What is it in man’s devious make-up that makes him round on the seemingly more wholesome and pleasurable aspects of his environment and suspect them of being causes of his misfortunes? Whatever it is, stimulants of all kinds (and especially coffee and caffeine) maintain a position high on the list of suspicion, despite a continuing lack of real evidence of any hazard to health.
—Editorial, British Medical Journal, 1976, I:1031
Coffee and caffeine have long been suspected of causing illnesses ranging from myocardial infarction, arrhythmias, hypertension, hyperlipidemia, gout, and anxiety, to fibrocystic breast disease, various cancers and birth defects, and osteoporosis. No other agent in the human environment has been as frequently associated with such a variety of chronic-degenerative, even malignant diseases.
—Siegfried Heyden, “Coffee and Cardiovascular Disease,” 1993
Caffeine and, before caffeine was identified, coffee, tea, and chocolate, have been said to cause, exacerbate, palliate, or cure an enormous variety of diseases and have also been said to confer marvelous benefits, including increases in both intellectual and physical capacities. If, like the great majority of people in the world, you use caffeine regularly, you are faced with a complex, confusing, and often apparently contradictory cacophony of traditional and contemporary claims about its effects on human health. In former centuries, caffeine lovers had no guidance but the often fanciful discourses of the medical men of their time. We are fortunate that, in the last half of the twentieth century, a explosion of general medical knowledge and a large number of controlled experiments have shed scientific light on many of caffeine’s effects. It has been often and truly said that caffeine is the most studied drug in history. Yet, because of its nearly universal use, the variety of its modes of consumption, its presence in and effects on nearly all bodily systems, and its occurrence in chemically complex foods and beverages, together with the complexity of the social and psychological factors that shape its use, caffeine may also be one of the least adequately understood. Despite tremendous scientific scrutiny, many central health questions about caffeine remain unanswered or even unaddressed.
Caffeine is like the air. You don’t see it and usually hardly notice it, but it’s there all the same, and it becomes part of you in a critical metabolic exchange that involves every cell in your body. Considering that the sensorium and biomass of the human race is virtually awash in caffeine, and has been besotted so for hundreds of years, and that an overwhelming majority of people in almost every nation, including young and old, healthy and infirm, rich and poor, has made the regular use of this psychoactive stimulant more popular than the habitual use of any other drug, what do we really know of caffeine? What do we know of what it is doing for us, doing to us, even doing to our unborn children? The answer, as should become clear after reviewing the very impressive record of studies presented in the following chapters and the appendices, and evaluating both the findings and limitations of this research, is, “not nearly as much as we need to know.”
The lack of adequate information about caffeine’s health effects is evident in the disagreements that exist among experts. For example, the FDA, as recently as the late 1980s, reaffirmed its earlier position that medical evidence demonstrated no adverse health consequences from caffeine in soft drinks, and the National Academy of Sciences’ National Research Council and the U.S. Surgeon General’s office agreed that no risk to health had been shown for moderate caffeine intake. In contrast, many researchers, adducing the complexity of caffeine’s effects on the human body and the many aspects of these effects that have received limited research attention, argue that such a “clean bill of health” is not fully justified.
The acute administration of caffeine under experimental conditions in which the subject has no tolerance to caffeine has been correlated with certain unmistakable physiological responses, including temporary increases in blood pressure, catecholamine levels, rennin activity, cortisol, free fatty acid levels, urine output, and gastric secretions. In contrast, regular caffeine consumption does not continue producing elevation in any of these levels. Nor does chronic caffeine ingestion elevate cholesterol or glucose levels. Older people using caffeine regularly demonstrate no change in blood pressure or heart rate, and even continuous heavy use does not increase the risk of developing high blood pressure. The most recent studies contradict earlier findings of a positive correlation between caffeine and heart attacks, kidney and bladder cancers, pancreatic cancer, anxiety, fibrocystic breast disease, and hyperlipidemia. Less clear is the evidence concerning the link between maternal caffeine consumption and the health of the newborn.1
Many beneficial effects of caffeine are well established, and others may be coming to light. Caffeine is a powerful bronchodilator in asthma patients and provides possible protection against the adverse pulmonary effects of smoking.2 It also increases the length of time that chronic, stable angina patients can walk without feeling pain. Some researchers think that caffeine is effective as a therapy for neonatal apnea and could be effective as a topical treatment of atopic dermatitis.3 It has long been recognized as an analgesic adjuvant, or enhancer of pain medications. Caffeine is also useful in averting acute hypotension (a sudden drop in blood pressure), such as that which sometimes occurs after breakfast, especially in the elderly; people experiencing this problem are advised to consume about 200–250 mg of caffeine, or about two cups of coffee, each day.4
The difficulties of interpreting health care studies are suggested by a juxtaposition of two articles that were published in 1983 in the New England Journal of Medicine. One study asserted that arrhythmias are induced in susceptible patients with about two cups of coffee or the equivalent amount of caffeine. The other challenged the significance of this conclusion, stating, “What is not yet appreciated is that ventricular premature beats are innocuous in the overwhelming majority of persons. They no more augur sudden death than a sneeze portends pneumonia.”5,6
Coffee and tea contain so many different pharmacologically active substances that there is no easy way to isolate the effects of caffeine from those of the other substances they contain. It has even been found that the method of preparation as well as the amount consumed alters the ultimate effects on human health, especially the effects on the cardiovascular system.
