case study on coffee addiction

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Coffee Addiction BIOLOGY INVESTIGATORY PROJECT 2019-20

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BackgroundAlcoholics Anonymous (AA) members represent an important and relatively understudied population for improving our understanding of alcohol dependence recovery since over one million Americans participate in the program. Further insight into coffee and cigarette use by these individuals is necessary given AA members’ apparent widespread consumption and the recognized health consequences and psychopharmacological actions of these substances.MethodsVolunteers were sought from all open-AA meetings in Nashville, TN during the summer of 2007 to complete a questionnaire (n=289, completion rate=94.1%) including timeline followback for coffee, cigarette, and alcohol consumption; the Alcoholics Anonymous Affiliation Scale; coffee consumption and effects questions; the Fagerstrom Test for Nicotine Dependence (FTND); and the Smoking Effects Questionnaire.ResultsMean (±SD) age of onset of alcohol consumption was 15.4±4.2 years and mean lifetime alcohol consumption was 1026.0±772.8 kg ethanol. Median declared alcohol abstinence was 2.1 years (range: 0 days–41.1 years) and median lifetime AA attendance was 1000.0 meetings (range: 4–44209 meetings); average AA affiliation score was 7.6±1.5. Most (88.5%) individuals consumed coffee and approximately 33% of coffee consumers drank more than four cups per day (M=3.9±3.9). The most common self-reported reasons for coffee consumption and coffee-associated behavioral changes were related to stimulatory effects. More than half (56.9%) of individuals in AA smoked cigarettes. Of those who smoked, 78.7% consumed at least half a pack of cigarettes per day (M=21.8±12.3). Smokers’ FTND scores were 5.8±2.4; over 60% of smokers were highly or very highly dependent. Reduced negative affect was the most important subjective effect of smoking.ConclusionsA greater proportion of AA participants drink coffee and smoke cigarettes in larger per capita amounts than observed in general US populations. The effects of these products as described by AA participants suggest significant stimulation and negative affect reduction. Fundamental knowledge of the quantitative and qualitative aspects of coffee and cigarette consumption among AA members will enable future research to discern their impact on alcohol abstinence and recovery.

Caffeine Addiction Symptoms and Withdrawal

Daniel B. Block, MD, is an award-winning, board-certified psychiatrist who operates a private practice in Pennsylvania.

What Is Caffeine Addiction?

• Caffeine Adverse Effects
• Caffeine Withdrawal
• Other Similar Disorders
• Are You Addicted to Caffeine?
• How to Cope

Caffeine addiction is the excessive and harmful use of caffeine over a period of time, such that it has negative effects on your health, social interactions, or other areas of your life.

Coffee and other caffeinated products can create a physical dependence, leading to chemical changes in the brain. Daily consumption can quickly lead to a caffeine addiction, characterized by cravings and withdrawal symptoms if intake is reduced or ceased.

According to the Centers for Disease Control and Prevention (CDC), approximately 80% of Americans consume caffeine daily.

To be clear, caffeine has been associated with many positive side effects. Research has connected this plant-derived stimulant to improved mood , relief from headaches , and perhaps a reduced risk of other major medical issues such as strokes , Parkinson's, and Alzheimer's . Large studies that tracked people over time found that coffee drinkers were less likely to die during follow-up.

Yet, some people experience negative issues due to caffeine use or have difficulty coping without caffeine. Though rare, there have even been cases of caffeine overdose.

Caffeine affects the brain's reward system, which triggers the release of a chemical called dopamine. Dopamine causes people to feel good, creating a reward cycle that motivates them to keep consuming it and experiencing that same level of reinforcement.

It also causes physiological dependence, which means that when you reduce or stop your caffeine intake, you will likely experience withdrawal symptoms like tiredness, headaches, and irritability .

When you have a caffeine addiction, it means that your caffeine use negatively disrupts your life, yet you're unable to stop consuming it. Or you consume it in amounts that are potentially dangerous to your health despite knowing that it may harm you mentally or physically.

Caffeine is the most widely used drug worldwide. Coffee and soda are the top caffeine sources in the United States, whereas African and Asian countries consume them in soda and tea . Caffeine is also present in many common foods (almost anything with chocolate ), making it easy to over-consume.

While caffeinated products like coffee, soda, and energy drinks are less reinforcing than other addictive substances, that does not mean they don't have potential adverse health effects.

Symptoms of Caffeine Addiction

Although caffeine addiction is not a formally recognized condition in the " Diagnostic and Statistical Manual of Mental Disorders (DSM-5) ," a manual used by clinicians to classify and diagnose mental health concerns, the publication mentions some caffeine-related issues, such as intoxication and withdrawal.

Caffeine intoxication, caffeine withdrawal, caffeine-induced anxiety disorder, and caffeine-induced sleep disorder are all recognized in the "DSM-5," and caffeine use disorder has been identified as requiring further study.

As caffeine is a stimulant, consuming too much can cause a cluster of symptoms associated with brain and nervous system stimulation. These symptoms include:

• Feeling shaky
• Increased blood pressure
• Nervousness
• Racing heart, or other heartbeat abnormalities
• Sleep issues

This type of addiction can even overlap with work addiction , as some people use the stimulating effects of this substance to perform better at their job mentally and/or physically.

As with all addictions, the pleasurable effects of caffeine can also sometimes mask other issues. Lack of energy and depression may underlie caffeine addiction. People may rely on caffeine to compensate for sleep disorders.

How Caffeine Can Negatively Affect Your Health

Caffeine has various effects on the body that are potentially harmful to your health. Caffeine has been associated with increased blood pressure and heart rhythm changes.

Some caffeinated products, such as coffee and soda, can cause gastrointestinal disturbances.

There is also a question of whether caffeine might increase your risk of osteoporosis. One study found this to be the case for women in menopause with high caffeine intake.

Caffeine can also decrease your health by disturbing your sleep if consumed within six hours of bedtime.

When you are sleep deprived, it makes it harder to function efficiently during the day. Sleep is also when your body heals, making it essential for total health and immune function.

Excessive caffeine intake can also have an impact on mental health. Increased anxiety can occur, particularly in those sensitive to caffeine's effects or who have a previously existing anxiety disorder. 

Some research has shown that caffeine may be linked to symptoms of psychosis and mania in people who have psychotic disorders or mood conditions.

Symptoms of Caffeine Withdrawal

Just as taking in too much caffeine can present issues, so can suddenly removing it from your diet. This can result in caffeine withdrawal , which produces symptoms that are the opposite of consuming too much. This effect can be especially profound in people who are addicted to caffeine.

The symptom most often noticed by people going through caffeine withdrawal is a headache, which may range from mild to severe.

Other symptoms associated with trying to cut back your caffeine habit or missing your daily "dose" are:

• Feeling tired or sleepy
• Reduced mental alertness
• Slower reaction times
• Worsened performance on memory tasks

Occasionally, people withdrawing from caffeine also experience flu-like symptoms, such as nausea as well as mood changes.

How Long Does Caffeine Withdrawal Last?

Symptoms of caffeine withdrawal typically start around 12 to 24 hours after your last caffeine dose. You may experience these symptoms for between two to nine days.

7 Quick Tips to Help with Caffeine Withdrawal

Caffeine addiction and other conditions.

The stimulating effects of caffeine can sometimes cause physical symptoms and behaviors that look and feel like—and therefore be easily confused with—other disorders. Therefore, it is important to let your doctor or mental health clinicians know how much caffeine you are consuming if you are being assessed for any condition.

Anxiety Disorders

For example, caffeine intoxication produces symptoms that can easily be confused with anxiety disorders , such as panic attacks. Too much caffeine can also worsen symptoms of these disorders by intensifying feelings of worry, causing racing thoughts, increasing heart rate, and preventing relaxation and good-quality sleep.

Other Conditions

People who are overstimulated with caffeine can also exhibit symptoms consistent with attention deficit disorders . Conversely, caffeine withdrawal shares similar symptoms with mood disorders . Other health concerns that can be confused with caffeine intoxication include:

• Manic episodes
• Panic disorder
• Generalized anxiety disorder
• Sleep disorders
• Migraine and other headaches
• Viral illnesses
• Sinus conditions
• Medication-induced side effects, such as akathisia or an inability to stay still

Substance Use

It can also be mistaken for and worsen symptoms of withdrawal from other substances, such as amphetamines  and cocaine . Stimulant drugs such as these are often cut with caffeine, increasing the likelihood that caffeine withdrawal is involved in withdrawal from these drugs.

Caffeine Can Induce Other Disorders

Some disorders are triggered by the use of caffeine. Examples of these types of disorders include caffeine-induced anxiety disorder and caffeine-induced sleep disorder.

Do You Have a Caffeine Addiction?

If you suspect that you are addicted to caffeine, such as if you have a coffee addiction, it is essential to take stock of your situation. Assessing your intake, the impact, and how you feel can help you better determine if you need to cut back.

Addiction involves excessive use of caffeine and relying on this stimulant to better cope with life despite any adverse effects you may be experiencing. To figure out whether you might be addicted, it helps to:

Assess Your Intake

Calculate how much caffeine you are consuming on a typical day. Remember that gourmet espresso, lattes, and cappuccino typically contain more caffeine than regular drip or instant coffee, soda, and other common caffeine-containing foods and drinks. Therefore, this should be accounted for when determining your normal intake.

Pay Attention to How You Feel

Make a note of any side effects you experience after consuming caffeine. Also, note any adverse effects you feel if you lower your normal intake or skip caffeine entirely. Pay attention to both mental and physical effects for a more complete picture of how you are impacted by its use.

Consider How Caffeine Affects Your Life

Think about your caffeine habit and how it affects your life as a whole. Do your relationships suffer if you don't get your morning coffee, for instance? Could your caffeine intake be contributing to your work anxiety ?

If you or a loved one are struggling with substance use or addiction, contact the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information on support and treatment facilities in your area.

For more mental health resources, see our National Helpline Database .

Coping With a Caffeine Addiction

Caffeine addiction is so common that we don't even notice it most of the time. But when you can greatly reduce or quit caffeine to reduce the adverse effects it is having on you, you may find it easier to get back in touch with your own natural energy and can relax when night falls.

If you consume more caffeine than is healthy, you can reduce your caffeine intake or cut it out completely.

If your responses to caffeine (or a lack of caffeine) affect you negatively, speak to your healthcare provider. Similarly, if you have another health condition that might be impacted by caffeine use, such as heart disease, or even if you are pregnant or breastfeeding, discuss options with your doctor immediately.

Make a Plan to Cut Back or Quit

The vicious cycle of addiction is often the same with caffeine as with other addictive substances. As the effects of the caffeine begin to wear off, you might feel a crash in energy and that you can't keep going without another boost. Your doctor can help you move past this without giving in.

Gradually Lower Your Caffeine Intake

Since stopping "cold turkey" can make you feel worse, most people need to reduce caffeine intake gradually rather than abruptly. Your doctor can help you devise a suitable plan based on your typical caffeine consumption. This can help reduce or eliminate any withdrawal effects.

How to Taper Your Caffeine Dose

Instead of cutting your caffeine intake abruptly, try reducing your regular intake by about 10% every two weeks. One way to do this is to reduce the strength of your caffeinated drinks by diluting them with a decaffeinated version.

Find Ways to Manage Withdrawal Symptoms

Withdrawal symptoms such as headache and fatigue may leave you wanting to reach for a cup of coffee or a can of soda, so finding ways to cope with these symptoms is essential. Consider using over-the-counter pain medications like Tylenol or ibuprofen to relieve headache symptoms. Other strategies that can help include:

• Getting enough sleep
• Drinking plenty of water
• Finding ways to stay busy
• Engaging in physical exercise to boost energy levels

Seek Help for Mental Health Symptoms

If you feel you are using caffeine to cope with an emotional problem, such as depression or anxiety , talk to your physician about treatment options. The right treatment could make a huge difference for you.

Caffeine addiction often overlaps with other behavioral addictions, such as sugar addiction . So, you might find that evaluating your caffeine intake also identifies other behaviors that need to be addressed.

Caffeine is a stimulant often consumed daily in many forms, including coffee, soda, tea, energy drinks, and chocolate. Low or moderate amounts are safe and may even have certain health benefits. Excessive intake, however, can adversely affect health and lead to caffeine addiction.

If you think you have a coffee addiction or that you are consuming too much caffeine, gradually lowering your intake can help you get control of your caffeine habit. 

Centers for Disease Control and Prevention. Caffeine and long work hours .

