Lifestyle Modification and Other Strategies To Reduce The Risk of Gout Flares and Progression of Gout - UpToDate

2/19/2021 Lifestyle modification and other strategies to reduce the risk of gout flares and progression of gout - UpToDate
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Lifestyle modification and other strategies to reduce the

risk of gout flares and progression of gout
Author: Tuhina Neogi, MD, PhD, FRCPC
Section Editor: Nicola Dalbeth, MBChB, MD, FRACP
Deputy Editor: Paul L Romain, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2021. | This topic last updated: Dec 01, 2019.
INTRODUCTION
Gout is monosodium urate crystal deposition disease. The long-term goals of therapy in
patients who have already experienced signs and symptoms of the disease (established or
prevalent gout) are to prevent recurrent gout flares and to reverse prior signs of the disease by
achieving and maintaining subsaturating serum urate concentrations. This is achieved by a
combination of approaches, including lifestyle modification and other strategies for risk
reduction, as well as urate-lowering drug therapy.
The prevention of gout flares and disease progression in people with gout by
nonpharmacologic lifestyle modifications for urate lowering and by risk reduction involving
drug choices for management of comorbid diseases (eg, hypertension) will be reviewed here.
Treatment with urate-lowering drugs, the role of surgery for treating tophi, the clinical
manifestations and diagnosis of gout, the prophylaxis and treatment of episodes of gout flares,
and issues related to asymptomatic hyperuricemia are discussed separately. (See
"Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout" and
"Clinical manifestations and diagnosis of gout" and "Treatment of gout flares" and
"Asymptomatic hyperuricemia".)
RATIONALE FOR MANAGEMENT APPROACHES
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Gout is monosodium urate crystal deposition disease manifested by gout flares, tophi, and
chronic gouty arthritis; it can result in joint damage. Management of gout entails lowering
serum urate levels below saturation to prevent gout flares and to aid resolution of tophi and
chronic gouty arthritis. Moreover, there is no evidence that serum urate reduction to levels that
remain above the limit of solubility carries with it clinical benefits equivalent to those achievable
at sustained subsaturating levels. The symptoms and signs of gout do not occur in the absence
of urate saturation of extracellular fluids, reflected by elevated serum urate concentrations and
monosodium urate crystal deposition in tissues and inflammatory responses to such crystal
deposition.
Management for the prevention of recurrent gout flares and damage to joints and other tissues
from monosodium urate crystal deposition includes urate-lowering drug therapy, lifestyle
modification, and other strategies for risk reduction. However, resolution of the monosodium
urate crystal burden in patients with gout may require many months to several years to attain,
even after subsaturating serum urate levels are achieved. During this period of crystal
dissolution, a risk for gout flare remains. During the early phase of urate-lowering therapy and
in the face of ongoing disease activity, concomitant antiinflammatory prophylaxis is
recommended.
MANAGEMENT PRINCIPLES
Upon resolution of a gout flare, the patient is said to have entered an intercritical (between
flares) period (see "Clinical manifestations and diagnosis of gout", section on 'Intercritical gout
and recurrent gout flares'); during this period, the following issues relevant to prevention of
gout flares and disease progression should be addressed:
● Patient education regarding [1-8]:
• The basis of symptoms related to gout

• Factors likely to provoke gout flares or disease progression
• The rationale for each component of the recommended therapeutic plan and the
benefits and potential harms of each of these components
Thorough patient education is essential to successful adherence to both nonpharmacologic

and pharmacologic approaches [9]. Deferring detailed patient education to an intercritical
period rather than during a gout flare is likely to find the patient more receptive to the
exchange of information and to provide the clinician time to gather the data needed to
create and convey an individualized treatment program incorporating patient preferences

and prior experiences.
● Reversible causes of hyperuricemia, which should be identified to facilitate lifestyle

modification and other changes that may be helpful in risk reduction [10-12]. (See 'Risk
reduction' below.)
● Management of comorbid diseases common in patients with gout, such as hypertension,

chronic renal functional impairment, cardiovascular disease, and the components of the
metabolic syndrome [13-15]; each of these is a risk factor for gout ( table 1). (See 'Risk
reduction' below.)
● The need for pharmacologic urate-lowering therapy [1,3-8]. (See "Pharmacologic urate-
lowering therapy and treatment of tophi in patients with gout", section on 'Indications'.)
● The need for prophylactic therapy, usually with colchicine or a nonsteroidal

antiinflammatory drug (NSAID), primarily to reduce the recurrence of gout flares during
initiation of urate-lowering therapy [2-8]. (See "Pharmacologic urate-lowering therapy and
treatment of tophi in patients with gout", section on 'Prophylaxis during initiation of urate-
lowering therapy'.)
Pharmacologic urate-lowering treatment to prevent recurrent gout flares and tophi is typically
indicated in patients with at least two flares annually or with clinical or imaging findings that
indicate chronic gouty arthritis or the development of tophi, as well as in selected patients with
renal impairment, urolithiasis, or marked hyperuricosuria. (See "Pharmacologic urate-lowering
therapy and treatment of tophi in patients with gout", section on 'Approach to drug therapy'.)
Even when initial consideration of these management principles indicates that introduction of
pharmacologic urate-lowering therapy is not indicated at the time of a given visit, application of
one or more of the lifestyle and risk-reduction strategies discussed may be appropriate on an
individualized basis. Some of these approaches may be appropriate as adjunctive measures in
patients with gout on urate-lowering therapy, but are generally not effective on their own in
patients for whom pharmacologic therapy is indicated, and can be considered in individuals
with asymptomatic hyperuricemia who may be interested in lowering their risk for developing
gout (see "Asymptomatic hyperuricemia", section on 'Evaluation'). Moreover, after clinical
remission is achieved in patients with gout, maintenance of remission usually requires
sustained urate subsaturation, typically maintained with pharmacologic therapy.
RISK REDUCTION
Role of risk-reduction measures — Gout is characterized by hyperuricemia, a factor that is

necessary but often insufficient alone to result in monosodium urate crystal formation and the
expression of gout. Hyperuricemia, in turn, has multiple antecedents; these include other
clinical disorders, genetic mutations and polymorphisms, and dietary, drug, and toxin
exposures, which result in either urate overproduction or, more commonly, impaired urate
disposal or a combination of these aberrations ( table 2 and table 3). (See
"Pathophysiology of gout" and "Asymptomatic hyperuricemia", section on 'Evaluation'.)
The lifestyle approaches to urate-lowering risk-reduction measures discussed here may play a
primary role in preventing incident gout in individuals at high risk for disease expression; they
may occasionally have a role in reducing risk in patients with gout but without a current
indication for initiating urate-lowering pharmacotherapy, as well as in those who are intolerant
of or unable to receive pharmacologic urate-lowering agents. These risk-reduction measures
also play an adjunctive role in patients with gout and an indication for urate-lowering
pharmacotherapy.
Urate-lowering pharmacotherapy for gout is, by definition, aimed directly at reversing

