A Wide-Eyed Approach to Caffeine

Caffeine is often found in analgesics because it lowers gastric pH, increases antinociceptive effects, drug absorption and gastric motility, and improves mood and reaction time (Lipton et al., 2017). It works to mitigate pain by activating the pain-suppressing noradenosine pathway and acting as a nonselective antagonist of adenosine A1, A2A and A2B receptors which speeds nerve cell communication and results in vasoconstriction (Lipton et al. 2017, Chen et al., 2018). Caffeine is an adenosine receptor antagonist and blocks the detection of pain by blocking adenosine receptors and inhibiting phosphodiesterases (Mantegazza et al., 1984).

Caffeine absorbs rapidly and has a half-life of 3–6 hours. This can cause consumers to become dependent on its stimulating effects. Overconsumption of caffeinated soda in adolescents has been associated with caffeine-induced headache. Adolescents consuming 200mg caffeine daily presented with daily headaches until soda intake was gradually discontinued over a two-week period (Hering-Hanit, R. & Gadoth, N., 2003). According to Juliano, et al. (2012), the mechanism of caffeine-withdrawal headache is believed to be an “increased functional sensitivity to endogenous adenosine via the upregulation of adenosine receptors.” In this study, participants consuming >100mg caffeine per day reported significantly higher incidence of headaches during caffeine abstinence (Juliano, L., et al., 2012).

Caffeine consumption has also been linked to side effects such as hypoglycemia and difficulty sleeping. In one study, caffeine triggered a decrease in middle cerebral artery velocity, and increased epinephrine. Participants reported feeling hypoglycemic marked by trembling, weakness, facial flushing and palpitations. Norepinephrine, growth hormone, and cortisol also increased as a result of caffeine intake (Kerr et al., 1993). Another study found that caffeine ingestion near bedtime affected individuals’ sleep regarding later bedtime, sleep duration, and fragmentation (Clark & Landolt, 2017).   

Not all side effects of caffeine are negative. Caffeine has been associated with improved mental performance on cognitive tasks and decreased cognitive decline with aging. It has also been shown that caffeine consumption in mid-life may reduce Alzheimer’s disease by up to 65% (Arendash & Cao, 2010).



Arendash, G. W., & Cao, C. (2010). Caffeine and coffee as therapeutics against Alzheimer’s disease. Journal of Alzheimer’s Disease: JAD20 Suppl 1S117-S126. doi:10.3233/JAD-2010-091249. Retrieved from

Chen, X., Chen, Z., Dong, Z., Liu, M. & Yu, S. (2018). Morphometric changes over the whole brain in caffeine-containing combination-analgesic-overuse headache. Molecular Pain; 14: 174. Retrieved from

Clark, & Landolt. (2017). Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep Medicine Reviews, 31(C), 70-78. Retrieved from

Hering-Hanit, R., & Gadoth, N. (2003). Caffeine-induced headache in children and adolescents. Cephalalgia: An International Journal of Headache, 23(5), 332-335. Retrieved from

Juliano, L. M., Huntley, E. D., Harrell, P. T., & Westerman, A. T. (2012). Development of the caffeine withdrawal symptom questionnaire: Caffeine withdrawal symptoms cluster into 7 factors. Drug and Alcohol Dependence, 124, 229-234. 10.1016/j.drugalcdep.2012.01.009 Retrieved from

Kerr, D., Sherwin, R. S., Pavalkis, F., Fayad, P. B., Sikorski, L., Rife, F., . . . During, M. J. (1993). Effect of caffeine on the recognition of and responses to hypoglycemia in humans. Annals of Internal Medicine, 119(8), 799-804. Retrieved from

Lipton, R., Diener, H., Robbins, M., Garas, S. & Patel, K. (2017). Caffeine in the management of patients with headache. The Journal of Headache and Pain 18(1): 107. Retrieved from

Mantegazza, P., Tammiso, R., Zambotti, F., Zecca, L. & Zonta, N. (1984). Purine involvement in morphine antinociception. Br. J. Pharmac; 83: 883-888. Retrieved from


Kate Daugherty is a Functional Nutritionist and Certified Nutrition Specialist candidate specializing in mind-body wellness. She combines a science-based approach with natural therapies to bring the physiological body into balance. Kate offers nutritional consultation and functional medicine healing at her clinic, The Facility, in Denver, Colorado. Read more about her nutritional approach here and her background here.

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