Nonpharmacologic strategies for the prevention and treatment of gout

INTRODUCTION — Gout, also known as monosodium urate crystal deposition disease, is a type of crystalline arthropathy that can cause recurrent episodes of inflammatory arthritis. In patients with gout, an excess of urate can cause monosodium urate crystals to precipitate in joints or other tissues where they elicit an inflammatory response. Thus, therapy for patients with chronic gout aims to reduce serum urate concentration to a level where crystals are less likely to form. While pharmacotherapy is required to achieve this for most patients, nonpharmacologic treatment strategies can also play an important adjunctive role in lowering serum urate concentration for people with gout.

This topic will review the role of nonpharmacologic strategies for the prevention and treatment of gout, including treatment of comorbid conditions, consideration of medications that affect urate balance, optimization of dietary composition, and patient education. Other aspects of the diagnosis and management of gout are reviewed separately:

●(See "Pathophysiology of gout".)

●(See "Clinical manifestations and diagnosis of gout".)

●(See "Treatment of gout flares".)

●(See "Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout".)

●(See "Asymptomatic hyperuricemia".)

GENERAL PRINCIPLES OF NONPHARMACOLOGIC STRATEGIES FOR GOUT

Overview — Symptoms of gout are driven by monosodium urate crystal deposition in tissues and subsequent inflammation. Maintaining the serum urate at a level below the threshold where crystals form can reduce the risk of gout flares and even help dissolve preexisting tophi.

Lowering serum urate can be achieved using both pharmacologic urate-lowering therapy as well as nonpharmacologic strategies. Most patients with gout require urate-lowering pharmacotherapy as the primary approach to treatment. This is because most of the factors that contribute to elevated serum urate levels, including various causes of increased urate production (table 1) and decreased urate excretion (table 2), are not modifiable. As an example, the main driver of serum urate level is renal urate underexcretion related to genetic variants [1]. However, there is also a role for nonpharmacologic strategies, which focus on reducing serum urate by addressing modifiable risk factors (table 3). Nonpharmacologic strategies include the following:

●Treatment of comorbid conditions – Some comorbid conditions are associated with an increased risk of gout (eg, obesity). Treating them may reduce the risk of developing gout and of subsequent gout flares. (See 'Treating comorbid conditions' below.)

●Addressing medications that affect urate balance – Certain medications affect serum urate, including aspirin and certain types of diuretics, and can sometimes be modified to reduce the risk of gout flares. (See 'Addressing medications that affect urate balance' below.)

●Modifying diet – Many modifiable aspects of diet can affect serum urate, such as intake of purines and alcohol. (See 'Modifying diet' below.)

●Exercise – Participating in an exercise program that is appropriate for a patient's age and physical status can help improve overall health and achieve or maintain an optimal weight.

Certain nonpharmacologic strategies that address modifiable risk factors, such as dietary changes, are sometimes called "lifestyle modification." However, some strategies may be outside of a patient's control and may require a multidisciplinary team of providers (eg, subspecialist management of comorbidities, nutrition and social work for education about and access to healthy food choices).

Nonpharmacologic treatment strategies are only one component of a comprehensive gout management program. Pharmacologic therapy is important for treatment of acute flares as well as prevention of future flares by lowering serum urate. Sometimes prophylactic therapy is required to reduce the risk of gout flares while starting urate-lowering therapy. These issues are discussed separately. (See "Treatment of gout flares" and "Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout".)

Whom to treat — Patients who have gout or who have a high risk of developing gout may both benefit from initiating nonpharmacologic therapeutic strategies to reduce serum urate:

●Patients with gout – Nonpharmacologic treatment strategies are rarely sufficient to control serum urate in patients with gout. However, they may be the primary focus for patients who do not have a current indication to start urate-lowering pharmacotherapy or patients who cannot tolerate pharmacologic therapy. Additionally, they are an important adjunct for patients who are on urate-lowering therapy.

●Patients at risk of developing gout – Nonpharmacologic treatment strategies may reduce the risk of developing gout for patients who have asymptomatic hyperuricemia or who have other significant risk factors for the development of gout (eg, strong family history). More information on the evaluation and management of asymptomatic hyperuricemia can be found elsewhere. (See "Asymptomatic hyperuricemia".)

Optimal timing of interventions — The optimal timing to start nonpharmacologic therapies may vary based on the type of treatment strategy and the complexity of the clinical situation. Certain nonpharmacologic treatment strategies, such as optimizing use of medications that contribute to hyperuricemia, are relatively quick to change and can easily be addressed in the immediate period following the diagnosis of gout. Other strategies, such as weight loss for comorbid obesity or dietary changes, require a significant investment of time and resources for both the provider and the patient. It may not be feasible to focus on these components when a patient has been newly diagnosed with gout. Instead, it may be preferable to wait until an "intercritical period" between gout flares.

