Caffeine

Revision as of 11:06, 22 October 2012 by User:Fellrnr (User talk:Fellrnr | contribs)

Revision as of 11:06, 22 October 2012 by User:Fellrnr (User talk:Fellrnr | contribs)

Common sources of Caffeine.

Caffeine is widely consumed by the general public and athletes, and moderate levels can improve athletic performance. Caffeine does not cause dehydration, but it can interfere with sleep. Caffeine in coffee does not seem as effective, so other sources should be used.

Contents

1 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[1]. Today, caffeine can improve performance in endurance running, and three of every four elite athletes take caffeine when competing[2]. Caffeine is one of the most widely used drugs in the world[3], with average daily intakes worldwide of 70mg/day, but higher in the US (~200mg/day) and the UK (~400mg/day)[4]. Caffeine has many effects on many different tissue types, directly and through its metabolites, as well as stimulating adrenaline release[5].

2 Performance

Studies have shown caffeine can improve performance by ~2%[6]. Though much greater improvements (~12%) have been shown in laboratory conditions, these are not likely to be seen in real world race conditions[6]. That ~2% represents 3.5 minutes on a 3 hour marathon, nearly 5 minutes on a 4 hour marathon. For the 5K, that represents 25 seconds on a 21 minute 5K, or 18 seconds on a 15 minute 5K. Caffeine tends to benefit fitter individuals more[6]. Caffeine may improve performance by reducing the RPE[7] and muscle pain[8].

2.1 Green Tea and Performance

There is relatively little research concerning the effect of tea on athletic performance. However, one study did show that the green tea extract increased fat burning and glucose tolerance during cycling at 60% V?O2max without affecting heart rate or overall energy consumption[9].

2.2 Coffee and Performance

When you take caffeine as coffee, it may not improve performance as it does when taken in other forms. One study showed that caffeine in coffee does not give a performance improvement where isolated caffeine does[10] and another showed no benefit from caffeinated coffee over decaffeinated coffee[11]. Some studies show a performance benefit from caffeinated coffee[12][13][14], but did not compare with caffeine alone. This may be because coffee contains hundreds if not thousands of compounds besides caffeine[5][15]. Some of these extra compounds of been shown to affect glucose metabolism[16]. It is been observed that decaffeinated coffee can reduce the absorption of glucose[17].

3 How much?

Most studies use 3-13mg/Kg, average 6mg, but within that dose range there was no obvious dose response[6]. 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[5]. 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[5]. Low levels of exercise (30% V?O2max) seem to increase the metabolism of caffeine[18], but higher intensities have no impact[19]. Below is a listing of caffeine in common beverages.

Source Caffeine (mg)
Brewed coffee 100-150+ per 8oz
Brewed decaf coffee 5 (range: 3-12)
Starbucks Espresso 75 per shot
Black Tea 28-46 per 8Oz
Oolong Tea 12-55 per 8Oz
Green Tea 8-36 per 8Oz
Soda - Cola 35 per 12oz Can (see 'soda' for details)
Soda – Mountain Dew 54 per 12oz Can
Red Bull 80 per 8.3oz Can

4 Caffeine and Dehydration

Caffeine does not impact performance in hot/humid conditions, nor act as a diuretic when running[20]. Caffeine at 360mg is a diuretic at rest, but not at 180mg or less[21]. Caffeine does not cause long term dehydration[22], and black tea has been shown to hydrate as well as water[23]. Caffeine does result in increased sodium excretion in the urine[24], but the significance of this unclear.

5 Caffeine Habituation

Surprisingly, there is no clear evidence that the performance benefits of caffeine vary with habitual caffeine usage[6]. Caffeine impacts caffeine naive more at rest than those habituated to caffeine, but the difference is far less during exercise[25]. Caffeine habituation has been shown to reduce the adrenaline response to caffeine, but most other responses remain similar [26]. Animal studies have shown that some tissues adapt to long term use of caffeine but other tissues do not appear to change at all[5].

6 Caffeine and DOMS

Caffeine has been shown to not only reduce the pain of Delayed Onset Muscle Soreness (DOMS)[27], but also reduces the associated weakness[28][29][30]. This reduction in weakness is important because although the soreness is delayed 24-72 hours after exercise, the muscle damage and resulting weakness happens within 30 minutes[31].

7 Caffeine Withdrawal

Withdrawal from Caffeine generally produces a headache and fatigue, with some evidence of anxiety[4]. Onset of withdrawal is typically 12-24 hours after the last intake, though occasionally as quickly as 3-6 hours, with symptoms after peaking 20-48 hours and lasting a week[4]. Small amounts of caffeine can help with withdrawal.

