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Specific open license. Mailing list. Variations in caffeine sensitivity and consumption may relate to polymorphisms in enzymes that degrade caffeine and in adenosine receptors, which are the primary targets of caffeine Caffeine works by binding to adenosine receptors located in the central and peripheral nervous systems as well as in various organs, such as the heart, and blood vessels. Adenosine is a molecule involved in numerous biochemical pathways, mostly for energy transfer in the form of adenosine triphosphate, the basic fuel of cells and signaling.
Adenosine is a neuromodulator that can promote sleep, affect memory and learning, and protect cells after insults. Adenosine can also act on several types of cognate receptors: for example, A1, A2a, A2b, and A3, which are G-coupled proteins.
In the central nervous system, activating A1 receptors inhibits the release of neurotransmitters, whereas activating A2a receptors promotes their release During early stages of brain development, the predominant effect of caffeine is to antagonize type 2A adenosine receptors, slowing down the migration speed of some neurons At toxic doses i.
The toxic dose effects are not considered here because, although they are of great concern to the medical profession and may be on the rise, they are still rare compared to other, non-lethal caffeine effects and the precise mechanism of caffeine toxicity has not been investigated in humans.
Caffeine is usually ingested. Caffeine is soluble in water and lipids, easily crosses the blood—brain barrier, and can be found in all body fluids, including saliva and cerebrospinal fluid. Importantly, caffeine ingested by women perinatally will be present in the umbilical cord and breast milk.
Hence, it will also be present in the fetus and in breastfed infants. Absorption by the small intestine does not seem to vary by sex, genetic background, environmental factors, or other variables 46 , although specific studies are still needed to confirm this premise.
Peak concentrations are important because the effects of caffeine depend in part on the length of time it remains in tissues. Clearly, the effects are age dependent and depend on complex genetic and environmental interactions.
Caffeine is primarily metabolized in the liver by the cytochrome P oxidase enzyme system; in particular, by the CYP1A2 enzyme. However, this oxidase enzyme system is also present in other tissues, including the brain Caffeine metabolism is affected by several factors, described in detail below. At least single-nucleotide polymorphisms can accelerate caffeine clearance The metabolic consequences of this polymorphism on caffeine downstream effects should be studied in humans.
Genetic variation i. The half-life of caffeine may also be increased in liver diseases, which decreases P activity The molecular targets of caffeine, namely the adenosine receptors, also have great genetic variability. For example, common variants of the gene encoding for the A2a receptor can disrupt sleep 51 or cause anxiety in some individuals 52 after ingesting caffeine.
More studies are needed to determine the effects of genetic variants on the consequences of caffeine consumption 53 , not only in the central nervous system but also in other organs, such as the heart The expression of the cytochrome P epoxygenases is regulated in a circadian manner Although this effect was discovered in cultured rodent cells, it may apply to many species, including humans The implications are particularly important because the effects of caffeine at least the duration of its activity will differ during the circadian cycle.
Because caffeine can alter sleep, it may also change the circadian rhythm, leading to a change in expression patterns for the cytochrome P One interesting hypothesis is whether caffeine consumption in adolescents and adults disrupts the expression of P in relation to its circadian rhythm.
If the expression is downregulated, the effects of caffeine could be prolonged and produce a negative feedback loop. The cytochrome P oxidase enzyme system is the same enzyme that metabolizes steroid hormones Thus, steroid hormones slow caffeine metabolism. In women, this effect slows the metabolism of caffeine during pregnancy and when taking oral contraceptives However, studies have not found marked differences in caffeine metabolism between the luteal and follicular phases of the menstrual cycle 57 , Oral contraceptives tend to double the half-life of caffeine The half-life of caffeine is on average 8.
This longer half-life means that the effects of caffeine will be longer lasting in women and in the fetus. Given the effects that caffeine may have on brain development, this increased half-life in pregnant women should be taken into account when considering safety issues. Elimination is likely to be at least as slow in the fetus. Fetal exposure to caffeine during pregnancy may potentially have long-lasting effects, especially in the brain.
Cigarette smoking doubles the rate of caffeine clearance by increasing liver enzyme activity, which may explain the higher rate of caffeine consumption among smokers Substantial alcohol intake increases the half-life of caffeine and decreases its clearance Arrows indicate whether caffeine increases, decreases, or has no impact on the outcome and the number of arrows indicates the strength of the relationship.