hyperuricemia and thus alleviating the risk of monosodium urate crystal formation and
deposition and the ensuing inflammatory and degenerative consequences. It should be
initiated as definitive therapy for patients with gout who meet indications for urate-lowering
therapy, as long as it is tolerable to the patient and subsaturating urate levels are reached and
maintained within approved dosing limits [1,3-8].
Importantly, there are examples of apparent modifiers of incident gout risk that have not
shown efficacy in risk reduction and/or practicality in patients with established gout that is
sufficient to support their routine therapeutic use. For this reason, we will describe here, where
relevant, whether sufficient evidence for clinical benefit (relative to risk) has been
demonstrated, in our view, to justify incorporating particular candidate risk-reduction initiatives
in the care of patients with established gout. Further, providers should take care to not blame
patients for their gout, particularly because renal urate underexcretion, with genetic
underpinnings, is the major contributor (see 'Dietary composition' below). The stigma
associated with the belief that gout is self-inflicted often impedes patients from seeking help or
sharing the severity and effects of their disease with health care providers, which can then
contribute to suboptimal management [16,17].
Evaluation of risk-reduction strategies — Two types of investigative approaches have been

taken to assess the benefits of lifestyle modifications and other nonpharmacologic strategies
for reducing the risk of gout. In one category are observational cohort investigations that have
identified risks for incident ("new") gout, usually in large, previously non-gout general
populations or community-based samples or samples with specific comorbidities that are

closely associated with gout. The other category includes smaller randomized trials, in which
candidate risk-influencing factors have been tested as a means to trigger or suppress disease
expression; these are typically performed in patients with gout. An observational case-crossover
study conducted among patients with gout has also provided insights into potential triggers for
gout flares [18]. These approaches have provided important information relevant to incident
gout risk and recurrent gout flare risk.
TREATMENT OF COMORBIDITIES
Weight reduction towards ideal body weight and moderation in ethanol consumption have each
been convincingly shown to reduce both the risk of incident gout and the expression of
established gout [19,20]. Other comorbidities have also been the subject of study.
Hyperuricemia and gout are frequently accompanied by one or more major disorders, such as
hypertension, obesity [21], diabetes, and hyperlipidemia, which are components of the
metabolic or insulin resistance syndrome [13-15]; cardiovascular disease; chronic renal
functional impairment; and certain dietary factors such as high alcohol or purine intake
[10,22,23]. These associations have raised the question of whether lifestyle and pharmacologic
(or even surgical) strategies aimed at treatment of one or more of these comorbidities might
suffice to reduce the risk of incident gout and/or the progression of gout.
The strongest evidence that this is the case in prevalent as well as incident gout is provided by
the results of weight reduction toward ideal body weight in obese patients [20,24-27] and of
moderation in ethanol consumption [19,22]. Each of these actions can reduce the risk of
incident gout and the expression of established gout [19,20]. (See 'Obesity and diet' below and
'Alcohol' below.)
Thus, depending upon the comorbidities present, lifestyle modifications and pharmacologic
management directed towards targets other than urate-lowering in gout patients might
include:
● Management of common comorbid diseases (see 'Hypertension and diuretics' below and
'Other drugs and diseases' below)
● Reduction to ideal body weight (see 'Weight loss' below)
● Changes in dietary composition (see below)
● Dietary supplementation, such as with cherries (see below)
● Reduction of alcohol intake (see 'Alcohol' below)
● Substitution, where possible, for medications and/or dietary additives that reduce urate
excretion or increase urate production (see below)
It is important to keep in mind that, in some patients, treatment of an accompanying disorder

may adversely affect gout management, as exemplified by the use of diuretics to treat
hypertension (see 'Hypertension and diuretics' below). Low-dose aspirin, commonly used for
cardiovascular risk reduction, may also increase serum urate (see 'Other drugs and diseases'
below). Nonetheless, given the importance of managing cardiovascular risk, the hyperuricemia
associated with a patient's gout can be managed with appropriate urate-lowering therapy in the
setting of low-dose aspirin or diuretics if necessary.
OBESITY AND DIET
We instruct overweight patients with gout in a healthy diet approach aimed at achieving weight
reduction (at a rate of three to five pounds per month) toward ideal body weight (calculator 1).
Increased adiposity and weight gain are risk factors for incident gout [21,28], while weight loss
in overweight patients is likely beneficial in reducing serum urate and gout symptoms in
patients with established gout [20,25-27]. (See 'Weight loss' below.)
The optimal diet composition to achieve this aim is under study [20], but it is likely to be one
allowing adequate protein intake, especially from low-fat dairy and/or plant sources, with
reduced intake from red meat or shellfish; replacement of simple sugars with complex
carbohydrates; and decreased saturated fat.
We also instruct patients that frequent consumption of alcohol-containing beverages and

sugar-sweetened juices or beverages containing high-fructose corn syrup should be minimized
or avoided. For the patient not requiring weight reduction, we also advise a diet with features
similar to that described above but directed at weight stabilization. (See 'Dietary composition'
below.)
Beyond weight loss, the purpose of focusing on many of these elements is to also aid patients
in avoiding potential triggers for their gout flares, though these factors may not necessarily
trigger flares in all patients.
Patients with established gout should participate in an exercise program appropriate to age
and comorbid status, in addition to the dietary recommendations. (See "Obesity in adults: Role
of physical activity and exercise".)
Weight loss — A number of studies, including a 2017 systematic review of longitudinal studies,
have documented reductions in serum urate and the reduced risk of incident and recurrent
gout flares in overweight and obese individuals who have undergone weight loss [20]. Findings
noted in the systematic review included beneficial effects of weight loss on serum urate levels,
achievement of serum urate target, and reduction in gout attacks. In patients who underwent
bariatric surgery, increased rates of unfavorable gouty events were noted only in the immediate
postoperative period. The studies identified were clinically heterogeneous and involved several
different interventions, thus limiting the strength of the evidence and precluding meta-analysis.
Given the limitations of the available data, additional prospective trials would be helpful.
As an example of such studies, the benefit of weight loss in reducing the risk for incident gout
was illustrated in the 12-year Health Professionals Follow-up Study that monitored a
prospective cohort of 47,150 men with no history of gout at baseline [21]. The risk of incident
gout was higher in men with a body mass index (BMI) of 25 kg/m2 or greater, and the
magnitude of the association became larger with increasing BMI. Men who had gained 13.6 kg
or more had a twofold increased risk of incident gout compared with men who maintained their
weight, while weight loss greater than 4.5 kg was associated with a reduced risk of incident
gout.
In addition, impressive results have been associated with profound weight loss in controlled
trials of patients undergoing bariatric surgery for severe obesity, usually in combination with
one or more commonly accompanying features of the metabolic syndrome [24,26,27]. Findings
include improvement in several aspects of impaired metabolic regulation, including
hyperuricemia, with clinical benefit in patients with established as well as incident gout. As
examples:
● Bariatric surgery was associated with a reduced frequency of incident gout, compared with
a control group who did not undergo such surgery, in a prospective interventional trial
involving nearly 4000 obese (BMI ≥34 kg/m2) but non-gouty patients in Sweden [24].
Participants undergoing bariatric surgery were matched for demographic and comorbid
features with a non-operated control group receiving a range of standard obesity
treatments. At two-year follow-up, BMI had decreased by 24 percent in the surgery group,
with no change in the control group; at 10-year follow-up, the corresponding changes from
baseline BMI were -17 and +2 percent for the respective groups. Bariatric surgery was
associated with less frequent incident gout over the 26-year follow-up period (138 surgically
treated patients versus 201 patients in the control group; after multivariable adjustment,
hazard ratio [HR] 0.60, 95% CI 0.48-0.75). Age, creatinine levels, serum urate ≥6.8 mg/dL,
use of medications associated with increased gout risk, and alcohol intake at baseline were
all associated with an increased risk for incident gout.
● At least two studies have supported the view that the weight loss associated with bariatric
surgery has beneficial, clinically important effects in patients with established gout:
• In one study, bariatric surgery reduced serum urate and rates of gout flares in patients
with gout. In this study, which involved 60 patients in New Zealand with BMI ≥35 kg/m2
and type 2 diabetes, of whom 12 had established gout and 48 were without gout, all
patients completed an initial dietary intervention for six months [26]. This resulted in a
mean weight loss of 5.5 kg but no change in serum urate from baseline. All patients
then underwent laparoscopic sleeve gastrectomy, with a further one-year follow-up,
during which serum urate levels were serially measured.
In the first postoperative month, serum urate levels and rates of gout flare increased in
both patients with and without gout, but thereafter diminished to values at one year
that were lower than at baseline. Serum urate levels at time of surgery exceeded
saturation in 10 of the 12 patients with gout, but at one year after surgery the
corresponding proportion was only 3 of 12. The study identified clinically relevant
reductions in serum urate after bariatric surgery in both groups who also had diabetes
and World Health Organization (WHO) class II or higher obesity. Baseline serum urate,
cessation of diuretics, and female sex all independently predicted change in the serum
urate at the final visit.
• Similarly, in another study, involving morbidly obese patients with gout, the effects of
bariatric surgery (in 99 patients) on the course of the disease were compared with the
effects of non-bariatric upper abdominal surgery (the control group, including 56
patients) [27]. The incidence of gout flares was significantly higher among the bariatric
surgery patients compared with the controls during the first postoperative month (18
versus 2 percent). However, in the bariatric surgery group, compared with the month
prior to surgery, gout flares were reduced during postoperative months 1 to 13 (from
24 to 8 percent), while they were unchanged in the non-bariatric surgical group. In
addition, the mean serum urate level decreased from a baseline of 9.1 mg/dL to a value
of 5.6 mg/dL at 13 months after bariatric surgery.
In addition to weight loss itself, dietary composition and its modification can also influence
serum urate; modifying the dietary composition in a fashion that may be best for reducing
serum urate is also a goal (see 'Dietary composition' below). Dietary therapy and other
strategies for the management of obesity are described in detail separately. (See "Obesity in
adults: Dietary therapy" and "Obesity in adults: Overview of management".)
Dietary composition — The major dietary classes and dietary composition can influence serum
urate levels in normal individuals and those with asymptomatic hyperuricemia or gout; these
effects have been a focus of numerous studies, as has the capacity of individual dietary
additives to benefit patients with established gout or, alternatively, serve as triggers for acute
gout flares. However, in a meta-analysis of data from population-based cohorts of patients of
European ancestry in the general population without a diagnosis of gout or use of urate-
lowering therapies, diet is estimated to be a very minor contributor to the population variance
of baseline levels of serum urate, and hence in the risk for gout, compared with common
genome-wide single nucleotide variation (≤0.3 versus 23.9 percent) [29].
The major energy-supplying nutritional classes consumed in the diet appear in a wide variety of
complex mixtures (contexts) determined in part by the sources (eg, animal, vegetable, plant)
from which they derive and the proportions ingested. The sources and proportions are subject
to geographic and genetic restrictions as well as societal and individual dietary preferences.
Major dietary classes and their contexts
Purines — Dietary purine restriction has proven to be an impractical means to manage

