Acute Effects of Coffee Consumption On Health Among Ambulatory Adults

The n e w e ng l a n d j o u r na l of m e dic i n e
Original Article
Acute Effects of Coffee Consumption

on Health among Ambulatory Adults
Gregory M. Marcus, M.D., David G. Rosenthal, M.D., Gregory Nah, M.S.,
Eric Vittinghoff, Ph.D., Christina Fang, B.A., Kelsey Ogomori, B.S., Sean Joyce, Sc.B.,
Defne Yilmaz, M.S., Vivian Yang, B.A., Tara Kessedjian, Emily Wilson, B.S.,
Michelle Yang, B.S., Kathleen Chang, B.S., Grace Wall, B.A., and Jeffrey E. Olgin, M.D.
A BS T R AC T
BACKGROUND
From the Division of Cardiology (G.M.M., Coffee is one of the most commonly consumed beverages in the world, but the
G.N., E.W., M.Y., K.C., G.W., J.E.O.), the acute health effects of coffee consumption remain uncertain.
Department of Epidemiology and Biosta-
tistics (E.V.), and the School of Medicine
METHODS
(K.O., S.J., V.Y.), University of California,
San Francisco, San Francisco, the Univer- We conducted a prospective, randomized, case-crossover trial to examine the ef-
sity of California, Irvine, School of Medi- fects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts,
cine, Irvine (C.F.); and the University of
California, Berkeley, Berkeley (D.Y., T.J.).
sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a
Dr. Marcus can be contacted at greg continuously recording electrocardiogram device, a wrist-worn accelerometer, and
.marcus@ucsf.edu or at 505 Parnassus a continuous glucose monitor. Participants downloaded a smartphone application
Ave., M1180B, San Francisco, CA 94143.
to collect geolocation data. We used daily text messages, sent over a period of 14
N Engl J Med 2023;388:1092-100. days, to randomly instruct participants to consume caffeinated coffee or avoid
DOI: 10.1056/NEJMoa2204737
Copyright © 2023 Massachusetts Medical Society.
caffeine. The primary outcome was the mean number of daily premature atrial
contractions. Adherence to the randomization assignment was assessed with the
CME use of real-time indicators recorded by the participants, daily surveys, reimburse-
at NEJM.org ments for date-stamped receipts for coffee purchases, and virtual monitoring
(geofencing) of coffee-shop visits.
RESULTS
The mean (±SD) age of the participants was 39±13 years; 51% were women, and
51% were non-Hispanic White. Adherence to the random assignments was as-
sessed to be high. The consumption of caffeinated coffee was associated with 58
daily premature atrial contractions as compared with 53 daily events on days when
caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20;
P = 0.10). The consumption of caffeinated coffee as compared with no caffeine
consumption was associated with 154 and 102 daily premature ventricular contrac-
tions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily
steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of
nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of
95 mg per deciliter and 96 mg per deciliter (mean difference, −0.41; 95% CI, −5.42
to 4.60).
CONCLUSIONS
In this randomized trial, the consumption of caffeinated coffee did not result in
significantly more daily premature atrial contractions than the avoidance of caf-
feine. (Funded by the University of California, San Francisco, and the National
Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.)
1092 n engl j med 388;12 nejm.org March 23, 2023
The New England Journal of Medicine

