In the world of fitness and nutrition, creatine monohydrate has long been hailed as a go-to supplement for building muscle strength and enhancing athletic performance. But recent scientific reviews are shifting the spotlight to its potential benefits for the brain, suggesting it could play a role in supporting cognitive function, neuroprotection, and even mental health. Two key publications—one from July 2025 and a fresh one released on January 20, 2026—provide compelling insights into how higher doses of creatine might elevate brain energy levels and performance, especially under stress. However, experts caution that while promising, the evidence is still preliminary and calls for more robust studies.

The 2025 Review: Higher Doses for Brain Bioenergetics

Published in the Journal of Psychiatry and Brain Science on July 23, 2025, the review by Nicholas Fabiano, MD, and Darren Candow, PhD, titled “Creatine Supplementation: More Is Likely Better for Brain Bioenergetics, Health and Function,” argues that creatine isn’t just for gym enthusiasts—it’s a potential ally for brain health. The brain consumes about 20% of the body’s energy at rest, relying heavily on adenosine triphosphate (ATP) for functions like thinking, memory, and decision-making. Creatine acts as a high-energy phosphate buffer, helping regenerate ATP quickly through phosphocreatine (PCr).

The authors highlight that while standard doses (around 5 grams per day) work well for muscles, the brain may require more—up to 10-20 grams daily—to achieve meaningful increases in creatine levels. Studies reviewed show that these higher doses can boost brain creatine by approximately 10%, with regional variations: up to 14.6% in the thalamus, 11.5% in white matter, 5.4% in the cerebellum, and 4.7% in gray matter. This elevation supports ATP production, offering neuroprotection and improved cognition, particularly during metabolic stress like sleep deprivation, hypoxia, or mental fatigue.

For instance:

• In sleep-deprived individuals, a single dose of about 25 grams improved cognitive performance and reduced fatigue.
• Among Alzheimer’s patients (average age 73), 20 grams daily for 8 weeks increased brain creatine by 11% and enhanced global cognition, including memory and language skills.
• For those with traumatic brain injury (TBI), doses of 0.4 grams per kg body weight for 6 months shortened amnesia duration and improved recovery metrics like disability and sociability.
• In depression, 2-10 grams daily augmented antidepressant effects, with higher doses (10 grams) doubling PCr increases in the frontal lobe compared to lower ones.

The review also explores innovative strategies to enhance brain uptake, such as combining creatine with glycocyamine (a precursor), using cyclocreatine analogs, intranasal delivery, or modulating the creatine transporter (CT1) protein. These could bypass limitations like the blood-brain barrier’s lower permeability compared to muscles.

The 2026 Update: Caution Amid Promise

Fast-forward to today, January 20, 2026: Candow, along with co-authors including Eric Rawson, PhD, and others, published a follow-up review in the Journal of Dietary Supplements titled “Creatine Supplementation and the Brain: Have We Put the Cart Before the Horse?” This piece takes a more measured tone, emphasizing that while creatine regulates brain bioenergetics, its full efficacy remains “largely unknown” due to challenges in accurately measuring brain creatine levels via magnetic resonance spectroscopy (MRS). Factors like voxel placement, signal quality, and analysis methods can skew results, leading to inconsistencies across studies.

The review reaffirms that supplementation can increase brain creatine in a dose- and duration-dependent way, with benefits shining through during acute stressors. For example, it helps mitigate cognitive deficits from sleep deprivation, mental fatigue, or low oxygen environments. There’s also emerging evidence for therapeutic applications:

• In Alzheimer’s disease, major depressive disorder, and mild TBI, creatine shows preliminary promise in improving symptoms.
• It may even enhance aspects of sleep quality.

However, the authors stress the limitations: results are preliminary, with inconsistent findings stemming from varying methodologies, small sample sizes, and short study durations. They argue that the field may be advancing claims ahead of solid evidence—hence the “cart before the horse” metaphor. A call for more rigorous, standardized trials is central, including larger cohorts, longer interventions, and better controls for measurement biases. Future research should also dissect mechanisms, like how creatine influences regional brain function and interacts with stressors or clinical conditions.

Safety and Practical Recommendations

Both reviews underscore creatine’s strong safety profile for healthy adults at standard doses (3-5 grams daily). No serious adverse events were reported in the studies examined, even at higher levels like 20 grams per day for weeks. That said, long-term effects of elevated doses on the brain warrant further scrutiny.

For those considering supplementation:

• Opt for Quality: Choose reputable sources like Creapure, a purified form of creatine monohydrate, to minimize impurities.
• Consult a Professional: Especially for doses above 5 grams or if you have pre-existing conditions (e.g., kidney issues), talk to a doctor. This is crucial for tailoring to individual needs, such as during pregnancy, aging, or mental health challenges.
• Dosing Strategy: Start with 3-5 grams daily for maintenance. For brain-specific benefits, higher loading (20 grams split into doses for 5-7 days) followed by maintenance might be explored under guidance, but evidence suggests sustained higher intake (10-20 grams) could be key—pending more data.
• Who Might Benefit?: Athletes under stress, older adults facing cognitive decline, vegetarians (who often have lower baseline creatine), or anyone dealing with sleep issues or mental fatigue.

The Bigger Picture: A Shift in Perspective

These reviews mark a paradigm shift: creatine is evolving from a muscle-centric supplement to a potential tool for holistic health, bridging physical and cognitive realms. Incorporating creatine could support brain resilience alongside habits like exercise, sleep, and nutrition. But remember, it’s not a magic pill—the evidence is exciting but early-stage.

As research progresses with more rigorous trials, we may unlock even greater applications. In the meantime, if you’re healthy and curious, starting with a quality supplement after a doctor’s nod could be a smart move. Stay tuned for updates in this rapidly evolving field.