Caffeine and the Brain: Part 1

Caffeine and the Brain: Part 1

Before switching to a Paleo Diet, many of us drank coffee on a regular basis.1 If not coffee, maybe an energy drink, espresso, or a diet or regular soda.2, 3 All of these beverages have one thing in common: caffeine. Caffeine is the world’s most popular psychoactive drug.4 Though a small amount (about 10%) of humans do not consume any of the stimulant, worldwide consumption is enough to make the average caffeine intake equivalent to about one drink, per person, per day.5, 6 With over 7 billion people in the world – that’s a LOT of caffeine.7

Caffeine is derived from plants, and acts as a pesticide.8, 9, 10 If that’s not disturbing enough, it’s also one of the most heavily sprayed crops, pesticide-wise, in the world.11, 12, 13, 14, 15, However, while pesticides can be destroyed in the roasting process, I would argue that anything sprayed heavily with pesticides, is not something worth consuming. Still feel comfortable nursing that cup next to you? Below, is a pest which burrows into and lays its eggs in coffee berries. It has genetically adapted from bacteria (via lateral gene transfer) which enables it to continue to invade coffee crops.16

Proc Natl Acad Sci U S A. Mar 13, 2012; 109(11): 4197–4202. Published online Feb 27, 2012.

Proc Natl Acad Sci U S A. Mar 13, 2012; 109(11): 4197–4202.
Published online Feb 27, 2012.

Since caffeine is so widely consumed, it is in the public’s interest to know exactly it is doing to your brain.17 Caffeine, chemically, is a member of the xanthine and alkaloid family.18 Other members of these families include cocaine, nicotine, morphine, psilocin, and codeine, to name but a few.19 Starting to second-guess that cup of coffee yet?

Caffeine, unfortunately, is one of the elements of “fast food America,” along with processed foods, added sugar, and television.20 A Paleo Diet is superior to this widespread way of living, in every single category.21 By taking time to savor your food, eating foods which make you healthier, and avoiding stimulants, you’ll maximize your own potential to be healthy.


Caffeine synthase and related methyltransferases in plants. Frontiers In Bioscience, Landmark, 9, 1833-1842, May 1, 2004

Here, we see the biosynthesis of caffeine. What we ultimately must understand from this process, is that theobromine is an important precursor to caffeine.22 Besides caffeine, theobromine itself has been studied to be the other psychopharmacologically active element in another, as-yet unnamed, caffeine-containing substance – chocolate.23 Beyond the psychopharmacological effects of theobromine, it also has been shown to be the main constituent that we come to crave when we eat chocolate.24 The other? Caffeine itself.

Caffeine Figure 3

Nutrients. Jan 2014; 6(1): 319–341.
Published online Jan 10, 2014.

Since we are all composed of different genetic and molecular material, our brains respond to caffeine differently.25, 26 In these diagrams, we see how different regions of the brain are affected and impacted by merely the sight of chocolate, which contains caffeine and theobromine.27 Some will immediately have activity in brain regions such as the pregenual cingulate cortex and medial orbitofrontal cortex.28 Others, will not.

Since chocolate is a multivariate compound, we must look at pure caffeine, to see what its effects are on your brain. Perhaps most alarmingly, caffeine restricts blood flow to the brain, by about 25%.29 This is not good. In the below two images, we can see the effects of reduced blood flow, graphically, in those who drink caffeine, and also the increase in blood flow, in those who are going through caffeine withdrawal.

Caffeine Figure 4

Hum Brain Mapp. Author manuscript; available in PMC Oct 1, 2010. Published in final edited form as:
Hum Brain Mapp. Oct 2009; 30(10): 3102–3114.

 Hum Brain Mapp. Author manuscript; available in PMC Oct 1, 2010. Published in final edited form as: Hum Brain Mapp. Oct 2009; 30(10): 3102–3114.

Hum Brain Mapp. Author manuscript; available in PMC Oct 1, 2010. Published in final edited form as:
Hum Brain Mapp. Oct 2009; 30(10): 3102–3114.

Besides these disturbing effects (cerebral blood flow is most definitely something you want more of, not less of), caffeine disrupts the ends of our DNA, causing aging.30 This process happens via telomeres, which normally protect the chromosome ends from degradation. Another suspect on this list? Alcohol, which shouldn’t be a surprise.31

A Paleo Diet removes these common vices, and instead offers healthy fats, nutrient-rich foods, and choices that help make you healthier. By taking time to savor your food, eating foods which make you healthier, and avoiding stimulants, you can reap the plethora of benefits offered by a Paleo lifestyle!


1. Gilbert RM. Caffeine consumption. Prog Clin Biol Res. 1984;158:185-213.

2. Heckman MA, Weil J, Gonzalez de mejia E. Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci. 2010;75(3):R77-87.

3. Persad LA. Energy drinks and the neurophysiological impact of caffeine. Front Neurosci. 2011;5:116.

4. Daly JW, Holmén J, Fredholm BB. [Is caffeine addictive? The most widely used psychoactive substance in the world affects same parts of the brain as cocaine]. Lakartidningen. 1998;95(51-52):5878-83.

5. Lovett R. Coffee: The demon drink? New Scientist. 2005;24:2518–2522.

6. Available at: // Accessed October 15, 2014.

7. Available at: // Accessed October 15, 2014.

8. Uefuji H, Tatsumi Y, Morimoto M, Kaothien-nakayama P, Ogita S, Sano H. Caffeine production in tobacco plants by simultaneous expression of three coffee N-methyltrasferases and its potential as a pest repellant. Plant Mol Biol. 2005;59(2):221-7.

9. Nathanson JA. Caffeine and related methylxanthines: possible naturally occurring pesticides. Science. 1984;226(4671):184-7.