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Copyright © 2023 Massachusetts Medical Society. All rights reserved.
Effects of Coffee Consumption among Adults
C
offee is one of the most commonly owned a smartphone with either an iOS or An-
consumed beverages in the world, yet its droid operating system, were able to use the
acute health effects remain largely un- Eureka smartphone application (app), and were
A Quick Take
known.1 Despite the common admonition that willing to abstain from coffee, caffeinated prod- is available at
coffee should be avoided owing to associated ucts, or minimally caffeinated products (decaf- NEJM.org
proarrhythmic effects,2,3 evidence in support of feinated coffee) for at least 2 consecutive days as
this warning is conflicting.4-8 The relevance of instructed over the 14-day trial period. We ex-
this frequently consumed substance to cardiac cluded persons who had a history of atrial fi-
ectopy has become more salient in light of ob- brillation or heart failure; had an implanted
servations that, in a population-based cohort of pacemaker or implantable cardioverter–defi-
older adults, more premature atrial contractions brillator; had been prescribed beta-blockers,
predicted new-onset atrial fibrillation9 and more nondihydropyridine calcium-channel blockers or
premature ventricular contractions were associ- Vaughn–Williams class 1 or 3 antiarrhythmic
ated with a heightened risk of heart failure.10,11 medications; or had a medical reason to avoid
In observational studies, coffee consumption has coffee.
been associated with lower rates of diabetes
and death, a finding that is often attributed to Trial Procedures
the possibility that caffeine stimulates increased Participants were randomly assigned to consume
physical activity.12-15 Coffee may suppress effec- caffeinated coffee or to avoid caffeine during
tive sleep, but objective measurements of this 2-day periods. The random assignments were
relationship in natural environments are scarce.16 made by means of daily text messages sent over
We conducted the Coffee and Real-time Atrial a 14-day period. In order to avoid cumulative ef-
and Ventricular Ectopy (CRAVE) trial to assess fects and enhance enrollment and retention, we
the acute effects of coffee consumption on car- constructed the randomization in pairs of off–
diac ectopy, physical activity, sleep, and glucose on or on–off days to ensure that a participant
levels by using continuously recording, wearable had no more than two consecutive days of coffee
sensors to assess healthy participants who were consumption or abstinence. The participants
randomly assigned to alternate between con- received their assignments at 8 p.m. for the next
suming and avoiding caffeinated coffee. day and received a follow-up reminder on the
assignment day at 8 a.m. (The assignment in-
structions and a description of the daily survey
Me thods
regarding coffee consumption are provided in
Trial Design and Participants Section S3.)
In this prospective, randomized, single-center, The participants were fitted with a continu-
14-day trial, we used a case-crossover design to ously recording electrocardiogram (ECG) patch
evaluate the effect of caffeinated coffee on health (Zio XT Patch, iRhythm), a clinical-grade moni-
defined as cardiac ectopy, activity levels, sleep tor that used an algorithm that had been vali-
minutes, and glucose levels. The trial was ap- dated against overreads performed by cardiolo-
proved by the institutional review board at the gists17; arrhythmias were confirmed by manual
University of California, San Francisco, and all review by a board-certified cardiac electrophysi-
the participants provided written informed con- ologist who was unaware of the consumption
sent. The contributions of the authors are listed assignments. The participants were encouraged
in Section S2 in the Supplementary Appendix, to keep the patch in place for the duration of the
available with the full text of this article at trial and were provided with a transparent adhe-
NEJM.org. The authors vouch for the accuracy and sive dressing to place over the device in case the
completeness of the data and for the fidelity of device adhesive failed. The participants down-
the trial to the protocol (available at NEJM.org). loaded the Eureka app (developed and main-
Participants were recruited through the use of tained by investigators at the University of Cali-
flyers, word of mouth, and social media. Eligible fornia, San Francisco) to their smartphones to
participants were at least 18 years of age, con- continuously monitor their geolocation in order
sumed caffeinated coffee at least once a year, to track visits made to coffee shops. They were
n engl j med 388;12 nejm.org March 23, 2023 1093

