From its origins as a humble Ethiopian pick-me-up to its current status as a fuel of our fast-paced world, coffee has been an object of fascination and passion, and a mirror for how we see the human body and nature. As the mysteries of its effects and chemical components have been uncovered, we are only now beginning to have a clear understanding of coffee's health impacts.

In the modern world, coffee has become a familiar part of everyday life. Coffee is a source of and medium for the stimulant caffeine, the most widely consumed psychoactive drug in the world. Despite its prevalence, very little was known about the health effects of coffee or caffeine until quite recently. Coffee was introduced to Europe in the late 16th century, caffeine was isolated in the early 19th century, and only recently has attention been directed to the plethora of other chemical constituents of this complex beverage.^2,3 

Diverse social, economic, and scientific factors have affected the historical development of coffee science. The health effects of coffee have been contested on both medical and moral grounds, and the history of coffee research is a case study of what Bruno Latour terms the “interruptions” and “translations” that go into the creation of scientific discovery.¹  The story of coffee consumption and health is also a history of Western science and the progression of medical understanding related to the development of the modern fields of biochemistry and physiology.

Coffee is derived from the seeds of the flowering plants of the genus Coffea. The small bushes are native to the higher elevations of tropical sub-Saharan Africa and parts of tropical Asia, with possible origins in the lowlands and semi-highlands of Ethiopia.^2,3  The first accounts of coffee consumption are found in Ethiopia among the Oromo peoples. The most common origin story is that of Kaldi, an Ethiopian goatherd who noticed the stimulating effect of the coffee plant on his goats. This led Kaldi to try the bush's bright red berries for himself, the story goes, and to share them with monks, who threw them in a fire. The roasted berries smelled enticing, and led them to grind and mix the roasted beans with water, yielding the first cup of coffee.²  While apocryphal, the Kaldi story is likely representative of the types of interactions that first led to coffee's identification and use.⁴ 

Islamic knowledge of coffee likely dates to the migrations of Muslims fleeing persecution in Mecca to the kingdom of Aksum, on the coast of modern Ethiopia, between ad 615 and 629. Some of the first possible mentions of coffee in medical texts date to the times of the Third Caliphate. The Islamic physician and astronomer Rhazes (852–932) described the qualities of a plant known as bunn and the beverage buncham in his lost medical text Al-Haiwi (The Continent). Rhazes describes coffee as “hot and dry and very good for the stomach”.⁵  Later, the Islamic doctor Avicenna (980–1037) included an entry for buncham in his text Al-Ganum fit-Tebb (The Canon of Medicine). He describes coffee as coming from Yemen and, expanding on Rhazes, explained that it “fortifies the members, cleans the skin, and dries up the humidities that are under it, and gives an excellent smell to all the body”.⁶  Both of these early accounts describe coffee and its effects within the confines of humoral theories of medicine, which would later be used by their counterparts in Europe. The descriptions of bunn and buncham by Rhazes and Avicenna seem to describe coffee, but curiously written references to coffee and its effects almost disappear from the time of Avicenna to the 15th century, almost 500 years. While documentation is sparse for coffee during this period, it is clear that it was known to and being utilized in the Islamic world, for when references to coffee reappear, it was fully integrated into the life of Yemeni Sufi monasteries.² 

Yemeni Sufis are the source of many modern cultural traditions and health beliefs of coffee use. Although Yemeni Muslims had encountered coffee use through their interactions with Ethiopia, the Sufis popularized the use of coffee within their religious ceremonies. Sufism emerged as a practice related to the mystical inner dimensions of Islam around the 9th century ad. Sufism rose to prominence by the 12th century, and was at the center of the “Golden Age” of Islam between the 13th and 16th centuries. Sufis found that the drink (qahwa) “drove away fatigue and lethargy, and brought to the body a certain sprightliness and vigor”,⁶  as described by the 15th century Sufi Dhabhani.

