Caffeine and Running
Caffeine can improve athletic performance, but it's as widely misunderstood as it is widely used.
- Moderate levels of caffeine can improve athletic performance by about 2%, which is about 5 minutes on a 4 hour marathon. This improvement appears to happen regardless of how regularly caffeine is used.
- For running, the best recommendation is a dose of 3 to 5 mg/kg before exercise, followed by 1 to 2 mg/kg periodically after that. For runners, a caffeinated energy gel is probably the best source.
- While it's commonly believed that caffeine causes dehydration, this is only true when high doses are given to those not used to it. Drinking a caffeinated beverage will produce about the same amount of urine, which is probably the source of the myth. People will drink caffeinated beverages when they're not thirsty, so they assume it's the caffeine that's causing them to need to urinate, not the fluid they've drunk.
- Obviously caffeine can interfere with sleep, but this effect can last much longer than you might expect. Even caffeine taken early in the morning can impact your nights' sleep.
- 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.
- 1 Introduction
- 2 Performance
- 3 How much?
- 4 Caffeine and Genetics
- 5 Caffeine, Blood Pressure and Heart Rate
- 6 Caffeine and Dehydration
- 7 Caffeine Habituation
- 8 Caffeine and DOMS
- 9 Caffeine Withdrawal
- 10 Caffeine and Sleep
- 11 Caffeine and Cramping
- 12 Caffeine as a Pain killer
- 13 Caffeine at altitude
- 14 Caffeine clearance
- 15 Glucose Absorption, Insulin Resistance and Glycemic index
- 16 Sources of Caffeine
- 17 Tea and Theanine
- 18 Caffeine, Running and Sudden Death
- 19 Caffeine and health
- 20 Restrictions on Caffeine for Competition
- 21 Ethics of Caffeine
- 22 Newborn babies and Caffeine
- 23 References
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. Today, caffeine can improve performance in endurance running, and three of every four elite athletes take caffeine when competing. Caffeine is one of the most widely used drugs in the world, with average daily intakes worldwide of 70mg/day, but higher in the US (~200mg/day) and the UK (~400mg/day). Caffeine has many effects on many different tissue types, directly and through its metabolites, as well as stimulating adrenaline release.
Studies have shown caffeine can improve performance by ~2%. Though much greater improvements (~12%) have been shown in laboratory conditions, these are not likely to be seen in real world race conditions. 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. Caffeine may improve performance by reducing the RPE and Muscle pain.
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% V̇O2max without affecting Heart Rate or overall energy consumption.
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 and another showed no benefit from caffeinated coffee over decaffeinated coffee. Some studies show a performance benefit from caffeinated coffee, but did not compare with caffeine alone. This may be because coffee contains hundreds if not thousands of compounds besides caffeine. Some of these extra compounds of been shown to affect glucose metabolism. It is been observed that decaffeinated coffee can reduce the absorption of glucose.
3 How much?
Most studies use 3-13mg/Kg, average 6mg, but within that dose range there was no obvious dose response. 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. 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. Low levels of exercise (30% V̇O2max) seem to increase the metabolism of caffeine, but higher intensities have no impact. Below is a listing of caffeine in common beverages.
|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 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. 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. Sometimes the subjects with the AA variant are called "fast metabolizers". (I had my genome tested using 23andme.com which showed I have the AA variant of CYP1A2/rs762551.)
- 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.
- 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.
- 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. 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%). 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. 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.
- Other factors beyond genetics impact CYP1A2 enzyme activity, with exercise, caffeine intake, broccoli all increasing it.
It seems rather counterintuitive to me that the faster you metabolize caffeine, the greater the benefit. It suggests that maybe it's a metabolite of caffeine that improves performance rather than the caffeine itself, but that's pure supposition on my part.
5 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.
5.1 Confounding factors
Understanding the effect of caffeine on blood pressure and heart rate is complicated by a number of factors. Do the subjects regularly use caffeine or are they caffeine naive? Do they have normal blood pressure or hypotension? How does exercise or non-exercise stress change the effect of caffeine? Should we look at acute or long term changes? There may be other underlying factors that influence the response to caffeine, such as nicotine consumption, or taking caffeine with food.
5.2 Acute Changes at Rest
At rest, caffeine increases blood pressure, but it may lower or slightly raise heart rate.
- Systolic blood pressure is increased by 3-7 mmHg.
- A meta-analysis showed that coffee increased systolic blood pressure by 2.4 mmHg, with each additional cup of coffee increasing by a further 0.8 mmHg.
- Diastolic blood pressure is increased by 2-4 mmHg.
- Coffee increases diastolic blood pressure by 1.2 mmHg, with each additional cup of coffee increasing by a further 0.5 mmHg.
- The change in blood pressure is due to an increase in peripheral vascular resistance rather than increased cardiac output.
- Most, but not all studies show that blood pressure increases are generally greater in people with borderline hypotension.
- The rise in blood pressure is seen while the subjects went about their normal activities.
- At rest, heart rate decreases with caffeine though one study showed no change.
- Most studies show that Heart Rate Variability is increased at rest, but one study showed no change in habitual caffeine users, and another showed a reduction in the caffeine naive.
- Caffeine withdrawal can reduce blood pressure by 5-6 mmHg.
- A review of the available research indicated that 7 studies showed that habitual caffeine users had a lower Blood Pressure response to acute caffeine compared with caffeine naive individuals, but 21 studies found no difference. One study showed a reduced increase in blood pressure after regular coffee drinking for four weeks.
- Older individuals may have a greater rise in blood pressure.
- Taking caffeine with food dampens the effect of the caffeine, probably because it decreases the absorption rate.
