1,3,7-Trimethyl-2,6-dioxopurine

Related Terms

1,3,7-Trimethylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, 3,7-dimethylxanthine, 7-methyltheophylline, acetaminophen-caffeine, adenosine antagonist, anhydrous caffeine, aspirin-acetaminophen-caffeine, aspirin-salicylamide-caffeine, black tea, bronchodilator, butalbital-aspirin-caffeine, C8H10N4O2, cacao beans, cafe?na (Spanish), caffea, caffedrine, caffeina citrata, caffeina citrata effervescens, caffeine anhydrous, caffeine choline, caffeine citrate, caffeine citrated intravenous, caffeine citrated oral, caffeine-sodium benzoate, chocolate, citrated caffeine, cocoa, Coffea, coffee, coffee beans, diuretic, effervescent citrated caffeine, energy drink, ergogenic aid, ergotamine-caffeine, espresso, green tea, guarana, guarana berries, kola nut, methylxanthine, orphenadrine-aspirin-caffeine, paraxanthine, psychoactive drug, soft drinks, stimulant, tea, theobromine, theophylline, trimethylxanthine, xanthine, yerba mate.
Select products and brand names: Cafcit?, Enerjets?, NoDoz?, NoDoz? Maximum Strength, Stay Awake?, Vivarin?.
Select combination products: Actamin? Super (acetaminophen and caffeine); Anacin?, Anacin? Advanced Headache Formula, Excedrin?, Goody's? Extra Strength, Goody's? Cool Orange, Vanquish? (acetaminophen, aspirin, and caffeine); Bayer? Headache Relief (aspirin and caffeine); Cafergot?, Cafetrate?, Cafertrine?, Ercaf?, Ergo-Caff?, Gotamine?, Migergot?, Wigraine? (ergotamine and caffeine); Fiorinal? (aspirin, butalbital, and caffeine); Fiorinal? with Codeine No. 3 (aspirin, butalbital, caffeine, and codeine), Medi-First? Pain Relief, Medi-First? Pain Zapper (aspirin, acetaminophen, salicylamide, caffeine); Midol? Complete (acetaminophen, pyrilamine maleate, and caffeine); Norgesic?, Norgesic? forte (orphenadrine citrate, aspirin, caffeine); Revive? energy mints (caffeine, guarana, ginseng, green tea, a?a? berry, mangosteen, and goji berry).
Note: Caffeine is found in many foods and drinks, including black tea, green tea, and yerba mate. Separate summaries are available on these topics. Products containing caffeine are not addressed in detail in this summary.

Background

Caffeine is a naturally occurring compound found in the leaves, seeds, or fruits of more than 60 plants, including coffee (Coffea arabica) beans, cacao (Theobroma cacao) beans, kola (Cola acuminata) nuts, guarana (Paullinia cupana) berries, and tea (Camellia sinensis) leaves. Caffeine is consumed regularly in the United States and throughout the world. It is found in many beverages, including coffee, chocolate, some energy drinks, and tea. More than seven kilograms of caffeine per person are consumed in the United States per year.
Caffeine was first discovered in 1819 by the German chemist Friedlieb Ferdinand Runge. He coined the term Kaffein, a chemical compound in coffee, which became caffeine in English.
Humans have consumed caffeine since the Stone Age. It was during this time that people discovered that chewing the seeds, bark, and leaves of certain plants reduced fatigue, increased awareness, and improved mood. The first known pot of tea dates back to 2737 BC, when the Chinese emperor Shen Nung boiled drinking water when the leaves of a nearby bush fell into the pot. Coffee was first noted in Africa around AD 575, when beans were used as money and eaten as food. Arabians of the 11th Century were known to have coffee beverages. In 1519, Spanish conquerors were treated to a chocolate drink by the Aztec emperor Montezuma. The world's first caffeinated soft drinks were created in the 1880s.
In people, caffeine may be useful to stimulate the heart and increase urine flow. Caffeine has been shown to affect mood, endurance, the brain, and blood vessels, as well as activity in both the stomach and colon. Caffeine has also been marketed as a weight loss tool and is often included in various weight loss supplements.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


In preterm infants, apnea is defined as the stoppage of breathing for 20 seconds or longer. It is one of the most common breathing disorders in the neonatal intensive care unit. Caffeine is a breathing stimulant commonly used to treat apnea. Scientific evidence supports the use of caffeine in the treatment and prevention of apnea in premature infants.

