Did you miss Caffeine and the Brain: Part 1? Read it HERE.
In Caffeine and the Brain: Part 1, we looked at how caffeine has become a universal habit and why it can be detrimental to achieving maximal health. We discussed the egregious consumption of a pesticide and stimulant, but how exactly does caffeine work, scientifically, once it gets inside our brain? It acts as a central nervous system stimulant,1 by binding to adenosine receptor sites, blocking adenosine from doing its job.2
Adenosine is an inhibitory neurotransmitter, which normally helps the body relax.3 This explains why caffeine causes sleep issues4 and alertness when sleep-deprived.5 Caffeine molecules are stopping adenosine from doing its job.6
However, your body is smart, and is a big believer in a thing called “homeostasis,” meaning it likes to keep things the same.7 So when you start drinking large amounts of caffeine8 your body makes more of these adenosine receptor sites, and you need more caffeine to block them, since you feel caffeine’s effects via blocking a large majority of these receptors.9, 10
Caffeine is a vasoconstrictor, narrowing blood vessels, and decreases blood flow, and sometimes used in pain relief medications.11 By blocking adenosine from doing its job, caffeine also increases respiratory rate.12 However, caffeine ingestion promotes neurotransmitter release (acetylcholine, monoamines, etc.) which is how it does its job, as a stimulant.13 Meanwhile, dopamine and glutamate are released in the nucleus accumbens (your brain’s pleasure center).14
When following a Paleo Diet and lifestyle, look to the scientific basis behind leaving caffeine out. It’s better to rely on your body’s own natural energy stores. Natural sleep and wake cycles are ideal, and help your body function optimally.15 This isn’t possible when you are drinking lots of caffeine.16
And, as most of you already likely know, caffeine also causes cortisol to be released.17 Your body thinks some kind of emergency is happening, and it wants to prepare you. Humans need extremely huge doses of caffeine in order for it to become toxic.18 However, other animals are not nearly as tolerant (hence its original use as a pesticide).19 Below is the effect seen on a spider, that has ingested caffeine.20
Interestingly, caffeine is legal and unregulated, which is not at all the case for basically every other psychoactive drug in the world.21 In fact, Dr. William Dement, professor from Stanford University, posits if caffeine were introduced today, it would not be made legal.22 The addictive nature and withdrawal effects are well-documented23 among the sleep, stimulant, and biochemical effects.24
Genetically, caffeine has a stronger effect on some individuals, compared to others.25 Humans with at least one C variant of CYP1A2, a gene, react less favorably to caffeine, and metabolize it slower.26 This could possibly explain the difference between you, and your friend who goes off the rails on just one cup of espresso.
Besides this scientific evidence, caffeine depletes magnesium stores, causing many effects downstream.27 These effects can be exhibited as: poor sleep, muscle cramps and chronic pain.28 About 50% of people in the United States are deficient in magnesium, whether due to too much caffeine, or not enough magnesium consumption to begin with, though it’s likely both.29
Caffeine, if consumed, is best kept at the ‘therapeutic’ dose, of 100-200mg per day.30 Incorporating caffeine into your Paleo Diet isn’t advisable, however, if you’re looking to maximize its effects. If looking to minimize your pesticide load, organic coffee is more ideal, and green tea offers L-theanine, which has a calming effect on the brain, along with lower amounts of caffeine, compared with coffee.31, 32
Lastly, let us not forget that the most beneficial beverage of all…water! A Paleo Diet should be hydrating, and keep your cells happy! Raise your glass (or bottle) to good health!
1. Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev. 1992;17(2):139-70.
2. Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004;61(7-8):857-72.
3. Ribeiro JA. Purinergic inhibition of neurotransmitter release in the central nervous system. Pharmacol Toxicol. 1995;77(5):299-305.
4. Snel J, Lorist MM. Effects of caffeine on sleep and cognition. Prog Brain Res. 2011;190:105-17.
5. Daniello A, Fievisohn E, Gregory TS. Modeling the effects of caffeine on the sleep/ wake cycle. Biomed Sci Instrum. 2012;48:73-80.