Additional confounding factors plaguing research into coffee’s effects are well summarized by Silvio Garattini, researcher and editor of Caffeine, Coffee, and Health, who comments that although there are many epidemiological studies on the health effects of caffeine and coffee, their probative value is limited by the high correlation between smoking or alcohol consumption and coffee drinking. That is, it is often almost impossible to isolate the effects arising from coffee from those arising instead from smoking or alcohol. Garattini points out that it is also difficult to come up with a universal definition of coffee consumption, because of the differences between types of coffee beans, different methods of roasting, and the varying ways of preparing coffee even in the same population. To make the situation worse, nondrinkers of coffee may also differ from coffee drinkers in their other dietary habits or aspects of their lifestyle, and in the disposition to different diseases.7
Individual differences in sensitivity to caffeine, differences that are often traced to inherited variations in the rate of caffeine metabolism, are another source of confusion. Few studies have been done pertaining to these differences. Although it seems likely that caffeine sensitivity, like most other quantifiable natural variables, should follow a normal bell curve of distribution, and therefore exhibit a range of values, some investigators recognize in some people a qualitatively different response than is observed in the general population. Anecdotal accounts of these unusual reactions suggest a peculiar sensitivity that goes beyond the range of normal distribution. Drug discrimination studies provide evidence for wide individual differences in sensitivity to caffeine and document that some people can detect remarkably small amounts of the drug. As reported in the Handbook of Experimental Pharmacology, in a chapter by Griffiths and Mumford, the lowest dose detected by research subjects ranged from 1.8 to 178 mg, with about 70 percent of them detecting 56 mg or less and about 35 percent detecting 18 mg or less.8 Other scientists have purportedly identified more unusual reactions. For example, researcher S.S.Hayreh, in a 1973 study, gives an account of his own extreme sensitivity to caffeine, which he describes as manifested in “dizziness, weakness, and tremors, lasting two hours, and my pulse-rate went very high,”9 effects he claims are experienced by many others. The significance of such observations remains uncertain, as researcher Jack James explains: “It is not clear whether these reactions represent pronounced, normal responses to a large caffeine dose, or whether the subject’s reactions denote a peculiar sensitivity to the drug.”10
An example of the equivocal and uncertain effects of caffeine is the current debate over whether caffeine is implicated in stimulating the symptoms of attention deficit disorder (ADD) or whether it is a possible cure for ADD or both. In other words, no one yet knows if it causes, relieves, or does not effect a given set of symptoms, an uncertainty reminiscent of the humoral debates of the sixteenth and seventeenth centuries as to whether coffee was “wet” or “dry” or “hot” or “cold” or all of these things at once.
Despite the daunting array of cautionary and compromising considerations, it is difficult not to acknowledge the concordant and apparently probative conclusions of certain large-scale, well-designed studies. For example, a study of more than twelve thousand men and women with high blood pressure and high cholesterol levels, the first large-scale prospective study of caffeine and all causes of death, concluded that there was no “relationship between coronary heart disease events or total mortality and coffee consumption”11 in this high-risk group. The same result—that is, an absence of any relation between caffeine consumption and all or any causes of death— was found by a 1990 study of forty-five thousand men, published in the NEJM,12 and also by the Framingham study,13 the Evans County study (1960–69),14 and the Gothenburg, Sweden, study.15
When evaluating the probative significance of these studies and the others referenced in this section, consider that any study demonstrating that there is no link between coffee and a given disease entity probably excludes any link with caffeine as well; while a study that demonstrates a link with coffee leaves open the question of whether caffeine or some other agent in coffee is responsible for the outcome.
The inquiry into the cardiovascular effects of caffeine is more than a century old, and clinical studies in human subjects have proliferated since the 1970s. It is now well established that the administration of caffeine to people without a history of its use produces both a transient mild pressor effect, or increase in blood pressure, and a biphasic effect on heart rate—that is, lower doses slow, and higher doses quicken, the heartbeat. Yet, despite such acute effects on people who haven’t used caffeine recently, virtually all studies reveal no long-term effect on the heart of any kind from caffeine.
How can this be? The development of a tolerance to caffeine, which is to say, a resistance to its effects, probably explains the disparity between the apparent acute, or immediate, effects of caffeine consumption on non-caffeine users and the absence of harmful consequences in long-term users. As the tolerance to the cardiovascular effects of caffeine develops, the impact initially observed quickly declines or even disappears. The one category of risk that has not been extensively considered is the long-term cardiovascular effects of occasional coffee drinking in people without a tolerance. This means that you may be safer drinking coffee every day than you would be doing so once or twice a week. Another area requiring investigation is the interaction between stress and caffeine consumption on long-term blood pressure levels. Extrapolating from the results of studies on caffeine and heart attacks, it appears, however, that even the combination of caffeine and stress will rarely have any clinical impact.16
Increased blood pressure is a cause of congestive heart failure and a major cause of death. An increase in either systolic pressure, which is the pressure associated with the contraction of the heart muscle, or diastolic pressure, which is associated with its relaxation, can be dangerous, but an elevated diastolic pressure, or lower number given in a blood pressure reading, is the more critical. Conversely, lowered blood pressure is associated with a lowered incidence of congestive heart failure and other cardiovascular diseases. It is therefore of significant interest to note that a 1989 Norwegian study of thirty thousand middle-aged men and women demonstrated that drinking more than one cup of coffee a day is positively correlated with a reduction in both systolic and diastolic blood pressure. In other words, people who drink a cup of coffee every day tend to have lower blood pressure than people who do not.17
The short-term effects of caffeine on blood pressure are just the opposite. People not used to caffeine experience an immediate increase in blood pressure, that is, a moderate pressor effect, and a related reduction in heart rate, or bradycardia, of brief duration, usually less than four hours. These effects apparently cease when caffeine is consumed regularly and a tolerance develops.18,19
These studies considered people with normal blood pressure. But what if your blood pressure is high to begin with? What will caffeine do to you then? In 1984 D. Robertson, a medical researcher, undertook a study of hypertensives and found that, as in the earlier study of people with normal pressure, acute responses of elevated blood pressure and slowed heart rate were observed to occur the first day and to disappear thereafter. Robertson concluded that the acute response to caffeine was actually less in hypertensives than in normal people, and that “tolerance developed rapidly and completely.” Other researchers have concluded that there was no association between caffeine consumption and all or any causes of mortality among this large group of hypertensives.
