High-Dose Creatine for Brain Health: Why 5g Isn't Enough
New research suggests the standard fitness dosage isn’t enough to fuel the mind—but navigating the brain’s defenses requires a massive shift in strategy.
This mini-review on creatine supplementation is a fascinating challenge to the status quo, proposing that the brain has metabolic requirements vastly different from our muscles. While taking large quantities has become a bit of a meme these days—with figures like Dr. Rhonda Patrick and Dr. Andrew Huberman discussing 10, 20, or even 40 grams a day—it seems like there is actually something substantial there. Fabiano and Candow’s paper highlights a critical physiological bottleneck: getting fuel past the blood-brain barrier is incredibly difficult, meaning the standard scoop in your morning shake might be falling short for cognitive longevity.
“The brain, although only accounting for 2% of body mass, utilizes approximately 20% of energy consumption at rest.”
What’s the Big Idea?
The biological reality is that the brain is stubborn when it comes to accepting help from the outside. While skeletal muscle has a robust transport system that eagerly soaks up creatine, the brain is guarded by a selective shield—the blood-brain barrier (BBB)—and lacks the same density of transporter proteins (CT1). In practical terms, this means the brain relies heavily on its own internal synthesis of creatine. However, during moments of high metabolic stress, such as solving complex problems or functioning on little sleep, that internal production often cannot keep up with the demand for rapid energy (ATP).
Building on that, the disparity between muscle saturation and brain saturation is striking. The review notes that magnetic resonance spectroscopy (MRS) scans show brain creatine levels rise significantly less than muscle levels after standard supplementation. In fact, single doses or short-term usage of standard amounts (like 5 grams) often show no statistically significant increase in the brain at all. This explains the push for higher numbers: to force enough creatine through that restrictive barrier, you likely need a systemic surplus far beyond what gym-goers have used for decades.
Why It Matters and What You Can Do
This research is a signal that we need to rethink dosing protocols if the goal is mental performance rather than physical size. The review points to compelling historical data to back this up, specifically regarding trauma. One standout example mentioned is a 2006 open-label study by Sakellaris et al., which looked at children and adolescents recovering from traumatic brain injury (TBI). The researchers administered a massive dose of 0.4 grams per kilogram of body weight—for a 50kg adolescent, that’s 20 grams a day. The results were profound: significant improvements in the duration of post-traumatic amnesia, time spent in intensive care, and overall cognitive recovery.
Beyond trauma, the implications extend to daily cognitive deficits. The paper discusses how high doses have successfully offset the cognitive crash associated with sleep deprivation and supported cognitive function in Alzheimer’s patients.
It’s a persuasive argument, though it presents a personal dilemma for many. Unfortunately for me, I can’t handle even 5 grams of creatine without feeling extremely agitated, which is frustrating because it does seem to reverse the effects of sleep deprivation for me. But for most people who don’t have this sensitivity, these findings offer a clear tactical advantage:
Consider “Brain Loading”: If you are tolerating 5 grams well but not feeling a mental boost, the data suggests increasing the dose (potentially up to 20 grams, split throughout the day) during demanding periods might be necessary to see changes on a cerebral level.
Target Acute Stressors: The benefits appear most pronounced during metabolic crises—like the TBI recovery mentioned above, severe mental fatigue, or periods of restricted sleep.
Vegans Should Prioritize This: Since vegetarians and vegans start with approximately 30% lower creatine stores, the impact of high-dose supplementation is often more dramatic and essential for leveling the playing field.
What’s Next on the Horizon
Innovation in this field is moving toward bypassing the blood-brain barrier entirely so we don’t have to rely on brute-forcing the system with massive doses. The paper explores the potential of Guanidinoacetic acid (GAA), a precursor that converts to creatine in the liver and may have superior transport kinetics into target tissues. There is even discussion of intranasal administration—sprays that could theoretically deliver creatine directly to the brain via the olfactory nerves, skipping the systemic hurdles of digestion and absorption.
Who knows, maybe soon we won’t need the giant scoops. If these delivery methods prove effective in humans, we could see a future where we target brain bioenergetics with precision, treating low brain energy as specifically as we treat a vitamin deficiency.
Safety, Ethics, and Caveats
Current medical understanding is still catching up to these high-dose protocols, and safety remains an open question for long-term use. The review critically notes that while “more is better” for efficacy (as seen in the TBI and Alzheimer’s data), we don’t yet know the optimal dose or if chronic high intake causes the body to downregulate its own transporters. There is a balance to strike between optimizing function and overwhelming the system.
And honestly, listening to your body is paramount. As I mentioned with my own reaction, more isn’t better if it makes you feel worse. While the meme of taking 40 grams captures attention, the reality is that biology is highly individual. The goal is to support the brain’s resilience, specifically in aging or stressed states, without introducing new side effects.
One Last Thing
If you are tracking your sleep or cognitive output and hitting a wall, this research suggests the solution might not be a different supplement, but simply a different dose of an old favorite.
Explore the Full Study
Creatine Supplementation: More Is Likely Better for Brain Bioenergetics, Health and Function
Fabiano, N., & Candow, D. (2025). Journal of Psychiatry and Brain Science, 10(4).
DOI: 10.20900/jpbs.20250006