Coffee

Other Name(s):

Cafe, Café, Café Arabica, Café Robusta, Caffea, Coffea arabica, Coffea arnoldiana, Coffea bukobensis, Coffea canephora, Coffea Cruda, Coffea liberica, Coffea robusta, Espresso, Expresso, Java, Mocha.

Overview

Coffee is a drink made from coffee beans, which are the roasted fruit of the Coffea arabica bush.

People drink coffee to relieve mental and physical fatigue and to increase mental alertness. Coffee is also used to prevent Parkinson's disease, gallstones, type 2 diabetes, gastrointestinal cancer, lung cancer, and breast cancer. Other uses include treatment of headache, low blood pressure, obesity, and attention deficit-hyperactivity disorder (ADHD).

Rectally, coffee is used as an enema to treat cancer. Coffee enemas are used as a part of the "Gerson Therapy." In the Gerson Therapy, cancer patients are treated with caffeinated coffee in the form of enemas every four hours on a daily basis. During the treatment people are given a diet of liver, vegetables, and a variety of medicines, including potassium, pepsin, Lugol's solution, niacin, pancreatin, and thyroid extracts. The Gerson Therapy is considered an unacceptable medical practice in the U.S., but continues to be used at The Hospital of the Baja California in Tijuana, Mexico, one mile from the U.S.

How does work?

Coffee contains caffeine. Caffeine works by stimulating the central nervous system (CNS), heart, and muscles.

Uses

Likely Effective for...

  • Mental alertness. Drinking coffee and other beverages that contain caffeine throughout the day seems to increase alertness and clear thinking. Caffeine can also improve alertness after sleep deprivation. Combining caffeine with glucose as an "energy drink" seems to improve mental performance better than either caffeine or glucose alone.

Possibly Effective for...

  • Reducing the risk of colorectal cancer. Some research suggests that drinking more than 3 cups of coffee daily may significantly reduce the risk of rectal cancer.
  • Preventing dizziness in older people caused by low blood pressure after eating a meal (postprandial hypotension). Drinking caffeinated beverages like coffee seems to increase blood pressure in elderly people who experience dizziness after meals.
  • Preventing or delaying Parkinson's disease. There is evidence that people who drink caffeinated beverages such as coffee, tea, and cola have a decreased risk of Parkinson's disease. For men, the effect seems to depend on the amount of caffeine consumed. Men who drink the most caffeinated coffee, 28 ounces (three to four cups) per day, seem to have the greatest reduction in risk. But drinking even 1 or 2 cups of coffee cuts their Parkinson's disease risk significantly. In women, the effect does not seem to depend so much on the amount of caffeine consumed. Moderate consumption of caffeinated coffee, 1-3 cups daily, provides the most reduction in risk in women. Interestingly, coffee does not seem to help prevent Parkinson's disease in people who smoke cigarettes.
  • Preventing gallstones. Drinking caffeinated beverages, including coffee, that provide at least 400 mg of caffeine per day seems to reduce the risk of developing gallstones. The greater the intake of caffeine, the lower the risk. Drinking 800 mg caffeine per day (four or more cups of coffee) has the greatest reduction in risk.
  • Preventing type 2 diabetes. Drinking caffeinated coffee seems to significantly reduce the risk of developing type 2 diabetes. As caffeine consumption goes up, the risk of developing diabetes goes down. But the effect seems to be different in different groups of people. In North American adults, drinking 6 or more cups of coffee per day is associated with a 54% lower risk of developing diabetes in men and a 29% lower risk in women. In European adults, drinking 5-6 cups of coffee per day reduces diabetes risk by 61% in women and 30% in men. Drinking 10 or more cups of coffee per day reduces diabetes risk by 79% in women and 55% in men. Japanese adults who drink 3 or more cups of coffee per day have a 42% lower risk of developing type 2 diabetes compared to those who drink only one cup per day or less. Decaffeinated coffee doesn't seem to lower the risk of getting diabetes.

