Table 4. Caffeine Content of Medications
Table 5. Diagnostic Criteria for Caffeine Intoxication
Table 6. Caffeine in Arabica Coffees of the World
appendix c
Additional Studies of Caffeine’s Physical Effects
Caffeine and the Cardiovascular System
At least one study, published in 1996 by Dr. Lucy Mead and Dr. Michael Klag, both of Johns Hopkins University, has found a dose-related correlation between coffee consumption and the development of high blood pressure. This long-term study of more than one thousand male former Johns Hopkins medical students began in 1947, when the study’s founder, Dr. Carolyn Thomas, sought to identify the risk factors for developing high blood pressure. This is the only major study that, after excluding confounders such as family history, elevated blood pressure at the beginning of the study, smoking, and obesity, identified a strong link between coffee and hypertension. If the results are borne out by future research, coffee and caffeine intake may be considered an important factor in the causes of hypertension. However, even Mead and Klag say that such a conclusion is premature.
An additional important study minimizing caffeine’s effect on pre-existing high blood pressure is the Hypertension Detection and Follow-up Program, “a community-based five-year (1974–79) collaborative trial of antihypertensive treatment.”1 The study considered more than ten thousand people between ages thirty and sixty-nine, from fourteen different population groups throughout the United States, who had a diastolic blood pressure of 90 Hg (high-normal) or above when the study began. After studying the subjects’ caffeine consumption from coffee, tea, and cola, researchers concluded there was no exacerbation of their condition owing to caffeine.
However, despite these results, the preponderance of studies suggests that caution among hypertensives may still be indicated. For example, a 1995 study by researcher B.H. Sung, “Caffeine Elevates Blood Pressure Response to Exercise in Mild Hypertensive Men,” published in the American Journal of Hypertension, found an increase in blood pressure, heart rate, and work load on the heart after taking caffeine, even in some nonhypertensive men. Sung tested thirty men, twelve of whom had normal blood pressure (under 130/80) and eighteen of whom suffered from mild hypertension (levels between 140/90 and 160/95), who were given about 300 mg of caffeine mixed with grapefruit juice. Although only one non-hypertensive subject experienced any adverse effects with caffeine ingestion, four of the hypertensive subjects exhibited readings above 230/120, and seven showed increases in blood pressure that the experimenters called “excessive.” The normotensive subjects demonstrated no increase in heart rate, while the hypertensive group exhibited significantly greater heart rates on the days they consumed caffeine. The authors concluded that caffeine may cause a constriction of small arteries throughout the body and that the effects were great enough that people with high blood pressure should avoid using caffeine before and during their exercise.2 Because fifty million Americans suffer from high blood pressure, if the effect is confirmed, this may be the most important danger caffeine offers to human health, apart from a still unevaluated threat posed by fetal or neonatal exposure.
Caffeine and Exercise: Good or Bad for Your Cardiovascular System?
Several studies have suggested that, in a healthy person, caffeine can actually improve the way the heart responds to exercise. For example, a 1995 study of caffeine conducted by Bruce Hardy, a pediatric cardiology fellow at Oregon Health Sciences University in Portland, and his colleagues at this institution found that, in patients with normal blood pressure, a dose of caffeine can help the heart handle exercise by slowing the heart rate, reducing blood pressure, and thus easing the work load on the heart. If these results seem surprising or even paradoxical to you, you are not alone. Hardy himself commented that “The outcomes of the study were a surprise to me. We would have thought the opposite would be true.” Although his conclusions were based on observations of lowered blood pressure and increased heart output in six healthy young men, Hardy asserted that it was plausible to imagine that people with heart disease (but without arrhythmia) could also benefit from an amount of caffeine equivalent to two cups of coffee. If this is so, it contradicts the conventional medical wisdom that has prompted doctors to routinely advise patients with heart problems to stop drinking coffee.