Nehlig A. Effects of coffee/caffeine on brain health and disease: What should I tell my patients? Pract Neurol . 2016;16(2):89-95. doi:10.1136/practneurol-2015-001162

Freedman N, Park Y, Abnet C, Hollenbeck A, Sinha R. Association of coffee drinking with total and cause-specific mortalitiy . N Engl J Med . 2012;366(20):1891-1904. doi:10.1056/NEJMoa1112010

Reyes C, Cornelis M. Caffeine in the diet: Country-level consumption and guidelines . Nutrients . 2018;10(11):1772. doi:10.3390/nu10111772

Addicott MA. Caffeine use disorder: A review of the evidence and future implications .  Curr Addict Rep . 2014;1(3):186-192. doi:10.1007/s40429-014-0024-9

Sweeney MM, Weaver DC, Vincent KB, Arria AM, Griffiths RR. Prevalence and correlates of caffeine use disorder symptoms among a united states sample . Journal of Caffeine and Adenosine Research . 2020;10(1):4-11. doi:10.1089/caff.2019.0020

Bodar V, Chen J, Gaziano JM, Albert C, Djoussé L. Coffee consumption and risk of atrial fibrillation in the Physicians' Health Study . J Am Heart Assoc . 2019;8(15):e011346. doi:10.1161/JAHA.118.011346

Temple JL, Bernard C, Lipshultz SE, Czachor JD, Westphal JA, Mestre MA. The safety of ingested caffeine: A comprehensive review .  Front Psychiatry . 2017;8:80. doi:10.3389/fpsyt.2017.00080

Costa A, Neto da Silva M, Brito L, et al. Osteoporosis in primary care: An opportunity to approach risk factors . Braz J Rheumat . 2016;56(2):111-116. doi:10.1016/j.rbre.2015.07.014

Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed . J Clin Sleep Med . 2013;9(11). doi:10.5664/jcsm.3170

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Lin YS, Weibel J, Landolt HP, et al. Time to recover from daily caffeine intake .  Front Nutr . 2022;8:787225. doi:10.3389/fnut.2021.787225

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National Institute of Mental Health. Depression basics .

By Elizabeth Hartney, BSc, MSc, MA, PhD Elizabeth Hartney, BSc, MSc, MA, PhD is a psychologist, professor, and Director of the Centre for Health Leadership and Research at Royal Roads University, Canada.  

The Case for Coffee: All the Latest Research to Defend Your Caffeine Addiction, in One Place

What we know about coffee's benefits so far, distilled

puuikibeach/Flickr

These days, coffee is practically a universal part of our modern workplace condition. Many of us harbor some secret fear that the gallons of brown liquid we're slurping every day is doing us no good. We cling to scraps of evidence -- like this one suggesting coffee contributes to your daily recommended fluid intake -- showing that coffee in superhuman amounts is safe. And we pour ourselves another when a new study comes out implying the stuff can make us even healthier than we already are.

Lately, coffee addicts have been winning little victories every few weeks. This time, it's a double win: a pair of studies suggesting that something about the drink may contain anti-aging and cancer-fighting properties.

One study , presented last week to the Society for Experimental Biology, appears to show an appreciable benefit in the muscle strength of mice who've been given caffeine. Researchers from Coventry University examined two main muscles -- the diaphragm and a key leg muscle called the extensor digitorum longus -- in their test animals before and after the treatment. They noticed a strong link between caffeine intake and better muscle performance among adult mice, with a somewhat weaker relationship for elderly subjects and a small, though still measurable, effect on juvenile mice. The scientists say their findings could be significant for people heading into their golden years, as muscles tend to weaken with age -- increasing the likelihood of trips, falls and other mishaps. Who wouldn't want to be able to maintain their muscle tone by sipping a cup of joe every morning?

The second of the two studies suggests that a moderate intake of caffeinated coffee is associated with a decreased risk for a common skin cancer, basal cell carcinoma. Looking at two large databases of men and women, Harvard researcher Jiali Han found that roughly 20 percent of nearly 113,000 study subjects developed basal cell carcinoma over two decades of follow-up. Among the participants, there was an inverse relationship between those who ate or drank caffeinated foods or beverages (coffee, tea, chocolate, etc.) and their risk for the cancer. Seemingly reinforcing the favorable finding for caffeine, decaf items seemed to have no link to basal cell carcinoma. Unfortunately, neither caffeine nor coffee had any bearing on two other forms of skin cancer studied, squamous cell carcinoma and melanoma.

The new results join a litany of fantastic recent findings in coffee research. Here's a quick roundup: The National Institutes of Health made a splash in May this year when their research noted a relationship between coffee consumption and a decreased risk for mortality:

Coffee-drinking men cut their risk for death by 12 percent after four to five cups of java, according to the study, which was led by the National Institutes of Health's Neal Freedman. Women who drank the same amount had their the risk of death reduced by 16 percent.

The report sparked some confusion, too, as coffee drinkers were also puzzlingly more -- yes, more -- likely to die. The reason? Coffee drinkers are also generally smokers. How can coffee drinkers can be both more and less likely to die seems like an arithmetic mystery -- but cut out smoking altogether, and the correlation between coffee and longer lives still stands. The lesson there may simply be to drink coffee and quit smoking.

We've also learned that coffee can  protect your heart , reduce the risk of  prostate and breast cancer , and  curb the risk of fibrosis among those with fatty liver disease. The research even extends to the bustling, steamy shops from which we procure our daily java fix: studies show being surrounded by a moderate amount of noise can actually  make you more creative .

With the evidence mounting in favor of coffee, it's hard not to pump your fist and declare your daily four-shot latte justified. True enough, it's worth remembering that most of these studies show correlations at best, and some of them don't even involve humans. The case for coffee isn't exactly slam-dunk for sure -- but then again, science never is.

Did we miss a piece of key research? Let us know in the comments.

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Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes

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This article has a correction. Please see:

• Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes - January 12, 2018
• Robin Poole , specialty registrar in public health 1 ,
• Oliver J Kennedy , graduate medical student 1 ,
• Paul Roderick , professor of public health 1 ,
• Jonathan A Fallowfield , NHS Research Scotland senior clinical fellow 2 ,
• Peter C Hayes , professor of hepatology 2 ,
• Julie Parkes , associate professor of public health 1
• 1 Academic Unit of Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, South Academic Block, Southampton General Hospital, Southampton, Hampshire SO16 6YD, UK
• 2 Medical Research Council/University of Edinburgh Centre for Inflammation Research, Queen’s Medical Research Institute, Edinburgh, EH16 4TJ, UK
• Correspondence to: R Poole r.poole{at}soton.ac.uk
• Accepted 16 October 2017

Objectives  To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes.

Design  Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome.

Data sources  PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references.

Eligibility criteria for selecting studies  Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded.

Results  The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83, 95% confidence interval 0.83 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions. Harmful associations were largely nullified by adequate adjustment for smoking, except in pregnancy, where high versus low/no consumption was associated with low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and second (1.12, 1.02 to 1.22) trimester, and pregnancy loss (1.46, 1.06 to 1.99). There was also an association between coffee drinking and risk of fracture in women but not in men.

Conclusion  Coffee consumption seems generally safe within usual levels of intake, with summary estimates indicating largest risk reduction for various health outcomes at three to four cups a day, and more likely to benefit health than harm. Robust randomised controlled trials are needed to understand whether the observed associations are causal. Importantly, outside of pregnancy, existing evidence suggests that coffee could be tested as an intervention without significant risk of causing harm. Women at increased risk of fracture should possibly be excluded.

Introduction

Coffee is one of the most commonly consumed beverages worldwide. 1 As such, even small individual health effects could be important on a population scale. There have been mixed conclusions as to whether coffee consumption is beneficial or harmful to health, and this varies between outcomes. 2 Roasted coffee is a complex mixture of over 1000 bioactive compounds, 3 some with potentially therapeutic antioxidant, anti-inflammatory, antifibrotic, or anticancer effects that provide biological plausibility for recent epidemiological associations. Key active compounds include caffeine, chlorogenic acids, and the diterpenes, cafestol and kahweol. The biochemistry of coffee has been documented extensively elsewhere. 4 Coffee undergoes a chemical metamorphosis from the unroasted green bean, and the type of bean (Arabica versus Robusta), degree of roasting, and preparation method including coffee grind setting and brew type, will all have an influence on the biochemical composition of the final cup. 5 6 7 An individual’s genotype and gut microbiome will then determine the bioavailability and type of coffee metabolites to which that individual is exposed. 8

Existing research has explored the associations between coffee as an exposure and a range of outcomes including all cause mortality, cancer, and diseases of the cardiovascular, metabolic, neurological, musculoskeletal, gastrointestinal, and liver systems, as well as outcomes associated with pregnancy. Most of this research has been observational in design, relying on evidence from cross sectional, case-control, or cohort studies, and often summarised by outcome through systematic review and meta-analysis. We have previously explored the relation between coffee consumption and liver cirrhosis 9 and hepatocellular carcinoma 10 and found significant beneficial associations for both. Observational evidence can suggest association but is unable to make causative claims, though methods based on Mendelian randomisation are less prone to confounding. Interventional research, ideally in the form of randomised controlled trials, is essential before we can fully understand coffee’s potential to prevent specific health outcomes.

Before an interventional approach is taken, however, it is important to systematically assess the totality of higher level evidence of the effects of coffee consumption on all health outcomes. This approach can help contextualise the magnitude of the association across health outcomes and importantly assess the existing research for any harm that could be associated with increased consumption. To assimilate the vast amount of research available on coffee consumption and health outcomes, we performed an umbrella review of existing meta-analyses.

Umbrella review methods

Umbrella reviews systematically search, organise, and evaluate existing evidence from multiple systematic reviews and/or meta-analyses on all health outcomes associated with a particular exposure. 11 We conducted a review of coffee consumption and multiple health outcomes by systematically searching for meta-analyses in which coffee consumption was all or part of the exposure of interest or where coffee consumption had been part of a subgroup analysis. Consumption, usually measured by cups a day, lends itself to combined estimates of effect in meta-analyses and we decided to include only meta-analyses in the umbrella review. Specifically, we excluded systematic reviews without meta-analysis.

Literature search

We searched PubMed, Embase, CINAHL, and the Cochrane Database of Systematic Reviews from inception to July 2017 for meta-analyses of observational or interventional studies that investigated the association between coffee consumption and any health outcome. We used the following search strategy: (coffee OR caffeine) AND (systematic review OR meta-analysis) using truncated terms for all fields, and following the SIGN guidance recommended search terms for systematic reviews and meta-analyses. 12 Two researchers (RP and OJK) independently screened the titles and abstracts and selected articles for full text review. They then independently reviewed full text articles for eligibility. A third researcher, PR, arbitrated any differences that could not be resolved by consensus. We also performed a manual search of the references of eligible articles.

Eligibility criteria and data extraction

Articles were eligible if they were meta-analyses and had been conducted with systematic methods. We included meta-analyses of both observational (cohort, case-control, and cross sectional with binary outcomes) and interventional studies (randomised controlled trials). Meta-analyses were included when they pooled any combination of relative risks, odds ratios, relative rates, or hazard ratios from studies comparing the same exposure with the same health outcome. Articles were included if the coffee exposure was in any adult population of any ethnicity or sex in all countries and all settings. Participants could be healthy or have pre-existing illness, be pregnant, and be habitual or non-habitual coffee drinkers. Articles were also included when the exposure was total coffee or coffee separated into caffeinated and decaffeinated status. We excluded meta-analyses of total caffeine exposure and health outcomes unless we could extract caffeine exposure from coffee separately from a subgroup analysis. Coffee contains numerous biologically active ingredients that can interact to produce unique health effects that could be different to effects of caffeine from other sources. Additionally, we were interested in coffee, rather than caffeine, as a potential intervention in a future randomised controlled trial. All health outcomes for which coffee consumption had been investigated as the exposure of interest were included, except studies of genetic polymorphisms for coffee metabolism. We included any study with comparisons of coffee exposure, including high versus low, any versus none, and any linear or non-linear dose-responses. If an article presented separate meta-analyses for more than one health outcome, we included each of these separately.

RP and OJK independently extracted data from eligible articles. From each meta-analysis, they extracted the first author, journal, year of publication, outcome(s) of interest, populations, number of studies, study design(s), measure(s) of coffee consumption, method(s) of capture of consumption measurement, consumption type(s), and sources of funding. For each eligible article they also extracted study specific exposure categories as defined by authors, risk estimates and corresponding confidence intervals, number of cases and controls (case-control studies), events, participant/person years and length of follow-up (cohort studies) or numbers in intervention and control groups (randomised controlled trials), type of risk used for pooling, and type of effect model used in the meta-analysis (fixed or random). When a meta-analysis considered a dose-response relation and published a P value for non-linearity this was also extracted. Finally, we extracted any estimate of variance between studies (τ 2 ), estimates of the proportion of variance reflecting true differences in effect size (I 2 ), and any presented measure of publication bias. Any difference in extracted data between the two researchers was resolved by consensus.

Assessment of methodological quality of included studies and quality of evidence

We assessed methodological quality of meta-analyses using AMSTAR, 13 a measurement tool to assess systematic reviews. AMSTAR has been shown to be a reliable and valid tool for quality assessment of systematic reviews and meta-analyses of both interventional and observational research. 13 14 AMSTAR includes ratings for quality in the search, analysis, and transparency of a meta-analysis. For the rating item for methodological quality in the analysis, we downgraded any study that had used a fixed rather than a random effects model for producing a summary estimate. We considered the random effects model the most appropriate to be used in pooling estimates because the heterogeneity in study designs, populations, methods of coffee preparation, and cup sizes meant we would not expect a single true effect size common to all studies.

