USA Availability Prescription and nonprescription drug also in food Pregnancy Category C

Uses. This drug is responsible for the stimulating jolt that coffee drinkers get. Many drinkers would probably be surprised to see caffeine listed as an ingredient in medicines they take. Caffeine is so widely used (typically in coffee, tea, soda, and chocolate) that it is scarcely considered a drug. Yet an overdose can be fatal.

Caffeine makes people more alert, and experimentation finds that it can help persons function more effectively during sleep deprivation. Caffeine is commonly used in the workplace to increase employees' energy and output. Laboratory measurements indicate that a single dose of 250 mg to 400 mg at the beginning of a night work shift is more effective than several smaller doses spread out during the work period. Some studies find that caffeine helps extroverts perform simple physical assignments but overstimulates introverts and thereby worsens their performance. Scientific measurements prove that caffeine, by itself or in combination with ephedrine, improves athletic performance.

Like some amphetamine class stimulants, caffeine has reduced hyperactivity in children when they received 600 mg daily, but it has been found ineffective for attention deficit hyperactivity disorder (ADHD).

Studies demonstrate caffeine can mildly help asthma sufferers. Theophyl-line, a drug commonly used to widen airways and help asthmatics breathe, is related to caffeine. Caffeine is a standard drug to help premature infants that have interruptions in breathing.

Rat experiments indicate that caffeine can promote weight loss. In humans a combination of caffeine and ephedrine has been used for that purpose. A study found that caffeine increased women's energy outlay and body temperature but that the temperature change correlated with smaller weight and waistlines only in younger women.

Caffeine has been suspected of promoting osteoporosis, a disease causing loss of bone density in older women; studies controlling other factors (such as cigarettes and drugs promoting calcium loss) found that caffeine had no tendency to reduce bone density, but one study published in 2000 and tracking almost 35,000 postmenopausal women found a slight correlation of caffeine usage to broken bones—a correlation implying loss of density. Coffee drinking is associated with loss of density. In contrast, examination of over 1,200 older women in England showed that tea drinkers were less likely to have osteoporosis, leading investigators to wonder if something in tea, other than caffeine, affects bone density.

Investigators examining caffeine consumption in a group of 8,000 men who were tracked for three decades discovered that the more caffeine someone ingested over the years, the less likely the person was to come down with Parkinson's disease. In a group of 46,000 men tracked for a decade, increased consumption of caffeinated coffee was linked to decreased likelihood of having gallstones; consumption of decaffeinated coffee did not have such a link. As one analyst pointed out, such associations are interesting but do not prove cause and effect; for example, perhaps some physical aspect leading to Parkinson's disease also makes caffeine beverages unappealing—thus persons without the disease would consume more caffeine beverages than sufferers do, but that consumption would not mean that caffeine prevents the affliction.

Mice experiments demonstrate that if caffeine is administered in the right amount and at the right time before exposure to radiation, the drug will allow mice to survive otherwise lethal amounts of radiation.

Drawbacks. In the 1990s, 20% of the U.S. population was believed to be using over 700 mg of caffeine each day. That is enough to produce behavior mimicking an anxiety neurosis. If a person only ingests caffeine through pharmaceutical preparations or food products with labels listing caffeine amounts, intake can easily be measured. The amount in a restaurant cup of coffee is more difficult to measure; one rule of thumb says 100 mg to 150 mg.

The substance can accelerate pulse rate; it can also make people more peevish and jumpy (even promote panic attacks) and interfere with getting good sleep. Caffeine can cause heartburn and increase urine output. Experimentation has confirmed that the drug's tendency to promote loss of body fluid will dry the vocal cords and affect voice quality.

Analysis of over 30 years of reports about caffeine and blood pressure found that the drug reliably increased blood pressure when persons began using it but that the effect did not persist in all users. Investigators measuring blood pressure among medical students found caffeine raising the readings far enough that anyone at risk for high blood pressure should avoid the drug during times of stress. Persons with coronary artery disease may be at significant risk for sudden cardiac arrest if they drink more than 10 cups of coffee a day.

Excessive doses can dangerously reduce blood potassium levels, damage muscles, produce extremely rapid heartbeat, and cause delirium and seizures. As the twenty-first century began a case report associated caffeine with retina damage in several persons.

Abuse factors. Coffee was formerly treated as an illicit drug. Centuries ago possession was a death penalty offense in Spain and the Near East. In the early twentieth century one standard medical textbook warned of coffee addiction peril, and another medical volume described coffee as a gateway to opiate addiction. In a modern study volunteers showed no particular desire for caffeine but did find that 300 mg mimicked some effects of dextroamphetamine. Although caffeine is not a scheduled substance, users can develop a physical dependence on the drug that results in withdrawal symptoms including weariness and headache. Such symptoms are not inevitable nor are they necessarily troubling to persons experiencing them. In 2000 an international panel of experts convened by European drug regulation agencies described caffeine's potential for dependence as low. Tolerance can develop to some of caffeine's effects.