Caffeine can influence objective and perceived cognitive performance by increasing alertness and wakefulness 66 — Acute caffeine can also improve performance on memory tasks 69 , Finally, caffeine improves psychomotor vigilance, such as reaction time 71 — The impact of caffeine appears to be greater under conditions that would negatively impact performance, such as acute caffeine withdrawal 74 — 76 or sleep deprivation 71 , In fact, studies that have employed long-term caffeine withdrawal methodology have consistently failed to find cognitive enhancing effects of acute caffeine 78 — Numerous preclinical studies have found that antagonizing adenosine receptors, including with caffeine, has neuroprotective effects during aging and in neurological disorders by slowing cognitive decline and the progression of the disorders [reviewed in Ref.
Based on these animal studies, several large longitudinal clinical studies in different countries have established an inverse relationship between coffee consumption and memory decline during normal aging 86 — However, a study of 4, women and 1, men reported that caffeine consumption reduced cognitive decline only in women In addition, a more recent study in a small group of women 89 failed to replicate the findings of the Ritchie study, demonstrating that more work is needed to understand the relationship between habitual caffeine consumption and cognitive performance.
Caffeine has long been used to treat pain. Since then, the vasoconstricting action of caffeine, secondary to adenosine receptor antagonism, has been associated with pain relief Several studies have reported that acute dietary caffeine consumption can reduce pain 98 , In general, acute intake of caffeine stimulates a modest increase in blood pressure both systolic and diastolic , effects on heart rate bradycardia or tachycardia, depending on dose , and neuroendocrine effects release of epinephrine, norepinephrine, and renin These effects suggest that the mechanism of action is an increase in intracellular calcium concentrations, the release of norepinephrine, and the sensitization of dopamine receptors.
These events may lead to supraventricular and ventricular tachyarrhythmias, especially at high doses. One proposed mechanism for caffeine-related cardiac arrhythmias is, again, the blockade of adenosine receptors , Patients with cardiac disease are often warned about the potential harmful effects of caffeine.
However, this advice has been based primarily on anecdote and folklore , Today, however, data suggest that caffeine does have cardiac effects, and arrhythmia is among them Moreover, effects that do exist differ by dose and between habitual and non-habitual users. This severity of these threats often depends on such factors as preexisting medical conditions as well as the quantity of the ingredients taken and the length of time a person has been exposed to these substances.
Many of the ingredients that include caffeine alone or in combination with other active substances have the potential to interact with prescription and over-the-counter medications. At typical caffeine doses, however, studies have documented mild changes in heart rate and blood pressure, a slight increase in sympathetic activity, and small changes in cardiac electrophysiological properties , — Caffeine is believed to improve endothelial cell function at rest by increasing intracellular calcium concentrations, which stimulates the expression of endothelial nitric oxide synthase, which in turn stimulates the endothelial cells to produce nitric oxide.
The nitric oxide then diffuses into vascular smooth muscle, which lies just underneath the endothelial cells, causing vasodilation Caffeine can also bind directly to the vascular smooth muscle cell receptors and, through similar mechanisms, cause vasoconstriction The above information not withstanding, consuming caffeine immediately before or during exercise can be harmful and may increase the risk for myocardial ischemia Indirect laboratory measures indicate that caffeine consumed immediately before exercising substantially reduces myocardial blood flow in healthy individuals Several mechanisms may explain this reduction , including the ability of caffeine to block adenosine receptors that modulate coronary vasomotor tone.
When caffeine blocks adenosine receptors, it reduces the ability of the coronary arteries to improve their flow commensurate with the increased myocardial demand of exercise, which could result in supply demand ischemia Seifert et al. National Poison Data System made between October 1, and September 30, related to caffeine exposure and energy drink consumption The overall incidence of moderate-to-major adverse effects of energy drink-related toxicity was The seven cases with major adverse effects consisted of three with seizure, two with non-ventricular dysrhythmia, one with ventricular dysrhythmia, and one with tachypnea.
Of the same 1, calls, concerned products containing caffeine only and concerned products with caffeine-containing additives, such as guarana a plant whose seeds are high in caffeine or taurine a naturally occurring organic acid often used as a nutritional supplement. The proportion of cases involving additives referred to a health-care facility was also significantly greater, as was the incidence of toxic effects of any severity.