The onset and severity of headache with caffeine withdrawal.
A similar chart of fatigue for caffeine withdrawal.

8 Caffeine and Sleep

Not surprisingly given it's a stimulant, caffeine interferes with sleep. Taking 100mg caffeine just before bedtime significantly interferes with sleep[32]. More significantly, taking 200 mg early in the morning will also significantly interfere with sleep[33]. This suggests that caffeine should be taken as early in the day as is practical, and those with sleep problems should reduce caffeine or avoid it completely.

Caffeine concentrations measured in the saliva, with 200mg administered at 7:10am.

9 Caffeine and Cramping

There is no research around any possible link between caffeine and Cramps, but there are a few anecdotal reports of a link between caffeine/coffee and Cramps[34][35][36].

10 Caffeine as a Pain killer

Caffeine is frequently added to over-the-counter pain medication to boost its effectiveness; without caffeine 40% more pain medication is required to have the same results[37]. Caffeine adds slightly to the relief of surgical pain from Acetaminophen (Paracetamol)[38] and caffeine can reduce headaches to an equivalent level as Acetaminophen (Paracetamol)[39]. Caffeine reduces muscle pain during exercise in both those that habitually take caffeine and those that caffeine naïve[8], though one study suggested this may only occur in hot conditions[40]. As noted above, caffeine can reduce the pain of DOMS[27].

11 Caffeine at altitude

The general recommendation to avoid caffeine at altitude does not seem to have a scientific basis. In fact, a number of the effects of caffeine have the potential to be beneficial at altitude[41]:

  • As noted above, caffeine does not produce dehydration, and there is little evidence that dehydration contributes to altitude sickness.
  • Caffeine tends to increase breathing, which may offset the depressed breathing seen at altitude.
  • The risk of a brain or lung edema at altitude is a serious concern, and there is the possibility that caffeine may help by constricting blood vessels without restricting oxygenation.
  • Caffeine may help alleviate the headache that is common with altitude sickness.
  • The lassitude seen at altitude may be offset by caffeine, and the exercise performance improvements at altitude may be even greater than at sea level.
  • While caffeine could reduce the altitude problems that prevent sleep, the stimulant nature of caffeine may offset these benefits.

Caffeine has a shorter duration of effect at high altitude, possibly due to increased blood flow to the liver, and withdrawal from caffeine would likely make altitude problems more severe[41].

12 Glucose Absorption, Insulin Resistance and Glycemic index

Caffeine changes the way glucose is absorbed, but this effect is different for those at rest compared with those exercising.

12.1 At Rest

Caffeine reduces glucose absorption at rest[42][43][44][45]. In tests on lean, obese, and Type 2 Diabetics, glucose absorption was impaired by caffeine, though exercise mitigated the reduction slightly in non-diabetics[46][47].

12.2 During Exercise

Unlike the effect of caffeine on sedentary or resting individuals, caffeine increases the absorption, uptake and metabolism of glucose during exercise[48][49]. Caffeine taken during exercise does not change Glycogen replenishment post-exercise[50], but caffeine taken with carbohydrate after exercise increased Glycogen replenishment and insulin levels compared with just carbohydrate[51][52]. One hypothesis for this difference is that caffeine reduces the effect of insulin, and non-insulin dependent glucose pathways predominate during exercise[50]. Caffeine taken 2 hours after exercise impairs glucose absorption, but to a lesser extent than in a completely rested state[53].

13 Sources of Caffeine

There are various sources of caffeine that are sometimes used by athletes.

13.1 Coffee

While coffee is a very common source of caffeine, there is evidence that caffeine taken in coffee is not as effective as other forms (see above for details). Also, coffee may cause Stomach Problems and Lower GI Problems in some individuals. Typical brewed coffee contains 100-150mg per cup[54] which compounds the problem of using coffee in sports. I would recommend using other sources of caffeine before or during runs.

13.2 Tea

Brewing time and levels of Caffeine (CF), the catechins epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC)[55].

It is claimed that tea is the second most popular drink after water[56], but it does not appear to be commonly used by athletes. Because the level of caffeine can vary dramatically with different types of tea, and different brewing methods, it is difficult to know how much caffeine is in a particular drink of tea. Generally black tea has more than oolong tea which has more than green tea[57]. Typically black tea contains 28 to 46mg of Caffeine per 8oz cup[54]. This unpredictability makes tea a problematic source of caffeine, though using the same tea and brewing for the same time will give reproducible levels, but you won't know the absolute caffeine intake.