Coffee spread as a stimulant, benefiting from Islamic dietary laws that strictly forbade the use of alcohol and other intoxicants. Yemeni Sufis used coffee to stay awake during their prayers, particularly the dhikr (ritual remembrance of God), during which short phrases were repeated to glorify God. These Sufi conclaves gathered on Monday and Friday evenings, and drank coffee at the beginning of a night of ritual recitations. From these religious meetings, the use and health effects of coffee spread throughout the Islamic world from the Yemeni peninsula. These same Sufi conclaves also gave rise to what would become the forerunner to the modern coffeehouse, as first Sufi intellectuals and later every strata of Islamic society began to enjoy the marqaha, or euphoria produced by coffee.² 

This obsession with coffee and the effects of caffeine in Mecca led to the first ban on coffee in 1511, which was soon repealed. A cycle of bans and repeals followed coffee across the Middle East as it gained followers. So by the time that the German physician and botanist Leonhard Rauwolf became the first European to write about coffee after his travels through the Middle East in 1573, coffee served in the hundreds of coffeehouses in the region's cities seemed to have been enjoyed for centuries.⁵ 

Sidney Mintz described the role of “drug foods” (such as cacao, coffee, tea, and sugar) as driving the age of exploration and European expansion in the 16th and 17th centuries. Such foods served as “proletarian hunger killers” that could increase productivity while substituting for more substantive nourishment. These products are all native to the tropics, and their addictive qualities drive an expansion of their markets.^7,8 

Relying on travelers' accounts, such as that by Rauwolf, European scholars of the 16th century realized that the beverage was likely the same one mentioned by Rhazes and Avicenna centuries earlier. Avicenna's Canon of Medicine had been translated in the 12th century, becoming the principal basis of medieval European medical knowledge and practice. Avicenna had updated and integrated the earlier medical treatises of both the Greek physician Hippocrates (460 bc–370 bc) and the Romano Greek physician Aelius Galenus (ad 129–199). Hippocratic-Galenic medicine dominated physiology from the 4th century bc until the mid-19th century through the work of Avicenna. Avicenna notably included coffee within the humoral system as “hot and dry in the first degree” and a useful beverage to balance the body's humors.⁵ 

Whereas the humoral system of Avicenna and his forebears was the theoretical basis for much of medical thought, the scientific revolution of the 16th and 17th centuries changed how coffee and its health effects were investigated. Some of the first controlled studies of the chemistry of coffee and its biological effects were being conducted as coffee became pervasive in Europe in the 17th century. These early studies were limited by the methodologies for quantification of chemical substances available at the time.³  Thus, the analysis of the physiological aspects of coffee in general preceded chemical quantitative information.

In the 17th century, coffee was widely seen as an alternative to alcohol, and was viewed by many doctors as a viable treatment for a wide range of ailments. As an herbal panacea, coffee was prescribed in the form of infusions, capsules, potions, or injections against a vast spectrum of diseases, from hernia to rheumatism, from colds to bronchitis. This is distinct from coffee's prevalent use as a beverage as part of the normal diet. It was included as a treatment in both the Materia Medica and the Codex Medicus, the authoritative manuals of pharmacology used until the 20th century; and up until the 19th century plant extracts formed the bulk of the medical curative resources. Still, the pharmacological use of coffee proceeded from its use as a food or drink.² 

Starting with its first introduction to Europe, the psychoactive effects of coffee gave rise to medical and moral concerns. Much of this was focused on the quantity of coffee consumed by individuals. The expression “use and abuse” of coffee became frequent in the vernacular of the 17th century.²  Often, those who were friends and family members of coffee drinkers worried about the health effects of over-consumption. Later, Goethe's interest in the chemical exploration of coffee began with his recognition of and limitation of his own coffee consumption.⁵ 

While coffee was viewed by many as a positive alternative to alcohol, there were also moral and scientific backlashes against this image. In 1674 women in London protested the rise in coffee consumption among men, calling it a “drying and enfeebling liquor” that weakened their men.⁹  And in 1670, a group of French doctors (seeing in this all-in-one remedy a threat to their livelihood) led a campaign against coffee, claiming it to be poisonous to the body.⁹ 

The modern chemical exploration of coffee began with the Swedish botanist Carolus Linnaeus (1707–1778), who described several physiological effects of coffee when he categorized and named the species Coffea arabica in 1737 (Figure 1.1). While the name incorrectly links coffee's origins to the Arabian peninsula, Linnaeus' formal categorization and explanation clearly demonstrates a knowledge of the benefits of coffee: “[coffee] might be considered useful by those who set a higher worth upon saving their time than on maintaining their lives and health”.¹⁰ 