Possibly Ineffective for...

  • Reducing the risk of digestive tract cancers, including esophageal, stomach, and colon cancers.
  • Reducing the risk of breast cancer.

Insufficient Evidence to Rate Effectiveness for...

  • Lung cancer. Some research concludes that drinking caffeinated coffee may help to prevent lung cancer, but other research disagrees. It's too early to draw firm conclusions. Meanwhile, some research suggests that drinking decaffeinated coffee may help to prevent lung cancer.
  • Gout. There is some evidence that both caffeinated and decaffeinated coffee seem to help to prevent gout, but caffeinated coffee works better.
  • Improving thinking. There is developing evidence suggesting that drinking more coffee over a lifetime might improve thinking skills among women older than 80 years of age.
  • Other conditions.
More evidence is needed to rate the effectiveness of coffee for these uses.

QUESTION

Parkinson's disease is only seen in people of advanced age. See Answer

Side Effects

Coffee is safe for most adults. Drinking more than 6 cups/day might cause “caffeinism” with symptoms such as anxiety or agitation. People who drink a lot of coffee every day may need to drink more coffee to get the same effects. They may also become “dependent” on coffee to the point that they develop withdrawal symptoms if they suddenly stop drinking it.

Coffee containing caffeine can cause insomnia, nervousness and restlessness, stomach upset, nausea and vomiting, increased heart and breathing rate, and other side effects. Consuming large amounts of coffee might also cause headache, anxiety, agitation, ringing in the ears, and irregular heartbeats.

Drinking unfiltered coffee can increase total cholesterol, low-density lipoprotein (LDL), and levels of another type of blood fat called triglycerides. This might increase the risk of developing heart disease. Using coffee filters helps to reduce these effects on cholesterol.

There is some concern that drinking more than 5 cups of coffee per day might not be safe for people with heart disease. But for people who don't have heart disease, drinking several cups daily does not seem to increase the chance of developing a heart problem.

There is also concern that occasional coffee drinking might trigger a heart attack in some people. People who usually don't drink more than one cup of coffee daily and also have multiple risk factors for heart disease seem to have an increased risk for heart attack within an hour after drinking coffee. But people who regularly drink greater amounts do not seem to have this risk.

Coffee might be unsafe when given rectally as an enema. Coffee enemas have been linked to cases of severe side effects including death.

Precautions

Pregnancy and breast-feeding: Caffeinated coffee is probably safe for pregnant women in amounts of 2 cups per day or less. This amount of coffee provides about 200 mg of caffeine. However, drinking more than this amount has been linked to an increased risk of miscarriage, premature birth, and low birth weight. These risks increase as the amount of coffee the mother drinks during pregnancy increases.

Drinking 1 or 2 of cups of coffee per day seems to be safe for breast-feeding mothers and their infants. But the caffeine in larger amounts can irritate a nursing infant's digestive tract and also cause sleep problems and irritability.

Children: It may be unsafe for children to drink caffeinated coffee. The side effects associated with caffeine are usually more severe in children than adults.

Anxiety disorders: The caffeine in coffee might make anxiety worse.

Bleeding disorders: There is some concern that coffee might make bleeding disorders worse.

Heart disease: Drinking unfiltered (boiled) coffee increases the amount of cholesterol and other fats in the blood, and also raises the level of homocysteine, all of which are associated with an increased risk of developing heart disease. Some research suggests an association between heart attacks and drinking coffee.

Diabetes: Some research suggests that caffeine contained in coffee might change the way people with diabetes process sugar. Caffeine has been reported to cause increases as well as decreases in blood sugar. Use caffeine with caution if you have diabetes and monitor your blood sugar carefully.

Diarrhea: Coffee contains caffeine. The caffeine in coffee, especially when taken in large amounts, can worsen diarrhea.

