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* Caffeine in coffee does not seem as effective at improving performance, so other sources should be used.
* Caffeine increases blood pressure, and should be avoided during exercise by those with high blood pressure.
* There may be genetic differences in the effect of caffeine; see the section on "Caffeine and Genetics" below for details.
=Introduction=
Man has been searching for ways of improving athletic performance since at least 400 BC, when the hearts of lion were believed to impart benefits<ref name="CaffLionHeart"/>. Today, caffeine can improve performance in endurance running, and three of every four elite athletes take caffeine when competing<ref name="CaffUse"/>. Caffeine is one of the most widely used drugs in the world<ref name="CaffWorld"/>, with average daily intakes worldwide of 70mg/day, but higher in the US (~200mg/day) and the UK (~400mg/day)<ref name="CaffDependence"/>. Caffeine has many effects on many different tissue types, directly and through its metabolites, as well as stimulating adrenaline release<ref name="CaffMetaAndPerf"/>.
=How much?=
Most studies use 3-13mg/Kg, average 6mg, but within that dose range there was no obvious dose response<ref name="CaffMeta"/>. A smaller intake of 3 to 5 mg/kg dose before exercise and then 1 to 2 mg/kg intakes during prolonged exercise has been recommended<ref name="CaffMetaAndPerf"/>. Too much caffeine (9 mg/kg), especially for those that do not regularly take caffeine, can cause impairment, such as becoming talkative, giddy, and unable to perform simple tasks such as telling the time<ref name="CaffMetaAndPerf"/>. Low levels of exercise (30% [[VO2max|V̇O<sub>2</sub>max]]) seem to increase the metabolism of caffeine<ref name="CafModEx"/>, but higher intensities have no impact<ref name="CafExThermal"/>. Below is a listing of caffeine in common beverages.
{| class="wikitable" style="margin-left: auto; margin-right: auto; border: none;"
! '''Source'''
! '''Caffeine (mg) '''
| 80 per 8.3oz Can
|}
=Caffeine and Genetics=
There is some research indicating that there are genetic differences that change how caffeine effects people, but the research is a little unclear. However, it seems that having your genome tested could provide valuable information into how to use caffeine. The enzyme CYP1A2 metabolizes many drugs, and it's been shown to be responsible for over 95% of the metabolism of caffeine<ref name="BegasKouvaras2007"/>. The CYP1A2 enzyme is produced by the CYP1A2 gene, and a genetic change at rs762551 impacts how the enzyme is produced, with AA having greater activity than the AC or CC genotypes<ref name="snpe_rs76"/>. Sometimes the subjects with the AA variant are called "fast metabolizers".
* A study of 101 recreationally competitive male athletes on a 10K cycling time trial with 2 or 4 mg/Kg caffeine, there was an improvement only in those with the AA variant of CYP1A2, with no effect on the AC and diminished performance for the CC<ref name="Guest-2018"/>.
* A study of 21 active subjects given 3 mg/Kg of caffeine and tested using a 30 second Wingate test showed performance improvements did not vary between AA and AC/CC variants, though AC/CC reported increased nervousness while the AA variants did not<ref name="Salinero-2017"/>.
* A study of caffeine and basketball related performance (jump, change of direction) in 19 elite basketball players found that caffeine benefited the AA variants slightly more than the AC/CC variants<ref name="Puente-2018"/>. Strangely, the AA variants suffered tended to suffer from insomnia in the 24 hours after the test (I'd have expected AA variants to clear the caffeine faster and thus not suffer from insomnia as much as other variants.)
* A study of 35 male recreationally competitive cyclists performing a simulated 40K time trial following 6 mg/Kg of caffeine showed the AA variants improved more (4.9%) with caffeine than the AC/CC variants (1.8%)<ref name="WomackSaunders2012"/>. Beyond those averages, 15 of 16 AA variants improved their time by at least 60 seconds, while that only happened for 10 of the 19 C variants.
* A study of 20 healthy but untrained subjects did not show any statistically significant improvement in performance with 225mg caffeine in either AA or C variants<ref name="AlgrainThomas2016"/>. Looking at the data, it appears that a larger group of subjects might be needed to provide the statistical power required.
* A study of 20 collage level tennis players showed that 6 mg/Kg caffeine improved intermittent treadmill performance with no differences between AA and C variants<ref name="KleinClawson2012"/>.
* Other factors beyond genetics impact CYP1A2 enzyme activity, with exercise, caffeine intake, broccoli all increasing it<ref name="Vistisen-1992"/>.
I had my genome tested using 23andme.com which showed I have the AA variant of CYP1A2/rs762551.
=Caffeine, Blood Pressure and Heart Rate=
Caffeine increases blood pressure at rest and under stress, including exercise stress. The effect of caffeine on heart rate is unclear, with both increases and decreases observed in studies. Generally caffeine decreases heart rate at rest and moderate intensity exercise, but increases it at maximal workloads.
Caffeine raises blood pressure during exercise, increasing the possibility of excessively high blood pressure. Caffeine can increase or decrease heart rate during exercise, possibly lowering it during lower intensity exercise and increasing it at highest intensities.
