Creatine Could Protect The Brain From Gut Inflammation

It started as a supplement for athletes, and now scientists are investigating the benefits of creatine for more than just muscle.

According to preliminary evidence, this natural organic compound could have perks for many parts of the body and brain even without exercise .

That idea remains contentious; however, a new study among rats suggests that creatine is highly effective at protecting the brain from a disrupted gut.

The findings, published in Brain, Behavior, and Immunity , are limited to animal models, but researchers in Spain believe there are clinical implications.

In individuals with gut-brain inflammatory disorders, they argue , creatine could be an "excellent candidate" to preserve brain health.

"From a clinical perspective, creatine supplementation emerges as a powerful, complementary and preventive strategy," the research team concludes , led by neurophysiologists Alejandro Ruiz-Calero and Maria Ortego-Domínguez at the University of Seville in Spain.

"… it restores hippocampal creatine content, preserves neuronal integrity, and normalizes neuronal excitability by selectively targeting parameters disrupted by inflammation."

Last year, some of the same researchers found that creatine supplementation in rodents reduced gut inflammation and disease-related damage within the intestine.

Their new experiments show perks for the hippocampus, too, which is a crucial brain region involved in learning and memory.

When rats with gut inflammation took creatine daily, the supplement successfully restored creatine levels in their hippocampus.

It also reduced inflammation and damage to neurons in this region.

The results align with several preliminary studies linking creatine supplementation to improved brain health.

The brain is known to use a huge amount of the body's energy, and creatine plays an important role in maintaining our cellular energy balance.

For humans, a typical omnivorous diet involves about 1 to 2 grams of creatine a day. This natural organic compound is also made by the liver, the kidneys, and the pancreas.

Once produced or consumed, it is mostly stored within muscle, but creatine can also cross the blood-brain barrier and be taken up by neurons and other brain cells.

What it does once it is in the central nervous system is less clear.

This new research suggests that creatine supplements may impact the health and function of certain brain cells.

The rodents in experiments were modeled on a human condition called ulcerative colitis, which, together with Crohn's disease, is considered a chronic inflammatory bowel disease (IBD).

Ulcerative colitis causes the immune system to attack the intestinal lining, leading to open sores in the colon and rectum.

But its symptoms are not confined to the gut. They are also apparent in the brain.

When IBD flares up and is considered 'active', patients often report brain fog , and display memory loss, attention deficits, and declining executive functions.

In rats with colitis, previous studies have shown that the disease leads to greater inflammation in the hippocampus.

Now, researchers in Spain have extended those results and shown that gut inflammation in rats can also lead to damage and dysfunction within hippocampal neurons.

The good news, however, is that oral doses of creatine seem to help.

Rats with colitis without creatine supplementation (above) versus those with creatine supplementation. (Ruiz-Calero et al., Brain, Behavior, and Immunity , 2026) In experiments, some rats were given water containing one gram of creatine per kilogram of their body weight.

Then 10 days later, the scientists induced symptoms of colitis. The daily creatine dose continued for the rest of the experiment.

In rats that took creatine but didn't have colitis, researchers did not measure a significant change to creatine levels in the hippocampus.

But in rats with colitis, creatine improved several markers of healthy brain activity.

"The supplementation restored hippocampal creatine levels, preserved neuronal integrity, and normalized impaired excitability," the authors conclude .

Interestingly, the research team found that the benefits of creatine for male rats with colitis were more apparent than for females.

This is probably because in males, the brain damage associated with colitis seems to be worse than in the opposite sex.

The findings suggest that some inflammatory conditions may impact the male and female brain differently, and that creatine supplementation may help prevent some of these ramifications.

"Beyond colitis, reduced brain creatine content has been linked to systemic and central nervous system inflammatory disorders, including neurodegeneration, traumatic brain injury, and neuropsychiatric disease," the authors explain .

But much of the research on creatine and the brain remains in the preclinical stage, so it is unclear how effective this supplement might be in humans.

Initial findings among rodents suggest that not everyone will benefit in the same way.

Earlier this year, on the Health vs Hype podcast, Jason Mitchell, the chief medical officer at healthcare company Geisinger, said that recent results on creatine and brain health were intriguing but hardly definitive.

"We don't have the data to say, yeah, this is something you should be taking for your brain, but I don't want to discount that. There are some studies out there."

Researchers from Spain have now added another to the list.

The research has been published in Brain, Behavior, and Immunity .

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