10. Hollingsworth RG, Armstrong JW, Campbell E. Caffeine as a repellent for slugs and snails. Nature. 2002;417(6892):915-6.

11. Ngowi AV, Maeda DN, Partanen TJ, Sanga MP, Mbise G. Acute health effects of organophosphorus pesticides on Tanzanian small-scale coffee growers. J Expo Anal Environ Epidemiol. 2001;11(4):335-9.

12. Available at: // Accessed October 15, 2014.

13. Acuña R, Padilla BE, Flórez-ramos CP, et al. Adaptive horizontal transfer of a bacterial gene to an invasive insect pest of coffee. Proc Natl Acad Sci USA. 2012;109(11):4197-202.

14. Sakamoto K, Nishizawa H, Manabe N. Behavior of pesticides in coffee beans during the roasting process. Shokuhin Eiseigaku Zasshi. 2012;53(5):233-6.

15. Cetinkaya M, Von düszeln J, Thiemann W, Silwar R. [Organochlorine pesticide residues in raw and roasted coffee and their degradation during the roasting process]. Z Lebensm Unters Forsch. 1984;179(1):5-8.

16. Ioannidis P, Lu Y, Kumar N, et al. Rapid transcriptome sequencing of an invasive pest, the brown marmorated stink bug Halyomorpha halys. BMC Genomics. 2014;15:738.

17. Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51(1):83-133.

18. Schimpl FC, Kiyota E, Mayer JL, Gonçalves JF, Da silva JF, Mazzafera P. Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit. Phytochemistry. 2014;105:25-36.

19. Available at: // Accessed October 15, 2014.

20. Pereira MA, Kartashov AI, Ebbeling CB, et al. Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Lancet. 2005;365(9453):36-42.

21. Mellberg C, Sandberg S, Ryberg M, et al. Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a 2-year randomized trial. Eur J Clin Nutr. 2014;68(3):350-7.

22. Judelson DA, Preston AG, Miller DL, Muñoz CX, Kellogg MD, Lieberman HR. Effects of theobromine and caffeine on mood and vigilance. J Clin Psychopharmacol. 2013;33(4):499-506.

23. Smit HJ, Gaffan EA, Rogers PJ. Methylxanthines are the psycho-pharmacologically active constituents of chocolate. Psychopharmacology (Berl). 2004;176(3-4):412-9.

24. Smit HJ, Blackburn RJ. Reinforcing effects of caffeine and theobromine as found in chocolate. Psychopharmacology (Berl). 2005;181(1):101-6.

25. 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.

26. Cornelis MC, Byrne EM, Esko T, et al. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry. 2014;

27. Asmaro D, Liotti M. High-caloric and chocolate stimuli processing in healthy humans: an integration of functional imaging and electrophysiological findings. Nutrients. 2014;6(1):319-41.

28. Rolls ET, Mccabe C. Enhanced affective brain representations of chocolate in cravers vs. non-cravers. Eur J Neurosci. 2007;26(4):1067-76.

29. Addicott MA, Yang LL, Peiffer AM, et al. The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate?. Hum Brain Mapp. 2009;30(10):3102-14.

30. Romano GH, Harari Y, Yehuda T, et al. Environmental stresses disrupt telomere length homeostasis. PLoS Genet. 2013;9(9):e1003721.

31. Strandberg TE, Strandberg AY, Saijonmaa O, Tilvis RS, Pitkälä KH, Fyhrquist F. Association between alcohol consumption in healthy midlife and telomere length in older men. The Helsinki Businessmen Study. Eur J Epidemiol. 2012;27(10):815-22.

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“8” Comments

  1. Coffee reminds me of how cigarettes used to be… People will justify it by any means, no matter what anyone says to the contrary. A drug is a drug and human beings weren’t designed to consume these things on a daily basis, let alone become dependent upon them to function. I see article after article on “health” blogs justifying the use of caffeine daily, some even stating they drank their coffee or espresso to “clear their head”. If you’re eating this wonderful, nutritious diet, you should not need a stimulant to clear your head.

    Having personally been subjecting to many of the negative effects of caffeine, I tend to agree it’s not something people should be consuming daily. Ever get really hungry before lunch time? Like shaky, light headed hungry? Think it was from a sugar crash or something? It’s more likely from that morning cup of coffee. And women especially can be negatively affected by the hormone disruption that caffeine causes.

    Look, if you want your caffeine, no one is stopping you, but can we please stop trying to pretend like coffee is “paleo” or even good for you on a daily basis?

    BTW -I am an addict just as much as the next person. I quit cold turkey after figuring out thst the above mentioned symptoms were caused by caffeine and went to organic, water processed decaf. The first time I decided to get a regular, I was an addict all over again. Then I started getting ocular migraines, quit again, then decided to have another after a few weeks for the awesome buzz I got after abstaining for so long. So even though this substance does nothing but horrible things to me, I continually seek it out.

  2. Article needs stronger arguments to be convincing in any way. Perhaps dive deeper into “caffeine disrupts the ends of our DNA, causing aging” – that sounds concerning. We’ve already gone Paleo – be careful knocking many folk’s final simple pleasure – a cup of morning joe.

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  9. I think many already recognize the concerns about caffeine, but when they are drinking 5-6 cups of coffee or Monsters per day it isn’t that easy just to stop or even cut back significantly. I think folks would appreciate and benefit from a protocol for ditching the caffeine that addresses withdrawal symptoms, addicition, etc.

  10. What about all the studies that show/imply better cognitive skills / cardiovascular health / avoidance of cancer with coffee and cacao consumption ? I appreciate that your effort on this and thanks for sharing it but it also seems to be narrow looking and reductionist to me. Right now, I need more to be convinced that coffee and cacao consumption would be rather harmful in the context of the Paleo diet or anything else.

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