Drug interactions. Caffeine itself can reduce headache, and an experiment involving hundreds of participants showed caffeine to substantially improve ibuprofen's ability to relieve headache. Phenylpropanolamine is a drug commonly found in remedies for colds. It seems to increase caffeine levels in a person using both drugs, and together the two can produce mood elevation, hyperactivity and manic behavior, confusion, high blood pressure, and stroke. In rat experiments, caffeine boosts the effects of cocaine and amphetamine, enough to transform normally tolerable doses into fatal ones. Human observations show that cocaine users tend to take lower doses of that drug if they also use caffeine. Perhaps the most common drug taken with caffeine is nicotine. Animal experiments find that interactions of that combination may make cigarette smoking more pleasurable. Cigarette smoking increases the body's rate of metabolizing caffeine, which decreases the influence from a given amount of caffeine; British researchers found that smokers tend to use more caffeine than nonsmokers. Birth control pills can double the time that a given amount of caffeine lasts in the body. The drug can reduce drowsiness produced by pentobarbital, and it can reduce diazepam's interference with cognitive function. Caffeine is a traditional remedy for alcohol intoxication, but in fact it does not speed alcohol's elimination from the body, although caffeine's stimulant properties may help a drunken person function better. Estrogen replacement therapy appears to interfere with women's ability to metabolize caffeine.

Cancer. Caffeine does not seem to produce cancer in animal experiments. Indeed, green and black tea reduce development of cancer in mice, an effect in which caffeine is believed to play a part. In humans, however, caffeine is suspected of promoting premenopausal ovarian cancer and also cancer of the pancreas and bladder.

Pregnancy. Experiments examining caffeine's influence on pregnancy yield conflicting results, which may indicate the question is particularly complex or may simply mean that caffeine is an "invalid variable" having no effect. Here are examples. A 1994 survey of 259 women in the Netherlands found that caffeine raised the likelihood of becoming pregnant, but when the same subject was examined in the 1980s among almost 2,000 women in Connecticut, caffeine was found to suppress fertility. During the 1990s a study of farm couples in Canada found that caffeine had no effect on fertility but that coffee-drinking women and tea-drinking men had lower birthrates, suggesting involvement of something besides caffeine in the natural products' effect. Rat experimen tation shows that caffeine reduces female fertility, produces smaller than usual offspring, and may affect brain development.

Research in Yugoslavia indicates that pregnant women who do not smoke cigarettes but do take more than 71 mg of caffeine daily have smaller infants. A British study found the opposite; slightly smaller infants came from cigarette-smoking women who used 1,000 mg or more of caffeine a week, but the effect was not seen in nonsmokers. Still other studies find no connection between caffeine and either birthweight or prematurity.

Caffeine affects vital signs in a human fetus even when the dose is so low as to have no influence on the pregnant woman.

Question has arisen about whether caffeine promotes spontaneous abortion; a study published in 1994 found 140 mg to 280 mg a day to pose a significant risk; a rigorous study published in 1999 was unable to find such a hazard among moderate caffeine users; and a study published in 1993 saw caffeine as reducing the incidence of spontaneous abortion. Still another study found that women who drank decaffeinated coffee were even more likely to experience a spontaneous abortion than women who drank caffeinated coffee. Research in New Zealand indicated that sudden infant death syndrome (SIDS) was more likely if a woman had ingested more than 400 mg of caffeine daily during pregnancy, but an examination of SIDS in Scandinavia found no correlation with caffeine use during or after pregnancy.

Instant coffee can damage DNA, but implications for general health or birth defects are unclear. Testing caffeine on mice produced birth defects in limbs, and tests on chicken embryos produced heart deformities. Chicken embryos, however, are so sensitive to various chemicals that such results are not considered a warning of human danger. Indeed, a substantial body of research indicates that caffeine causes no human birth defects.

Evidence does exist that caffeine can increase the likelihood of birth defects caused by alcohol and tobacco. An Egyptian study found that caffeine increases alcohol birth defects in rats.

A statistical study showed that women who use more than 300 mg of caffeine daily around the time of conception and who do not smoke are less likely to have infants with Down syndrome.

Given all the uncertainties, pregnant women are advised to use caffeine "moderately"—no more than 200 mg to 300 mg daily (150 mg or less is considered "minimal").

Caffeine increases milk production in nursing mothers and passes into the milk but appears unharmful to infants if the women are moderate users. On occasions when mothers use a lot of caffeine, however, their nursing infants may be fussier and have more trouble sleeping. A dose lasts longer in infants than in older persons.

Additional scientific information may be found in:

Anderson, M.E., et al. "Improved 2000-Meter Rowing Performance in Competitive Oarswomen after Caffeine Ingestion." International Journal of Sport Nutrition and Exercise Metabolism 10 (2000): 464-75. Eskenazi, B. "Caffeine—Filtering the Facts." New England Journal of Medicine 341 (1999): 1688-89.

Golding, J. "Reproduction and Caffeine Consumption—A Literature Review." Early Human Development 43 (1995): 1-14.

Marsden, G., and J. Leach. "Effects of Alcohol and Caffeine on Maritime Navigational Skills." Ergonomics 43 (2000): 17-26.

Nurminen, M.-L., et al. "Coffee, Caffeine and Blood Pressure: A Critical Review." European Journal of Clinical Nutrition 53 (1999): 831-39.

Reyner, L.A., and J.A. Horne. "Early Morning Driver Sleepiness: Effectiveness of 200 Mg Caffeine." Psychophysiology 37 (2000): 251-56.

Smit, H.J., and P.J. Rogers. "Effects of Low Doses of Caffeine on Cognitive Performance, Mood and Thirst in Low and Higher Caffeine Consumers." Psychopharmacology (Berlin) 152 (2000): 167-73.

Tanda, G., and S.R. Goldberg. "Alteration of the Behavioral Effects of Nicotine by Chronic Caffeine Exposure." Pharmacology, Biochemistry, and Behavior 66 (2000): 47-64.

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