A Comprehensive Overview of the Risks and Benefits of Coffee Consumption: Coffee consumption and human health…

Abstract

Findings on both the health benefits and the potentially harmful effects of coffee consumption have been contradictory. However, the general scientific consensus is that moderate, regular coffee drinking by healthy individuals is either essentially benign or mildly beneficial. Results and generalizations are complicated by a number of factors, including differences in age, gender, health status, type of coffee preparation, serving size, and source of coffee. Coffee may have potential health benefits and risks, but causality cannot be established for either with the research currently available as these are largely based on observational data. This review aimed to provide a comprehensive overview of the risks and benefits of coffee consumption on health outcomes. A systematic search (search terms: "coffee" OR "coffee adj3" [consum* or intake* or drink*]) of the literature (from 1970; humans; in English) using the electronic databases "OVID," "CINAHL," and "Web of Knowledge" returned 12405 results. Duplicates were removed, studies were screened (based on inclusion/exclusion criteria), and the remaining eligible studies (n = 1277) were used to collate an exhaustive list of the potential health benefits and risks of coffee consumption, which were grouped and are discussed with regard to major diseases/conditions (mortality, cardiovascular disease, cancer, and metabolic/liver/neurological disorders), at-risk/vulnerable groups, and specific coffee constituents. This qualitative assessment has shown that the health benefits (or null effects) clearly outweigh the risks of moderate coffee consumption in adult consumers for the majority of health outcomes considered. Results from this research may aid further qualitative and quantitative deterministic risk-benefit assessments of coffee consumption.

Full text

A Comprehensive Overview of the Risks
and Benefits of Coffee Consumption
L. Kirsty Pourshahidi, Luciano Navarini, Marino Petracco, and J.J. Strain
Abstract: Findings on both the health benefits and the potentially harmful effects of coffee consumption have been
contradictory. However, the general scientific consensus is that moderate, regular coffee drinking by healthy individuals
is either essentially benign or mildly beneficial. Results and generalizations are complicated by a number of factors,
including differences in age, gender, health status, type of coffee preparation, serving size, and source of coffee. Coffee
may have potential health benefits and risks, but causality cannot be established for either with the research currently
available as these are largely based on observational data. This review aimed to provide a comprehensive overview of the
risks and benefits of coffee consumption on health outcomes. A systematic search (search terms: “coffee” OR “coffee
adj3” [consum*or intake*or drink*]) of the literature (from 1970; humans; in English) using the electronic databases
“OVID,” “CINAHL,” and “Web of Knowledge” returned 12405 results. Duplicates were removed, studies were screened
(based on inclusion/exclusion criteria), and the remaining eligible studies (n=1277) were used to collate an exhaustive
list of the potential health benefits and risks of coffee consumption, which were grouped and are discussed with regard
to major diseases/conditions (mortality, cardiovascular disease, cancer, and metabolic/liver/neurological disorders), at-
risk/vulnerable groups, and specific coffee constituents. This qualitative assessment has shown that the health benefits (or
null effects) clearly outweigh the risks of moderate coffee consumption in adult consumers for the majority of health
outcomes considered. Results from this research may aid further qualitative and quantitative deterministic risk–benefit
assessments of coffee consumption.
Keywords: benefit, coffee, health, human, risk
Introduction
Coffee is a widely consumed beverage worldwide and extensive
scientific research has been conducted to examine the relationship
between coffee consumption and a wide range of chronic diseases
and health outcomes, including total mortality, many cancers, car-
diometabolic risk, liver disorders, and neurological conditions.
Such effects have been attributed to many different bioactive con-
stituents of coffee, including caffeine (methylxanthine), chloro-
genic acids (polyphenol), diterpenes, and other phenolics, some
of which may also potentially have additive or synergistic effects.
Although both findings on the potential health benefits and
harmful effects of coffee consumption have historically been re-
ported, the general consensus is that moderate, regular coffee
drinking by healthy individuals is either essentially benign or
mildly beneficial (George and others 2008; Cano-Marquina and
others 2013; O’Keefe and others 2013; Fardet and Boirie 2014).
Findings to-date are largely based on observational data, albeit
from large prospective cohort studies and case–control and cross-
MS 20151797 Submitted 28/10/2015, Accepted 7/3/2016. Authors Pourshahidi
and Strain are with Northern Ireland Centre for Food and Health (NICHE),
Univ. of Ulster, Coleraine, BT52 1SA, UK Authors Navarini and Petracco are
with illycaff`
e s.p.a, Trieste, Italy. Direct inquiries to author Pourshahidi (E-mail:
k.pourshahidi@ulster.ac.uk)
sectional data. However, heterogeneity between study populations
and designs, and also lack of control for many other confounding
factors, add limitations to the existing literature. Moreover, studies
or meta-analyses to-date typically focus on single disease outcomes
or endpoints and few (if any) weigh up the benefits and risks on
multiple health outcomes.
Therefore, the aim of this review was to provide a comprehen-
sive overview of the risks and benefits of coffee consumption on
health outcomes.