Another exercise benefit for some heart patients was asserted in a 1984 study 3 that claimed caffeine was a “booster of pain-free walking time for patients with chronic stable angina.”4 This study found that drinking a couple cups of coffee increased the time such patients could exercise by as much as 12 percent, while decaffeinated coffee had no effect.
Caffeine and the Digestive System: Ulcers and Upset Stomach
In our effort to disentangle the gastrointestinal effects of caffeine from those of coffee, we quickly encounter the peculiar fact that, while caffeine will stimulate the release of water and sodium from the small intestine, coffee will not do so, suggesting that some agent in coffee may neutralize caffeine’s effect in this regard. As most of us have experienced, coffee stimulates motility in the distal colon, that is, it promotes defecation; however, because this effect also occurs with decaffeinated coffee, it may have nothing to do with caffeine itself.
In a 1975 study by Cohen and Booth at the University of Pennsylvania,5 the investigators found that coffee, whether caffeinated or decaffeinated, produced statistically significantly higher peak levels of gastric acid than caffeine alone. Parallel differences were found in their effects on esophageal-sphincter tone. As of this writing, the ingredient in coffee responsible for these effects on gastric acid and esophagealsphincter tone has not been determined.6
Several studies subsequent to the work of Cohen and Booth have failed to find any causal relationship between caffeine and the incidence or exacerbation of peptic ulcers, although most of these considered caffeine’s effects only tangentially, and interfering variables were not well excluded. In any case, it is clear that drinking decaffeinated coffee is not a recommended alternative to regular coffee for patients with either a peptic ulcer or gastroesophageal reflux, a condition that commonly produces the symptoms of heartburn.
Caffeine and PMS
Premenstrual syndrome (PMS), striking between four and fourteen days before the menstrual period, may affect half of all women, and it encompasses a broader variety of symptoms than Gulf War syndrome. Some of the more than one hundred symptoms that have been blamed on this condition are: irritability, tiredness, breast swelling and tenderness, headache, anxiety, depression, cravings for sweet or salty foods, acne, and changes in sleep patterns. It may last for a couple of days into the period and generally gets worse with age. The reasons for it are not known, but some relief, for the women it afflicts and the men who keep company with them, is ardently sought.
Since the mid-1980s, some researchers have suggested that caffeine use throughout the cycle may aggravate PMS. One of the first studies to provide solid evidence for this idea was conducted by Heinke Bonnlander, with results published in 1990 in the American Journal of Public Health. The study considered almost nine hundred women to find connections between diet and PMS, including an assessment of caffeine intake from all sources.7 Women who drank eight to ten cups a day of coffee, tea, or cola were seven times more likely to have PMS than women who had no caffeine. Those who drank even one eight-ounce glass of a beverage containing caffeine were 50 percent more likely to suffer from PMS than women who drank none. Bonn-lander concluded that there was a dose-related correlation between caffeine intake and the severity of PMS. As she puts it, “The more caffeine you have, the more severe PMS appears to be. Some people appear to be quite sensitive to caffeine,” although she advises that more studies are needed to confirm her findings.
A pamphlet issued jointly by Medical Economics and Organon Inc., makers of a popular oral contraceptive, Desogen, quotes an excerpt from The PDR Family Guide to Women’s Health and Prescription Drugs summarizing caffeine’s purported
effect on PMS:
Caffeine is a major culprit of PMS symptoms.... Caffeine can exaggerate PMS-related problems such as anxiety, insomnia, nervousness, and irritability, and it can interfere with carbohydrate metabolism by depleting your body of vitamin B. Reducing your caffeine intake…can provide almost instant relief. In fact, some doctors routinely advise eliminating caffeine from the diet before every menstrual period as a first step in coping with PMS.8
Caffeine may make PMS worse, but, because PMS is known to be linked to low calcium intake, depletion of the vitamin B complex, drops in serotonin levels, inadequate exercise, and many other factors, simply abstaining from caffeine is unlikely to allieviate all of its symptoms.
