The World of Caffeine (50 page)

In a Norwegian cohort study on coffee use of more than fifteen thousand people, from 1967 to 1978, no significant positive correlation was found between coffee use and any disease, including all cancers.
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In 1990 the International Agency for Research of Cancer, after performing an extensive review of research on digestive, bladder and urinary tract, breast, and other
cancer sites, published a monograph summarizing findings on coffee and cancer. The results tended to confirm the Norwegian study’s conclusions. They specifically excluded any link between caffeine use and the incidence of cancer of the oral cavity, esophagus, stomach, liver, breast, ovaries, kidney, or the lympho-recticular system, including Hodgkin’s disease, non-Hodgkin’s lymphomas, and lymphatic and myeloid leukemia.

By all accounts exposure to caffeine begins early for most people, very early. More than 75 percent of infants tested exhibit detectable levels of caffeine in their blood at birth.
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Even though small children and adolescents apparently ingest less caffeine than most adults, their exposure, measured in terms of serum levels, may be higher, because the concentration of caffeine in the body is a function of body weight. However, one 1991 study determined that children five to eighteen have an average intake of just under 40 mg, about half of a cup of coffee, and that this averages to the equivalent of 1 mg/kg,
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much less than the adult mean intake of 3 mg/kg.
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Unfortunately, such broad averaging of children from preschool age to college age, with widely varying body weights and patterns of caffeine usage, does little to reassure us about the more extreme components that are lost in taking the mean value.

The best overall estimates of caffeine consumption levels in infants and children are more than twenty years old. They were compiled by the National Academy of Sciences GRAS Survey Committee in 1977.
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So far, caffeine has made the GRAS list, being “generally recognized as safe,” every year. The committee’s results indicated that about 18 percent of infants under two years old consumed some caffeine in any given two-week interval. In the six- to eleven-month-old group, the mean intake of the entire group was 4.2 mg a day, but the mean intake of those who consumed caffeine was an incredible 77 mg a day. Although this is about as much as in a typical cup of coffee, it should be remembered the exposure of infants is much higher than it is for adults, because of the immaturity of the infant’s metabolic pathways and its dramatically smaller body weight. In this age group, exposure occurred chiefly as a result of mothers administering cola to their children as a remedy for colic.

Perhaps you have always taken it for granted that a substance in general use by children must be safe for them. Unfortunately, this may not be true. A recent study of more than six hundred preschool children in Long Island found a positive correlation between high caffeine use and reports by parents of uncontrollable energy or hyperactivity, impulsiveness, headaches, restlessness, and other behavioral problems. Because these symptoms are all associated with attention deficit disorder (ADD), Dr. Mitchell Schare of Hofstra University, who conducted the study, suggests that many diagnoses of ADD may actually be misdiagnoses based on problems actually arising from caffeine use. On the other side of the question, other studies apparently demonstrate that children diagnosed as hyperactive are no more sensitive than adults to caffeine,
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and a 1984 study concluded that caffeine was not a cause of ADD.
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In 1994, the
Journal of Child and Adolescent Psychiatry
published a study of children ages eight to twelve warning that, although caffeine may improve children’s attention to detail and their manual dexterity, it also increases their anxiety. The researcher expressed concern over the findings, because caffeine is widely used, even among the youngest children, while its effects on them have not been extensively studied. Because caffeine, in addition to being found in coffee and hot tea, is also found in carbonated soft drinks, iced tea, and hot chocolate, which are favorite drinks of children, the paradox of the “unstudied most widely studied drug” emerges most critically in relation to the lack of knowledge about its health effect on the young. In children and teenagers the dietary sources of caffeine, in order of importance, were found to be tea, soft drinks, and coffee. Chocolate foods and beverages were the lowest of these dietary sources of caffeine, but they constitute the major source of dietary theobromine for children as well as adults. The statistical breakdown for preschooler caffeine consumption: iced tea (mostly bottled, e.g., Snapple, Arizona), 42 percent; colas (all brands), 35 percent; and all others (chocolate milk, hot tea, coffee, non-cola soft drinks), 23 percent.
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After decades of speculation, beginning with the Wiley debates early in the century, information is coming to light that gives new life to concerns about targeting children as consumers of caffeinated soft drinks. Studies in the last decade have shown that children respond to the caffeine in soft drinks the way we would expect them to respond to an addictive drug. One concluded that children eleven to fifteen are sensitive to the reinforcing effects of caffeine levels in soft drinks,
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while another actually demonstrated caffeine withdrawal in children ten years old after they stopped drinking soda. Obviously parents should be mindful of the habit-forming potential of caffeine when considering what beverages to permit their children.

Because of the risks we have adumbrated and other fears, some consumer groups concerned with children’s health issues have spoken out against advertising that they believe encourages children to use pills of any kind, including vitamins and caffeine. The Action for Children’s Television (ACT) group succeeded in persuading the Federal Trade Commission to ban vitamin ads directed at children in 1972. In the early 1980s, the same group questioned the propriety of television ads for caffeine pills in shows directed primarily at young children. The ad to which they refer showed one child admonishing another child, who was nodding at his desk, “If you don’t graduate, we’re in trouble. Here, revive with Vivarin.”
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These ads have since been discontinued, and Vivarin and other producers of caffeine-based alertness aids are careful to target only an adult market.