Methods
A systematic search for the appropriate literature (from 1970,
limited to humans and available in English) was conducted using
the online electronic databases “OVID” (AMED, FSTA, EM-
BASE, MEDLINE [PubMED], PSYCinfo), “CINAHL” (aca-
demic journals only), and “Web of Knowledge: Web of Science
with Conference Proceedings,” together with manual searches of
reference lists.
Searches were conducted using coffee as a broad search term, or
within 3 words of consumption/consume(r), intake(s), or drink(s)
(“coffee” OR “coffee adj3” [consum*or intake*or drink*]).
Duplicates were then removed, and remaining studies were
screened for eligibility based on set inclusion and exclusion criteria
(Table 1). To be eligible for inclusion, studies must have been
conducted in humans and have reported original data linking the
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Coffee consumption and human health . . .
Table 1–Study inclusion/exclusion criteria.
Inclusion criteria Exclusion criteria
Human observational and intervention original research studies In vitro or animal studies, systematic reviews or meta-analyses
Examined coffee consumption and reported health outcome(s) No health outcome
English No original data (for example, letters/editorials)
Published 1970 to 30 June 2015 Not available in English
Published before 1970
Figure 1–Study selection and screening.
effect of coffee consumption on a specified health outcome(s). All
types of coffee were included as relevant (such as instant, filtered,
cafetiere, or boiled), although those studies concerned with the
effect of caffeine per se were excluded.
Eligible studies were then qualitatively evaluated and were used
to collate an exhaustive list of the potential health benefits and
harmful effects of coffee consumption. Health benefits and risks
were grouped and discussed with regard to:
rtotal mortality;
rcardiovascular disease (CVD);
rcancers;
rmetabolic health (for example, diabetes, metabolic syndrome,
insulin resistance, weight gain);
rliver disorders (for example, nonalcoholic fatty liver disease,
cirrhosis);
rgastrointestinal conditions (for example, peptic/gastric ulcers,
dyspepsia, bowel function);
rneurological disorders (for example, Alzheimer’s disease, de-
mentia, cognitive function/decline, mental health);
rother miscellaneous health outcomes/conditions.
Additional risks of coffee consumption were also discussed ac-
cording to at-risk/vulnerable groups (for example, pregnancy, el-
derly) and specific “bioactive” constituents identified during the
literature search (such as, caffeine, diterpenes, acrylamide, furan,
mycotoxins).
Results
The study selection and screening process is illustrated in
Figure 1. Initially, 12329 results were returned following the liter-
ature searches. An additional 76 studies were identified by email
alerts updating the searches within the Web of Knowledge database
(total, n=12405 studies).
After screening to remove duplicate citations (n=6047) and
exclusion of the studies deemed unsuitable for inclusion (n=
5081) based on the predetermined inclusion/exclusion criter ia, a
total of 1277 studies were included in the review. This represented
approximately 10% of those studies identified by the original search
strategy.
For each category of the health conditions/outcome discussed
below, example citations are included to highlight the key points.
A complete bibliography list of all studies reviewed is included as
Supplementary Material.
Cancer
Coffee consumption has been linked to cancer risk or incidence
in virtually every tissue type in the body, with the most commonly
reported subsites being colorectal, bladder/urinary tract, pancre-
atic, and female-specific and breast cancers. A total of 352 (27.6%)
studies have reported links between coffee consumption and can-
cer, and these are typically observational (Table 2). Only the more
mechanistic studies are tested using an intervention study design.
Observational findings have for the majority reported a bene-
ficial or null effect of coffee consumption on cancer, with the
exception of bladder/urinary tract cancers where the risks of
coffee consumption are more commonly reported. An increased
risk of bladder/urinary cancer, however, was typically only re-
ported in males, not females (Hartge and others 1983; Marrett
and others 1983; Clavel and Cordier 1991; Zeegers and others
2001) and nonsmokers compared to smokers (Pujolar and oth-
ers 1993). Negative interactions with alcohol (Donato and others
1997) were also evident, together with an influence of certain
genetic polymorphisms (such as CYP1A2; Pavanello and others
2010). Moreover, other studies only reported an increased risk
of cancer of the urinary system to be evident in consumers of
Turkish coffee (Akdas and others 1990), high coffee consumers
(40+cups per week; Slattery and others 1988), or have failed to
demonstrate a dose–response (Simon and others 1975; D’Avanzo
and others 1992), which suggested that such associations are
noncausal.
Similar modifiers of risk are also noted in the observational
evidence for other types of cancer. Coffee drinking appears to
increase the risk of gastric (Galanis and others 1998) and col-
orectal cancer in men (Slattery and others 1990; Boutron-Ruault
and others 1999; Yamada and others 2014) but not in women
(Lee and others 2007), although the authors queried if the former
was just a chance finding (Galanis and others 1998). The risk of
pancreatic cancer also appears to be higher in smokers (Gorham
and others 1988; Harnack and others 1997) and nonconsumers
of alcohol (Clavel and others 1989), whilereas genetic polymor-
phisms (CYP1A2 and GSTM1/GSTT1) can modify the relation-
ship between coffee consumption and risk of breast (Kotsopoulos
and others 2007; Bageman and others 2008; Ayari and others
2013), ovarian (Goodman and others 2003), and skin (Fortes and
others 2009, 2013) cancer. In some instances, only caffeinated
coffee appears to be protective when compared with decaffeinated
coffee (for example, in skin, endometrial, and some gastric can-
cers; Abel and others 2007; Bhoo-Pathy and others 2015; Sanikini
and others 2015) but in other studies, the opposite is true (for ex-
ample, for ovarian, rectal and lung cancers; Michels and others
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Coffee consumption and human health . . .
