Reply to Letter to the Editor,“Creatine loading for chronic migraine?”

We read the comments to our paper published in Cephalalgia (1) with great interest. In his comments, Dr. Ostojic (2) suggests that the reduced thalamic total creatine levels we observed in chronic migraine (CM) patients could potentially be remediated with oral creatine supplementation. It was further suggested that this could lead to a reduction in migraine symptoms. Dr. Ostojic nicely lists several potential hurdles that may have to be overcome for the therapy to be successful in CM patients. Here, we wish to further elaborate on the proposition put forward by Dr. Ostojic. Oral creatine supplementation for 2–4 weeks may increase brain creatine levels by about 8–15% in healthy adults (3,4), with the highest increase observed in the thalamus after 4 weeks of continuous administration (3). These results, however, should be interpreted with caution as they need to be confirmed in a larger study cohort. In our study, total creatine levels were reduced by about 10% (6.34 mM vs. 7.04 mM) in CM patients. Hence, the magnitude of the required change is within the range obtainable with oral supplementation. Furthermore, it has been suggested that the effects of creatine supplementation on brain function could be larger in conditions with chronic depletion of brain creatine (5). Modulation of thalamic creatine levels by supplementation furthermore has the potential to answer whether the observed total creatine reduction is a consequence of the headaches or if it contributes directly to generation or maintenance of the headaches. It would also be possible to examine whether the reduced total creatine levels are coupled to the concomitant reductions in thalamic total N-acetylaspartate observed in our study; that is, whether altered energy homeostasis leads to compromised neuronal health. It is noteworthy that a study on creatine supplementation in CM would have to control for the diet (vegetarian vs. non-vegetarian) and exercise patterns, as both can influence the available creatine levels (5). Finally, the long-term effects of creatine supplementation on endogenous creatine synthesis in the brain remains largely unknown and require further studies.