gout, despite urate being the end product of purine metabolism. Furthermore, with the
availability of potent antihyperuricemic drugs, this dietary approach is rarely necessary and
infrequently employed, except in individuals with severe renal insufficiency or intolerance of
pharmacologic therapy.
Dietary composition, as well as dietary volume, has been suspected as a risk factor of gout for
more than a century [30]. Early recognition of the presence of crystals of urate, the end product
of human purine metabolism, in gouty lesions prompted recommendation of severely purine-
restricted diets for patients with gout prior to the availability of urate-lowering
pharmacotherapy. Although such diets can reduce daily urinary uric acid excretion by 200 to
400 mg/day, mean serum urate concentrations decrease only about 1 mg/dL (59 micromol/L),
and diets with restricted purine (and protein) contents are unpalatable and often ineffective in
the management of hyperuricemia and gout in patients with normal dietary habits.
Of interest in this regard, in the prospective Health Professionals Follow-up Study, neither the
intake of purine-rich vegetables nor total protein intake was associated with an increased risk of
incident gout [12]. This finding was consistent with findings from an online case-crossover
study in which higher intake of animal-derived purines was associated with greater risk of gout
flares than vegetable sources of purines [23]. The results of these and additional studies
addressing the overall contexts within which specific major dietary components are ingested
support the view that differences in the contexts of individual dietary components contribute to
variable outcomes in evaluating individual dietary classes as risk factors for gout versus triggers
for gout flares, particularly in the context of the priming "first-signal" and "second-signal"
required for NLRP3 inflammasome activation leading to the inflammatory manifestations of
gout flares that may be provided by long-chain fatty acids in the diet [31]. (See 'Proteins' below.)
Proteins — Increasing amounts of meat and seafood in the diet are significantly

associated with an increased risk of incident gout but have not been shown to have an adverse
effect upon patients with established gout in clinical trials, though the case-crossover study
mentioned above reported a higher risk of gout flares with higher intake of animal sources of
purines [23]. However, the source of protein may be important, as studies in an Asian
population found that soy and non-soy legume ingestion was associated with a reduced risk of
incident gout. Low-fat dairy has also been found to reduce incident gout, but reduced gouty
attacks in patients with established gout have not been demonstrated.
Despite the lack of evidence for benefit from changes in dietary protein content on the course
of prevalent (ie, established) gout, published guidelines for management of patients with
prevalent gout continue to recommend increased low-fat dairy and reduced meat and seafood
intake in patients with gout [1,3,4,7,8]. The 2012 American College of Rheumatology gout
treatment guidelines are in the process of being updated. In light of the apparent benefit of
these dietary changes in comorbidities common among gout patients (eg, hypertension), it is
our view that these recommendations are appropriate for overweight patients with gout as
long as they are well tolerated, readily available to patients, and recognized as being of
uncertain benefit.
The association of increasing meat and seafood intake with gout is well illustrated in the
prospective observational study of 47,150 male health professionals without a history of gout at
baseline [12]. Those in the highest quintile of meat consumption had an increased risk of
incident gout compared with those in the lowest quintile (adjusted HR 1.41, 95% CI 1.07-1.86);
those consuming the largest amount of fish had an increased risk of gout compared with those
in the lowest quintile (HR of 1.51, 95% CI 1.17-1.95). A cross-sectional study of a nationally
representative adult population in the United States similarly found that high levels of meat and
seafood consumption were associated with higher serum urate concentrations [11].
An additional study in an Asian population, in whom plant-sourced protein reduced risk of gout,
supported the view that the source of dietary protein consumed is an important factor
influencing incident gout risk [32]. In two Chinese populations in Singapore, total protein intake
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mainly from poultry, fish, and shellfish was associated with an increased risk of incident gout,
but protein intake largely from soy and legumes was associated with a reduced risk.
The evidence also suggests that ingestion of dairy products reduces incident gout. In contrast
to meat and seafood intake, the highest quintile of dairy product consumption was associated
with a nearly 50 percent reduction in incident gout risk compared with the lowest quintile [12].
The adjusted risk ratio of incident gout per additional daily serving of dairy products was 0.82
(95% CI, 0.75-0.90) and was primarily restricted to intake of low-fat milk. These findings,
combined with cross-sectional studies in normal individuals showing an inverse relationship
between dairy/milk product intake and serum urate levels [11,33,34] and the identification of
two milk fractions with antiinflammatory properties in an in vitro model of gouty inflammation
[35], provided the background for a randomized trial of a dietary intervention (addition of a low-
fat dairy product equivalent to two daily servings) in the management of patients with
established gout.
Despite the effects of low-fat dairy intake as a means to mitigate incident gout, it was not found
in a randomized trial to provide similar benefit in patients with established gout. In this trial,
120 patients with poorly controlled gout (ie, at least two gout flares in the preceding four
months) first underwent a one-month noninterventional run-in period, during which baseline
gout flares and demographic data were recorded [36]. Participants were then randomly
assigned to one of three study arms, in which their pretrial diets were supplemented for three
months by daily treatment with a powdered preparation of either lactose (non-low-fat dairy
control) or skim milk powder (SMP, 15 g protein; low-fat dairy control); or SMP plus the two
"antiinflammatory" milk fractions (enriched SMP [36]). The low-fat dairy extract (SMP) treatment
alone did not improve any of the endpoints, including serum urate, in these patients with gout,
although the primary endpoint of reduction in gout flares from baseline was achieved in the
group receiving enriched SMP, as was the secondary endpoint of increased fractional urinary
excretion of urate. Prior studies documented acute reductions in serum urate levels with SMP
given as a single but much higher dose of 80 g [34]. Whether sustained higher-dose SMP
treatment would prove clinically efficacious and practical in the longer term is uncertain.
Carbohydrates — We concur with recommendations from multiple medical organizations