An interesting aside is that, in days gone by, caffeine was sometimes used by anesthetists during surgery to increase dangerously low blood pressure. Its effect was transitory, and it would not be considered reliable enough to be the drug of choice today. Dr. Adriani, who was the anesthetist in chief at Charity Hospital New Orleans for many years, describes this procedure in a 1940 textbook he wrote. One of his students gave the following account in 1996: “I’m a Vintage’ nurse anesthetist. In my salad days, I used caffeine sodium benzoate as a stimulant to raise a patient’s blood pressure, during surgery. It is no longer used, as there are better drugs available. The dose I used was .5 gram, given subcutaneously.”
Lipids comprise a group of organic compounds, including fatty acids, waxes, phospholipids, and steroids, that are stored in the body as fat and used as energy reserves. Lipids contain cholesterol, as do all animal fats, and elevated serum cholesterol levels are strongly correlated with heart attacks, strokes, and early death.
Since the phenomenon was first noticed in 1970, many studies have confirmed that the use of unfiltered (sometimes mislabeled “boiled”) coffee can contribute significantly to an increase in serum cholesterol levels in both men and women, especially in those whose levels were elevated to begin with. A 1990 thesis published in the Netherlands reviewing twenty-four studies differentiated the effects of different brewing methods. In conclusions supported by subsequent European studies, the author found filtered coffee produced little if any increase in cholesterol levels, while in contrast unfiltered coffee was correlated with an increase amounting to as much as 15 percent. The fact that different brewing methods produce such a variation in effects on lipid levels may help explain why the cholesterol-raising effects of coffee have been shown to vary widely between different nationalities. A dramatic example of this effect is the substantial drop of cholesterol levels over the last fifteen years in Finland paralleling the change from infusion to filter-drip as the most popular method of brewing coffee.
Most researchers think that some strong, naturally occurring ingredient of coffee is responsible for these effects and that caffeine is in no way implicated. Roasting itself forms fatty acids such as cafestol, kahweol, and their derivatives. Most of these lipids remain in the spent grounds, but the amount that get into your coffee cup can vary from 1 to 40 mg, depending on the fineness of the grind and the method of preparation. Many researchers think that there is an as yet unknown substance, present in the oil of all coffees, that acts as a cholesterol-raising factor.20 In any event, caffeine consumption levels seem to have no correlation with cholesterol levels.
More significantly for lay readers, the Framingham Heart Study also found that levels of coffee consumption had “no influence on the rate of coronary heart disease,” 21 and the study found no evidence to support the hypothesis that the level of caffeine consumption is related to the death rates from strokes in hypertensive patients.
Hemostasis is any process which stops bleeding, notably including the body’s coagulation process, or clotting. Fibrinolysis is the process by which the body breaks down clots, averting thrombosis, a pathological condition in which a thrombus, or blood clot, forms within a blood vessel. In an artery supplying the brain, these clots can result in a stroke, and in an artery supplying the heart, they can result in a heart attack.
No effect by either coffee or caffeine on the coagulation process has been observed.
However, very curious and interesting effects of caffeine on fibrinolysis have been suggested by recent research. In order to understand the importance of these effects, consider that reduced fibrinolysis is strongly associated with an increase in heart attacks. That is to say, when the process of breaking down clots is rendered less efficient, the resulting undissolved blockages can become dangerous and even life threatening. Conversely, an increase in the efficiency of fibrinolysis can help protect against heart attacks; drugs are now used to boost the body’s ability in this respect, helping to dissolve blood clots that the body cannot handle. Because studies have found that clot-dissolving time is reduced by regular coffee drinking but remains unaffected by decaffeinated coffee drinking, many researchers think that caffeine is probably the agent responsible for this difference. If this is true, caffeine must operate in effectively the same way as certain pharmaceutical products designed to reduce the risks of heart attacks and strokes, thus counterbalancing the otherwise deleterious effects of coffee on clotting time.23
Asthma, a respiratory disorder marked by a reversible airway obstruction, with attending difficulty in breathing, wheezing, cough, and thick mucus production, is the most common breathing affliction. As many as 10 percent of children suffer from asthma to the extent that they require medical treatment.24 Caffeine, at first administered in the vehicle of strong coffee, has been used to relieve the symptoms of asthma for hundreds of years. Its primary respiratory effect is an increase in the respiratory rate, which corresponds closely with plasma caffeine levels. In patients with asthma, caffeine functions as a relaxant of bronchial tissue or a bronchodilator. Today, theophylline, another methylxanthine, is also widely used for the same purpose, because it has almost twice the potency in this respect and is thought to be less toxic to the central nervous system than caffeine. Widespread experience in treating newborns with caffeine for neonatal apnea, or arrested breathing, which often occurs in premature infants, has presented an unusual opportunity to study its possible toxic effects. Although some agitation does occur at the levels used in treatment, there is an absence of toxicity in newborns. However, as with other potential detrimental effects of the methylxanthines, a definitive answer about its possible effects on growth and development awaits further research, for which reason the treatment of infants with caffeine is discontinued as soon as possible, usually after only a few weeks.