5.3 Acute Changes During Exercise
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, while others show a decrease. 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.
|Study||Subjects||Caffeine||Exercise||Caffeine's effect on Heart Rate|
|Bell 1998||Caffeine Habituated||5mg/Kg||85% V̇O2max||Increased at 5 min but not 10 min|
|McNaughton 1987||Caffeine Naïve||Incremental to exhaustion||HR Increased|
|Bell 2002||Both Habituated and Naïve||5mg/Kg||80% V̇O2max||HR Increased in both groups|
|Sasaki 1987||200mg||Incremental to exhaustion||HR Increased|
|Sung 1995||Caffeine Habituated||30 min cycling||HR Increase in hypotensive, not normotensive|
|Sullivan 1992||3.3mg/Kg||45% V̇O2max||No change|
|Turley 2006||5mg/Kg||25 and 50watt cycling (children)||No change|
|Gaesser 1985||Caffeine Habituated||200mg||Incremental to exhaustion||HR lower at moderate work rates, no change at high work rates|
|McClaran 2007||Caffeine Naïve, Trained||1.5 or 3.0 mg/Kg||Incremental and maximal||HR lower at submaximal (30-63% V̇O2max) but not maximum workloads|
- The effect of caffeine on blood pressure is more consistent, with most studies showing an increase.
- Blood pressure during exercise can become excessive (> 230 for systolic or > 120 for diastolic). Caffeine increases the risk of excessive blood pressure in normotensive individuals, but the risk is greater in people who are hypertensive . There are recommendations that hypertensive individuals avoid caffeine during exercise.
- Heart Rate Variability goes down with exercise, but this decrease is reduced with caffeine.
- Caffeine did not alter Maximum Heart Rate in one study.
5.4 Caffeine Changes During Non-Exercise Stress
Non-exercise stress includes things like mental arithmetic, rapid information processing, final exams. An analysis of 21 studies that looked at caffeine and non-exercise stress found that:
- Heart rate changes:
- 13 showed no change in heart rate, both at rest and under stress.
- 3 decrease in heart rate at rest, but an increase under stress.
- 3 no change in heart rate at rest, but an increase under stress.
- 2 showed a decrease both at rest and under stress.
- Nearly all studies showed an increase in blood pressure for both the at rest and stress conditions.
6 Caffeine and Dehydration
Caffeine does not impact performance in hot/humid conditions, nor act as a diuretic when running. Caffeine at 360mg is a diuretic at rest, but not at 180mg or less. Caffeine does not cause long term dehydration, and black tea has been shown to hydrate as well as water. Caffeine does result in increased sodium excretion in the urine, but the significance of this unclear.
7 Caffeine Habituation
Surprisingly, there is no clear evidence that the performance benefits of caffeine vary with habitual caffeine usage. Caffeine impacts caffeine naive more at rest than those habituated to caffeine, but the difference is far less during exercise. Caffeine habituation has been shown to reduce the adrenaline response to caffeine, but most other responses remain similar . Animal studies have shown that some tissues adapt to long term use of caffeine but other tissues do not appear to change at all.
8 Caffeine and DOMS
Caffeine has been shown to not only reduce the pain of Delayed Onset Muscle Soreness (DOMS), but also reduces the associated weakness. 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.
9 Caffeine Withdrawal
Withdrawal from Caffeine generally produces a headache and fatigue, with some evidence of anxiety. 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. Small amounts of caffeine can help with withdrawal.
10 Caffeine and Sleep
Not surprisingly given it's a stimulant, caffeine interferes with sleep. Taking 100mg caffeine just before bedtime significantly interferes with sleep. More significantly, taking 200 mg early in the morning will also significantly interfere with sleep. 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.
11 Caffeine and Cramping
12 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. Caffeine adds slightly to the relief of surgical pain from Acetaminophen (Paracetamol) and caffeine can reduce headaches to an equivalent level as Acetaminophen (Paracetamol). Caffeine reduces muscle pain during exercise in both those that habitually take caffeine and those that caffeine naïve, though one study suggested this may only occur in hot conditions. As noted above, caffeine can reduce the pain of DOMS.
13 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:
- 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.
14 Caffeine clearance
Caffeine is rapidly absorbed, and its clearance varies with multiple variables, including exercise. It seems that exercise might increase clearance, which in turn might increase the needed dosage for ultra-endurance events.
- About 99% of consumed caffeine is absorbed within 45 minutes, with peak concentrations after about 30 minutes.
- Caffeine half-life is generally 2.5-5 hours with some dose dependency and individual variability.
- A study found that lean subjects cleared caffeine faster than the obese, with the half life of 2.6 hours rather than 4.4 hours.
- An hour's light exercise (30% V̇O2max) reduced the half life from 4 hours to 2.3 hours in healthy subjects.
- A study of 14 active (V̇O2max of 50) subjects (8 women) found no change in caffeine clearance with exercise. Subjects exercised for 1.5 hours at 60-65% of V̇O2max, starting 1 hour after ingesting 6 mg/Kg of caffeine. Half life was ~6 hours.
- The half-life of caffeine seems dose dependent. In healthy subjects, the half-life at 70mg was 4.5 hours, at 200mg was 60 hours, and at 300mg was 6.4 hours. (Impaired liver function can dramatically increase the half-life to 25-30 hours.)
- Caffeine is metabolized by the liver enzyme CYP1A2 and the activity of this enzyme can be affected by drugs and diet, with tobacco and chargrilled meat increasing levels.