for the avoidance of sugar-sweetened beverages as a means to mitigate the risk of incident
gout and the risk of progressive disease in those with established gout [1,3-8].
Considerable interest has been directed to the role of high intake of simple sugars (fructose,
sucrose) as risk factors for incident gout. In two large, high-quality prospective cohort studies,
46,393 male health professionals [37] and 78,906 female nurses [38], none of whom had gout at
inception, were tracked over 12 and 22 years, respectively, with data collected every two years
with regard to weight, medications, and medical conditions, and with validated food frequency
questionnaires every four years. The questionnaires inquired regarding ingestion of more than
130 different foods and beverages, with a focus on fructose intake. In the two studies, a total of
1533 cases of incident gout were reported and confirmed. In a systematic review of these
studies of fructose intake, the risk for incident gout, comparing the highest and lowest quintiles
of fructose intake, while accounting for percent of energy from total carbohydrates and
adjusting for potential confounders, was increased overall (risk ratio [RR] 1.62, 95% CI 1.28-
2.03), for men (RR 1.81, 95% CI 1.31-2.50), and for women (RR 1.44, 95% CI 1.04-2.00) [39].
Adjustments in the final analysis included age, total energy intake, BMI, diuretic use,
hypertension, renal failure, menopause, alcohol, vitamin C, caffeine, and percent of energy
from carbohydrates. In the male health professionals study, the main dietary sources of
fructose were orange juice, sugar-sweetened beverages, apples, raisins, and oranges [37]. In
neither study was drinking diet soft drinks associated with an increased risk for incident gout.
Investigations in New Zealand [40,41] and elsewhere [42] have supported these findings with
respect to hyperuricemia and the risk of developing gout; these studies provide reasonable
mechanistic and genetic epidemiologic bases that support our approach and the
recommendations of multiple professional medical organizations for avoidance of sugar-
sweetened beverages to prevent and manage gout as well as common comorbidities, such as
obesity and type 2 diabetes [1,3-5,7].
One concern with the data regarding the role of sugar-sweetened beverages as a risk for gout
was inconsistency with respect to establishing associations of such beverages with
hyperuricemia, an issue not addressed in the above prospective cohort studies. One study,
however, found that high BMI was an important co-determinant mediating the relationship of
sugar-sweetened beverage intake and serum urate concentration in both a large cross-
sectional population and in patients with established gout [40]; in addition, renal tubular urate
excretion was shown to be impaired in patients with high BMI, compared with normal BMI, in
response to a fructose load, thus likely contributing to hyperuricemia in the former group.
Some sugar-sweetened beverages also contain caffeine, which has a chemical structure similar
to the xanthine oxidase inhibitor (XOI) allopurinol; whether there are some contrasting effects
that may explain some inconsistencies is not clear. Further, a genetically determined alteration
in the function of the renal urate/glucose/fructose transporter (SLC2A9) favoring a
hyperuricemic response to sucrose intake has been identified among individuals with prevalent
gout, further supporting reduction of sugar-sweetened beverage intake in gout management
[41]. Finally, physiologic mechanisms have been identified through which fructose intake can
increase urate production [42] as well as reduce renal urate excretion.
Specific dietary products providing potential gout benefit or increased risk — Additional

studies have attempted to identify individual dietary supplements that provide clinical benefit
to gout patients or, conversely, warrant avoidance as triggers for gout flares.
● Cherries – Some evidence and anecdotal reports suggest a beneficial role of cherry
ingestion as a nonpharmacologic modifier of the course of established gout [18,43]. Based
upon the available data, we discuss dietary supplementation with cherries with our patients
with established gout and accede to their wishes regarding initiation or continuation of
therapy (usually 10 to 12 cherries once or twice daily). However, further study is needed,
and we do not advise cherry ingestion as primary or sole treatment for gout flare or gout
flare prevention.
In response to reports of a beneficial effect on the expression of established gout by the

addition of cherries to the diet, an internet-based crossover study assessed the effect of
cherry intake on recurrence of gout flares in patients with established gout [18]. In all, 633
patients with gout and at least one gout flare in the preceding year were enrolled to
complete a series of study questionnaires during a one-year study period. Each patient
provided detailed information for at least one two-day intercritical control period and at
least one two-day hazard period immediately preceding onset of a flare. For both control
and hazard periods, patients were assessed for the extent of cherry use, other potential
triggers for flare (including diet, alcohol use, purine intake, diuretic use, infections, injuries,
anti-gout medication use), and characteristics of the flare. The design of crossover studies
of this type and the timing of exposure measurements in relation to gout attacks permit
each patient to serve as his or her own control, thus eliminating potentially confounding
risk factors that are constant within an individual but would differ among study subjects
[44].
In the trial, 42 percent of study participants reported using cherries in their diets, the great
majority as fresh cherry fruit rather than cherry extract. During the study period, 1247
flares were reported. Cherry intake over a two-day period was associated with a 35 percent
lower risk of gout attacks compared with no cherry intake (adjusted odds ratio [OR] 0.65
[95% CI 0.50, 0.85]). There was a trend to decreased flare risk with increased cherry
consumption up to three servings (10 to 12 cherries per serving) over two days, and the
inverse association of cherry intake with gout flare was independent of sex and BMI.
In addition, the mitigating effect of cherry intake on flare recurrence was reduced during
periods of increased alcohol or purine consumption but was increased during allopurinol
or colchicine use. These observations require further mechanistic studies and confirmation
in randomized trials.
● Vitamin C – Vitamin C has a mild but persistent urate-lowering effect, but evidence is
lacking for any clinical benefit in patients with established gout. We do not routinely
recommend supplemental vitamin C therapy for established gout in persons with daily
intakes of the vitamin meeting current standards. We do, however, describe the available
evidence to our patients and accommodate to the wishes of individual patients regarding
vitamin C supplementation at a dose not exceeding 500 mg daily.
The urate-lowering effect of vitamin C in people without gout was illustrated in a trial that
randomly assigned nonsmoking adults to 500 mg of vitamin C or placebo [45]. Vitamin C
significantly reduced serum urate levels by a mean of 0.5 mg/dL (30 micromol/L) compared
with no change with placebo. A urate-lowering effect of vitamin C in asymptomatic
hyperuricemic individuals was supported in a meta-analysis, which showed the effect to be
dose-related and greater with higher baseline serum urate levels [46]. In addition, the
relative risk of incident gout was reduced with increasing daily doses of vitamin C beyond
500 mg compared with total daily vitamin C intakes <250 mg [47].
However, in a randomized trial in patients with existing gout, intake of 500 mg of