also fitted with a Bluetooth-enabled, wrist-worn ventricular tachycardia, daily step counts, daily
accelerometer to quantify step counts18,19 and minutes of sleep, mean daily serum glucose
duration of sleep20,21 (inferred from actigraphy levels, and interactions between each out-
measured with the use of Fitbit INSPIRE devices), come and caffeine-metabolism–related genetic
with data collected by means of an automated variants.26,27
programming interface that was integrated with
the Eureka app, and a Bluetooth-enabled, con- Statistical Analysis
tinuously recording glucose monitoring device Normally distributed continuous variables are
routinely used in clinical practice by patients reported as means ±SD. Analyses were con-
with diabetes to calculate insulin doses22,23 (Dex- ducted according to the intention-to-treat prin-
com G6, Dexcom), with data collected by means ciple. As-treated effects were also assessed ac-
of the Dexcom mobile app. cording to the number of coffee drinks consumed
Participant adherence to the randomization as measured by the activation of the ECG moni-
assignment was assessed in four ways. Partici- tor button by the participant.
pants were instructed to press an activator but- We used negative binomial models with ro-
ton on the ECG patch when they had consumed bust standard errors to account for clustering
a standard 8-ounce cup of coffee or two stan- among participants and with adjustment for day
dard 1-ounce shots of espresso. Pressing the of the week as a fixed effect to assess outcomes
button assigned a time stamp to every drink that involved counts (to calculate rate ratios of
consumed; this process had been previously mean daily counts of premature atrial or ven-
validated for real-time assessment of consump- tricular contractions on days participants were
tion of alcoholic drinks.24 Participants were assigned to coffee versus no caffeine). Logistic
queried each morning about their coffee con- models with robust standard errors were used to
sumption on the previous day and were instruct- assess the presence or absence of outcome mea-
ed that the time stamps and daily survey were sures. We assessed normally distributed contin-
to include every coffee drink they consumed, uous outcomes (step counts, minutes asleep, and
whether at home or elsewhere. Participants were glucose levels) with the use of generalized linear
offered reimbursement for coffee drinks they mixed models with random effects to account
purchased for immediate consumption if they for clustering within the participant population
provided date-stamped receipts, regardless of and adjusted for day of the week. We examined
how those dates corresponded to their assigned heterogeneity by tertiles of the caffeine-metabo-
consumption. For participants who reported at lism–related polygenic score (classified as slow,
baseline that they visited particular coffee shops intermediate, and fast caffeine metabolizers)
for the sole purpose of coffee consumption, the between randomization assignment and out-
Eureka app was used to track visits to those lo- comes. Treatment of missing data is described
cations with the use of smartphone-based geo- in Section S4 and Tables S1 through S6 in the
fencing.25 Supplementary Appendix. To acknowledge the
possibility that data were not missing complete-
DNA Sample Collection and Analysis ly at random and to address incomplete ECG
DNA was collected and purified from saliva and monitoring data in some participants, the pri-
genotyped for seven caffeine-related, single- mary outcome analysis was conducted with the
nucleotide polymorphisms with the use of a real- use of inverse probability weighting.
time polymerase-chain-reaction assay (TaqMan Assuming seven cycles each of coffee expo-
Master Mix and Applied Biosystems 7300).26-28 sure and caffeine avoidance and using a two-
tailed alpha of 0.05, we calculated that 80 par-
Trial Outcomes ticipants would provide the trial with 80%
The primary outcome was the number of prema- power to detect a clinically relevant increase of
ture atrial contractions per 24-hour period. Sec- 30% in premature atrial contractions9 (Table S7).
ondary outcomes were the daily number of pre- A two-tailed P value of less than 0.05 was con-
mature ventricular contractions, daily number sidered to indicate statistical significance. The
of episodes of supraventricular tachycardia or widths of the confidence intervals have not been

adjusted for multiplicity and thus should not be Table 1. Characteristics of 100 Participants at Baseline.*
used to reject or not reject the effects of coffee
consumption. Statistical analyses were performed Characteristic Value
with the use of Stata software, version 16 (Stata- Mean (±SD) age — yr 39±13
Corp). Female sex — % 51
Race or ethnic group — %†
R e sult s Non-Hispanic White 51
Participants Black 8
Of 113 potential participants screened for the Asian 34
trial, 13 did not meet the entry criteria and were Pacific Islander 1
excluded (Table S8). The first participant under- Hispanic 8
went randomization on May 23, 2019, and the Other 6
final date of observation for the last participant
Median BMI (interquartile range)‡ 24 (22–26)
was March 25, 2020. The characteristics of the
Hypertension — % 3
100 participants at baseline are shown in Table 1.
The ages of the participants included each decade Diabetes mellitus — % 1
of life from 20 years of age to more than 70 Coronary artery disease 0
years (Table S9). Demographic characteristics of Usual coffee consumption — %
the participants were representative of the popu- <1 cup per mo 5
lation of the city of San Francisco (Table S10).
1–3 cups per mo 6
The amount of coffee that the participants re-
2–5 cups per wk 14
ported consuming at baseline varied, with the
largest proportion of participants consuming one 6–7 cups per wk 21
coffee drink a day. However, coffee consumption 1 cup per day 29
ranged from less than one coffee drink per 2–3 cups per day 22
month to four or five coffee drinks per day. 4–5 cups per day 3
Assessments of adherence to the randomiza-
tion assignments revealed imperfect adherence, * Because 100 participants were enrolled, numbers and
percentages are the same.
but the majority of participants followed the in- † Race or ethnic group was reported by the participants,
structions to consume caffeinated coffee or avoid who could choose more than one group.
caffeine on the majority of days (Tables S11 ‡ Body-mass index (BMI) is the weight in kilograms divided
by the square of the height in meters.
through S16 and Fig. S1). Participants who were
adherent to the assignments as ascertained by
real-time activation of the ECG time-stamp but- Outcomes
ton were more likely to be White and to con- The participants wore the ECG monitor for a
sume coffee at a lower usual frequency than median of 13.3 days (interquartile range, 12.2 to
participants who did not adhere to the assign- 13.8). In the intention-to-treat analyses, days on
ments (Table S4). When adherence was assessed which participants were assigned to coffee con-
with the use of daily surveys, the participants sumption were associated with a mean of 58
who were more likely to adhere to the random premature atrial contractions per day, as com-
assignments were those who were observed to pared with a mean of 53 premature atrial con-
usually consume coffee less frequently than those tractions per day on caffeine-avoidance days
who were not adherent to the assignments. On (rate ratio, 1.09; 95% confidence interval [CI],
the basis of the responses to the daily surveys, 0.98 to 1.20; P = 0.10) (Table 2). On days on
we observed no between-group differences ac- which participants were assigned to coffee con-
cording to race in the adherence to assignments sumption, the mean number of premature ven-
(Table S5). The participants often drank more tricular contractions per day was 154, as com-
than their baseline usual amounts of coffee on pared with 102 on days they were instructed to
days when they were assigned to consume coffee consume no caffeine (rate ratio, 1.51; 95% CI,
(Table S17). 1.18 to 1.94). The number of episodes of nonsus-