The noticeable physiological effects of coffee stimulated an interest in plant chemistry that led to the discovery of coffee's primary bioactive component, caffeine, in the early 19th century. The chemical exploration of coffee was stimulated by the curiosity of the German poet and naturalist Johann Wolfgang von Goethe (1749–1832).⁵  Goethe, like many of his fellow Europeans, had fallen in love with the exotic drink to the point where he eventually had to reduce intake for health reasons. This personal experience led Goethe to question how coffee produced these dramatic effects on the human body. In 1819, he sought out his young countryman Friedlieb Ferdinand Runge (1795–1867) who had by accident discovered that an extract of the nightshade plant would dilate his eyes. Goethe asked for a demonstration and then asked Runge to pursue an exploration into coffee, which resulted in the discovery of caffeine in the same year.¹¹  Runge would also go on to promote quinine, the key component in the bark of the cinchona tree used to fight malaria, and invent paper chromatography.⁵ 

Coffee studies in 18th-century medical journals sought to explain the mechanisms for coffee's physiological action and effects emphasized nervous and vasomotor stimulation. By the end of the 18th century, advancements in quantitative chemistry led to the discovery of both chemical elements and modern chemical reactions. These new understandings were applied to the investigation of nutrition and helped with the identification of dangerous food adulterants (used at least since 1770).¹²  They also improved the predictions of the biological effects of specific substances, including coffee. The theories of coffee's chemical activity were documented and replicated worldwide in medical compendia.¹² 

The growth of coffee drinking and the advanced institutionalization of science in France, Germany, and Great Britain occurred simultaneously, turning coffee into an object of great interest among European scholars who relied heavily on its physiological effects in their daily work and lives. In 19th century Europe, the development of chemistry and physiology framed the transformation of coffee and its effects from a curious and exciting import form the Middle East into a medical and scientific fact.³  From this period onward, publications on coffee and its effects on health greatly increased. In the first half of the 19th century, medical controversies plagued the therapeutic use of caffeine in chronic conditions such as heart and circulation problems. By 1827, it became clear that caffeine had chemical and physiological properties similar to those of theine, a substance separately isolated from the tea plant. This similarity was later understood to be due to the fact that both plants contained caffeine. In 1838, its analogy with quinine and strychnine was proven, and they would later all be found to belong to the same family of organic compounds. The discovery of the major biochemical component of coffee in 1819 led to an explosion in the interest in and research on coffee's chemistry. A growing number of researchers and publications were dedicated to the exploration of coffee's chemistry and biological role.¹¹ 

Early 19th century conventional wisdom in physiology held that organic processes were caused by non-physical “vital” forces (food that excited the organs contributed to the vitality of the individual). Coffee, with its well-known stimulating effects, was viewed within this paradigm. The renowned German chemist Justus von Liebig (1803–1873), famous for his advances in the study of nitrogen and plant nutrition, supported such an idea, also believing that the “empyreumatic (decomposed due to burning) bodies formed during coffee roasting” could prevent undesired fermentative and putrefactive body reactions.¹³ 

Similarly, the French physician François Magendie (1783–1855), who revolutionized physiology through his experiments with nutrients, included coffee as a remedy for infections.¹⁴  His fellow countryman Claude Bernard (1813–1878), the first to demonstrate that molecules of food were broken into smaller compounds in the organism and rearranged to build new substances, studied the effects of coffee on blood pressure.¹⁵ 

Before the invention of pasteurization and antimicrobial drugs in the 19th century, infectious diseases represented the leading international health concern. In this period, coffee was seen as an auxiliary resource to fight massive public health problems due to its antiseptic and health-recovering properties. Since the second half of the 17th century, it had been recommended as a treatment against “fevers” and “plagues” like cholera and malaria. Both contagionists (who believed that diseases were transmitted through physical contact) and miasmatic-theory advocates (for whom infections derived from putrefied air of rotting organic matters) considered coffee as an efficacious air and body disinfectant due to its warmth and bitterness.¹⁶  Additionally, coffee's antipyretic (fever-reducing) powers, azote (nitrogen) content, and ability of stimulating organs, were considered curative.¹⁷  After the French microbiologist Louis Pasteur (1822–1895) proposed the germ theory in the late 19th century, coffee was seen as having an antipathogenic action.¹⁸ 

In addition to coffee's effects on infections, its influence on heart and vasomotor systems was the first physiological effect identified, and remains as one of the most studied disease mechanisms related to coffee bioactivity. Early research concentrated on coffee's effects on arterial diameter and heart pulsation frequency.¹⁹  Between 1874 and 1913, 27 relevant publications on the issue appeared; the influence of coffee on the cardiovascular system was an area of high interest.