13.3 Gels ($2-8/100mg)

Gels are available with and without caffeine, and the caffeinated variety normally has 25mg, though some go as high as 100mg. The higher caffeine concentrations often include a coffee extract, which may limit the benefits. Given that gels typically cost $1-2 per gel, the caffeine cost is $2-8/100mg. See Comparison of Energy Gels for more details.

13.4 Soda

The caffeine levels in soda vary widely, with some common values shown below.

Soda Caffeine per 12oz[58]
Coca-Cola 33.9mg
Diet Coke 46.3mg
Pepsi 38.9mg
Diet Pepsi 36.7mg
Dr Pepper 42.6mg
Diet Dr Pepper 44.1mg
Mountain Dew 54.8mg
Diet Mountain Dew 55.2mg
Vault Zero 74mg

Typically soda makes a poor sports drink as it contains too much sugar, is too carbonated and additives like phosphoric acid can upset the digestive system. However, ultrarunners used to regularly use soda that had been left to go flat and then often diluted with water[59]. This is something to practice in training before using during a race.

13.5 Energy Drinks

There are many different types of energy drink available on the market today. Frequently they are a mixture of many different substances that are believed in some way to be stimulating. Energy drinks should be used with caution, as the substances they contain may not have been scientifically evaluated, especially in the combinations provided. Energy drinks often contain carbohydrate, but the specific types of carbohydrate and the concentration used may not be appropriate to athletic events. The caffeine content of energy drinks is often 200-300mg per can[60], which is quite high, but lower than a Starbucks Venti brewed coffee which typically has 400+mg[61].

13.6 Red Bull ($3-6/100mg)

I've tried a few different energy drinks, and the only one I use now is Red Bull. Red Bull is only lightly carbonated, is not too sweet for my taste, and while the mixture of glucose and sucrose is not great for sports drink, it's better than many of the alternatives. One study has shown that the added Taurine, B vitamins and other ingredients do not add any benefit over the just taking the caffeine[62]. However, I like the taste, and my expectation of a benefit provides a useful placebo. Red Bull contains about 80mg of caffeine per 8oz can[63], which is slightly less than the equivalent volume of coffee.

13.7 Energy Shots

Energy shots are more convenient than energy drinks due to their small size and portability. However, they concentrated form can easily cause stomach upsets in addition to the problems noted in energy drinks above.

13.8 Caffeine Tablets ($0.03/100mg)

Caffeine tablets have the advantage of low-cost, predictable caffeine content, and portability. Compared with other sources of caffeine, these tablets are 1/100th the cost. I use Natrol tables, which are 200mg per tablet. I cut them into halves using a Pill Cutter, then it's easy to bite off a smaller amount as needed. I carry these in my Portable Pharmacy.

14 Tea and Theanine

Theanine is an amino acid found in tea, primarily green tea. Theanine calms the mind without inducing drowsiness, achieving a relaxed but alert mental state[64]. Theanine has a number of benefits:

  • It has been shown to improve and sustain long term attention[65], acting as a stimulant, even without caffeine[66].
  • When combined with caffeine, theanine reduces distractions[67].
  • Theanine reduces blood pressure[68] and can offset the rise in blood pressure that comes from caffeine[69].
  • Three components of green tea (Catechins, Caffeine and Theanine) reduce obesity in mice[70].
  • Tea may help reduce dementia[71], and tea improves learning in rats[68].
  • Theanine and cystine may help reduce the immune system depression of high intensity training[72][73].

15 Caffeine, Running and Sudden Death

While rare, the sudden death of a runner does occur and often makes the news. Running is estimated to have a mortality rate of about 1 in 7,000 runners, or one death per 396,000 man-hours[74]. Sudden death during a marathon is rarer, at less than 1 in 50,000[75][76].

15.1 Primary Causes of Sudden Death in Athletes

Sudden death in young competitive athletes (<35 years of age) is mostly due to congenital heart problems, but in older athletes it is usually Coronary artery disease[77][78].

15.2 Myocardial Blood Flow and Heart Attacks

The heart not only pumps blood but, like any muscle, it requires its own supply of blood as well. If this blood supply, called myocardial blood flow, is interrupted the result is a Myocardial infarction or heart attack. Coronary artery disease, which reduces the myocardial blood flow, is the most common cause of sudden death worldwide.

15.3 Caffeine and Myocardial Blood Flow

A moderate amount of caffeine does not change the myocardial blood flow at rest, but during exercise the caffeine significantly reduces the flow[79][80]. This decrease in myocardial blood flow is worse at altitude[80] and in people with Coronary artery disease[79]. (These changes were seen with 200mg of caffeine, but the studies did not try other amounts to see of the effect varies with dose.) The change in myocardial blood flow is not a risk factor for healthy individuals[79][80], but for those with Coronary artery disease the combination of caffeine and exercise may exacerbate their condition.

