Can Creatine Protect Your Brain From an Inflamed Gut?

Creatine has spent decades as a gym supplement. You scoop it into a shake, you lift heavier, you move on. But researchers keep finding reasons to study creatine for parts of the body that have nothing to do with biceps. The brain tops that list.

A new study from the University of Seville in Spain adds a twist I find fascinating as a gastroenterologist. In rats with chronic gut inflammation, daily creatine protected a key memory center of the brain from inflammation, nerve cell loss and faulty electrical signaling.

This is an animal study. It doesn’t prove creatine will do the same for you. But it points straight at something I tell patients every week: what happens in your gut doesn’t stay in your gut.

Your Gut Talks to Your Brain, and Inflammation Gets Loud

The gut-brain axis is the two-way communication network between your digestive tract and your central nervous system. Nerves, hormones, immune cells and gut microbes all send signals along it. Most of the time, that conversation keeps you healthy.

Problems start when the gut is chronically inflamed, as in inflammatory bowel disease (IBD), the umbrella term for Crohn’s disease and ulcerative colitis. In ulcerative colitis, the immune system attacks the lining of the colon and rectum, causing open sores, bleeding and cramping.

Inflammatory signals from the gut can travel to the brain and spark inflammation there, too. My IBD patients describe brain fog during flares. They forget things and struggle to focus. Research backs them up: people with active IBD often show memory problems, attention deficits and weaker executive function. They also have higher rates of anxiety and depression.

For years, we treated these symptoms as a side note to the disease in the intestines. That view is changing. The brain effects are part of the disease, and they deserve treatment of their own.

What Creatine Actually Does in Your Body

Creatine is a natural compound your liver, kidneys and pancreas make from amino acids. You also get it from red meat and fish, about 1 to 2 grams a day on a typical diet.

Most of your creatine sits in your muscles, where it helps regenerate ATP, the molecule your cells run on, when energy demand spikes. That’s why it helps with short bursts of intense exercise. But muscle isn’t the only tissue with big energy needs. Your brain makes up about 2% of your body weight and uses roughly 20% of its energy. Creatine crosses the blood-brain barrier, and brain cells take it up.

Scientists have linked low brain creatine to several inflammatory conditions, including neurodegenerative disease, traumatic brain injury and certain psychiatric disorders. What creatine does once it’s inside the brain is still not fully understood. This new research starts to fill that gap.

Inside the Seville Study

The research, published in Brain, Behavior, and Immunity, was led by neurophysiologists Alejandro Ruiz-Calero and María Ortego-Domínguez. In 2025, the same team showed that creatine reduced gut inflammation in rats with colitis and prevented anxiety- and depression-like behavior. This time, they focused on the hippocampus, the brain region that handles learning and memory.

Young male and female rats were split into four groups: healthy rats with or without creatine, and rats with chronic colitis with or without creatine. The colitis came in cycles of flare-ups and remission, the way ulcerative colitis behaves in people. Creatine went into the drinking water at 1 gram per kilogram of body weight per day, starting 10 days before colitis was induced.

After more than a month, the researchers examined the rats’ hippocampi. They measured inflammatory molecules, counted neurons and recorded electrical activity one cell at a time. Here’s what they found:

• Gut inflammation drained the brain’s creatine in both male and female rats.
• The brain’s immune cells switched on. Microglia became activated in both sexes, and inflammatory molecules rose.
• Neurons got damaged. Male rats lost neurons in a hippocampal region called CA1.
• Electrical signaling went off track. In males, the current needed to trigger a nerve signal rose by about 60%.
• Creatine largely prevented all of it. Supplemented rats with colitis had hippocampal creatine levels 20% to 30% higher than unsupplemented ones, matching healthy animals. Creatine blocked the brain inflammation in both sexes and preserved neuron structure and electrical activity in males.

One detail stands out. In healthy rats, creatine didn’t push neurons beyond normal. It acted only on what the disease had disrupted. The authors called creatine a powerful, complementary and preventive strategy from a clinical point of view.

Why Males and Females Responded Differently

Male rats took a much bigger hit from colitis, with more brain inflammation, neuron loss and electrical dysfunction. Female rats had inflammation too, but their neurons kept their structure and normal signaling.

So creatine looked more effective in males. Co-author María D. Vázquez-Carretero says that likely reflects the males’ greater damage, not a difference in how each sex responds to creatine. In females, creatine strongly suppressed tumor necrosis factor, a major target of IBD medications.