Table 2–Number of studies investigating cancer and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Type of cancer ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Colorectal 28 30 11
Bladder/urinary tract 3 33 33
Pancreas 5 35 7
Female-specific (ovarian,
endometrial, vulva)
15 17 8
Breast 15 18 5
Prostate 8 14 4
Oral/upper aerodigestive tract 13 5 5
Gastric 6 9 7
Mechanisms (DNA damage, DNA
integrity, oxidative damage)
592 4
Carcinomas (hepatocellular,
squamous/basal cell, soft tissue)
14 5
Renal/kidney2113
Skin 9 3
Lung/respiratory tract 2 4 4
All types (or tobacco-related) 2 4
Lymphoma’s 2 2 1
Leukemia 211
Liver 4
Brain/glioma 1 1 2
Thyroid 1 1
Gallbaldder/bile ducts 1
Total 138 9 195 0 95 0
aTotal number of studies, n=352.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
2005; Baker and others 2005, 2007). Comparisons between other
types of coffee preparations also produce equivocal results within
the literature, for example for boiled (not filtered) versus filtered
coffee (Nilsson and others 2010; Tverdal 2015) or hot versus iced
coffee (Green and others 2014), and risks are also typically associ-
ated with heavy coffee consumption (Gullo and others 1995; Efird
and others 2004; Luo and others 2007; Lueth and others 2008;
Bissonauth and others 2009) or coffee abuse (Uzcudun and others
2002) compared to light/moderate coffee consumption. Finally,
for some cancers, risks also appear to be more apparent in younger
adults (<60 years; Gallus and others 2007), with a null or benefi-
cial (inverse) effect of coffee consumption on cancer risk becom-
ing apparent only in older adults after more than 35 years coffee
consumption (Kokic and others 1996), or in postmenopausal com-
pared to premenopausal females (Kuper and others 2000; Koizumi
and others 2008).
More consistently, positive or beneficial associations between
coffee consumption and cancer risk are evident in the mecha-
nistic studies, and as alluded to above, this evidence more often
than not comes from intervention studies. Such research reports a
protective or beneficial effect of coffee consumption on antioxi-
dant status (Bakuradze and others 2011), oxidative DNA damage
(Steinkellner and others 2005; Hoelzl and others 2010; Misik and
others 2010; Bakuradze and others 2011; Hori and others 2014),
urine mutagenicity (Aeschbacher and Chappuis 1981), and DNA
strand breaks/integrity (Bakuradze and others 2014, 2015). Over-
all, these data from intervention studies would suggest that coffee
can have a beneficial role in terms of reducing the risk of some
cancers.
Cardiovascular disease
A total of 273 (21.4%) studies have reported links between cof-
fee consumption and cardiovascular disease (CVD), and they are
mainly observational, although some evidence from intervention
studies is reported, particularly for hyperlipidemias, hypercholes-
terolemia, and blood pressure (Table 3). Such studies have reported
on a number of different outcomes or disease endpoints, ranging
from mechanistic studies focusing on individual risk factors (or
causes of such) to those reporting adverse events such as myocar-
dial infarction, heart failure, or stroke.
Within CVD, the major ity of evidence has reported negative (or
null) associations between coffee consumption and blood choles-
terol (that is, an increased risk of hypercholesterolemia). Such
inverse associations though are mainly caused by the consumption
of cafetiere (Urgert and others 1995, 1996), French-press (De
Roos and others 2000), Arabic (el Shabrawy Ali and Felimban
1993), or boiled coffee (Bonaa and others 1988; Bak and Grobbee
1989; Pietinen and others 1990; Lindahl and others 1991; Ahola
and others 1991; Van Dusseldorp and others 1991; Fried and
others 1992), as compared to filtered coffee preparations. A direct
dose-dependent effect is also evident (Aro and others 1990;
D’Avanzo and others 1993) and another study has quantified
a 1.66 and 1.58 mg/dL increase in Low density lipoprotein
(LDL)-cholesterol per daily cup of coffee consumed by men
and women, respectively (Berndt and others 1993). Moreover,
abstinence from coffee for at least 6 weeks will lower cholesterol
concentrations in the general population (Christensen and others
2001) and in hypercholesterolemic patients (Forde and others
1985). This negative effect of coffee on cholesterol concentrations,
particularly from boiled coffee, is owing to higher concentrations
of diterpenes (kahweol and cafestol) in such coffee preparations
(deGroot and others 1996; Gross and others 1997; Naidoo and
others 2011). However, 4 randomized controlled trials have
shown that diterpenes have lipoprotein(a)-reducing potential, but
the authors concluded that their well-known adverse side effects
on LDL cholesterol preclude their use as such (Urgert and others
1997). Of interest, an inverse relationship has been reported
between coffee consumption and triglyceride concentrations
(Carson and others 1994; Lancaster and others 1994; Miyake and
others 1999), which requires further investigation.