One caveat to this study is that information on preexisting medical conditions was not available for the cases studied. Research in this area should attempt to include and account for preexisting health conditions. Researchers have also expressed concern about unintentional caffeine consumption and an increase in overconsumption of caffeinated energy drinks in children and young adults.
For example, Bronstein et al. A study of to year olds admitted to urban emergency rooms in the U. In March , 18 scientific and medical experts sent the FDA commissioner a report summarizing the research findings on energy drink consumption in children. Furthermore, the Institute of Medicine has recommended that drinks containing caffeine should not be sold to children at school Death from caffeine ingestion appears to be rare.
This rarity may be related, in part, to the marked gastric irritation from caffeine that results in spontaneous emesis. Nevertheless, several hospitalizations and some deaths from caffeine toxicity have been reported Most deaths after caffeine intoxication were caused by overdoses of diet pills and stimulants, and most have occurred in young patients without known underlying heart disease or any variant of normal, such as mitral valve prolapse.
In one non-fatal adverse event report, no predisposing factors or structural cardiac abnormality were associated with atrial fibrillation In this case, caffeine-induced atrial fibrillation spontaneously reverted to normal sinus rhythm. Caffeine consumption is associated with fertility indices in some studies but not in others. An extensive literature review by the Oak Ridge National Laboratory concluded that chronic caffeine intake in humans is related to adverse effects on conception and reproduction, such as delayed conception and decreased fecundity.
In addition, some researchers argue that any association between caffeine intake and reproductive outcomes may be explained by other variables, such as maternal smoking or substance use and that research should address confounding, as well as errors in measuring exposure Reports regarding caffeine consumption and spontaneous abortions have also been conflicting.
Weng et al. A meta-analysis by Chen et al. Similar findings were reported by Li et al. However, Savitz et al. This finding suggests that recall bias may explain the increased hazards of spontaneous abortion reported by Weng et al. No clear association has been found in humans between moderate doses of caffeine ingestion during pregnancy and birth defects, including congenital heart disease For example, the National Birth Defects Prevention Study found variable results for this possible association Other studies have found that the frequency of all congenital malformations, including congenital heart defects, was no higher than expected among women who drank between four and eight cups of coffee daily during their pregnancy , The consequences of caffeine consumption during pregnancy on offspring have recently been studied in mice Caffeine consumption by the dam the human equivalent of two to three cups of coffee per day was associated with caffeine concentrations in the offspring brain that were similar to those in the umbilical cords of women drinking two to three cups of coffee per day At early stages of development, specific types of neurons arise in particular brain regions and then migrate to their target areas.
As a result, these neurons were late at being incorporated into the circuitry, with negative consequences: pups were more susceptible to seizures, and in adulthood, in utero exposed mice had mild cognitive deficits. This study was the first to document that caffeine exposure during pregnancy could harm the offspring. Generalizing the results of animal studies to humans is always speculative, but these results strongly justify conducting prospective studies in humans.
Interestingly, in keeping with animal data, greater exposure to caffeine during pregnancy is associated with a lower IQ in children at age 5. This finding again supports the need for additional studies in humans. Several studies have reported a significant negative association between maternal caffeine consumption and birth weight 84 , 85 , — However, two other large prospective cohort studies reported a dose-dependent positive association between caffeine intake during pregnancy and the risk of adverse birth weight-related outcomes, such as fetal growth restriction and small for gestational age babies , In these studies, caffeine intake and adverse birth weight-related outcomes were found at all amounts of maternal caffeine intake.
Two separate meta-analyses of different sets of studies by Rhee et al. Another study by Hoyt et al. Taken together, these studies provide substantial evidence of a negative association between maternal caffeine consumption and infant birth weight.
Even so, the studies all relied on maternal self-report about caffeine intake; thus, the data may not be accurate. Furthermore, it is possible that additional variables, not controlled for in the analyses, could explain these relationships. For example, chronic sleep loss during pregnancy is also associated with poor birth outcomes, including low birth weight Thus, pregnant women with disrupted sleep might use more caffeine to increase alertness, so the impact on birth weight could be related to short sleep duration and not to caffeine.
