The brain runs on energy
Creatine helps cells recycle the energy they need to function—including cells in the brain.
PRECLINICAL RESEARCH
THE HIT IS ONLY THE BEGINNING.
New Research on Creatine HCl and Traumatic Brain Injury
Researchers examined how Creatine HCl influenced biological responses after a controlled brain injury in subjects.
The study examined Creatine HCl supplementation before and after injury, including measures of inflammation, brain-cell survival, and communication between brain cells.
The study examined Creatine HCl supplementation before and after a controlled brain injury in mice.
Preclinical research, not a human clinical trial. These findings do not establish prevention or treatment of concussion or traumatic brain injury.
THE BIG IDEA
WHY THIS RESEARCH MATTERS
The major harmful effects of concussions and traumatic brain injury (TBI) are the damage they cause to brain cells, but also the brain inflammation that happens after the head trauma.
The effects of an injury continue after impact
A traumatic injury can trigger ongoing cellular stress and inflammation after the initial hit.
Researchers are exploring creatine’s potential role
This study investigated how Creatine HCl affected key biological signs before and after injury.
A CLOSER LOOK
WHAT DID THE STUDY EXAMINE?
Researchers used a controlled preclinical model to explore how Creatine HCl might influence the brain’s biological response before and after a traumatic injury.
Before injury
Creatine HCl was provided before a controlled traumatic brain injury.
After injury
Supplementation continued after the injury so researchers could observe the brain’s response.
What researchers measured
Researchers examined signs involving inflammation, brain-cell survival, and communication between brain cells.
See the study design at a glance
This preclinical study was conducted in two-month-old male and female mice by researchers from the University of Nebraska Medical Center and the University of Manitoba. Researchers used a controlled cortical impact model of traumatic brain injury and randomly assigned the mice to four groups: water before and after injury; water before injury followed by Creatine HCl; Creatine HCl before and after injury at the same dose; or Creatine HCl before injury followed by a higher post-injury dose.
Creatine HCl was administered daily for seven days before injury and 14 days afterward, with post-injury supplementation beginning 30 minutes after the procedure. At 14 days, researchers evaluated gross tissue damage, blood biomarkers, glial activity, neuronal degeneration, and changes in communication between brain cells.
The Creatine HCl used in the study was supplied by Vireo Systems. The authors declared no competing interests. The manuscript was posted to bioRxiv on October 22, 2026, as a preprint and has not yet been peer reviewed.
READ THE FULL STUDY
PRECLINICAL RESEARCH
WHAT RESEARCHERS OBSERVED
ENCOURAGING FINDINGS
The study reported differences in several biological measures after injury.
FINDING 01
Less inflammation
Researchers observed lower signs of brain inflammation following Creatine HCl supplementation.*
FINDING 02
Signs of greater brain-cell survival
The findings included encouraging differences in the survival of brain cells (neurons) following Creatine HCl supplementation.*
FINDING 03
Changes in brain-cell communication
Researchers also observed encouraging differences in how important connections (synapses) were protected after injury.*
FINDING 04
Male and female responses were not always the same
Some findings varied between male and female subjects, but both experienced improved outcomes and less brain cell damage with Creatine HCl supplementation.*
EXPERT CONVERSATION
THE STUDY, IN THEIR WORDS
Mark Faulkner, Dr. Miller, and Dr. Wagner sit down to unpack the new Creatine HCl study—why it was conducted, what stood out, and what researchers still need to learn.
Mark Faulkner
Founder & CEO, Vireo Systems, parent company to CON-CRĒT® Creatine
Dr. Don Miller
PhD - Study co-author and Professor of Pharmacology & Therapeutics, University of Manitoba
Dr. Jon Wagner
PharmD - Pharmacokinetics and Biopharmaceutics Expert and Scientific Advisor Board Member
This conversation discusses preclinical research. The source page identifies the study as a preprint that has not been peer reviewed. The study findings do not establish prevention or treatment of traumatic brain injury. Speaker affiliations are listed below the video.
QUESTIONS, ANSWERED
WHAT TO KNOW ABOUT THIS RESEARCH
Quick answers about the study, what it found, and what researchers still need to learn.
Was this study conducted in people?No—this was preclinical research.
No. This was preclinical research. Additional studies would be needed to determine whether similar effects occur in humans.
Does this mean Creatine HCl prevents concussions?No. This research does not establish prevention or treatment.*
No. This study does not establish that Creatine HCl prevents, diagnoses, treats, or cures concussion or traumatic brain injury.
Why are researchers studying creatine and the brain?Creatine helps cells recycle energy.
Creatine helps cells recycle energy. Because the brain has high and changing energy demands, researchers are studying how creatine may support several aspects of brain function and health.
What form of creatine was studied?The researchers studied CON-CRĒT Creatine HCl.
The researchers studied Creatine HCl. The findings should not automatically be generalized to other forms of creatine.*
Where can I read the complete study?The full preprint is available on bioRxiv.
The complete manuscript is available on bioRxiv. It was posted on October 22, 2026, as a preprint and has not yet been peer reviewed.
READ THE FULL STUDY
Study details and sources
Study title:
Sex-Dependent Effects of Creatine Hydrochloride on Neuroinflammation, Neuronal Survival, and Inhibitory Synaptic Remodeling Following Traumatic Brain Injury in Mice
Authors:
Johnny W. Zigmond, Benjamin G. Lamberty, Gretchen J. Simon, Jonathan M. Wood, Natalie M. Elliott, Don W. Miller, and Kelly L. Stauch
Research institutions:
University of Nebraska Medical Center, Department of Neurological Sciences, and the University of Manitoba, Department of Pharmacology and Therapeutics
Publication status:
Posted to bioRxiv on October 22, 2026. This manuscript is a preprint and has not yet been peer reviewed.
Study disclosures:
The Creatine HCl used in the study was supplied by Vireo Systems. The authors declared no competing interests.
Facility support:
The authors acknowledged the University of Nebraska Medical Center Tissue Sciences Facility, which receives support from Buffett Cancer Center Support Grant P30 CA036727 and the UNMC Department of Pathology, Microbiology and Immunology.
Full citation:
Zigmond JW, Lamberty BG, Simon GJ, et al. Sex-Dependent Effects of Creatine Hydrochloride on Neuroinflammation, Neuronal Survival, and Inhibitory Synaptic Remodeling Following Traumatic Brain Injury in Mice. bioRxiv. 2026. doi:10.64898/2026.10.21.760461.
This page discusses preclinical research in mice, not a human clinical trial, and is provided for educational purposes. These findings do not establish that Creatine HCl prevents or treats traumatic brain injury or any disease. Anyone with a suspected concussion or brain injury should seek evaluation from a qualified healthcare provider.