Risks of raised blood pressure/hypertension in coffee consumers
are also apparent within the literature, and this pressor effect may
be caused by a coffee-induced increase in adrenaline concentra-
tions (Smits and others 1986a,b; Palatini and others 2009). The
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Coffee consumption and human health . . .
Table 3–Number of studies investigating cardiovascular disease (CVD) and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Type of CVD/CV outcome ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Hypercholesterolemia/lipidemia 6 4 29 13 37 14
Blood Pressure/hypertension 9 5 11 7 15 11
Myocardial infarction 1 10 1 13 2
CVD 5 9 7 4
Homocysteine 2 4 3 10 6
CHD 2 8 12
Stroke/blood clot/clotting 7 3 2 6 1
Coronary events 2 1 4 7
Endothelial function 4 1 1 1 2 1
Hemodynamic effects/hemostasis 1 3 2
Gout/uric acid 3 1 2
Heart rate 1 2 1 1 1
CAD 113
Heart failure 1 2 1
Atherosclerosis 1 1 1 1
IHD 3
CRP (inflammation) 2 1
Aortic/coronary calcification 2 1
Peripheral arterial occlusive disease 2
Haptoglobin levels 1
Myelodysplastic syndromes 1
Total 48 20 88 30 119 42
CVD, cardiovascular disease; CHD, coronary heart disease; CAD, coronary artery disease; IHD, ischemic heart disease; CRP, C-reactive protein.
aTotal number of studies, n=273.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
pressor effect, however, was observed more often than not in
coffee na¨
ıve individuals, with no effect seen in habitual drinkers
(Corti and others 2002) or those who have adapted to heavy cof-
fee consumption (8 cups per day for 4 weeks; Ammon and others
1983). Furthermore, although abstinence from coffee for 9 weeks
was able to decrease blood pressure in normotensives (Bak and
Grobbee 1990), others have shown no effect on ambulatory blood
pressure measurements (Eggertsen and others 1993), nor on the
prospective risk of developing hypertension over 33 years (Basile
2002). Indeed, benefits of coffee consumption on blood pressure
have also been reported in human intervention studies conducted
in both normotensive and mildly hypertensive adults (Awaad and
others 2011), and in coffee drinkers with the rapid *1A/*1A geno-
type, compared to the increased risk observed in those with the
slow CYP1A2*1F genotype (rapid vs. slow caffeine metabolizers,
respectively; Palatini and others 2009).
Coffee consumers also appear to be at an increased risk of higher
homocysteine concentrations, an independent risk factor for CVD
(Strandhagen and others 2003; Strandhagen and others 2004; Slow
and others 2004). This relationship may be driven by the chloro-
genic acid (Piters and others 1985) rather than the trigonelline
content of coffee (Slow and others 2004), but, can be modified by
folic acid (Strandhagen and others 2003), particularly in those with
the TT polymorphism of the methylenetetrahydrofolate reductase
(MTHFR) gene which codes for the MTHFR enzyme.
For some outcomes (such as myocardial infarction), the in-
creased risk seen in coffee drinkers is dependent on family history
(Azevedo and Barros 2006), CYP1A2 genotype (Cornelis and
others 2006) and type of coffee preparation (boiled vs. filtered;
Hammar and others 2003), thus highlighting the importance of
adequately controlling for these and other confounders in such
studies. Although, coffee polyphenols (extracted from green cof-
fee beans and given as a single oral ingestion) have been reported
to have a beneficial effect on endothelial function (Ochiai and
others 2014), the opposite or at least a null effect is seen when ei-
ther caffeinated or decaffeinated coffee, respectively, is consumed
as a beverage (Buscemi and others 2010). For other outcomes,
U- or J-shaped risks of coffee consumption have been reported
(Panagiotakos and others 2003; Enga and others 2011). Although
such a relationship would suggest that the cardiovascular benefits
are achieved by moderate (compared to null/little or heavy/high)
coffee consumption, differences in the definition of “moderate
consumption” make it difficult to compare and draw adequate
conclusions between the studies.
Metabolic health
The vast majority of evidence investigating coffee consumption
and metabolic health (Table 4) consistently shows a beneficial (in-
verse) association with the risk of type 2 diabetes (n=126; 9.9%
studies). These associations are at least in part mediated by a de-
creased insulin resistance (or improved insulin sensitivity) and/or
improved glucose tolerance. Direct effects on glucose tolerance
appear to be caused by the antagonistic effect of chlorogenic acid
(with/without caffeine) on glucose transport, shifting glucose ab-
sorption to more distal parts of the intestine (Johnston and others
2003), rather than acting through the incretin hormones. Other
mechanisms of action suggested include associations with low-
grade systematic inflammation (C-reactive protein and sCD163;
Arsenault and others 2009; Chacon 2014), oxidative stress (Baku-
radze and others 2011), and sex-hormone binding globulin (Goto
and others 2011, 2014). Results may also be different depending
on the range of body mass index categories included within the
study (Arsenault and others 2009; Otake and others 2014), and
the use of hormone replacement therapy (HRT; Catalano and
others 2008; Arsenault and others 2009), again highlighting these
as important confounders.