Irritable bowel syndrome (IBS): Coffee contains caffeine. The caffeine in coffee, especially when taken in large amounts, can worsen diarrhea and might worsen symptoms of IBS.

Glaucoma: Drinking caffeinated coffee increases pressure inside the eye. The increase starts within 30 minutes and lasts for at least 90 minutes.

High blood pressure: Drinking caffeinated coffee might increase blood pressure in people with high blood pressure. However, this effect might be less in people who drink coffee regularly.

Thinning bones (osteoporosis): Drinking caffeinated coffee can increase the amount of calcium that is flushed out in the urine. This might weaken bones. If you have osteoporosis, limit caffeine consumption to less than 300 mg per day (approximately 2-3 cups of coffee). Taking calcium supplements may help to make up for calcium that is lost. Postmenopausal women who have an inherited condition that keeps them from processing vitamin D normally, should be especially cautious when using caffeine.

Interactions


EphedrineInteraction Rating: Major Do not take this combination.

Stimulant drugs speed up the nervous system. The caffeine in coffee and ephedrine are both stimulant drugs. Drinking coffee and taking ephedrine might cause too much stimulation and sometimes serious side effects and heart problems. Do not take caffeine-containing products and ephedrine at the same time.


Adenosine (Adenocard)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The caffeine in coffee might block the affects of adenosine (Adenocard). Adenosine (Adenocard) is often used by doctors to do a test on the heart. This test is called a cardiac stress test. Stop consuming coffee or other caffeine-containing products at least 24 hours before a cardiac stress test.


AlcoholInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Alcohol can decrease how quickly the body breaks down caffeine. Taking coffee along with alcohol might cause too much caffeine in the bloodstream and caffeine side effects including jitteriness, headache, and fast heartbeat.


Alendronate (Fosamax)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Coffee can decrease how much alendronate (Fosamax) the body absorbs. Taking coffee and alendronate (Fosamax) at the same time can decrease the effectiveness of alendronate (Fosamax). Don't drink coffee within two hours of taking alendronate (Fosamax).


Antibiotics (Quinolone antibiotics)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down caffeine to get rid of it. Some antibiotics might decrease how quickly the body breaks down caffeine. Taking these antibiotics along with coffee can increase the risk of side effects including jitteriness, headache, increased heart rate, and other side effects.

Some antibiotics that decrease how quickly the body breaks down caffeine include ciprofloxacin (Cipro), enoxacin (Penetrex), norfloxacin (Chibroxin, Noroxin), sparfloxacin (Zagam), trovafloxacin (Trovan), and grepafloxacin (Raxar).


Birth control pills (Contraceptive drugs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Birth control pills can decrease how quickly the body breaks down caffeine. Taking coffee along with birth control pills can cause jitteriness, headache, fast heartbeat, and other side effects.

Some birth control pills include ethinyl estradiol and levonorgestrel (Triphasil), ethinyl estradiol and norethindrone (Ortho-Novum 1/35, Ortho-Novum 7/7/7), and others.


Clozapine (Clozaril)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down clozapine (Clozaril) to get rid of it. The caffeine in coffee might decrease how fast the body breaks down clozapine (Clozaril). Taking coffee along with clozapine (Clozaril) can increase the effects and side effects of clozapine (Clozaril).


Dipyridamole (Persantine)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The caffeine in coffee might block the affects of dipyridamole (Persantine). Dipyridamole (Persantine) is often used by doctors to do a test on the heart. This test is called a cardiac stress test. Stop drinking coffee or other caffeine-containing products at least 24 hours before a cardiac stress test.


Disulfiram (Antabuse)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Disulfiram (Antabuse) can decrease how quickly the body gets rid of caffeine. Taking coffee along with disulfiram (Antabuse) might increase the effects and side effects of coffee including jitteriness, hyperactivity, irritability, and others.


EstrogensInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Estrogens can decrease how quickly the body breaks down caffeine. Taking estrogen pills and drinking coffee can cause jitteriness, headache, fast heartbeat, and other side effects. If you take estrogen pills limit your caffeine intake.

