Your Muscles May Be Talking to Your Brain — Here’s Where Creatine Fits In
Interest in creatine supplements usually whittles down to camps: Those seeking support for strength and recovery and those seeking the compound’s brain benefits. And yes, research shows creatine supports both aspects primarily through creatine’s ability to help cells generate energy. But these benefits aren’t siloed.
A recent review article published this year specifically looked at creatine’s role in the muscle-brain axis1. Here’s what you need to know
Muscles talk to your brain (literally)
When you move, your muscle fibers secrete small proteins called myokines. Myokines then communicate with other organs to regulate processes like metabolism, inflammation, and brain function.
Not every myokine has been shown to impact cognition, but these six were identified by the study authors as ones with the clearest link to brain health.
- BDNF: Central to neuroplasticity and learning, BDNF is one of the most studied exercise-induced myokines.
- Cathepsin B: Induces BDNF expression in the hippocampus and supports memory.
- IL-6: Wait, isn’t IL-6 a marker of inflammation? It can be. IL-6 can also be produced by immune cells as part of an inflammatory response. So when there’s chronic inflammation, IL-6 levels are high and that’s bad for health. But, when the muscle secrete IL-6, it acts as a beneficial signal. It helps regulate energy balance, supports mood, and triggers the release of anti-inflammatory molecules.
- IGF-1: Crosses into the brain, supports neurogenesis and neuron survival.
- Irisin: This myokine helps stimulate BDNF expression in the hippocampus (part of the brain that regulates memory, learning, and emotion).
- Lactate: Once thought of as just the burn in your muscles, lactate also acts as a signaling molecule that supports neurotrophic pathways, blood–brain barrier integrity, and brain development.
Where does creatine fit in?
This study outlines four key pathways through which creatine may influence the muscle–brain axis, ranging from enhanced muscle energy to direct effects on neuronal signaling.
Creatine may enhance the myokine response to exercise.
Creatine helps muscle cells regenerate ATP more efficiently. So by improving ATP availability, creatine could allow muscles to contract more effectively, potentially shifting the magnitude or timing of myokine release.
More research is needed to confirm this, but the researchers of this study cite it as a likely mechanism.
Creatine supports muscle hypertrophy, and bigger, healthier muscles release more myokines.
Creatine consistently increases training volume, strength, and lean mass (when paired with a strength training program). Those adaptations alone can change myokine output, especially IGF-1 and irisin, both of which influence brain plasticity.
Creatine improves insulin sensitivity, which may further shape myokine signaling.
Better insulin signaling enhances glucose uptake in muscle and is linked to increased irisin, BDNF, and exercise-induced IL-6. These signals help regulate neuroinflammation and support memory and mood regulation.
Creatine has direct effects inside the brain.
Independent of muscle, creatine helps stabilize energy production in neurons, reduces oxidative stress, and influences neurotransmitter systems like serotonin and dopamine.
This may explain why creatine has shown promise as an additional therapy for depression in emerging clinical trials.
How to supplement with creatine
If you’re looking to improve both muscle and brain health, then it’s time to add creatine to your routine.
For most folks, taking 5 grams of creatine daily (not just on days you work out) is linked to noticeable benefits. To really target cognitive health, a higher 10-gram daily dose is more effective.
There are various types of creatine, but a creatine monohydrate powder is the best (as it’s widely studied and has high bioavailability.)
Women have been loving this creatine powder to help tone and sculpt their muscles, and this is a great creatine for brain health as it also includes 500 milligrams of citicoline (which is especially beneficial for memory).
The takeaway
By improving how muscles use and store energy, creatine may influence myokines that support cognition, mood, and neural resilience.
It’s an early signal that supporting your muscles may be one meaningful way to support your brain.