Coffee intake (3 ×250 mL/day for 4 weeks) can also de-
crease energy intake, by improving satiety hormones (ghrelin and
serotonin) and therefore decreasing levels of body fat (Bakuradze
and others 2014). Moreover, others have shown that either the
mannooligosaccharides (Kumao and Fujii 2006) or polyphenols
(chlorogenic acid; Soga and others 2013) in coffee can increase or
stimulate postprandial fat utilization, thus promoting excretion of
fat in the feces.
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Coffee consumption and human health . . .
Table 4–Number of studies investigating metabolic health and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Metabolic outcome ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Type 2 diabetes 33 1 4 1
Obesity/body weight/fat 8 10 8 1 3
IGT 951324
Insulin resistance/sensitivity 6 3 4
Metabolic syndrome 6 3 2
Diabetes (all) 7
Inflammation/oxidative stress 2 2 1
Metabolic health 2 1 1 1
Type 1 diabetes 3
Satiety regulation 1 2
Exercise performance/fitness 1 1
Gestational diabetes 1
Total 7224221010 5
aTotal number of studies, n=126.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
Although some studies have shown an adverse effect on the risk
of metabolic syndrome, this has only been shown, for example, for
higher coffee consumption (>3 cups/day), particularly of instant
coffees with excess sugar and powdered creamer (Kim and others
2014), and therefore these results must be interpreted with caution.
Neurological disorders
Coffee consumption has been positively linked to improvements
in (or a decreased risk of) a number of neurological disorders, with
the most commonly reported being Parkinson’s disease, cognitive
decline/function, and mental health. A total of 94 (7.4%) studies
have reported links between coffee consumption and neurological
outcomes, and they are typically observational (Table 5).
Overall, coffee has been shown to be beneficially associated
with the risk of Parkinson’s disease (Ross and others 2000; Tan
and others 2003; Hosseini Tabatabaei and others 2013; van der
Mark and others 2014), with a dose–response protective relation-
ship apparent (Tan and others 2003), but possibly only in males
(Savica and others 2013; Ascherio and others 2001) and female
non-HRT users (Ascherio and others 2004; Ascherio and others
Mar 2003). Additive effects were also apparent with preceding
diabetes (D’Amelio and others 2009) and smoking (Grandinetti
and others 1994; Powers and others 2008). Although some studies
reported an effect of certain genetic polymorphisms (for exam-
ple, adenosine A2A receptor, CYP1A2, and AP06; Tan and oth-
ers 2006; McCulloch and others 2008; Popat and others 2011),
others have shown no such generic–environmental interactions
(Facheris and others 2008; Chung and others 2013). The protec-
tive effect of coffee on the risk of Parkinson’s disease is at least
in part due to certain alkaloid compounds within coffee acting as
monoamine oxidase inhibitors (Herraiz and Chaparro 2006).
The protective effect of coffee on cognitive decline/function
may be more apparent in females compared to males (Johnson-
Kozlow and others 2002; Arab and others 2011) and such effects on
psychomotor/cognitive performance (Natu and Agarwal 1997) are
more likely to be due to caffeine consumption (Johnson-Kozlow
and others 2002), rather than the chlorogenic acids within coffee
(Camfield and others 2013). Furthermore, it has been postulated
that antioxidants in coffee capable of decreasing reactive oxygen
species may give rise to a reduction in the risk of Alzheimer’s
disease (Kotyczka and others 2011).
Gastrointestinal conditions
Gastrointestinal (GI) complaints have been traditionally linked
in the literature with coffee consumption, with null/adverse asso-
ciations with reflux, ulcers, heartburn, and dyspepsia most com-
monly reported. A total of 73 (5.7%) studies have reported links
between coffee consumption and GI conditions, the majority be-
ing observational studies (Table 6).
Although negative findings are apparent, suggesting an increased
risk of GI complaints in coffee consumers, such negative asso-
ciations are weak at best, and are only reported in univariate,
not multivariate analyses (Bhatia and others 2011); for (unusu-
ally) high coffee consumption (Schlemper and others 1996); they
are perceived side effects by the consumer or patient rather than
being tested/diagnosed (Ostensen and others 1985; Eisig and oth-
ers 1989; Sihvo and Hemminki 1999); or they are only reported
in coffee-sensitive/susceptible individuals (Cohen 1980; DiBaise
2003). Moreover, some of the adverse effects are from acute feed-
ing studies, where coffee is either directly instilled into the stomach
or given intra- or orogastrically (Cohen 1980; Coffey and others
1986; Boekema and others 2001), so results are not comparable
to normal habitual coffee consumption. Others have suggested
that variability in coffee-induced gastric responses may be caused
by differences in bean processing (Van Deventer and others 1992;
DiBaise 2003; Rubach and others 2014), such as dark or light
roasting.
Finally, beneficial effects of moderate coffee consumption on
gut health offer some promise for additional benefits of coffee
drinking among the general population. Such effects have been
reported by 4 intervention studies to-date and include improve-
ments in the fecal microbiota (Umemura and others 2004; Jaquet
and others 2009; Walton and others 2010), and improved colonic
fermentation (Scazzina and others 2011). These positive findings
warrant confirmation in larger and longer-term studies.
