CLINICAL RESEARCH STUDY
Alcohol Consumption as a Trigger of Recurrent
Yuqing Zhang, DSc,aRyan Woods, MPH,bChristine E. Chaisson, MPH,bTuhina Neogi, MD,aJingbo Niu, MD,a
Timothy E. McAlindon, MD, MPH,cDavid Hunter, MD, PhDa
aBoston University Clinical Epidemiology Research and Training Unit, the Department of Medicine at Boston Medical Center;bThe
Data Coordinating Center, Boston University School of Public Health,cThe New England Medical Center, Boston, Mass.
however, this hypothesis has not been formally tested.
We conducted an Internet-based case-crossover study to assess several putative risk factors,
including alcohol consumption, thought to trigger recurrent gout attacks. Subjects who had an attack within
the past year were recruited online and asked to provide access to medical records pertaining to their gout.
Data were obtained on the amount and type of alcoholic beverage consumed on each day over the 2-day
period before a gout attack and on each day over a 2-day period during the intercritical period. We
examined the amount and type of alcohol consumption and the risk of recurrent gout attacks using a
conditional logistic regression adjusting for diuretic use and purine intake.
A total of 197 subjects were recruited online over a 10-month period. Of those, 179 (91%)
fulfilled the American College of Rheumatology Criteria for gout. Compared with no alcohol consumption,
odds ratios for recurrent gout attacks were 1.1, 0.9, 2.0, and 2.5 for 1 to 2, 3 to 4, 5 to 6, and 7 or more
drinks consumed over the 2-day period, respectively (P?.005). A dose-response relationship of risk of
gout attacks was more evident for alcohol consumed over the last 24 hours. An increased risk of recurrent
gout attacks was found for each type of beverage consumed.
Alcohol consumption triggers recurrent gout attacks. This effect was likely to occur
within 24 hours after its consumption. © 2006 Elsevier Inc. All rights reserved.
Alcohol consumption has long been considered a trigger for recurrent gout attacks;
Alcohol; Recurrent gout attacks; Internet; Case-crossover study
Gout is a common form of inflammatory arthritis, often
causing recurrent episodes of pain and swelling of certain
joints. Although the pathophysiology of gout is well under-
stood and clinically efficacious therapies are available, re-
cent studies have shown that the prevalence and incidence
of gout in the United States are increasing.1-4Recurrent gout
attacks are often attributed to “triggers,” that is, precipitat-
ing factors immediately before gout attacks. Avoidance of
triggers is a central preventive strategy in the management
of gout. To date, few epidemiologic studies have been
conducted to identify the potential triggers for recurrent
gout and assess their effects owing to methodologic and
Previous studies have shown that alcohol consumption
increases the level of serum uric acid5-8and that excess
intake of alcohol is associated with an increased risk of
initial occurrence of gout.9-13Results from the Health Pro-
fessionals Follow-up Study showed that the risk of incident
gout attack increased as the amount of alcohol consumed
increased and that this risk varied according to the type of
alcoholic beverage consumed. Beer conferred a larger risk
than spirits, whereas moderate wine drinking did not in-
Supported by an Arthritis Foundation Clinical Science Grant, a grant
from the Department of Medicine, Boston University School of Medicine,
National Institutes of Health AR47785, and by TAP Pharmaceutical Co.
Requests for reprints should be addressed to Yuqing Zhang, DSc,
A203, Boston University School of Medicine, 715 Albany St, Boston, MA
E-mail address: email@example.com
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved.
