New Study is Best News for Older Creatine Supplement Users
For years, creatine has lived almost exclusively in the world of gyms and protein shakers. Mention it, and most people picture heavier lifts and bigger muscles.
But a new review in the Journal of Dietary Supplements asks a much more interesting question: what has creatine been doing in the brain all this time?
The paper, “Creatine Supplementation and the Brain: Have We Put the Cart Before the Horse?” (DOI: 10.1080/19390211.2026.2616440), pulls together decades of human trials, animal experiments, and neuroimaging studies to examine how creatine actually interacts with brain biology. Instead of chasing bold claims about “mental performance,” the authors zoom in on something more fundamental: brain energy.
The Brain Runs on Energy—Not Hype
Creatine is not a stimulant. It doesn’t act like caffeine, and it doesn’t “turn on” neurons. Its primary biological role is far less flashy and far more essential: buffering cellular energy.
Inside cells, creatine helps recycle ATP, the molecule often described as the cell’s energy currency. This process—known as the phosphocreatine system—acts as a rapid energy reserve. It’s well established in muscle physiology, but it’s just as present in the brain (Wyss & Kaddurah-Daouk, 2000).
Neurons are metabolically demanding. They fire, reset ion gradients, release neurotransmitters, and maintain membrane potentials—all of which cost energy. When demand spikes or supply falters, performance drops. The review argues that creatine’s cognitive and clinical effects make sense only in that energetic context.
When Does Creatine Matter Most?
One of the most compelling themes in the review is conditional benefit. Creatine’s effects appear strongest when the brain is under strain.
1. Sleep Deprivation
Several studies show that creatine supplementation can improve aspects of cognition during sleep loss, including reaction time and working memory (McMorris et al., 2006). Sleep deprivation increases metabolic stress in the brain. If creatine enhances phosphocreatine availability, it may help stabilize ATP supply during those high-demand states.
2. Aging
Brain creatine levels and energy metabolism tend to decline with age. Some trials report modest cognitive improvements in older adults following supplementation, particularly in tasks involving memory and processing speed (Rae et al., 2003). The effect sizes aren’t dramatic—but they’re consistent with the energy-buffer hypothesis.
3. Depression and Neurological Conditions
There’s growing interest in creatine as an adjunctive treatment in major depressive disorder. Early trials suggest potential benefits when combined with standard therapies (Lyoo et al., 2012). In neurological disorders characterized by mitochondrial dysfunction—such as Parkinson’s and Huntington’s disease—creatine has also been investigated, with mixed but biologically plausible results.
Across these scenarios, a pattern emerges: when energy demand is elevated or metabolic efficiency is compromised, creatine seems more likely to matter.
Why Young, Healthy Adults See Less
In contrast, studies in young, well-rested, metabolically stable individuals often find small or inconsistent cognitive effects. That inconsistency has fueled skepticism around creatine as a “nootropic.”
But the review reframes the issue: if brain energy metabolism is already functioning optimally, adding more creatine may not produce noticeable gains. It’s not a stimulant. It doesn’t override biology. It supports existing energy systems.
That distinction is critical. Creatine may be foundational, but it is not performance magic.
Measuring Brain Creatine Is Harder Than It Sounds
Another important contribution of the review is methodological. Much of the brain research relies on magnetic resonance spectroscopy (MRS), a neuroimaging technique that can estimate concentrations of brain metabolites, including creatine.
However, measuring small changes in brain creatine is technically challenging. Brain uptake is slower and more tightly regulated than muscle uptake. Supplementation protocols that saturate muscle in days may take weeks—or longer—to meaningfully alter brain concentrations.
This helps explain why dosing strategy and duration matter more for brain studies than for muscle research. Short-term supplementation may simply be insufficient to detect central effects.
A Biologically Essential Compound
Creatine is not exotic. The body synthesizes it from amino acids, and it’s obtained from dietary sources like meat and fish. Its role in cellular energetics is evolutionarily conserved. In that sense, the review positions creatine not as a trendy cognitive enhancer, but as a core component of bioenergetic regulation.
The authors argue that the real question is no longer whether creatine is relevant to brain function. The accumulated literature suggests that it is. The more nuanced question is: under what physiological conditions does that relevance translate into measurable benefit?
That shift—from “Does it boost performance?” to “How does it support energy under stress?”—may mark a turning point in how creatine is discussed outside the gym.
The Bottom Line
Creatine does not sharpen the mind through stimulation. It appears to support it through stability—especially when metabolic demand is high or resilience is low.
As neuroimaging techniques improve and longer-term trials accumulate, creatine’s role in brain health may become clearer. For now, the evidence suggests something less sensational but more interesting: the brain, like muscle, depends on reliable energy buffering. Creatine is part of that system.
Not a shortcut. Not a miracle. But possibly a quiet piece of the brain’s energetic foundation.
Selected References
-
Rae, C., et al. (2003). Oral creatine monohydrate supplementation improves brain performance. Proceedings of the Royal Society B.
-
McMorris, T., et al. (2006). Creatine supplementation and cognitive performance after sleep deprivation. Physiology & Behavior.
-
Lyoo, I. K., et al. (2012). A randomized, double-blind, placebo-controlled trial of creatine augmentation in women with major depressive disorder. American Journal of Psychiatry.
-
Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological Reviews.
-
“Creatine Supplementation and the Brain: Have We Put the Cart Before the Horse?” Journal of Dietary Supplements. DOI: 10.1080/19390211.2026.2616440