Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Expanding the role of Australian community dietitians in gout management.

AIM: Gout is a common form of inflammatory arthritis with suboptimal management. Management guidelines for gout highlight the importance of both pharmacological and non-pharmacological treatments. Dietitians can potentially assist in improving gout's associated dietary and lifestyle factors, and thereby play a role in improving its management. The aim of this study was to investigate perspectives of Australian community dietitians on whether their role in gout management could be expanded to improve management and treatment of gout. METHOD: A snowballing recruitment strategy was used. Dietitians known to the research team were invited to participate and then they suggested further dietitians. Semi-structured interviews (one-on-one) were conducted with 16 dietitians. The focus was on their experiences of contributing to the management of gout, including any barriers and facilitators experienced. Interviews were transcribed verbatim and independently analyzed by 2 reviewers to identify themes. RESULTS: The main reported role of dietitians in gout management was providing patient education. An identified facilitator was dietitians' understanding of gout and its dietary management. Barriers included the emphasis placed on medications for treatment by clinicians and patients, consultation costs, limitations in the evidence for the efficacy of dietary changes and lack of specific training in gout for dietitians. Dietitians predominantly managed the other metabolic conditions commonly associated with gout. CONCLUSION: Currently, the role dietitians play in gout management is limited. However, dietitians have the potential to take on larger roles in gout education and can also indirectly contribute by way of management of commonly associated comorbidities in gout patients.

A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout.

The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: -0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by -0.48 mg/dL (95% CI: -0.98, 0.01) compared to DDG by -0.05 mg/dL (95% CI: -0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: -34.0, -8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.

A Randomized Internet-Based Pilot Feasibility and Planning Study of Cherry Extract and Diet Modification in Gout.

OBJECTIVE: The aim of this study was to conduct a 9-month pilot Internet randomized controlled trial (RCT) of cherry extract and diet modification in gout to assess the feasibility of an Internet study and obtain effect estimates. METHODS: After providing online informed consent in response to Internet advertisements and social media or clinic flyers, 84 people with physician-confirmed gout were randomized to either cherry extract 3,600 mg/d (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via Internet and phone calls. The primary objective was the feasibility of an Internet study, and secondary objectives were to obtain effect estimates for gout flares, functional ability assessed with the Health Assessment Questionnaire (HAQ), and adverse events (AEs) for future trials. RESULTS: Of the 84 people randomized, overall completion rates were more than 80% for most study procedures up to 6 months and similar for the 2 active comparators. Improvements were seen in gout flares and HAQ scores in cherry extract and diet modification groups at 9 months compared with baseline: gout flares per month, 0.22 versus 0.36 (p = 0.049) and 0.28 versus 0.31 (p = 0.76); proportion with any gout flare, 56% versus 98% (p < 0.0001) and 65% versus 98% (p = 0.0002); and mean ± standard deviation HAQ score, 0.28 ± 0.54 versus 0.55 ± 0.68 (p = 0.001) and 0.23 ± 0.40 versus 0.48 ± 0.61 (p = 0.06), respectively. Any AEs and gastrointestinal symptoms/AEs at 9 months in cherry extract and diet modification groups were 3% versus 0% and 28% versus 27%, respectively. CONCLUSIONS: An Internet gout RCT is feasible for nonpharmacological gout treatments. A hypothesis-testing, large Internet RCT of cherry extract versus placebo is needed.

Determination of total purine and purine base content of 80 food products to aid nutritional therapy for gout and hyperuricemia.