Liver disorders
A total number of 72 (5.6%) studies have investigated the
effect of coffee consumption on liver disorders, namely, liver
function/enzymes in general and gallstones/gallstone disease
(Table 7). Overall, this evidence, largely from observational
studies, is showing coffee to have a protective effect on the liver.
In general, coffee may offer protection against alcohol-induced
liver damage/impairment (Corrao and others 1994; Tanaka
and others 1998; Honjo and others 2001; Klatsky and others
2006; Ikeda and others 2010; Marotta and others 2013) and
alcohol-induced hepatic inflammation (Maki and others 2010),
which does not appear to be related to the caffeine content
(Corrao and others 2001; Xiao and others 2014), or antioxidant
activity (Gutierrez-Grobe and others 2012). In some studies,
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Coffee consumption and human health . . .
Table 5–Number of studies investigating neurological disorders and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Type of neurological outcome ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Parkinson’s disease 23 9 1
Cognitive function/decline 12 3 7
Depression/anxiety 6 3 1
Headache/migraine 3 6
Sucide 2 3
Pain 1 1 2
Mental health/disease 2 2
Restless leg syndrome 3
Mood 1 2
Stress 1 2
Blepharospasm 2
Sympathetic nerve activity 1 1
Multiple sclerosis 1
Amyotrophic lateral sclerosis 1
Multiple system atrophy 1
Total 515221231
aTotal number of studies, n=94.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
Table 6–Number of studies investigating gastrointestinal (GI) conditions and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Type of GI outcome ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Reflux 1 9 6
Peptic ulcer disease 8 1 1
Bowel/colonsymptoms 114211
Duodenal ulcer 5 1
Dyspepsia 4 2
Helicobacter pylori 41
Gastric acid secretion 1 1 2
Gastric emptying 2 2
Gut microbiotia/colonic
fermentation
4
Inflammatroy conditions (gastritis,
duodenitis, ulcerative colitis, IBD)
21
Pancreatic function 1 1 1
Heartburn 3
Proximal stomach function 1 2
Gastric ulcer 1 1
Anal fisure 1 1
Intraoesophageal tempature 1
Postoperative ileus 1
Total 4 10 40 7 14 8
GI, gastrointestinal; IBD, inflammatory bowel disease.
aTotal number of studies, n=73.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
such beneficial effects are more evident in males (Pintus and
Mascia 1996; Danielsson and others 2013) and smokers (Kono and
others 1994), compared to females and nonsmokers, respectively.
Strong cafetiere (vs. filtered) coffee, however, may show the
opposite effect. Drinking 5 to 6 cups per day negatively affected
the integrity of liver cells in a 24-week randomized-controlled in-
tervention study (Urgert and others 1996). There is debate in the
literature, however, if the compounds which might be responsible
for such effects are the diterpenes, for example kahweol within
coffee oil (Urgert and others 1996; Boekschoten and others 2004).
Mortality
Overall, coffee consumption has been associated with a reduced
risk of total/all-cause and cause-specific mortality, particularly for
CVD and coronary heart disease (CHD; n=62; 4.9% studies;
Table 8). In contrast, in some of the earlier studies conducted 20+
years ago, CHD or ischemic heart disease (IHD) mortality was
inversely associated with coffee consumption (Heyden and oth-
ers 1976; Hennekens and others 1976; Hemminki and Pesonen
1977; LeGrady and others 1987; Tverdal and others 1990; Klatsky
and others 1993). In these studies, however, risks were related to
sale of coffee, not consumption (Hemminki and Pesonen 1977),
none/very low (0 to 1 cups), or very high (6 to 9+cups) daily
consumption (LeGrady and others 1987; Tverdal and others 1990)
or associated risks were minimal (Hennekens and others 1976) and
therefore results should be interpreted with caution. Similar to the
discussion previously for other conditions, the link between coffee
consumption and mortality seems to vary inconsistently by gender
(Tverdal and others 1990; Jazbec and others 2003; Leurs and others
2010; Liu and others 2013), HRT users versus nonusers (Ascherio
and others 2004), and smoking status (Rosengren and Wilhelm-
sen 1991; Odegaard and others 2015), but remains beneficial in
the majority of evidence, when populations are considered as a
whole.
Other conditions/health outcomes
In addition to all of the health relationships outlined above, a
number of other conditions or health outcomes have also been
linked to coffee consumption. A total of 155 (12.1%) studies are
676 ComprehensiveReviews in Food Science and Food Safety rVol. 15, 2016 C2016 Institute of Food Technologists®

Coffee consumption and human health . . .