Nineteenth-century studies predominantly focused on caffeine's effects on the bodies' circulatory system with a specific interest in its ability to increase heart and other muscle pulsations. For example, in 1860 the German physician Carl von Voit (1831–1908), one of the founders of the modern field of dietetics, experimented with caffeine's effects on animal musculature.²⁰  Other chemists, however, sought to better understand caffeine's relationship with other compounds. Between 1882 and 1906, the German chemist Hermann Emil Fischer (1852–1919) demonstrated that a variety of substances from living organisms shared a similar structure and could be derived from one another. At first theoretical, Fischer's research showed that chemicals seemingly as disparate as caffeine, adenine, xanthine, and uric acid were all in a family he called purines. Fischer also synthesized caffeine from its chemical components in 1895, and derived the structural formula for caffeine in 1897.²¹  For his work on caffeine and the other purines, Fischer won the 1902 Nobel Prize for Chemistry. Until recently, caffeine remained the dominant subject of coffee's chemical investigations.

The discovery and exploration of the chemistry of caffeine also led to research aimed at reducing its unwanted effects. Publications relating to the search for caffeine-free coffee date back to around the time of Fischer's research and include prominent publications like Merck's 1911 Materia Medica.²²  At that time, new coffee species and varieties with low levels of caffeine were pursued through botanical research and breeding, as caffeine's heightened presence in some species of the Coffea genus evolved as a defense against insect herbivory. By the end of the 19th century, at least 15 works on caffeine-free coffees were published, including two in The Lancet. The first decaffeination process was developed in 1903 by the German merchant Ludwig Roselius, who discovered that the repeated application of solvents removed between 80 and 99% of coffee's caffeine content. Such coffees were popularized with industrialization, as consumers sought to ameliorate the negative effects of the over-consumption of caffeine.⁹ 

Over time, the perception of coffee changed from a “quasi non-food” into a functional food. In the 19th century, apart from nitrogen, no important levels of the then known nutrients were found in coffee. In the view of physiology of the time, however, the fixed nitrogen in coffee was related to “animalized” substances (resemblance with compounds of animals' bodies) and thus positive for facilitating the body's repair. Thus, coffee became highly recommended in the treatment of and recovery from illnesses.^14,15 

In 1850, the French physiologist M. Gasparin argued to the Academy of Sciences of Paris that while the food regimen of Belgian miners encompassed a substantially low quantity and quality of foods, their muscular strength was due to the ability of coffee to decrease fatigue and hunger. As evidence, he pointed to the reduction of urea, a sign of fewer nutritive combustions.²³  Gasparin gained followers for his perspective until the 1870s, but opponents alleged that urea was diluted by the increased diuresis provoked by coffee. In 1882, Brazilian scholar Eduardo Guimarães conducted dog experiments on the intake and metabolism of nitrogen-fixed and hydrocarbonate foods. He concluded that coffee acted in different ways depending on the nutritional status of the subject, making undernourishment more pronounced in undernourished dogs, and saving reserves in well-nourished ones.^24a 

Continued scientific advances between 1850 and 1930 turned attention to nutrition and nutrients, with human dietary patterns becoming a relevant part of public health as scientists began to solidify the connections and interactions between chemicals and living organisms. A major breakthrough in these interaction studies was the discovery of enzymes, macromolecular biological catalysts, by the French chemist Anselme Payen in 1833. Enzymes accelerate chemical reactions and convert molecules from one type to another and are critical for many processes within the human body, such as digestion. In the 1920s and 1930s, enzymes were demonstrated to be composed of proteins. These discoveries dramatically improved the description and interpretation of organic reactions, particularly those of the human body. Critically, many drugs, such as the alkaloid caffeine in coffee, affect enzyme function, mainly through inhibition of enzyme catalyzation.^24b 