 A


In preterm infants, apnea is defined as the stoppage of breathing for 20 seconds or longer. It is one of the most common breathing disorders in the neonatal intensive care unit. Caffeine is a breathing stimulant commonly used to treat apnea. Scientific evidence supports the use of caffeine in the treatment and prevention of apnea in premature infants.

 A


Caffeine has a long history of use for enhancing mood and cognitive (mental) function. Caffeine may be useful when consumed prior to a cognition-related task. It also appears to heighten working memory and improve reaction time, but it has less effect on long-term memory.

 A


Caffeine has a long history of use for enhancing mood and cognitive (mental) function. Caffeine may be useful when consumed prior to a cognition-related task. It also appears to heighten working memory and improve reaction time, but it has less effect on long-term memory.

 A


Caffeine is a known stimulant that may enhance endurance and performance when used before exercise, particularly in low-to-moderate doses. Caffeine in dry form appears to be more beneficial than coffee or tea. However, its use as a performance-enhancing agent remains controversial. Caffeine should be used with caution, as it may increase blood pressure, heart rate, and urine flow.

 A


Caffeine is a known stimulant that may enhance endurance and performance when used before exercise, particularly in low-to-moderate doses. Caffeine in dry form appears to be more beneficial than coffee or tea. However, its use as a performance-enhancing agent remains controversial. Caffeine should be used with caution, as it may increase blood pressure, heart rate, and urine flow.

 A


Caffeine is a weak type of methylxanthine. Methylxanthines are a class of drugs that open the airways and promote airflow. As such, these types of agents are used to help manage conditions whereby airflow is restricted, such as asthma and chronic obstructive pulmonary disease (COPD). Research suggests that caffeine reduces asthma symptoms, including exercise-induced airway constriction. Caffeine has also been suggested to reduce airway muscle fatigue.

 A


Caffeine is a weak type of methylxanthine. Methylxanthines are a class of drugs that open the airways and promote airflow. As such, these types of agents are used to help manage conditions whereby airflow is restricted, such as asthma and chronic obstructive pulmonary disease (COPD). Research suggests that caffeine reduces asthma symptoms, including exercise-induced airway constriction. Caffeine has also been suggested to reduce airway muscle fatigue.

 A


Evidence suggests that caffeine may have pain-relieving effects. In particular, caffeine has shown useful effects for relieving hypnic migraines (headaches that occur during sleep) and headaches that occur after punctures to the lower back. Although promising, more well-designed trials are needed in this area.

 B


Evidence suggests that caffeine may have pain-relieving effects. In particular, caffeine has shown useful effects for relieving hypnic migraines (headaches that occur during sleep) and headaches that occur after punctures to the lower back. Although promising, more well-designed trials are needed in this area.

 B


There is conflicting evidence supporting the use of caffeine in the treatment of ADHD in children. Additional research is needed in this area.

 C


There is conflicting evidence supporting the use of caffeine in the treatment of ADHD in children. Additional research is needed in this area.

 C


Caffeine and coffee may lower the risk of type 2 diabetes and prevent exercise-induced low blood sugar in type 1 diabetes. However, the research in this area is not consistent, as caffeine has been previously associated with impaired glucose tolerance and insulin sensitivity. Additional research is needed in this area.

 C


Caffeine and coffee may lower the risk of type 2 diabetes and prevent exercise-induced low blood sugar in type 1 diabetes. However, the research in this area is not consistent, as caffeine has been previously associated with impaired glucose tolerance and insulin sensitivity. Additional research is needed in this area.