Role of patient education — Patient education is essential for patients with gout to explain the rationale for and importance of different therapeutic approaches, including nonpharmacologic ones [2,3]. We discuss the following elements with patients [4-11]:

●Signs and symptoms of gout flares

●Factors that increase the risk of gout flares and/or disease progression

●The rationale, anticipated benefits, and potential harms of each component of the recommended therapeutic plan

●Common misconceptions about gout (eg, that gout is a "rich man's disease")

It is important to discuss nonpharmacologic interventions in a sensitive and nonjudgmental way, as was informally recommended by the American College of Rheumatology (ACR) gout management guideline panel [12]. Patients with gout may feel guilty or judged by others, which can lead to suboptimal care by making patients hesitant to report symptoms and/or participate in care [13,14]. By providing patient education and a nonjudgmental atmosphere, providers can help patients better understand and engage with all aspects of their gout treatment plan.

Resources for patients are listed below. (See 'Information for patients' below.)

TREATING COMORBID CONDITIONS — Certain comorbid conditions increase the risk of developing gout and may contribute to the risk of subsequent gout flares and disease severity in patients with gout. Treating such conditions may mitigate these risks.

Overweight and obesity — In patients with overweight or obesity, we provide counseling about how weight reduction may decrease their risk of developing gout and reduce urate levels, thereby decreasing risk of flares and tophi. Specifically, we discuss the goal of gradual weight loss (at a rate of three to five pounds per month) towards ideal body weight (calculator 1). The specific weight reduction strategies depend on the patient and their other comorbidities but typically include dietary changes and increased exercise. An overview of the management of obesity is provided separately. (See 'Modifying diet' below and "Obesity in adults: Dietary therapy" and "Obesity in adults: Role of physical activity and exercise" and "Obesity in adults: Overview of management".)

Increased adiposity and weight gain are risk factors for incident gout [15,16]. A large, long-term, prospective cohort study of males without gout at baseline showed that the risk of incident gout was higher among males with a body mass index (BMI) of 25 kg/m² or greater, and the magnitude of the association became larger with increasing BMI [15]. Males who had gained 13.6 kg or more had a twofold increased risk of incident gout compared with men who maintained their weight.

Data from observational studies have shown that weight reduction towards ideal body weight is associated with a reduced risk of incident gout and possibly an improvement in the symptoms of established gout [15,17-22]. In the large cohort study of males without gout cited above, males who had a weight loss of greater than 4.5 kg had a reduced risk of incident gout compared with those who maintained their weight [15]. Weight loss for patients with gout with overweight or obesity may also reduce the risk of flares. A systematic review of longitudinal studies found low-quality evidence that weight loss reduced the serum urate level and risk of gout attacks among patients with gout with overweight or obesity [17]. Limitations to the analysis included heterogeneity among the study interventions and the observational nature of most studies.

Multiple observational studies have shown benefits of bariatric surgery in reducing the incidence and severity of gout [19,21,22]. A meta-analysis noted that serum urate reductions occurred as early as three months postoperatively and persisted at least through three years based upon the few studies that had long-term follow-up [18]. In addition, two studies reported a reduction in gout flares [22,23]. However, the risk of gout flare may be elevated in the immediate postoperative period [17]. Indications for and outcomes of bariatric surgery are discussed in detail elsewhere. (See "Bariatric surgery for management of obesity: Indications and preoperative preparation" and "Outcomes of bariatric surgery".)

Hypertension — Patients with gout who have comorbid hypertension should be treated for high blood pressure as otherwise indicated. Management of hypertension is described in detail elsewhere. (See "Overview of hypertension in adults", section on 'Treatment'.)

Primary hypertension is associated with hyperuricemia [24] and gout [15]. A large, long-term, prospective cohort study of males without gout at baseline found that the risk of incident gout was significantly increased among males with hypertension, compared with those without hypertension, after adjusting for diuretic use (relative risk [RR] 2.31, 95% CI 1.96-2.72) [15].

There is no clear evidence linking the successful treatment of hypertension with a reduced risk of incident gout or improvement in gout symptoms.

Agents used for the treatment of hypertension can impact serum urate levels and are addressed below. (See 'Diuretics and other antihypertensives' below.)

Diabetes mellitus — Limited data suggest that management of comorbid diabetes mellitus may improve outcomes for patients with gout [25-27]. In a meta-analysis of five randomized controlled trials evaluating the use of sodium-glucose cotransporter (SGLT2) inhibitors for the treatment of diabetes or heart failure, patients receiving SGLT2 inhibitors had a reduced risk of gout flare (as measured by a report of gout flare or starting medications for gout) compared with those taking placebo (hazard ratio [HR] 0.55, 95% CI 0.45-0.67) [26]. In addition, cohort studies of patients with gout and type 2 diabetes have found lower risks of gout flare, myocardial infarction, and/or all-cause mortality after initiation of a SGLT2 inhibitor compared with initiation of a glucagon-like peptide 1 (GLP-1) receptor agonist or dipeptidyl peptidase 4 (DPP-4) inhibitor [25,27]. The management of diabetes mellitus is described in detail elsewhere. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus".)