Things may not be so simple, as about 85% of caffeine is metabolized to Paraxanthine  and Paraxanthine in mice is a stronger stimulant than caffeine, while similar in humans. Paraxanthine has a half-life of 3.1-4.1 hours, and levels become higher than caffeine after 8-10 hours (There is a common genetic mutation in dogs that prevents the formation of CYP1A2, making these dogs unable to metabolize caffeine and some other substances.)
15 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.
15.1 At Rest
Caffeine reduces glucose absorption at rest. In tests on lean, obese, and Type 2 Diabetics, glucose absorption was impaired by caffeine, though exercise mitigated the reduction slightly in non-diabetics.
15.2 During Exercise
Unlike the effect of caffeine on sedentary or resting individuals, caffeine increases the absorption, uptake and metabolism of glucose during exercise. Caffeine taken during exercise does not change Glycogen replenishment post-exercise, but caffeine taken with carbohydrate after exercise increased Glycogen replenishment and insulin levels compared with just carbohydrate. One hypothesis for this difference is that caffeine reduces the effect of insulin, and non-insulin dependent glucose pathways predominate during exercise. Caffeine taken 2 hours after exercise impairs glucose absorption, but to a lesser extent than in a completely rested state.
16 Sources of Caffeine
There are various sources of caffeine that are sometimes used by athletes.
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 which compounds the problem of using coffee in sports. I would recommend using other sources of caffeine before or during runs.
It is claimed that tea is the second most popular drink after water, 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. Typically black tea contains 28 to 46mg of Caffeine per 8oz cup. 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.
16.3 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.
The caffeine levels in soda vary widely, with some common values shown below.
|Soda||Caffeine per 12oz|
|Diet Dr Pepper||44.1mg|
|Diet Mountain Dew||55.2mg|
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. This is something to practice in training before using during a race.
16.5 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, which is quite high, but lower than a Starbucks Venti brewed coffee which typically has 400+mg.
16.6 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. 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, which is slightly less than the equivalent volume of coffee.
16.7 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.
16.8 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.
17 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. Theanine has a number of benefits:
- It has been shown to improve and sustain long term attention, acting as a stimulant, even without caffeine.
- When combined with caffeine, theanine reduces distractions.
- Theanine reduces blood pressure and can offset the rise in blood pressure that comes from caffeine.
- Three components of green tea (Catechins, Caffeine and Theanine) reduce obesity in mice.
- Tea may help reduce dementia, and tea improves learning in rats.
- Theanine and cystine may help reduce the immune system depression of high intensity training.
18 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. Sudden death during a marathon is rarer, at less than 1 in 50,000.
18.1 Primary Causes of Sudden Death in Athletes
18.2 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.
18.3 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. This decrease in myocardial blood flow is worse at altitude and in people with Coronary artery disease. (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, but for those with Coronary artery disease the combination of caffeine and exercise may exacerbate their condition.
18.4 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 . In fact, an animal study showed that moderate caffeine reduces the risk of atrial fibrillation. A study giving recent heart attacks 450mg of caffeine showed no change in the risk of arrythmia. Giving 200mg of caffeine before a bicycle stress test to patients who have malignant ventricular arrhythmias made no difference. However, there are anecdotal reports of people having arrhythmia triggered by caffeine. Note that a caffeine overdoes can result in heart problems.
18.5 Caffeine and Blood Pressure
As noted above, blood pressure during exercise rise to an excessive level (> 230 for systolic or > 120 for diastolic). Taking caffeine can increase the risk of excessive blood pressure in people with normal blood pressure, but the risk is greater in people who already have high blood pressure. Some authorities recommendation that individuals with high blood pressure do not take caffeine with exercise.
18.6 Evaluating the risks
Because coronary artery disease may not have any initial symptoms, risk evaluation is tricky. Some runners who died suddenly had high cholesterol, high blood pressure or chest pains. 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.
19 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.
Both green and black tea contain similarly high levels of antioxidants. Green tea contains high levels of EGCG, which has been shown to inhibit cancer cell proliferation. This EGCG may help trigger natural cell death which in turn may help treat both obesity and osteoporosis. 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.
19.2 Coffee and Cancer
Caffeine intake (coffee and other forms) is linked to lower rates of the most common type of skin cancer and coffee drinking is associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers.
19.3 Coffee and Type 2 Diabetes
Coffee drinking is associated with a substantially lower risk of type 2 diabetes, including decaffeinated. 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. 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 .
- Coffee (including decaffeinated) is correlated with reduced markers of insulin secretion, especially in obese and overweight women.
- One study found the T2DM risk was only reduced in tea and coffee drinkers who had previously lost weight.
20 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. It is still restricted by the NCAA at similarly high concentrations. 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. A study of caffeine showed that even 9mg/kg was less than the NCAA threshold for the test subjects, but another study showed that doses of 9mg or above could result in a positive test for some individuals.
21 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:
- It has the potential to improve performance
- It has the potential to harm the health of the athlete
- 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.
22 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
- 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, 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 31-132 hours (average 82 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. Even if the mother breast feeds, the varying levels of caffeine may cause withdrawal symptoms. Also, caffeine has been shown to increase fetal Heart Rate. There is research indicating that Caffeine may not reduce to subtherapeutic levels until around 11-12 days.