Although this conclusion is speculative, it highlights the importance of considering additional variables when interpreting correlational data. Caffeine may cause irritability and sleep disruption in nursing infants whose mothers consume caffeine , but the findings are equivocal In addition, some evidence indicates that caffeine intake can reduce production of breast milk Mothers are often advised by their doctors to reduce or eliminate caffeine intake if they feel that their infant shows signs of caffeine sensitivity, but there is no evidence in the literature of detrimental effects of caffeine ingestion during lactation in the general population.
Few studies have examined the impact of maternal caffeine intake on outcomes after infancy. A study by Li et al. The above studies are correlational; thus, causation cannot be determined. In addition, the maternal caffeine intake in these studies was estimated based on self-reports. One potential explanation for the discrepancies described above is the method used to determine caffeine use. In the study by Klebanoff and Keim , , which found no significant relationship between maternal caffeine intake and outcomes after infancy, measured serum caffeine concentrations and did not use self-report , By contrast, the studies that found significant relationships between maternal intake and measures in the offspring after infancy relied exclusively on retrospective self-reports, several years after the fact, about prenatal caffeine consumption by mothers after they gave birth and during the first two trimesters of pregnancy, respectively.
Caffeine intake was estimated from food-frequency questionnaires or interviews in which women reported how often and how much they consumed coffee, tea, and soda. Other variables affecting self-reported caffeine consumption and offspring behavioral outcomes might explain these relationships, but in the study that relied entirely on serum concentrations, such variables were not identified.
These studies also measured different outcomes in the offspring. Klebanoff and Keim , had the most comprehensive battery of cognitive and behavioral outcomes, but Galera et al. Meaningful comparisons of studies are difficult when the methods for assessing caffeine intake and the outcomes are different.
Research with objective measures of caffeine intake and standard outcomes is needed. Most of the research examining linkages between caffeine and cancer has been conducted on coffee and tea and not on caffeine specifically, which makes it difficult to determine the mechanism. The International Agency for Research on Cancer has concluded that the evidence is insufficient to conclude that caffeine, as consumed by a typical coffee drinker, is carcinogenic Several large prospective trials have reached the same conclusion , , Furthermore, Nawrot et al.
In addition, caffeine intake of 4. However, these studies did not examine whether a decrease in caffeine intake was associated with improvements in overactive bladder symptoms. Studies should address this issue. According to www. Because of the popularity of caffeine, clinicians should be conscious of the pharmacokinetic interactions between dietary caffeine and over-the-counter and prescription medications, and they should provide the necessary guidance to the patient including dietary restrictions.
We also recommend that the potential interaction with these drugs be appropriately addressed on the labeling. Caffeine has a diuretic effect , , Similar studies should be conducted in populations that vary by health status, age, and sex. Pregnant women and fetuses may be particularly vulnerable to the effects of caffeine. Caffeine is a biologically active molecule that can act on multiple targets and affect numerous functions positively or negatively.
At early stages of fetal development, caffeine may have deleterious effects Many psychoactive compounds can cross the placental barrier and alter the development of the fetal brain. Once caffeine enters the fetal circulation, it is metabolized slowly because neither the placenta nor the fetus itself has cytochrome P, the enzyme that metabolizes caffeine This reduced caffeine metabolism results in a longer half-life and increased caffeine exposure to the fetus , This decline has been attributed to FDA warnings that excess caffeine consumption during pregnancy may adversely affect neonates Data on caffeine consumption during lactation are limited.
Young children may be vulnerable to the effects of caffeine because they weigh less. Thus, the physiological impact of a single soda in a child may be equivalent to the impact of two cups of coffee in an average-sized adult. Adolescents may also be particularly vulnerable to the sleep-disrupting effects of caffeine because they may also use caffeinated beverages to stay awake , Data have been collected in children and adolescents using dose—response and placebo-controlled research methods.
None of the results suggest that caffeine at these doses is acutely harmful to children and adolescents Some studies suggest an association between caffeine consumption and longer term behavioral problems in youth, such as anger, violence, sleep disturbances, and alcohol and drug use , In a study of 3, to year olds, self-reported caffeine intake was strongly associated with self-reported violent behavior and conduct disorders Other effects in these studies included nervousness, fidgeting, jitteriness, restlessness, hyperactivity, and sleeplessness , , When children were stratified by prestudy caffeine intake, emotions and behaviors differed between low- and high-dose consumers , Children consuming high doses were more easily frustrated and were more nervous during baseline tests than were the children consuming lower doses.