Table 2. Daily Frequency of Arrhythmia.
Coffee Caffeine
Outcome Consumption Avoidance Treatment Effect*
daily mean no.

Premature atrial contractions 58 53 1.09 (0.98–1.20)†
Premature ventricular contractions 154 102 1.51 (1.18–1.94)
Episodes of nonsustained supraventricular 0.17 0.20 0.83 (0.68–1.02)
tachycardia
Episodes of nonsustained ventricular 0.01 0.01 1.14 (0.43–2.99)‡
tachycardia
* The estimates are adjusted for the day of the week. The widths of the confidence intervals have not been adjusted for
multiplicity and cannot be used to reject or not reject effects of coffee consumption. The treatment effect for episodes
of nonsustained ventricular tachycardia is shown as an odds ratio; the other treatment effects are rate ratios.
† P = 0.10.
‡ An insufficient number of episodes of nonsustained ventricular tachycardia precluded an accurate negative binomial
model, so a logistic model with robust standard errors for the presence or absence of an episode was used.
tained supraventricular tachycardia was similar treated analyses also suggested an association
on coffee-consumption days and caffeine-avoid- between more caffeinated coffee consumed and
ance days (mean, 0.17 episodes and 0.20 epi- more steps. (Details of the as-treated analyses
sodes, respectively; rate ratio, 0.83; 95% CI, 0.68 are provided in Section S5.)
to 1.02), as was the number of episodes of non- In the intention-to-treat analysis, assignment
sustained ventricular tachycardia (mean, 0.01 to coffee consumption was associated with a
episodes and 0.01 episodes, respectively; rate ra- mean of 397 minutes of sleep per night, as com-
tio, 1.14; 95% CI, 0.43 to 2.99). The frequencies of pared with 432 minutes on caffeine-avoidance
observed arrhythmias are shown in Table S18. days (mean difference, 36 fewer minutes of sleep
The as-treated analyses suggested similar re- per night; 95% CI, 25 to 47) (Fig. 2). In the as-
lationships between the number of coffee drinks treated analyses, consumption of more coffee
consumed and episodes of premature atrial con- was associated with less sleep.
tractions and arrhythmias. Among participants On days when participants consumed coffee,
who drank more than one coffee drink per day, the daily average glucose levels were 95 mg per
the as-treated analysis suggested that the rela- deciliter, as compared with 96 mg per deciliter
tionship between the number of coffee drinks on caffeine-avoidance days (mean difference,
consumed per day and premature ventricular −0.41; 95% CI, −5.42 to 4.60). No relationships
contractions appeared similar to that shown in between assigned consumption or as-treated
the intention-to-treat analysis; however, among consumption and daily average glucose levels
participants who consumed only one coffee were observed (Table S20). Results remained
drink per day, the as-treated analysis suggested consistent among participants who routinely con-
a lack of relationship between the number of sumed at least one coffee drink per day at base-
coffee drinks per day and episodes of premature line and participants who did not (Table S21).
ventricular contractions (Table S19). No substantial differences according to caf-
Step-count data were available from 86 par- feine-related genotype were observed with re-
ticipants, sleep data from 81, and glucose data gard to the amount of coffee consumed (Table
from 87; missing data were the result of techni- S22). The associations between the variants and
cal problems in every case. In the intention-to- premature atrial contractions, premature ven-
treat analysis, assignment to consume coffee tricular contractions, daily steps, and daily sleep
was associated with a daily mean of 10,646 steps minutes are shown in Table S23. There was no
(recorded by a Fitbit) as compared with 9665 consistent pattern observed in the associations
steps recorded on days on which participants were between the variants and the health measures.
assigned to avoid caffeine (mean difference, Participants with genetic variants that are asso-
1058; 95% CI, 441 to 1675) (Fig. 1). The as- ciated with faster caffeine metabolism appeared