Table 7–Number of studies investigating liver disorders and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Liver outcome ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Liver enzymes/function 25 1 3 1 3
Gallstones/gallstone disease 8 1 10 3
Cirrhosis 6
Fibrosis 4 1
NAFLD/fatty liver disease 4 1
Hepatitis C 2 2
Liver disease 1 1
Cholangitis 1
Choledocholithiasis 1
Hepatic drug metabolism 1
Hepatic inflammation 1
Total 524172 3 3
aTotal number of studies, n=72.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
Table 8–Number of studies investigating mortality and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Mortality outcome ObservationalaInterventionbObservationalaInterventionbObservationalaInterventionb
Total/all-cause 14 13 3
CVD/CHD 10 10 6
Cirrhosis 6 1
Cancer (all types) 5 1
Pancreatic cancer 3 3
Prostate cancer 3
Breast/overian cancer 2 1
Respiratory disease 2
Infection/inflammatory disease 2
Parkinson’s disease 1 1
Hepatocellular carcinoma 2
Urinary bladder cancer 1 1
Diatetes 1
Injuries/accidents 1
Oral/pharyngeal cancer 1
Suicide 1
Colon cancer 1
Total 410390160
CVD, cardiovascular disease; CHD, coronary heart disease.
aTotal number of studies, n=62.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
Table 9–Number of studies investigating other conditions and coffee consumption by outcome and type of study.a
Benefit Null effect Risk
Health condition/outcome ObservationalbInterventioncObservationalbInterventioncObservationalbInterventionc
Bone health 3 22 18
Renal (Kidney/Urinary) 7 1 9 1 6
Hormonal conditions/disturbance 5 4 2 3
Nutritionalstatus 3 2171
Fertility 1 6 6
Eye health/vision 1 2 2 2
Sleep conditions 2 1 1 3
Respiratory health 3 2 1
Prostate conditions 1 5
Skin conditions 1 3 1
Ageing 1 2 1
Pancreatic health 1 2 1
Female health 3 1
Other 8 1 4 4
Total 372675543
aTotal number of studies, n=155.
bIncluding cross-sectional, case–control, retrospective, prospective, and longitudinal studies.
cIncluding controlled/noncontrolled, randomised/nonrandomised parallel, and crossover studies.
listed in Table 9 and corresponding conditions within each cate-
gory are listed in Table 10.
Overall, the other most frequently reported condition associated
with coffee consumption is poor bone health. Although approx-
imately half of the studies included in the current review have
shown a null effect on bone outcomes (22 out of 43), a simi-
lar proportion has also reported adverse effects (18 out of 43).
These adverse effects are reported only in lean compared to over-
weight/obese individuals (Korpelainen and others 2003), and in
females, not males (Meyer and others 1997), with high daily coffee
consumption (Meyer and others 1997; El Maghraoui and others
2010). Nevertheless, others have shown that the adverse effects on
C2016 Institute of Food Technologists®Vol.15,2016 rComprehensiveReviewsin Food Science and Food Safety 677

Coffee consumption and human health . . .
Table 10–Details of other conditions related to coffee consumption within the literature.
Category List of conditions
Bone health Risk for osteoporosis; bone mineral density; bone fragility; bone loss; hip fracture; fracture risk; fracture prevalence;
perimenopausal fractures; markers of bone metabolism; T-score variability; risk of rheumatoid arthritis;
musculoskeletal pain
Renal (kidney/urinary) Interstitial cystitis; urinary incontinence; urinary/kidney stones; nephrolithiasis; chronic kidney disease; nocturia;
dehydration; estimated glomerular filtration rate; glomerular function (urinary hydrogen peroxide); hypokalemia;
bladder pain syndrome; IgA nephropathy;
Hormonal Menstrual disturbances; premenstrual syndrome; menstrual function (menstrual pattern, dysmenorrhea);
menopausal/climacteric symptoms (hot flashes and night sweats); onset of menopause; salivary cortisol; sex hormone
and other hormone levels (estradiol, testosterone); erectile dysfunction; anterior pituitary hormones
Nutritional status Iron status/stores; prenatal zinc deficiency; total antioxidant capacity; iron deficiency anemia; B-vitamin status;
tocopherol (adipose tissue content); selenium levels (toenail); serum β-carotene and α-tocopherol; dietary/nutritional
behaviours
Fertility Sperm progressive motility; semen quality; male infertility (azoospermia or oligospermia); sperm aneuploidy; fecundity;
time to pregnancy
Eye health/vision Intraocular pressure; exfoliation glaucoma/glaucoma suspect; macular edema; cataract; age-related maculopathy;
choroidal thickness
Sleep conditions Insomnia; drowsiness; sleep problems; alertness, sleep onset and sleep quality; alertness and performance
Respiratory health MRSA nasal carriage; pulmonary function; bronchial asthma;
Prostate conditions Benign prostatic hyperplasia; prostatic hypertrophy
Skin conditions Psoriasis; dermatoses; skin photoprotection
Aging Skin aging; frailty; health-related quality of life; reaching 90 years of age
Pancreatic health Pancreatitis; chronic calcific pancreatitis of the tropics; pancreatic ductal adenocarcinoma
Female health Fibrocystic breasts; benign breast disease; endometriosis
Other Thyroid disease; serum uric acid/hyperuricemia; acute hyperammonemia; urinary vanilmandelic acid levels; tinnitus;
hearing function; periodontal health/disease; oral clefts
bone mineral density can be offset by milk, typically consumed
with coffee (Barrett-Connor and others 1994), and are only ev-
ident in those with the rapid CYP1A2 CC genotype (Hallstrom
and others 2010), and may not translate into an increase in fracture
risk in the longer-term (Trimpou and others 2010; Hallstrom and
others 2013). Additional research is clearly warranted to elucidate
the effect of coffee consumption on bone health.