The American Journal of Medicine (2006) 119, 800.e13-800.e18
Although many people believe that alcohol intake trig-
gers recurrent gout attacks, we are unaware of any study that
has formally tested this hypothesis. Clarification of such
associations has potential implications for gout manage-
ment. First, many patients with gout have other comorbidi-
ties, including obesity, type-2
diabetes mellitus, dyslipidemia,
hypertension, and coronary heart
shown that light-to-moderate
alcohol intake is associated with
a reduction of risk for these
diseases.21-25Quantifying the re-
lation of amount of alcohol con-
sumption to the risk of recurrent
gout attacks will allow these pa-
tients to make informed deci-
sions about their alcohol con-
sumption. Second, although the
results from the Health Profes-
sionals Follow-up Study found
the effect on the development of
gout varied based on the type of
alcoholic beverage consumed,
such findings need to be verified
with regard to recurrent gout
Assessing whether alcohol in-
take triggers recurrent gout attacks
is challenging. A case-control
study poses serious problems for
control selection, whereas a cohort
design is unwieldy for participants and investigators and
extremely expensive. Both designs also pose problems of
recruitment. We conducted an Internet-based case-cross-
over study to assess the relation of amount and type of
alcoholic beverages to the risk of recurrent gout attacks. We
also estimated the approximate time interval in which a
recurrent attack would occur after alcohol consumption.
dcc2.bumc.bu.edu/GOUT) on an independent secure server
within the Boston University Medical Center domain. The
study website provided information about the study, invited
applicants to participate, administered a screening question-
naire, linked eligible respondents to an online consent form,
and administered additional questionnaires to assess risk
factors and features of respondents’ recurrent gout attacks.
The study was advertised on the Google search engine
(www.Google.com) by linking an advertisement to the
search term “gout.” When a search was conducted contain-
ing the keyword “gout,” a study advertisement appeared on
the screen. Interested individuals who clicked on the box
containing our advertisement were immediately directed to
the study website. To be eligible for the study, a subject had
a websiteforthisstudy (https://
to: report a diagnosis of gout by a physician, have had a gout
attack within the past 12 months, be at least 18 years of age,
reside in the United States, and be willing to release medical
records pertaining to gout diagnosis and treatment. All sub-
jects were asked to complete an electronic informed consent
form before taking part in the
study. In addition, a hard-copy
consent form was mailed to each
subject along with a Research Au-
thorization and Medical Record
Eligible subjects were asked to
complete baseline questionnaires.
These included Sociodemographic
Questionnaire (name, age, gender,
home address, home and work
phone number, e-mail address,
date of birth, years of education,
and household income) and Med-
ical History Questionnaire (medi-
cation use, self-reported comor-
When a recurrent gout attack
occurred, subjects completed a
which inquired about the date of
the attack, clinical symptoms,
medication used to treat the attack,
and frequency as well as quantity
of potential risk factors, including
alcohol consumption, on each of
two 24-hour periods before the gout attack. Subjects com-
pleted a Control-period Questionnaire during an attack-free
interval at four time points: at study entry, and at 3, 6, and
9 months of follow-up. The questions used to assess the risk
factors over the control period were the same as those used
in the hazard period.
Questions on alcohol consumption included the number
of servings of beer, wine, or spirits (either straight or in a
mixed drink) consumed on each day over the control or
hazard periods. The serving sizes were provided along with
color images of standard drink sizes and containers, that is,
12-ounce bottle or can of beer; 5-ounce glass of wine, and
1 to 1.5 ounces of spirits. Other potential risk factors, such
as foods rich in purine and diuretic use were also collected
over the control and hazard period. The total purine intake
from food was estimated using established food purine
We obtained medical records pertaining to the partici-
pant’s gout history and/or a checklist of gout symptoms
completed by the subject’s physician. A rheumatologist
reviewed all medical records and the checklist information.
We used information abstracted from medical records or the
checklist, and data collected from the questionnaires sub-
mitted by the participant to confirm the diagnosis of gout
● Although the pathophysiology of gout is
well characterized and clinically effica-
cious therapies are available, many pa-
tients with gout continue to experience
● Alcohol consumption has long been con-
sidered a trigger for recurrent gout at-
tacks; however, this hypothesis has not
been formally tested.