30,000
Caffeine avoidance Coffee consumption
25,000
Mean No. of Steps per Day
20,000
15,000
10,000
5,000
0
Participants
Figure 1. Daily Step Count for Each Participant on Days of Coffee Consumption and Days of Caffeine Avoidance.
The x axis shows the mean daily step count for each participant for all days on which the participant was randomly assigned to avoid
caffeine (blue) or to consume coffee (orange). Data for each participant are grouped in pairs and ordered according to the magnitude of
the participants’ step counts on days they were randomly assigned to avoid caffeine. The vertical black bars indicate standard devia-
tions. Step-count data were available for 86 of the 100 participants.
700
Caffeine avoidance Coffee consumption
600
Mean No. of Minutes of Sleep
500
400
300
200
100
0
Participants
Figure 2. Minutes Asleep for Each Participant after Coffee Consumption and Caffeine Avoidance.
The x axis shows the mean number of minutes of sleep for each participant after all days on which the participant was randomly as-
signed to avoid caffeine (blue) and to consume coffee (orange). Data for each participant are grouped in pairs and ordered according to
the magnitude of the time participants were asleep on days on which they were randomly assigned to consume coffee. The vertical black
bars indicate standard deviations. Sleep data were available for 81 of the 100 participants.
to have more premature ventricular contractions slower caffeine metabolism appeared to have
when they consumed coffee, and participants greater reductions in sleep minutes when they
with genetic variants that are associated with consumed coffee.

Discussion hood of premature ventricular contractions as

shown on a 2-minute ECG,4 a finding that is
Among 100 healthy adults, the consumption of consistent with our current findings. Our analy-
caffeinated coffee did not result in more daily ses of as-treated coffee consumption indicated
premature atrial contractions than the avoidance that there was a lack of association between a
of caffeine. Our results further suggest that both single cup of coffee and premature ventricular
assignment to daily coffee consumption and contractions but suggested that there might be
greater-than-normal coffee consumption were a possible association between consumption of
associated with more recorded daily steps taken, more than one coffee drink per day and prema-
fewer minutes of sleep per night, and poten- ture ventricular contractions in our trial partici-
tially more daily premature ventricular contrac- pants.
tions among persons who consumed more than Coffee drinkers have consistently had reduced
one coffee drink per day. mortality in prospective cohort studies, but the
Cardiac ectopy is a nearly universal human mechanism for this result remains unknown.12,13,35
phenomenon, but recent evidence from a popu- Because caffeine may enhance physical perfor-
lation-based cohort of older adults showed that mance,14,36 some investigators have speculated
a greater frequency of premature atrial contrac- that coffee consumption may lead to more
tions predicts new-onset atrial fibrillation9,29 and physical activity, one of the most important
that persons who have more premature ventricu- determinants of overall health and longevity.37
lar contractions are at an increased risk for heart Random assignment to coffee consumption re-
failure.10,29 Thus, interest has focused on identify- sulted in a median of 1000 more steps per par-
ing common exposures that might influence the ticipant per day in our trial. An additional 1000
frequency of common cardiac ectopy. Despite steps per day has been associated with a 6% to
admonitions that the avoidance of caffeinated 15% reduction in mortality,38 effect sizes that are
beverages minimizes arrhythmias,3,30 random- remarkably similar to the magnitude of mortal-
ized trials of the acute effects of coffee on car- ity benefit observed among coffee drinkers.12,13,35
diac ectopy were lacking. Our trial produced no However, the current trial was not equipped to
evidence of statistically significant relationships determine precisely why participants took more
between coffee consumption and the frequency steps when they consumed more coffee.
of premature atrial contractions, findings that Sleep has emerged as an important factor in
are consistent with those of previous observa- multiple health outcomes, including the risk of
tional studies that used evidence derived from cardiovascular disease, cancer, and cognition
patient-reported general coffee consumption and issues, as well as in overall mortality.39,40 Coffee
24-hour Holter monitoring.5 Evidence from re- notoriously disrupts sleep; however, observa-
cent observational studies suggests that coffee tional studies are not well-suited to quantify this
drinkers have a lower risk of atrial fibrillation relationship owing to confounding by indication
than nondrinkers,6,8 a finding that has been at- (persons with the worst caffeine-induced insom-
tributed to the antiinflammatory or antivagal nia are more likely to minimize consumption).
effects of coffee, given evidence that supports Although an hour less sleep per night correlates
the roles of inflammation31 and vagal tone32,33 as with substantially worse outcomes, the effects
harbingers of atrial arrhythmias. of losing 30 minutes of sleep, as observed in our
Caffeine is a nonselective adenosine receptor trial, are less certain.41 However, for persons
antagonist, an inhibitor of phosphodiesterases, with difficulty sleeping, these data provide evi-
and a direct agonist of the ryanodine receptor, dence from among participants studied in their
which enhances calcium release from the sarco- natural environments that coffee consumption
plasmic reticulum. Such calcium release is known can indeed influence this crucial activity. The
to result in afterdepolarizations, which, if large results raise the possibility that coffee consump-
enough, can result in a premature ventricular tion had little effect in participants who were
contraction.11,34 One of the few reports to de- fast caffeine metabolizers, whereas those who
scribe a positive relationship between coffee and were the slowest caffeine metabolizers had the
arrhythmias showed that the larger the daily most exaggerated effects. These findings sug-
consumption of coffee, the greater the likeli- gest that an individualized approach to coffee