supplemental vitamin C daily had no discernible effect on the course of established gout,
and mean serum urate reductions attributable to the vitamin with or without concomitant
allopurinol administration were minimal and unlikely to provide clinical benefit at the
commonly recommended supplemental dose studied [48].
Whether more robust/clinically meaningful urate-lowering is achievable and safe at higher

doses of vitamin C administered to established gout patients remains to be determined.
● Coffee – We do not support initiation of higher coffee intake for purposes of preventing
incident gout or altering the course of established gout. High coffee intake (eg, four to five
cups daily) is associated with a substantial reduction in the relative risk of incident gout
compared with no coffee intake (RR 0.60, 95% CI 0.41-0.87) [49]. The reduction in risk is
slightly less with decaffeinated coffee and is not shared with frequent tea intake.
However, in patients with prevalent gout, serum urate levels with intake of >4 cups of
coffee daily are reduced, compared with no coffee intake, only by a relatively small amount
(mean difference of -0.42 mg/dL, 95% CI 1.01-0.17) [50]. Outcomes of clinical trials in which
increasing amounts of coffee have been added to the diets of patients with established
gout have not been reported.
● Fish and omega-3 fatty acid consumption – Some evidence supports the potential benefit
of omega-3 polyunsaturated fatty acids (n-3 PUFA), which are thought to have
antiinflammatory properties, for the reduction of gout flare risk. In an internet-based study
involving 724 patients with established gout, the risk of a gout flare was reduced in
individuals reporting dietary consumption of fatty fish rich in n-3 PUFA during the 48 hours
preceding a flare compared with the 48 hours preceding a flare-free period (OR 0.74, 95%
CI 0.54-0.99) [51]. By contrast, intake of n-3 PUFA supplements alone (taken in a self-
directed manner) did not reduce such risk (OR 1.01, 95% CI 0.63-1.60). This difference might
be related to the substantially lower dose of n-3 PUFA that is usually taken as a supplement
compared with the level in fatty fish. The hypothesis that higher-dose supplement use may
be comparably beneficial, and serve as a means to avoid high levels of dietary purine intake
that may be undesirable, remains to be examined before high-dose n-3 PUFA supplements
can be recommended for gout flare prevention.
● Other proposed supplements – Among other dietary supplements that have been
reported to be beneficial in patients with established gout are dietary fiber and folate [52];
evidence of consistent benefit with either of these agents is needed before advising their
use for this purpose.
Dietary triggers of gout flares — There are some gout patients with dietary habits that
consistently provoke the occurrence of acute gouty arthritis. Fatty meals have been implicated
in precipitating flares [53].
Whole diet approaches — There is some limited evidence to suggest that whole diet
approaches, rather than modification of one or a few individual dietary components, may have
potential benefit in preventing incident gout and in the treatment of established gout; one such
diet is the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in fruits,
vegetables, and low-fat dairy products and is well documented and used to reduce blood
pressure and for prevention of cardiovascular disease [54]. (See "Diet in the treatment and
prevention of hypertension", section on 'Dietary Approaches to Stop Hypertension trial'.)
Consideration of more complete dietary combinations for serum urate reduction and clinical
efficacy in gout patients has been prompted by difficulties in confirming or reconciling
differences in the proposed benefits of individual dietary components or additives as influences
on the risk of incident and established gout in a variable diet context [25,55,56].
Considerable differences exist worldwide in the prevalence of the metabolic syndrome. These
differences appear, at least in part, to associate with differences in the diets traditionally
consumed in the respective societies and have prompted investigations to compare the effects
of dietary patterns commonly preferred in lower-risk populations on the expression and
outcomes of metabolic syndrome components when administered to persons in higher-risk
societies [55]. The DASH diet emphasizes fruits, vegetables, and low-fat dairy foods but reduces
consumption of saturated and total fat and cholesterol [54]. This diet also includes whole
grains, poultry, fish, and nuts and contains smaller amounts of red meat, sweets, and sugar-
containing beverages than are in the typical American diet.
Evidence from the DASH trials has suggested that the diet can result in lowering of serum urate
levels and incident gout:
● In the original randomized crossover DASH-sodium feeding trial, which examined the
effects of the diet and sodium intake on blood pressure, the DASH diet was compared with
an "average American" control diet in prehypertensive or stage-1 hypertensive persons
[54]. After two weeks of a high-sodium-containing control diet, patients were randomized
to either the DASH diet or the control diet for three 30-day periods (separated by five days
each), differing only in the low-, medium-, or high-sodium content in the assigned diet.
Results of that trial showed that the DASH diet lowered blood pressure substantially and
that low sodium consumption further lowered blood pressure.
An ancillary analysis of stored samples obtained from 103 participants enrolled at a single
study site in the DASH-sodium trial showed that serum urate levels were significantly
reduced by the DASH diet (in a baseline serum urate-dependent manner) and further
reduced by increasing sodium intake from low to medium or high level [56]. Among the 51
participants in this study who received the DASH diet, none had gout, but eight had serum
urate ≥7 mg/dL, and among these eight, the mean reduction of urate was 1.3 mg/dL,
compared with participants receiving the control diet [56].
● Although the urate-lowering effect of the DASH diet has not been documented in
established gout patients, comparison of subjects without gout at baseline in the Health
Professionals Follow-up Study 26-year cohort, based upon their adherence to a dietary
pattern resembling the DASH diet versus a "Western dietary pattern," showed that a higher
DASH dietary pattern score was associated with a lower risk of incident gout, while a higher
Western dietary pattern was associated with an increased risk [55]. Adjusted relative risks
for these findings were independent of potential confounders such as age, BMI,
hypertension, diuretic use, and alcohol intake.
These findings warrant extension in randomized trials in patients with established gout; they
appear to provide promising data in support of this approach to dietary management as an
adjunct to other means of urate-lowering therapy that may also address other common
comorbidities that exist in individuals with gout.
ALCOHOL
We take the following approach to counseling patients with respect to use of alcoholic
beverages:
● In patients with levels of alcohol intake that are generally viewed as safe or moderate (eg,
one to two drinks of beer, spirits, or wine daily), but who are at high risk for incident gout,
and in all patients with established gout, we discuss the evidence linking acute excesses or
chronic intake of beer, spirits, and wine to the risks for gout flare and disease progression
with the patient, and we advise reduction in alcohol intake. (See "Risky drinking and alcohol
use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and
diagnosis".)
● In patients with established gout maintaining goal range serum urate levels on
pharmacologic urate-lowering therapy, small amounts of alcohol intake are unlikely to
trigger flares or promote disease progression.
● In patients who report unhealthy or risky (ie, potentially hazardous) use of alcoholic
beverages, we counsel the patient about the inherent dangers to their health and the well-
being of themselves and others. We stress the need for cessation of or moderation in
alcohol use and offer to direct them to social and professional assistance in doing so. (See
"Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical
manifestations, course, assessment, and diagnosis".)
The risks for gout imparted by alcohol, whether imbibed in the form of beer, distilled liquor, or
wine, have been examined in several studies. As examples [10,19,22]:
● The risk of incident gout was increased in association with use of beer or liquor, but not
wine, in a large prospective study of the effects of alcohol intake on incident gout that
followed health professional men with no prior history of the disease [10]. Rates of incident
gout among drinkers of similar amounts of alcohol per day in one of the three beverage
categories were compared with those among nondrinkers. Drinking two or more beers per
day increased the risk of incident gout 2.5-fold compared with no beer intake. The risk of
gout was also increased in men who drank a similar amount of liquor per day, although the
risk was lower than with beer (1.6-fold compared with no alcohol use). By contrast, intake of
two or more four-ounce glasses (approximately 120 mL/glass) of wine per day was not
associated with an increased risk of gout, suggesting that moderate wine intake might not
increase the risk of incident gout. However, because wine consumption is generally
associated with a variety of healthy lifestyle behaviors, it is possible that the effects of wine
were not discernable due to confounding by such factors.
● Beer, liquor, and wine were all associated with an increased risk of gout flare in patients
with established gout and at least one gout flare in the prior year who were analyzed in an
internet-based crossover study of the effects of alcohol intake on the risk of gout flares
[19]. The study involved 724 patients (78 percent men) who served as their own controls,
which means that the healthy lifestyle behaviors that are constant within an individual
would not confound the association. A significant dose-response relationship was found
between the amount of alcohol (beer, liquor, or wine) consumed and risk of gout flare:
higher number of servings of alcohol consumed in the preceding 24 hours (≤1, >1 to 2, and
>2 to 4 drinks) were associated with odds ratios (OR) for gout flares of 1.13, 95% CI 0.80-
1.58; OR 1.36, 95% CI 1.00-1.88; OR 1.51, 95% CI 1.09-2.09, respectively, compared with no
alcohol intake in the prior 24 hours.
Unlike the risk of incident gout, which was only associated with beer or liquor in the study
cited above, the risk of gout flare was increased with all three types of alcohol, including