Everyone knows from common experience that cigarette smokers have a far higher likelihood of being caffeine fanciers as well. Perhaps, as in Walsh’s words, “Under such a fact there may be more significance than science has yet elicited”—more significance than has been understood until recently, that is. Medical researcher D.R.Lima, in 1989, investigated the theory that caffeine might help protect smokers against the development of chronic bronchitis and pulmonary edema.25 Both smokers and non-smokers were tested after smoking a cigarette with or without an accompanying cup of coffee. Coffee was found to provide protection against the adverse pulmonary effects of smoking. In researcher Jack James’ words, “The investigators concluded that regular intake of coffee might be beneficial to smokers in delaying the development of chronic obstructive lung disease.”26 Obviously more research is needed to define these benefits more precisely. However, based on current results of studies of caffeine’s effects on pulmonary function, we can responsibly assert that caffeine may have important therapeutic potential in this respect.
In the 1970s, the American Heart Association recommended that people who wanted to quit smoking should concurrently stop drinking coffee and eliminate all sources of caffeine. Subsequent studies have suggested that the American Heart Association’s strategy only complicates matters. After all, sudden withdrawal from caffeine can have unpleasant consequences that certainly won’t ameliorate the withdrawal effects of stopping cigarette smoking and may even make them more difficult to cope with.
However, one caveat for those attempting to quit smoking is in order. We now know that cigarettes increase the rate of caffeine metabolism and shorten or attenuate its effects in smokers. This means that smokers must consume more caffeine to achieve the same effects as non-smokers, which may be one reason smokers drink more coffee than non-smokers. Therefore, cigarette smokers who are cutting down or eliminating tobacco should reduce their caffeine intake, especially if it was high to begin with, because, in the absence of smoking, caffeine will have a much stronger and longer-lasting effect on them than they had been accustomed to experiencing. To put it simply, if a heavy smoker is used to drinking four cups of strong coffee to wake up, he might find that, after discontinuing his cigarette habit, two cups will accomplish the same purpose.27
No disease inspires more dread than cancer, perhaps in part because, in our aging population, cancer’s incidence is on the rise. Although more potent treatments are developed every year, we are still far from attaining a complete understanding of what cancer is and what its causes are, and people are reasonably afraid of anything that they think causes the disease. In recent decades caffeine has sometimes been called a carcinogen; for example, a 1981 study created a concern more than a link with pancreatic cancer. As it turned out, this fear was unfounded.
Since early studies indicated a positive correlation between caffeine in high concentrations and cancer in animals, this connection has been widely studied. Results, however, have been contradictory, even though doses so high that they are unlikely ever to be experienced by people have invariably been used: Depending on the dose, the timing of administration, and the experimental protocol, caffeine appears to raise or lower cancer incidence.28
Much of the information putatively pertaining to caffeine as a possible cause of cancer is compromised by the fact that most studies have been based on usage profiles of coffee, not of caffeine itself, and because coffee contains more than 100 active chemicals, it presents a particularly complex matrix, within which it is difficult to disentangle the singular role of caffeine. We must wonder, for example, if or to what extent the suggestions of a positive correlation between coffee and bladder cancer are related to its caffeine content. Certainly skepticism about the role of caffeine is aroused when we consider those studies of bladder cancer in which the results of the use of decaffeinated coffee were indistinguishable from the results of the use of regular coffee.29 Coffee contains several other suspected carcinogens, including creosote, pymdine, and miscellaneous tars, all created by the heat of roasting,30 and some claim that the polycyclic aromatic hydrocarbons that are responsible for coffee’s taste and smell also cause cancer, although the fact that coffee contributes less that. 1 percent of dietary intake of these substances makes that notion seem alarmist.31 In addition, there are sticklers who admonish that carcinogenic dioxins in bleached coffee filters leach into the drink. To confuse matters even more, cafestol and kahweol, present in your cup of coffee in amounts proportional to the oil content, are non-mutagenic and in animal experiments have shown cancer-protective activity with relatively large doses.32
However, despite this confusion, because the possible relationship between coffee and cancer has been so extensively considered in the past thirty years, while there has been very little investigation of caffeine and cancer and tumor activity apart from the matrix of coffee, it is worth reviewing summaries of these results for whatever light they may shed on the question of caffeine.
Fibrocystic breast disease, a condition characterized by benign fibrous lumps in the breast, is not dangerous, but it can be very painful, and the cysts that it produces drive many women to their doctors for tests to rule out breast cancer. Since the late 1970s, some researchers have suspected a causal link between caffeine and this condition, and an early study suggested that caffeine abstinence might reduce symptoms of the disease. A 1986 National Cancer Institute (NCI) study of over three thousand women found no evidence of any correlation between caffeine use and benign tumors, fibrocystic breast disease, or breast tenderness.33 However, a subsequent study by the institute of more than fifteen hundred women concluded that women consuming 250 mg of caffeine (about as much as in two cups of coffee) daily experienced a 50 percent increase in the condition, while those consuming 500 mg experienced nearly a 150 percent increase. Such results have led one researcher to claim that a caffeine-free regimen supplemented by 800 mg of vitamin E daily can provide substantial relief for two-thirds of women with fibrocystic breast disease.34
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.35 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.36 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,37 much less than the adult mean intake of 3 mg/kg.38 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 1977.39 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,40 and a 1984 study concluded that caffeine was not a cause of ADD.41
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.42
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,43 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.”44 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”45
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.46 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.47
The clinical use of theophylline is more frequent than that of caffeine.48 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.
Sources and Clinical Effects of Methylxanthines Effects are listed in order of clinical significance.
Caffeine
Sources: Coffee, tea, cola nuts, maté, guarana.
Effects: Stimulant of central nervous system, cardiac muscle, and respiratory system,
diuretic. Delays fatigue.
Theophylline
Sources: Tea
Effects: Cardiac stimulant, smooth muscle relaxant, diuretic, vasodilator.