Some estrogen pills include conjugated equine estrogens (Premarin), ethinyl estradiol, estradiol, and others.


Fluvoxamine (Luvox)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Fluvoxamine (Luvox) can decrease how quickly the body breaks down caffeine. Taking caffeine along with fluvoxamine (Luvox) might cause too much caffeine in the body, and increase the effects and side effects of caffeine.


Levothyroxine (Synthroid, Levothroid, Levoxyl, and others)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Drinking some types of coffee might reduce the amount of levothyroxine that is absorbed when taken by mouth. This can decrease how well levothyroxine works. Avoid drinking coffee at the same time that you take levothyroxine and for an hour afterwards.


LithiumInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Your body naturally gets rid of lithium. The caffeine in coffee can increase how quickly your body gets rid of lithium. If you take products that contain caffeine and you take lithium, stop taking caffeine products slowly. Stopping caffeine too quickly can increase the side effects of lithium.


Medications for asthma (Beta-adrenergic agonists)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Coffee contains caffeine. Caffeine can stimulate the heart. Some medications for asthma can also stimulate the heart. Taking caffeine with some medications for asthma might cause too much stimulation and cause heart problems.

Some medications for asthma include albuterol (Proventil, Ventolin, Volmax), metaproterenol (Alupent), terbutaline (Bricanyl, Brethine), and isoproterenol (Isuprel).


Medications for depression (MAOIs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The caffeine in coffee can stimulate the body. Some medications used for depression can also stimulate the body. Drinking coffee and taking some medications for depression might cause too much stimulation and serious side effects including fast heartbeat, high blood pressure, nervousness, and others.

Some of these medications used for depression include phenelzine (Nardil), tranylcypromine (Parnate), and others.


Medications for depression (Tricyclic antidepressants)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Coffee contains chemicals called tannins. Tannins can bind to many medications and decrease how much medicine the body absorbs. To avoid this interaction avoid coffee one hour before and two hours after taking medications for depression called tricyclic antidepressants.

Some medications for depression include amitriptyline (Elavil) or imipramine (Tofranil, Janimine).


Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Coffee might slow blood clotting. Taking coffee along with medications that also slow clotting might increase the chances of bruising and bleeding.

Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.


Pentobarbital (Nembutal)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The stimulant effects of the caffeine in coffee can block the sleep-producing effects of pentobarbital.


PhenothiazinesInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Coffee contains chemicals called tannins. Tannins can bind to many medications and decrease how much medicine the body absorbs. To avoid this interaction, avoid coffee one hour before and two hours after taking phenothiazine medications.

Some phenothiazine medications include fluphenazine (Permitil, Prolixin), chlorpromazine (Thorazine), haloperidol (Haldol), prochlorperazine (Compazine), thioridazine (Mellaril), and trifluoperazine (Stelazine).


PhenylpropanolamineInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The caffeine in coffee can stimulate the body. Phenylpropanolamine can also stimulate the body. Taking caffeine and phenylpropanolamine together might cause too much stimulation and increase heartbeat, blood pressure, and cause nervousness.


Riluzole (Rilutek)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down riluzole (Rilutek) to get rid of it. Drinking coffee can decrease how fast the body breaks down riluzole (Rilutek) and increase the effects and side effects of riluzole.


Stimulant drugsInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Stimulant drugs speed up the nervous system. By speeding up the nervous system, stimulant medications can make you feel jittery and speed up your heartbeat. The caffeine in coffee can also speed up the nervous system. Drinking coffee along with stimulant drugs might cause serious problems including increased heart rate and high blood pressure. Avoid taking stimulant drugs along with coffee.

Some stimulant drugs include diethylpropion (Tenuate), epinephrine, phentermine (Ionamin), pseudoephedrine (Sudafed), and many others.


TheophyllineInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The caffeine in coffee works similarly to theophylline. Caffeine can also decrease how quickly the body gets rid of theophylline. Drinking coffee and taking theophylline might increase the effects and side effects of theophylline.


Verapamil (Calan, Covera, Isoptin, Verelan)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Verapamil (Calan, Covera, Isoptin, Verelan) can decrease how quickly the body gets rid of caffeine. Drinking coffee and taking verapamil (Calan, Covera, Isoptin, Verelan) can increase the risk of side effects for coffee including jitteriness, headache, and an increased heartbeat.


Cimetidine (Tagamet)Interaction Rating: Minor Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Cimetidine (Tagamet) can decrease how quickly your body breaks down caffeine. Taking cimetidine (Tagamet) along with coffee might increase the chance of caffeine side effects including jitteriness, headache, fast heartbeat, and others.


Fluconazole (Diflucan)Interaction Rating: Minor Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Fluconazole (Diflucan) might decrease how quickly the body gets rid of caffeine. Taking fluconazole (Diflucan) and drinking coffee might increase the effects and side effects of coffee including nervousness, anxiety, and insomnia.


Medications for diabetes (Antidiabetes drugs)Interaction Rating: Minor Be cautious with this combination.Talk with your health provider.

Coffee might increase blood sugar. Diabetes medications are used to lower blood sugar. By increasing blood sugar, coffee might decrease the effectiveness of diabetes medications. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.

Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.


Mexiletine (Mexitil)Interaction Rating: Minor Be cautious with this combination.Talk with your health provider.

Coffee contains caffeine. The body breaks down caffeine to get rid of it. Mexiletine (Mexitil) can decrease how quickly the body breaks down caffeine. Taking Mexiletine (Mexitil) along with coffee might increase the caffeine effects and side effects of coffee.


Terbinafine (Lamisil)Interaction Rating: Minor Be cautious with this combination.Talk with your health provider.

The body breaks down the caffeine in coffee to get rid of it. Terbinafine (Lamisil) can decrease how fast the body gets rid of caffeine and increase the risk of side effects including jitteriness, headache, increased heartbeat, and other effects.

Dosing

The following doses have been studied in scientific research:

BY MOUTH:

  • For headache or improving mental alertness: The typical dose of caffeine is up to 250 mg per day, about 2 cups of coffee.
  • For preventing Parkinson's disease: Three to four cups (28 oz) of caffeinated coffee per day or 421 mg to 2716 mg total caffeine. However, a significantly lower risk of developing Parkinson's disease has also been associated with as little as 124 mg to 208 mg of caffeine (approximately one to two cups of coffee). In women, more moderate caffeinated coffee intake, one to three cups per day, seems to be best.
  • For preventing gallstone disease: 400 mg or more of caffeine per day (two or more cups of coffee). However, drinking at least 800 mg caffeine per day (four or more cups of coffee) seems to be most effective.
  • For preventing type 2 diabetes: 900 mg caffeine per day (6 or more cups of coffee per day) long-term.
Use filtered coffee to avoid some unwanted side effects. Choice of coffee, grind, ratio of coffee to water, and other factors determine flavor and strength of the coffee.

Caffeine content of coffee (per average cup): Percolated, 100-150 mg caffeine; instant, 85-100 mg caffeine; and decaffeinated, approximately 8 mg caffeine. Darker roasts contain less caffeine due to the roasting process.

SLIDESHOW

Dementia, Alzheimer's Disease, and Aging Brains See Slideshow

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

References

Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. View abstract.

Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. View abstract.

American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. View abstract.

Anon. Filtering the news about coffee. University of California, Berkeley Wellness Letter 2001:17:1-2.

Anon. Roasting process to pump up cancer fighting properties of coffee unveiled by oncology sciences corp. PRNewswire 2000; Jun 30. www.prnewswire.com (Accessed 3 July 2000).

Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. View abstract.

Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. View abstract.