wine (OR 2.38, 95% CI 1.57-3.62, for >1 to 2 five-ounce [approximately 150 mL/glass] drinks
of wine).
The combinations of increased alcohol and high purine consumption or diuretic use were
associated with higher risk of flares, while allopurinol and, to a lesser degree, colchicine
reduced the effects.
HYPERTENSION AND DIURETICS
Primary hypertension (formerly called "essential" hypertension) and diuretic use are both
independently associated with hyperuricemia [57] and gout [21]. However, given the
cardiovascular benefits of thiazide diuretics in patients with hypertension and the low cost of
these agents in patients being treated with these agents, we switch to another antihypertensive
drug only if the hyperuricemia is not controlled with adequately dosed urate-lowering therapy,
and the hypertension can be easily controlled by another agent and if cost is not a significant
issue. Losartan in particular has uricosuric effects and may be a good alternative agent. The
management of hypertension and diuretic-induced hyperuricemia and gout are discussed in
detail separately. (See "Choice of drug therapy in primary (essential) hypertension" and
"Diuretic-induced hyperuricemia and gout".)
As an illustration of the role of both primary hypertension and diuretic use, in the Health
Professionals Follow-up Study, the risk of incident gout was significantly increased among men
with hypertension, compared with those without hypertension, after adjusting for diuretic use
(relative risk [RR] 2.31, 95% CI 1.96-2.72) [21]. Similarly, after adjusting for the presence of
hypertension, the risk of gout among men taking a diuretic was also increased compared with
those not on a diuretic agent (RR 1.77, 95% CI 1.60-8.14).
In a large, population-based, case-control study that confirmed that a greater risk of gout was
associated with the use of loop, thiazide, and thiazide-like diuretics, the thiazide and loop
diuretics appeared to confer similar risks, but potassium-sparing agents were not associated
with an increased risk [58]. Finally, in an online case-crossover study of patients with established
gout, recent diuretic use was confirmed as a trigger for recurrent acute gout flares [59].
The rise in serum urate with the most common diuretic used to treat hypertension,
hydrochlorothiazide, is relatively small at low doses ( figure 1) and can be minimized by
concurrent therapy with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II
receptor blocker (ARB). In addition, the ARB losartan reduces serum urate via a modest
uricosuric effect that appears to plateau at a dose of 50 mg/day and is not seen or is less
pronounced with other ARBs and with ACE inhibitors [60]. Gout patients who need an
antihypertensive agent may thus also benefit from the uricosuric effect of losartan and avoid
the need for further xanthine oxidase inhibitor (XOI) dose escalation or use of an alternative
uricosuric drug to lower urate concentrations. (See "Use of thiazide diuretics in patients with
primary (essential) hypertension" and "Diuretic-induced hyperuricemia and gout", section on
'Benefits of angiotensin inhibition and losartan'.)
Other nondiuretic antihypertensives may also affect urate levels and the risk of gout. Beta-
blockers have been reported to increase serum urate [61,62] and the risk of incident gout [63],
while calcium-channel blockers have been found to decrease both urate levels [64,65] and
incident gout risk [63].
OTHER DRUGS AND DISEASES
● Aspirin – Patients with gout who require aspirin for cardiovascular prophylaxis should
undergo the same monitoring and treatment as other patients with gout. However,
discontinuation of aspirin is generally not required because gout flare is unlikely to be an
early adverse consequence of low-dose aspirin treatment in patients who are not
hyperuricemic prior to initiation of treatment, and adequate urate-lowering therapy should
mitigate effects of low-dose aspirin.
Aspirin has paradoxical effects on renal uric acid excretion [66,67]. Treatment with doses of
aspirin up to 2 to 3 g daily causes urate retention [68-70], unlike higher doses, which are
uricosuric. Low-dose aspirin (75 to 325 mg/day), administered for cardiovascular
prophylaxis, can increase serum urate levels and rates of gout flares in patients with
prevalent gout [70], although urate-lowering therapy with allopurinol or probenecid
reverses the risk of recurrent flare. Patients should be encouraged to take their medication
on a daily basis (ie, be adherent) to minimize fluctuations in urate that can arise with
intermittent use of these medications. (See "Pharmacologic urate-lowering therapy and
treatment of tophi in patients with gout", section on 'Side effects and interactions'.)
● Fenofibrate and hyperlipidemia – Fenofibrate, a fibric acid derivative used for the
treatment of hyperlipidemia, has modest uricosuric activity. In a short-term unblinded
study of 10 patients with gout who were already being treated with allopurinol, the
addition of fenofibrate (200 mg/day) resulted in a 19 percent reduction in serum urate and
a mean increase in uric acid renal clearance of 36 percent [71]. In gout patients with
hypertriglyceridemia, fenofibrate may provide adjunctive urate-lowering. (See "Low density
lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors",
section on 'Fibrates'.).
● Cystic fibrosis – Patients with cystic fibrosis may develop dysuria, crystalluria,
hyperuricemia, hyperuricosuria, and, in some cases, chronic gouty arthritis during the
course of high-dose treatment with purine-rich pancreatic extract therapy [72,73]. Such
patients may benefit from dose reduction, with a return to more normal serum urate
concentrations. (See "Cystic fibrosis: Assessment and management of pancreatic
insufficiency", section on 'Pancreatic enzyme replacement therapy'.)
PROGNOSIS
In patients with gout who do not yet meet indications for urate-lowering therapy, it would be
reasonable to consider lifestyle modifications and other risk reduction approaches. However,
for patients with gout who have indications for urate-lowering therapy, pharmacologic urate-
lowering therapy is necessary to achieve and maintain a target serum urate level to manage the
clinical manifestations of the disease; lifestyle modification and risk reduction approaches
should be considered adjunctive.
Preventing recurrent flares, chronic gouty arthritis, and the development of tophi requires the
long-term use of drugs that reduce the serum urate concentration either by decreasing urate
synthesis (xanthine oxidase inhibitors [XOIs]) or by enhancing renal excretion of uric acid
(uricosuric agents) or both. For severe refractory gout, a modified uricase therapy (eg,
pegloticase) may be required. The choice of specific drug therapy depends upon several factors.
Such pharmacologic urate-lowering measures are also effective in most patients with
tophaceous gout, although surgical intervention may be a needed adjunct to medical
management in a few patients with complications due to tophaceous disease. (See
"Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout".)
Suboptimal clinical outcomes have been well-documented in gout patients, despite the
available therapies and their demonstrated potential for substantial clinical benefit, both in
terms of recurrent gout flares and of progression to tophi and chronic gouty arthritis [74,75].
Impediments to successful management have been identified, highlighting the importance of
improved patient and clinician education and communication [16,76]. Indeed, in a trial of nurse-
led care, which involved patient engagement and education, versus usual care by general
practitioners, patients randomized to the nurse-led arm had significantly better outcomes in
terms of serum urate target achievement, as well as clinically relevant flare and tophi reduction
[77]. The factors associated with suboptimal outcomes are discussed in more detail separately.
(See "Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout",
section on 'Prognosis'.)
RECOMMENDATIONS OF MAJOR GROUPS
Several professional organizations and expert groups have published and/or updated
guidelines or recommendations for the management of gout. Although most aspects of our
approach to lifestyle and risk reduction are generally consistent with those addressed by these
groups, the American College of Physicians guidelines question the evidence basis for many of
these approaches, other than patient education and initiatives aimed at promoting general
health, as applied specifically to the prevention of incident gout and the management of
patients with prevalent gout. The various guidelines and these differences are discussed
elsewhere. The American College of Rheumatology are updating their 2012 gout guidelines.
(See "Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout",
section on 'Recommendations of major groups' and 'Society guideline links' below.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Gout and other crystal
disorders".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Gout (The Basics)")
● Beyond the Basics topics (see "Patient education: Gout (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● The symptoms and signs of gout arise from biologic responses to monosodium urate
crystal deposited in tissues as a result of urate saturation of extracellular fluids. Long-term
success in achieving the therapeutic goal of sustained reduction of serum urate levels to a
subsaturating range in patients with existing (prevalent) gout is attended by clinical
benefits that include cessation of gout flares, resolution of tophi, and improvement in
patient physical function and health-related quality of life. Complete clinical remission often
requires many months to several years to achieve, due to the slow reduction in the body
monosodium urate crystal burden that has accumulated in most patients over years of
hyperuricemia preceding the onset of gout. Maintenance of remission usually requires
sustained lifestyle and/or pharmacologic treatment to assure sustained urate
subsaturation. (See 'Introduction' above and 'Rationale for management approaches'
above.)
● The asymptomatic interval (intercritical period) between gout flares (ie, after a flare has
resolved) is the preferred time to introduce an individualized management plan
incorporating patient education and preferences and data on the patient's gout history,
comorbidities, medications, lifestyle, and evidence of gout disease activity. The therapeutic
approach to prevention of recurrent gout flares, tophi, chronic gouty arthritis, and joint
damage includes initiation of lifestyle and risk-reduction actions, when appropriate as
adjuncts, to urate-lowering pharmacotherapy tailored to each patient. (See 'Management
principles' above.)
● Lifestyle and comorbidity treatment-related characteristics associated with either increases