The consumption of highly caffeinated energy drinks has been associated with elevated blood pressure, altered heart rates, and severe cardiac events in children, adolescents, and young adults, especially those with underlying cardiovascular diseases , , , These findings show how the acute effects of caffeine on heart rate might result in cardiovascular events requiring hospitalization, especially in at-risk young adults.
High doses of caffeine may exacerbate cardiac conditions for which stimulants are contraindicated — In particular, ion channelopathies and hypertrophic cardiomyopathy, which is the most prevalent genetic cardiomyopathy in children and young adults 0.
Another population that may be at risk for adverse effects of caffeine are patients with mental illness. Caffeine antagonism of adenosine receptors can result in enhanced dopaminergic signaling, thought to be due to a combination of increased dopamine release , , upregulation of dopamine receptors, and increased affinity of dopamine receptors for dopamine in the striatum and nucleus accumbens Furthermore, adenosine receptors can form heterodimers with dopamine receptors , which can modulate dopamine signaling.
For other mental illness, such as schizophrenia, caffeine may exacerbate psychotic symptoms , although the majority of this literature is informed by case studies, with very few double-blind placebo-controlled studies There is also good evidence that higher caffeine use is associated with greater reporting of anxiety symptoms , and may increase risk of symptom relapse and suicide among bipolar disorder patients Finally, there is strong empirical evidence that caffeine potentiates the rewarding effects of drugs of abuse — , which suggests that caffeine use can increase vulnerability to substance use disorder The lack of randomized control trials on the impact of caffeine in patients with mental illness makes it difficult to determine safe doses, effects of acute and chronic caffeine, and potential interactions between caffeine and medications.
Currently, there are no specific recommendations for caffeine consumption for individuals with mental or psychiatric illness, but it may be worth consideration by physicians and psychologists treating patients with mental illness. Another increasingly popular form of caffeine consumption is to mix alcohol with energy drinks. In fact, there are several recent reviews on this topic — We will briefly highlight this literature here.
In , the FDA removed pre-mixed alcohol-energy drinks from the market because caffeine was determined to be an unsafe additive to alcohol, 4 in part because it promoted excessive drinking However, energy drinks can be legally mixed with alcohol in the U.
The research on alcohol-mixed energy drinks is still developing, and the vast majority has been conducted in the U. Much of this research consists of surveys of college-age young adults immediately after they leave bars where they have been drinking — Self-report is often unreliable, but self-report while intoxicated may be particularly problematic. Similarly, intoxication may confound retrospective assessments of alcohol consumption and related behaviors and attitudes.
More recently, several well-controlled, objective, laboratory-based studies on the impact of alcohol-mixed energy drinks have been conducted. In many studies, the combination of alcohol and energy drinks results in higher rates of binge drinking, reductions in perceived intoxication, faster rates of self-paced alcohol consumption, or increases in risk taking behavior , — These data are equivocal, however, with studies showing that caffeine combined with alcohol does not always increase the amount of alcohol consumed or does not have an impact on risk taking behavior , Potential reasons for these discrepancies may be difference in the doses of caffeine and alcohol, differences in the administration paradigm, and an influence of expectancy of caffeine effects on alcohol intoxication More work is needed in this area to be able to draw stronger conclusions.
Caffeine-related disorder not otherwise specified classifies symptoms related to caffeine use or withdrawal that do not fit into the aforementioned categories.
The latest edition of the DSM has officially recognized caffeine withdrawal disorder and outlines guidelines for criteria for caffeine use disorder in a section on emerging measures and models The diagnosis of caffeine withdrawal syndrome is empirically based on detailed analyses of decades of studies of symptoms [reviewed by Juliano and Griffiths ].
Caffeine withdrawal disorder is diagnosed when an individual experiences clinically significant impairment related to withdrawal symptoms after abrupt cessation of caffeine intake, including headache, difficulty concentrating, fatigue, nausea, flu-like symptoms, and changes in mood.
Ongoing research on caffeine withdrawal suggests that this continues to be an important problem and will help refine and clarify this diagnosis , Avoidance of caffeine withdrawal, with or without a diagnosis of caffeine withdrawal disorder, may motivate individuals to consume more caffeine.
This could result in chronic, excessive consumption of caffeine. When this excess consumption results in clinically significant impairment, an individual may meet the criteria for caffeine use disorder — Having these proposed criteria outlined will allow researchers to collect data to provide reliable and valid empirical studies of the prevalence of this phenomenon This is critical because the progression of inclusion of caffeine-related diagnoses is directly related to an increase in empirical support for such disorders.