We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group classification to assess the quality of evidence for each outcome included in the umbrella review. 15 The GRADE approach categorises evidence from systematic reviews and meta-analyses into “high,” “moderate,” “low,” or “very low” quality. Study design dictates baseline quality of the evidence but other factors can decrease or increase the quality level. For example, unexplained heterogeneity or high probability of publication bias could decrease the quality of the evidence, and a large magnitude of effect or dose-response gradient could increase it.

Method of analysis

We reanalysed each meta-analysis using the DerSimonian and Laird random effects model, which takes into account variance between and within studies. 16 We did this through extraction of exposure and outcome data, as published in each meta-analysis article, when these were available in sufficient detail. We did not review the primary study articles included in each meta-analysis. As is conventional for risk ratios, we computed the summary estimates using the log scale to maintain symmetry in the analysis and took the exponential to return the result to the original metric. We produced the τ 2 statistic as an estimate of true variation in the summary estimate and the I 2 statistic as an estimate of proportion of variance reflecting true differences in effect size. We also calculated an estimate for publication bias with Egger’s regression test 17 for any reanalyses that included at least 10 studies. A P value <0.1 was considered significant for Egger’s test. We did not reanalyse any of the dose-response meta-analyses because of the scarcity of published estimates for number of cases and controls/participants and estimates for each dose of coffee exposure needed for a dose-response analysis. When we were interested in the apparent effect modification by sex, we conducted a test of interaction using the method published by Altman and Bland. 18

We constructed forest plots from the extracted and/or reanalysed data to display three categories of exposure for any health outcome (high versus low (or none), any (regular) versus none, and one extra cup a day (relative to none) in which that category of exposure was available. Each article presented a meta-analysis with one or more of these exposure categories or calculated combined estimates for a range of cups a day exposures for which a non-linear dose-response had been identified. A single health outcome per category of exposure was included in a forest plot representing the most recent study available. If two or more studies were published within the same 24 month period for the same category of exposure and same outcome, we selected the one with the highest number of cohort studies. We used a final tier of highest AMSTAR score if two studies published in the same period had the same number of cohort studies. When a meta-analysis included both cohort and case-control studies and when subgroup analysis was published by study design, we selected the cohort design subanalysis for inclusion in the summary forest plots or reanalysed when possible. This was deemed to represent the higher form of evidence as it was not affected by recall and selection bias and was less likely to be biased by reverse causality that can affect case-control studies. When linear dose-response analyses presented results for two or three extra cups a day we converted this to one extra cup a day by taking the square or cube root respectively (A Crippa, personal communication, 2017). We included heterogeneity, represented by the τ 2 statistic, and publication bias, represented by Egger’s test. When we could not reanalyse data from a meta-analysis we included summary data as extracted from the meta-analysis article and whichever measure of heterogeneity or publication bias, if any, was available.

Patient involvement

This study was informed by feedback from a patient and public involvement focus group and from an independent survey of patients with chronic liver disease in secondary care. This preliminary work showed enthusiasm from patients in participating in a randomised controlled trial involving coffee as an intervention and in finding out more information about the wider benefits and potential harms of increasing coffee intake. Furthermore, the results of this umbrella review were also disseminated during a recent focus group session that had been arranged to gather opinions regarding the acceptability of qualitative research to investigate patterns of coffee drinking in people with non-alcoholic fatty liver disease.

Figure 1 ⇓ shows the results of the systematic search and selection of eligible studies. The search yielded 201 meta-analyses of observational research in 135 articles with 67 unique outcomes and 17 meta-analyses of randomised-controlled trials in six articles with nine unique outcomes. The median number of meta-analyses per outcome for observational research was two (interquartile range 1-4, range 1-11). Twenty two outcomes had only a single meta-analysis. For meta-analyses of randomised controlled trials, outcomes were limited to systolic and diastolic blood pressure, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, and three outcomes related to pregnancy: preterm birth, small for gestational age, and birth weight. Figures 2-4 ⇓ show summary data for the meta-analyses selected as the highest form of evidence for coffee consumption and each outcome for high versus low (or none) or any (regular) versus no consumption and one extra cup a day coffee consumption. These show risk estimates for each outcome from 10 most harmful associations to the 10 most beneficial associations. Full versions of the forest plots are available in appendix 1. Figure 5 ⇓ shows the associations with consumption of decaffeinated coffee across the three exposure categories, and figures 6-9 ⇓ show interventional exposures for coffee versus control for outcomes of blood pressure, lipids, and outcomes related to pregnancy. Risk estimates across different exposure categories for each outcome, grouped by body system, are available in figures A-I in appendix 2.

Fig 1  Flowchart of selection of studies for inclusion in umbrella review on coffee consumption and health

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Fig 2  High versus low coffee consumption and associations with multiple health outcomes. Estimates are relative risks and effect models are random unless noted otherwise. For type 2 diabetes, P value was significant for non-linearity. No of events/total for leukaemia could not be split from other outcomes. All estimates were from our own reanalysis apart from preterm birth in first and third trimester and leukaemia

Fig 3  Any versus no coffee consumption and associations with multiple health outcomes. Estimates are relative risks and effect models are random unless noted otherwise. All estimates were from our own reanalysis apart from acute leukaemia, urinary tract cancer, and colorectal cancer

Fig 4  Consumption of one extra cup of coffee a day and associations with multiple health outcomes. Estimates are relative risks and effect models are random unless noted otherwise. No dose response analyses were re-analysed

Fig 5  Consumption of decaffeinated coffee and associations with multiple health outcomes. Estimates are relative risks and effect models are random unless noted otherwise

Fig 6  Coffee consumption in randomised controlled trials 35 and change (mean difference) in blood pressure in random effects model. Estimates are from our own analysis

Fig 7  Coffee consumption in randomised controlled trials 36 and change (mean difference) in cholesterol concentration. Effects are random unless noted otherwise

Fig 8  Coffee consumption in randomised controlled trials 86 and effects (relative risk) on birth outcomes

Fig 9  Coffee consumption in randomised controlled trials 86 and change (mean difference) in birth weight

The most commonly studied exposure was high versus low (or no) coffee consumption, and significance was reached for beneficial associations with 19 health outcomes and harmful associations with six. The 34 remaining outcomes were either negatively or positively associated but without reaching significance. Similarly, in comparisons of any (regular) with no consumption, significance was reached for beneficial associations with 11 outcomes and harmful associations with three. Finally, for one extra cup a day, significance was reached for beneficial associations with 11 outcomes and harmful associations with three. Eight out of 18 studies 19 20 21 22 23 24 25 26 27 that tested for non-linearity for the association with one extra cup a day found significant evidence for this.

All cause mortality

In the most recent meta-analysis, by Grosso and colleagues, the highest exposure category (seven cups a day) of a non-linear dose-response analysis was associated with a 10% lower risk of all cause mortality (relative risk 0.90, 95% confidence interval 0.85 to 0.96), 28 but summary estimates indicated that the largest reduction in relative risk was associated with the consumption of three cups a day (0.83, 0.83 to 0.88) compared with no consumption. Stratification by sex produced similar results. In a separate article, and despite a significant test for non-linearity (P<0.001), authors performed a linear dose-response analysis and found consumption of one extra cup a day was associated with a 4% lower risk of all cause mortality (0.96, 0.94 to 0.97). 27 The apparently beneficial association between coffee and all cause mortality was consistent across all earlier meta-analyses. High versus low intake of decaffeinated coffee was also associated with lower all cause mortality, with summary estimates indicating largest benefit at three cups a day (0.83, 0.85 to 0.89) 28 in a non-linear dose-response analysis.

Cardiovascular disease

Coffee consumption was consistently associated with a lower risk of mortality from all causes of cardiovascular disease, coronary heart disease, and stroke in a non-linear relation, with summary estimates indicating largest reduction in relative risk at three cups a day. 28 Compared with non-drinkers, risks were reduced by 19% (relative risk 0.81, 95% confidence interval 0.72 to 0.90) for mortality from cardiovascular disease, 16% (0.84, 0.71 to 0.99) for mortality from coronary heart disease, and 30% (0.70, 0.80 to 0.90) for mortality from stroke, at this level of intake. Increasing consumption to above three cups a day was not associated with harm, but the beneficial effect was less pronounced, and the estimates did not reach significance at the highest intakes. In stratification by sex within the same article, women seemed to benefit more than men at higher levels of consumption for outcomes of mortality from cardiovascular disease and coronary heart disease but less so from stroke. 28 In a separate meta-analysis, that did not test for non-linearity, an exposure of one extra cup a day was associated with a 2% reduced risk of cardiovascular mortality (0.98, 0.95 to 1.00). 29 There was also evidence of benefit in relation to high versus low coffee consumption after myocardial infarction and lower risk of mortality (hazard ratio 0.55, 95% confidence interval 0.45 to 0.67). 30

Coffee consumption was non-linearly associated with a lower risk of incident cardiovascular disease (relative risk 0.85, 95% confidence interval 0.80 to 0.90), coronary heart disease (0.90, 0.84 to 0.97), and stroke (0.80, 0.75 to 0.86), with these summary estimates indicating the largest benefits at consumptions of three to five cups a day. 19 There was no apparent modification of this association by sex. Risk was also lower for the comparison of high versus low consumption but did not reach significance. Any versus no consumption was also associated with a beneficial effect on stroke (0.89, 0.81 to 0.97). 31 High versus low coffee and one extra cup a day were both associated with a lower risk of atrial fibrillation but neither reached significance. 32 There was no significant association between consumption and risk of venous thromboembolism. 33 There was a non-linear association between consumption and heart failure, with summary estimates indicating the largest benefit at four cups a day (0.89, 0.81 to 0.99), 24 with a slightly higher risk of heart failure at consumption of 10 or more cups a day (1.01, 0.90 to 1.14), though this did not reach significance. 24 For hypertension, there were no significant estimates of risk at any level of consumption in a non-linear dose-response analysis 34 nor in comparisons of any versus none. 35 There was no clear benefit in comparisons of high with low decaffeinated consumption and cardiovascular disease. 19

In a meta-analysis of randomised controlled trials, coffee consumption had a marginally beneficial association with blood pressure when compared with control but failed to reach significance. 35 Consumption does, however, seem consistently associated with unfavourable changes to the lipid profile, with mean differences in total cholesterol (0.19 mmol/L, 95% confidence interval 0.10 mmol/L to 0.28 mmol/L), 36 low density lipoprotein cholesterol (0.14 mmol/L, 0.04 mmol/L to 0.25 mmol/L), 36 and triglyceride (0.14 mmol/L, 0.04 mmol/L to 0.24 mmol/L) 36 higher in the coffee intervention arms than the control arms (1 mmol/L cholesterol = 38.6 mg/dL, 1 mmol/L triglyceride = 88.5 mg/dL 37 ). Consumption was associated with lower high density cholesterol (−0.002 mmol/L, −0.02 mmol/L to 0.54 mol/L), but this did not reach significance. The increases in cholesterol concentration were mitigated with filtered coffee, with a marginal rise in concentration (mean difference 0.09 mmol/L, 0.02 to 0.17) 36 and no significant changes to low density lipoprotein cholesterol or triglycerides compared with unfiltered (boiled) coffee. Similarly, decaffeinated coffee seemed to have negligible effect on the lipid profile. 36

A meta-analysis of 40 cohort studies showed a lower incidence of cancer for high versus low coffee consumption (relative risk 0.82, 95% confidence interval 0.74 to 0.89), 38 any versus no consumption (0.87, 0.82 to 0.92), 38 and one extra cup a day (0.97, 0.96 to 0.98). 38 In a separate article, in non-smokers there was a 2% lower risk of mortality from cancer for exposure of one extra cup a day (0.98, 0.96 to 1.00). 28 For smokers, the article provided results only from a non-linear analysis, and the risk of mortality from cancer increased at all levels of coffee exposure, reaching significance above four cups a day.

High versus low coffee consumption was associated with a lower risk of prostate cancer, 39 endometrial cancer, 40 melanoma, 41 oral cancer, 39 leukaemia, 38 non-melanoma skin cancer, 42 and liver cancer. 43 For prostate, 44 endometrial, 39 melanoma, 45 and liver cancer 43 there were also significant linear dose-response relations indicating benefit.