Other comorbidities — Multiple other comorbid conditions have been associated with gout, including metabolic syndrome or insulin resistance [28-30]; cardiovascular disease; chronic kidney disease; and psoriasis. However, it is unclear to what extent the treatment of these comorbid conditions can impact the risk of incident gout or gout flares.

ADDRESSING MEDICATIONS THAT AFFECT URATE BALANCE — Many medications can cause elevations or reductions in serum urate. Depending on the clinical context and indications for therapy, medications can be adjusted or substituted with alternatives to reduce the risk of gout flares.

Diuretics and other antihypertensives — Certain antihypertensive medications may impact the serum urate level and the risk of gout. As examples:

●Thiazide (eg, hydrochlorothiazide) and loop (eg, furosemide) diuretics are independent risk factors for hyperuricemia, incident gout, and gout flares [15,24,31,32], while potassium-sparing diuretics (eg, spironolactone) are not [33].

●Beta blockers have been reported to increase serum urate and the risk of incident gout [32,34,35].

●Calcium channel blockers have been found to decrease both urate levels and incident gout risk [32,36,37].

●The angiotensin II receptor blocker (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 angiotensin-converting enzyme (ACE) inhibitors [38].

When starting antihypertensive therapy for a patient who has gout or who is at high risk of developing gout, it may be reasonable to use medications known to decrease the serum urate level (eg, losartan) instead of medications that increase it (eg, hydrochlorothiazide). For patients with gout who are already taking an antihypertensive medication that is associated with hyperuricemia, various approaches may be reasonable depending on the clinical context. These include potentially decreasing or stopping the antihypertensive medication that increases serum urate or substituting or adding an alternative antihypertensive therapy that reduces serum urate. As an example, the increase in serum urate caused by low doses of hydrochlorothiazide is relatively small (figure 1) and may be counteracted by adding concurrent therapy with losartan. Optimal management of diuretics in patients with hyperuricemia or gout is discussed in detail elsewhere. (See "Diuretic-induced hyperuricemia and gout".)

Aspirin — Aspirin has paradoxical effects on renal urate excretion and therefore serum urate levels [39,40]. Higher doses (above 3 g/day) can decrease serum urate, whereas low to moderate doses (up to 3 g/day) can increase serum urate and the risk of flare for patients with gout [41-43]. However, this increase in serum urate can be counteracted with urate-lowering pharmacotherapy if needed and should not preclude the use of aspirin for important indications like cardiovascular prophylaxis.

When patients take low-dose aspirin (75 to 325 mg/day) for cardiovascular prophylaxis, we continue aspirin and adjust urate-lowering therapy as needed. We also counsel patients to take aspirin daily as prescribed since intermittent use can cause fluctuations in serum urate and subsequent gout flares. Our approach is largely consistent with the 2020 American College of Rheumatology (ACR) gout treatment guidelines [44]. A detailed discussion of the use of aspirin for cardiovascular prophylaxis is provided elsewhere. (See "Aspirin in the primary prevention of cardiovascular disease and cancer" and "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)

Fenofibrate — Fenofibrate, a fibric acid derivative used for the treatment of hypertriglyceridemia, has modest uricosuric activity, and limited data suggest that it can decrease serum urate in patients with gout [45]. For patients who are being treated for hypertriglyceridemia, the presence of gout or elevated serum urate should not prompt the initiation of or switch to fenofibrate unless fenofibrate is otherwise indicated. This is because potential adverse effects of fenofibrate (eg, serious drug-induced liver injury) outweigh the potential benefit of a small reduction in serum urate. This is in keeping with the 2020 ACR gout treatment guidelines [44]. The use of fenofibrate in treating hypertriglyceridemia, including a discussion of adverse effects, is detailed elsewhere. (See "Hypertriglyceridemia in adults: Management", section on 'Fibrates'.)

Other medications

●Calcineurin inhibitors – Calcineurin inhibitors (CNIs) increase serum urate and the risk of gout [46]; the extent to which the effect may be more pronounced with cyclosporine compared with tacrolimus is unclear [47,48]. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Metabolic abnormalities'.)

For patients who have gout and are taking a CNI, management of the CNI depends upon the comorbid condition being treated. Factors to consider in choosing a CNI are covered in separate topic reviews. As an example, the management of hyperuricemia and gout in patients with a kidney transplant is discussed elsewhere. (See "Kidney transplantation in adults: Hyperuricemia and gout in kidney transplant recipients".)

●Pancreatic enzyme replacement – Patients with cystic fibrosis who are taking purine-rich pancreatic enzyme replacement therapy can develop an array of related complications including hyperuricemia, hyperuricosuria, crystalluria, and even chronic gouty arthritis [49,50]. Such patients may benefit from reducing the dose of pancreatic enzyme replacement therapy. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency", section on 'Pancreatic enzyme replacement therapy'.)