Recommended safety thresholds vary, however. However, the recommended intake is much lower for pregnant or nursing mothers. For most children, adolescents, and young adults, safe levels of caffeine consumption have not been established. Because deleterious effects of heavy caffeine use have been documented in those who have cardiovascular issues, studies of safe doses and the effects of chronic use are paramount in understanding the implications of caffeine.
This research should seek to better characterize the effects of caffeine use before, during, and after exercise, the interactions of caffeine use with alcohol and medications, such as stimulants, and the effects of prolonged caffeine use. Such information will also help health-care leaders to work with families, schools, and other community services to change marketing strategies, improve the dissemination of information, and identify at-risk behaviors and age groups.
Finally, the health-care providers and regulatory agencies must begin collecting and archiving better data on the adverse events and health effects of caffeine consumption to improve estimates about its scope, effects, and outcomes. Analyses of a comprehensive, centralized database would help direct research, education, and funding to support these populations.
In addition, agencies like the U. FDA and Health Canada need to initiate programs to educate consumers, especially children and adolescents, about the dangers of highly caffeinated products, to reconsider applying the U. Because of the potentially harmful adverse effects and developmental effects of caffeine, the consensus among the research and medical communities is that any dietary intake of caffeinated energy drinks should be discouraged for all children , Due to the potentially harmful health effects of caffeine, dietary intake should be discouraged for all children.
Because the actual stimulant content of energy drinks is hard to determine, energy drinks pose an even greater health risk than simple caffeine. Therefore, energy drinks are not appropriate for children and adolescents and should never be consumed In , Health Canada convened an Expert Panel 6 on Caffeinated Energy Drinks to develop a plan to more effectively address the safety concerns related to caffeinated energy drinks currently marketed in Canada.
The Panel issued their recommendations to Health Canada in the fall of Components of this approach include regulating product formulation and labeling, addressing potential health risks and adverse effects, providing enhanced education and communication to consumers, and addressing uncertainties and data gaps through research on long-term effects. Long-term research was made a priority, to further investigate risks to consumers, to identify serious adverse event signals such as cardiac events and to a lesser extent, seizures , and finally to better manage caffeine labeling and dosing limits.
However, the data show that women of childbearing age and children may be at higher risk from caffeine, which has therefore led to separate guidelines for these at-risk groups. However, several products containing stimulant drugs do not have a natural health product license and exemption numbers that clearly describe their caffeine content. Therefore, the Panel recommended that Health Canada ensure that all products meet strict labeling that includes a full disclosure of the exact caffeine dose.
Finally, the Panel recommended that Health Canada, in collaboration with the provinces and territories, consider beginning a surveillance system in sentinel emergency rooms across the country to actively search for serious adverse drug reactions associated with consuming drinks containing stimulant drugs with or without alcohol or other products.
A similar database, The Canadian Health Measures Survey, 8 launched in , contains data from voluntary household interviews that collects important health information e. Several questions remain about caffeine consumption and patterns of intake. These sources are often overlooked in large national surveys and, thus, caffeine intake may be underestimated. Second, caffeine may be indirectly harmful because it is consumed with other substances that are harmful.
For example, coffee drinking may promote donut eating or cigarette smoking, or energy drink consumption may promote alcohol intake. Third, future studies need to investigate absorption, distribution, metabolism, and excretion of caffeine occurring in non-natural forms such as encapsulated forms , which may influence pharmacokinetics, and thus effects.
Finally, most research has relied on self-report and correlational analysis, which limits the ability to determine causality and directionality. Despite all that is known about caffeine intake and safety of caffeine consumption, certain gaps in our knowledge need to be addressed:. Identifying at-risk populations for caffeine toxicity. We already know that small children and pregnant women, as well as individuals with cardiac or vascular disease, are likely to be particularly vulnerable to the harmful effects of caffeine.
Furthermore, there is some evidence that individuals with mental illness may also be at risk for harmful effects of caffeine on symptoms, but the majority of these relationships have been described in case studies.
More randomized control trials need to be conducted in patients with mental illness to determine safe doses for caffeine ingestion. In addition to the known vulnerable populations, there may be individuals, such as the elderly or individuals with underlying medical conditions, who are not part of any vulnerable population but who, for genetic or metabolic reasons, may be susceptible to harmful effects.