There were consistent harmful associations for coffee consumption with lung cancer for high versus low consumption (odds ratio 1.59, 95% confidence interval 1.26 to 2.00), 46 any versus none (relative risk 1.28, 1.12 to 1.47), 47 and one extra cup a day (1.04, 1.03 to 1.05). 47 The effect was diminished, however, in studies that adjusted for smoking, and the association was not seen in never smokers. In the most recent meta-analysis, any versus no consumption in people who had never smoked was associated with an 8% lower risk of lung cancer (0.92, 0.75 to 1.10), 47 and in studies that adjusted for smoking the risk estimate was reduced (1.03, 0.95 to 1.12) 47 compared with the overall analysis, and neither reached significance. In contrast, a meta-analysis of two studies showed that high versus low consumption of decaffeinated coffee was associated with a lower risk of lung cancer. 48

A single meta-analysis found an association between any versus no coffee consumption and higher risk of any urinary tract cancer (odds ratio 1.18, 95% confidence interval 1.01 to 1.38). 49 In other meta-analyses of cohort studies of bladder cancer and renal cancer separately, however, associations did not reach significance. 39

No significant association was found between coffee consumption and gastric, 39 50 51 colorectal, 20 39 52 colon, 20 52 rectal, 20 52 ovarian, 39 53 thyroid, 54 55 breast, 38 39 56 pancreatic, 57 oesophageal, 39 58 or laryngeal cancers 59 and lymphoma 39 60 or glioma. 61

Liver and gastrointestinal outcomes

In addition to beneficial associations with liver cancer, all categories of coffee exposure were associated with lower risk for a range of liver outcomes. Any versus no coffee consumption was associated with a 29% lower risk of non-alcoholic fatty liver disease (relative risk 0.71, 0.60 to 0.85), 62 a 27% lower risk for liver fibrosis (odds ratio 0.73, 0.56 to 0.94), 63 and a 39% lower risk for liver cirrhosis (0.61, 0.45 to 0.84). 63 Coffee consumption was also associated with a lower risk of cirrhosis with high versus low consumption (0.69, 0.44 to 1.07) 63 and one extra cup a day (relative risk 0.83, 0.78 to 0.88). 9 Exposure to one extra cup a day was also significantly associated with a lower risk of mortality from cirrhosis (0.74, 0.59 to 0.86). 9 In a single article, 43 for meta-analyses of consumption and chronic liver disease, high versus low (0.35, 0.22 to 0.56), any versus none (0.62, 0.47 to 0.82), and one extra cup a day (0.74, 0.65 to 0.83) were all associated with benefit.

Coffee consumption was also consistently associated with significantly lower risk of gallstone disease. 25 A non-linear dose response was also apparent, though risk sequentially reduced as consumption increased from two to six cups a day. 25 High versus low consumption was associated with a marginally higher risk of gastro-oesophageal reflux disease, but this did not reach significance. 64

Metabolic disease

Coffee consumption was consistently associated with a lower risk of type 2 diabetes for high versus low consumption (relative risk 0.70, 95% confidence interval 0.65 to 0.75) 21 and one extra cup a day (0.94, 0.93 to 0.95). 65 There was some evidence for a non-linear dose-response, but the risk was still lower for each dose of increased consumption between one and six cups. 21 Consumption of decaffeinated coffee also seemed to have similar associations of comparable magnitude. 21 For metabolic syndrome high versus low coffee consumption was associated with 9% lower risk (0.91, 0.86 to 0.95). 26 High versus low consumption was also significantly associated with a lower risk of renal stones 66 and gout. 67

Renal outcomes

Coffee consumption of any versus none was associated with a lower risk of urinary incontinence 68 and chronic kidney disease, 69 but neither association reached significance, and the meta-analyses included cross sectional studies.

Musculoskeletal outcomes

There is inconsistency in the association between coffee consumption and musculoskeletal outcomes. There were no significant overall associations between high versus low consumption or one extra cup a day coffee and risk of fracture 70 71 or hip fracture. 72 73 In subgroup analysis by sex, however, high versus low consumption was associated with an increased risk of fracture in women (relative risk 1.14, 95% confidence interval 1.05 to 1.24) and a decreased risk in men (0.76, 0.62 to 0.94) 70 (test of interaction (ratio of relative risks (women:men) 1.50, 1.20 to 1.88; P<0.001). There was a non-significant association between high versus low consumption and risk of hip fracture in a subgroup analysis of women (relative risk 1.27, 0.94 to 1.72) 72 but not men (0.53, 0.38 to 1.00) 72 (test of interaction 2.40, 1.35 to 4.24; P<0.01). For consumption of one extra cup a day there was also an association with increased risk of fracture in women (relative risk 1.05, 1.02 to 1.07) 71 but a lower risk in men (0.91, 0.87 to 0.95) 71 (test of interaction 1.15, 1.10 to 1.21; P<0.001). These results suggest that sex might be a significant effect modifier in the association between coffee and risk of fracture. Associations were also found for total and decaffeinated coffee consumption and higher risk of rheumatoid arthritis, 74 75 but neither reached significance.

Neurological outcomes

Coffee consumption was consistently associated with a lower risk of Parkinson’s disease, even after adjustment for smoking, and across all categories of exposure. 22 76 77 Decaffeinated coffee was associated with a lower risk of Parkinson’s disease, which did not reach significance. 22 Consumption had a consistent association with lower risk of depression 78 79 and cognitive disorders, especially for Alzheimer’s disease (relative risk 0.73, 95% confidence interval 0.55 to 0.97) 80 in meta-analyses of cohort studies.

Gynaecological outcomes

Exposures of any versus no coffee consumption were associated with a higher risk of endometriosis but did not reach significance. 81

Antenatal exposure to coffee

There is some consistency in evidence for harmful associations of coffee consumption with different outcomes related to pregnancy. High versus low consumption was associated with a higher risk of low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), 82 pregnancy loss (1.46, 1.06 to 1.99), 23 first trimester preterm birth (1.22, 1.00 to 1.49), 83 and second trimester preterm birth (1.12, 1.02 to 1.22). 83 No significant association, however, was found for any category of coffee consumption and third trimester preterm birth, 83 neural tube defects, 84 and congenital malformations of the oral cleft 85 or cardiovascular system. 85 Only one study was included in a Cochrane meta-analysis of randomised controlled trials investigating coffee caffeine consumption on birth weight, preterm birth, and small for gestational age, and none of the outcomes reached significance. 86

There is also consistency in associations between high versus low coffee consumption in pregnancy and a higher risk of childhood leukaemia (odds ratio 1.57, 95% confidence interval 1.16 to 2.11) 87 and any versus no consumption (1.44, 1.07 to 1.92). 88 89

Heterogeneity of included studies

We were able to re-analyse by random effects, 83% of comparisons for high versus low and 79% for any versus none, but none for one extra cup a day. About 40% of the 83 meta-analyses that we re-analysed had significant heterogeneity, and 90% of these had an I 2 >50%. The individual studies within each meta-analysis varied by many factors, including the geography and ethnicity of the population of interest, the type of coffee consumed, the method of ascertainment of coffee consumption, the measure of coffee exposure, duration of follow-up, and outcome assessment. For the 54 that we were unable to re-analyse, 19% had significant heterogeneity, and 27% of meta-analyses did not publish heterogeneity for the studies included in the specific exposure comparison. Only four studies that we were unable to re-analyse used a fixed effects model.

Publication bias of included studies

We performed Egger’s regression test in only 40% of the meta-analyses in our reanalysis because the remaining 60% contained insufficient numbers of studies. In those that we reanalysed, 20% had statistical evidence of publication bias. This included high versus low comparisons for type 2 diabetes (P=0.049), 21 stroke (P=0.09), 19 gastro-oesophageal reflux disease (P=0.04), 64 bladder cancer (P<0.01), 39 endometrial cancer (P=0.03), 40 and hip fracture (P=0.02), 72 and in the meta-analysis of randomised controlled trials for total cholesterol (P<0.01). For meta-analyses that we were unable to reanalyse, none reported significant publication bias or they did not conduct or publish a statistical test for publication bias for the specific exposure comparison. This could have been in part because of low number of studies included in the pooling. It is possible, however, that unmeasured publication bias exists in many of the summary estimates we have presented and not assessed.

AMSTAR and GRADE classification of included studies

The median AMSTAR score achieved across all studies was 5 out of 11 (range 2-9, interquartile range 5-7). Eleven studies were downgraded on method of meta-analysis because they used a fixed, rather than random effects, model. Appendix 3 provides a breakdown of AMSTAR scores for studies representing each outcome. In terms of quality of evidence for each outcome, about 25% were rated as being of “low” and 75% as “very low” quality with the GRADE classification. Even the meta-analyses of randomised controlled trials were graded as low quality of evidence because of risk of bias, inconsistency, or imprecision. Only outcomes identified as having a significant dose-response effect, or large magnitude of effect, without significant other biases reached a GRADE classification of “low” compared with the majority rating of “very low.” Appendix 4 shows a breakdown of GRADE scores for studies representing each outcome.

Principal findings and possible explanations

Coffee consumption is more often associated with benefit than harm for a range of health outcomes across multiple measures of exposure, including high versus low, any versus none, and one extra cup a day. Exposure to coffee has been the subject of numerous meta-analyses on a diverse range of health outcomes. We carried out this umbrella review to bring this existing evidence together and draw conclusions for the overall effects of coffee consumption on health. We identified 201 meta-analyses of observational research with 67 unique outcomes and 17 meta-analyses of randomised controlled trials with nine unique outcomes.

The conclusion of benefit associated with coffee consumption was supported by significant associations with lower risk for the generic outcomes of all cause mortality, 28 cardiovascular mortality, 28 and total cancer. 38 Consumption was associated with a lower risk of specific cancers, including prostate cancer, 39 44 90 endometrial cancer, 39 40 91 melanoma, 41 45 non-melanoma skin cancer, 42 and liver cancer. 43 Consumption also had beneficial associations with metabolic conditions including type 2 diabetes, 21 65 metabolic syndrome, 26 gallstones, 25 gout, 67 and renal stones 66 and for liver conditions including hepatic fibrosis, 63 cirrhosis, 9 63 cirrhosis mortality, 9 and chronic liver disease combined. 43 The beneficial associations between consumption and liver conditions stand out as consistently having the highest magnitude compared with other outcomes across exposure categories. Finally, there seems to be beneficial associations between coffee consumption and Parkinson’s disease, 22 76 77 depression, 78 79 and Alzheimer’s disease. 80

Overall, there is no consistent evidence of harmful associations between coffee consumption and health outcomes, except for those related to pregnancy and for risk of fracture in women. After adjustment for smoking, consumption in pregnancy seems to be associated with harmful outcomes related to low birth weight, 82 preterm birth, 83 and pregnancy loss. 23 These associations were seen in subgroup analyses from articles investigating total caffeine exposure, which showed similar associations, and from a single meta-analysis for each outcome. There were also harmful associations between consumption and congenital malformations, though these did not reach significance. 85 The half life of caffeine is known to double during pregnancy, 92 and therefore the relative dose of caffeine from equivalent per cup consumption will be much higher than consumption outside pregnancy. Caffeine is also known to easily cross the placenta, 93 and activity of the caffeine metabolising enzyme, CYP1A2, is low in the fetus, resulting in prolonged fetal exposure to caffeine. 94 Though we found no significant associations between coffee exposure and neural tube defects, 84 for this outcome, all bar one of the included studies were of case-control design and therefore prone to recall bias. Maternal exposure to coffee had a harmful association with acute leukaemia of childhood, 87 88 89 but evidence for this also came from case-control studies.

The effect of the association between coffee consumption and risk of fracture was modified by sex. While there was no overall significant association with risk, the most recent meta-analyses found a 14% increased risk for high versus low consumption 70 and 0.6% increased risk for one extra cup a day 71 in women. Conversely, in men consumption was beneficially associated with a lower risk of fracture. Caffeine has been proposed as the component of coffee linked to the increased risk in women, with potential influence on calcium absorption 95 and bone mineral density. 96 A recent comprehensive systematic review of the health effects of caffeine, however, concluded, with regard to bone health, that a caffeine intake of 400 mg/day (about four cups of coffee) was not associated with adverse effects on the risk of fracture, falls, bone mineral density, or calcium metabolism. 97 There is limited evidence at higher intakes of caffeine to draw firmer conclusions. Notably, many of the studies included in the meta-analyses of coffee consumption and risk of fracture did not adjust for important confounders such as body mass index (BMI), smoking, or intakes of calcium, vitamin D, and alcohol. Some studies suggest that caffeine consumption is associated only with a lower risk of low bone mineral density in women with inadequate calcium intake, 98 and that only a small amount of milk added to coffee would be needed to offset any negative effects on calcium absorption. 95 The type of coffee consumed might therefore be an important factor. Coffee and caffeine have also been linked to oestrogen metabolism in premenopausal women 99 and increased concentrations of sex hormone binding globulin (SHBG) in observational research of postmenopausal women. 100 The increased globulin concentration was associated with lower concentrations of unbound testosterone but not unbound oestradiol. 100 Low concentrations of oestradiol and high concentrations of sex hormone binding globulin are known to be associated with risk of fracture. 101 102 An effect of coffee consumption on sex hormone binding globulin, however, has not been supported in small scale randomised controlled trials. 103 Coffee has been shown to be beneficially associated with oestrogen receptor negative, but not positive, breast cancer. 56 There is consistent evidence, however, to suggest that coffee consumption is associated with a lower risk of endometrial cancer 40 and no clear evidence for associations with ovarian cancer. 39 53 The effect of coffee consumption on endogenous sex hormones could therefore be beneficial for some hormone dependent cancers but increase the risk of fracture in women with inadequate dietary calcium 98 or with multiple risk factors for osteoporosis. 104

When meta-analyses have suggested associations between coffee consumption and higher risk of other diseases, such as lung cancer, this can largely be explained by inadequate adjustment for smoking. Smoking is known to be positively associated with coffee consumption 105 and with many health outcomes and could act as both a confounder and effect modifier. Galarraga and Boffetta examined the possible confounding by smoking in two ways in their recent meta-analysis 47 of coffee consumption and risk of lung cancer. Firstly, they performed the meta-analysis in those who had never smoked and detected no harmful association. Next, they performed the meta-analysis in only those studies that adjusted for smoking, and the magnitude of the apparent harmful association was reduced and was no longer significant. It is likely that residual confounding by smoking, despite some adjustment, can explain this apparent harmful association. A similar pattern was seen in stratification by smoking for coffee consumption and mortality from cancer in the recent meta-analysis by Grosso and colleagues. 28 The authors highlighted the positive association between coffee consumption and smoking and concluded that residual confounding by smoking was the likely explanation.