MODIFYING DIET

Overview of dietary modification — Certain foods can increase serum urate or the risk of gout flares. Such foods generally should be minimized (or even avoided when possible) for patients who have or are at high risk for developing gout. In addition, adopting certain dietary practices, such as healthy whole-diet approaches, may be beneficial in reducing the risk of gout or gout flares.

In most patients with hyperuricemia or gout, we counsel them about potential modification of the following components:

●Reducing consumption of foods that potentially trigger gout flares including:

•High-purine foods (eg, red meat, shellfish) (see 'Reduce purine intake' below)

•Alcoholic beverages of all types

•High-fructose corn syrup and sugar-sweetened beverages

●Considering whole-diet approaches such as the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets

●Obtaining adequate dietary protein from plant-based and/or low-fat dairy sources

Our approach is largely consistent with that outlined by the 2020 American College of Rheumatology (ACR) gout treatment guideline [44].

If patients have a normal body mass index (BMI; 18.5 to 24.9 mg/kg²), we discuss the importance of maintaining a healthy weight. If patients have overweight or obesity, they may benefit from additional modifications directed at weight reduction. (See 'Overweight and obesity' above and "Obesity in adults: Dietary therapy".)

There are several limitations to consider when advising patients about the potential impact of dietary changes on the risk of gout or gout flares. Diet plays a limited role overall in reducing serum urate levels and therefore should be just one component of a comprehensive plan to manage gout. This may be a contrast to common public perceptions of gout, which often portray gout as the result of poor dietary choices. In addition, evidence to support most dietary changes is limited, since most studies are observational and randomized controlled trials are rare. It is inherently challenging to study the impact of a specific dietary component, as the effect may be modified by the source, preparation, and overall context of the food (eg, the role of raw plant-based protein as part of a vegetarian diet).

Reduce purine intake — For patients who have established gout or are at risk of developing gout, we suggest reducing dietary purine intake, especially purines derived from animal sources (eg, red meat). Reduction of dietary purine intake is supported by the ACR recommendations for gout management [44]. We additionally counsel patients about ways to ensure they obtain adequate daily protein when they reduce purine intake, since some common high-purine foods are also rich in proteins (eg, red meat, seafood). In patients with gout have a serum urate at or below their goal level on stable urate-lowering therapy, purine rich foods may not trigger flares or promote disease progression.

Purines are aromatic, nitrogen-containing, heterocyclic molecules and include adenine and guanine. Purine metabolism produces urate. Certain foods have higher concentrations of purines, including red meat, organ meats, certain kinds of seafood (eg, sardines, shellfish), and certain vegetables (eg, green peas, spinach, asparagus), though the purine content in vegetables is much lower than in animal sources.

There is an increased risk of gout among patients with higher intake of purine-rich foods, including proteins that contain high levels of purines. Protein intake itself is not associated with an increased risk of gout [51]. The effect on serum urate and gout risk may vary depending on the source of purines or protein:

●In a prospective cohort study of 633 patients with gout that compared the level of purine intake in the two days preceding a gout flare, the risk of gout flare was increased almost fivefold for patients who scored in the highest quintile of purine intake compared with those in the lowest quintile (odds ratio [OR] 4.76) [52]. The risk of gout flare was higher when purines were derived from animal versus vegetable sources.

●Several studies have found a relationship between higher levels of meat and/or seafood consumption and increased levels of serum urate and/or incident gout [15,53,54]. As an example, in a prospective observational study of 47,150 male health professionals without gout, patients in the highest quintile of meat consumption had an increased risk of incident gout compared with those in the lowest quintile (adjusted hazard ratio [HR] 1.41, 95% CI 1.07-1.86) [15]. Likewise, those in the highest quintile of fish consumption had an increased risk of gout compared with those in the lowest quintile (HR 1.51, 95% CI 1.17-1.95).

●A prospective study of health professionals did not identify an increased risk of incident gout among patients with high intake of purine-rich vegetables [51].

In people with hyperuricemia, purine-restricted diets can modestly reduce serum urate levels. Prior to the availability of urate-lowering pharmacotherapy, severely purine-restricted diets were used to treat gout and could reduce daily urinary urate excretion by 200 to 400 mg/day. However, mean serum urate concentrations decrease only approximately 1 mg/dL (59 micromol/L) [55]. Diets that severely restrict purines may be unpalatable and impractical to implement and are therefore usually reserved for patients who have limited therapeutic options (eg, patients who do not tolerate pharmacotherapy).

Reducing purine intake may have a limited role in patients who have achieved goal serum urate through other means. A small trial randomly assigned patients with gout to a control intervention or an educational intervention that focused on reducing purine intake [56]. All patients were on urate-lowering therapy and had a serum urate within the goal range. The intervention resulted in better knowledge and dietary modification but did not change serum urate levels.