- Search for the Competitive Edge: A History of Dietary Fads and Supplements http://jn.nutrition.org/content/127/5/869S.full
- Prevalence of caffeine use in elite ... [Appl Physiol Nutr Metab. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21854160
- Gilbert RM. Caffeine consumption. In : Spiller GA, editor. The methylxanthine beverages and foods, Alan R. Liss; 1984. p. 185-213
- Psychopharmacology, Volume 94, Number 4 - SpringerLink http://www.springerlink.com/content/wl412194360xj32t/
- Caffeine and exercise: metabolism and per... [Can J Appl Physiol. 1994] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/8081318
- Effects of caffeine ingestion o... [Int J Sport Nutr Exerc Metab. 2004] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/15657469
- Effects of caffeine ingestion on rati... [Scand J Med Sci Sports. 2005] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/15773860
- Effect of caffeine on quadricep... [Int J Sport Nutr Exerc Metab. 2009] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/19478340
- MC. Venables, CJ. Hulston, HR. Cox, AE. Jeukendrup, Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans., Am J Clin Nutr, volume 87, issue 3, pages 778-84, Mar 2008, PMID 18326618
- Metabolic and exercise endurance effects of coffee and caffeine ingestion http://jap.physiology.org/content/85/3/883.abstract
- Butts and Crowell (1985) Effect of caffeine ingestion on cardiorespiratory endurance in men and women http://www.getcited.org/pub/103341768
- 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/
- Effects of caffeine ingestion on metabolism a... [Med Sci Sports. 1978] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/723503
- Failure of caffeine to affect substrate... [Med Sci Sports Exerc. 1985] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/3982273
- BMC Cancer | Full text | Coffee consumption and risk of cancers: a meta-analysis of cohort studies http://www.biomedcentral.com/1471-2407/11/96/
- 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
- 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
- Effects of moderate exercise on the pha... [Eur J Clin Pharmacol. 1991] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/2060565
- Effects of exercise and thermal stress on caf... [J Appl Physiol. 2002] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/12235049
- 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 02693879, doi 10.1002/bmc.736
- rs762551 – SNPedia, snpedia.com !!work!!, 18 March 2019 !!access-date!!, https://www.snpedia.com/index.php/Rs762551
- 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 10.1249/MSS.0000000000001596, PMID 29509641
- 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 10.3390/nu9030269, PMID 28287486
- 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 10.1371/journal.pone.0195943, PMID 29668752
- 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 1550-2783, doi 10.1186/1550-2783-9-7
- 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 2156-5783, doi 10.1089/jcr.2015.0029
- 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 2156-5783, doi 10.1089/jcr.2012.0019
- 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 1394840
- KA. Perkins, JE. Sexton, RL. Stiller, C. Fonte, A. DiMarco, J. Goettler, A. Scierka, Subjective and cardiovascular responses to nicotine combined with caffeine during rest and casual activity., Psychopharmacology (Berl), volume 113, issue 3-4, pages 438-44, Jan 1994, PMID 7862856
- M. Hasenfratz, F. Jaquet, D. Aeschbach, K. Bättig, Interactions of smoking and lunch with the effects of caffeine on cardiovascular functions and information processing, Human Psychopharmacology: Clinical and Experimental, volume 6, issue 4, 1991, pages 277–284, ISSN 0885-6222, doi 10.1002/hup.470060403
- Hugo P Sondermeijer, Alexander G.J van Marle, Peter Kamen, Henry Krum, Acute effects of caffeine on heart rate variability, The American Journal of Cardiology, volume 90, issue 8, 2002, pages 906–907, ISSN 00029149, doi 10.1016/S0002-9149(02)02725-X
- TR. Hartley, WR. Lovallo, TL. Whitsett, Cardiovascular effects of caffeine in men and women., Am J Cardiol, volume 93, issue 8, pages 1022-6, Apr 2004, doi 10.1016/j.amjcard.2003.12.057, PMID 15081447
- Kenneth R. Turley, Jonathan W. Gerst, Effects of Caffeine on Physiological Responses to Exercise in Young Boys and Girls, Medicine & Science in Sports & Exercise, volume 38, issue 3, 2006, pages 520–526, ISSN 0195-9131, doi 10.1249/01.mss.0000191189.40436.73
- Jee, Sun Ha, et al. "The effect of chronic coffee drinking on blood pressure a meta-analysis of controlled clinical trials." Hypertension 33.2 (1999): 647-652.