For randomised controlled trials, coffee has been given as an intervention for only short durations and limited to a small number of outcomes, including blood pressure, lipid profiles, and one trial in pregnancy. There does seem to be consistent evidence for small increases in concentrations of total cholesterol, low density lipoprotein cholesterol, and triglyceride in meta-analyses of randomised controlled trials, and this is believed to be caused by the action of diterpenes. 106 The method of preparation is an important factor as instant and filtered coffee contain negligible amounts of diterpenes compared with espresso, with even higher amounts in boiled and cafetière coffee. 106 In the meta-analysis we included in our review, the effect of filtered coffee consumption on lipids was negligible or failed to reach significance compared with unfiltered coffee. Studies also suggest, however, that the dose of diterpenes needed to cause hypercholesterolaemia is likely to be much higher than the dose needed for beneficial anticarcinogenic effects. 107 For unfiltered coffee, the clinical relevance of such small increases in total cholesterol, low density lipoprotein cholesterol, and triglyceride due to coffee are difficult to extrapolate, especially as coffee consumption does not seem to be associated with adverse cardiovascular outcomes, including mortality after myocardial infarction. 30 Changes in the lipid profile associated with coffee also reversed with abstinence. 106

When dose-response analyses have been conducted and when these have suggested non-linearity—for example in all cause mortality, cardiovascular disease mortality, cardiovascular disease, and heart failure—summary estimates indicate that the largest relative risk reduction is associated with intakes of three to four cups a day. Importantly, increase in consumption beyond this intake does not seem to be associated with increased risk of harm, rather the magnitude of the benefit is reduced. In type 2 diabetes, despite significant non-linearity, relative risk reduced sequentially from one through to six cups a day. Estimates from higher intakes are likely to include a smaller number of participants, and this could be reflected in the imprecision observed for some outcomes at these levels of consumption.

Coffee contains a complex mixture of bioactive compounds with plausible biological mechanisms for benefiting health. It has been shown to contribute a large proportion of daily intake of dietary antioxidant, greater than tea, fruit, and vegetables. 108 Chlorogenic acid is the most abundant antioxidant in coffee; though it is degraded by roasting, alternative antioxidant organic compounds are formed. 109 Caffeine also has significant antioxidant effects. The diterpenes, cafestol and kahweol, induce enzymes involved in carcinogen detoxification and stimulation of intracellular antioxidant defence, 107 contributing towards an anticarcinogenic effect. These antioxidant and anti-inflammatory effects are also likely to be responsible for the mechanism behind the beneficial associations between coffee consumption and liver fibrosis, cirrhosis, and liver cancer 110 that our umbrella review found had the greatest magnitude of effect compared with other outcomes. Additionally, caffeine could have direct antifibrotic effects by preventing hepatic stellate cell adhesion and activation. 111

Decaffeinated coffee is compositionally similar to caffeinated coffee apart from having little or no caffeine. 112 In our umbrella review we identified 16 unique outcomes for associations with decaffeinated coffee. Decaffeinated coffee was beneficially associated with all cause and cardiovascular mortality in a non-linear dose-response, with summary estimates indicating the largest relative risk reduction at intakes of two to four cups a day and of similar magnitude to caffeinated coffee. Marginal benefit in the association between decaffeinated coffee and cancer mortality did not reach significance. The associations between high versus low consumption of decaffeinated coffee and lower risk of type 2 diabetes 21 and endometrial cancer 40 were of a similar magnitude to total or caffeinated coffee, and there was a small beneficial association between decaffeinated coffee and lung cancer. 48 The other outcomes investigated for decaffeinated coffee showed no significant associations, though it should be noted that meta-analyses of consumption would have much lower power to detect an effect. Importantly, there were no convincing harmful associations between decaffeinated coffee and any health outcome. People who drink decaffeinated coffee might be different from those who drink caffeinated coffee, and most coffee assessment tools do not adequately account for people who might have switched from caffeinated to decaffeinated coffee. 113

Strengths and weaknesses and in relation to other studies

The umbrella review has systematically summarised the current evidence for coffee consumption and all health outcomes for which a previous meta-analysis had been conducted. It used systematic methods that included a robust search strategy of four scientific literature databases with independent study selection and extraction by two investigators. When possible, we repeated each meta-analysis with a standardised approach that included the use of random effects analysis and produced measures of heterogeneity and publication bias to allow better comparison across outcomes. We also used standard approaches to assess quality of methods (AMSTAR) and quality of the evidence (GRADE).

AMSTAR has good evidence of validity and reliability. 13 The AMSTAR score assisted us in identifying the highest quality of evidence for each outcome. It also allows judgment regarding quality of the meta-analysis presented for each outcome. A high AMSTAR score for a meta-analysis, however, does not equate to high quality of the original studies, and the assessment and use of quality scoring of the original studies accounts for only two of 11 possible AMSTAR points. Additionally, appropriate method of analysis, accounting for one score of quality, can be subjective. We downgraded any meta-analysis that used a fixed effects model irrespective of heterogeneity for reasons discussed previously. The AMSTAR system, however, allows only a 1 point loss for a poor analysis technique and would not capture multiple issues within an individual meta-analysis.

One recurring issue for many of the included meta-analyses was the assumption that summary relative risk could be pooled from a combination of odds ratio, relative rates, and hazard ratios so that they could combine studies with differing measures. Statistically, the odds ratio is similar to the relative risk when the outcome is uncommon 114 but will always be more extreme. 114 Similarly, for rare events, relative rates and hazard ratios are similar to the relative risk when censoring is uncommon or evenly distributed between exposed and unexposed groups. 114 Many meta-analyses stated their assumption but included insufficient information to allow us to judge the suitability of the pooling. Notably, only one meta-analysis produced a summary statistic with hazard ratios. 53 We did not downgrade the AMSTAR score when this assumption had been made, and we did not downgrade meta-analyses for failing to consider uncertainty in variance estimates as this was universally unstated. 115 Furthermore, the computation of dose-response meta-analyses should use methods that account for lack of independence in comparisons (same unexposed group), such as those proposed by Greenland and Longnecker. 116 Reassuringly, most dose-response meta-analyses we included in our summary tables cited this method.

Most of the studies we included were meta-analyses of observational studies. One strength of the umbrella review was the inclusion only of cohort studies, or subgroup analyses of cohort studies when available, in preference to summary estimates from a combination of study designs. In meta-analyses that we were unable to re-analyse and when subgroup analysis did not allow the disentanglement of study design, the presented results were from the combined estimates of all included studies. Observational research, however, is low quality in the hierarchy of evidence and with GRADE classification most outcomes are recognised as having very low or low quality of evidence where a dose-response relation exists. Large effect sizes of >2 or <0.5 can permit observational evidence to be upgraded in GRADE, and only the association between high versus low coffee consumption and both liver cancer 43 and chronic liver disease 43 reached this magnitude. In fact, associations between coffee consumption and liver outcomes consistently had larger effect sizes than other outcomes across exposure categories. Our reanalysis did not change our GRADE classification for any outcome.

A possible limitation of our review was that we did not reanalyse any of the dose-response meta-analyses as the data needed to compute these were not generally available in the articles. We did not review the primary studies included in each of the meta-analyses that would have facilitated this. We decided that reanalysing the dose-response data was unlikely to result in changes to the GRADE classification. In our reanalysis of the comparison of high versus low and any versus no coffee, we used data available in the published meta-analyses and therefore assumed the exposure and estimate data for component studies had been published accurately.

We were able to produce estimates for publication bias using Egger’s test for meta-analyses containing 10 or more studies. 17 Egger’s test is not recommended with fewer studies. We were unable to conduct alternative tests, such as Peters’ test, 117 which is more appropriate for binary outcomes, because this needed cases and non-cases for each level of exposure and this detail was largely unavailable in the meta-analyses. We did not calculate excess significance tests, which attempt to detect reporting bias by comparing the number of studies that have formally significant results with the number expected, based on the sum of the statistical powers from individual studies, and using an effect size equal to the largest study in the meta-analysis. 118 Excess significance tests, however, have not been fully evaluated and are not therefore currently recommended as an alternative to traditional tests of publication bias. 119 Further bias in methods could have occurred if the same meta-analysis authors conducted multiple meta-analyses for different health outcomes. There was also an overlap of health outcomes with data from the same original cohort studies. While the associations for different health outcomes were statistically independent, any methodological issues in design or conduct of the original cohorts could represent repeated bias filtering through the totality of evidence.

The beneficial association between coffee consumption and all cause mortality highlighted in our umbrella review is in agreement with two recently published cohort studies. The first was a large cohort study of 521 330 participants followed for a mean period of 16 years in 10 European countries, during which time there were 41 693 deaths. 120 The highest quarter of coffee consumption, when compared with no coffee consumption, was associated with a 12% lower risk of all cause mortality in men (hazard ratio 0.88, 95% confidence interval 0.82 to 0.95) and a 7% lower risk in women (0.93, 0.82 to 0.95). Coffee was also beneficially associated with a range of cause specific mortality, including mortality from digestive tract disease in men and women and from circulatory and cerebrovascular disease in women. The study was able to adjust for a large number of potential confounding factors, including education, lifestyle (smoking, alcohol, physical activity), dietary factors, and BMI. Importantly, the study found no harmful associations between coffee consumption and mortality, apart from the highest quarter versus no coffee consumption and increased risk of mortality from ovarian cancer (1.31, 1.07 to 1.61). No prevailing hypothesis was cited. In our umbrella review, high versus low coffee consumption was associated with an 8% increased risk and one extra cup a day with a 2% increased risk of incident ovarian cancer, but neither reached significance.

In the second study, a North American cohort of 185 855 participants was followed for a mean duration of 16 years, during which 58 397 participants died. 121 After adjustment for smoking and other factors, consumption of four or more cups of coffee a day was associated with an 18% lower risk of mortality (hazard ratio 0.82, 95% confidence interval 0.78 to 0.87). The findings were consistent across subgroups stratified by ethnicity that included African Americans, Japanese Americans, Latino, and white populations. Associations were also similar in men and women. Mortality from heart disease, cancer, chronic lower respiratory disease, stroke, diabetes, and kidney disease was also beneficially associated with coffee consumption. Importantly, no harmful associations were identified. Subtypes of cancer mortality, however, were not published.

Many of the associations between coffee consumption and health outcomes, which are largely from cohort studies, could be affected by residual confounding. Smoking, age, BMI, and alcohol consumption are all associated with coffee consumption and a considerable number of health outcomes. These relations might differ in magnitude and even direction between populations. Residual confounding by smoking could reduce a beneficial association or increase a harmful association when smoking is also associated with an outcome. Coffee could also be a surrogate marker for factors that are associated with beneficial health such as higher income, education, or lower deprivation, which could be confounding the observed beneficial associations. The design of randomised controlled trials can reduce the risk of confounding because the known and unknown confounders are distributed randomly between intervention and control groups. Mendelian randomisation studies can also help to reduce the effects of confounding from random distribution of confounders between genotypes of known function related to the outcome of interest. The association between coffee consumption and lower risk of type 2 diabetes 122 and all cause and cardiovascular mortality 123 was found to have no genetic evidence for a causal relation in Mendelian randomisation studies, suggesting residual confounding could result in the observed associations in other studies. The authors point out, however, that the Mendelian randomisation approach relies on the assumption of linearity between all categories of coffee intake and might not capture non-linear differences. The same genetic variability in coffee and caffeine metabolism could influence the magnitude, frequency, and duration of exposure to caffeine and other coffee bioactive compounds. Palatini and colleagues found that the risk of hypertension associated with coffee varied depending on the CYP1A2 genotype. 124 Those with alleles for slow caffeine metabolism were at increased risk of hypertension compared with those with alleles for fast caffeine metabolism.

Bias from reverse causality can also occur in observational studies. In case-control studies, symptoms from disease might have led people to reduce their intake of coffee. When possible, we included meta-analyses of cohort studies or cohort subgroup analyses in our review as they are less prone to this type of bias. Even prospective cohort studies, however, can be affected by reverse causality bias, in which participants who were apparently healthy at recruitment might have reduced their coffee intake because of early symptoms of a disease.