Limit alcohol intake — For patients with established gout or who are at risk for developing gout, we suggest limiting alcohol intake. If patients with gout have a serum urate at or below their goal level on stable urate-lowering therapy, small amounts of alcohol may be unlikely to trigger flares or promote disease progression for most patients. If patients report unhealthy or risky use of alcohol beverages, we counsel the patient about the risks of alcohol intake to their health and refer them for professional assistance. (See "Risky drinking and alcohol use disorder: Epidemiology, clinical features, adverse consequences, screening, and assessment".)

Alcohol intake can increase the risk of developing gout. As an example, a large, prospective cohort study of health professional males without gout found an increased risk of incident gout among those consuming beer or hard liquor compared with those not consuming alcohol (relative risk [RR] per 12 ounce serving of beer per day 1.49, 95% CI 1.32-1.70, and RR per drink or shot per day 1.15, 95% CI 1.04-1.28) [57]. The risk of incident gout was not different for those consuming moderate amounts of wine (two or more four-ounce glasses); this may be because of confounding since wine consumption is often associated with healthy lifestyle behaviors.

For patients with gout, drinking alcohol increases the risk of flare compared with abstaining from alcohol [58,59]. In a case-crossover study of people with gout, all forms of alcohol (beer, liquor, and wine) were associated with an increased risk of flare within 24 hours when compared with no alcohol consumption [59]. The relationship between alcohol intake and gout flare was dose-dependent: when compared with people who did not drink within 24 hours, those reporting more than one to two drinks had an OR of gout flare of 1.36 (95% CI 1.00-1.88), while those reporting more than two to four drinks had an OR of 1.51 (1.09-2.09). People who reported alcohol use together with high purine consumption and/or diuretic use also had a higher risk of flares. By contrast, the risk was attenuated for people who drank alcohol while taking allopurinol and, to a lesser degree, colchicine.

Tophaceous gout is also associated with alcohol intake. A cohort study of patients with gout found that the risk of having tophi detected by ultrasound was greater among patients with excessive alcohol intake (>70 g/week), longer history of alcohol exposure (≥10 years), consumption of hard liquor, and consumption of beer (OR 1.79, 95% CI 1.16 to 2.78; 1.96, 95% CI 1.22 to 3.15; 1.81, 95% CI 1.11 to 2.95; and 1.66, 95% CI 1.03 to 2.68, respectively) [60].

Other health effects of alcohol intake are discussed separately. (See "Healthy diet in adults", section on 'Alcohol' and "Overview of the risks and benefits of alcohol consumption".)

Reduce intake of high-fructose corn syrup and sugar-sweetened beverages — Intake of high-fructose corn syrup and sugar-sweetened beverages can increase serum urate and the risk of incident gout. We counsel patients about reducing the intake of such foods. This is consistent with recommendations from multiple medical organizations, including the ACR and the European Alliance of Associations for Rheumatology (EULAR, formerly known as the European League Against Rheumatism) [6-11,44]. Other negative health effects of high-fructose corn syrup and sugar-sweetened beverages are discussed elsewhere. (See "Healthy diet in adults", section on 'Added sugars and sugar-sweetened beverages'.)

Intake of simple sugars like fructose can increase serum urate. A study that gave patients 1 g of fructose per kg of body weight found that the serum urate level increased by 1 to 2 mg/dL after two hours [61]. This effect may be due to increased urate production [62] and reduced renal urate excretion. There is also a genetic variant in the renal urate/glucose/fructose transporter (SLC2A9) that favors a hyperuricemic response to sucrose intake among individuals with gout [63]. Elevated BMI may mediate the relationship between intake of sugar-sweetened beverages and serum urate; urate excretion was reduced after a fructose load in patients who had a high BMI compared with those who had a normal BMI [64].

Several studies have examined the relationship between high intake of simple sugars (fructose, sucrose) and incident gout [62-67]. As an example, two large prospective cohort studies included 46,393 male health professionals [65] and 78,906 female nurses [66] without gout and had 12 and 22 years of follow-up, respectively. A systematic review of these studies found that the risk of incident gout was higher for those in the highest versus lowest quintiles of fructose intake (risk ratio 1.62, 95% CI 1.28-2.03) [67]. In the male health professionals study, the main dietary sources of fructose were orange juice, sugar-sweetened beverages, apples, raisins, and oranges [65]. Drinking diet soft drinks was not associated with an increased risk for incident gout in either study.

Use whole-diet approaches — We discuss whole-diet approaches with patients with hyperuricemia or gout and the potential for such changes to improve serum urate. Examples of whole-diet approaches include the DASH and Mediterranean diets. Both of these diets emphasize intake of fruits and vegetables; the DASH diet additionally focuses on low-fat dairy, while the Mediterranean diet prioritizes whole grains, beans, nuts, and seeds. These diets are discussed in detail elsewhere. (See "Healthy diet in adults", section on 'DASH diet' and "Healthy diet in adults", section on 'Mediterranean diet'.)