- GA. Pincomb, WR. Lovallo, BS. McKey, BH. Sung, RB. Passey, SA. Everson, MF. Wilson, Acute blood pressure elevations with caffeine in men with borderline systemic hypertension., Am J Cardiol, volume 77, issue 4, pages 270-4, Feb 1996, PMID 8607407
- GA. Pincomb, WR. Lovallo, RB. Passey, TL. Whitsett, SM. Silverstein, MF. Wilson, Effects of caffeine on vascular resistance, cardiac output and myocardial contractility in young men., Am J Cardiol, volume 56, issue 1, pages 119-22, Jul 1985, PMID 4014015
- Bong Hee Sung, William R. Lovallo, Gwendolyn A. Pincomb, Michael F. Wilson, Effects of caffeine on blood pressure response during exercise in normotensive healthy young men, The American Journal of Cardiology, volume 65, issue 13, 1990, pages 909–913, ISSN 00029149, doi 10.1016/0002-9149(90)91435-9
- BH. Sung, WR. Lovallo, T. Whitsett, MF. Wilson, Caffeine elevates blood pressure response to exercise in mild hypertensive men., Am J Hypertens, volume 8, issue 12 Pt 1, pages 1184-8, Dec 1995, PMID 8998252
- T. R. Hartley, B. H. Sung, G. A. Pincomb, T. L. Whitsett, M. F. Wilson, W. R. Lovallo, Hypertension Risk Status and Effect of Caffeine on Blood Pressure, Hypertension, volume 36, issue 1, 2000, pages 137–141, ISSN 0194-911X, doi 10.1161/01.HYP.36.1.137
- WR. Lovallo, GA. Pincomb, BH. Sung, SA. Everson, RB. Passey, MF. Wilson, Hypertension risk and caffeine's effect on cardiovascular activity during mental stress in young men., Health Psychol, volume 10, issue 4, pages 236-43, 1991, PMID 1915209
- PJ. Green, J. Suls, The effects of caffeine on ambulatory blood pressure, heart rate, and mood in coffee drinkers., J Behav Med, volume 19, issue 2, pages 111-28, Apr 1996, PMID 9132505
- TL. Whitsett, CV. Manion, HD. Christensen, Cardiovascular effects of coffee and caffeine., Am J Cardiol, volume 53, issue 7, pages 918-22, Mar 1984, PMID 6702647
- VK. Yeragani, S. Krishnan, HJ. Engels, R. Gretebeck, Effects of caffeine on linear and nonlinear measures of heart rate variability before and after exercise., Depress Anxiety, volume 21, issue 3, pages 130-4, 2005, doi 10.1002/da.20061, PMID 15965989
- EV. Kolodiĭchuk, EB. Arushanian, [The effect of caffeine on the cardiac intervalogram indices depending on the ovarian cycle phase in women]., Farmakol Toksikol, volume 54, issue 6, pages 28-30, PMID 1804688
- Y. Nishijima, T. Ikeda, M. Takamatsu, Y. Kiso, H. Shibata, T. Fushiki, T. Moritani, Influence of caffeine ingestion on autonomic nervous activity during endurance exercise in humans., Eur J Appl Physiol, volume 87, issue 6, pages 475-80, Oct 2002, doi 10.1007/s00421-002-0678-1, PMID 12355185
- Robert Rauh, Michaela Burkert, Martin Siepmann, Michael Mueck-Weymann, Acute effects of caffeine on heart rate variability in habitual caffeine consumers, Clinical Physiology and Functional Imaging, volume 26, issue 3, 2006, pages 163–166, ISSN 1475-0961, doi 10.1111/j.1475-097X.2006.00663.x
- B Phillips-Bute, Caffeine Withdrawal Symptoms Following Brief Caffeine Deprivation, Physiology & Behavior, volume 63, issue 1, 1997, pages 35–39, ISSN 00319384, doi 10.1016/S0031-9384(97)00384-3
- Peter J. Green, Robert Kirby, Jerry Suls, The effects of caffeine on blood pressure and heart rate: A review, Annals of Behavioral Medicine, volume 18, issue 3, 1996, pages 201–216, ISSN 0883-6612, doi 10.1007/BF02883398
- HP. Ammon, PR. Bieck, D. Mandalaz, EJ. Verspohl, Adaptation of blood pressure to continuous heavy coffee drinking in young volunteers. A double-blind crossover study., Br J Clin Pharmacol, volume 15, issue 6, pages 701-6, Jun 1983, PMID 6871070
- JL. Izzo, A. Ghosal, T. Kwong, RB. Freeman, JR. Jaenike, Age and prior caffeine use alter the cardiovascular and adrenomedullary responses to oral caffeine., Am J Cardiol, volume 52, issue 7, pages 769-73, Oct 1983, PMID 6353897
- DG. Bell, I. Jacobs, J. Zamecnik, Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise., Eur J Appl Physiol Occup Physiol, volume 77, issue 5, pages 427-33, Apr 1998, doi 10.1007/s004210050355, PMID 9562293
- Lars Mcnaughton, Two Levels of Caffeine Ingestion on Blood Lactate and Free Fatty Acid Responses during Incremental Exercise, Research Quarterly for Exercise and Sport, volume 58, issue 3, 1987, pages 255–259, ISSN 0270-1367, doi 10.1080/02701367.1987.10605458
- H. Sasaki, I. Takaoka, T. Ishiko, Effects of sucrose or caffeine ingestion on running performance and biochemical responses to endurance running., Int J Sports Med, volume 8, issue 3, pages 203-7, Jun 1987, doi 10.1055/s-2008-1025656, PMID 3623782
- DG. Bell, TM. McLellan, Exercise endurance 1, 3, and 6 h after caffeine ingestion in caffeine users and nonusers., J Appl Physiol (1985), volume 93, issue 4, pages 1227-34, Oct 2002, doi 10.1152/japplphysiol.00187.2002, PMID 12235019
- Sullivan, James J., Knowlton, Ronald G., Brown, Dale D., 1992, Journal of Cardiopulmonary Rehabilitation and Prevention, Caffeine Affects Heart Rate and Blood Pressure Response to Prolonged Walking, http://journals.lww.com/jcrjournal/Fulltext/1992/11000/Caffeine_Affects_Heart_Rate_and_Blood_Pressure.8.aspx
- GA. Gaesser, RG. Rich, Influence of caffeine on blood lactate response during incremental exercise., Int J Sports Med, volume 6, issue 4, pages 207-11, Aug 1985, doi 10.1055/s-2008-1025841, PMID 4044104
