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.
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.
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.
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.
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
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 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 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.
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).
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.
Methylxanthines have proved valuable in relieving apnea, or arrested breathing, in premature infants. Traditionally, theophylline has been chosen for this purpose, because a 1921 study demonstrated its greater potency in this respect, but more recently caffeine has been preferred by many physicians because the regimes for dosing (in part resulting from the longer half-life of caffeine in infants) are more easily managed and also because, paradoxically, administering theophylline to infants results in a greater buildup of caffeine in their systems than does the administration of caffeine.
Because of its purported value as an analgesic adjuvant, caffeine has been used for decades in both non-narcotic and narcotic painkillers. Are these benefits genuine? Doctors disagree. One study demonstrated that the potency of analgesics compounded with caffeine was 40 percent greater than the same analgesics without caffeine. This means that, if you add caffeine to aspirin, for example, you will only need about two-thirds as much aspirin to achieve the same result as with aspirin alone. However, this does not mean that caffeine together with aspirin can relieve more intense pain than aspirin alone.20
Caffeine has been especially credited with the relief of headache pain, an effect that has been associated with its action as an adenosine antagonist. Caffeine has demonstrated vasoconstrictor effects on cerebral blood vessels, and it is believed that this action may augment its value in treating headaches, such as migraines, in which vasodilatation is a contributing factor. In addition, caffeine has a specific effect that can help migraine sufferers: It enhances the action of ergotamine, used in the treatment of migraine. This discovery was made by migraine patients who noted that strong coffee provided symptomatic relief, especially when combined with ergot alkaloids. The benefit is believed to result from the fact that caffeine increases ergotamine’s oral and rectal absorption.
In at least one instance, caffeine was the cause of a major headache for one of the leading pharmaceutical companies. Excedrin, an over-the-counter Bristol-Myers Squibb analgesic, contains acetaminophen and caffeine. Recently, however, two 1,000bottle lots of Excedrin caplets were accidentally filled with 200 mg of pure caffeine, as much as in a NoDoz caffeine caplet, another Bristol-Myers Squibb product. Evidently the Excedrin gel tabs were being filled on the same processing line as NoDoz, and, despite all the computerized tracking, someone made a mistake. Bristol-Myers Squibb set up an 800 number to answer consumer questions and recalled the pills in question. Although the company feared an avalanche of bad publicity, the story received little news coverage. A company spokeswoman told us, “One adverse event was documented”: a woman who, after taking the pills, was “treated and released,” although what she was treated for was not specified. The company maintains that “untoward reactions to caffeine are not usually observed” at doses of less than 1,000 milligrams, but acknowledged that sensitivity to caffeine varies widely and that some people might have problems at lower doses.
A study by Dr. Margaret Moline of the New York Hospital-Cornell Medical Center, presented to the Boston Sleep Research Society in 1994, suggested that jet lag can be averted with judicious use of caffeine.21 Moline isolated five middle-aged men from clocks, televisions, windows, or any other external indicia of the passage of time. All the men followed their natural sleep schedules and received only a placebo for the first five days. After this, they were allowed to go to sleep at their normal time, but were awakened six hours earlier than usual and given either a pill containing 200 mg of caffeine or a placebo. This sleep displacement simulated the displacement experienced by travelers from New York to London. The results strongly suggested that a subject who took caffeine helped to reset his body’s clock with less intense disturbances and of a shorter duration than a subject who was given the placebo.
Books on jet lag often advise abstaining from caffeine for a week or two before a flight and then drinking several strong cups of coffee or tea at the correct hour to reset your biological clock to daytime after arriving at your destination. We have tried this and found that it works remarkably well.
We do not know enough to say if, or under what conditions, or for which subjects, or in what doses, caffeine can contribute to efforts to lose weight. Because it is evident that it can do so sometimes, for some people, anyone with a weight problem may be well advised to give caffeine a careful try, if he has no problems using caffeine to begin with.
Caffeine’s therapeutic effects on low blood pressure caused by failure of the autonomic regulatory system, a condition afflicting about fifty thousand Americans, was investigated by researchers at Vanderbilt University Medical School in 1985. They administered two and one-half cups of coffee a day to patients with low blood pressure caused by autonomic failure, a disorder of the blood pressure regulatory mechanism that results in pressure so low that victims often faint when they stand up, especially after eating a meal. The autonomic nervous system controls the motor functions of the heart, lungs, intestines, and other internal organs. When experiencing autonomic failure, the body does not respond properly to conditions in which it needs to raise the blood pressure, such as while standing up or eating.
Caffeine has been shown to raise blood pressure in normal subjects, but only if they have not had any coffee in several days. Usually this effect wears off when coffee is consumed regularly. Nevertheless, as a result of his study, David Robertson, in a report in the New England Journal of Medicine, concluded, “We now advise our patients with autonomic failure to drink two cups of coffee with breakfast and to abstain for the rest of the day.”22
The International Olympic Committee, convinced that caffeine has positive ergogenic effects—that is, that an athlete can increase output or endurance by using caffeine—has restricted the urine levels of caffeine that competing athletes may exhibit after a competition. Laboratory studies, however, are not so clear if or when or to what degree these beneficial effects occur, whether they are more or less likely to be observed in trained athletes than in people in average condition, whether they are observed more in relation to certain muscle groups, whether they are observed only when the activity in question is sustained at a very high level for a very long time, and other similar questions.
Atopic dermatitis may be treatable with topical use of caffeine. Topical treatment with 30 percent caffeine in a hydrophilic base or in a hydrocortisone cream produces improvement in various forms of this skin condition, including pruritus, erythema, scaling, lichenification, oozing, and dermatitis. The improvement may be related to caffeine’s ability to liberate water from epidermal and subcutaneous tissues.23
A high intake of caffeine may be associated with a lower incidence and slower pro-gression of Parkinson’s disease. A study reported in the Journal of the American Medical Association (May 24, 2000), led by G.Webster Ross, M.D., staff neurologist at the Department of Veterans Affairs in Honolulu, analyzed thirty years of data from the Honolulu Heart Program, which has followed more than 8,000 Japanese-American men since 1965. Age-adjusted incidence of Parkinson disease dropped dramatically, from 10.4 per 10,000 man-years in men who drank no coffee to 1.9 per 10,000 manyears in men who drank over 28 ounces, or about five 6-ounce cups, a day. A similar decline was observed for caffeine intake from sources other than coffee. Ross concluded that “caffeine has a medicinal effect. It could be treating motor symptoms.”
As reported in an interview in HealthScout (May 23, 2000), Abraham Lieberman, M.D., professor of neurology at the University of Miami and medical director of the National Parkinson Foundation, attributes the possible role of caffeine in preventing Parkinson’s Disease to its ability to block adenosine receptors and increase the levels of dopamine, which are low in people suffering from the disease. However, Lieberman maintains, further long-term studies of the progression of the disease are needed to establish the treatment potential of caffeine in Parkinson’s disease more definitively.
Clinical Actions of the Methylxanthines
| Desired Action | Preferred Agent |
| Cerebral Stimulation | Caffeine (Coffee) |
| Coronary Dilation | Theophylline (Tea) |
| Diuresis | Theobromine (Chocolate) |
| Respiratory Stimulant for Premature Infants | Caffeine or Theophylline |