Arnlov J, Vessby B. Coffee consumption and insulin sensitivity. JAMA 2004;291:1199-201.

Ascherio A, Zhang SM, Hernan MA, et al. Prospective study of caffeine intake and risk of Parkinson's disease in men and women. Proceedings 125th Ann Mtg Am Neurological Assn. Boston, MA: 2000;Oct 15-18:42 (abstract 53).

Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5.. View abstract.

Bak AA, Grobbee DE. The effect of serum cholesterol levels of coffee brewed by filtering or boiling. N Engl J Med 1989;321:1432-7. View abstract.

Baker JA, McCann SE, Reid ME, et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer 2005;52:15-21. View abstract.

Bara AI, Barley EA. Caffeine for asthma. Cochrane Database Syst Rev 2001;4:CD001112.. View abstract.

Baylin A, Hernandez-Diaz S, Kabagambe EK, et al. Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction. Epidemiology 2006;17:506-11. View abstract.

Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. View abstract.

Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. View abstract.

Benowitz NL, Osterloh J, Goldschlager N, et al. Massive catecholamine release from caffeine poisoning. JAMA 1982;248:1097-8. View abstract.

Benvenga S. Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 2008;18:293-301. View abstract.

Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003;18:343-51.. View abstract.

Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66.. View abstract.

Brenner H, Rothenbacher D, Bode G, Adler G. Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study. BMJ 1997;315:1489-92. View abstract.

Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.

Brown BT. Treating cancer with coffee enemas and diet. JAMA 1993;269:1635-6.

Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. View abstract.

Cannon ME, Cooke CT, McCarthy JS. Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products. Med J Aust 2001;174:520-1. View abstract.

Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. View abstract.

Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. View abstract.

Checkoway H, Powers K, Smith-Weller T, et al. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002;155:732-8.. View abstract.

Chiu KM. Efficacy of calcium supplements on bone mass in postmenopausal women. J Gerontol A Biol Sci Med Sci 1999;54:M275-80. View abstract.

Choi HK, Willett W, Curhan G. Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum 2007;56:2049-55. View abstract.

de Roos B, Caslake MJ, Stalenhoef AF, et al. The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects. Am J Clin Nutr 2001;73:45-52. View abstract.

Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. View abstract.

Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. View abstract.

Durlach PJ. The effects of a low dose of caffeine on cognitive performance. Psychopharmacology (Berl) 1998;140:116-9. View abstract.

Durrant KL. Known and hidden sources of caffeine in drug, food, and natural products. J Am Pharm Assoc 2002;42:625-37. View abstract.

Ernst E. Colonic irrigation and the theory of autointoxication: A triumph of ignorance over science. J Clin Gastroenterol 1997;24:196-8. View abstract.

Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. View abstract.

FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).

Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. View abstract.

Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. View abstract.

Food and Nutrition Board, Institute of Medicine. Nutrition during lactation. Washington, DC: National Academy Press, 1991. Available at: http://books.nap.edu/books/0309043913/html.

Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. View abstract.

Gerson M. The cure of advanced cancer by diet therapy: a summary of 30 years of clinical experimentation. Physiol Chem Phys 1978;10:449-64. View abstract.

Gertz BJ, Holland SD, Kline WF, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 1995;58:288-98. View abstract.

Green S. A critique of the rationale for cancer treatment with coffee enemas and diet. JAMA 1992;268:3224-7.

Grubben MJ, Boers GH, Blom HJ, et al. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr 2000;71:480-4. View abstract.

Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. View abstract.

Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005;118:998-1003.. View abstract.

Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. View abstract.

Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. View abstract.

Hartman TJ, Tangrea JA, Pietinen P, et al. Tea and coffee consumption and risk of colon and rectal cancer in middle-aged Finnish men. Nutr Cancer 1998;31:41-8. View abstract.

Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. View abstract.

Heliovaara M, Aho K, Knekt P, et al. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis 2000;59:631-5. View abstract.