The Federal Substance Abuse and Mental Health Services Administration reported that from to , the number of emergency room visits involving energy drinks doubled across the U. Identifying and warning at-risk individuals to avoid caffeine-containing products would be desirable. Determining how best to disseminate information about caffeine content in a meaningful and truthful way without causing alarm. Although the preponderance of evidence suggests that caffeine is safe for most people, there may be reasons to limit caffeine use in some populations.
Providing more information about safe levels may be useful, but the information must be understandable to the population and based on evidence, rather than on supposition. Adding information about caffeine content on the products themselves may not be enough. The best way to educate consumers about safe levels of caffeine consumption needs to be determined. Conducting prospective, longitudinal studies to determine how caffeine use relates to behavioral and health-related outcomes , such as the duration and quality of sleep, potential for abuse, and impact on the use of other substances, including controlled cigarettes and e-cigarettes and uncontrolled marijuana, cocaine drugs.
Cross-sectional data suggest that caffeine use is generally safe, but rigorous longitudinal studies have not yet determined the effect of chronic caffeine consumption on development in children and adolescents. Further exploring the potential health benefits of caffeine. Although much of this document has focused on potential harmful effects of caffeine, some health benefits of caffeine remain under explored. In particular, some research suggests that caffeine may slow age-related cognitive decline , , reduce risk of some neurological disorders 90 , , , and promote longevity Developing better systems of documenting and sharing adverse events.
In addition to identifying at-risk or vulnerable populations, as mentioned earlier, and potentially dangerous combinations of caffeine with other substances e. Systematically collecting all adverse events, poison center data, and emergency room visits associated with caffeine consumption for example, energy drink consumption , together with more comprehensive evaluation of additional risk factors, is necessary to accurately determine the risks of toxicity for youth and other vulnerable individuals.
Improving knowledge of the potential dangers from consuming energy drinks before, during, and after athletic activity will be essential to identify the potential dangers of direct and implied claims of enhanced athletic performance, which is common in energy drink marketing. Long-term systematic assessment of energy drink and general caffeine intake at the population level, specifically intake by youth, should be a priority.
When taken together, the literature reviewed here suggests that ingested caffeine is relatively safe at doses typically found in commercially available foods and beverages. There are some trends in caffeine consumption, such as alcohol-mixed energy drinks, that may increase risk of harm. There are also some populations, such as pregnant women, children, and individuals with mental illness, who may also be considered vulnerable for harmful effects of caffeine.
Excess caffeine consumption is increasingly being recognized by health-care professionals and by regulatory agencies as potentially harmful. More research needs to be conducted to address these emerging concerns and provide empirical support for the recommendations.
JC, JW, and MM helped gather additional references and prepare the manuscript after the initial major review of the literature was conducted. The authors prepared this comprehensive review at the request of the American Association for the Advancement of Science.
Once the draft was completed, we were given permission to publish the manuscript. SL has served as an expert for legal cases involving caffeine-containing energy drinks. Because of this, only absolute caffeine intake is shown in this section.
National Center for Biotechnology Information , U. Journal List Front Psychiatry v. Front Psychiatry. Published online May Jennifer L. Czachor , 4 Joslyn A. Westphal , 4 and Miriam A. Mestre 4.
Steven E. Jason D. Joslyn A. Miriam A. Author information Article notes Copyright and License information Disclaimer. Temple, ude. Specialty section: This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry. Received Jan 30; Accepted Apr The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these terms. This article has been cited by other articles in PMC. Abstract Caffeine is the most widely consumed psychoactive drug in the world. Keywords: caffeine, energy drinks, pregnancy, children, adolescence. Introduction Caffeine is the most widely consumed psychoactive drug in the world 1 and one of the most comprehensively studied ingredients in the food supply.
Dietary Sources of Caffeine Adults commonly consume caffeine in coffee and tea, both of which contain natural caffeine in their leaves or beans 6. Trends in Caffeine Consumption Trends in caffeine consumption have been stable among adults for the past two decades 6. The Pharmacokinetics of Caffeine Caffeine works by binding to adenosine receptors located in the central and peripheral nervous systems as well as in various organs, such as the heart, and blood vessels. Absorption and Metabolism Caffeine is usually ingested.
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