Key themes in 20th-century coffee research evolved from the 19th century, when biology was summoned to help explain social behaviors, with investigations focused on coffee's influence on intellectual and moral conditions.²⁵  In fact, much of the scientific debate over levels of coffee consumption was rooted in social and moral fears about caffeism (an addiction to coffee), especially in the period between 1885 and 1920. Despite these social concerns, however, the effects of coffee on the body have long been recognized to not be strictly related to ingested quantities. It is also linked with acclimatization, since an individual's tolerance for caffeine changes with the amount and regularity of coffee consumption. It is well known that recommended intake values are highly dependent on a number of variables including the great irregularity in the metabolism of coffee substances among subjects, depending on physiological adaptations, action of gut microflora, co-ingested foods, specimens and varieties of beans, and their levels of maturation and roasting.^26,27 

Although rarely given as a specific value, such as cups per day, “moderate use” has been and continues to be the chief recommendation of scientific research since caffeine's discovery. In the 19th century moderate dietetic intake of coffee was considered to appropriately excite brain activities, intellectual abilities, resistance to fatigue, and organs.²⁸  In exaggerated quantities, however, coffee was recognized to be deleterious to health and its classification could change from nutritious food into poison.²⁹  Pharmacologically, since the 19th century, a toxic dose was recognized as exceeding by several times ordinary human use. Defining healthy levels of consumption and pharmacological doses is still problematic, although 2015 US Food and Drug Administration guidelines recommend up to five cups of coffee per day.³⁰ 

While coffee, tea, and chocolate have often been lumped together as vehicles for caffeine, it has been found that the actions of each may be somewhat different due to their preparation or the presence of other constituents that modify the effects of caffeine. Recent epidemiologic studies have allowed researchers to identify distinctions in their effects on disease prevalence.^31a  However, beyond the physiological effects of caffeine, many early studies of coffee's effects on human health focused on its impact as an addictive drug or its concurrent use with other addictive drugs, primarily alcohol or tobacco.^31b–31d 

In the 19th century, coffee was recommended as a method to fight against alcoholism by enhancing spiritual wellbeing and reducing alcohol-driven brain activity.³²  From the 1960s to the 1990s, a different research trend began with scientific concern about the possible synergistic effects of coffee and cigarette smoking to liver health.³³  Studies in the 1990s in alcoholics on hepatic effects showed liver functions were improved greatly by coffee consumption as documented by liver enzyme levels. By the end of that decade, it was demonstrated that coffee's use while smoking actually prevented hepatic damage in rats. As for other health conditions, the simultaneous use of coffee, tobacco, and alcohol has been linked to impaired lipoprotein profile and heart condition³⁴  and neoplastic pathologies epidemiology.³⁵  Continued research on this subject indicated a role for coffee in the reduction of risks of cirrhosis, particularly in alcoholics.³⁶ 

Recent work looking at the relationship of ages of onset for use of coffee, tobacco, and alcohol found that among a sample of AA participants “coffee does not precede initiation of regular smoking or alcohol drinking as might be anticipated for a gateway drug”.³⁷  Another study found a correlation between coffee use and sobriety.^38a  In early studies the effects of coffee on health were confounded because coffee and smoking tended to occur together. It was not until statistical techniques were able to parse out the toxic effects of cigarette smoking (and other harmful associated lifestyle effects) that health risks related to coffee consumption were contended^38b,38c  and the beneficial effects of coffee consumption on health emerged.^38d–38f 

Studies on the connections of coffee and neurological systems have been guided by two key questions that emerged in the 19th century: the direct action of coffee on neurological and psychological conditions and the mediation, via the nervous system, of the influence of coffee on different organs. In the 1970s, as the use of psychedelic drugs in the Western world increased, studies evaluated the possible modification of their action by coffee. In the 1980s, the relationships between coffee and anxiety were examined and, in the 2000s, the risk of suicide. In the late 1990s, methods such as power spectral analysis allowed researchers to monitor the caffeine modulation of nerves and evidenced a dual action of coffee, alerting and relaxing the central nervous system, by increasing the activity of both sympathetic and parasympathetic systems.³⁹  Coffee has also been associated with reduced risks of Parkinson's disease, cognitive decline, and Alzheimer's disease.^40–43 

