HPLC Confirms Caffeine Dose to Fight Fatigue

Researchers at the 991st Hospital of Joint Logistic Support Force of People's Liberation Army (Xiangyang, Hubei, China)looked at whether skipping a nap made people mentally tired, using heart rate patterns, performance on thinking tasks, and how tired people said they felt to measure it. The researchers also tested whether caffeine tablets could help reverse that mental tiredness. To make sure the caffeine dose was accurate, content was quantified using high-performance liquid chromatography (HPLC). A paper based on this research was published in the journal Frontiers in Public Health.¹

Why Does Sleep Loss Matter, and Why Is Tracking Mental Fatigue Important?

Sleep is essential for keeping the body running normally. Even a small amount of missed sleep can affect how well the brain works, making it harder to focus or remember things.^2-4 Studies have shown that even short-term sleep loss can hurt various brain functions such as staying alert, thinking quickly, focusing, and remembering things. Because of this, finding reliable ways to track and treat mental fatigue is especially important for people in certain jobs, like those involving safety, quick decision-making, or long hours.^5,6

Does Skipping a Nap Cause Measurable Mental Fatigue, and Can Caffeine Reverse It?

For this early-stage pilot study, researchers recruited ten healthy people who normally took naps regularly. Everyone in the study had their nap taken away to make them mentally tired, and everyone eventually got the caffeine tablet; there was no separate placebo group, and people weren't randomly assigned to different groups. Researchers measured how sleepy people felt, how well they could focus on a computer-based attention task, and their heart rate patterns at several points during the study, then compared these before and after giving people the caffeine tablet. Without caffeine, people reported feeling notably sleepier after skipping their nap compared to earlier on, but their performance on the attention task didn't worsen. Their heart rate patterns did shift somewhat, but these changes were more likely tied to the natural rise and fall of alertness throughout the day rather than being a clear, statistically meaningful effect. After taking the low-dose caffeine tablet, people didn't report feeling sleepier, and their accuracy on the attention task improved in a way that was statistically meaningful. Their heart rate patterns also changed in ways that were statistically meaningful, suggesting the caffeine was having a real, measurable effect on their body and focus.¹

“In this pilot study,” write the authors of the paper,¹ “the alignment between subjective and objective indices suggests that low-dose COT is associated with favorable changes in the MF state of volunteers following sleep deprivation.”

That said, because this was a small, exploratory study, these results are just a starting point; the researchers believe that larger studies are needed where participants are randomly assigned to either caffeine or a fake pill (without knowing which one they received) to confirm whether these effects really hold up. Future research, in their opinion, should also look at whether different caffeine doses matter, whether men and women respond differently, and how the time of day affects heart-rate-based measures of tiredness. It would also help to combine heart rate data with other measurements (such as brain oxygen levels, stress hormone levels in saliva, and eye movement tracking) alongside performance tests, to get a fuller picture of mental fatigue. Larger, well-designed studies across multiple research sites, according to the research team, would help confirm whether this approach for measuring mental fatigue truly works and how it compares to other existing methods. Ultimately, in the minds of the researchers, this kind of research could help doctors and researchers develop more precise, targeted ways to treat or prevent mental fatigue.¹

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References

1. Fan, Y. Z.; Li, S. Y.; Lin, X. L. et al. The Intervention Effect of Caffeine Oral Tablets on Mental Fatigue Induced by Nap Deprivation: Based on Assessments of Heart Rate Variability, Cognitive Performance and Subjective Fatigue-A Pilot Study. Front Public Health 2026, 14, 1830975.DOI: 10.3389/fpubh.2026.1830975
2. Axelsson, J.; Ingre, M.; Kecklund, G. et al. Sleepiness as Motivation: A Potential Mechanism for How Sleep Deprivation Affects Behavior. Sleep 2020, 43 (6), zsz291. DOI: 10.1093/sleep/zsz291
3. Cullen, T.; Thomas, G.; Wadley, A. J. Sleep Deprivation: Cytokine and Neuroendocrine Effects on Perception of Effort. Med Sci Sports Exerc. 2020, 52 (4), 909-918. DOI: 10.1249/MSS.0000000000002207
4. Gordji-Nejad, A.; Matusch, A.; Kleedörfer, S. et al. Single Dose Creatine Improves Cognitive Performance and Induces Changes in Cerebral High Energy Phosphates During Sleep Deprivation. Sci Rep. 2024, 14 (1), 4937. DOI: 10.1038/s41598-024-54249-9
5. Kayser, K. C.; Puig, V. A.; Estepp, J. R. Predicting and Mitigating Fatigue Effects Due to Sleep Deprivation: A Review. Front Neurosci. 2022, 16, 930280.DOI: 10.3389/fnins.2022.930280
6. Lu, K.; Sjörs Dahlman, A.; Karlsson, J. et al. Detecting Driver Fatigue Using Heart Rate Variability: A Systematic Review. Accid Anal Prev. 2022, 178, 106830. DOI: 10.1016/j.aap.2022.106830