● In this study, we demonstrated that al-
cohol consumption, even a light-to-
moderate amount, triggers recurrent
● Thus, subjects with established gout
should avoid drinking alcohol to de-
crease their risk of recurrent gout
800.e14The American Journal of Medicine, Vol 119, No 9, September 2006
according to American College of Rheumatology (ACR)
Criteria for gout.27A subject was considered as having a
confirmed history of gout if his/her medical record showed
the presence of characteristic urate crystals either in the
joint fluids or in tophus, or presence of at least 6 of the 12
clinical, laboratory, and radiography phenomenon listed in
Total alcohol consumption (grams) for each day and over
the 2-day period was calculated by multiplying the average
alcohol content in beer, wine, and spirits times the number
of drinks consumed over the specified period. The total
alcohol intake per day (in grams) was estimated as ([0.57 ?
the number of cocktails per day] ? [0.44 ? the number of
bottle or cans of beers per day] ? [0.40 ? the number of
glasses of wine per day]) ? 28.35. This latter term repre-
sents 28.35 g of alcohol per fluid ounce.28One typical drink
is approximately 12 g of alcohol. The total alcohol intake on
each day and over the 2-day period was divided into five
categories: no alcohol consumption, 1 to 2 drinks, 3 to 4
drinks, 5 to 6 drinks, and more than 6 drinks.
We examined the relation of total alcohol consumption
to the risk of recurrent gout attacks using a conditional
logistic regression model. In a multivariable regression
model, we adjusted for diuretic use and total purine intake
in foods. We estimated the approximate effect-period of
alcohol intake on the risk of recurrent gout attacks by
comparing the odds ratios of alcohol consumed over the last
24 hours with that of over 25 to 48 hours before attack.
Either overestimation or underestimation of the effect-
period would, in general, result in nondifferential exposure
misclassification and would therefore tend to dilute the
association. Thus, the better estimate of the effect-period is
the one that maximizes the odds ratio.29
We also assessed the effect of each specific alcoholic
beverage on the risk of recurrent gout attacks. We first
examined the independent effect of each type of alcoholic
beverage and then evaluated whether this effect, if it exists,
is the result of components other than alcohol. To do this we
added the total alcohol intake, diuretic use, purine-rich food
intake, and number of drinks of specific alcoholic beverages
to the multivariable regression model.
Of 197 subjects who completed both Hazard-period and
Control-period Questionnaires, 179 subjects (91%) fulfilled
the ACR Criteria for gout.27Gout diagnosis was confirmed
by the presence of the crystal in only 37 subjects (19%). A
total of 186 subjects (94.4%) returned a signed Medical
Record Release Form. Of those, we obtained 172 subjects’
medical records or physician’s checklists from their physi-
cians, and 164 (95.3%) met ACR Criteria for gout.27
The characteristics of the participants are presented in
Table 1. The average age of the subjects was 52 years.
Participants were predominantly male (80%) and white
(88%), and more than half received a college education.
Subjects were recruited from 41 states and the District of
Columbia. During the 1-year follow-up period, 321 recur-
rent gout attacks occurred. The median time between the
date of the gout attack and the date of completion of the
Hazard-period Questionnaire was 2 days.
During the follow-up period, 53 subjects did not con-
sume any alcoholic beverage, 13 drank only wine, 29 drank
only beer, 14 drank only liquor, and the remaining 88
subjects drank more than one type of alcoholic beverage. As
shown in Table 2, compared with the group with no alcohol
consumption over 48 hours, the odds ratios for recurrent
gout attacks were 1.1, 0.9, 2.0, and 2.5 for consumption of
1 to 2, 3 to 4, 5 to 6, and 7 or more alcoholic drinks over 48
hours before gout attack, respectively (P?.005). When the
effect of amount of alcohol consumed during the different
time periods was examined, an apparent dose-response re-
lation was observed for amount of alcohol consumed over
the last 24 hours before gout attack (P?.023). Such a
pattern, however, was not evident for alcohol consumed
over the 25- to 48-hour period before recurrent gout attacks.