 C


Limited evidence suggests that caffeine may have positive effects on physical capacity in patients with intermittent claudication (muscle pain in the limbs). Additional research is needed to confirm early results.

 C


Limited evidence suggests that caffeine may have positive effects on physical capacity in patients with intermittent claudication (muscle pain in the limbs). Additional research is needed to confirm early results.

 C


Preliminary evidence suggests that caffeine improves alertness and appetite during the nutritional rehabilitation of children and may therefore have positive effects as an added therapy in the treatment of kwashiorkor (a form of childhood malnutrition). More high-quality research is needed in this area before any firm conclusions can be made.

 C


Preliminary evidence suggests that caffeine improves alertness and appetite during the nutritional rehabilitation of children and may therefore have positive effects as an added therapy in the treatment of kwashiorkor (a form of childhood malnutrition). More high-quality research is needed in this area before any firm conclusions can be made.

 C


Preliminary research suggests that caffeine may have beneficial effects against excess tissue buildup in the liver and that it may be associated with a lower risk of liver disease. However, well-designed trials are needed in this area before any firm conclusions can be drawn.

 C


Preliminary research suggests that caffeine may have beneficial effects against excess tissue buildup in the liver and that it may be associated with a lower risk of liver disease. However, well-designed trials are needed in this area before any firm conclusions can be drawn.

 C


Caffeine is well known for its mood-changing effects. However, current evidence on the relationship between caffeine and depression risk is conflicting, with some studies showing beneficial effects and others showing a lack of effect. Further high-quality research is needed in this area before any firm conclusions can be made.

 C


Caffeine is well known for its mood-changing effects. However, current evidence on the relationship between caffeine and depression risk is conflicting, with some studies showing beneficial effects and others showing a lack of effect. Further high-quality research is needed in this area before any firm conclusions can be made.

 C


Limited evidence suggests that the effects of caffeine are similar to those of d-amphetamine. D-amphetamine is a drug known to promote alertness and focus. Although this is promising, additional research is needed to clarify these early findings.

 C


Limited evidence suggests that the effects of caffeine are similar to those of d-amphetamine. D-amphetamine is a drug known to promote alertness and focus. Although this is promising, additional research is needed to clarify these early findings.

 C


Evidence suggests that caffeine may have pain-relieving effects. According to early research, caffeine has shown beneficial effects against headache- and muscle ache-related pain. More well-designed trials are needed in this area before any firm conclusions can be drawn.

 C


Evidence suggests that caffeine may have pain-relieving effects. According to early research, caffeine has shown beneficial effects against headache- and muscle ache-related pain. More well-designed trials are needed in this area before any firm conclusions can be drawn.

 C


Limited evidence suggests that increased coffee and caffeine consumption may be related to decreased risk of Parkinson's disease. Further high-quality research is needed in this area before any firm conclusions can be drawn.

 C


Limited evidence suggests that increased coffee and caffeine consumption may be related to decreased risk of Parkinson's disease. Further high-quality research is needed in this area before any firm conclusions can be drawn.

 C


The skin application of caffeine for the treatment of wrinkles, stretch marks, and cellulite is growing in popularity. However, the effect of caffeine alone cannot be determined, as most products contain a mixture of agents. Further research assessing the use of caffeine alone is needed in this area.

 C


The skin application of caffeine for the treatment of wrinkles, stretch marks, and cellulite is growing in popularity. However, the effect of caffeine alone cannot be determined, as most products contain a mixture of agents. Further research assessing the use of caffeine alone is needed in this area.

 C


Both theophylline and caffeine are types of methylxanthines. Methylxanthines are a class of drugs that narrow blood vessels in the brain. Due to this effect, early research suggests that theophylline may be useful in stroke patients. However, the effect of caffeine in this area is unclear. More high-quality trials are needed before a conclusion can be drawn.

 C


Both theophylline and caffeine are types of methylxanthines. Methylxanthines are a class of drugs that narrow blood vessels in the brain. Due to this effect, early research suggests that theophylline may be useful in stroke patients. However, the effect of caffeine in this area is unclear. More high-quality trials are needed before a conclusion can be drawn.

