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 significa
nce 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.
Caffeine and the Cardiovascular System
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.”
Caffeine and Cholesterol, Heart Attacks, and Coronary Heart Disease
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.
Caffeine and Hemostasis and Fibrinolysis22
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 coff
ee 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
Caffeine and the Respiratory System
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.
The World of Caffeine Page 40