Caffeine and Osteoporosis
Osteoporosis, or abnormal loss of bony tissue, is a common bane of postmenopausal women, frequently resulting in fractures, pain, especially in the back of the neck, and a stooping posture. Because bone mass is primarily calcium, any factor that decreases the amount or absorption of calcium, such as long-term steroid therapy or immobilization, is a risk factor for this condition. A study by Heaney and Recker asserted a borderline association between caffeine consumption and increased levels of calcium excretion, but not with decreases in calcium absorption efficiency. A later study by Burger-Lux, Heaney, and Stegman, conducted in 1990, examined the effects of a moderate dose of caffeine (400 mg a day) on the calcium economy in healthy premenopausal women. Although the results showed a slight decrease in bone accretion, accelerated bone loss, and calcium pool turnover, the authors concluded that their findings supported the view that “moderate caffeine intake does not belong among factors that increase osteoporosis risk, at least for those women with higher calcium intakes.”9
The Framingham Study, in evaluating the effects of long-term caffeine use over a twelve-year period, found that even one cup of coffee a day increased the risk of hip fracture, an injury commonly associated with osteoporosis, by almost 70 percent.10 This dramatic increase of fracture rates is commonly confirmed by practicing orthopedic specialists.
The best recent study of the association of lifetime intake of coffee to bone mineral density of the hip and spine, which considered nearly one thousand postmenopausal women, was conducted by Barett-Connor and reported in JAMA in 1994. The bone density of the subjects at the hip and spine was measured by the degree to which they absorbed X-rays. Her study concluded that lifetime caffeinated coffee intake is positively correlated with reduced bone mineral density at both the hip and the spine, and that this correlation was observed independently of age, obesity, years since menopause, or the use of tobacco, estrogen, alcohol, thiazides, and calcium supplements.11 The same study also found, though, “Bone density did not vary by lifetime coffee intake in women who reported drinking at least one glass of milk per day during most of their adult lives.12 The authors caution that this includes women who drank considerably more milk than one glass a day. The research also suggests that only milk does the trick: Calcium supplements provided no protection against caffeine-induced bone shrinkage.13
Caffeine and the Elderly
Whatever effect caffeine has on you when you are young, you should be alert to changes that may occur in these effects as you grow older. In addition, because coffee consumption generally increases between adolescence and middle age, at which time it usually levels off, the effects of caffeine over time may increase accordingly.
Several studies have compared the differences in response to caffeine between older and younger people.
In 1988 Swift and Tiplady examined how the effects of caffeine on psychomotor performance changes with age.14 A series of tests were administered to twelve subjects; six were eighteen to thirty-seven, and the other six were sixty-five to seventyfive. Both age groups demonstrated clear improvements in performance with caffeine use, but the profiles of these improvements were different in older and younger subjects. In results consistent with other studies of centrally acting drugs, the younger group was improved more on tasks depending on motor speed, while the old folks exhibited more improvement in attention and choice reaction time. Although not statistically dispositive, the data suggested that the elderly, overall, show a greater response to caffeine than the young.
Because the sleep time of people over fifty may be as much as two hours less than that of younger people, additional loss of sleep time, such as can be occasioned by caffeine, can represent a proportionally greater loss.15 Many older people who have difficulty falling asleep are unaware that their medicines may contain caffeine. For example, Anacin and Excedrin, over-the-counter painkillers, and Darvon, a prescription painkiller, contain doses of caffeine that might keep many people awake. The Iowa 65+Rural Health Study of three thousand people over sixty-five found that 5 percent were using medicines that contained caffeine, and that the ones who were doing so were twice as likely as the others to report problems falling asleep. The same study failed to discover any such correlation between sleep problems and coffee drinking. Perhaps this was because, in contrast with their spotty knowledge about their medications, people are universally aware that coffee contains caffeine, and therefore avoid drinking it in the evening.