 C


Early research suggests that caffeine may be useful for weight loss, particularly when combined with other agents, such as green tea. Although caffeine has shown some positive effects on urine flow, exercise performance, heat production, and feelings of fullness, conflicting results have been seen with respect to its effects on blood sugar levels. Further studies are needed in this area before any firm conclusions can be drawn.

 C


Early research suggests that caffeine may be useful for weight loss, particularly when combined with other agents, such as green tea. Although caffeine has shown some positive effects on urine flow, exercise performance, heat production, and feelings of fullness, conflicting results have been seen with respect to its effects on blood sugar levels. Further studies are needed in this area before any firm conclusions can be drawn.

 C
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Dosing

Adults (18 years and older)
For alertness, 200 milligrams of caffeine has been taken by mouth for different durations.
For cocaine dependence, 300-1,200 milligrams of caffeine has been taken by mouth three times daily (with or without biperiden) for 10 days.
For cognitive performance, 50-600 milligrams of caffeine has been taken by mouth daily for various durations. In sleep-deprived people, 800 milligrams of caffeinated chewing gum has been taken by mouth throughout the night for four days (in 200-milligram doses every two hours).
For type 2 diabetes, about 400 milligrams daily has been taken. In type 1 diabetes, 200 milligrams of caffeine has been taken by mouth daily for three months.
For exercise performance, 1-9 milligrams of caffeine per kilogram of body weight or 200-300 milligrams of caffeine has been taken by mouth prior to exercise.
For headache, a cup of caffeinated coffee or a combination of caffeine and pain relievers (such as aspirin or acetaminophen) have been taken. A single 300-milligram dose of caffeine has also been taken by mouth after childbirth, in women with postdural puncture headache. 300-500 milligrams of caffeine has been injected into the veins once or twice daily. Single or repeated doses of 0.5 grams of caffeine sodium benzoate have been injected into the veins or muscles.
For intermittent claudication (muscle pain in the limbs), six milligrams of caffeine per kilogram of body weight has been taken by mouth prior to physical performance testing.
For liver disease, about two cups of coffee have been taken by mouth daily.
For mood, a caffeinated cup of coffee containing around 75 milligrams of caffeine has been taken by mouth prior to mood testing.
For obsessive compulsive disorder (OCD), 300 milligrams of caffeine in addition to either a serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) agent has been taken by mouth daily for five weeks.
For pain, 5-10 milligrams of caffeine per kilogram of body weight has been taken by mouth one hour prior to moderate-to-high-intensity exercise testing.
For Parkinson's disease, a 300-milligram increase in caffeine intake has been taken.
For respiratory disorders, 5-9 milligrams of caffeine per kilogram of body weight has been taken by mouth.
For weight loss, about 50-200 milligrams of caffeine is contained in each pill of common, commercially available weight loss supplements.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Interactions