15.4 Caffeine and Irregular Heart Beats

Cardiac arrhythmias (irregular heartbeats) are a group of conditions where the heart does not beat normally and can be a life threatening emergency. There is a common belief that caffeine is linked to some types of arrhythmias, but this does not seem scientifically supported for [81][82][83]. In fact, an animal study showed that moderate caffeine reduces the risk of atrial fibrillation[81]. A study giving recent heart attacks 450mg of caffeine showed no change in the risk of arrythmia[84]. Giving 200mg of caffeine before a bicycle stress test to patients who have malignant ventricular arrhythmias made no difference[85]. However, there are anecdotal reports of people having arrhythmia triggered by caffeine. Note that a caffeine overdoes can result in heart problems[83].

15.5 Evaluating the risks

Because coronary artery disease may not have any initial symptoms[86], risk evaluation is tricky. Some runners who died suddenly had high cholesterol, high blood pressure or chest pains[78]. Other risk factors include diabetes, smoking, family history of heart attacks, obesity, long term alcohol use. If you have any risk factors for coronary artery disease, it would be prudent to talk to a healthcare professional.

16 Caffeine and health

For most people, caffeine is generally taken as tea or coffee, to the bulk of the scientific evidence around the health impact of caffeine is based on these beverages.

16.1 Tea

Both green and black tea contain similarly high levels of antioxidants[87]. Green tea contains high levels of EGCG, which has been shown to inhibit cancer cell proliferation[88][89]. This EGCG may help trigger natural cell death which in turn may help treat both obesity and osteoporosis[90]. Green tea consumption has been linked to a reduction in upper GI cancers and green team may also help with lung, liver, prostate and breast cancers[91].

16.2 Coffee and Cancer

Caffeine intake (coffee and other forms) is linked to lower rates of the most common type of skin cancer[92] and coffee drinking is associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers[15].

16.3 Coffee and Type 2 Diabetes

Coffee drinking is associated with a substantially lower risk of type 2 diabetes[16][93], including decaffeinated[94]. However, coffee drinking is associated with a number of lifestyle risks, such as smoking, inactivity, and poor diet, and adjustments for these risks may overly strengthen the potential anti-diabetic benefits of coffee drinking[16]. There are a number of possible mechanisms behind the reduction in type II diabetes:

  • In postmenopausal women, coffee increases the hormone SHRB that may account for the diabetes reduction [95].
  • Coffee (including decaffeinated) is correlated with reduced markers of insulin secretion, especially in obese and overweight women[96].
  • One study found the T2DM risk was only reduced in tea and coffee drinkers who had previously lost weight[97].

17 Restrictions on Caffeine for Competition

Caffeine was removed from the World Anti-Doping Agency (WADA) list in 2004; prior to that it was restricted at high levels based on urine concentration[98]. It is still restricted by the NCAA at similarly high concentrations[99]. The level of caffeine intake required to exceed the NCAA threshold varies dramatically (x16) between individuals, and for a given individual at different times, with some people at risk of exceeding the permitted level on 3 cups of regular coffee per day and others able to take excessive levels[100]. A study of caffeine showed that even 9mg/kg was less than the NCAA threshold for the test subjects[101], but another study showed that doses of 9mg or above could result in a positive test for some individuals[102].

18 Ethics of Caffeine

At its most simplistic level, caffeine is permitted for use in competition, so if we consider "ethics" as simply "following the rules", then caffeine is ethical. If we look at the broader ethical implications of caffeine however, things become a little more nebulous. The World Anti-Doping Agency (WADA) may consider controlling a substance or method if it meets two of these three conditions:

  1. It has the potential to improve performance
  2. It has the potential to harm the health of the athlete
  3. It violates the "spirit of sport"

Clearly caffeine meets criteria #1, but not #2 (if anything, caffeine may be beneficial to health). So does the use of caffeine violate the spirit of the sport? Let's compare the use of caffeine with the use of carbohydrate:

  • Both caffeine and carbohydrate have been shown to improve performance
  • Neither caffeine nor carbohydrate are essential for life
  • The vast majority of people routinely take caffeine, and nearly everybody takes carbohydrate
  • There are few health risks with caffeine, and other than Fructose, carbohydrate is generally considered safe
  • While both caffeine and carbohydrate are found naturally in plants, it is common for them to be consumed in highly refined forms
  • Athletes frequently consume caffeine and/or carbohydrate for the sole purpose of improving performance
  • Any athlete that does not effectively use either caffeine or carbohydrate is at a distinct disadvantage

This comparison indicates to me that caffeine is not against the spirit of the sport, or unethical.