* The effect of Caffeine on heart rate during exercise is ambiguous, with some studies showing an increase in heart rate<ref name="Bell-1998"/><ref name="Mcnaughton1987"/><ref name="Sasaki-1987"/><ref name="Sung-1995"/><ref name="Bell-2002"/>, while others show a decrease<ref name="Sullivan-1992"/><ref name="TurleyGerst2006"/><ref name="Gaesser-1985"/><ref name="McClaranWetter2007"/><ref name="SungLovallo1990"/>. Examining the studies in more detail however, and it appears that the increase in heart rate may be mostly at the highest intensities, with caffeine reducing heart rate at the lower intensities. The effect does not appear different for those that are caffeine habituated or those that are caffeine naïve.
{| class="wikitable" style="margin-left: auto; margin-right: auto; border: none;"
! Study
! Subjects
==Soda==
The caffeine levels in soda vary widely, with some common values shown below.
{| class="wikitable" style="margin-left: auto; margin-right: auto; border: none;"
! Soda
! Caffeine per 12oz<ref name="ChouBell2007"/>
<ref name="Flockhart-2007">Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). "/clinpharm/ddis/clinical-table/" Accessed June 2015.</ref>
<ref name="AretzGeyer2011">J. S. Aretz, J. Geyer, Detection of the CYP1A2 1117C > T polymorphism in 14 dog breeds, Journal of Veterinary Pharmacology and Therapeutics, volume 34, issue 1, 2011, pages 98–100, ISSN [http://www.worldcat.org/issn/01407783 01407783], doi [http://dx.doi.org/10.1111/j.1365-2885.2010.01222.x 10.1111/j.1365-2885.2010.01222.x]</ref>
<ref name="KleinClawson2012">Courtney S. Klein, Adam Clawson, Michael Martin, Michael J. Saunders, Judith A. Flohr, Marta K. Bechtel, Wade Dunham, Melyssa Hancock, Christopher J. Womack, The Effect of Caffeine on Performance in Collegiate Tennis Players, Journal of Caffeine Research, volume 2, issue 3, 2012, pages 111–116, ISSN [http://www.worldcat.org/issn/2156-5783 2156-5783], doi [http://dx.doi.org/10.1089/jcr.2012.0019 10.1089/jcr.2012.0019]</ref>
<ref name="AlgrainThomas2016">Haya A. Algrain, Rebecca M. Thomas, Andres E. Carrillo, Emily J. Ryan, Chul-Ho Kim, Robert B. Lettan, Edward J. Ryan, The Effects of a Polymorphism in the Cytochrome P450 CYP1A2 Gene on Performance Enhancement with Caffeine in Recreational Cyclists, Journal of Caffeine Research, volume 6, issue 1, 2016, pages 34–39, ISSN [http://www.worldcat.org/issn/2156-5783 2156-5783], doi [http://dx.doi.org/10.1089/jcr.2015.0029 10.1089/jcr.2015.0029]</ref>
<ref name="Vistisen-1992">K. Vistisen, HE. Poulsen, S. Loft, Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine., Carcinogenesis, volume 13, issue 9, pages 1561-8, Sep 1992, PMID [http://www.ncbi.nlm.nih.gov/pubmed/1394840 1394840]</ref>
<ref name="WomackSaunders2012">Christopher J Womack, Michael J Saunders, Marta K Bechtel, David J Bolton, Michael Martin, Nicholas D Luden, Wade Dunham, Melyssa Hancock, The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine, Journal of the International Society of Sports Nutrition, volume 9, issue 1, 2012, ISSN [http://www.worldcat.org/issn/1550-2783 1550-2783], doi [http://dx.doi.org/10.1186/1550-2783-9-7 10.1186/1550-2783-9-7]</ref>
<ref name="Puente-2018">C. Puente, J. Abián-Vicén, J. Del Coso, B. Lara, JJ. Salinero, The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance., PLoS One, volume 13, issue 4, pages e0195943, 2018, doi [http://dx.doi.org/10.1371/journal.pone.0195943 10.1371/journal.pone.0195943], PMID [http://www.ncbi.nlm.nih.gov/pubmed/29668752 29668752]</ref>
<ref name="Salinero-2017">JJ. Salinero, B. Lara, D. Ruiz-Vicente, F. Areces, C. Puente-Torres, C. Gallo-Salazar, T. Pascual, J. Del Coso, CYP1A2 Genotype Variations Do Not Modify the Benefits and Drawbacks of Caffeine during Exercise: A Pilot Study., Nutrients, volume 9, issue 3, Mar 2017, doi [http://dx.doi.org/10.3390/nu9030269 10.3390/nu9030269], PMID [http://www.ncbi.nlm.nih.gov/pubmed/28287486 28287486]</ref>
<ref name="BegasKouvaras2007">E. Begas, E. Kouvaras, A. Tsakalof, S. Papakosta, E. K. Asprodini, In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratios, Biomedical Chromatography, volume 21, issue 2, 2007, pages 190–200, ISSN [http://www.worldcat.org/issn/02693879 02693879], doi [http://dx.doi.org/10.1002/bmc.736 10.1002/bmc.736]</ref>
<ref name="Guest-2018">N. Guest, P. Corey, J. Vescovi, A. El-Sohemy, Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes., Med Sci Sports Exerc, volume 50, issue 8, pages 1570-1578, 08 2018, doi [http://dx.doi.org/10.1249/MSS.0000000000001596 10.1249/MSS.0000000000001596], PMID [http://www.ncbi.nlm.nih.gov/pubmed/29509641 29509641]</ref>
<ref name="snpe_rs76">rs762551 – SNPedia, snpedia.com !!work!!, 18 March 2019 !!access-date!!, [https://www.snpedia.com/index.php/Rs762551 https://www.snpedia.com/index.php/Rs762551]</ref>
</references>