BLUF (Bottom Line Up Front)
This study tested whether taking a single high dose of creatine monohydrate (0.35 g/kg bodyweight) could reduce the effects of sleep deprivation on mental performance and brain energy levels. Compared to a placebo, creatine improved memory, attention, and mental processing speed, and changed how the brain used and stored energy. These effects appeared within 3.5 hours, peaked at 4 hours, and lasted for up to 9 hours. The results challenge the idea that creatine only works after weeks of supplementation.
Purpose of the Study
To determine whether an acute, high single dose of oral creatine could counteract the cognitive and metabolic decline caused by sleep deprivation in healthy adults.
Subjects
- Number of Participants: 15 healthy adults (8 female)
- Age: 20 to 28 years (average 23 years)
- Health Screening: No diagnosed sleep disorders, neurological or psychiatric conditions, or medication use
- Controls: No caffeine or alcohol for 48 hours before testing; regular sleep patterns monitored for 2 weeks prior
- Ethics: Approved by RWTH Aachen University ethics board
Methods
- Design: Double-blind, placebo-controlled, randomized crossover
- Protocol: Two overnight lab sessions with 21 hours of continuous wakefulness. Each participant completed both sessions—one with creatine and one with placebo—at least 5 days apart.
- Intervention:
- 0.35 g/kg creatine monohydrate or matching placebo (cornstarch) taken at 8:30 p.m.
- Testing Times: Baseline at 6:00 p.m., then again at 12:00 a.m., 2:00 a.m., and 4:00 a.m.
- Cognitive Tests Included:
- Word memory test
- Forward digit span (short-term memory)
- Psychomotor vigilance test (reaction time)
- Triple N-back (working memory)
- Logic, language, and numeric problem-solving tasks
- Brain Imaging: Magnetic resonance spectroscopy to measure phosphocreatine (PCr), inorganic phosphate (Pi), adenosine triphosphate beta (ATP-β), total creatine (tCr), brain pH, and other metabolites in multiple brain regions
Key Findings
1. Creatine Increased Cognitive Performance Under Sleep Deprivation
Compared to placebo, creatine:
- Increased word memory test accuracy by 10.3%
- Increased processing speed in:
- Word memory task by 17.7%
- Language task by 29.1%
- Logic task by 16.0%
- Numeric task by 24.0%
- Increased numeric task accuracy by 13.9% at 2:00 a.m.
- Decreased fatigue by 8% at 2:00 a.m. and 4:00 a.m.
- Improved reaction time during the psychomotor vigilance test
2. Creatine Changed Brain Energy Metabolism
The researchers measured several key indicators of how the brain manages and uses energy. Compared to placebo, creatine:
- Increased the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) in several regions. This ratio is a marker of the brain’s energy reserve. A higher PCr/Pi suggests better ability to regenerate energy (ATP) during stress.
- Increased total creatine (tCr) in the left medial parietal region by 4.2%. This indicates successful delivery of creatine to brain cells—something previously believed to require weeks of supplementation.
- Decreased adenosine triphosphate beta (ATP-β) levels in several motor and premotor brain regions by 13–18%. ATP-β is the energy “spend” signal, so this drop reflects energy being used—especially in areas doing more cognitive work.
- Maintained brain pH levels, while pH dropped significantly in the placebo condition. A drop in pH reflects increasing acidity in the brain due to metabolic fatigue. Creatine prevented this acidification.
Put simply, creatine boosted the brain’s fuel storage (PCr), improved its ability to make energy quickly (higher PCr/Pi), and allowed it to spend that energy where needed (lower ATP-β), without tipping into acidity or energy crash.
3. Effects Were Time-Dependent
- Creatine’s benefits began at 3.5 hours post-ingestion, peaked around 4 hours, and lasted up to 9 hours.
4. Brain Energy Levels Tracked with Mental Performance
- Higher PCr/Pi levels were linked with better performance on numeric problem-solving and digit span memory tasks
- Lower ATP-β levels were associated with faster reaction times on the vigilance test
5. Creatine Was Well Tolerated
- In this study, a single dose of creatine at 0.35 g/kg bodyweight was safe and well tolerated with no side effects reported. No participants experienced gastric discomfort or other physical complaints.
Conclusion
A single, large oral dose of creatine improved mental performance and brain energy markers during 21 hours of sleep deprivation. Creatine increased energy availability, prevented metabolic stress, and helped maintain cognitive function. These results overturn the assumption that brain effects of creatine require long-term loading. The key factor appears to be high energy demand combined with high creatine availability, which may trigger acute uptake into the brain.
Bibliography
Gordji-Nejad, A., Matusch, A., Kleedörfer, S., Patel, H.J., Drzezga, A., Elmenhorst, D., Binkofski, F., & Bauer, A. (2024). Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports, 14(4937). https://doi.org/10.1038/s41598-024-54249-9
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