Dose-Dependent Effects of Caffeine on Cognitive Performance, Hormonal Regulation, and Gut Microbiota across Adulthood

Dose-Dependent Effects of Caffeine on Cognitive Performance and Gut Microbiota

Authors

  • Sidra Hasnain Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan
  • Faiza Naheed Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
  • Aiman Mahmood Faculty of Pharmacy, Minhaj University, Lahore, Pakistan
  • Umar Raees Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan
  • Maria Fareed Siddiqui Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan
  • Maha Ikram Faculty of Health Sciences, Charles Darwin University, Darwin, Australia

DOI:

https://doi.org/10.54393/df.v7i2.213

Keywords:

Caffeine, Cognitive Performance, Reaction Time, Gut Microbiota, Cortisol, Adrenaline, Dose-Response

Abstract

Caffeine is a psychoactive drug that has a wide range of uses, including being consumed to increase alertness and cognitive function. Recently, there has also been some evidence that caffeine can influence biochemical markers and gut microbiota composition, which also requires further research. Objectives: To assess the dose-dependent effects of caffeine on reaction time, alertness, and cognitive performance in various demographic groups and to investigate its biochemical and microbiological effects. Methods: This study used a double-masked, quasi-experimental design. Participants were given caffeine in low (50 mg), moderate (100 mg), or high (200 mg) doses in separate sessions with a 48-hour washout period and placebo control. Reaction time, self-reported alertness, and cognitive task performance were measured. The blood and stool samples were taken before and after caffeine consumption to assess cortisol, adrenaline, and gut microbiota profiles using 16S rRNA sequencing. Results: No statistically significant differences in reaction time and alertness were observed between any of the caffeine doses (p>0.050). A significant reduction in cortisol levels was observed at the higher dose (p=0.048), but no change in adrenaline levels was seen. No significant differences in the relative abundance of bacterial phyla were found, except for Firmicutes, which was moderately up-regulated by caffeine (p=0.049). Performance improvements showed trends favoring younger adults, though these were not statistically significant. Conclusions: This hypothesis‑generating study demonstrates trends toward dose‑dependent hormonal and microbial modulation (notably a reduction in cortisol at 200 mg and an increase in Firmicutes at 100 mg). However, no statistically significant cognitive enhancements were observed. These preliminary findings warrant confirmation in larger, adequately powered studies before clinical recommendations can be made.

References

1. Reddy VS, Shiva S, Manikantan S, Ramakrishna S. Pharmacology of Caffeine and Its Effects on the Human Body. European Journal of Medicinal Chemistry Reports. 2024 Apr; 10: 100138. doi: 10.1016/j.ejmcr.2024.100138.

2. Hasnain A, Kabir M, Siddiqui MF, Jafferi A, Rafi U. Diet, Lifestyle and Immunity. Diet Factor (Journal of Nutritional and Food Sciences). 2020 Dec: 09-12. doi: 10.54393/df.v1i02.17.

3. Guest NS, VanDusseldorp TA, Nelson MT, Grgic J, Schoenfeld BJ, Jenkins ND et al. International Society of Sports Nutrition Position Stand: Caffeine and Exercise Performance. Journal of the International Society of Sports Nutrition. 2021 Jan; 18(1): 1. doi: 10.1186/s12970-020-00383-4.

4. Hussain A, Koser N, Aun SM, Siddiqui MF, Malik S, Ali SA. Deciphering the Role of Probiotics in Mental Health: A Systematic Literature Review of Psychobiotics. Beneficial Microbes. 2024 Nov; 16(2): 135-56. doi: 10.1163/18762891-bja00053.

5. Parry D, Iqbal S, Harrap I, Oeppen RS, Brennan PA. Caffeine: Benefits and Drawbacks for Technical Performance. British Journal of Oral and Maxillofacial Surgery. 2023 Apr; 61(3): 198-201. doi: 10.1016/j.bjoms.2023.01.007.

6. Bougrine H, Ammar A, Salem A, Trabelsi K, Jahrami H, Chtourou H et al. Effects of Various Caffeine Doses on Cognitive Abilities in Female Athletes with Low Caffeine Consumption. Brain Sciences. 2024 Mar; 14(3): 280. doi: 10.3390/brainsci14030280.

7. Kim H, Kang SH, Kim SH, Kim SH, Hwang J, Kim JG et al. Drinking Coffee Enhances Neurocognitive Function by Reorganizing Brain Functional Connectivity. Scientific Reports. 2021 Jul; 11(1): 14381. doi: 10.1038/s41598-021-93849-7.