- Steven R McClaran, Thomas J Wetter, Low doses of caffeine reduce heart rate during submaximal cycle ergometry, Journal of the International Society of Sports Nutrition, volume 4, issue 1, 2007, pages 11, ISSN 1550-2783, doi 10.1186/1550-2783-4-11
- Gwendolyn A. Pincomb, Michael F. Wilson, Bong Hee Sung, Richard B. Passey, William R. Lovallo, Effects of caffeine on pressor regulation during rest and exercise in men at risk for hypertension, American Heart Journal, volume 122, issue 4, 1991, pages 1107–1115, ISSN 00028703, doi 10.1016/0002-8703(91)90479-2
- Myth buster: caffeine does not exhibit a di... [Indian J Med Res. 2010] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/20693584
- Renal and cardiovascular effects of caffeine... [Clin Sci (Lond). 1987] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/3297472
- Fluid, electrolyte, and renal i... [Int J Sport Nutr Exerc Metab. 2005] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/16131696
- Black tea is not significantly different from wate... [Br J Nutr. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21450118
- Natriuretic effect of caffeine: assessment o... [Clin Sci (Lond). 2002] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/12401118
- European Journal of Applied Physiology and Occupational Physiology, Volume 62, Number 6 - SpringerLink http://www.springerlink.com/content/u37082130426tl56/
- Caffeine metabolism and epinephrine responses during exercise in users and nonusers http://jap.physiology.org/content/75/2/805.abstract
- The effects of caffeine on perceived pain of muscles http://scholarsresearchlibrary.com/ABR-vol2-iss6/ABR-2011-2-6-16-21.pdf
- Caffeine Attenuates Delayed-Onset Muscle Pain and Force Loss Following Eccentric Exercise http://www.jpain.org/article/S1526-5900%2806%2901023-6/abstract
- Excitation-contraction uncoupling: major... [Exerc Sport Sci Rev. 2001] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/11337828
- Intracellular calcium and force in single mouse mu... [J Physiol. 1995] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/8568662
- 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
- HP. Landolt, DJ. Dijk, SE. Gaus, AA. Borbély, Caffeine reduces low-frequency delta activity in the human sleep EEG., Neuropsychopharmacology, volume 12, issue 3, pages 229-38, May 1995, doi 10.1016/0893-133X(94)00079-F, PMID 7612156
- HP. Landolt, E. Werth, AA. Borbély, DJ. Dijk, Caffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at night., Brain Res, volume 675, issue 1-2, pages 67-74, Mar 1995, PMID 7796154
- Judith Stern, Coffee and muscle cramps, Neuromuscular Disorders, volume 21, issue 5, 2011, pages 375, ISSN 09608966, doi 10.1016/j.nmd.2011.03.007
- Victor Dubowitz, Muscle cramps and coffee, Neuromuscular Disorders, volume 21, issue 3, 2011, pages 235, ISSN 09608966, doi 10.1016/j.nmd.2011.01.004
- N.C. Voermans, B.G. van Engelen, Coffee and muscle cramps, Neuromuscular Disorders, volume 21, issue 12, 2011, pages 832, ISSN 09608966, doi 10.1016/j.nmd.2011.07.006
- JAMA Network | JAMA: The Journal of the American Medical Association | Caffeine as an Analgesic Adjuvant http://jama.jamanetwork.com/article.aspx?articleid=392180
- 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
- The analgesic effects of caffeine in headache. [Pain. 1991] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/2052380
- Caffeine lowers muscle pain during exercise in... [Physiol Behav. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21163281
- Caffeine at high altitude: java at base cAMP. [High Alt Med Biol. 2010] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/20367483
- Astrid Nehlig, Stephen P. H. Alexander, Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption, Pharmacological Reviews, volume 70, issue 2, 2018, pages 384–411, ISSN 0031-6997, doi 10.1124/pr.117.014407
- Simonetta Camandola, Natalie Plick, Mark P. Mattson, Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease, Neurochemical Research, volume 44, issue 1, 2018, pages 214–227, ISSN 0364-3190, doi 10.1007/s11064-018-2492-0
- GH. Kamimori, SM. Somani, RG. Knowlton, RM. Perkins, The effects of obesity and exercise on the pharmacokinetics of caffeine in lean and obese volunteers., Eur J Clin Pharmacol, volume 31, issue 5, pages 595-600, 1987, PMID 3830245
- K. Collomp, F. Anselme, M. Audran, JP. Gay, JL. Chanal, C. Prefaut, Effects of moderate exercise on the pharmacokinetics of caffeine., Eur J Clin Pharmacol, volume 40, issue 3, pages 279-82, 1991, PMID 2060565
- C. McLean, T. E. Graham, Effects of exercise and thermal stress on caffeine pharmacokinetics in men and eumenorrheic women, Journal of Applied Physiology, volume 93, issue 4, 2002, pages 1471–1478, ISSN 8750-7587, doi 10.1152/japplphysiol.00762.2000
- Wendy S C Cheng, Therese L Murphy, Maree T Smith, W Graham E Cooksley, June W Halliday, Lawrie W Powell, Dose-dependent pharmacokinetics of caffeine in humans: Relevance as a test of quantitative liver function, Clinical Pharmacology and Therapeutics, volume 47, issue 4, 1990, pages 516–524, ISSN 0009-9236, doi 10.1038/clpt.1990.66
- Werner Kalow, Bing-Kou Tang, The use of caffeine for enzyme assays: A critical appraisal, Clinical Pharmacology and Therapeutics, volume 53, issue 5, 1993, pages 503–514, ISSN 0009-9236, doi 10.1038/clpt.1993.63
- Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). "/clinpharm/ddis/clinical-table/" Accessed June 2015.