Interactions with Drugs
Caffeine may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin?) or heparin, antiplatelet drugs such as clopidogrel (Plavix?), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin?, Advil?) or naproxen (Naprosyn?, Aleve?).
Caffeine may raise blood sugar levels. Caution is advised when using medications that may affect blood sugar (such as metformin). Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Caffeine may increase blood pressure. Caution is advised in patients taking drugs, herbs, or supplements that may affect blood pressure.
Caffeine may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system (e.g., ticlopidine). As a result, the levels of these drugs may be altered in the blood and may change the intended effects. Patients taking any medication should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
Caffeine may also interact with adenosine, agents that affect dopamine, agents that increase urine production, agents that mimic sympathetic nervous system activity (e.g., phenylpropanolamine (PPA)), agents that narrow and widen blood vessels (e.g., nifedipine), agents that regulate heart rate, agents that widen airways, alcohol, Alzheimer's agents, amphetamine, antiandrogens (e.g., flutamide), antiasthma drugs (e.g., furafylline), antibiotics, anticancer drugs (e.g., cisplatin, cyclophosphamide, doxorubicin, ifosfamide, mitomycin C, pazopanib, and temozolomide), antidepressants, antifungals (e.g., terfenadine), antiglaucoma agents, antiobesity agents (e.g., ephedrine), antiparkinsonians (e.g., levodopa), antipsychotics (e.g., phenothiazines), antipyrine, antiseizure drugs (e.g., carbamazepine, ethosuximide, felbamate, phenobarbital, phenytoin, terfenadine, and valproic acid), antiulcer agents (e.g., cimetidine), barbiturates (e.g., pentobarbital), benzodiazepines (e.g., lorazepam), beta-agonists, beta-blockers (e.g., propranolol), calcium salts, celecoxib, central nervous system (CNS) depressants (e.g., diazepam, midazolam, triazolam, zolpidem, zopiclone), clozapine, CNS stimulants, cocaine, contraceptives, corticosteroids, darifenacin, decongestants, dipyridamole, disulfiram, drugs that may lower the seizure threshold, ergot derivatives, estrogens, flubendiamide, fluconazole, fluvoxamine, growth hormone, H2 blockers, hydrocortisone, immune system-lowering agents, inotropes, iron salts, lipid-lowering drugs, lithium, magnesium supplements, methoxsalen, methylenedioxymethamphetamine (MDMA, or "Ecstasy"), methylphenidate, methylxanthines, mexiletine, morphine, nicotine, oseltamivir (Tamiflu?), pain relievers (e.g., acetaminophen, aspirin, ibuprofen, and tramadol), perazine, potassium salts, potassium-depleting drugs, proton pump inhibitors (PPIs) (e.g., omeprazole), quinolones (e.g., ciprofloxacin), riluzole, rosuvastatin, sedatives, terbinafine, and theophylline.

Attribution

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Dellermalm J, Segerdahl M, Grass S. Caffeine does not attenuate experimentally induced ischemic pain in healthy subjects. Acta Anaesthesiol Scand 2009;53(10):1288-1292.
Goldstein ER, Ziegenfuss T, Kalman D, et al. International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr 2010;7(1):5.
Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev 2010;(1):CD000273.
Ker K, Edwards PJ, Felix LM, et al. Caffeine for the prevention of injuries and errors in shift workers. Cochrane Database Syst Rev 2010;(5):CD008508.
MacKenzie T, Comi R, Sluss P, et al. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698.
Momsen AH, Jensen MB, Norager CB, et al. Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication. Br J Surg 2010;97(10):1503-1510.
Noordzij M, Uiterwaal CS, Arends LR, et al. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens 2005;23(5):921-928.
Olson CA, Thornton JA, Adam GE, et al. Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood. J Clin Psychopharmacol 2010;30(5):573-578.
Pfaffenrath V, Diener HC, Pageler L, et al. OTC analgesics in headache treatment: open-label phase vs randomized double-blind phase of a large clinical trial. Headache 2009;49(5):638-645.
Simmonds MJ, Minahan CL, Sabapathy S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur J Appl Physiol 2010;109(2):287-295.
Skinner TL, Jenkins DG, Coombes JS, et al. Dose response of caffeine on 2000-m rowing performance. Med Sci Sports Exerc 2010;42(3):571-576.
Smillie LD, Gokcen E. Caffeine enhances working memory for extraverts. Biol Psychol 2010;85(3):496-498.
Turk MW, Yang K, Hravnak M, et al. Randomized clinical trials of weight loss maintenance: a review. J Cardiovasc Nurs 2009;24(1):58-80.
VanHaitsma TA, Mickleborough T, Stage JM, et al. Comparative effects of caffeine and albuterol on the bronchoconstrictor response to exercise in asthmatic athletes. Int J Sports Med 2010;31(4):231-236.
Welsh EJ, Bara A, Barley E, et al. Caffeine for asthma. Cochrane Database Syst Rev 2010;(1):CD001112.