Health effects of coffee: Where do we stand?
It would make things easier if the caffeine content were listed on food labels so you would know if you've exceeded the mg level that most health experts say . The verdict on coffee is mostly positive these days, but it hasn't always been so well-received. Drinking around three cups of coffee a day has been linked to a lower risk of death “from any cause” in two new large-scale studies. The habits.
Smoking may accelerate the pre-systemic i. Pregnancy decreases the clearance and excretion of caffeine, thus the latter and its metabolites, such as theophylline, can accumulate in the body [ 34 ].
Variations in enzyme activity, especially with regard to CYP1A2, are reported. As a result, there is a growing effort to identify genetic polymorphisms influencing caffeine metabolism[ 2639 ]. Mechanisms of Action The potential effects of caffeine, at the cellular level, can be explained by three mechanisms of action: Antagonism of Adenosine Caffeine blocks adenosine receptors, mainly A1 and A2A subtypes, competitively antagonizing their action [ 4041 ] and causing an increased release of dopamine, noradrenalin, and glutamate [ 4243 ].
Caffeine is able to reduce cerebral blood flow [ 44 ]. It is also able to reduce myocardial blood flow, by inhibiting A1, A2A and A2B adenosine receptors in blood vessels and limiting adenosine-mediated vasodilation [ 45 ].
A1 receptors can be found in almost all brain areas. The highest concentration is in the cerebral and cerebellar cortices, the hippocampus, and a number of thalamic nuclei [ 4647 ], whereas only a modest concentration is found in the corpus striatum, i. Pre-synaptic A1 receptors inhibiting the release of neurotransmitters are present in almost all types of neurons.
There is significant evidence of a relationship between adenosine A2A and dopamine D1 receptors [ 42 ].
Adenosine A2A and D2 receptors show a high concentration in the dopamine-rich areas of the brain, i. There is little evidence supporting their presence outside these areas, even if, according to recent functional neuroimaging studies, they may be present in the cerebral cortex and the hippocampus.
The blockade of A2A receptors in the basal ganglia, i.
Coffee and health: What does the research say? - Mayo Clinic
These effects largely depend on an intact dopaminergic neurotransmission. Finally, it has been shown that the effects of caffeine in low doses can be replicated by a selective A2A receptor antagonist, but not by a selective A1 receptor antagonist [ 49 ]. These findings suggest that the interaction between caffeine in high doses and dopaminergic transmission finds its roots in the increase of post-synaptic D2 receptor transmission.
The ability of caffeine to block adenosine receptors can be observed also at low doses, such as those contained in a single cup of coffee. Other mechanisms of action, such as the mobilization of intracellular calcium and the inhibition of phosphodiesterases, require higher doses of caffeine, unlikely to be obtained with the common daily dietary sources of caffeine.
Mobilization of Intracellular Calcium Caffeine can induce calcium release from the sarcoplasmic reticulum [ 50 ] and can also inhibit its reuptake [ 51 ]. Through these mechanisms, caffeine can increase contractility during submaximal contractions in habitual and nonhabitual caffeine users. Intracellular calcium determines the activation of endothelial nitric oxide synthase eNOSwith the production of higher quantities of nitric oxide [ 47 ].
Therefore, some of the effects induced by caffeine might be partly mediated by neuromuscular function modulation and contractile force increase in the skeletal muscles [ 5253 ]. A potential counter effect of caffeine is represented by diuresis stimulation, accountable for ergolytic effects in endurance athletes during prolonged workouts and competitions [ 54 ].
Inhibition of Phosphodiesterases Caffeine acts as a nonselective competitive inhibitor of phosphodiesterases [ 55 ]. These enzymes hydrolyze the phosphodiester linkages in molecules, such as cyclic adenosine monophosphate cAMPinhibiting their degradation.
It also activates protein kinase A, which in turn phosphorylates several enzymes implicated in glucose and lipid metabolism [ 57 ]. These mechanisms of action require very high doses of caffeine, unlikely to be present in the standard diet, which contains moderate amounts of caffeine.
Further mechanisms of action describe the use of caffeine in sport activities and as a dietary supplement that are described below. Increase of Post-exercise Muscle Glycogen Accumulation Faster recovery following intense exercise, mediated by a higher rate of glycogen resynthesis, has been described [ 58 ].
It has been maintained that caffeine ingestion has no effect on glycogen stacking during recovery from exercise in recreational athletes [ 59 ]. Although this finding deserves further investigation in broader population samples recreational and professional athletes, untrained individuals and occasions during exercise or recoverycaffeine in addition to post-exercise carbohydrates consumption seems to be able to stimulate glycogen resynthesis.
Increase of Fatty Acid Oxidation The increase of lipolysis determines a decreased dependence from glycogen use [ 61 ].
