Coffee and tea are among the plants that are highest in caffeine. Their use as beverages makes caffeine the most consumed psychoactive agent in the world. Coffee is commonly used to increase alertness and work productivity. Synthetic caffeine is added to soft drinks, energy drinks, and products intended to reduce fatigue or promote weight loss.

The caffeine content varies with the type of drink: It is high in coffee, energy drinks, and caffeine tablets; intermediate in tea; and low in soft drinks. Coffee is the predominant source of the caffeine ingested by adults. The evidence for caffeine’s effects on people is ambiguous, and some risks and benefits deserve special attention because of the impact they may have on our health.

Characteristics of Caffeine

Caffeine is a methylxanthine that is completely absorbed 45 minutes after ingestion, peaking between 15 minutes and 2 hours. The half-life of caffeine varies according to age. In adults, it is 2.5-4.5 hours; in newborns, 80 hours; in children older than 6 months, it remains stable over time with respect to weight. Smoking accelerates caffeine metabolism by reducing the half-life by 50%. Oral contraceptives, however, double caffeine’s half-life. Caffeine metabolism is reduced during pregnancy (it is greater in the first trimester), with a half-life of more than 15 hours. Caffeine clearance can be slowed by several classes of drugs (eg, quinolones, cardiovascular drugs, bronchodilators, and antidepressants) that increase its half-life because they are metabolized by the same liver enzymes.

Caffeine passes the blood-brain barrier and, having an adenosine-like structure, inhibits adenosine’s effects by binding to adenosine receptors. In the brain, caffeine reduces fatigue, increases alertness, reduces reaction times, may reduce the risk for depression, and increases the effectiveness of nonsteroidal anti-inflammatory drugs in treating headaches and other types of pain.

Caffeine and Chronic Diseases

The evidence available on the relationship between caffeine and health has several methodological limitations. Observations of the acute effects of caffeine may not reflect long-term effects because tolerance to caffeine’s effects may develop over time. Smoking and unhealthy lifestyles are confounding factors in epidemiological studies of caffeine intake. In addition, the estimate of the amount and frequency of caffeine intake is often inaccurate because it is mainly based on self-assessment systems. Finally, prospective studies of caffeine consumption are mainly based on coffee and tea consumption, but it is unclear how much the observed outcomes can be translated to intake of other beverages such as energy drinks.

Considering the very high prevalence of arterial hypertension worldwide (31.1% of adults), many questions have been raised about the influence of coffee consumption on blood pressure (BP) and the risk for arterial hypertension. Administration of 200-300 mg caffeine is shown to induce a mean increase of 8.1 mm Hg systolic BP and 5.7 mm Hg diastolic BP. The increase is observed in the first hour after caffeine intake and lasts no longer than 3 hours.

Yet, the moderate and usual consumption of coffee does not increase, but may even reduce, the risk of developing high BP. In contrast, occasional coffee consumption can have hypertensive effects, and moderate and usual consumption in patients with high BP does not appear to increase the risk for uncontrolled BP and can reduce the risk for death from any cause. The inverse association between coffee consumption and hypertension risk was confirmed in a review and meta-analysis of cross-sectional and cohort studies.

With respect to lipid metabolism, cholesterol levels may increase after caffeine consumption due to cafestol. Concentrations of cafestol are high in unfiltered coffee, intermediate in espresso and moka pot coffee, and negligible in instant or filtered coffee. Studies on the impact of coffee on lipid levels have led to inconsistent results, however. Data have shown that people who drink more coffee have higher triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels. Other data have shown that caffeine promotes LDL receptor expression and clearance of LDL cholesterol.

Experimental and cohort studies have not shown an association between coffee consumption and atrial fibrillation (AF). In fact, evidence suggests that coffee consumption tends to reduce the risk for AF in a dose-response relationship. Similarly, coffee consumption is not associated with increased risk for cardiovascular events in the general population or among patients with a history of hypertension, diabetes, or cardiovascular disease.

The Coffee and Real-Time Atrial and Ventricular Ectopy study evaluated the acute effects of coffee consumption on cardiac ectopy using wearable sensors with continuous recording. It did not demonstrate any increase in daily premature atrial contractions with coffee consumption, compared with abstaining from caffeine. 

In patients with type 2 diabetes, a study performed in Japan showed that coffee consumption was associated with reduced all-cause mortality. The results suggested a dose-response relationship, and drinking coffee and green tea appeared to reduce mortality risk further. The results were not generalizable, however, because of the study population’s ethnic homogeneity.

Dose and Toxicity

Caffeine at high doses (> 400 mg daily) and in susceptible patients can induce anxiety, but the effects of caffeine on sleep and anxiety can differ from patient to patient. This variation reflects differences in caffeine metabolism rate and adenosine receptor gene variants.

High caffeine intake can stimulate diuresis, but without causing damaging effects on hydration when taking moderate doses of caffeine (≤ 400 mg daily) for long periods. Stopping caffeine suddenly, in a regular consumer, can lead to withdrawal symptoms such as headache, asthenia, decreased attention, depressed mood, and flulike symptoms.

The toxic effects of caffeine occur with intake > 1.2 g. A dose of 10-14 g is considered fatal. Caffeine overdose is rare when considering traditional methods of intake (coffee and tea) because 70-100 cups of coffee should be sufficient for caffeine poisoning. Severe events can occur following the use of caffeine tablets or as energy drinks for the following reasons:

• The episodic consumption of caffeine does not allow for tolerance to develop.
• Young people are more vulnerable to the effects of caffeine.
• Caffeine has a synergistic effect in combination with other components in energy drinks.
• Taking caffeine in combination with alcohol or intense exertion causes serious, even fatal, outcomes.

Products Containing Caffeine

Evidence supports the relationship between high consumption (approximately 1 L) of energy drinks with a caffeine content of 320 mg and short-term cardiovascular adverse events, such as increased BP, QT-segment prolongation corrected for heart rate, and palpitations. These tests prompt the recommendation to avoid consuming these beverages in high quantities and in association with alcohol.

Weight loss products generally contain caffeine coupled with herbal extracts that are expected to improve fat metabolism, lipolysis, and oxidation. These products, because of their easy availability, presumed benefits, and high caffeine concentration, may be more susceptible to misuse because they can be taken in larger portions than recommended. The combination of multiple ingredients, concentrated amounts of caffeine, and excessive consumption increases the likelihood of adverse effects.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.