Caffeine
Caffeine is the most widely consumed psychoactive substance in the world, with coffee and tea representing our main dietary sources (1). The mechanism by which caffeine exerts its effects is now largely accepted to be through non-selective antagonism of adenosine A1 and A2A receptors (1), with A1 receptors being more closely related to neural activation and A2A receptor antagonism leading to vascular effects, including vasoconstriction and a reduction in cerebral blood flow (CBF) (1).
Caffeine has been shown to reduce cerebral blood velocity and CBF assessed using a number of different techniques (2-7). A linear dose relationship has been observed between reductions in CBF and caffeine following doses of 1,2.5 and 5mg/kg caffeine (8). Effects of caffeine on CBF are also dependent upon the level of caffeine habitually consumed. In a withdrawn state, habitual high consumers exhibit higher resting CBF as compared to low consumers, and caffeine use is significantly positively correlated with CBF following both placebo and caffeine (9,10). Caffeine has consistently been shown to improve reaction times (11-13) and alertness (14).
L-Theanine
L-theanine is a naturally occurring amino acid found almost uniquely in tea (Camellia sinensis), where it co-exists with caffeine. Its chemical structure is similar to that of the neurotransmitter glutamic acid (15)
Anxiolytic effects have been reported, whereby 200mg L-theanine reduced acute stress responses (subjective perception, heart rate and salivary immunoglobulin A) induced by a mental arithmetic task (16), and a 250 mg dose of L-theanine slowed reaction time on a visual probe task, indicating reduced anxiety (17). EEG studies have also provided some support for these findings with increases in resting alpha activity observed following 50 mg (18) and 200mg L-theanine (18), which the authors interpret as being indicative of relaxation. A dose of250mg of L-theanine has also been shown to decrease tonic alpha activity during task performance (19).
Synergistic effects
In terms of cognitive function, L-theanine in isolation has been shown to engender decrements in performance (20,21). However, when administered together, L-theanine modulates or potentiates the effects of caffeine. For instance, Haskell et al. (22) reported that a number of effects were evident following a combination of L-theanine and caffeine that were not apparent when each treatment was administered alone; these included increased speed on several tasks, improved semantic memory and increased alertness. Other studies have employed lower doses of L-theanine (~100mg) and caffeine(~50mg) to explore these effects (23-25), providing support for the findings from studies of higher doses, in terms of improved accuracy (19) and speed (23) on tasks of attention, and improvements to measures of memory (20).
L-theanine has also been shown to antagonise the unwanted physiological effects of caffeine. Rogers et al. (17) demonstrated that although systolic and diastolic blood pressure were significantly higher following the administration of caffeine when compared to placebo or L-theanine alone, the combination of the two compounds led to an attenuation of this effect.
The combined effect of L-theanine and caffeine on cognitive performances clearly evidenced the beneficial impression on recognition, visual information processing, attention and moods (23,24). Recently, Einother, Martens, Rycroft, and De Bruin (23) have reported that L-theanine and caffeine improve task switching.
References
1. Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133
2. Chen YF, Parrish TB (2009b) Caffeine’s effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism. NeuroImage 44:647–652
3. Hasse CG, Becka M, Kuhlmann J, Wensing G (2005) Influences of caffeine, acetazolamide and cognitve stimulation on cerebral blood flow velocities. Prog Neuro-Psychopharmacol Biol Psychiatry 29: 549–556
4. Kennedy DO, Haskell CF (2011) Cerebral blood flow and behavioural effects of caffeine in habitual and non-habitual consumers of caffeine: A near infrared spectroscopy study. Biol Psychol 86:298–306
5. Laurienti PJ, Field AS, Burdette JH, Maldjian JA, Yen YF, Moody DM (2003) Relationship between caffeine-induced changes in resting cerebral perfusion and blood oxygenation level-dependent signal. Am J Neuroradiol 24:1607–1611
6. Mathew RJ, Wilson WH (1991) Substance Abuse and Cerebral Blood Flow. Am J Psychiatry 148:292–305
7. Rack-Gomer AL, Liau J, Liu TT (2009) Caffeine reduces resting-state BOLD functional connectivity in the motor cortex. NeuroImage 46: 56–63
8. Chen YF, Parrish TB (2009a) Caffeine dose effect on activation-induced BOLD and CBF responses. NeuroImage 46:577–583
9. AddicottMA, Yang LL, Peiffer AM, Burnett LR, Burdette JH, ChenMY, Hayasaka S, Kraft RA, Maldjian JA, Laurienti PJ (2009) The effect of daily caffeine use on cerebral blood flow: how much caffeine can we tolerate? Hum Brain Mapp 30:3102–3114
10. Field AS, Laurienti PJ, Yen YF, Burdette JH,Moody DM (2003) Dietary caffeine consumption and withdrawal: Confounding variables in quantitative cerebral perfusion studies? Radiology 227:129–135
11. Childs E, de Wit H (2006) Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. Psychopharmacology 185:514–523
12. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB (2008) The effects of L-theanine caffeine and their combination on cognition and mood. Biol Psychol 77:113–122
13. Smit HJ, Rogers PJ (2000) Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers. Psychopharmacology 152:167–173
14. Quinlan PT, Lane J, Moore KL, Aspen J, Rycroft JA, O’Brien DC (2000) The acute physiological and mood effects of tea and coffee: The role of caffeine level. Pharmacol Biochem Behav 66:19–28
15. Nathan PJ, Lu K, GrayM, Oliver C (2006) The neuropharmacology of Ltheanine( N-ethyl-L-glutamine):Apossible neuroprotective and cognitive enhancing agent. J Herb Pharmacother 6:21–30
16. Kimura K, Ozeki M, Juneja LR, Ohira H (2007) L-Theanine reduces psychological and physiological stress responses. Biol Psychol 74: 39–45
17. Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW (2008) Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology 195:569–577
18. Nobre AC, Rao A, Owen GN (2008) L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr 17:167–168
19. Juneja LR, Chu DC, Okubo T, Nagato Y, Yokogoshi H (1999) L-theanine - a unique amino acid of green tea and its relaxation effect in humans. Trends Food Sci Technol 10:199–204
20. Gomez-Ramirez M, Higgins BA, Rycroft JA, Owen GN, Mahoney J, Shpaner M, Foxe JJ (2007) The deployment of intersensory selective attention: A high-density electrical mapping study of the effects of theanine. Clin Neuropharmacol 30:25–38
21. Gomez-Ramirez M, Kelly SP, Montesi JL, Foxe JJ (2009) The Effects of L-theanine on alpha-band oscillatory brain activity during a visuospatial attention task. Brain Topogr 22:44–51
22. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB (2008) The effects of L-theanine caffeine and their combination on cognition and mood. Biol Psychol 77:113–122
23. Einother SJL, Martens VEG, Rycroft JA, De Bruin EA (2010) LTheanine and caffeine improve task switching but not intersensory attention or subjective alertness. Appetite 54:406–409
24. Kelly SP, Gomez-RamirezM,Montesi JL, Foxe JJ (2008) L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance. J Nutr 138:1572–1577
25. Owen GN, Parnell H, De Bruin EA, Rycroft JA (2008) The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci 11:193–198