Caffeine switches the substrate preference from glycogen to lipids by stimulating HSL activity and inhibiting glycogen phosphorylase activity [ 62 ]. Effects on the Cardiovascular System Caffeine has several effects on the cardiovascular system, which have been examined thoroughly with conflicting result.
Many mechanisms have been suggested in relation to caffeine toxicity, which primarily affects the cardiovascular system. In the heart, adenosine acts through specific receptors and is a negative inotropic and chronotropic agent. This results in positive inotropic and chronotropic effects, accountable for an augmented heart rate and conductivity [ 63 ].
In fact, higher concentrations of caffeine increase intracellular cAMP and cyclic guanosine monophosphate cGMP by a nonspecific phosphodiesterases inhibition, which affects cardiac contractility secondary to calcium release.
The latter mechanism may increase the susceptibility for arrhythmias.
This determines an increased risk of ventricular arrhythmias [ 64 ]. According to the aforementioned mechanisms, arrhythmic episodes have been hypothesized to be responsible for death in cases of lethal intoxication. Caffeine, especially at high doses, leads to palpitations and arrhythmias, such as atrial fibrillation and supraventricular and ventricular ectopic beats the latter also known as premature ventricular contractions, PVCs [ 65 ].
It must be underlined that the positive inotropic effects of caffeine are reinforced by the positive chronotropic effects of guarana, a substance that is frequently added to energy drinks and contains caffeine, theobromine, and theophylline [ 66 ]. Numerous physiological and epidemiological human studies have investigated the link between caffeine and both atrial and ventricular arrhythmias [ 69 ], but their results are not always in agreement. The first human studies were carried out using invasive electrophysiology.
Opposite results were found in the left atrium, whose refractory period paradoxically increased with caffeine intake. As regards the effects of caffeine on the human electrocardiogram [ 69 ] after the intake of moderate amounts of caffeine [ 72 ] or high-caffeine energy drinks [ 73 ], it was noticed that caffeine does not acutely induce any statistically and clinically significant changes in P-wave indices, i.
In addition, studies of individuals performed with continuous electrocardiographic monitoring suggested that caffeine has a limited effect on the circuits underlying ventricular arrhythmias [ 697677 ]. Therefore, despite increases in adrenaline levels, caffeine appears to have no proarrhythmic effect even in patients with clinical ventricular arrhythmias; caffeine showed no capacity of modifying the inducibility or severity of arrhythmias in patients with malignant ventricular arrhythmias [ 77 ] and did not induce an increase of cardiac ectopy, neither atrial nor ventricular, in patients with a high prevalence of baseline ectopy [ 69 ].
Furthermore, in high-risk patients with recent myocardial infarction no increase in the frequency or severity of PVCs or arrhythmias was found [ 69 ]. It is interesting to note that although adrenaline concentration increases with caffeine ingestion, the degree of the release is six times lower than the boost noted during exercise [ 78 ].
Larger-scale epidemiological studies found no increased risk of development of atrial arrhythmias after caffeine intake in healthy subjects [ 69 ]. A recent meta-analysis [ 79 ] suggested that it is unlikely that the chronic consumption of caffeine causes or contributes to atrial fibrillation. Furthermore, as atrial fibrosis is an important substrate for atrial fibrillation and caffeine has antifibrotic properties [ 81 - 84 ], this finding might encourage the search for effective antifibrosis agents or the use of caffeine to prevent atrial fibrillation.
The same authors found a very significant association between heavy coffee intake 10 cups per day and increased risk of sudden cardiac death in patients with a history of coronary artery disease who suffered from sudden cardiac arrest vs. However, a possible limitation may be represented by the fact that only two of the controls drank more than 10 cups of coffee per day Some researchers have conjectured that caffeine is a vasoconstrictive substance [ 808586 ].
In vitro studies have found that the concentration of intracellular calcium in vascular smooth muscle is modified by caffeine and this phenomenon could directly determine variations of coronary artery tone [ 67 ]. Caffeine has been shown to elevate blood pressure in both normotensive and hypertensive prone men, partly by inhibiting adenosine action, leading to elevated noradrenalin release and vasoconstriction [ 8788 ].
A number of studies have demonstrated that acute caffeine ingestion increases blood pressure and catecholamine levels and decreases heart rate [ 7489 ]. It is well known that adenosine causes vasodilation, thus, the antagonization of adenosine receptors may induce vasoconstriction. By contrast, caffeine also augments endothelium-dependent vasodilation by agonist stimulation of endogenous nitric oxide production in young, healthy individuals.