- S. Guerreiro, D. Toulorge, E. Hirsch, M. Marien, P. Sokoloff, P. P. Michel, Paraxanthine, the Primary Metabolite of Caffeine, Provides Protection against Dopaminergic Cell Death via Stimulation of Ryanodine Receptor Channels, Molecular Pharmacology, volume 74, issue 4, 2008, pages 980–989, ISSN 0026-895X, doi 10.1124/mol.108.048207
- M. Okuro, N. Fujiki, N. Kotorii, Y. Ishimaru, P. Sokoloff, S. Nishino, Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice., Sleep, volume 33, issue 7, pages 930-42, Jul 2010, PMID 20614853
- Neal L. Benowitz, Peyton Jacob, Haim Mayan, Charles Denaro, Sympathomimetic effects of paraxanthine and caffeine in humans*, Clinical Pharmacology & Therapeutics, volume 58, issue 6, 1995, pages 684–691, ISSN 0009-9236, doi 10.1016/0009-9236(95)90025-X
- 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 01407783, doi 10.1111/j.1365-2885.2010.01222.x
- 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
- Caffeine Can Decrease Insulin Sensitivity in Humans http://care.diabetesjournals.org/content/25/2/364.abstract?ijkey=0d78b20406d1b0da6a363f1b00847b0434751e49&keytype2=tf_ipsecsha
- Effects of caffeine on glucose tolerance: a ... [Eur J Clin Nutr. 1998] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/9846599?dopt=Abstract
- ingentaconnect Caffeine ingestion elevates plasma insulin response in humans dur... http://www.ingentaconnect.com/content/nrc/cjpp/2001/00000079/00000007/art00002
- 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
- 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
- Caffeine increases exogenous carbohydrate oxidation during exercise http://jap.physiology.org/content/99/3/844.full
- Gastrointestinal function during exercise: comparison of water, sports drink, and sports drink with caffeine http://jap.physiology.org/content/89/3/1079.full
- 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
- High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine http://jap.physiology.org/content/105/1/7.long
- High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine http://www.jappl.org/content/105/1/7.full
- 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
- ML. Bunker, M. McWilliams, Caffeine content of common beverages., J Am Diet Assoc, volume 74, issue 1, pages 28-32, Jan 1979, PMID 762339
- Yoko Shishikura, Santosh Khokhar, Factors affecting the levels of catechins and caffeine in tea beverage: estimated daily intakes and antioxidant activity, Journal of the Science of Food and Agriculture, volume 85, issue 12, 2005, pages 2125–2133, ISSN 0022-5142, doi 10.1002/jsfa.2206
- author Alan Macfarlane, Iris Macfarlane !!coauthors!!, The Empire of Tea, publisher The Overlook Press, isbn 1-58567-493-1, page 32, 2004
- YS. Lin, YJ. Tsai, JS. Tsay, JK. Lin, Factors affecting the levels of tea polyphenols and caffeine in tea leaves., J Agric Food Chem, volume 51, issue 7, pages 1864-73, Mar 2003, doi 10.1021/jf021066b, PMID 12643643
- K.-H. Chou, L.N. Bell, Caffeine Content of Prepackaged National-Brand and Private-Label Carbonated Beverages, Journal of Food Science, volume 72, issue 6, 2007, pages C337–C342, ISSN 0022-1147, doi 10.1111/j.1750-3841.2007.00414.x
- Fueling Properly for an Ultra | Running Times Magazine http://runningtimes.com/Article.aspx?ArticleID=21791
- Caffeine Content of Drinks http://www.energyfiend.com/the-caffeine-database
- The Complete Guide to Starbucks Caffeine http://www.energyfiend.com/the-complete-guide-to-starbucks-caffeine
- RW. Pettitt, JD. Niemeyer, PJ. Sexton, A. Lipetzky, SR. Murray, Do the non-caffeine ingredients of energy drinks affect metabolic responses to heavy exercise?, J Strength Cond Res, Oct 2012, doi 10.1519/JSC.0b013e3182736e31, PMID 23037611
- 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
- L-theanine, a natural constituent in te... [Asia Pac J Clin Nutr. 2008] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18296328
- The effects of L-theanine on alpha-band oscilla... [Brain Topogr. 2009] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18841456
- Source density analysis of the human E... [Nutr Neurosci. 2007 Jun-Aug] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18019399
- Psychological effects of dietary components of tea:... [Nutr Rev. 2008] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/18254874
- 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
- Time for tea: mood, blood pressure... [Psychopharmacology (Berl). 2008] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/17891480
- 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
- Tea and cognitive health in late life: c... [J Nutr Health Aging. 2012] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/22237999
- Effects of oral supplementation wi... [Biosci Biotechnol Biochem. 2009] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/19352043
- 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
- PD. Thompson, EJ. Funk, RA. Carleton, WQ. Sturner, Incidence of death during jogging in Rhode Island from 1975 through 1980., JAMA, volume 247, issue 18, pages 2535-8, May 1982, PMID 6978411
- Barry J. Maron, Liviu C. Poliac, William O. Roberts, Risk for sudden cardiac death associated with marathon running, Journal of the American College of Cardiology, volume 28, issue 2, 1996, pages 428–431, ISSN 07351097, doi 10.1016/0735-1097(96)00137-4
- William O. Roberts, Barry J. Maron, Evidence for Decreasing Occurrence of Sudden Cardiac Death Associated With the Marathon, Journal of the American College of Cardiology, volume 46, issue 7, 2005, pages 1373–1374, ISSN 07351097, doi 10.1016/j.jacc.2005.07.008