19 Newborn babies and Caffeine

Newborn babies may be subject to higher levels of caffeine from breast milk than one would expect. If we assume:

  • A 3 Kg baby (6.6Lb)
  • A milk intake of 500 to 900 ml/day[103]
  • The nursing mother's caffeine intake of 200mg/day (one double shot espresso),

We get a resulting caffeine concentration in the milk of 4ug/ml to 8ug/ml[104], which is a total caffeine intake of between 2mg to 13mg, or 0.6 to 4 mg/Kg body weight. The upper end of that level is quite high. However, the baby's half-life for caffeine is 60-100 hours, compared with an adult's 2-10 hour half-life, so the caffeine will build up over time. A 24 hour half live (which is easier to calculate) would result in about a 3mg to 26mg, which is 1 to 8 mg/Kg. I'm guessing that would result in the baby not sleeping well! Conversely, a baby whose mother takes caffeine during pregnancy and is then given formula milk may undergo caffeine withdrawal after birth[105]. Even if the mother breast feeds, the varying levels of caffeine may cause withdrawal symptoms[106]. Also, caffeine has been shown to increase fetal heart rate[107].

20 References

  1. Search for the Competitive Edge: A History of Dietary Fads and Supplements http://jn.nutrition.org/content/127/5/869S.full
  2. Prevalence of caffeine use in elite ... [Appl Physiol Nutr Metab. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21854160
  3. Gilbert RM. Caffeine consumption. In : Spiller GA, editor. The methylxanthine beverages and foods, Alan R. Liss; 1984. p. 185-213
  4. 4.0 4.1 4.2 Psychopharmacology, Volume 94, Number 4 - SpringerLink http://www.springerlink.com/content/wl412194360xj32t/
  5. 5.0 5.1 5.2 5.3 5.4 Caffeine and exercise: metabolism and per... [Can J Appl Physiol. 1994] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/8081318
  6. 6.0 6.1 6.2 6.3 6.4 Effects of caffeine ingestion o... [Int J Sport Nutr Exerc Metab. 2004] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/15657469
  7. Effects of caffeine ingestion on rati... [Scand J Med Sci Sports. 2005] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/15773860
  8. 8.0 8.1 Effect of caffeine on quadricep... [Int J Sport Nutr Exerc Metab. 2009] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/19478340
  9. Venables, MC.; Hulston, CJ.; Cox, HR.; Jeukendrup, AE. (Mar 2008). "Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans.". Am J Clin Nutr 87 (3): 778-84. Template:citation/identifier.
  10. Metabolic and exercise endurance effects of coffee and caffeine ingestion http://jap.physiology.org/content/85/3/883.abstract
  11. Butts and Crowell (1985) Effect of caffeine ingestion on cardiorespiratory endurance in men and women http://www.getcited.org/pub/103341768
  12. Effect of caffeinated coffee on running speed, respiratory factors, blood lactate and perceived exertion during 1500-m treadmill running. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1478936/
  13. Effects of caffeine ingestion on metabolism a... [Med Sci Sports. 1978] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/723503
  14. Failure of caffeine to affect substrate... [Med Sci Sports Exerc. 1985] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/3982273
  15. 15.0 15.1 BMC Cancer | Full text | Coffee consumption and risk of cancers: a meta-analysis of cohort studies http://www.biomedcentral.com/1471-2407/11/96/
  16. 16.0 16.1 16.2 JAMA Network | JAMA: The Journal of the American Medical Association | Coffee Consumption and Risk of Type 2 DiabetesA Systematic Review http://jama.jamanetwork.com/article.aspx?articleid=201177
  17. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine http://www.ajcn.org/content/78/4/728.abstract
  18. Effects of moderate exercise on the pha... [Eur J Clin Pharmacol. 1991] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/2060565
  19. Effects of exercise and thermal stress on caf... [J Appl Physiol. 2002] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/12235049
  20. Myth buster: caffeine does not exhibit a di... [Indian J Med Res. 2010] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/20693584
  21. Renal and cardiovascular effects of caffeine... [Clin Sci (Lond). 1987] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/3297472
  22. Fluid, electrolyte, and renal i... [Int J Sport Nutr Exerc Metab. 2005] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/16131696