When the effect of specific alcoholic beverage (ie, beer,
wine, or spirits) was assessed separately, the risk of recur-
rent gout attack increased as the number of drinks of each
specific alcoholic beverage increased (Table 3). The results
were similar when we limited our analysis to subjects who
only drank one type of alcoholic beverage. However, with
further adjustment for total alcohol consumption, none of
the specific alcoholic beverages were associated with an
based Case-crossover Study of Gout, 2003 to 2004
Characteristics of Participants in the Internet-
Sex (n, %)
Age (median, range)
Education (n, %)
High school graduate
Some college/technical school
Completed professional or graduate
Household income (n, %)
Race (n, %)
Number of days between attack date and
log-on (median, range)
Years of disease duration (median, range)
800.e15 Zhang et alAlcohol Consumption and Gout Attacks
increased risk of recurrent gout attacks, suggesting that the
total amount of ethanol intake, rather than a particular com-
ponent of a specific alcoholic beverage, may be responsible
for the increased risk.
When we limited the analyses to the subjects whose gout
diagnoses fulfilled ACR Criteria (n ? 179), the results were
similar. Compared with the nondrinking category, the odds
ratios for each increased category of alcohol intake con-
sumed within the last 48 hours were 1.2 (95% confidence
interval [CI]: 0.6-2.1), 1.0 (95% CI: 0.4-2.2), 2.0 (95% CI:
0.9-4.7), and 3.0 (95% CI: 1.2-7.7), respectively (P?.003).
Although alcohol has long been considered a risk factor trig-
gering recurrent gout attacks, to our knowledge, this is the first
study that has formally tested this hypothesis. Our results
suggest that alcohol intake, irrespective of the type of beverage
consumed, was associated with an increased risk of recurrent
gout attacks. The effect-period of alcohol was short, likely to
occur within the first 24 hours after alcohol consumption.
Although many studies have found that alcohol con-
sumption increases the levels of uric acid,5-7its relation to
Alcohol Consumption and Risk of Recurrent Gout aAttack
(number of drinks)
Number of hazard
Number of control
Within last 48 h
Within last 24 h
Within last 25-48 h
OR ? odds ratio; CI ? confidence interval.
*Adjusted for purine intake and diuretic use.
Specific Alcoholic Beverage Intake Over the Last 48 Hours and Risk of Recurrent Gout Attack
Specific alcoholic beverage
intake (number of drinks)
Number of hazard
Number of control
OR ? odds ratio; CI ? confidence interval.
*Adjusted for purine intake, and diuretic use.
†Adjusting for purine intake, diuretic use, and total ethanol consumption.
800.e16 The American Journal of Medicine, Vol 119, No 9, September 2006
the risk of incident gout attack has not been consistent.
Hochberg et al.30found no association between alcohol use
and risk of development of gout among participants in two
cohort studies. However, the number of incident gout cases
in that study was small, and more than 90% of the partici-
pants drank alcohol at the baseline examination. Results
from the Normative Aging Study reported that alcohol con-
sumption increased the risk for the initial gout attack, but
such an association disappeared when additional adjustment
was made for the baseline serum levels of uric acid.16It is
debatable whether one should adjust for serum levels of uric
acid when effect of alcohol consumption on the risk of gout
attacks is evaluated. If alcohol affects the risk of gout
attacks through its effect on uric acid, then uric acid level
should not be adjusted for. Recently, Choi et al.14showed a
strong dose-response relationship between the amount of
alcohol consumed and the initial gout attack. In the current
study, we confirmed that alcohol intake, even a light-to-
moderate amount, will trigger recurrent gout attacks.