Most meta-analyses produced summary effects from individual studies that measured coffee exposure by number of cups a day. Some individual studies, however, used number of times a day, servings a day, millilitres a day, cups a week, times a week, cups a month, and drinkers versus non-drinkers to measure coffee consumption. There is no universally recognised standard coffee cup size, and the bioactive components of coffee in a single cup will vary depending on the type of bean (such as Arabica or Robusta), degree of roasting, and method of preparation, including the quantity of bean, grind setting, and brew type used. Therefore, studies that are comparing coffee consumption by cup measures could be comparing ranges of exposures. The range of number of cups a day classified as both high and low consumption from different individual studies varied substantially for inclusion in each meta-analysis. High versus low consumption was the most commonly used measure of exposure. Consistent results across meta-analyses and categories of exposure, however, suggest that measurement of cups a day produces a reasonable differential in exposure. Additionally, any misclassification in exposure is likely to be non-differential and would more likely dilute any risk estimate rather than strengthen it, pushing it towards the null.

The inclusion criteria for the umbrella review meant that some systematic reviews were omitted when they did not do any pooled analysis. Meta-analyses in relation to coffee consumption, however, have been done on most health outcomes for which there is also a systematic review, except for respiratory outcomes 125 and sleep disturbance. 126 There could also be important well conducted studies that have assessed coffee consumption in relation to outcomes for which no investigators have attempted to perform any combined review, whether pooling the estimate or not. Additionally, the umbrella review has investigated defined health outcomes rather than physiological outcomes. This means there could be physiological effects of coffee such as increased heart rate, stimulation of the central nervous system, and feelings of anxiety that have not been captured in this review and must be considered should individuals be taking drugs that have similar physiological effects or in those trying to avert anxiety.

Despite our broad inclusion criteria, we identified only one meta-analysis that focused on a population of people with established disease. This was a meta-analysis of two small cohort studies investigating risk of mortality in people who had experienced a myocardial infarction. 30 In contrast, most meta-analyses estimated the association between coffee consumption and outcomes in general population cohorts rather than those selected by pre-existing disease. Our summation of the existing body of evidence should therefore be viewed in this context and suggests that the association of coffee consumption in modifying the natural history of established disease remains unclear.

We extracted details of conflicts of interest and funding declarations from articles selected in the umbrella review. Only one article declared support from an organisation linked to the coffee industry, and a second article stated that their authors contributed to the same organisation. Neither of these articles was selected to represent the respective outcome in the summary figures, and all references for studies not included in the summary tables are available on request. We did not review the primary studies included in each meta-analysis and cannot comment on whether any of these studies were funded by organisations linked to the coffee industry.

Conclusions and recommendations

Coffee consumption has been investigated for associations with a diverse range of health outcomes. This umbrella review has systematically assimilated this vast amount of existing evidence where it has been published in a meta-analysis. Most of this evidence comes from observational research that provides only low or very low quality evidence. Beneficial associations between coffee consumption and liver outcomes (fibrosis, cirrhosis, chronic liver disease, and liver cancer) have relatively large and consistent effect sizes compared with other outcomes. Consumption is also beneficially associated with a range of other health outcomes and importantly does not seem to have definitive harmful associations with any outcomes outside of pregnancy. The association between consumption and risk of fracture in women remains uncertain but warrants further investigation. Residual confounding could explain some of the observed associations, and Mendelian randomisation studies could be applied to a range of outcomes, including risk of fracture, to help examine this issue. Randomised controlled trials that change long term behaviour, and with valid proxies of outcomes important to patients, could offer more definitive conclusions and could be especially useful in relation to coffee consumption and chronic liver disease. Reassuringly, our analysis indicates that future randomised controlled trials in which the intervention is increasing coffee consumption, within usual levels of intake, possibly optimised at three to four cups a day, would be unlikely to result in significant harm to participants. Pregnancy, or risk of pregnancy, and women with higher a risk of fracture, however, would be justified exclusion criteria for participation in a coffee treatment study.

What is already known on this topic

Coffee is highly consumed worldwide and could have positive health benefits, especially in chronic liver disease

Beneficial or harmful associations of drinking coffee seem to vary between health outcomes of interest

Understanding associations of coffee and health is important, especially in relation to exploring harmful associations, before interventional research is conducted

What this study adds

Coffee drinking seems safe within usual patterns of consumption, except during pregnancy and in women at increased risk of fracture

Existing evidence is observational and of lower quality, and randomised controlled trials are needed

A future randomised controlled trial in which the intervention is increasing coffee consumption would be unlikely to result in significant harm to participants

Contributors: RP conceptualised the umbrella review, conducted the search, study selection, data extraction, and drafted and revised the paper. OJK conceptualised the umbrella review, conducted the study selection and data extraction, and revised the draft paper. JP conceptualised the umbrella review and revised the draft paper. JAF revised the draft paper. PCH revised the draft paper. PR conceptualised the umbrella review, arbitrated the study selection, and revised the draft paper. All authors reviewed and approved the final version of the manuscript. RP is guarantor.

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors; the authors remain independent of any funding influence.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; JAF reports research grants from GlaxoSmithKline and from Intercept Pharmaceuticals, and personal fees from Novartis and from Merck, outside the submitted work; PCH reports personal fees from MSD, personal fees from Gilead, personal fees from Abbvie, personal fees from Jannsen, personal fees from BMS, personal fees from Pfizer, grants and personal fees from Roche, personal fees from Novartis, outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: Not required.

Data sharing: References for studies included in the umbrella review but not selected to represent the outcome in the summary figures are available on request.

Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

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June 21, 2018

The Healthy Addiction? Coffee Study Finds More Health Benefits

New research in mice details the mechanism of how caffeine seems to help the heart

By David Noonan

Farhad J Parsa Getty Images

It’s enough to make a tea drinker buy an espresso machine. In a new study scientists in Germany report they were able to modify a common age-related defect in the hearts of mice with doses of caffeine equivalent to four to five cups of coffee a day for a human. The paper—the latest addition to a growing body of research that supports the health benefits of drinking coffee—describes how the molecular action of caffeine appears to enhance the function of heart cells and protect them from damage.

It remains to be seen whether these findings will ultimately have any bearing on humans, but Joachim Altschmied of Heinrich Heine-University in Düesseldorf, who led the study with his colleague Judith Haendeler, says “the old idea that you shouldn’t drink coffee if you have heart problems is clearly not the case anymore.”

Previous research had suggested as much. For example, a 2017 report in the Annual Review of Nutrition , which analyzed the results of more than 100 coffee and caffeine studies, found coffee was associated with a probable decreased risk of cardiovascular disease—as well as type 2 diabetes and several kinds of cancer. The new paper, published Thursday in PLOS Biology , identifies a specific cellular mechanism by which coffee consumption may improve heart health.

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The study builds on earlier work in which the two scientists showed caffeine ramps up the functional capacity of the cells that line blood vessels. The drug does so by getting into cells and stoking the mitochondria, structures within the cells that burn oxygen as they turn glucose into energy.“Mitochondria are the powerhouses of the cells,” Haendeler says. One of the things they run on is a protein known as p27. As Haendeler and Altschmied discovered (and describe in the current paper), caffeine works its magic in the major types of heart cells by increasing the amount of p27 in their mitochondria.  

After the researchers induced myocardial infarction in the mice during their experiments, the extra stores of p27 in the caffeinated cells apparently prevented damaged heart muscle cells from dying. The paper says the mitochondrial p27 also triggered the creation of cells armed with strong fibers to withstand mechanical forces, and promoted repairs to the linings of blood vessels and the inner chambers of the heart. To confirm the protein’s importance, the scientists engineered mice with a p27 deficiency. Those mice were found to have impaired mitochondrial function that did not improve with caffeine.

The researchers also looked at caffeine’s potential role in modifying a common effect of aging in mice and humans: reduced respiratory capacity among mitochondria. (In this context “respiratory” refers to a complex sequence of biochemical events within the organelle .)

For this part of the experiment, 22-month-old mice received caffeine—the daily equivalent of four to five cups of coffee in humans—in their drinking water for 10 days. That was sufficient to raise their mitochondrial respiration to the levels observed in six-month-old mice, according to the study. Analysis showed the old mice had roughly double the amount of p27 in their mitochondria after the 10 days of caffeine.

Although this latest news about the potential health benefits of coffee involves just a single animal study, tea drinkers might well feel they are coming out on the wrong end of the coffee equation. According to the National Coffee Association, 64 percent of Americans 18 and over drink at least one cup of coffee a day, with an average daily consumption of 3.2 cups. Three cups of a typical breakfast tea contain  less than 150 milligrams of caffeine, compared with the nearly 500 milligrams in the same amount of brewed coffee. So tea drinkers might wonder if they are missing out on a potential health benefit and should start drinking the other stuff.

“Absolutely not,” says Donald Hensrud, medical director of Mayo Clinic's Healthy Living Program. “You have to enjoy life, and if you enjoy tea, keep on enjoying it. It’s all good. There are health benefits to coffee, to black tea and to green tea.” But there can also be problems associated with higher doses of caffeine, he notes. The amount in more than two cups of coffee a day, for example, can interfere with conception and increase the risk of miscarriage. And, he says, because individuals metabolize caffeine at different rates, slow metabolizers may be more susceptible to side effects such as heartburn, insomnia, heart palpitations and irritability.

Haendeler, who drinks six cups of coffee a day, says it can be part of a healthy lifestyle—but is no miracle cure. And she is quick to point out there are no shortcuts to good health. “If you hear about this study and decide to drink coffee but you do nothing else—no exercise, no proper diet—then, of course, this will not work,” she says. “You cannot simply decide, ‘Okay, I’m sitting here and drinking four, five or six cups of coffee and everything is fine.'”

Caffeine addiction and determinants of caffeine consumption among health care providers: a descriptive national study

Affiliation.

• 1 Department of Public Health and Community Medicine, Faculty of Medicine, Zagazig University, Egypt. [email protected].
• PMID: 37140274
• DOI: 10.26355/eurrev_202304_32093

Objective: Caffeine is the most commonly used psychostimulant compound with a long history of worldwide consumption. Consuming low to moderate doses of caffeine is generally safe and quite beneficial; however, several clinical studies show that high doses could be toxic. Additionally, caffeine users can become dependent on the drug and find themselves unable to reduce consumption despite impending and recurrent health problems associated with continued use. This study was conducted to explore the prevalence, determinants, and positive and negative effects of caffeine consumption among governmental health care providers (HCPs) who were caffeine users. It aims to determine the frequency of caffeine dependence and addiction in the Kingdom of Saudi Arabia (KSA) in January 2020.

Subjects and methods: This cross-sectional study recruited 600 randomly selected HCPs from all regions of KSA, who fulfilled the selection criteria through a self-administrated, online-validated questionnaire composed of three main parts using the DSM-IV to diagnose dependence and probable addiction.

Results: The majority of the studied HCPs were females (67.8%), nonsmokers (82.0%), and Saudis (80.5%), with a mean age of 35 years. According to the DSM-IV, the prevalence of caffeine consumption was 94.3%. Caffeine dependence was reported in 270 (47.7%), while 345 (60.9%) were diagnosed as addicts. The most commonly consumed caffeine-containing substances were coffee and its variants/types (70%), tea (59%), and chocolate (52%), with each person spending about 220 SR per week on them. The main reported adverse effects, in descending order, were sleep disturbances, stomach problems, and cardiac symptoms. The most positive effects reported of caffeine consumption were feeling active, alert, confident, and happy. These findings were significantly affected by sex, occupation, and general health.

Conclusions: Caffeine use, dependence, and addiction are common among government HCPs in KSA. Caffeine has both positive and negative effects on this population and further research is necessary to better understand the long-term consequences of caffeine consumption.

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Caffeine Addiction: How Much Is Too Much?

Anxiety, fatigue, and general uneasiness may be signs it’s time to cut back

• Addiction Symptoms
• Withdrawal Symptoms
• Addiction Quantity
• Drinking Less Caffeine

Caffeine dependence and addiction are caffeine use disorders, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the handbook used by healthcare providers to diagnose mental disorders. These terms are used interchangeably, though researchers prefer the term "dependence" because it is used most frequently in published literature.

This article explains caffeine addiction and withdrawal symptoms, how much caffeine can cause dependence, and how to drink less caffeine.

fcafotodigital / Getty Images

Symptoms That Suggest Caffeine Addiction

So, is caffeine an actual addiction? The short answer is, yes, it can be.

"Addiction," in general, is an older term that has more recently been updated in favor of more accurate phrasing: substance use disorder . People with substance use disorders do not control their substance use despite harmful consequences. In the case of caffeine, consequences may include anxiety, insomnia, and nausea.

According to the DSM-5, caffeine use disorder is defined as "a problematic pattern of caffeine use leading to clinically significant impairment or distress." For diagnosis, this must be accompanied by the first three symptoms on the following list and may have the symptoms listed after those:

• Persistent desire or unsuccessful attempts to reduce or control caffeine use
• Continued caffeine use despite knowing it results in physical or psychological problems
• Withdrawal symptoms when not using
• Ingesting larger amounts or over a longer period than intended
• Recurrent caffeine use that results in interference with work, school, or home responsibilities
• Continued caffeine use despite social or interpersonal problems
• Tolerance (needing increased amounts of caffeine)
• Spending a great deal of time trying to obtain caffeine or recover from its effects
• Craving caffeine

Caffeine Sensitivity, Dependence, and Withdrawal

Caffeine sensitivity describes how strongly a person reacts to caffeine. If you have low sensitivity, you may need to drink more caffeine to feel the desired effects. However, if you have high sensitivity, you may feel effects more quickly, including unwanted side effects like nervousness.