There is some limited evidence to suggest that whole diet approaches may reduce serum urate and the risk of incident gout. The prevalence of gout and related conditions, such as metabolic syndrome, differ worldwide and may be partially related to diet [68]. Supportive evidence for specific diets includes the following:

●DASH diet – Evidence from the DASH trials have suggested that the diet can lower serum urate levels and the risk of incident gout; however, it has not been studied extensively in patients with gout. The original trial compared the DASH diet with a control diet in prehypertensive or stage 1 hypertensive persons without gout. A small ancillary analysis noted that the DASH diet led to lower serum urate levels when compared with the control diet; the effect was more pronounced in eight patients with high baseline urate (≥7 mg/dL) (mean reduction of 1.3 mg/dL, 95% CI -2.5 to -0.08) [69]. Similarly, a large longitudinal cohort study found that people who had higher DASH dietary pattern scores had a lower risk of incident gout, whereas people with higher Western dietary pattern scores had a higher risk of incident gout (adjusted RR for extreme fifths 0.68, 95% CI 0.57-0.80; and 1.42, 95% CI 1.16-1.74], respectively) [68].

●Mediterranean diet – The Mediterranean diet has been associated with lower likelihood of hyperuricemia and lower mean serum urate in secondary analyses of two trials [70,71]. As an example, a controlled trial randomly assigned patients with moderate obesity and elevated serum urate (≥416 micromol/L) to one of three diets: a low-calorie Mediterranean diet, a low-calorie and low-fat diet, or an unrestricted calorie, low-carbohydrate diet [70]. It found that serum urate was reduced at 6 and 24 months for all patients, without significant differences between the groups (mean change at six months of -119, -113, and -143 micromol/L, respectively).

Whole-diet approaches may also be beneficial for patients with gout who have common comorbid conditions, such as hypertension and metabolic syndrome. (See "Diet in the treatment and prevention of hypertension" and "Metabolic syndrome (insulin resistance syndrome or syndrome X)", section on 'Diet'.)

Additional dietary modifications with limited evidence — Limited data suggest that additional dietary modifications may reduce serum urate levels, the risk of incident gout, and/or the risk of gout flares.

●Foods that may increase risk of gout and/or worsen gout symptoms – Fatty meals have been implicated in precipitating flares [72], which may be related to long-chain fatty acids priming the "first signal" and "second signal" required for NLRP3 inflammasome activation, which leads to the inflammatory manifestations of gout flares [73].

●Foods that may decrease risk of incident gout and/or gout flares

•Low-fat dairy products – Intake of low-fat dairy products may be beneficial for patients with gout or who are at risk of developing gout. The 2020 ACR recommendations for gout management do not include opinions on low-fat dairy products because of limited evidence [12], although previously published guidelines had recommended increasing intake of low-fat dairy foods [4,6,7,10,11]. Dietary intake of low-fat dairy products can be recommended to patients with gout for overall health benefits, which are discussed elsewhere. (See "Healthy diet in adults", section on 'Reduced-fat dairy'.)

Consumption of low-fat dairy products has been associated with a decreased risk of developing gout and lower serum urate levels. In a large observational study of male health professionals, the risk of incident gout was nearly 50 percent lower when comparing people in the highest and lowest quintiles of dairy product consumption (RR 0.56, 95% CI 0.42-0.74) [51]. The adjusted risk ratio of incident gout per additional daily serving of dairy products was 0.82, 95% CI 0.75-0.90; this benefit was primarily restricted to intake of low-fat dairy products. In addition, several cross-sectional studies in people without gout have shown that dairy product intake is associated with lower serum urate levels [53,74,75]. One small randomized trial in healthy males found that milk-based supplements acutely lowered serum urate levels to a greater extent than soy-based supplements; each supplement was very high in protein (80 g/day) [75].

For patients with established gout, there is no strong evidence to suggest that intake of low-fat dairy products reduces gout flares. In a trial in which patients with recurrent gout flares (ie, ≥2 flares in the preceding four months) were randomly assigned to one of three dietary supplements (control supplement with lactose, standard skim milk powder [SMP, equivalent increase of two servings of low-fat dairy per day], or enriched SMP containing "anti-inflammatory" milk fractions) for three months, there was no significant difference in the change in gout flares between standard SMP supplementation and the lactose control [76]. Enriched SMP supplementation led to a greater reduction in gout flares as well as improvements in fractional excretion of urate and self-reported pain when compared with the lactose control.

•Cherries – Limited evidence suggests that dietary supplementation with cherries may reduce the risk of gout flares [77-79]. We discuss cherry intake with patients with gout if they are interested and if it is otherwise appropriate (eg, no diabetes). The ACR recommendations for the management of gout do not include opinions on cherry supplementation because of limited evidence [12].

