For years, creatine has been a go-to supplement for athletes aiming to enhance strength and performance. But science now tells a much bigger story and has helped us to understand that creatine plays a critical role not only in powering muscle, but also in fueling the brain. In this post, we’re exploring the most recent science on this fascinating molecule and why the effects on metabolism and immunity may be key to its potential brain benefits.
How Creatine Provides Energetic Support to the Brain
At its core, creatine is an amino acid-derived compound naturally produced in your liver, kidneys, and pancreas. The molecule is also found in our diet, especially in red meat and fish. The true potential of creatine centers on what it does inside your cells.
Creatine’s best-studied role is as a short-term energy reserve, helping cells replenish adenosine triphosphate (ATP)—their primary energy currency. During moments of high demand, like intense exercise or mental exertion, multiple organs in the body tap into phosphocreatine (a storage form of creatine) to rapidly regenerate ATP. It’s believed that without sufficient creatine, your cells—especially in the brain and muscles—may struggle to keep up with energetic needs.
The relative value of creatine’s energy boosting capabilities may be most relevant in the brain. This is because the brain uses up a disproportionate amount of ATP to power our daily cognitive functions. Our neurons in particular are major energy utilizers, taking up the majority of our brain’s energy to create and package neurotransmitters, send signals across synapses and reset after data transfer. Importantly, a host of studies have shown that as we age, our brains may have more trouble getting consistent access to fuel for these reactions, and this lack of availability of ATP may increase the risk for cognitive decline.
As the primary energy hubs for our cells, mitochondria are a key part of the creatine story. Mitochondrial dysfunction (states in which mitochondria have trouble producing enough energy due to inherited issues or damage from exposures) is believed to be a major contributor to states as diverse as diabetes and heart disease, but also to neurodegenerative diseases, fatigue, brain fog and various mental health problems. Early and primarily preclinical data are providing a signal that creatine’s mitochondrial energy-augmenting abilities might render it a valuable consideration for these states.
Why Creatine May Provide Brain Immune Support
Beyond replenishment of metabolic energy in our cells, recent work has highlighted the potential of creatine to alter our immune cell signaling. Preclinical work suggests that creatine might decrease certain receptors on immune cells, potentially decreasing the extent of an immune response (which could be beneficial in the case of lowering unhealthy inflammation but potentially problematic in the context of infection). Additional research indicates that creatine may promote buildup of an anti-inflammatory cell called an M2 macrophage and increase anti-inflammatory pathway activation. In human studies to date, creatine supplementation has been shown to decrease exercise-related inflammation
Immune-related findings around creatine may have significant implications for brain health, as it’s now well known that the relative state of immune activation and particularly inflammation within the brain is a major driver of certain cognitive and mental health issues. In addition, it’s known that brain inflammation may suppress neuroplasticity—the brain’s ability to rewire itself, and could contribute to such disparate issues as brain fog and even violent behavior.
In a very recent set of preclinical studies, creatine has shown promise in effecting positive changes in the brain specifically by way of the immune system. One 2024 mouse model study found that the combination of creatine and exercise lead to a decrease in inflammatory pathways and a decrease in the activation of the brain’s immune cells (called microglia), while a second 2024 study showed that creatine was able to reverse experimentally-created brain inflammation in rats. Further research will need to explore whether creatine may specifically improve brain states by way of inflammatory pathways.
Creatine Use
The most common form of supplementation is creatine monohydrate, widely studied and generally regarded as safe for long-term use. Typically, 3-5 grams a day is the studied dose in research, and timing seems less important than once believed. Some may be concerned about kidney issues with creatine dosing. While recent research suggests that these considerations are likely overblown, it is always best to speak with your healthcare practitioner before starting a supplement, especially if you have a preexisting issue you are being monitored for.
*Statements above are not intended to diagnose, treat, cure, or prevent disease. You should always consult your healthcare provider for individual recommendations and treatment.