CAFFEINE IS A PSYCHOACTIVE DRUG THAT OCCURS naturally in many foods and beverages including coffee, tea, chocolate, and cocoa. It has found its way into many commercial soft drinks because of its proven mild stimulant effect and relative safety when consumed in small amounts. But caffeine can produce beneficial effects in one individual and potentially harmful effects in another. Many pain relievers contain caffeine added to aspirin or acetaminophen to potentiate the effects of these agents.

Caffeine is the most widely used psychoactive substance. More than 100 billion doses of caffeine are consumed annually in North America. Caffeine occurs naturally in more than 60 plant species worldwide, and the drinking of tea in China dates back to around 2500 BC.
 
BIOCHEMISTRY

Caffeine is a xanthine derivative — 1, 3, 7-trimethylxanthine. Other naturally occurring xanthines include the well-known theophylline (the major constituent in tea) and theobromine. Coffee is a major source of caffeine and chlorogenic acid and also contains a substantial amount of magnesium and other micronutrients. Caffeine is a powerful central nervous stimulant and moderate doses of 200 mg contained in two cups of coffee activate the cerebral cortex sufficiently to slow changes in an individual’s electroencephalogram (EEG). Caffeine is also a mild cardiac stimulant.

EFFECTS

Cardiovascular
Caffeine has mild and variable effects on the heart rate, the heart muscle, blood pressure, blood flow, and blood cholesterol.

1. Heart Rate
Caffeine generally increases the heart rate. After ingestion of caffeine a mild decrease in heart rate may be observed within the first hour followed by an increase in heart rate during the following two hours. Chronic caffeine use elevates the resting heart rate and significant reductions in heart rate are observed upon cessation of caffeine intake. Caffeine also stimulates the medullary vagal nerve nuclei and thus causes a mild decrease in heart rate depending on the dose and time of ingestion.

A genuine tachycardia, heart rate greater than 100 beats per minute, is not often observed. Arrhythmias that cause a sensation of palpitations may be precipitated, however, by two or three cups of coffee daily in susceptible individuals. Patients with paroxysmal atrial tachycardia, (AV nodal reentrant tachycardia) and those with atrial or ventricular premature beats may note an increase in the frequency of these beats and pronounced increase in heart rates may be precipitated. In these individuals cessation of caffeine intake is often beneficial. However, the most common arrhythmia encountered in medical practice, atrial fibrillation, is not adversely affected by caffeine intake.

2. Heart Muscle
Caffeine has a direct stimulant effect on the heart muscle and causes an increase in the force of myocardial contraction (i.e., an inotropic effect). The inotropic effects are, however, minimal compared to that of digoxin, the mild inotropic agent commonly used to treat heart failure. Because of the increase in the force of myocardial contractility and increase in the heart rate, the cardiac output increases slightly. This effect is important in patients with heart failure in whom two cups of coffee daily may induce a minimal benefit without harm.

3. Blood Pressure
Effects of caffeine on blood pressure are controversial. Single doses can cause a small increase in blood pressure in users; the increase in blood pressure appears to be somewhat greater in nonusers who occasionally consume coffee. One or two cups of coffee can increase blood pressure slightly in habitual users, they have no effect on chronic coffee drinkers. Significant reduction in blood pressure has been observed in chronic users who abstain, but the methodology in several studies on hypertension and caffeine use has been questioned. It is not known whether caffeine interacts unfavorably with antihypertensive medications.

4. Heart Attacks
The link between caffeine consumption and heart attacks remains controversial. The studies done in 1980 failed to implicate coffee consumption, but two studies since 1985 have shown an apparent link between heavy coffee use and heart attacks. Carefully organized studies with sound methodology are required to clarify this important issue.

5. Blood Flow and Blood Vessels
Caffeine dilates systemic blood vessels, small arteries, and arterioles, but it constricts extracranial vessels that are believed to aid in the relief of migraine headaches. Cafergot, a drug used for migraines, contains 100 mg of caffeine and 1 mg of ergotamine.

Chronic caffeine intake appears partially responsible for increased blood cholesterol levels. Although this effect is controversial, discontinuing coffee moderately reduces total blood cholesterol levels less than 7%.

Diabetes, Coffee, and the Heart
Most diabetics succumb to a fatal or nonfatal heart attack, or heart failure. A recent study in The Netherlands has shown that heavy coffee consumption was associated with a substantially lower risk of clinical type 2 diabetes. It is unfortunate that such a large intake of caffeine is required to produce such a beneficial effect. The phenol chlorogenic acid reduces glucose absorption and oxidative stress in vitro and inhibits hydrolysis of glucose-6-phosphate, which could reduce glucose output in the liver. Coffee contains substantial amounts of magnesium that could improve insulin sensitivity and insulin secretion and has been associated with a lower risk of type 2 diabetes. The epidemic of diabetes worldwide continues and any strategy that can be added to the armamentarium to prevent diabetes would be welcome.

Clinical Study: van Dam et al.
Van Dam investigated the association between coffee consumption and risk of clinical type 2 diabetes in 17,111 Dutch men and women aged 50–60. During 125,774 person-years of follow up, 306 new cases of type 2 diabetes were reported.

After adjustment for potential confounders, individuals who drank at least 7 cups of coffee daily were 0.05 times as likely as those who drank 2 cups of coffee daily to develop type 2 diabetes ( p¼0.0002). Higher coffee consumption was associated with a lower risk of type 2 diabetes. It is known that caffeine acutely lowers insulin sensitivity. In a small intervention study, increased coffee consumption for two weeks reduced fasting blood glucose, whereas the substitution of decaffeinated coffee for caffeinated coffee for 3 weeks did not affect blood glucose.