Supportive evidence for cherries in gout is limited [77-79]. A case-crossover study of patients with gout found that patients who reported eating cherries or cherry extract over a two-day period were less likely to have a gout flare when compared with patients who did not eat cherries (adjusted OR 0.65, 95% CI 0.50-0.85; and 0.55, 95% CI 0.30-0.98, respectively) [78]. This benefit appeared to occur with up to three servings of cherries in a two-day period; additional servings were not associated with further benefit. However, in a four-week trial of 50 patients with gout and hyperuricemia (serum urate >0.36 micromol/L), participants randomly assigned to tart cherry juice concentrate did not have significantly lower serum urate, higher urinary urate excretion, or lower gout 28-day flare risk compared with participants receiving placebo [79].

•Vitamin C supplementation – We do not encourage vitamin C supplementation for patients with gout who otherwise have adequate dietary intake of vitamin C. The ACR gout guidelines do not make a specific recommendation regarding vitamin C supplementation due to clinically insignificant effects on serum urate among people with gout [12]. The daily requirements, main sources, and toxicities of vitamin C are discussed in detail elsewhere but notably include risk of oxalate kidney stones in males. (See "Overview of water-soluble vitamins", section on 'Vitamin C (ascorbic acid)'.)

Vitamin C may lower serum urate among people without gout and reduce the risk of incident gout. In a double-blinded trial of participants without gout who were randomly assigned to receive vitamin C supplementation (500 mg/day) or placebo, serum urate levels at two months were reduced with vitamin C supplementation but not with placebo (mean change -0.5 mg/dL [95% CI -0.6 to -0.3] versus 0.09 mg/dL [95% CI -0.05 to 0.2]) [80]. A meta-analysis of randomized controlled trials also found that vitamin C supplementation reduced serum urate in participants without gout who had high serum urate [80,81]. The dose of vitamin C may matter; in a prospective cohort study of males without gout, the RR of incident gout was lower with higher daily doses of vitamin C (≥500 mg) compared with lower total daily vitamin C intake (≤250 mg) (RR per 500 mg increase in total daily vitamin C supplementation of 0.83, 95% CI 0.77-0.90) [82].

However, for patients with gout, evidence to support use of vitamin C is very limited. In a randomized trial in people with gout and hyperuricemia, participants taking daily vitamin C supplementation (500 mg) for eight weeks did not have a significant reduction in serum urate when compared with those taking allopurinol therapy [82].

•Coffee – We do not counsel patients who have or are at risk of developing gout to increase coffee intake due to insufficient evidence and potential adverse effects of high caffeine consumption. The various risks and benefits of caffeinated beverages are detailed elsewhere. (See "Benefits and risks of caffeine and caffeinated beverages".)

For patients at risk of developing gout, high coffee intake (eg, four to five cups daily) has been associated with a lower relative risk of incident gout compared with no coffee intake (RR 0.60, 95% CI 0.41-0.87) [83]. The reduction in risk was slightly less with decaffeinated coffee and was not observed with frequent tea intake. However, in patients with gout, high coffee intake (>4 cups daily) was only associated with a relatively small reduction in serum urate when compared with no coffee intake (mean difference of -0.42 mg/dL, 95% CI -1.01 to 0.17) [84].

•Fish and omega-3 fatty acids – For patients who have gout, increasing intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) may be beneficial. Limited evidence suggests that n-3 PUFA may reduce the risk of gout flares. In a case-crossover study of patients with gout, the risk of a gout flare was lower for patients who reported eating fish with high levels of n-3 PUFA during the preceding two days compared with patients who did not eat such fish [85]. By contrast, taking n-3 PUFA supplements did not reduce the risk of gout flare, potentially because supplements typically have lower amounts of n-3 PUFA than fish. A small pilot feasibility trial in which adults with gout were randomly assigned to take omega-3 fatty acids or placebo (olive oil capsules) while initiating urate-lowering therapy did not demonstrate a difference in flares over 28 weeks; this could be because the study was not powered to detect a difference in flares [86]. Dietary intake of omega-3 fatty acids is discussed in detail elsewhere. (See "Fish oil: Physiologic effects and administration" and "Healthy diet in adults", section on 'Healthy fats'.)

•Other proposed supplements – Limited data suggest that dietary fiber and folate may also reduce the risk of incident gout [87]. However, evidence is insufficient to recommend dietary supplementation. Information on other indications for dietary fiber and folate are described elsewhere. (See "Healthy diet in adults", section on 'Fiber' and "Vitamin intake and disease prevention", section on 'Folic acid'.)