Theobromine:
Sources: Cacao, also present in traces in cola nuts and tea.
Effects: Diuretic, smooth muscle relaxant, cardiac stimulant, vasodilator.
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.49,50 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,51 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.52
Second, the livers of the fetus and newborn are unable to metabolize caffeine. Because of the incapacity of their hepatic enzyme systems, their livers cannot transform caffeine into its metabolites, so the drug lingers in their systems much longer than in either children or adults, until it is finally excreted, virtually unchanged, in the urine.53 One researcher found the mean elimination time in infants being treated for apnea with caffeine was one hundred hours, fifteen times the adult average, and other scientists report a range up to about 350 hours in premature infants.54 These dramatic metabolic decrements, however, are short-lived. The infant’s capacity to metabolize caffeine progressively increases in the first months of life until it reaches the adult level of three to seven hours by the eighth month,55 though full maturity of the metabolic pathways of caffeine may not be achieved until the end of the first year.56
Because the risk of gross morphological abnormalities is high only in the first trimester, one would not expect that a decrease in the mother’s ability to metabolize caffeine occurring later in the pregancy could significantly increase the risk of these abnormalities. Happily, the latest studies convincingly exclude maternal caffeine use as a cause of such gross morphological abnormalities in human infants.
Teratology, from the Greek roots meaning “the study of monsters,” is the examination of congenital abnormalities and defects. Teratologies are often associated with maternal exposure to drugs or chemicals, because the fetus is much more vulnerable than either a child or an adult to their adverse effects, with different risks attaching to different stages of fetal development. As we have seen, the greatest risk for gross morphological defects, which is to say, for obvious deformations of the skeleton, face, or major organs, is associated with the first trimester. Although all drugs and chemicals come under scrutiny with regard to such dangers, there are special reasons caffeine has been singled out for concern.
The structural similarity between caffeine and some of the building blocks of DNA—that is, the DNA base pairs adenine and guanine57—sometimes called the “DNA purines,” raised the ominous possibility that caffeine may interfere with the functioning or replication of genetic material. This threat spurred extensive laboratory investigations and epidemiological studies, for if caffeine does interfere with DNA, there is no limit to the severity or extent of the dangers it would pose. Nowhere would these dangers be more acute than in the first weeks following conception, when each cell is a repository of information needed for the development of a major bodily system, and when damage to the DNA of any one cell could result in a gross malformation. According to a 1992 review of the literature published by the Johns Hopkins University School of Hygiene and Public Health, scientists posit several mechanisms by which caffeine could inflict genetic damage:58
Despite this menacing list of hypothetical mechanisms and a clear determination that caffeine is “mutagenic in bacteria, fungi, plants and human cell cultures,”59 no epidemiological association has been demonstrated between caffeine use and adverse outcomes of pregnancy, with particularly reassuring exclusionary findings with regard to major malformations. Although gross morphological defects can consistently be induced in laboratory animals by administering toxic doses of caffeine, producing serum levels that would be fatal in people, no relationship between maternal caffeine consumption and congenital skeletal malformations or malformations of any organs has been found in human beings.60 Studies suggesting caffeine’s harmful effects on the fetus prompted the FDA, in 1980, to institute a recommendation that pregnant women should eliminate caffeine intake or keep it as low as possible. However, a shift in the scientific estimate of caffeine’s reproductive dangers is represented by the reassessment of this warning made by the FDA in 1984. At that time, Dr. Sanford Miller, director of the FDA’s Bureau of Foods, said that caffeine during gestation is probably acceptable if limited to the amount in two or three cups of coffee daily, and that fears about its effects were based on animal studies in which enormous amounts were given to pregnant rats in a single dose. Today, although caffeine is no longer suspect in major teratologies, the original FDA warning remains in place, and has been recently reaffirmed, because of fears relating to less obvious injuries.61
Much less attention has been paid to the effects of caffeine on premature births, spontaneous abortions, or the comparatively subtle processes of intrauterine development. Because the risks of low birthweight and other less obvious abnormalities increase throughout pregnancy, the progressively slowing metabolic passage of caffeine poses a greater threat of these dangers than of gross morphological defects. Unfortunately, there is still considerable uncertainty about caffeine’s effect on such subtler defects. However, widespread experience treating newborns with caffeine for apnea, which provides an unusual opportunity to study its possible toxic effects, strongly suggests that “the fetus during the later states of pregnancy…should be fairly robust to the systemic levels associated with typical patterns of maternal caffeine consumption.”62
Virtually all of the larger and better constructed studies demonstrate no correlation of prematurity with caffeine use.63,64 However, the literature remains contradictory as to whether caffeine has any correlation with spontaneous abortions. A number of major studies 65,66 found no significant as sociation. In contrast, a 1992 study of more than fifty thousand pregnant women 67 reported a small but significant dose-dependent increase in spontaneous abortions. Those who believe the increase in the miscarriage rate is real explain it by offering an unsubstantiated conjecture that caffeine enters the egg just before the opportunity for implantation and may interfere with implantation, so that the blastocyst, or fertilized egg, is lost or develops abnormally.68
Almost forty years ago, two scientists issued a warning about the potential dangers to fetal development resulting from paternal caffeine consumption immediately prior to conception. Noting that the concentration in sperm cells is virtually identical to the serum levels, they stated, “germ cells are bathed in a caffeine solution of fluctuating concentration.”69 The significance of this effect is still unknown today.