  23. Black tea is not significantly different from wate... [Br J Nutr. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21450118
  24. Natriuretic effect of caffeine: assessment o... [Clin Sci (Lond). 2002] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/12401118
  25. European Journal of Applied Physiology and Occupational Physiology, Volume 62, Number 6 - SpringerLink http://www.springerlink.com/content/u37082130426tl56/
  26. Caffeine metabolism and epinephrine responses during exercise in users and nonusers http://jap.physiology.org/content/75/2/805.abstract
  27. 27.0 27.1 The effects of caffeine on perceived pain of muscles http://scholarsresearchlibrary.com/ABR-vol2-iss6/ABR-2011-2-6-16-21.pdf
  28. Caffeine Attenuates Delayed-Onset Muscle Pain and Force Loss Following Eccentric Exercise http://www.jpain.org/article/S1526-5900%2806%2901023-6/abstract
  29. Excitation-contraction uncoupling: major... [Exerc Sport Sci Rev. 2001] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/11337828
  30. Intracellular calcium and force in single mouse mu... [J Physiol. 1995] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/8568662
  31. Comparison of the symptoms of exercise-induced muscle damage after an initial and repeated bout of plyometric exercise in men and boys http://jap.physiology.org/cgi/content/full/99/3/1174
  32. Landolt, HP.; Dijk, DJ.; Gaus, SE.; Borbély, AA. (May 1995). "Caffeine reduces low-frequency delta activity in the human sleep EEG.". Neuropsychopharmacology 12 (3): 229-38. Template:citation/identifier. Template:citation/identifier.
  33. Landolt, HP.; Werth, E.; Borbély, AA.; Dijk, DJ. (Mar 1995). "Caffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at night.". Brain Res 675 (1-2): 67-74. Template:citation/identifier.
  34. Template:cite journal
  35. Template:cite journal
  36. Template:cite journal
  37. JAMA Network | JAMA: The Journal of the American Medical Association | Caffeine as an Analgesic Adjuvant http://jama.jamanetwork.com/article.aspx?articleid=392180
  38. Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain–a meta-analysis - Zhang - 2008 - Journal of Clinical Pharmacy and Therapeutics - Wiley Online Library http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.1996.tb01148.x/abstract
  39. The analgesic effects of caffeine in headache. [Pain. 1991] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/2052380
  40. Caffeine lowers muscle pain during exercise in... [Physiol Behav. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21163281
  41. 41.0 41.1 Caffeine at high altitude: java at base cAMP. [High Alt Med Biol. 2010] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/20367483
  42. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine http://www.ajcn.org/content/78/4/728.abstract
  43. Caffeine Can Decrease Insulin Sensitivity in Humans http://care.diabetesjournals.org/content/25/2/364.abstract?ijkey=0d78b20406d1b0da6a363f1b00847b0434751e49&keytype2=tf_ipsecsha
  44. Effects of caffeine on glucose tolerance: a ... [Eur J Clin Nutr. 1998] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/9846599?dopt=Abstract
  45. ingentaconnect Caffeine ingestion elevates plasma insulin response in humans dur... http://www.ingentaconnect.com/content/nrc/cjpp/2001/00000079/00000007/art00002
  46. Caffeine Ingestion Is Associated With Reductions in Glucose Uptake Independent of Obesity and Type 2 Diabetes Before and After Exercise Training http://care.diabetesjournals.org/content/28/3/566.short
  47. Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss http://www.ajcn.org/content/80/1/22.short
  48. Caffeine increases exogenous carbohydrate oxidation during exercise http://jap.physiology.org/content/99/3/844.full
  49. Gastrointestinal function during exercise: comparison of water, sports drink, and sports drink with caffeine http://jap.physiology.org/content/89/3/1079.full
  50. 50.0 50.1 Caffeine ingestion does not impede the resynthesis of proglycogen and macroglycogen after prolonged exercise and carbohydrate supplementation in humans http://jap.physiology.org/content/96/3/943.full
  51. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine http://jap.physiology.org/content/105/1/7.long
  52. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine http://www.jappl.org/content/105/1/7.full
