Coffee, Caffeine, and Health
By Jeff Shenfeld PGY-3
Coffee and tea both contain significant amounts of caffeine, and are among the most popular beverages in the world. Caffeine is found naturally in a wide variety of plants, and can also be synthesized and added to foods and beverages. In addition to reducing fatigue, caffeine has been used as a treatment for apnea of prematurity in infants, and has been combined with analgesic agents in various pain medications. In the United States, 85% of adults consume caffeine daily, with the average caffeine intake being 135 mg per day, or roughly 1.5 standard cups of coffee.
Caffeine, a methylxanthine, is nearly completely absorbed 45 minutes after ingestion. It is able to cross the blood-brain barrier, and in the liver, is metabolized by cytochrome P-450. The molecular structure of caffeine is similar to that of adenosine, which allows caffeine to bind to adenosine receptors and inhibit its effects. Accumulation of adenosine in the brain inhibits arousal and increases drowsiness. Moderate caffeine intake can antagonize the effects of adenosine.
At high doses and in sensitive individuals, caffeine can increase sleep latency, reduce sleep quality, induce anxiety, dysphoria, and psychomotor agitation. Toxic effects are estimated to occur with intakes of 1.2g or higher, and a dose of 10-14g is thought to be fatal. Quitting caffeine intake after habitual consumption can lead to withdrawal symptoms including headache, fatigue, and depressed mood.
Epidemiologic studies of caffeine intake and health outcomes are limited by the development of tolerance to caffeine, and the potential confounding of smoking or other lifestyle factors in caffeine users. Meta-analyses of trials assessing the effect of caffeine on blood pressure found that isolated caffeine intake (pure caffeine, not in the form of coffee or another beverage) results in a modest increase in systolic and diastolic blood pressure. However, in trials of caffeinated coffee, no substantial effect on blood pressure was found, even in individuals with hypertension.
Cafestol, a cholesterol-raising compound, is found in high concentrations in unfiltered coffee. A randomized trial found that high consumption of unfiltered coffee raised LDL levels more than filtered coffee, and predicted a 11% higher risk of major cardiovascular events. Experimental studies in humans did not show an association between caffeine intake and atrial fibrillation. Findings of many prospective studies have shown that consumption of up to six cups of filtered, caffeinated coffee per day, as compared with no coffee consumption, is not associated with increased risk of coronary artery disease and stroke.
Caffeine stimulates with sympathetic nervous system and may improve energy balance by reducing appetite and increasing the basal metabolic rate and food-induced thermogenesis. Caffeine intake reduced insulin sensitivity in the short term, as it inhibits the storage of glucose as glycogen in muscle. However, studies have found that tolerance develops for the adverse effect of caffeine, and long-term effects such as reduced hepatic insulin resistance and reduced risk of type 2 diabetes may offset the adverse short-term effects.
Many prospective cohort studies have been done which provide strong evidence that coffee and caffeine consumption are not associated with increased incidence of cancer or rate of death from cancer. Inverse associations have been noted between coffee consumption and endometrial cancer, hepatocellular carcinoma, melanoma, non-melanoma skin cancer, breast cancer, and prostate cancer.
Coffee has been repeatedly associated with lower risk of liver fibrosis and cirrhosis. This may be related to adenosine receptor antagonism, as adenosine promotes tissue remodeling and fibrinogenesis. Caffeine intake is associated with reduced risk of gallstones, likely due to the inhibition absorption of gallbladder fluid, increasing cholecystokinin secretion, and stimulating gallbladder contraction.
Caffeinated coffee intake has been shown to have an inverse association with the risk of Parkinson’s disease. This relationship was not seen with decaffeinated coffee. This may be a result of caffeine inhibiting nigrostriatal dopaminergic neurotoxic effects through adenosine receptor antagonism. Caffeine consumption has also been associated with reduced risks of depression and suicide. Consumption of 2 to 5 cups standard cups of coffee per day has been associated with reduced mortality in cohort studies around the world.
There has been significant research into the health outcomes associated with caffeine. This large body of evidence suggests that caffeine intake does not increase the risk of cardiovascular disease and cancer. Consumption of caffeinated coffee has consistently been associated with a reduced risk of several chronic diseases. However, high levels of caffeine intake can lead to adverse effects. Current evidence does not warrant the use of caffeine or coffee intake for disease prevention, but moderate consumption may play a role in a healthy lifestyle.
Dam, Rob M. Van, et al. “Coffee, Caffeine, and Health.” New England Journal of Medicine, vol. 383, no. 4, 2020, pp. 369–378., doi:10.1056/nejmra1816604.