or reductions in incident (new-onset) gout have been identified, suggesting means for
improvement in the primary prevention of gout. However, some apparent modifiers of
incident gout risk have not shown efficacy or practicality in reducing risk of symptoms and
disease progression in patients with established gout. (See 'Risk reduction' above.)
● We instruct overweight patients with gout in healthy diet approaches, along with an
exercise program within the limits set by patient age and comorbid status, which permits a
modest (three to five pounds per month) weight loss toward ideal body weight (calculator
1). Increased adiposity and weight gain are risk factors for incident gout, while weight loss
in overweight patients is likely beneficial in reducing serum urate and gout symptoms in
patients with established gout. (See 'Obesity and diet' above and 'Weight loss' above.)
● Severely purine- or protein-restricted diets are not recommended to prevent or treat gout.
Such diets are unpalatable, have only modest serum urate-lowering effects in patients with
normal dietary habits, and reduce serum urate levels by an average of only 1 mg/dL.
However, we do advise dietary moderation in purine precursor intake with our patients as
such modification may help mitigate triggering flares. (See 'Obesity and diet' above and
'Dietary composition' above and 'Purines' above and 'Proteins' above.)
● The optimal diet composition to achieve and sustain weight loss and reduced gout risk is
uncertain but is likely to have many features of the Dietary Approaches to Stop
Hypertension (DASH) diet, which is used for prevention of hypertension and cardiovascular
disease. This diet emphasizes an increased proportion of protein from low-fat dairy
products, reduced red meat and shellfish intake, replacement of simple sugars by complex
carbohydrates, and a decrease in saturated fat. Patients with gout, particularly those with
high body mass index (BMI), should avoid or replace sugar-sweetened juices and beverages
containing fructose. (See 'Obesity and diet' above and 'Whole diet approaches' above.)
● Regardless of the need for weight loss, we discuss diet with all gout patients, focusing on
dietary volume and composition and the use of dietary additives with regard to their
proposed benefits in urate-lowering or gout flare trigger avoidance. We often suggest a
diet similar in pattern to that of the DASH diet. We stress avoidance of weight gain and
potential triggers for gout flare (eg, alcohol binges, high purine/protein and fatty meals,
variable medication adherence) and relate the evidence for the efficacy, harms, and
appropriate use, if any, of dietary additives, including cherries, vitamin C, coffee, and
others. (See 'Specific dietary products providing potential gout benefit or increased risk'
above and 'Alcohol' above and 'Dietary triggers of gout flares' above and 'Management
principles' above and 'Whole diet approaches' above.)
● In patients with gout who imbibe alcohol in low-risk or moderate amounts (eg, one to two
drinks of beer, spirits, or wine daily or less frequently but in binge fashion), we describe the
link of chronic intake or acute excesses of beer, spirits, or wine to the risks for gout flare,
and we counsel reduction in alcohol intake. In patients with gout maintaining goal range
serum urate levels on pharmacologic urate-lowering therapy, small amounts of alcohol
intake are unlikely to trigger flares or promote disease progression. We instruct all patients,
with gout or otherwise, who report imbibing hazardous amounts of alcoholic beverages
about the inherent dangers to their health and the well-being of themselves and others,
stress the need for cessation of or moderation in alcohol use, and offer to direct them to
social and professional assistance in doing so. (See 'Alcohol' above.)
● Primary hypertension (essential hypertension) and diuretic use are each independently
associated with hyperuricemia and gout. Patients with hypertension who become
hyperuricemic or experience gout flares while being treated with thiazide diuretics may
consider switching to another antihypertensive drug only if their hyperuricemia is difficult
to manage with optimal urate-lowering therapy, and if their hypertension can be easily
controlled by another agent and cost is not a significant issue. Losartan has modest
uricosuric effects, unique among angiotensin II receptor blockers, and may be an
alternative to a diuretic. Other antihypertension therapies have effects on serum urate
levels and risk of incident gout; loop (but not potassium-sparing) diuretics and beta-
blockers increase and calcium channel blockers decrease urate levels. (See 'Hypertension
and diuretics' above.)
● Low-dose aspirin (75 to 325 mg/day) administered for cardiovascular prophylaxis increases
serum urate levels and rates of gout flares in patients with gout. Discontinuation of low-
dose aspirin therapy is generally not necessary in patients requiring cardiovascular
prophylaxis because urate-lowering pharmacotherapy with allopurinol or probenecid
reverses the risk for recurrent gout flare in aspirin-treated patients, and gout flare is
unlikely to be an early adverse consequence of low-dose aspirin treatment in patients who
are not hyperuricemic prior to aspirin treatment. Patients should be counseled about the
importance of medication adherence as a means of mitigating against serum urate
fluctuations with intermittent medication use, which may contribute to triggering of gout
flares. (See 'Other drugs and diseases' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Michael A Becker, MD, who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
Topic 105886 Version 16.0
GRAPHICS
Risk factors for hyperuricemia and gout (may not be causal)
Nonmodifiable risk factors Modifiable risk factors
Age Obesity
Gender Hypertension
Ethnicity Hyperlipidemia
Genetic variants Cardiovascular disease
Diabetes mellitus
Chronic kidney disease
Dietary factors
Alcohol
Medications altering urate balance
Graphic 98500 Version 3.0
Causes of hyperuricemia due to increased purine biosynthesis and/or urate production
Inherited enzyme defects leading to purine overproduction (rare monogenic disorders)