- Barry J. Maron, Stephen E. Epstein, William C. Roberts, Causes of sudden death in competitive athletes, Journal of the American College of Cardiology, volume 7, issue 1, 1986, pages 204–214, ISSN 07351097, doi 10.1016/S0735-1097(86)80283-2
- Bruce F. Waller, William C. Roberts, Sudden death while running in conditioned runners aged 40 years or over, The American Journal of Cardiology, volume 45, issue 6, 1980, pages 1292–1300, ISSN 00029149, doi 10.1016/0002-9149(80)90491-9
- M. Namdar, T. Schepis, P. Koepfli, O. Gaemperli, PT. Siegrist, R. Grathwohl, I. Valenta, R. Delaloye, M. Klainguti, Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controls., PLoS One, volume 4, issue 5, pages e5665, 2009, doi 10.1371/journal.pone.0005665, PMID 19479069
- M. Namdar, P. Koepfli, R. Grathwohl, PT. Siegrist, M. Klainguti, T. Schepis, R. Delaloye, CA. Wyss, SP. Fleischmann, Caffeine decreases exercise-induced myocardial flow reserve., J Am Coll Cardiol, volume 47, issue 2, pages 405-10, Jan 2006, doi 10.1016/j.jacc.2005.08.064, PMID 16412869
- Abdul Rashid, Mujahid Hines, Benjamin J. Scherlag, William S. Yamanashi, William Lovallo, The effects of caffeine on the inducibility of atrial fibrillation, Journal of Electrocardiology, volume 39, issue 4, 2006, pages 421–425, ISSN 00220736, doi 10.1016/j.jelectrocard.2005.12.007
- MB. Katan, E. Schouten, Caffeine and arrhythmia., Am J Clin Nutr, volume 81, issue 3, pages 539-40, Mar 2005, PMID 15755819
- DJ. Pelchovitz, JJ. Goldberger, Caffeine and cardiac arrhythmias: a review of the evidence., Am J Med, volume 124, issue 4, pages 284-9, Apr 2011, doi 10.1016/j.amjmed.2010.10.017, PMID 21435415
- MG. Myers, L. Harris, High dose caffeine and ventricular arrhythmias., Can J Cardiol, volume 6, issue 3, pages 95-8, Apr 1990, PMID 1692755
- TB. Graboys, CM. Blatt, B. Lown, The effect of caffeine on ventricular ectopic activity in patients with malignant ventricular arrhythmia., Arch Intern Med, volume 149, issue 3, pages 637-9, Mar 1989, PMID 2465748
- Coronary artery disease: Symptoms - MayoClinic.com http://www.mayoclinic.com/health/coronary-artery-disease/DS00064/DSECTION=symptoms
- 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
- Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway http://www.sciencedirect.com/science/article/pii/S0304383506001960
- 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
- ingentaconnect Novel Treatments for Obesity and Osteoporosis: Targeting Apoptoti... http://www.ingentaconnect.com/content/ben/cmc/2005/00000012/00000019/art00003
- Tea and cancer prevention: epidemiological stu... [Pharmacol Res. 2011] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/21419224
- Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin http://cancerres.aacrjournals.org/content/72/13/3282.abstract
- Annals of Internal Medicine | Coffee Consumption and Risk for Type 2 Diabetes Mellitus http://annals.org/article.aspx?volume=140&issue=1&page=1
- Coffee, Caffeine, and Risk of Type 2 Diabetes http://care.diabetesjournals.org/content/29/2/398.abstract?ijkey=0aa1ab4745bc811da4ab34ed66604d4462b97615&keytype2=tf_ipsecsha
- 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
- 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
- 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
- 2012 Prohibited List - World Anti-Doping Agency http://www.wada-ama.org/en/Resources/Q-and-A/2012-Prohibited-List/
- 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
- Caffeine renal clearance and urine caffe... [Br J Clin Pharmacol. 1991] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/2049248
- TE. Graham, LL. Spriet, Performance and metabolic responses to a high caffeine dose during prolonged exercise., J Appl Physiol, volume 71, issue 6, pages 2292-8, Dec 1991, PMID 1778925
- WJ. Pasman, MA. van Baak, AE. Jeukendrup, A. de Haan, The effect of different dosages of caffeine on endurance performance time., Int J Sports Med, volume 16, issue 4, pages 225-30, May 1995, doi 10.1055/s-2007-972996, PMID 7657415
- How much expressed milk will my baby need? : KellyMom http://www.kellymom.com/bf/pumping/milkcalc.html
- S. Stavchansky, A. Combs, R. Sagraves, M. Delgado, A. Joshi, Pharmacokinetics of caffeine in breast milk and plasma after single oral administration of caffeine to lactating mothers., Biopharm Drug Dispos, volume 9, issue 3, pages 285-99, PMID 3395670
- Parsons, William D., and Allen H. Neims. "Prolonged half-life of caffeine in healthy term newborn infants." Journal of Pediatrics 98.4 (1981): 640-641.
- JD. McGowan, RE. Altman, WP. Kanto, Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine., South Med J, volume 81, issue 9, pages 1092-4, Sep 1988, PMID 3420441
- I. Martín, MA. López-Vílchez, A. Mur, O. García-Algar, S. Rossi, E. Marchei, S. Pichini, Neonatal withdrawal syndrome after chronic maternal drinking of mate., Ther Drug Monit, volume 29, issue 1, pages 127-9, Feb 2007, doi 10.1097/FTD.0b013e31803257ed, PMID 17304161
- G. Buscicchio, M. Piemontese, L. Gentilucci, F. Ferretti, AL. Tranquilli, The effects of maternal caffeine and chocolate intake on fetal heart rate., J Matern Fetal Neonatal Med, volume 25, issue 5, pages 528-30, May 2012, doi 10.3109/14767058.2011.636104, PMID 22502981
- J. Doyle, D. Davidson, S. Katz, M. Varela, D. Demeglio, J. DeCristofaro, Apnea of prematurity and caffeine pharmacokinetics: potential impact on hospital discharge., J Perinatol, volume 36, issue 2, pages 141-4, Feb 2016, doi 10.1038/jp.2015.167, PMID 26562367