Caffeine dependence means your body requires caffeine each day. You may have trouble focusing without it, have trouble not using it, or experience withdrawal when you can't have it.

Caffeine withdrawal is a group of symptoms that accompany not having caffeine. These commonly include headaches and drowsiness.

Caffeine Withdrawal Symptoms

If your body depends on caffeine, you may experience withdrawal symptoms when you don't have it. Caffeine withdrawal symptoms commonly include the following:

• Irritability
• Depressed mood
• Difficulty concentrating
• Flu-like symptoms

Caffeine withdrawal symptoms can start as soon as 12 to 24 hours after stopping caffeine and last up to a little over a week.

Caffeine Quantity: How Much Makes You Addicted?

How much caffeine do you have to drink a day to be considered addicted? Since everyone's sensitivity is different, there isn't an exact number for how much caffeine is too much . Plus, factors like body weight and medications can influence how caffeine affects a person.

Instead of a specific quantity, caffeine addiction or dependence is marked by behaviors and increasing tolerance to caffeine. In other words, needing to consume larger amounts than you did in the past for the same effect means your tolerance has increased. Increasing tolerance is one of the key symptoms of caffeine use disorder.

The Food and Drug Administration (FDA) has set the upper limit for most healthy adults at 400 milligrams (mg) daily—around four cups of coffee.

People who are pregnant or breastfeeding should consume far less. Experts recommend no more than 200 mg daily while pregnant, while capping caffeine at 300 mg daily during lactation.

Beverages With Higher Caffeine Content

Some drinks have excessive amounts of caffeine. Consuming these, especially regularly, could make your tolerance higher and withdrawal symptoms worse. Examples of high-caffeine drinks include energy drinks (or concentrated drops) and espresso.

Highly concentrated caffeine, like pure powdered or liquid concentrate caffeine, can also be dangerous. According to the FDA, just 1 teaspoon of pure powdered caffeine can contain as much caffeine as 28 cups of coffee, while 4 ounces of liquid, highly concentrated caffeine contains as much as 20 cups. These levels are toxic and dangerous.

How to Drink Less Caffeine

If you are looking for strategies to reduce caffeine use, it's best to cut back gradually. Researchers recommend tapering down over a period of four to six weeks. Doing so will help your body adjust to the reduced levels over time and lessen the chances of experiencing withdrawal symptoms.

In one study, participants who used a gradual tapering-off method reduced their caffeine consumption as follows, based on their usual caffeine intake before starting the reduction:

• Week 1: Consume 75% of usual daily caffeine intake.
• Week 2: Consume 50% of usual caffeine intake.
• Week 3: Consume 25% of usual caffeine intake.
• Week 4: Consume 12.5% of usual caffeine intake.
• Week 5: Consume less than 50 mg of caffeine per day.

You could modify the above guidelines depending on your goals to suit your needs.

Alternative Drinks With Less Caffeine

As you work to reduce your caffeine consumption, replacing your typical coffee or soda with another drink can help. Here are some other lower-caffeine alternatives to try:

• Mushroom coffee
• Sparkling water
• Lemon water

Adjusting to a different drink can take time. That's why tapering your coffee intake while slowly substituting some of your caffeine with other low- or no-caffeine beverages can help.

Caffeine addiction or dependence is called caffeine use disorder. If you have trouble stopping drinking caffeine, you keep using it even though it causes problems, or you have withdrawal symptoms, you may have caffeine dependence.

Gradually reducing how much caffeine you consume may help limit the likelihood of experiencing withdrawal symptoms.

Meredith SE, Juliano LM, Hughes JR, Griffiths RR. Caffeine use disorder: a comprehensive review and research agenda .  J Caffeine Res . 2013;3(3):114-130. doi:10.1089/jcr.2013.0016

American Psychiatric Association. What is a substance use disorder? .

Sweeney MM, Weaver DC, Vincent KB, Arria AM, Griffiths RR. Prevalence and correlates of caffeine use disorder symptoms among a United States sample .  J Caffeine Adenosine Res . 2020;10(1):4-11. doi:10.1089/caff.2019.0020

Rodda S, Booth N, McKean J, Chung A, Park JJ, Ware P. Mechanisms for the reduction of caffeine consumption: what, how and why .  Drug Alcohol Depend . 2020;212:108024. doi:10.1016/j.drugalcdep.2020.108024

Food and Drug Administration. Spilling the beans: how much caffeine is too much?

Centers for Disease Control and Prevention. Maternal diet .

American College of Obstetricians and Gynecologists. How much coffee can I drink while pregnant? .

Food and Drug Administration. Pure and highly concentrated caffeine .

Evatt DP, Juliano LM, Griffiths RR. A brief manualized treatment for problematic caffeine use: a randomized control trial .  J Consult Clin Psychol . 2016;84(2):113-121. doi:10.1037/ccp0000064

By Kathi Valeii Valeii is a Michigan-based freelance writer with a bachelor's degree in communication from Purdue Global.

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Caffeine Use Disorder: A Review of the Evidence and Future Implications

Merideth a. addicott.

Department of Psychiatry and Behavioral Sciences, Duke-UNC Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina, USA

The latest edition of the Diagnostic and Statistical Manual (DSM-5) has introduced new provisions for caffeine-related disorders. Caffeine Withdrawal is now an officially recognized diagnosis, and criteria for caffeine use disorder have been proposed for additional study. caffeine use disorder is intended to be characterized by cognitive, behavioral, and physiological symptoms indicative of caffeine use despite significant caffeine-related problems, similar to other Substance Use Disorders. However, since nonproblematic caffeine use is so common and widespread, it may be difficult for some health professionals to accept that caffeine use can result in the same types of pathological behaviors caused by alcohol, cocaine, opiates, or other drugs of abuse. Yet there is evidence that some individuals are psychologically and physiologically dependent on caffeine, although the prevalence and severity of these problems is unknown. This article reviews the recent changes to the DSM, the concerns regarding these changes, and some potential impacts these changes could have on caffeine consumers.

Introduction

After centuries of cultivation and consumption, our relationship with caffeine has just undergone a major change. The latest version of the Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition (DSM-5) now includes Caffeine Withdrawal Disorder and proposes a set of criteria for caffeine use disorder [ 1 ]. What effect will this have on us and America’s most popular psychostimulant?

Caffeine is generally considered a functional or beneficial drug because it can improve mood and alertness at low doses. At high doses, caffeine produces aversive intoxicating effects. For this reason, caffeine consumption is typically self-limiting and compatible with a social and productive life [ 2 ]. Caffeine is thought to have little to no abuse liability, but perhaps its modest reinforcing effects enhance the desirability of beverages that already have pleasant flavors and aromas, such as coffee, tea, and soft drinks. For many of us who sit behind computer screens all day, these caffeinated beverages help us focus our attention and provide a welcome excuse to get up from our chairs once in a while. Although the question of whether we are all collectively dependent on caffeine has been raised [ 3 ], coffee drinking is thought to be “more a dedicated habit than a compulsive addiction” [ 4 ].

The majority of people who use caffeine safely every day may find it difficult to understand how caffeine use could become disordered or problematic. Of course, many coffee drinkers probably have had a personal experience with withdrawal symptoms if they skipped their morning coffee, but the remedy for that is simply a cup of coffee. But what if someone were convinced he could not function without caffeine? What if he took increasingly greater amounts of caffeine to improve his ability to function, until he began to experience the effects of caffeine intoxication or withdrawal more days than not? What if he were told that his caffeine use was physically harming his body, but he could not reduce his use? At what point does caffeine use become disordered?

A few studies have suggested that some individuals meet the criteria for substance dependence regarding their caffeine use. However, many questions remain regarding the prevalence, development, and severity of disordered caffeine use. To help answer these questions and guide future research on this topic, the DSM-5 proposes a set of criteria for caffeine use disorder (CUD). This article reviews the caffeine-related changes to the DSM and the recent research and evidence for disordered caffeine use.

DSM-IV Caffeine-Related Diagnoses

Caffeine withdrawal.

The fourth edition of the DSM (DSM-IV) recognized four caffeine-related diagnoses: Caffeine Intoxication, Caffeine-Induced Anxiety Disorder, Caffeine-Induced Sleep Disorder, and Caffeine-Related Disorder Not Otherwise Specified (NOS) [ 5 ]. The criteria for Caffeine Intoxication included recent caffeine use, usually in excess of 250 mg, and 5 or more symptoms that develop shortly thereafter, such as restlessness, nervousness, insomnia, gastrointestinal disturbance, and tachycardia. Of the caffeine-related diagnoses included in the DSM-IV, caffeine withdrawal is notably absent, although a proposed set of criteria was included to encourage future research. The DSM-IV recognized that “some individuals who drink large amounts of coffee display some aspects of dependence on caffeine and exhibit tolerance and perhaps withdrawal. However, the data are insufficient at this time to determine whether these symptoms are associated with clinically significant impairment that meets the criteria for Substance Dependence or Substance Abuse” ([ 5 ], page 212).

Over the past 30 years, there have been a large number of studies characterizing caffeine withdrawal symptoms (for review, see [ 6 , 7 ]). As a result, the DSM-5 includes diagnostic criteria for Caffeine Withdrawal, which consists of prolonged daily use of caffeine and 3 or more withdrawal symptoms occurring within 24 hours of abrupt cessation or reduction of caffeine use. These symptoms include headache, marked fatigue or drowsiness, dysphoric mood/depressed mood/irritability, difficulty concentrating, and flu-like symptoms [ 1 ].

Caffeine Dependence

Concurrent with research on caffeine withdrawal, investigators have also been studying caffeine’s abuse potential. Although the DSM-IV included a Substance Dependence diagnosis for every other recognized substance, there were no criteria or proposed criteria for caffeine dependence. Therefore, investigators adapted the DSM-IV Substance Dependence criteria for caffeine use to use in their research. The criteria for Substance Dependence consisted of a maladaptive pattern of substance use with clinically significant impairment manifested by 3 or more symptoms within a 12 month period. These symptoms included: 1) tolerance, 2) withdrawal, 3) substance used in larger amounts or over a longer period than intended, 4) a persistent desire or unsuccessful effort to control use, 5) a great deal of time spent obtaining, using, or recovering from the substance, 6) forgoing important activities because of the substance, 7) and substance use continued despite knowledge of having a persistent or recurrent physical or psychological problem likely to be caused or exacerbated by the substance (i.e., ‘use despite harm’) [ 5 ].

There have been four notable studies that have investigated caffeine dependence. Strain et al. recruited participants who believed they were psychologically or physiologically dependent on caffeine. The authors reported that 16 out of 27 subjects met 3 out of 4 criteria for caffeine dependence including tolerance, withdrawal, persistent desire/unsuccessful efforts to control use, and ‘use despite harm’ (e.g., using caffeine against medical advice) [ 8 ]. A similar study by Juliano et al. reported that 93% of 94 subjects met 3 out of 7 criteria for caffeine dependence, and 55% of subjects met 5 out of 7 criteria. Most of the interviewees reported at least one serious attempt to quit or reduce caffeine without success and 43% were advised by a health professional to reduce caffeine use for health reasons (including cardiovascular problems, fibrocystic breast disease, pregnancy, anxiety, headaches, sleep difficulties, or to reduce caloric intake from caffeinated soft drinks) [ 9 ]. Another study by Striley et al. recruited subjects who were expected to have high rates of drug use/abuse. The authors reported that 35% of 167 subjects endorsed 3 out of 7 caffeine dependence criteria [ 10 ]. Lastly, Hughes et al. conducted random phone surveys of Vermont residents. They reported that 30% of 162 subjects endorsed 3 or more criteria, with the highest percentage of people endorsing a desire to control caffeine use, followed by spending a great deal of time with the drug, and using more caffeine than intended [ 11 ].

In summary, these studies suggest that caffeine use has the features of substance dependence for some individuals. Furthermore, they suggest that not all caffeine users can simply quit on their own, which is an attitude probably held by some health professionals [ 9 ]. However, these studies have several limitations. Three of the studies used targeted subject samples [ 8 – 10 ], and so the prevalence of caffeine dependence in the general population cannot be estimated. Additionally, in two of the studies, interviews were not conducted by psychiatric clinicians, so issues of severity and harm related to caffeine dependence may not have been adequately addressed [ 10 , 11 ]. The studies on caffeine dependence reviewed here were conducted prior to the publication of the DSM-5 in 2013. Although caffeine dependence did not become an officially recognized diagnosis in this edition, these and other studies elicited interest in the psychiatric community to learn more about disordered caffeine use.