  53. Caffeine-Induced Impairment of Insulin Action but Not Insulin Signaling in Human Skeletal Muscle Is Reduced by Exercise http://diabetes.diabetesjournals.org/content/51/3/583.full
  54. 54.0 54.1 Bunker, ML.; McWilliams, M. (Jan 1979). "Caffeine content of common beverages.". J Am Diet Assoc 74 (1): 28-32. Template:citation/identifier.
  55. Template:cite journal
  56. Template:cite book
  57. Lin, YS.; Tsai, YJ.; Tsay, JS.; Lin, JK. (Mar 2003). "Factors affecting the levels of tea polyphenols and caffeine in tea leaves.". J Agric Food Chem 51 (7): 1864-73. Template:citation/identifier. Template:citation/identifier.
  58. Template:cite journal
  59. Fueling Properly for an Ultra | Running Times Magazine http://runningtimes.com/Article.aspx?ArticleID=21791
  60. Caffeine Content of Drinks http://www.energyfiend.com/the-caffeine-database\#
  61. The Complete Guide to Starbucks Caffeine http://www.energyfiend.com/the-complete-guide-to-starbucks-caffeine
  62. Pettitt, RW.; Niemeyer, JD.; Sexton, PJ.; Lipetzky, A.; Murray, SR. (Oct 2012). "Do the non-caffeine ingredients of energy drinks affect metabolic responses to heavy exercise?". J Strength Cond Res. Template:citation/identifier. Template:citation/identifier.
  63. Nutrition Facts and Analysis for Energy drink, RED BULL, with added caffeine, niacin, pantothenic acid, vitamins B6 and B12 http://nutritiondata.self.com/facts/beverages/7399/2
  64. L-theanine, a natural constituent in te... [Asia Pac J Clin Nutr. 2008] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18296328
  65. The effects of L-theanine on alpha-band oscilla... [Brain Topogr. 2009] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18841456
  66. Source density analysis of the human E... [Nutr Neurosci. 2007 Jun-Aug] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18019399
  67. Psychological effects of dietary components of tea:... [Nutr Rev. 2008] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18254874
  68. 68.0 68.1 ScienceDirect.com - Trends in Food Science & Technology - L-theanine—a unique amino acid of green tea and its relaxation effect in humans http://www.sciencedirect.com/science/article/pii/S0924224499000448
  69. Time for tea: mood, blood pressure... [Psychopharmacology (Berl). 2008] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/17891480
  70. Anti-obesity Effects of Three Major Components of Green Tea, Catechins, Caffeine and Theanine, in Mice http://iv.iiarjournals.org/content/18/1/55.short
  71. Tea and cognitive health in late life: c... [J Nutr Health Aging. 2012] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/22237999
  72. Effects of oral supplementation wi... [Biosci Biotechnol Biochem. 2009] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/19352043
  73. Cystine and Theanine Supplementation Restores High-Intensity... : The Journal of Strength & Conditioning Research http://journals.lww.com/nsca-jscr/Abstract/2010/03000/Cystine_and_Theanine_Supplementation_Restores.34.aspx
  74. Thompson, PD.; Funk, EJ.; Carleton, RA.; Sturner, WQ. (May 1982). "Incidence of death during jogging in Rhode Island from 1975 through 1980.". JAMA 247 (18): 2535-8. Template:citation/identifier.
  75. Template:cite journal
  76. Template:cite journal
  77. Template:cite journal
  78. 78.0 78.1 Template:cite journal
  79. 79.0 79.1 79.2 Namdar, M.; Schepis, T.; Koepfli, P.; Gaemperli, O.; Siegrist, PT.; Grathwohl, R.; Valenta, I.; Delaloye, R. et al. (2009). "Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controls.". PLoS One 4 (5): e5665. Template:citation/identifier. Template:citation/identifier.
  80. 80.0 80.1 80.2 Namdar, M.; Koepfli, P.; Grathwohl, R.; Siegrist, PT.; Klainguti, M.; Schepis, T.; Delaloye, R.; Wyss, CA. et al. (Jan 2006). "Caffeine decreases exercise-induced myocardial flow reserve.". J Am Coll Cardiol 47 (2): 405-10. Template:citation/identifier. Template:citation/identifier.
  81. 81.0 81.1 Template:cite journal
  82. Katan, MB.; Schouten, E. (Mar 2005). "Caffeine and arrhythmia.". Am J Clin Nutr 81 (3): 539-40. Template:citation/identifier.
  83. 83.0 83.1 Pelchovitz, DJ.; Goldberger, JJ. (Apr 2011). "Caffeine and cardiac arrhythmias: a review of the evidence.". Am J Med 124 (4): 284-9. Template:citation/identifier. Template:citation/identifier.