8. Zhang B, Liu Y, Wang X, Deng Y, Zheng X. Cognition and Brain Activation in Response of Various Doses of Caffeine: A Near-Infrared Spectroscopy Study. Frontiers in Psychology. 2020 Jul; 11: 1393. doi: 10.3389/fpsyg.2020.01393.

9. Haskell-Ramsay CF, Jackson PA, Forster JS, Dodd FL, Bowerbank SL, Kennedy DO. The Acute Effects of Caffeinated Black Coffee on Cognition and Mood in Healthy Young and Older Adults. Nutrients. 2018 Sep; 10(10): 1386. doi: 10.3390/nu10101386.

10. Nehlig A. Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption. Pharmacological Reviews. 2018 Apr; 70(2): 384-411. doi: https://doi.org/10.1124/pr.117.014407

11. Demura S, Aoki H, Mizusawa T, Soukura K, Noda M, Sato T. Gender Differences in Coffee Consumption and Its Effects in Young People. Food and Nutrition Sciences. 2013 Jul; 4(7): 748. doi: 10.4236/fns.2013.47096.

12. Liu C, Wang L, Zhang C, Hu Z, Tang J, Xue J et al. Caffeine Intake and Anxiety: A Meta-Analysis. Frontiers in Psychology. 2024 Feb; 15: 1270246. doi: 10.3389/fpsyg.2024.1270246.

13. Ridho FM, Maulidina AA, Allifiah BP. Correlation Between Salivary Cortisol Levels in Patients with Psychological Stress and Incidence of Recurrent Aphthous Stomatitis: A Scoping Review. Indonesian Journal of Dentistry. 2024 Apr; 4(1): 23-33. doi: https://doi.org/10.26714/ijd.v4i1.14026

14. Kaur J, Gandhi J, Sharma S. Physiology, cortisol. InStatPearls [Internet] 2025 Dec 1. StatPearls Publishing.

15. Pedroza Matute S and Iyavoo S. Exploring the Gut Microbiota: Lifestyle Choices, Disease Associations, and Personal Genomics. Frontiers in Nutrition. 2023 Oct; 10: 1225120. doi: 10.3389/fnut.2023.1225120.

16. Diamond E, Hewlett K, Penumutchu S, Belenky A, Belenky P. Coffee Consumption Modulates Amoxicillin-Induced Dysbiosis in the Murine Gut Microbiome. Frontiers in Microbiology. 2021 Jun; 12: 637282. doi: 10.3389/fmicb.2021.637282.

17. Saygili S, Hegde S, Shi XZ. Effects of Coffee on Gut Microbiota and Bowel Functions in Health and Diseases: A Literature Review. Nutrients. 2024 Sep; 16(18): 3155. doi: 10.3390/nu16183155.

18. Rosa F, Marigliano B, Mannucci S, Candelli M, Savioli G, Merra G et al. Coffee and Microbiota: A Narrative Review. Current Issues in Molecular Biology. 2024 Jan; 46(1): 896-908. doi: 10.3390/cimb46010057.

19. Butt O, Jafri L, Rani R, Ghazanfar S, Iqbal S. Pediococcus Pentosaceus Strain SPARC2 as a Potential Probiotic Food Supplement: Genomic Insight, Probiotic Potential, and Biosafety Profiling in BALB/c Mice. Archives of Microbiology. 2025 Nov; 207(11): 1-7. doi: 10.1007/s00203-025-04496-9.

20. Irfan H, Ghori I, Ajmal W, Bibi B, Ghazanfar S, Adnan M, Ansari AA. Functional Genomics and Probiotic Traits of Lactiplantibacillus plantarum MB685 from Fermented Broccoli: Gut Health and Metabolic Insights. Molecular Nutrition & Food Research. 2026 Jan; 70(1): e70209. doi: 10.1002/mnfr.70209.

Downloads

Published

2026-06-30

Issue

Section

Original Article

How to Cite

Hasnain, S., Naheed, F., Mahmood, A., Raees, U., Siddiqui, M. F., & Ikram, M. (2026). Dose-Dependent Effects of Caffeine on Cognitive Performance, Hormonal Regulation, and Gut Microbiota across Adulthood: Dose-Dependent Effects of Caffeine on Cognitive Performance and Gut Microbiota. DIET FACTOR (Journal of Nutritional and Food Sciences), 7(2), 15-20. https://doi.org/10.54393/df.v7i2.213

Similar Articles

31-40 of 47

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)