INTRODUCTION — Gout is an inflammatory arthritis due to monosodium urate crystal deposition disease. The long-term goals of therapy in patients who have already experienced signs and symptoms of the disease (established 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, primarily with urate-lowering therapy, and includes lifestyle modification as an adjunct when appropriate.
The prevention of gout flares and disease progression in people with gout by nonpharmacologic lifestyle modifications for urate lowering, avoidance of flare triggers, 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 — Gout is a disease caused by monosodium urate crystal deposition with clinical manifestations of gout flares, tophi, and/or 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 only to levels that still 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 as the primary approach, with adjunctive lifestyle modification and other strategies for risk reduction that can be helpful. 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 pharmacologic and nonpharmacologic 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. However, the 2020 American College of Rheumatology (ACR) Gout Treatment Guidelines recognized that in some practice settings, it may be less feasible to have patients return after a flare has resolved for initiation of urate-lowering therapy, and thus urate-lowering therapy initiation may need to be considered during a flare [10].
●Reversible causes of hyperuricemia, which should be identified to facilitate lifestyle modification and other changes that may be helpful in risk reduction [11-13]. (See 'Risk reduction' below.)
●Management of comorbid diseases common in patients with gout, such as hypertension, chronic renal functional impairment, and the components of the metabolic syndrome [14-16]; 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 advised in patients with at least two flares annually or with clinical or imaging findings that indicate chronic gouty arthritis (ie, radiographic erosion) or the presence of tophi [10]. Initiation of urate-lowering therapy may be considered for those with infrequent flares or for those with their first flare who also have renal impairment, urolithiasis, or marked hyperuricemia [10]. (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 genetic mutations and polymorphisms, other clinical disorders, 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 role in preventing incident gout in individuals at high risk for disease expression or 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 erosive consequences. It should be initiated as definitive therapy for patients with gout who meet indications for urate-lowering therapy, with a goal of achieving and maintaining subsaturating urate levels within approved and tolerated 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 [17,18].
Evaluation of risk-reduction strategies — Two types of study designs have assessed the benefits of lifestyle modifications and other nonpharmacologic strategies for reducing the risk of gout. Observational cohort investigations have evaluated 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. Randomized trials in which lifestyle modifications have been assessed primarily for effects on hyperuricemia have been conducted in general non-gout samples and few in patients with gout. An observational case-crossover study conducted among patients with gout has also provided insights into potential triggers for gout flares [19]. 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 [20,21]. 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 [22], diabetes, and hyperlipidemia, which are components of the metabolic syndrome or insulin resistance [14-16]; cardiovascular disease; chronic renal functional impairment; and certain dietary factors such as high alcohol or purine intake [11,23,24]. These associations have raised the question of whether lifestyle and pharmacologic 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. In addition, gout may contribute to adverse outcomes for some of these comorbidities. For example, observational data suggest that gout flares may be associated with a transient increase in cardiovascular events following a flare [25].
A number of studies support the benefit of weight loss [21,26-30] and of moderation in ethanol consumption [20,23]. Each of these actions can reduce the risk of incident gout and the expression of established gout [20,21,26]. (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, appropriate, and safe to do so, 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 use and dosing of urate-lowering therapy in the setting of low-dose aspirin or diuretics if necessary.
OBESITY AND DIET — We educate overweight patients with gout about 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 [22,31], while weight loss in overweight patients is likely beneficial in reducing serum urate and gout symptoms in patients with established gout [21,26,28-30]. (See 'Weight loss' below.)
The optimal diet composition for gout is likely to be one allowing adequate protein intake, especially from low-fat dairy and/or plant sources, with reduced intake from animal sources of purine such as red meat or shellfish; replacement of simple sugars with complex carbohydrates; and decreased saturated fat. (See 'Whole diet approaches' below.)