Finally, for all other categor ies of health outcomes identified,
results are equivocal and therefore conclusions on the benefit, risk,
or null effect of coffee consumption cannot be determined based
on the current literature.
Additional risks
Additional risks of coffee consumption were apparent for preg-
nant women (for example, relative to pregnancy complications,
birth outcomes, or the health of the infant). Although these risks
were noted in 26 out of the 50 studies, many were linked with
higher coffee consumption (Olsen and others 1991; Armstrong
and others 1992; Parazzini and others 1998, 2005; Bech and oth-
ers 2005; Werler and others 2015) and approximately the same
number of studies (22 out of 50) also reported null (no) effects on
such adverse events of pregnancy (Borlee and others 1978; Zhang
and others 2010; Conde and others 2010, 2011; Alonso and others
2012). Indeed, some studies did report positive (beneficial) effects
on certain pregnancy/infant health outcomes, such as the risk of
pre-term delivery (Petridou and others 1996) or childhood acute
leukemia (Clavel and others 2005). Many of these studies state
caffeine as responsible for the adverse events noted. However, in
support of those that have shown null effects, the European Food
Safety Authority (EFSA) recently concluded that habitual caffeine
consumption (200 mg/d) does not give rise to safety concerns for
the fetus (EFSA 2015).
Finally, a number of other studies (n=45) were identified by
the literature search that highlighted coffee as a potential source of
certain unwanted/toxic constituents, such as ochratoxin A (Stud-
erRohr and others 1994, 1995), furan (Crews and others 2009;
Altaki and others 2011), heavy metals (Taylor and others 2013;
Nedzarek and others 2013) and acrylamide (Bjellaas and others
2007; Eerola and others 2007). For the most part, however, such
studies did report that measured/estimated intake levels were well
below estimated daily acceptable intakes or that coffee was not a
major source, therefore deemed safe (Perez de Obanos and others
2005; Akdemir and others 2010; Guenther and others 2010; Ates
and others 2011; Coronel and others 2012). Moreover, the ben-
eficial effects of other “bioactive” components, such as chloro-
genic acids, phenolic acids, and melanoids, add further support
to the beneficial effect of coffee as a beverage (Olthof and oth-
ers 2001; Borrelli and others 2002; Monteiro and others 2007;
Rufian-Henares and de la Cueva 2009; Fumeaux and others 2010;
Fogliano and Morales 2011; Farrell and others 2012; Lardeau and
Poquet 2013).
Conclusions
Overall, results of this comprehensive review show that the
health benefits (or null effects) clearly outweigh the risks of mod-
erate coffee consumption in adult consumers for the majority
of health outcomes considered. This finding is largely based on
observational data and, moreover, major interactions were noted
between coffee consumption and other lifestyle habits (such as
smoking/alcohol/HRT).
Additional randomized clinical trials are warranted, particularly
in relation to cardiovascular risk factors or endpoints and gastroin-
testinal disorders. This research should distinguish effects of coffee
consumption as a beverage, rather than quantify effects of caffeine
intake per se, adequately quantify/define coffee consumption, and
take account of all potential confounding factors. Consideration
should also be given to the type of coffee preparation or brew-
ing method, any potential influences of relevant genetic poly-
morphisms (for example, CYP2A1), and the population group of
interest (for example, healthy individuals vs. patient groups and
habitual vs. nonhabitual coffee drinkers).
Future Work
Results from this research may aid further qualitative and quan-
titative risk–benefit assessments of coffee consumption, using pub-
lished approaches (Hoekstra and others 2012; Verhagen and others
2012; Boobis and others 2013; Vidry and others 2013; Hart and
others 2013) and further activities emphasizing the potential ben-
678 ComprehensiveReviews in Food Science and Food Safety rVol. 15, 2016 C2016 Institute of Food Technologists®

Coffee consumption and human health . . .
efits should be pursued. As such, the potential benefits for public
health of consuming coffee or not consuming coffee could be
calculated for the most convincing benefits (for example, type 2
diabetes and neurological and/or hepatic disorders). The potential
public health benefits can be quantified in terms of more Qual-
ity Adjusted Life Years (QALYs) or less Disability Adjusted Life
Years (DALYs; Hart and others 2013) for countries and popula-
tion groups of interest, depending on the availability of population
level dietary consumption data.
Acknowledgments
Professor Hans Verhagen is acknowledged for his introduction
to risk–benefit assessment. The authors also thank illycaff `
e s.p.a.,
for funding this research.
Conflicts of Interest
Even though some financial support for this study was provided
by the company (illycaff`
e s.p.a.), the authors declare no conflict
of interest regarding this objective search and summary of the
published literature.
Authors’ Contributions
L.K.P. was responsible for study design, searching the literature,
interpreting, results, and preparing the manuscript; L.N., M.P.,
and J.J.S. were responsible for study design and drafting the fi-
nal manuscript. All authors reviewed the final manuscript before
submission.
Supporting Information
Additional Supporting Information may be found in the onlinle
version of this article at the publisher’ website:
Supplementary Material.
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