EXERCISE — Patients with established gout may benefit from participating in an exercise program to help improve overall health and maintain or achieve an optimal weight. There is little evidence to support exercise as a way to specifically reduce the risk of developing gout or gout flares. However, exercise can improve overall health and can be used as part of a holistic treatment approach to many conditions that commonly co-occur with gout (eg, hypertension, obesity). (See "The benefits and risks of aerobic exercise", section on 'Benefits of exercise' and "Obesity in adults: Role of physical activity and exercise" and "Exercise in the treatment and prevention of hypertension".)

When discussing an exercise regimen with patients, providers should consider the patient's age and other comorbid conditions. Further guidance for prescribing physical activity and exercise is provided elsewhere. (See "Exercise prescription and guidance for adults" and "Exercise for adults: Terminology, patient assessment, and medical clearance".)

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 5^th to 6^th 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 10^th to 12^th 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

●General principles – Nonpharmacologic treatment strategies for gout prevention and treatment focus on modifiable risk factors (table 3) and include treating comorbid conditions, addressing medications that affect urate balance, modifying diet, and increasing exercise. Such strategies may be of benefit for patients with gout or who are at risk of developing gout. However, urate-lowering pharmacotherapy is needed for most patients with gout. (See 'General principles of nonpharmacologic strategies for gout' above.)

●Treatment of comorbid conditions – Certain comorbid conditions (eg, obesity, chronic kidney disease) increase the risk of developing gout and may contribute to the risk of subsequent gout flares and disease severity in patients with gout. Treating such conditions may mitigate these risks. (See 'Treating comorbid conditions' above.)

In patients with overweight or obesity, we provide counseling about how weight reduction may decrease their risk of developing gout and reduce urate levels, thereby decreasing risk of flares and tophi. Specifically, we discuss the goal of gradual weight loss (at a rate of three to five pounds per month) towards ideal body weight (calculator 1). (See 'Overweight and obesity' above.)

●Addressing medications that affect urate balance – Many medications can affect serum urate. Depending on the clinical context and indications for therapy, medications can be adjusted or substituted with alternatives to reduce the risk of gout flares. (See 'Addressing medications that affect urate balance' above.)

•Diuretics and other antihypertensives – When starting antihypertensive therapy for a patient who has gout or who is at high risk of developing gout, it may be reasonable to use medications known to decrease the serum urate level (eg, losartan) instead of medications that increase it (eg, hydrochlorothiazide). For patients with gout who are already taking an antihypertensive medication that is associated with hyperuricemia, various approaches may be reasonable depending on the clinical context. (See 'Diuretics and other antihypertensives' above and "Diuretic-induced hyperuricemia and gout".)

•Aspirin – Therapeutic doses of aspirin can increase serum urate and the risk of flare for patients with gout. When patients require low-dose aspirin for secondary cardiovascular prevention, we continue aspirin and adjust urate-lowering therapy as needed. We also counsel patients to take aspirin daily as prescribed to avoid fluctuations in serum urate that may trigger gout flares. (See 'Aspirin' above.)

●Modifying diet – Foods that can increase serum urate or the risk of gout flares generally should be minimized (or even avoided when possible) for patients who have or are at high risk for developing gout. In addition, adopting certain dietary practices, such as healthy whole-diet approaches, may be beneficial in reducing the risk of gout or gout flares. (See 'Overview of dietary modification' above.)

•Reduce purine intake – For patients who have established gout or are at risk of developing gout, we suggest reducing dietary purine intake (Grade 2C), especially purines derived from animal sources. We additionally counsel patients about ways to ensure they obtain adequate daily protein when they reduce purine intake, since some common high-purine foods are also rich in proteins (eg, red meat, seafood). In patients with gout have a serum urate at or below their goal level on stable urate-lowering therapy, purine-rich foods may not trigger flares or promote disease progression. (See 'Reduce purine intake' above.)

•Limit alcohol intake – For patients with established gout or who are at risk for developing gout, we suggest limiting intake of all forms of alcoholic beverages (Grade 2C). In patients with gout have a serum urate at or below their goal level on stable urate-lowering therapy, small amounts of alcohol may be unlikely to trigger flares or promote disease progression for most patients. (See 'Limit alcohol intake' above.)

•Reduce intake of high-fructose corn syrup and sugar-sweetened beverages – Intake of high-fructose corn syrup and sugar-sweetened beverages can increase serum urate and the risk of incident gout and other diseases. We counsel patients about reducing the intake of such foods. (See 'Reduce intake of high-fructose corn syrup and sugar-sweetened beverages' above and "Healthy diet in adults", section on 'Added sugars and sugar-sweetened beverages'.)

•Use whole-diet approaches – We discuss whole-diet approaches with patients with hyperuricemia or gout and the potential for such changes to improve serum urate (eg, Dietary Approaches to Stop Hypertension [DASH] and Mediterranean diets). (See 'Use whole-diet approaches' above.)

●Exercise – Patients with established gout may benefit from participating in an exercise program to help improve overall health and maintain or achieve an optimal weight. (See 'Exercise' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael A Becker, MD, who contributed to an earlier version of this topic review.