In the 19th century, coffee's effects on the gastrointestinal system motivated many debates, primarily due to the symptoms and sensations it caused: delayed digestion, flatulence, and more pronounced peristalsis. Between 1878 and 1914, 28 works were published on the matter. Since the 1980s new gastrointestinal function tests help better explain how the stimulation of gastric acid secretion, of the esophageal sphincter, and of the secretion of gastric hormones takes place in relation to coffee intake.⁴⁴ 

Studies of coffee have moved beyond simply equating coffee with caffeine, and have attempted to demonstrate coffee and caffeine's relationship with specific health problems and concerns. As one of the world's most commonly consumed beverages, coffee and its constituents, including caffeine and a plethora of other compounds, have the possibility to make a large positive or negative impact on the health of many people. While there has been some debate over coffee's efficacy to directly change health outcomes, a growing number of studies show that coffee may not be associated with poor health outcomes, as was previously thought. In fact, one recent large-scale study (following over 400 000 individuals) found that “coffee consumption was inversely associated with total and cause-specific mortality.”⁴⁵ 

While the specific mechanisms remained poorly understood, coffee was definitively anchored to what is now known as the energy metabolism. By 1915, it was known that caffeine increases the metabolic rate, although through mechanisms not fully understood until 1969.⁴⁶  From the 1960s, investigations established coffee as an enhancer of energy expenditure. In the 2000s, it was clearly demonstrated that caffeine activates energy metabolism by stimulating lipid oxidation and release of catecholamines, and regulating the expression of the mitochondrial uncoupling protein (UCP) gene family involved in energy metabolism and thermoregulation.⁴⁷  There has also recently been growing evidence to indicate that, in a dose-dependent way, individuals could be protective against type 2 diabetes. Recent studies show that there are different mechanisms of action for type 2 diabetes prevention, most of them related to antioxidant and other effects of coffee's chlorogenic acids and their lactones or quinides formed during roasting.⁴⁸ 

Recent studies have also examined the relationship of coffee and the global epidemic of obesity.^49a  While definitive evidence is still lacking, many believe that coffee consumption may be inversely related to weight gain. For instance, coffee mannooligosaccharides are experimentally capable of helping body weight reduction, while there is some evidence that coffee consumption in males may hinder the falling of serum levels of cortisol,^49b  a hormone linked to visceral adiposity.^49c  By the end of the 1970s, the new trend comprised studies on the effects of coffee on the bioavailability of mineral and trace elements, with special focus on the impairment of calcium balance and its effects on bone growth and repair, a topic currently still being investigated.^50a 

Coffee has been linked to positive outcomes in epidemiological studies for diseases as varied as Alzheimer's and prostate cancer. However, it is critical to note that every health study on coffee is referring to and utilizing plain black coffee. Common coffee drinking practices such as adding sugar, creamer, or milk can alter the health values and outcomes of coffee consumption.^50b  Similarly, differences in preparation, such as filtration, and other variables must be considered with respect to health expectations.^50c  Most contemporary epidemiological studies of the effects of coffee consumption on various health concerns account for these variables using statistical methods.^50d 

By the turn of the 20th century, research into the chemistry of coffee branched beyond the study of caffeine to examine other compounds found within the plant. The chemistry of coffee is complex and these compounds number in the hundreds. Some are now more extensively studied due to their potential bioactivity: chlorogenic acid, caffeic acid, trigonelline, and others.⁵¹ 

Recent studies have also begun to examine the role of absorption, bioavailability, and the biotransformation of key coffee compounds beyond caffeine,⁵²  such as polyphenols⁵³  and chlorogenic and caffeic acids.^54a  While many of these components were discovered in the 19th century, many of these substances were considered to have no biological effects until the 1920s.⁵  Studies on the bioavailability of chlorogenic and caffeic acids started in the 1950s, in the same period when the first isomers of chlorogenic acid were identified.^54b  These studies expanded in the 1990s, as a new field of research explored the antioxidant abilities of these compounds.^54c  These antioxidants are critical as they could help prevent a series of epidemiologically challenging degenerative diseases. Among the most studied and important effects is that of preventing type 2 diabetes.²  Additionally, coffee is rich in anti-carcinogenic polyphenols, such as chlorogenic acids, that have been ascribed as in vitro antigenotoxic (preventing damage to gene information, such as that associated with mutations that may lead to cancer).⁵⁵  For example, chlorogenic and caffeic acids may be potentially effective in preventing the mutagenic and carcinogenic reactions of intestinal carcinomas.^56,57  Although caffeine is often cited as a possible risk factor for breast cancer, decreased or no risk of such cancer was detected in women consuming coffee, probably due to the polyphenols.⁵⁸ 