DSM-5 Caffeine-Related Diagnoses

The fifth edition of the DSM (DSM-5) includes Caffeine Intoxication, Caffeine Withdrawal, Other Caffeine-Induced Disorders (e.g., Anxiety and Sleep Disorders), and Unspecified Caffeine-Related Disorder. In this edition, Substance Abuse and Substance Dependence are now represented by Substance Use Disorder (SUD), which is applied to all classes of substances except for caffeine. For this diagnosis, individuals must endorse at least 2 of the following criteria: 1) substance used in larger amounts or over longer period than intended, 2) a persistent desire or unsuccessful effort to control use, 3) a great deal of time spent obtaining, using, or recovering from the substance, 4) craving the substance, 5) substance use interfering with ability to fulfill major obligations, 6) substance use despite social problems related to use, 7) important occupational or social activities given up because of substance use, 8) recurrent use in situations when it is physically hazardous, 9) ‘use despite harm’, 10) tolerance, and 11) withdrawal [ 1 ].

The DSM-5 does not include a diagnosis of caffeine use disorder (CUD) because, according the APA, it is not yet clear to what extent it is a clinically significant disorder. However, caffeine use disorder is included in Section III (Emerging Measures and Models) of the DSM-5 to encourage further research on the impact of this condition [ 12 ]. The proposed CUD criteria are the same as other SUD; however, the CUD diagnosis is designed to be more conservative. For a CUD diagnosis, all three of the following criteria need to be endorsed: 1) a persistent desire or unsuccessful effort to control use, 2) ‘use despite harm’, and 3) withdrawal. This higher threshold is intended to prevent over-diagnosis of CUD given the prevalence of nonproblematic caffeine use in the general population [ 1 ]. These proposed criteria are intended to encourage more research on the reliability, validity, and prevalence of CUD, as well as its functional consequences on the lives of those affected by it.

Current literature on caffeine use disorder

There are 3 notable articles that summarize the current attitudes and information regarding Caffeine Withdrawal and CUD. First, a roundtable discussion with Drs. Hughes, Griffiths, Juliano, and Budney provides an excellent overview of the caffeine-related changes to the DSM-5 and explains some of the decision-making process behind the revisions, as well as the concerns about Caffeine Withdrawal and CUD over-diagnosis [ 13** ]. The discussants explain how the more conservative criteria for CUD than other SUDs should help prevent over-diagnosis, but at the same time, diagnoses included in the DSM should not be exceedingly rare. Thus, more information is needed on the prevalence of CUD before deciding whether it belongs in the DSM. Another issue raised by the panel is that there is a common perception of caffeine being a functional drug; in fact, there has been a substantial amount of research on its benefits (for review, see [ 14 ]). However, once caffeine (or any other substance) has been determined to be an addictive drug, then prejudices against discussing any potentially beneficial effects often develop in the psychiatric community [ 13** ]. This conflict of interest could interfere with future caffeine research.

A second article complements some of the issues raised by the roundtable concerning attitudes among the psychiatric community, including both researchers and clinicians. Budney et al. (2013) investigated popular opinions about caffeine dependence/CUD among members of professional societies relevant to addiction. An overwhelming majority (95%) of those surveyed believed that caffeine cessation can produce withdrawal and 73% thought withdrawal could have clinical importance, but fewer than half thought caffeine withdrawal should be in the DSM. A small majority (58%) of respondents thought that some individuals could develop CUD, and 44% believed CUD should be a DSM diagnosis [ 15 ]. These attitudes will be influenced by research published over the next few years and could affect what caffeine-related diagnoses are included in the next edition of the DSM.

Lastly, Meredith et al. provides a comprehensive review of studies on caffeine use/abuse/dependence and summarizes the existing evidence in support of the 3 primary CUD criteria. The authors also present a number of research directions needed to further support and understand CUD. As the authors note, the prevalence of CUD is difficult to estimate from existing studies since DSM-IV criteria for caffeine dependence was used previously and the current criteria for CUD is slightly different [ 16** ].

Use Despite Harm

Before CUD can become an official diagnosis, more research is needed on the severity of symptoms of the 3 primary criteria: 1) a persistent desire or unsuccessful effort to control use, 2) substance use continued despite knowledge of having a persistent or recurrent physical or psychological problem likely to be caused or exacerbated by the substance (i.e., ‘use despite harm’), and 3) withdrawal [ 1 ]. In this author’s opinion, criterion 2 is the most contentious issue and in need clarification. Some authors appear to accept that caffeine consumption is associated with negative health effects (e.g., [ 9 , 10 ]) while others believe that it is not (e.g., [ 2 , 11 , 17 ]). These opinions can influence research directions and hypotheses; therefore, closer examination of this criterion is needed to promote consensus on what health problems can define ‘use despite harm’ for CUD.

Evidence for physical problems caused or exacerbated by caffeine

Large, acute doses of caffeine are known to cause caffeine intoxication, which can cause a significant threat to one’s health and require medical attention. McCarthy et al. reviewed caffeine-related calls to a state poison control center. Out of 254 reported cases of caffeine abuse, 106 patients were managed in an emergency department and 34 were hospitalized and/or admitted to an intensive care unit [ 18* ]. In addition, Ogawa and Ueki presented 2 case reports of individuals whose daily caffeine use escalated until symptoms of caffeine intoxication made medical intervention necessary [ 19* ]. Clearly, caffeine intoxication is a medically significant health problem. However, could an otherwise healthy individual meet the criterion for ‘use despite harm’ by consuming a low to moderate daily dose of caffeine? A review by Nawrot et al. on caffeine and health recommended that doses up to 400 mg/day are safe [ 20 ]; however, it is difficult to determine the health effects of low to moderate daily doses of caffeine because the effects of caffeine cannot be easily separated from the effects of caffeinated beverages, usually coffee, tea, soft drinks, or energy drinks. The antioxidant effects of polyphenols in tea and coffee are thought to have health benefits, while the excess sugars in soft drinks and energy drinks can be detrimental. Despite these confounds, there has actually been a great deal of research on the health effects of caffeine. However, the data are inconsistent.

A review of the literature on caffeine and health is outside the scope of this article, but a brief example may be informative: Caffeine causes a small, temporary increase in blood pressure in normotensive adults. Tolerance may develop to these effects in some people, but caffeine could pose a threat to patients with, or at risk for, hypertension. Some studies have suggested an increased risk of sustained hypertension following coffee consumption (e.g., [ 21 ], while others have not found a significant relationship (e.g., [ 22 ]). Even two recent meta-analyses on caffeine and hypertension arrived at different conclusions: one found no evidence of a relationship [ 23 ] and the other found an elevated risk of hypertension associated with 1–3 cups of coffee per day, but not with 3 or more cups per day [ 24 ].

Clinicians make recommendations to their patients based on their knowledge of the literature, but the literature on caffeine and health is enormous and complicated. In at least two of the studies on caffeine dependence, subjects met the criteria for ‘use despite harm’ if they admitted using caffeine against medical advice [ 8 , 9 ]. If a clinician who read about an association between caffeine and hypertension (e.g., [ 21 ]) recommended to her hypertensive patient to stop drinking coffee and he did not, should that patient meet the criteria for ‘use despite harm’ even though another physician who read a different article (e.g., [ 22 ]) would not have made the same recommendation?

To this author’s knowledge, low to moderate daily caffeine intake has not been proven to cause significant and irreversible health problems that would warrant medical intervention. That is not to say that caffeine does not or cannot have negative health effects, but researchers and clinicians need to agree on what physical health problems can be caused by chronic low to moderate caffeine intake. Whether or not low to moderate daily doses of caffeine can cause physical harm is an important issue to resolve since medical professionals recommend limiting/eliminating caffeine intake to some of their patients, and health concerns are a common reason for individuals to want to modify their caffeine use [ 9 ]. Furthermore, the fate of CUD in the next edition of the DSM may depend on the definition of ‘use despite harm’, since the other two primary criteria for CUD (i.e., a persistent desire or unsuccessful effort to control use and withdrawal) could potentially be endorsed at any daily dose, even while consuming as little as 100 mg/day [ 25 ].

Evidence for psychological problems caused or exacerbated by caffeine

The DSM-5 recognizes that some features of CUD may be positively associated with other psychiatric diagnoses [ 1 ], and there have been studies investigating whether caffeine use or withdrawal can exacerbate existing psychiatric symptoms. In particular, the anxiogenic effects of high caffeine doses can aggravate symptoms of anxiety, panic disorder, and insomnia (for review, see [ 17 , 26 ]). In fact, a review of eight studies that administered a caffeine challenge to patients with panic disorder found that caffeine aggravated symptoms of anxiety and panic disorder in every study [ 27 ]. While this review provides strong evidence that caffeine can exacerbate anxiety and panic disorder, these studies were caffeine challenges and not representative of the patients’ normal caffeine intake. Patterns of actual caffeine consumption among psychiatric patients have been shown to be similar to matched controls; however, maximum lifetime intake was higher among patients [ 28 ]. In addition, the prevalence of caffeine dependence and intoxication was reportedly higher in patients, who endorsed consuming more caffeine than intended, having a desire to cut down, and using caffeine despite harm more often than controls [ 28 ]. However, even among psychiatric patients, caffeine can act as a functional drug. Low to moderate daily doses of caffeine can reduce anxiety and elevate mood, and may even improve symptoms of attention-deficit hyperactivity disorder, although large scale clinical trials have not been conducted [ 17 ]. To date, the evidence suggests that caffeine use is associated with, but does not cause, psychiatric and substance use disorders [ 29 ]. The research on caffeine use and psychiatric disorders raises the possibility of increased risk for CUD or caffeine intoxication due to disordered use among certain patient populations and more studies are needed on the prevalence of caffeine use among individuals with psychiatric problems.

Co-use with Other Substances

Another potential contribution to disordered caffeine use is co-use with other substances. Caffeine may facilitate the effects of other drugs of abuse [ 2 ]. In particular, combining caffeinated energy drinks with alcoholic beverages has become a popular phenomenon because high doses of caffeine may offset the subjective intoxicating effects of alcohol; this is problematic because the objective intoxicating effects of alcohol are not affected [ 30 ]. Furthermore, the co-use of caffeine and sugary soft drinks may cause cross-sensitization, especially among children, and this could lead to poor dietary habits across the lifespan [ 31** ]. Too many caffeinated soft drinks in one’s diet could increase the risk of obesity [ 32 ] and dental caries [ 33 ] in children and adolescents.

In conclusion, future research on CUD must demonstrate that enough people, but not too many, meet the criteria for disordered caffeine use, and that the severity and frequency of problems resulting from this use significantly interfere with their well-being and daily function. In addition, tests of the reliability and validity of CUD criteria are needed, as well as clinical treatment options and their efficacy. If the same standard of harm can be met for caffeine as for other drugs of abuse, then perhaps in another 20 years caffeine use disorder will be an official diagnosis in the DSM-6. Official recognition of CUD could significantly impact popular opinions towards caffeinated beverages and affect their legal regulation. After all, twenty years ago, caffeine withdrawal was not an officially recognized diagnosis in the DSM-IV [ 5 ], but now there is sufficient evidence of caffeine withdrawal to warrant inclusion in the DSM-5. Many people are now aware that chronic caffeine use can result in physical dependence and there has been pressure on manufacturers of caffeinated beverages to disclose their products’ caffeine content. Some researchers have even recommended warning labels on caffeinated beverages [ 34 ].

The roundtable discussion raised an important issue: if caffeine use were proven harmful in some capacity, then a bias may develop among researchers against discussing any of its potential benefits on health, cognition, or arousal [ 13** ]. In this event, could there also be public backlash against caffeine consumption? If so, there may be legislative pressure to limit access to caffeine, or to apply age-restrictions on who can purchase and consume caffeine, in order to reduce the likelihood of caffeine-related problems among the general population. However, considering the amount of trade and commerce surrounding caffeinated beverages, caffeine use is not only a public health concern, but a major economic concern as well. It would not be surprising if coffee, tea, soft drink, and energy drink industries took an active role in dissuading official recognition of CUD in the DSM, especially if that recognition meant increased regulation of caffeinated products.

The recent research on caffeine has important considerations for health professionals and consumers. It appears that not all consumers are aware they are dependent on caffeine, or realize that their fatigue, headache, nausea or other symptoms are related to caffeine withdrawal, instead of an illness [ 13** ]. Several authors recommend increasing awareness among both clinicians and patients about the relationship between caffeine use, health, and psychiatric disorders [ 19* , 28 , 34 ], and also recommend including caffeine use assessments during psychiatric evaluations [ 26 ]. Importantly, the last survey of caffeine use in America was published in 2005 [ 35 ] and this information needs updating. Lastly, a survey of what clinicians are recommending to their patients regarding caffeine use would be valuable information for researchers and health professionals. In addition to these recommendations, there are many more potential avenues for future caffeine research. On the other hand, since caffeine is the most widely used psychoactive drug in the world and there are upwards of 20,000 research articles on caffeine, there may be little left to learn about this substance and our relationship with it.

Acknowledgments

This work was supported by National Institutes of Health grants K01 DA033347 (NIDA).

Conflict of Interest Merideth A. Addicott declares she has no conflict of interest.

Compliance with Ethics Guidelines

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by the author.

Papers of particular interest, published recently, have been highlighted as:

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** Of major importance

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