The team’s earlier work found that female rats with colitis showed more anxiety-like behavior, while males showed more brain inflammation. Men and women don’t always experience disease the same way. Research that studies both sexes catches differences that male-only studies miss.

What This Means for You (and What It Doesn’t)

Supplement headlines tend to outrun the science. The researchers themselves warn against reading this as proof that creatine treats IBD or that people with colitis should take it to protect their brains.

Keep these limits in mind:

• It was done in rats. Plenty of rodent results never pan out in humans.
• It tested prevention, not treatment. The rats got creatine before colitis began.
• It measured cells, not memory. The team didn’t test whether the rats learned or remembered better.
• The groups were small, with five to seven animals per group for each measurement.
• The dose was high. One gram per kilogram per day doesn’t translate directly to a human dose.
• The mechanism is unclear. Creatine may work by calming gut inflammation, acting on brain cells directly, or both.

The human evidence on creatine for brain health is still early. Some studies suggest benefits for memory and mental fatigue, especially in people who are sleep-deprived, older or eating little meat. Others show little effect. Geisinger’s chief medical officer Jason Mitchell said on the Health vs Hype podcast this year that the data aren’t strong enough to tell everyone to take creatine for their brain, but the existing studies shouldn’t be dismissed. I agree.

Creatine monohydrate is one of the most studied supplements available, with a good safety record in healthy adults at 3 to 5 grams a day. But if you have IBD, kidney disease or take regular medications, talk to your doctor first. Creatine can also raise a kidney blood test called creatinine, so your care team should know you’re taking it.

The bigger lesson goes beyond any single supplement. Calm the inflammation in your gut, and you may be protecting your brain.

My Personal RX on Protecting Your Brain Through Your Gut

After more than 20 years as a gastroenterologist, I’m convinced that brain health starts in the gut. You don’t need IBD for this to matter. Low-grade gut inflammation from poor diet, stress and short sleep is common, and your brain feels it.

Here’s what I recommend:

1. Eat fiber every day. Aim for 25 to 35 grams from vegetables, fruits, beans, oats and whole grains to feed the gut bacteria that keep inflammation in check.
2. Add fermented foods. Plain yogurt, kefir, sauerkraut and kimchi bring in beneficial microbes.
3. Support your gut-brain axis directly. My MindBiotic chews were formulated with the gut-brain connection in mind.
4. Ask your doctor about creatine. For healthy adults, 3 to 5 grams of creatine monohydrate a day is the well-studied dose. If you have IBD, kidney issues or take medications, get the green light first.
5. Eat for low inflammation. Build meals around colorful produce, olive oil, nuts and fatty fish like salmon and sardines.
6. Cut back on ultra-processed foods. Packaged snacks, sugary drinks and processed meats are linked to gut inflammation.
7. Protect your sleep. Get seven to nine hours. Magnesium Essentials can help you wind down in the evening.
8. Manage stress daily. Stress hormones affect gut function. Ten minutes of deep breathing, prayer or a walk outside helps.
9. Move your body. Regular exercise improves gut bacteria diversity and supports memory. Pair it with strength training, and creatine pulls double duty.
10. Take a whole-system approach. My Gut Brain Reset Bundle pulls the key pieces together, and my Protocol for Optimizing Your Health & Wellbeing guide walks you through nutrition, movement and mindset.

If you live with IBD and notice brain fog or mood changes, tell your gastroenterologist. Those symptoms are real, they’re connected to your gut, and they deserve attention.

Sources:

1. Cassella, C. (2026, October 14). Creatine could protect the brain from gut inflammation. ScienceAlert. https://www.sciencealert.com/creatine-could-protect-the-brain-from-gut-inflammation
2. Ruiz-Calero, A., Ortego-Domínguez, M., Vázquez-Carretero, M. D., Sotelo-Parrilla, G., Martínez-Gómez, N., Calonge, M. L., Pardillo-Díaz, R., Castro, C., Nunez-Abades, P., Peral, M. J., Carrascal, L., & García-Miranda, P. (2026). Modulating effects of creatine prevent sex-dependent hippocampal neuroinflammation, neuronal damage, and electrophysiological dysfunction induced by chronic colitis. Brain, Behavior, and Immunity, 138, 106929. https://doi.org/10.1016/j.bbi.2026.106929