truly cycle creatine you will have to take at least 4 weeks off. Creatine levels take at least one month to return to pre-supplement levels. It may be important to take the entire month off because one speculated mechanism of creatine transporter downregulation is that when the intracellular levels (levels inside the muscle cell) are increased the creatine transporters are taken down and not replaced as long as creatine levels remain elevated. Thus it might take as long as a month for creatine transporters to return to normal after chronic creatine supplementation. Keep in mind that no one has actually shown that long-term supplementation with creatine is a bad thing.

Source: Mol Cell Biochem 1998 Jul;184(1-2):427-37
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