Caffeine is useful in averting hypotension after eating among the elderly, especially that which occurs after eating breakfast. Patients with hypotension related to autonomic failure are advised to consume 200–250 mg of caffeine, or about two cups of coffee, with their breakfast.16
Older people often complain of cold hands and feet. Frequently, the cause is often undetermined and their condition may not be serious. Possible causes include poor circulation owing to diseased arteries, a side effect of certain medications, stress, or Raynaud’s disease (a disorder that affects the flow of blood to the fingers and sometimes the toes). For people suffering from cold hands and feet, it may be important to avoid caffeine, which constricts blood vessels and could exacerbate the underlying condition.
One happy note: A recent University of Michigan study suggested that, for older people, caffeine may have aphrodisiac powers, because its researchers found that the elderly were more likely to have remained sexually active if they were coffee drinkers.
Caffeine and the Eyes
Caffeine may affect your eyes by constricting blood vessels, thereby increasing intraocular pressure and, with it, increasing your risk of developing glaucoma. Although no one has suggested that caffeine can in and of itself be regarded as a cause of glaucoma, one study indicated that in people genetically predisposed to developing the disease, coffee can increase their risk. Another study found that glaucoma patients who drink two cups of coffee a day show an increase in intraocular pressure, while normal patients who consumed two cups of coffee show no such increase. The greatest increases in intraocular pressure were found to occur in those who drink their coffee very quickly, consuming four cups an hour.
Caffeine also temporarily dilates the eyes, like other stimulants such as cocaine or amphetamine or adrenaline, and can therefore make it difficult to do close work, because dilated eyes cannot focus easily at short range.
Caffeine and Nutrition
Caffeine has been found to alter nutritional homeostasis—that is, the body’s ability to maintain the proper levels of various nutrients, such as calcium, magnesium, and zinc—in experiments on pregnant rats. Theoretically caffeine may have similar effects in humans, although this has not been confirmed.
Caffeine consumed within one hour of eating may interfere with the absorption of dietary iron.17 One study of maternal hemoglobin in non-smoking, teetotaler Costa Rican women found that iron deficiency occurred almost twice as frequently in coffee drinkers and that iron levels were also lower in their breast milk.
Grapefruit juice, which has been implicated in significantly altering the effects of several medicines, is known to raise the blood levels of caffeine.
Summary of the Medical Applications of Caffeine
In recent years there has been a resurgence of interest in the therapeutic use of the natural
methylxanthines and synthetic derivatives thereof, principally as a result of increased knowledge of their cellular basis of action and their pharmacokinetic properties.
—Theodore W.Rall, “Drugs Used in the Treatment of Asthma,” 1990 18
Studies performed in the first half of the twentieth century in the pharmacology of caffeine and other methylxanthines confirmed traditional beliefs about their moodelevating and analeptic powers and revealed other significant pharmacolgical properties that were subsequently put into therapeutic use. Although more effective treatments have displaced many of these early applications, new uses have more recently come to light. The methylxanthines share many pharmacological properties, but they can be distinguished in terms of the degree of some of their primary effects. The therapeutic uses of each is, obviously, determined in relation to these effects.19 Most of caffeine’s applications depend on its effect as a diuretic, cardiac muscle stimulant, central nervous system stimulant, smooth muscle relaxant, or elevator of plasma levels of FFA (free fatty acids).
Caffeine and Relieving and Preventing Pulmonary Problems
As we have repeatedly noted, caffeine and the other methylxanthines have long been used to help alleviate the symptoms of asthma. Less well known are studies demonstrating a protective effect of coffee drinking on the pulmonary complications of cigarette smoking. We have seen that smokers metabolize caffeine more rapidly than non-smokers, so that the caffeine exposure of a smoker who drank a cup of coffee would be lower than the exposure of the non-smoker, a fact that may account for the obviously increased rate of coffee consumption among smokers. Perhaps the occult destiny adduced by Walsh for caffeine is present here as well: For, strange to say, the increase in caffeine metabolism caused by smoking seems to result in an increase in use of caffeine, which in turn protects the smoker from the hazards of lung damage.
The World of Caffeine Page 49