Since 1980, a few animal studies have apparently confirmed an association between behavioral abnormalities in the fetus and maternal use of caffeine, raising concerns that similar effects may obtain in people. However, there have been few studies of neurobehavioral effects in humans, and these have conflicting results. One prospective study, which followed children from before birth to age seven, showed caffeine had no effects on the neurodevelopment of infants or children.70 In contrast, another showed “poor neuromuscular development and greater arousal and irritability in neonates.”71
Dr. Leo Leader of the School of Obstetrics and Gynecology at the University of New South Wales has also investigated the effect coffee has on unborn babies. His early findings suggest that, within about twenty minutes after the mother drinks a cup of coffee, the caffeine stimulates fetal movement. Other studies have already shown that caffeine intensifies the contraction of the heart and that even moderate doses of caffeine (200 mg) decrease placental blood flow.72
In a more speculative vein, generalized prenatal learning ability has been purportedly measured by determining how long a fetus takes to stop reacting to the repeated buzzing of an electric toothbrush pressed to the outside of a mother’s stomach. Initially, the fetal heart rate increases and the fetus demonstrates increased movement. Then, through a basic learning response called “habituation,” normal babies stop reacting between ten and fifty buzzes. Leader has demonstrated that fetuses who were able to demonstrate habituation did significantly better in tests of movement, socialization, language, and behavior between a year and two years after birth than those who were not. Chemicals ingested by the mother can cause an immediate reaction in the fetus’s ability to learn. For example, for about two hours after a mother smoked a cigarette, the fetal ability to respond to the buzzing was found to be absent or impaired. Dr. Leader intends to test if caffeine accelerates or slows the fetal response to the buzzing toothbrush.
Can a pregnant woman addict a fetus to caffeine? In other words, if a woman uses coffee, tea, or caffeinated soft drinks during pregnancy, can her baby be born with the symptoms of caffeine withdrawal? A 1988 study identified five babies who were born suffering from withdrawal syndrome; however, the levels of caffeine used by their mothers were remarkably large, averaging fifteen cups of coffee or two quarts of cola each day.73 Another study, completed the same year, found that eight children of heavy-caffeine-using mothers demonstrated unusual levels of irritability, jitteriness, and vomiting, with an absence of any of the usual causes for such symptoms.74 Some investigators have speculated that caffeine withdrawal could be implicated in neonatal apnea (an idea bolstered by the fact that caffeine is an effective treatment for apnea) and sudden infant death syndrome (SIDS), while others suggest the possibility that maternal caffeine use during pregnancy may be associated with childhood diabetes.75
If a woman continues drinking caffeinated beverages while nursing, the caffeine from her breast milk enters the infant’s system at a time when the child metabolizes it imperfectly or not at all. Thus the effect on the infant is multiplied many times during a period in which its neurodevelopment can still be affected.76 Despite the obvious possibility of a hazard, the Association of Women’s Health, Obstetric & Neonatal Nurses published a pamphlet in cooperation with IFIC, the public relations arm of a food industry-sponsored scientific organization, advising:
The American Academy of Pediatrics Committee on Drugs has reviewed the effects of caffeine on breast feeding and reported that moderate caffeine consumption has no effect on breast feeding.
As with all foods, pregnant and lactating women should apply the principle of moderation.... A reasonable guideline is around 300 mg daily.77
Perhaps no area of concern over caffeine’s effect on health has a longer history or has been the subject of more confusion than fertility. Long before caffeine had been isolated, coffee was charged with reducing fertility in both men and women and with reducing the sexual appetites of men. As we saw, the latter effect was the subject of heated broadsides against coffeehouses from the distaff side in seventeenth-century London.
Repeated studies have failed to find a dose-related correlation between caffeine consumption and the risk of either delayed conception or persistent infertility in women. A typical example is a retrospective study of more than two thousand postdelivery women that found no association with delayed conception.78 It concluded that the average time to conception (four or five months) for women who consumed the equivalent of one cup of coffee a week was similar to the time to conception for those who consumed more than two cups a day. In addition, the study found that caffeine consumption was not a risk factor for primary infertility. However, because other studies suggest that caffeine intake can contribute to delaying conception, perhaps the best advice for women who are intending to become pregnant is to minimize or eliminate caffeine intake, at least until more proof of its consequences has been gathered.79
Because caffeine permeates every cell of the body with ease, the concentrations of caffeine in male gonadal tissue and seminal fluid are virtually identical to those that occur in the blood. Therefore it has been widely conjectured that caffeine has doserelated effects on the number and structure of spermatozoa. Its varying effects on sperm motility are well-documented.80 When semen is exposed to high concentrations of caffeine immediately prior to artificial insemination, the increased motility is sufficient to double a woman’s chances of getting pregnant. It is not known if there are deleterious effects on the sperm that may later increase the likelihood of miscarriage. Oddly enough, the profile of some of caffeine’s effects on sperm observed both in vitro and in vivo closely resembles that predicted by the Yerkes-Dodson principle, enunciated in 1908, that the “relationship between arousal and performance efficiency takes the form of an inverted-U,”81 which is to say that performance is best at intermediate arousal levels and drops off in states of low arousal, such as when a person is bored or tired, or in states of high arousal, as when a person is anxious or under stress. This means that the effects of caffeine on sperm cells increase with the dose until a certain level is reached, whereupon additional doses of the drug have less and less impact, and still higher doses progressively reverse its initial effects.
Researchers L.Dlugosz and M.B.Bracken comment on these findings:
In several in vitro assays, human sperm motility and sperm progression increased with the addition of caffeine. However in other assays, more detrimental effects on spermatozoa ultrastructure and penetrating ability were observed at high concentrations than at low concentrations of caffeine. In a study of 446 men attending an infertility clinic, men who drank 1–2 cups of coffee per day had increased sperm motility and density compared with subjects who drank no coffee. However, men who drank more than 2 cups per day had decreased sperm motility and density…. Current data are too sparse to draw conclusions about the effects of caffeine consumption on male infertility.82
Thus, although the effect of large doses on fertility in men is still undetermined, moderate doses of caffeine may even help a man to father a child, and the dynamics of caffeine’s effects on sperm seem to resemble those ascribed to alcohol on sexual performance in the traditional aphorism, “A little stimulates; a lot depresses.”