consumption may be the most appropriate ily limit generalizability and should pose less of
method for determining the effects on health. a threat to internal validity. Adherence assess-
Despite epidemiologic evidence that coffee ments were also not complete for all participants,
drinkers have a lower risk of diabetes than per- but the four approaches that were used relied on
sons who avoid coffee,13 we found no evidence different methods of ascertainment and consis-
that coffee consumption was associated with tently favored general compliance with the ran-
mean daily glucose levels. This finding may have domization assignment. The Fitbit is not a clin-
occurred because coffee consumption was ac- ical-grade device, so the estimates regarding
companied by other intake rich in simple carbo- sleep durations that were obtained from the de-
hydrates. It may also suggest that the conse- vice may not fully quantify the exact amount of
quences of coffee consumption on diabetes risk time asleep,21 and markers of sleep efficiency
are long term and may reflect such factors as other than sleep duration were not captured.
antiinflammatory effects or ramifications of Finally, although participants were instructed
more regular physical activity. specifically to consume caffeinated coffee, we
It is important to acknowledge several limita- cannot disentangle the effects specific to caf-
tions of our trial. First, the trial was relatively feine as compared with other ingredients in the
small; however, the case-crossover design allowed various types of coffee drinks that were allowed.
for generally more than 10 different assessments Consumption of caffeinated coffee was not
per participant. The trial was not blinded, so we associated with a change in the number of daily
cannot exclude the possibility that other influ- premature atrial contractions among participants.
ences concomitant with coffee exposure were Findings from secondary analyses that should
the actual causal factors. Regarding the relation- be interpreted as hypothesis-generating suggest
ship between coffee exposure and the outcome that coffee consumption may be associated with
measures, the effects of caffeine withdrawal may more premature ventricular contractions and
have been operative; therefore, although with- more physical activity but less sleep. No appar-
drawal probably increased the magnitude of the ent relationship between coffee consumption
measurements observed, changes attributed to and serum glucose levels was observed. These
such phenomena would further support the role findings suggest protean health-related conse-
of coffee (or caffeine) itself as the culprit source. quences of consuming this common beverage
The trial population was relatively young and and provide both clinicians and patients with
healthy, so extrapolation to other populations, information that may assist in customizing con-
including those with frequent premature atrial or sumption of coffee to appropriately fit with in-
ventricular contractions, may not be appropriate. dividual health goals.
Although the continuously recording devices
facilitate complete data capture for outcome as- Supported by a Cardiology Innovation Award from the Uni-
versity of California, San Francisco, and by the National Insti-
sessments, those outcomes were included only tutes of Health; Dexcom donated continuous glucose monitors
while (or if) those devices were worn. However, for the trial.
given the case-crossover nature of the analyses Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
(for which each participant served as the con- A data sharing statement provided by the authors is available
trol), these missing outcome data would primar- with the full text of this article at NEJM.org.
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Acute Effects of Coffee Consumption On Health Among Ambulatory Adults

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The n e w e ng l a n d j o u r na l of m e dic i n e

Acute Effects of Coffee Consumption

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Table 2. Daily Frequency of Arrhythmia.

daily mean no.

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Discussion hood of premature ventricular contractions as

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The New England Journal of Medicine

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