Several biologic mechanisms have been proposed to ex-
plain the relation of alcohol consumption to the risk of
incident gout. Studies have demonstrated that alcohol con-
sumption causes accelerated hepatic breakdown of adeno-
sine triphosphate and urate production.31Others also found
that consumption of lead-tainted moonshine results in
chronic renal tubular damage, eventually leading to second-
ary hyperuricemia and “saturnine” gout secondary to
chronic lead poisoning.15The high purine content in some
alcoholic beverages, such as beer, is another potential ex-
planatory factor associated with an increased risk of gout
attacks.32Our results suggest that the effect of alcohol on
these biologic mechanisms and its subsequent predisposi-
tion to gout attacks occurs within a short period of time,
perhaps less than 24 hours.
Numerous studies have shown that light-to-moderate al-
cohol consumption is inversely associated with coronary
heart disease and metabolic syndrome.15-20Both conditions
are common among subjects with gout. Thus, elucidation of
the relation of light-to-moderate alcohol consumption to the
risk of recurrent gout attacks has important clinical impli-
cations. For example, in the current study we found that a
light-to-moderate amount of alcohol intake increases the
risk of recurrent gout attacks within the first 24 hours and
that the effect is not trivial. Thus, subjects with gout should
avoid drinking alcoholic beverages entirely, despite the sal-
utary effects of light-to-moderate alcohol intake on other
We did not find that the effect of alcohol consumption on
the risk of recurrent gout attacks varied according to bev-
erage type. Our data suggest that risk of recurrent gout
attacks increases regardless of which type of alcoholic bev-
erage is consumed. We believe that the total amount of
ethanol, rather than other components in different types of
alcoholic beverages, is responsible for triggering recurrent
Studying the triggering effect of alcohol intake on the
risk of recurrent gout attacks is challenging. In a case-
control study, selection of control group poses a serious
problem because neither healthy subjects from the commu-
nity nor patients with other diseases from a hospital are
optimal comparison groups for cases with recurrent gout
attacks. Ideally, the control group should be selected from
subjects who have a history of gout and are currently in
remission. However, few, if any, subjects would seek health
care in the absence of a recurrent gout attack, and thus
identification and recruitment of such subjects are difficult.
Another approach would be to assemble a group of subjects
with a history of gout, and then follow them up for the
recurrence of gout attacks. However, because we are inter-
ested in risk factors triggering unpredictable recurrent acute
events within a short latency period, we would have to
assess exposures repeatedly on all cohort members. The cost
would be high and the respondent burden considerable.
In this study we applied 2 approaches, the case-crossover
study design and the Internet, to conduct an innovative
epidemiologic study that addressed this challenging and
clinically important question. This methodology enables us
to recruit subjects with intercritical gout from large geo-
graphic areas, such as the whole United States. Furthermore,
this method allowed us to assess both exposure and disease
occurrence in real-time, which minimizes the potential re-
Our study has some limitations. First, although we used
validated questionnaires to assess the risk factors for gout,
including alcohol consumption, and subjects were asked to
recall these putative risk factors occurring within the last 48
hours, it is still possible that misclassification of risk factors
may have occurred. Such misclassification, if it occurred, is
likely to be nondifferential and would bias the results to-
ward the null. Second, the current study design allowed us
to assess the effects of changing level of alcohol consump-
tion on the risk of recurrent gout attacks; however, it is not
ideal for examining the effects of a chronic, constant level
of alcohol consumption. Nevertheless, we foresee no major
problem in that our study may not include subjects who are
chronically addicted to alcohol because it is hard to argue
that the biologic relations of alcohol consumption to the risk
of recurrent gout attacks would differ for those who drink
alcohol intermittently from those who drink alcohol chron-
ically. Finally, the number of subjects who only drank a
specific type of alcoholic beverage was relatively small;
thus, we do not have adequate power to assess the dose-
response relationship between intake of specific alcoholic
beverage and the risk of recurrent gout attacks.
The present study found that alcohol intake, even a light-
to-moderate amount, triggers recurrent gout attacks. We
suggest that subjects with established gout avoid drinking
alcohol to lower their risk of recurrent gout attacks.
800.e17Zhang et al Alcohol Consumption and Gout Attacks
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