Coffee & Health
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New research could help understand how caffeine consumption affects the brain and body

September 13, 2017

Experiments on human neuron cells may explain caffeine’s effects on disease risk, memory, and alertness.

New research has investigated caffeine’s effect on neurons at dose levels comparable with normal consumption habits. The study is a timely exploration of the cellular processes that may help explain caffeine’s many physiological effects, such as increasing alertness1,2, and potential ability to reduce risk of neurodegenerative diseases3-7.

Researchers from Sweden, Finland, the UK and Japan conducted the first study of caffeine-induced perturbation of gene expression changes in a human neuronal cell model – the closest model of the human central nervous system. Their paper, ‘Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth’8, is now online ahead of print in Scientific Reports.

The study results showed that caffeine promotes neuronal connections, providing possible mechanistic insights into caffeine’s enhancing effects on memory and cognition.

The researchers stimulated neurons with normal consumption levels of caffeine (3 μM and 10 μM), over periods of 1, 3 and 9 hours. The results showed dosage-dependent activation of immediate early genes after 1 hour. Immediate early genes are genes that respond rapidly – often within minutes – to cellular stimuli. Some of these genes are linked to the immune system, and others are linked to learning and memory.

The experiment revealed that caffeine upregulated some neuronal processes, and downregulated others. Upregulation ‘boosts’ the signal to a cell, much like boosting radio signal to ensure the message is delivered. Downregulation reduces the signal to the cell. A cell will receive signals from various sources – such as the immune and nervous systems – that tell it what to do.

The study identified novel genes that respond to caffeine stimulation and suggests potential mechanisms for the effects of caffeine on neuronal cells.

Caffeine was found to downregulate immune system processes and upregulate neuronal projection development processes (which are linked to memory and other neuronal connectivity). Overall, more genes were downregulated than upregulated by caffeine, but the higher the caffeine dose in the experiment, the more immediate early genes were activated.

Professor Juha Kere of the Karolinska Institutet, Sweden, and one of the paper’s authors, said: “The caffeine in coffee is one of the most widely-consumed psychoactive substances in the world, but we know relatively little about how it affects neurons and their cellular function. Learning more about how caffeine affects our bodies at this level could help explain why coffee and caffeine seem to reduce risk of certain diseases, and improve memory and cognition.”

Professor Kere continued: “For example, our research shows that inhibition on neuronal connectivity is downregulated by normal levels of caffeine – similar levels to what you might drink in a day. This might well help understanding in part why coffee has been suggested to improve memory and protect against memory loss in the elderly.”


Notes to editors

  • The paper ‘Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth’ can be read online:
  • This paper was funded in part by ISIC but this has not in any way affected the production or content of the research. The authors have declared no conflict of interest.


  1. Lorist M.M. and Tops M. (2003) Caffeine, fatigue, and cognition. Brain Cogn, 53(1):82-94.
  2. Lazarus M. et al. (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J. Neurosci, 31(27):10067-75.
  3. Quintana J.L.B et al. (2007) Alzheimer’s disease and coffee: a quantitative review. Neurol. Res, 29(1):91-5.
  4. Santos C. et al. (2010) Caffeine intake and dementia: systematic review and meta-analysis. J. Alzheimers. Dis, 20 Suppl 1:S187-204.
  5. Fredholm B.B. et al. (1999) Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use. Pharmacol. Rev, 51(1):83-133.
  6. Costa J. et al. (2010) Caffeine exposure and the risk of Parkinson’s disease: a systematic review and meta-analysis of observational studies. J. Alzheimers. Dis, 20 Suppl 1:S221-38.
  7. Qi H. and Li S. (2014) Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatr. Gerontol. Int, 14(2):430-9.
  8. Yu N. et al. (2017) Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth. Sci. Rep, published online ahead of print.

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