How does creatine get into muscle?

  1. What is creatine?
  2. How does creatine work?
  3. What are natural sources of creatine?
  4. How does creatine get into muscle?
  5. Do all muscles respond to creatine?
  6. Does everyone respond to creatine?



From the blood creatine is transported into skeletal muscle by special transporter molecules expressed on the muscle surface. In essence, these transporters harness the energy of sodium entering the cell to transport creatine inward. Furthermore, given that in a living cell sodium levels are much higher outside than inside, creatine transport is unidirectional – inward.

Transporter function is regulated by other physiological processes. For example, creatine transporter activity is enhanced by co-ingestion of highly glycemic foods, an effect mediated by insulin release. Insulin stimulates the extrusion of sodium from the cell, thereby creating a ionic environment conducive for creatine transport (see previous paragraph). Therefore, taking measures to improve one’s insulin sensitivity should enhance creatine uptake into skeletal muscle.

The activity of these creatine transporters is also influenced by the presence of creatine itself in the following manners: (1) elevated plasma creatine interrupts creatine uptake into skeletal muscle via these transporters; (2) the synthesis of creatine from amino acids is also stopped by elevated plasma creatine. These are nothing more than examples of normal regulatory feedback processes that are common in cell biology. However, how exogenous creatine supplementation influences these processes in humans is still an open issue. This is why it is often recommended to periodically stop taking creatine to let the body recuperate (see (Question #7). Omitting the load phase from supplementation will also mitigate this drawback of creatine supplementation (see (Question #7).

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