Once upon a time, men who wished to set themselves on a thorny quest chose to pursue the Holy Grail, the cup used by Christ at the Last Supper, a draught from which would confer all earthly and heavenly benisons. Today the quest for the Grail has been replaced by the quest for a “fat pill,” a safe, pharmacologically active chemical that a person can ingest to reduce and keep off excess fat. Presumably the scientist who discovers and the first company that markets such a wondrous medicament will eclipse Bill Gates and Microsoft as the greatest financial success story in modern times.
The key words here are “safe” and “reduce and keep off.” Many stimulants, especially powerful ones such as amphetamines and cocaine, effectively suppress appetite and increase metabolic rates. In other words, they help burn fat at a faster rate than normal. The problem is that their use is not safe and that, irrespective of their dangers, the capacity, at least of cocaine, to reduce your appetite seems to wear off as usage continues. A full range of amphetamine derivatives have been legal prescription drugs for decades, but they are rarely prescribed today, as some of them once were, as treatments for obesity or aids for weight loss. To fill the void left by their removal, natural medicine enthusiasts have marketed a variety of quack nostrums promising to “burn fat” or “speed up metabolism.”
Despite repeated claims of tabloid headlines touting these breakthroughs, few people believe that such a fat-burning substance actually exists or is even in the early stages of development. The amazing truth, however, is that common caffeine might be the fat-burning wonder drug everyone has been looking for all along.
Dr. John William Daly, one of the most respected researchers on the pharmacology of caffeine, states in his 1993 review paper “The Mechanism of Action of Caffeine”83 that, in addition to its effects on the cardiovascular, respiratory, renal, and central nervous systems, caffeine affects adipose (fat) tissue by stimulating lipolysis, that is, by increasing the catabolism, or burning, of fat. Additionally, caffeine partially blocks the effect of adenosine and adenosine analogs, neurotransmitters that inhibit lipolysis. In other words, caffeine enables your body to burn fat faster and might help you to lose weight.
There is some clinical evidence of this effect. People undertaking exercise studies under controlled conditions demonstrate more weight loss if their exercise was preceded by a very hefty dose of caffeine. Caffeine increases the level of circulating fatty acids, so-called free fatty acids, or FFA, released from adipose tissue. Between one and two hours after consumption, or according to other studies, three to four hours or more after consumption, caffeine has been shown, under certain conditions, to increase the oxidation of these as fuel and hence to enhance fat oxidation. Caffeine has been used for years by runners and endurance athletes to improve performance, presumably by enhancing fatty acid metabolism. It seems effective in those who are not habitual users. Some studies suggest that this effect is most pronounced during longduration low-intensity exercise, where lipids play a more important role in energy production, and that the effects are most noticeable in persons who are not highly trained athletes.
Caffeine may also work in other ways to help weight loss. It increases basal metabolic rate and resting metabolic rate, in both lean and obese subjects, by as much as 15 percent, and keeps these rates elevated for at least two hours after ingestion.84 Additionally, there is ample anecdotal evidence that caffeine, like other stimulants, such as amphetamine and cocaine, is an appetite suppressant.
The practical question remains: Can caffeine be an effective aid to weight loss, and if so, under what conditions and to what degree will it augment the efforts of diet and exercise in shedding pounds? As with so many questions about caffeine and health, the answer seems to be a combination of “it depends” and “nobody knows.” There have been many studies of the interaction of caffeine and exercise and of the effects of caffeine on levels of FFA and fat oxidation. The conclusions are apparently contradictory, providing support for just about any combination of conclusions you might choose to argue. The effects of caffeine on energy output, endurance, and fat metabolism vary widely on account of many factors: the complexity of the human system, the variations in how much caffeine is consumed, how long before the trial it is consumed, how long the exercise is continued, the physical condition of the subject, the tolerance of the subject to caffeine, and which muscles are being used in the exercise. Psychogenic effects may also be important: People may not perceive themselves as growing tired when they have ingested caffeine, and therefore they may continue their efforts longer. More carefully designed studies are needed to define the contributions of this slew of confounders. Meanwhile, there is good evidence that caffeine can help at least some people doing some exercises to do them longer and burn more fat while doing them.
There is a widespread conviction among many athletes and sportsmen that caffeine boosts performance in terms of endurance and energy output, and that, in short, using caffeine helps you to increase your speed and capacity to lift weights, and in general to excel in athletic pursuits. Many long-distance cyclists, runners, and crosscountry skiers use caffeine during competition. Even racehorses are sometimes doped with and tested for caffeine.