Patients also benefit from being informed 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, though specific impact on gout outcomes has not been studied to date; the aim is to optimize overall health and weight. (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 persons with obesity and who are overweight who have undergone weight loss [21]. 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 flares. 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 [22]. 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, profound weight loss in patients undergoing bariatric surgery for severe obesity, usually in combination with one or more commonly accompanying features of the metabolic syndrome [27,29,30], has been associated with improvement in several aspects of impaired metabolic regulation, including hyperuricemia, with clinical benefit in patients with established as well as incident gout. A 2019 meta-analysis noted that serum urate reductions occur as early as three months postoperatively and persisted at least through three years based upon the few studies that had long-term follow-up [26]. In addition, two studies reported reduction in gout flares [30,32]. 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 persons with obesity with a BMI ≥34 kg/m2 for male and ≥38 kg/m2 for female but non-gouty patients in Sweden [27]. 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 [29]. 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 persons with WHO class III obesity (BMI ≥40 kg/m2) 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) [30]. 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 — 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) [33].
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 [34]. Early recognition of the presence of urate crystals, a result of hyperuricemia as the end product of human purine metabolism, in gout 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 approximately 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. Further, severe reductions in purine in a diet must be substituted with other dietary components; often in Western diets, this may lead to compensatory higher consumption of carbohydrates and fats.
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 [13]. 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 [24]. 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 [35]. (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 a case-crossover study reported a higher risk of gout flares with higher intake of animal sources of purines but not vegetable sources [24] (see 'Purines' above). Thus, the source of protein may be important; as an example, in an Asian study sample (Chinese persons living in Singapore), soy and non-soy legume ingestion was associated with a reduced risk of incident gout [36]. Low-fat dairy has also been found to reduce incident gout [13], but reduced gout flares 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 established gout, prior published guidelines for management of patients with gout have recommended increased low-fat dairy and reduced meat and seafood intake in patients with gout [1,3,4,7,8]. However, the 2020 American College of Rheumatology (ACR) gout treatment guideline conditionally recommends limiting alcohol, purines, and high-fructose corn syrup intake, while vitamin C supplementation is conditionally recommended against, and no recommendations were made for dairy or cherry intake due to low/very low certainty of the evidence, precluding specific recommendations [10]. In light of the apparent benefit of some of these dietary modifications for overall health and in certain comorbidities common among gout patients (eg, hypertension, diabetes), 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 [13]. 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 [12].
An additional study in an Asian population (Chinese persons living in Singapore), 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 [36]. In two Chinese populations in Singapore, total protein intake 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 same observational study that evaluated meat and seafood intake in male health professionals also reported 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 [13]. 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 [12,37,38] and the identification of two milk fractions with antiinflammatory properties in an in vitro model of gouty inflammation [39], 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 [40]. 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 [40]). 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 [38]. Whether sustained higher-dose SMP treatment would prove clinically efficacious and practical in the longer term is uncertain.
Carbohydrates — Multiple medical organizations recommend limiting or avoiding sugar-sweetened beverages or those containing high-fructose corn syrup 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 [41] and 78,906 female nurses [42], 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) [43]. 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 [41]. In neither study was drinking diet soft drinks associated with an increased risk for incident gout.
Investigations in New Zealand [44,45] and elsewhere [46] 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 mediated the relationship of sugar-sweetened beverage intake and serum urate concentration in both a large cross-sectional population and in patients with established gout [44]; 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 [45]. Finally, physiologic mechanisms have been identified through which fructose intake can increase urate production [46] 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.
Factors that may have potential beneficial effects
●Cherries – Some evidence and anecdotal reports suggest a beneficial role of cherry ingestion as a nonpharmacologic modifier of the course of established gout [19,47]. Based upon the available data, we discuss dietary supplementation with cherries with our patients with established gout if interested and otherwise appropriate (eg, no diabetes; 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 [19]. 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 self-controlled crossover studies of this type and the timing of exposure measurements in relation to gout flares 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 [48].
In the study, 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.
However, in a randomized controlled trial of 50 people with gout and hyperuricemia, tart cherry juice concentrate had no significant effect on reduction in serum urate area under the curve, urine urate excretion, change in urinary anthocyanin, or frequency of gout flares over the 28-day study period [49]. Allopurinol use did not modify the effect of cherry on serum urate or urine urate excretion. Thus, if cherries or cherry extract exert their effects on flares over a longer time period, the effect does not appear to be through modification of serum urate.
●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 [50]. 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 [51]. 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 [52].