  84. Myers, MG.; Harris, L. (Apr 1990). "High dose caffeine and ventricular arrhythmias.". Can J Cardiol 6 (3): 95-8. Template:citation/identifier.
  85. Graboys, TB.; Blatt, CM.; Lown, B. (Mar 1989). "The effect of caffeine on ventricular ectopic activity in patients with malignant ventricular arrhythmia.". Arch Intern Med 149 (3): 637-9. Template:citation/identifier.
  86. Coronary artery disease: Symptoms - MayoClinic.com http://www.mayoclinic.com/health/coronary-artery-disease/DS00064/DSECTION=symptoms
  87. Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods – 2007 http://www.webcitation.org/query?url=http%3A%2F%2Fwww.ars.usda.gov%2FSP2UserFiles%2FPlace%2F12354500%2FData%2FORAC%2FORAC07.pdf&date=2009-05-23
  88. Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway http://www.sciencedirect.com/science/article/pii/S0304383506001960
  89. Apoptotic effect of green tea polyphenol (EGCG) on cervical carcinoma cells - Asif Siddiqui - 2010 - Diagnostic Cytopathology - Wiley Online Library http://onlinelibrary.wiley.com/doi/10.1002/dc.21434/abstract
  90. ingentaconnect Novel Treatments for Obesity and Osteoporosis: Targeting Apoptoti... http://www.ingentaconnect.com/content/ben/cmc/2005/00000012/00000019/art00003
  91. Tea and cancer prevention: epidemiological stu... [Pharmacol Res. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21419224
  92. Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin http://cancerres.aacrjournals.org/content/72/13/3282.abstract
  93. Annals of Internal Medicine | Coffee Consumption and Risk for Type 2 Diabetes Mellitus http://annals.org/article.aspx?volume=140&issue=1&page=1
  94. Coffee, Caffeine, and Risk of Type 2 Diabetes http://care.diabetesjournals.org/content/29/2/398.abstract?ijkey=0aa1ab4745bc811da4ab34ed66604d4462b97615&keytype2=tf_ipsecsha
  95. Coffee and Caffeine Consumption in Relation to Sex Hormone–Binding Globulin and Risk of Type 2 Diabetes in Postmenopausal Women http://diabetes.diabetesjournals.org/content/60/1/269.short
  96. Caffeinated Coffee, Decaffeinated Coffee, and Caffeine in Relation to Plasma C-Peptide Levels, a Marker of Insulin Secretion, in U.S. Women http://care.diabetesjournals.org/content/28/6/1390.abstract?ijkey=3d4c0a5aa75e45f1690789634957ab9f0a6f0e13&keytype2=tf_ipsecsha
  97. Coffee, tea and diabetes: the role of weig... [Int J Obes (Lond). 2005] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/15925959?dopt=Abstract
  98. 2012 Prohibited List - World Anti-Doping Agency http://www.wada-ama.org/en/Resources/Q-and-A/2012-Prohibited-List/
  99. NCAA Banned Drug List - NCAA.org http://www.ncaa.org/wps/wcm/connect/public/NCAA/Health+and+Safety/Drug+Testing/Resources/NCAA+banned+drugs+list
  100. Caffeine renal clearance and urine caffe... [Br J Clin Pharmacol. 1991] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/2049248
  101. Graham, TE.; Spriet, LL. (Dec 1991). "Performance and metabolic responses to a high caffeine dose during prolonged exercise.". J Appl Physiol 71 (6): 2292-8. Template:citation/identifier.
  102. Pasman, WJ.; van Baak, MA.; Jeukendrup, AE.; de Haan, A. (May 1995). "The effect of different dosages of caffeine on endurance performance time.". Int J Sports Med 16 (4): 225-30. Template:citation/identifier. Template:citation/identifier.
  103. How much expressed milk will my baby need? : KellyMom http://www.kellymom.com/bf/pumping/milkcalc.html
  104. Stavchansky, S.; Combs, A.; Sagraves, R.; Delgado, M.; Joshi, A.. "Pharmacokinetics of caffeine in breast milk and plasma after single oral administration of caffeine to lactating mothers.". Biopharm Drug Dispos 9 (3): 285-99. Template:citation/identifier.
  105. McGowan, JD.; Altman, RE.; Kanto, WP. (Sep 1988). "Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine.". South Med J 81 (9): 1092-4. Template:citation/identifier.
  106. Martín, I.; López-Vílchez, MA.; Mur, A.; García-Algar, O.; Rossi, S.; Marchei, E.; Pichini, S. (Feb 2007). "Neonatal withdrawal syndrome after chronic maternal drinking of mate.". Ther Drug Monit 29 (1): 127-9. Template:citation/identifier. Template:citation/identifier.
  107. Buscicchio, G.; Piemontese, M.; Gentilucci, L.; Ferretti, F.; Tranquilli, AL. (May 2012). "The effects of maternal caffeine and chocolate intake on fetal heart rate.". J Matern Fetal Neonatal Med 25 (5): 528-30. Template:citation/identifier. Template:citation/identifier.