Heseltine D, Dakkak M, woodhouse K, et al. The effect of caffeine on postprandial hypotension in the elderly. J Am Geriatr Soc 1991;39:160-4. View abstract.

Hindmarch I, Quinlan PT, Moore KL, Parkin C. The effects of black tea and other beverages on aspects of cognition and psychomotor performance. Psychopharmacol 1998;139:230-8. View abstract.

Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. View abstract.

Holmgren P, Norden-Pettersson L, Ahlner J. Caffeine fatalities--four case reports. Forensic Sci Int 2004;139:71-3. View abstract.

Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. View abstract.

Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. View abstract.

Inoue M, Tajima K, Hirose K, et al. Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan. Cancer Causes Control 1998;9:209-16.. View abstract.

Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html.

Iso H, Date C, Wakai K, et al; JACC Study Group. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006;144:554-62. View abstract.

Jacobsen BK, Heuch I. Coffee, K-ras mutations and pancreatic cancer: a heterogeneous aetiology or an artefact? J Epidemiol Community Health 2000;54:654-5.

Jee SH, He J, Appel LJ, et al. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2001:153:353-62. View abstract.

Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3. View abstract.

Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. View abstract.

Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, et al. Coffee consumption and cognitive function among older adults. Am J Epidemiol 2002;156:842-50.. View abstract.

Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29. View abstract.

Kamimori GH, Penetar DM, Headley DB, et al. Effect of three caffeine doses on plasma catecholamines and alertness during prolonged wakefulness. Eur J Clin Pharmacol 2000;56:537-44.. View abstract.

Klag MJ, Wang NY, Meoni LA, et al. Coffee intake and risk of hypertension: The John Hopkins precursors study. Arch Intern Med 2002;162:657-62. View abstract.

Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. View abstract.

Kleemola P, Jousilahti P, Pietinen P, et al. Coffee consumption and the risk of coronary heart disease and death. Arch Intern Med 2000;160:3393-400.. View abstract.

Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. View abstract.

Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130. View abstract.

Kuper HE, Mucci LA, Trichopoulos D. Coffee, pancreatic cancer, and the question of causation. J Epidemiol Community Health 2000;54:650-1.

Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. View abstract.

Lane JD, Barkauskas CE, Surwit RS, Feinglos MN. Caffeine impairs glucose metabolism in type 2 diabetes. Diabetes Care 2004;27:2047-8. View abstract.

Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. View abstract.

Leitzmann MF, Willett WC, Rimm EB, et al. A Prospective study of coffee consumption and the risk of symptomatic gallstone disease in men. JAMA 1999;281:2106-12. View abstract.

Leson CL, McGuigan MA, Bryson SM. Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol 1988;26:407-15. View abstract.

Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61. View abstract.

Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006;113:2045-53. View abstract.

Margolin KA, Green MR. Polymicrobial enteric septicemia from coffee enemas. West J Med 1984;140:460.

Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. View abstract.

Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. View abstract.

May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. View abstract.

McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. View abstract.

Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. View abstract.

Michaud DS, Giovannucci E, Willett WC, et al. Coffee and alcohol consumption and risk of pancreatic cancer in two prospective United States cohorts. Cancer Epidemiol Biomarkers Prev 2001;10:429-37. View abstract.

Michels KB, Holmberg L, Bergkvist L, Wolk A. Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women. Ann Epidemiol 2002;12:21-6. View abstract.

Migliardi JR, Armellino JJ, Friedman M, et al. Caffeine as an analgesic adjuvant in tension headache. Clin Pharmacol Ther 1994;56:576-86. View abstract.

Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. View abstract.

Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183.

Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. View abstract.

Olthof MR, Hollman PC, Zock PL, Katan MB. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am J Clin Nutr 2001;73:532-8. View abstract.

Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133:3228-32. View abstract.

Petrie HJ, Chown SE, Belfie LM, et al. Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss. Am J Clin Nutr 2004;80:22-8. View abstract.

Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. View abstract.

Porta M, Malats N, Alguacil J, et al. Coffee, pancreatic cancer, and K-ras mutations: updating the research agenda. J Epidemiol Community Health 2000;54:656-9.

Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. View abstract.

Rakic V, Beilin LJ, Burke V. Effect of coffee and tea drinking on postprandial hypotension in older men and women. Clin Exp Pharmacol Physiol 1996;23:559-63. View abstract.

Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. View abstract.

Reed A, James N, Sikora K. Juices, coffee enemas, and cancer. Lancet 1990;336:677-8.

Robinson LE, Savani S, Battram DS, et al. Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes. J Nutr 2004;134:2528-33. View abstract.

Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of parkinson disease. JAMA 2000;283:2674-9. View abstract.

Ruhl CE, Everhart JE. Association of coffee consumption with gallbladder disease. Am J Epidemiol 2000;152:1034-8. View abstract.

Salazar-Martinez E, Willett WC, Ascherio A, et al. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med 2004;140:1-8. View abstract.

Samarrae WA, Truswell AS. Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Atherosclerosis 1977;26:255-60. View abstract.

Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. View abstract.

Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. View abstract.

Schabath MB, Hernandez LM, Wu X, et al. Dietary phytoestrogens and lung cancer risk. JAMA 2005;294:1493-1504. View abstract.

Scholey AB, Kennedy DO. Cognitive and physiological effects of an "energy drink:" an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions. Psychopharmacology (Berl) 2004;176:320-30. View abstract.

Shils ME, Herman MG. Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 1982;58:323-39.

Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9. View abstract.

Smith A. Effects of caffeine on human behavior. Food Chem Toxicol 2002;40:1243-55. View abstract.

Stanek EJ, Melko GP, Charland SL. Xanthine interference with dipyridamole-thallium-201 myocardial imaging. Pharmacother 1995;29:425-7. View abstract.

Tajima K, Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan. Jpn J Cancer Res 1985;76:705-16.. View abstract.

Tavani A, La Vecchia C. Coffee and cancer: a review of epidemiological studies, 1990-1999. Eur J Cancer Prev 2000;9:241-56. View abstract.

Tavani A, Pregnolato A, La Vecchia C, et al. Coffee consumption and the risk of breast cancer. Eur J Cancer Prev 1998;7:77-82. View abstract.

The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.

Tofler OB, Foy S, Ng K, et al. Coffee and coronary heart disease. Heart Lung and Circulation 2001;10:116-20.

Tuomilehto J, Hu G, Bidel S, et al. Coffee Consumption and Risk of Type 2 Diabetes Mellitus Among Middle-aged Finnish Men and Women. JAMA 2004;291:1213-9. View abstract.

Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. View abstract.

Urgert R, Meyboom S, Kuilman M, et al. Comparison of effect of cafetiere and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial. BMJ 1996;313:1362-6.. View abstract.

Urgert R, Vliet TV, Zock PL, et al. Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers. Am J Clin Nutr 2000;72:1107-10. View abstract.

Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3. View abstract.

Vandeberghe K, Gillis N, Van Leemputte M, et al. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996;80:452-7. View abstract.

Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. View abstract.

Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. View abstract.

Wallach J. Interpretation of Diagnostic Tests. A synopsis of Laboratory Medicine. Fifth ed; Boston, MA: Little Brown, 1992.

Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. View abstract.

Watson JM, Sherwin RS, Deary IJ, et al. Dissociation of augmented physiological, hormonal and cognitive responses to hypoglycaemia with sustained caffeine use. Clin Sci (Lond) 2003;104:447-54. View abstract.

Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8. View abstract.

Williams MH, Branch JD. Creatine supplementation and exercise performance: an update. J Am Coll Nutr 1998;17:216-34. View abstract.

Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. View abstract.

Wisborg K, Kesmodel U, Bech BH, et al. Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study. BMJ 2003;326:420.. View abstract.

Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7. View abstract.