6. Ribeiro JA, Sebastião AM. Caffeine and adenosine. J Alzheimers Dis. 2010;20 Suppl 1:S3-15.
7. Houseknecht KL, Portocarrero CP. Leptin and its receptors: regulators of whole-body energy homeostasis. Domest Anim Endocrinol. 1998;15(6):457-75.
8. Pallarés JG, Fernández-elías VE, Ortega JF, Muñoz G, Muñoz-guerra J, Mora-rodríguez R. Neuromuscular responses to incremental caffeine doses: performance and side effects. Med Sci Sports Exerc. 2013;45(11):2184-92.
9. Kaplan GB, Greenblatt DJ, Ehrenberg BL, et al. Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. J Clin Pharmacol. 1997;37(8):693-703.
10. Holtzman SG, Mante S, Minneman KP. Role of adenosine receptors in caffeine tolerance. J Pharmacol Exp Ther. 1991;256(1):62-8.
11. Dager SR, Layton ME, Strauss W, et al. Human brain metabolic response to caffeine and the effects of tolerance. Am J Psychiatry. 1999;156(2):229-37.
12. Barry RJ, Clarke AR, Johnstone SJ, Rushby JA. Timing of caffeine’s impact on autonomic and central nervous system measures: clarification of arousal effects. Biol Psychol. 2008;77(3):304-16.
13. Rossi S, De chiara V, Musella A, et al. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors. Mol Nutr Food Res. 2010;54(4):525-31.
14. Solinas M, Ferré S, You ZB, Karcz-kubicha M, Popoli P, Goldberg SR. Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. J Neurosci. 2002;22(15):6321-4.
15. Krystal AD. How the circadian rhythm affects sleep, wakefulness, and overall health: background for understanding shift work disorder. J Clin Psychiatry. 2012;73(2):e05.
16. Sherman H, Gutman R, Chapnik N, Meylan J, Le coutre J, Froy O. Caffeine alters circadian rhythms and expression of disease and metabolic markers. Int J Biochem Cell Biol. 2011;43(5):829-38.
17. Lovallo WR, Whitsett TL, Al’absi M, Sung BH, Vincent AS, Wilson MF. Caffeine stimulation of cortisol secretion across the waking hours in relation to caffeine intake levels. Psychosom Med. 2005;67(5):734-9.
18. Kerrigan S, Lindsey T. Fatal caffeine overdose: two case reports. Forensic Sci Int. 2005;153(1):67-9.
19. Bonati M, Jiritano L, Bortolotti A, et al. Caffeine distribution in acute toxic response among inbred mice. Toxicol Lett. 1985;29(1):25-31.
20. Witt PN. Drugs alter web-building of spiders: a review and evaluation. Behav Sci. 1971;16(1):98-113.
21. Reissig CJ, Strain EC, Griffiths RR. Caffeinated energy drinks–a growing problem. Drug Alcohol Depend. 2009;99(1-3):1-10.
22. Dement, W. and Vaughan, C. (1999). The promise of sleep. 1st ed. New York: Delacorte Press.
23. Griffiths RR, Chausmer AL. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi. 2000;20(5):223-31.
24. Smith JE, Lawrence AD, Diukova A, Wise RG, Rogers PJ. Storm in a coffee cup: caffeine modifies brain activation to social signals of threat. Soc Cogn Affect Neurosci. 2012;7(7):831-40.
25. Cornelis MC, Byrne EM, Esko T, et al. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry. 2014;
26. Available at: //www.pharmgkb.org/pathway/PA165884757. Accessed October 15, 2014.
27. Kynast-gales SA, Massey LK. Effect of caffeine on circadian excretion of urinary calcium and magnesium. J Am Coll Nutr. 1994;13(5):467-72.
28. Johnson S. The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses. 2001;56(2):163-70.
29. Al-ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis. 1994;24(5):737-52.
30. Jenkins NT, Trilk JL, Singhal A, O’connor PJ, Cureton KJ. Ergogenic effects of low doses of caffeine on cycling performance. Int J Sport Nutr Exerc Metab. 2008;18(3):328-42.
31. Cabrera C, Artacho R, Giménez R. Beneficial effects of green tea–a review. J Am Coll Nutr. 2006;25(2):79-99.
32. Chacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: a literature review. Chin Med. 2010;5:13.