The belief in the power of caffeine to augment athletic capacity is reflected in a 1962 decision by the International Olympic Committee (IOC) to restrict caffeine use by participants in the games to a urinary concentration of 15 mg/litre. The uncertainty about the effects of caffeine is reflected in the IOC’s repeated flip-flops over whether to continue restricting it and, if so, how much to allow in the serum levels of participants. Subsequent to the initial ban, the IOC dropped caffeine from its list of restricted drugs, and then, in 1984, restored it. Athletes alleged that, because of wide variations in the metabolism of caffeine among individuals, consumption of as little as 350 mg had caused some participants to nearly flunk the test. Because readings above the allowable level are regarded as deliberate attempts to “dope” the athlete, a 1988 study by researcher van der Merwe attempted to determine how much caffeine would put a competitor out of action. He administered varying amounts of caffeine by serving coffee, tea, and soft drinks to nine healthy subjects, within a fifteen-minute period. Although the doses ranged up to 1,000 mg, as much as in ten cups of coffee, no urinary levels were found to exceed 14 mg/litre, as measured three hours after ingestion. Consistent with other researchers, van der Merwe found that about 75 to 90 percent of the ingested caffeine appeared in the urine and the observed concentrations were independent of the dietary source. He concluded that it was impossible to flunk the IOC test as a result of the ordinary consumption of caffeinated beverages and that any athlete who failed to pass should be presumed to have resorted to caffeine to enhance his performance.85 Although a number of athletes have run into trouble over their urinary levels of caffeine, so far the IOC itself has disqualified only one participant on this account, an Australian pentathlon competitor in the Seoul Olympics in l988.86
Interest in caffeine’s benefits to exercise increased in the late 1970s after studies from the Human Performance Laboratory at Ball State University suggested that 200 mg of caffeine exerted a significant effect on an athlete’s endurance. Other studies have failed to confirm this conclusion, and some have suggested that the observed improvements were a consequence of a placebo effect. Determining the answer comes down to evaluating whether caffeine has ergogenic effects—that is, whether it can improve aerobic performance or the capacity of the body for physical work.
The body gets the energy needed to power muscles in at least three different ways, depending on whether the energy expenditure is of short, moderate, or extended duration. Energy is also burned differently by muscles of different sizes. For example, the large muscles of the legs, used in treadmill walking, burn energy differently from the smaller leg muscles, primarily used in cycling, which may be more responsive to the benefits of lipid mobilization. In addition, people in excellent physical condition, such as athletes, burn energy differently from people in a more ordinary state of dilapidation. Other variables include caffeine dose, pre-exercise food consumption, and individual variations in response and tolerance. All of these factors confuse our attempts to make sense out of the apparently inconsistent research findings about the effects of caffeine on energy output, endurance, and weight loss.
The basic theory underlying claims that caffeine can improve athletic performance is based on three assertions. The first is its ability to increase the efficiency with which the body burns fat, already alluded to in the weight-loss discussion above. This is considered the primary source of caffeine’s power to act as an ergogenic aid and to increase endurance for intense exercise, especially when duration approaches or exceeds one hour. Increased FFA mobilization delays the depletion of glycogen by encouraging the muscles to use fat as fuel, making the spared glycogen available to delay exhaustion, especially at high exercise intensities for which glycogen sparing is critical. This effect is minimized at exercise below the anaerobic threshold, that is, in low-intensity exercise, and experiments have shown that ingesting 400 mg of caffeine before such exercise did not affect either FFA or carbohydrate utilization.
The second claim is caffeine’s ability to reduce the rate of glycogen consumption— that is, it increases the efficiency with which the body burns sugars. Because glycogen is a primary source of energy for exercise, exhaustion occurs and exercise intensity must generally be reduced once glycogen has been depleted. This glycogen-sparing effect is greatest in the first fifteen minutes of exercise, during which glycogen utilization declines as much as 50 percent. The saved glycogen remains available during the later stages of exercise with the result that the athlete can continue longer before exhaustion occurs.
The third assertion is caffeine’s power to lower the rate of perceived exertion (RPE)—that is, to reduce our sense of fatigue. Some studies have shown that when athletes are asked to rate how hard they are working, some report significantly less exertion after consuming caffeine.
The popularity of sports snacks is increasing as athletes and exercisers search for anything that can give them an edge. When the National Academy of Sciences evaluated six purported performance boosters for the U.S. Army, the only ones they endorsed as effective were those that contained carbohydrates or caffeine. Although other ingredients might show promise, no claims can be supported without further research. These conclusions have been bolstered by studies, such as the one which demonstrated that the intake of sucrose, with or without caffeine, improved running time and distance from about forty minutes and six miles to about fifty-five minutes and nine miles.87 Other studies showed that consumption of about 900 mg of caffeine, which produce urinary levels just within the limits of the IOC, increased endurance time from fifty to more than seventy minutes.
In their quest for a chemical means of improving performance, many turn to over-the-counter combination products that contain both caffeine and ephedrine. An example of such a product is Formula One, a nostrum touted by its manufacturers as the “world’s first scientifically valid, gimmick free approach to weight management,” which contains a combination of ma-huang and cola nut. This combination was recently banned by the FDA in a new ruling that outlawed all products containing a combination of caffeine and ephedrine, stating that they can cause “severe injury or death in some people who consume them.”
We should be mindful of a range of possible impairments in performance that may counterbalance the possible improvements in output that may be obtained with caffeine. By increasing digestive secretions, caffeine may cause stomach discomfort and thereby impede performance. And perhaps more important, because caffeine is a diuretic, it may promote excess urination, which in turn could lead to dehydration, one of the primary problems for athletes, especially endurance athletes, because the fatigue experienced as a result of dehydration is indistinguishable from the normal fatigue of hard training. Excessive urination can also cause a loss of vitamins and minerals essential to peak athletic performance, although it must be noted that some studies have found no effect from caffeine on either fluid balance or thermoregulation during exercise. In light of such considerations, however, athletes should be mindful of the possibility that intestinal problems or dehydration might create an acute disadvantage in the middle of an athletic event which more than offsets any earlier advantage.
In summary, the effects of caffeine as an athletic performance booster are still uncertain. It remains for future researchers to satisfactorily evaluate caffeine’s effect on an ordinary activity such as walking, by designing an experiment comparing the effect of a range of caffeine doses on well-hydrated, moderately trained subjects walking in controlled environments for an extended time. Such low-intensity exercise studies would help determine caffeine’s part in FFA mobilization.88