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 [53].
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) was 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) [54]. The reduction in risk was slightly less with decaffeinated coffee and was not shared with frequent tea intake.
However, in patients with prevalent gout, serum urate levels with intake of >4 cups of coffee daily were 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) [55]. 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) [56]. 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 [57]; evidence of consistent benefit with either of these agents is needed before advising their use for this purpose.
Factors that may have potentially detrimental effects
●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 [58].
Other factors as reviewed elsewhere in the topic review include purines, alcohol, and high-fructose corn syrup or sugar-sweetened beverages. (See 'Purines' above and 'Carbohydrates' above and 'Alcohol' below.)
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 [11,20,23]:
●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 [11]. 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 [20]. 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.
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 [59]. (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 [28,60,61].
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 [60]. The DASH diet emphasizes fruits, vegetables, and low-fat dairy foods but reduces consumption of saturated and total fat and cholesterol [59]. 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 [59]. 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 [61]. 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 [61].
●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 [60]. Adjusted relative risks for these findings were independent of potential confounders such as age, BMI, hypertension, diuretic use, and alcohol intake. Nonetheless, effects on recurrent flares or tophi have not yet been demonstrated.
The Mediterranean diet focuses on intake of plant proteins, whole grains, fish, use of monounsaturated fat (eg, olive oil for cooking and salad dressing), with moderate wine consumption, and low intake of red meat and refined grains [62]. This diet has also been associated with lower likelihood of hyperuricemia and lower mean serum urate in secondary analyses of two trials [63,64].
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.
HYPERTENSION AND DIURETICS — Primary hypertension (formerly called "essential" hypertension) and diuretic use are both independently associated with hyperuricemia [65] and gout [22]. 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) [22]. 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 [66]. 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 [67].
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 [68]. 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 [69,70] and the risk of incident gout [71], while calcium-channel blockers have been found to decrease both urate levels [72,73] and incident gout risk [71].
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 not recommended given the risk of adverse cardiovascular events in individuals who are on low-dose aspirin for an appropriate cardiovascular risk reduction indication.
Aspirin has paradoxical effects on renal uric acid excretion [74,75]. Treatment with doses of aspirin up to 2 to 3 g daily causes urate retention [76-78], 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 [78], although urate-lowering therapy with allopurinol or probenecid mitigates the risk of recurrent flare. In addition, 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. Further, adequate dosing of urate-lowering therapy should overcome any potential urate-raising effects of low-dose aspirin. 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 [79]. In gout patients with hypertriglyceridemia, fenofibrate may provide adjunctive urate-lowering. However, the 2020 American College of Rheumatology (ACR) gout treatment guideline conditionally recommends against adding or switching to fenofibrate due to the risks, including side effects, being felt to outweigh any potential benefits [10]. (See "Low-density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors", section on 'Fibrates'.)
●Calcineurin inhibitors – Calcineurin inhibitors are commonly used in transplant patients. Cyclosporine A in particular increases serum urate and increases the risk of gout more so than tacrolimus. When appropriate, patients with gout who have a transplanted organ should be considered for management with mycophenolate mofetil as the preferred antirejection medication (see appropriate topic reviews).
●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 [80,81]. 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 other 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. (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 [82,83]. Impediments to successful management have been identified, highlighting the importance of improved patient and clinician education and communication [17,84]. 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 [85]. 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, including the American College of Rheumatology (ACR) [10]. 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. (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 clinically evident gout. Maintenance of remission usually requires sustained pharmacologic treatment and/or lifestyle modifications 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, when feasible, 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 urate-lowering pharmacotherapy as well as lifestyle and risk-reduction actions when appropriate as adjuncts. (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 intake 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 or Mediterranean diet. These diets emphasize an increased proportion of protein from plant sources, reduced red meat, 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 or Mediterranean diet. We stress avoidance of weight gain and potential triggers for gout flare (eg, alcohol, 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 '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 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 recommended in patients requiring cardiovascular prophylaxis because urate-lowering pharmacotherapy with allopurinol or probenecid attenuates 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 UpToDate editorial staff acknowledges Michael A Becker, MD, who contributed to an earlier version of this topic review.