In recent years, genetic and molecular medicine allowed studies of polymorphisms that evidenced the complexity of the individual mechanisms linking coffee compounds' metabolism to cancer onset or prevention. In 2009 it was demonstrated that trigonelline is a phytoestrogen with potential anticancer action.^6,49a,72a  Coffee diterpenes were shown to induce in vitro human leukemia cell apoptosis.⁵⁹  A 2010 study with Japanese women indicated lower morbidity and mortality among those consuming coffee; deaths attributed to cancer did not seem to be associated with coffee intake, with the exception of colon-rectal cancer.⁶⁰  However, methylpyridinium, formed in the roasting process, and chlorogenic acids are potentially capable of reducing risks of colon cancer.⁶¹  Nevertheless, the relationship between coffee and cancer remains uncertain. Although coffee intake seems to be linked with greater risk of certain types of cancer (such as those of stomach, lung, and bladder), recent investigations indicate that when isolated from other factors, such as smoking and drug use, coffee intake can possibly protect against most types of cancer.⁶² 

Several cancer types have been scrutinized since the 1970s and studies of coffee's effects on cancer have intensified since the 1990s. Prospective studies monitoring thousands of individuals for several years have generated an enormous amount of data on coffee and cancer. By the 2000s, a consensus emerged that coffee is a potential protective agent against several types of cancer. A 2011 meta-analytical study looking at the relationship of coffee to all cancers found that the more coffee consumed the better the protection against cancer.⁶³  More specifically, coffee has been found to lower the relative risk of liver cancers by more than 40%, which has been confirmed by other research.^64–66  Coffee drinking has also been linked to positive outcomes for breast cancer, lung cancer, and prostate cancer.^67–69 

Drinking coffee has been demonstrated to decrease the risk for liver disease, type 2 diabetes, and general mortality.^70–72a  Coffee's effects on respiration have been investigated, mainly due to the caffeine's bronchodilator action, a basis for the very old recommendation of coffee for asthma and bronchitis. Coffee's antiallergic function due to pyridine and its use in rhinitis have also been explored.^72b 

As lifestyles and diets shifted in the 20th century, cardiovascular disease became a major cause of illness. Coffee was implicated as a possible agent in the causation of the tripod-condition encompassing hypercholesterolemia, hypertension, and acute myocardial infarction.⁷³  In the mid-1990s diterpenes of boiled coffee were discovered to elevate blood cholesterol.⁷⁴  However, as new trends in epidemiology resulted in more sophisticated cohort and case–control studies that could statistically parcel out confounding variables, the perspective on coffee's relationship to heart health shifted, much as it did for the interactions of smoking and other lifestyle variables. Some studies claimed the antioxidant potential of coffee could help prevent cardiovascular diseases.⁷⁵  It was also demonstrated that the quantity and frequency of coffee intake could influence the risks of hypertension, coronary diseases, and stroke. In 2014, a systematic review of studies looking at the long-term heart effects of coffee consumption found that those who consumed a moderate amount of coffee had the lowest risk for heart problems.⁷⁶  Similar studies demonstrated a positive relationship between coffee consumption and the prevention of stroke and heart failure.^77–79 

Since its discovery in East Africa, coffee has fascinated the peoples and societies exposed to its bitter flavor and psychostimulatory effects. Our changing understanding of coffee reflects the development of various theories of the human body and the natural world. In the Western tradition, coffee's effects on the body were first seen as part of a humoral system of balance that has been replaced by a complex chemical understanding of how organic systems work and interact. Within these changing contexts, coffee has variously been seen to have either a positive or a negative effect on overall human health.

The history of the relationship of coffee to human health and physiology is also a history of complex social, economic, and scientific narratives. The use and perspectives of coffee are tightly linked to the medicalization of our understandings of drugs and food. Many of the historical problems and controversies that were associated with the use of coffee are now linked to methodological gaps, inter- and intra-individual differences, interrelationships among food substances, form of roasting and brew preparation, and differences in coffee composition related to various aspects of growth and production.