Caffeine is frequently added to amphetamines, amphetamine-based hallucinogens, LSD, cocaine, and even heroin to augment their psychoactive effects. For example, Reuters reported that French customs agents arrested a woman at a toll both north of Paris on December 26, 1994. In the rented car were her two children, twelve pounds of heroin, and enough paracetamol and caffeine to cut it into 150,000 doses worth nearly $3 million on the street.

In 1984 prosecutors secured the first Philadelphia conviction on record for intent to distribute a look-alike drug substance. In this case, the guilty party had been found with more than fifteen hundred caffeine capsules that resembled “black beauties,” bathtub amphetamines that have been sold in the form of black capsules since the 1960s. Although he faced up to five years’ imprisonment, he received three years’ probation and a $300 fine. “You can buy them legitimately,” an assistant district attorney said of the seized caffeine capsules. “You just can’t sell them”
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In 1996 customs officers in Hong Kong searched a suspicious car parked at a garage and discovered a camera bag under the driver’s seat containing a pound of relatively pure heroin and a pound of caffeine powder. In a follow-up bust, officers uncovered a heroin cutting operation at an apartment, including about five pounds of heroin, thirty pounds of caffeine, and equipment to mix the two. Adding caffeine gives a chemical boost to the drug, simulating a popular and extremely dangerous combination of heroin and cocaine called a “speedball.”

Rave parties are usually large wild dance bashes in which many of the participants take potent psychedelic and stimulant drug combinations to help them stay awake to drink and dance all night. The most popular drug is the street drug ecstasy, a combination of several psychoactive drugs, most often including an amphetamine derivative, LSD, and caffeine. Recently a police raid in Perth, Australia, recovered a batch of ten off-white, imperfectly pressed tablets of ecstasy that contained, along with the usual ingredients, a dangerous addition: heroin. Caffeine has already been implicated in an incident at a Los Angeles New Year’s Eve rave party in which dozens of partygoers were hospitalized with serious symptoms, including difficulty breathing and hallucinations. Police confiscated about ten thousand vials of Biolife FX, bottled by Biolife Bioproducts Ltd., based in San Diego. Tests showed that the key active ingredients were caffeine and kava kava, an extract of the African kava root that creates a mild depressant or hypnotic effect. All the partygoers recovered. The FDA is currently investigating whether to take action against the manufacturer for failing to adequately warn consumers about the high level of caffeine in the product.

Theobromine is relatively weak, milligram for milligram, compared with its sister methylxanthines, caffeine or theophylline.
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Nevertheless, because cacao contains eight times more theobromine than it does caffeine, theobromine is nearly as important to its stimulating effects as the smaller amount of caffeine.
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The clinical use of theophylline is more frequent than that of caffeine.
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Unlike caffeine, which is readily available in effective doses from a variety of natural sources, theophylline, where it does occur, is present in such small amounts that its effects are negligible. Therefore, to reach effective doses, theophylline must be specially administered. Theophylline is used in several effective inhalers, such as Primatene Mist, for bronchodilation. However, the FDA, after receiving reports of life-threatening side effects and even death, recently declared over-the-counter
oral
combination drug preparations containing theophylline, such as Primatene tablets, to be neither safe nor effective.

There is particular concern over the increased danger posed by the combination of theophylline and ephedrine, which occurs in bronchodilator products as well as OTC cough and cold remedies. The FDA, which would like to remove them from the market, also cites the fact that these products are often sold as weight control or muscle building agents, for which purposes their effectiveness has not been proved.

Although all three are closely related chemically, caffeine, theophylline, and theobromine have different profiles of action. A brief summary of these effects, listed in order of their clinical significance, follows.

The nature of caffeine’s effects on birth abnormalities and fertility is probably the most urgent unresolved question that remains to be addressed by future researchers. In this section we present what is known today about these effects and, in
Appendix D
, explain the formidable methodological confounders—that is, factors that confuse the interpretation of the data— that researchers in this area must surmount before these effects can be understood.

The consensus of the medical and scientific community is that, to avoid risk to the fetus, women ought to curtail caffeine use during pregnancy, although authorities differ about the nature or extent of the dangers of failing to do so. But the worrisome fact is that, despite this admonition, most women using caffeine continue throughout pregnancy, with an average intake among users of more than 200 mg a day. As a result, the great majority of babies begin life with detectable levels of the drug in their blood.
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Because fetal exposur to caffeine is so pervasive, any unfavorable effect on the health of the newborn, even one with a very low incidence, could mean tens of thousands of defective births a year in the United States alone. It is therefore critical to investigate the effect of caffeine exposure on the outcomes of pregnancy as exhaustively as possible.

Two facts about caffeine metabolism increase concern over the harm that could be posed by maternal caffeine use.

First, caffeine metabolism dramatically slows during gestation. The metabolic rate drops progressively, falling to one-half normal during the second trimester, and to one-third normal during the third trimester,
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before returning to normal within the week following delivery. This means that caffeine that is ingested by the woman in the last few months of pregnancy will remain in her system three times longer than usual, and, consequently, that the exposure of her unborn child to caffeine will last three times longer.
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