A double-blind, randomized study [ 55 ] showed that caffeine ingestion produced an increase in systolic and diastolic blood pressures in the brachial artery, in agreement with previous studies that highlighted how acute caffeine ingestion elevated peripheral blood pressure [ 808691 ] and augmented the forearm blood flow response to acetylcholine, an endothelium-dependent vasodilator. It has been reported that caffeine stimulates nitric oxide synthesis in the endothelium via the release of calcium from the endoplasmic reticulum by activating the ryanodine-sensitive calcium channel and inhibiting the breakdown of cGMP in the aorta: A balance between the vasodilatory effect of caffeine as an endothelium-dependent vasodilator and its vasoconstrictive effect as an adenosine receptor antagonist may control vascular function.
High caffeine concentrations may cause marked hypotension secondary to vasodilation and, thus, ventricular fibrillation, which could be a possible mechanism of cardiovascular collapse [ 93 ]. Blood pressure changes induced by acute caffeine ingestion need to be further investigated. Therefore, there seems to be a relevant acute effect of caffeine ingestion on central hemodynamics, but not on peripheral pressure. Several factors, such as age, exercise-induced stress, and hypertension, have been reported to influence blood pressure changes induced by caffeine [ 86 ].
Review on Health Benefit and Risk of Coffee Consumption
These observations highlight the importance of keeping fairly constant any confounding factor when carrying out experimental studies, in order to assess correctly the blood pressure changes during caffeine administration.
Similarly, case-control and prospective studies have shown differing result with regard to the risk of myocardial infarction among patient with high coffee intake. There are case reports [ 6796 ] of coronary artery vasospasm induced by caffeine-containing energy drinks, but there is not enough evidence to support a relationship between caffeine and vasospasm. In vitro, caffeine has physiological effects on the concentration of intracellular calcium in the vascular smooth muscle and could induce coronary vasospasm; in vivo, caffeine reduces myocardial blood flow during exercise [ 97 ].
Hide Caption 7 of 15 Photos: Coffee will make you go blind — Postum's ads against coffee were especially negative, claiming that coffee was as bad as morphine, cocaine, nicotine or strychnine and could cause blindness.
Hide Caption 8 of 15 Photos: Coffee's health history headline: Coffee stunts your growth — Medical concerns and negative public beliefs about the benefits of coffee rose in the early s.
Good Housekeeping magazine wrote about how coffee stunts growth. Hide Caption 9 of 15 Photos: Coffee will give you bad grades, kids — In a Science magazine article, 80, elementary and junior high kids were asked about their coffee drinking habits.
Health effects of coffee: Where do we stand?
Researchers found the "startling" fact that most of them drank more than a cup of coffee a day, which was compared with scholarship with mostly negative results. Hide Caption 10 of 15 Photos: Coffee on TV, a New England Journal of Medicine study found a short-term rise in blood pressure after three cups of coffee. Hide Caption 11 of 15 Photos: Coffee's health history era headline: Time for meta-analysis — Now begins the era of the meta-analysis, in which researchers look at hundreds of studies and apply scientific principles to find those which do the best job of randomizing and controlling for compounding factors, such as smoking.
The results for coffee: But first, a couple of negatives: That finding was repeated in a meta-analysis. So if this is a risk factor in your family history, you might want to switch to tea. And a meta-analysis found a correlation between coffee consumption and lung disease, but the study found it impossible to completely eliminate the confounding effects of smoking. Hide Caption 12 of 15 Photos: Coffee's health history headlines: Coffee reduces risk of stroke and some cancers — A meta-analysis of 11 studies on the link between stroke risk and coffee consumption between andwith nearly a half a million participants, found no negative connection.
And a meta-analysis of studies between and found four or more cups a day had a preventative effect on your risk for stroke.
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Those findings were replicated in in two other studies. As for prostate cancer, a study followed nearly 59, men from to and found drinking coffee to be highly associated with lower risk for the lethal form of the disease. Hide Caption 13 of 15 Photos: Coffee's health history A similar analysis of studies on heart failure found four cups a day provided the lowest risk for heart failure, and you had to drink a whopping 10 cups a day to get a bad association.
And overall heart disease? A meta-analysis of 36 studies with more than 1. Hide Caption 14 of 15 Photos: Coffee is practically a health food — How about coffee's effects on your overall risk of death? One analysis of 20 studiesand another that included 17 studiesboth of which included more than a million people, found that drinking coffee reduced your total mortality risk slightly.
And as a sign of the times, inthe US Department of Agriculture agreed that "coffee can be incorporated into a healthy lifestyle," especially if you stay within three and five cups a day a maximum of milligrams of caffeine and avoid fattening cream and sugar. You can read its analysis of data here. Hide Caption 15 of 15 As you know, the news on coffee has not always been positive; in fact, the argument over the merits of your daily cup of joe dates back centuries.
Let's take a look at the timeline. Coffee leads to illegal sex Legend has it that coffee was discovered by Kaldi, an Ethiopian goatherd, after he caught his suddenly frisky goats eating glossy green leaves and red berries and then tried it for himself.
But it was the Arabs who first started coffeehouses, and that's where coffee got its first black mark.