Hypoxanthine-guanine phosphoribosyltransferase deficiency
Phosphoribosylpyrophosphate synthetase overactivity
Glucose-6-phosphatase deficiency (glycogen storage disease, type I)
Clinical disorders leading to purine and/or urate overproduction

Myeloproliferative disorders
Lymphoproliferative disorders
Malignancies
Hemolytic disorders
Psoriasis
Obesity
Tissue hypoxia
Down syndrome
Glycogen storage diseases (types III, V, VII)
Drug-, diet-, or toxin-induced purine and/or urate overproduction

Ethanol
Excessive dietary purine ingestion
Pancreatic extract
Fructose
Vitamin B12 deficiency
Ethylamino-1,3,4-thiadiazole
4-amino-5-imidazole carboxamide riboside
Cytotoxic drugs
Causes of hyperuricemia due to decreased uric acid clearance
Clinical disorders
Chronic renal insufficiency of any form
Lead nephropathy (saturnine gout)
Effective volume depletion (eg, fluid losses, heart failure)
Diabetic or starvation ketoacidosis
Lactic acidosis
Preeclampsia
Obesity
Hyperparathyroidism
Hypothyroidism
Sarcoidosis
Chronic beryllium disease
Rare monogenic disorders causing decreased uric acid clearance

Autosomal dominant tubulointerstitial kidney disease caused by UMOD pathogenic variants
Glomerulocystic kidney disease
Common variants in genes encoding transporters that regulate renal or gut uric acid clearance
(numerous; genes with largest reported effect are shown)
SLC2A9
ABCG2
SLC17A1
SLC22A11
PDZK1
SLC16A9
SLC22A12
Drug- or diet-induced
Diuretics (thiazides and loop diuretics)
Cyclosporine and tacrolimus
Low-dose salicylates
Ethambutol
Pyrazinamide
Ethanol
Levodopa
Methoxyflurane
Laxative abuse (alkalosis)
Salt restriction
Nicotinic acid
Dose dependence of thiazide-induced side effects
Metabolic complications induced by bendrofluazide in relation to daily dose (multiply by 10 to

get equivalent doses of hydrochlorothiazide). Increasing the dose led to progressive
hypokalemia and hyperuricemia and a greater likelihood of a mild elevation in the FBG, all
without a further reduction in the systemic blood pressure. Each treatment group contained
approximately 52 patients.
FBG: fasting blood glucose.
Data from: Carlsen JE, Kober L, Torp-Pedersen C, Johansen P. Relation between dose of bendrofluazide,
antihypertensive effect, and adverse biochemical effects. BMJ 1990; 300:975.

Lifestyle Modification and Other Strategies To Reduce The Risk of Gout Flares and Progression of Gout - UpToDate

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Lifestyle Modification and Other Strategies To Reduce The Risk of Gout Flares and Progression of Gout - UpToDate

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2/19/2021 Lifestyle modification and other strategies to reduce the risk of gout flares and progression of gout - UpToDate

Official reprint from UpToDate®

Lifestyle modification and other strategies to reduce the

RATIONALE FOR MANAGEMENT APPROACHES

● Patient education regarding [1-8]:

• The basis of symptoms related to gout

Thorough patient education is essential to successful adherence to both nonpharmacologic

create and convey an individualized treatment program incorporating patient preferences

● Reversible causes of hyperuricemia, which should be identified to facilitate lifestyle

● Management of comorbid diseases common in patients with gout, such as hypertension,

● The need for prophylactic therapy, usually with colchicine or a nonsteroidal

Role of risk-reduction measures — Gout is characterized by hyperuricemia, a factor that is

Urate-lowering pharmacotherapy for gout is, by definition, aimed directly at reversing

Evaluation of risk-reduction strategies — Two types of investigative approaches have been

populations or community-based samples or samples with specific comorbidities that are

It is important to keep in mind that, in some patients, treatment of an accompanying disorder

OBESITY AND DIET

We also instruct patients that frequent consumption of alcohol-containing beverages and

Major dietary classes and their contexts

Purines — Dietary purine restriction has proven to be an impractical means to manage

Proteins — Increasing amounts of meat and seafood in the diet are significantly

Carbohydrates — We concur with recommendations from multiple medical organizations

Specific dietary products providing potential gout benefit or increased risk — Additional

In response to reports of a beneficial effect on the expression of established gout by the

However, in a randomized trial in patients with existing gout, intake of 500 mg of

Whether more robust/clinically meaningful urate-lowering is achievable and safe at higher

HYPERTENSION AND DIURETICS

OTHER DRUGS AND DISEASES

RECOMMENDATIONS OF MAJOR GROUPS

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

● Basics topics (see "Patient education: Gout (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Lifestyle and comorbidity treatment-related characteristics associated with either increases

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Topic 105886 Version 16.0

Risk factors for hyperuricemia and gout (may not be causal)

Nonmodifiable risk factors Modifiable risk factors

Graphic 98500 Version 3.0

Causes of hyperuricemia due to increased purine biosynthesis and/or urate production

Inherited enzyme defects leading to purine overproduction (rare monogenic disorders)

Phosphoribosylpyrophosphate synthetase overactivity

Glucose-6-phosphatase deficiency (glycogen storage disease, type I)

Clinical disorders leading to purine and/or urate overproduction

Glycogen storage diseases (types III, V, VII)

Drug-, diet-, or toxin-induced purine and/or urate overproduction

Excessive dietary purine ingestion

Vitamin B12 deficiency

4-amino-5-imidazole carboxamide riboside

Graphic 80891 Version 5.0

Lead nephropathy (saturnine gout)

Effective volume depletion (eg, fluid losses, heart failure)

Diabetic or starvation ketoacidosis

Chronic beryllium disease

Rare monogenic disorders causing decreased uric acid clearance

Glomerulocystic kidney disease

Cyclosporine and tacrolimus

Laxative abuse (alkalosis)

Graphic 66799 Version 8.0

Dose dependence of thiazide-induced side effects

Metabolic complications induced by bendrofluazide in relation to daily dose (multiply by 10 to

FBG: fasting blood glucose.

Graphic 69912 Version 5.0