The aim of this work is to facilitate the nutritional therapy of gout and hyperuricemia. In Japan, patients with gout or hyperuricemia are recommended to consume less than 400 mg of dietary purines per day. When receiving nutritional therapy for gout or hyperuricemia, purine-rich foods (>200 mg/100 g) should be eaten in even lower quantities. The purine content of foods reported in this study are as follows: noodles, 0.6-12.1 mg/100 g; bread, 4.4 mg/100 g; peas or seeds, 19.6-67.1 mg/100 g; dairy, 0.0-1.4 mg/100 g; Japanese vegetables, 0.9-47.1 mg/100 g; seasonings, 0.7-847.1 mg/100 g; meat or fish, 19.0-385.4 mg/100 g; fish milt, 375.4-559.8 mg/100 g; and supplements, 81.9-516.0 mg/100 g. Foods containing very large amounts of purine (>300 mg/100 g) included anchovy, cutlassfish (hairtail), cod milt, globefish milt, dried Chinese soup stock, dried yeast, a Euglena supplement, and a Lactobacillus supplement. When eating these high-purine food or supplements, the quantity taken at one meal should be limited, especially milt because they typically consumed amount of 20-30 g is equivalent to 75-168 mg total purines. This is 20%-40% of the recommended daily amount (400 mg/day) for patients with gout or hyperuricemia. Thus, these patients should restrict the amount of purine-rich foods they consume. Good dietary habits with a good balance of nutrients are recommended.

Effect of tart cherry juice on risk of gout attacks: protocol for a randomised controlled trial.

INTRODUCTION: Gout is a painful form of inflammatory arthritis associated with several comorbidities, particularly cardiovascular disease. Cherries, which are rich in anti-inflammatory and antioxidative bioactive compounds, are proposed to be efficacious in preventing and treating gout, but recommendations to patients are conflicting. Cherry consumption has been demonstrated to lower serum urate levels and inflammation in several small studies. One observational case cross-over study reported that cherry consumption was associated with reduced risk of recurrent gout attacks. This preliminary evidence requires substantiation. The proposed randomised clinical trial aims to test the effect of consumption of tart cherry juice on risk of gout attacks. METHODS AND ANALYSIS: This 12-month, parallel, double-blind, randomised, placebo-controlled trial will recruit 120 individuals (aged 18-80 years) with a clinical diagnosis of gout who have self-reported a gout flare in the previous year. Participants will be randomly assigned to an intervention group, which will receive Montmorency tart cherry juice daily for a 12-month period, or a corresponding placebo group, which will receive a cherry-flavoured placebo drink. The primary study outcome is change in frequency of self-reported gout attacks. Secondary outcome measures include attack intensity, serum urate concentration, fractional excretion of uric acid, biomarkers of inflammation, blood lipids and other markers of cardiovascular risk. Other secondary outcome measures will be changes in physical activity and functional status. Statistical analysis will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the National Research Ethics Service, Yorkshire and The Humber-Leeds West Research Ethics Committee (ref: 18/SW/0262). Results of the trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03621215.

Dietary Interventions for Gout and Effect on Cardiovascular Risk Factors: A Systematic Review.

Gout is one of the most prevalent inflammatory rheumatic disease. It is preceded by hyperuricemia and associated with an increased risk for cardiovascular disease, both related to unhealthy diets. The objective of this systematic review is to better define the most appropriate diet addressing both disease activity and traditional cardiovascular risk factors in hyperuricemic patients. We included clinical trials with patients diagnosed with hyperuricemia or gout, investigating the effect of dietary interventions on serum uric acid (SUA) levels, gout flares and-if available-cardiovascular risk factors. Eighteen articles were included, which were too heterogeneous to perform a meta-analysis. Overall, the risk of bias of the studies was moderate to high. We distinguished four groups of dietary interventions: Calorie restriction and fasting, purine-low diets, Mediterranean-style diets, and supplements. Overall, fasting resulted in an increase of SUA, whilst small (SUA change +0.3 to -2.9 mg/dL) but significant effects were found after low-calorie, purine-low, and Mediterranean-style diets. Studies investigating the effect on cardiovascular risk factors were limited and inconclusive. Since Mediterranean-style diets/DASH (Dietary Approach to Stop Hypertension) have shown to be effective for the reduction of cardiovascular risk factors in other at-risk populations, we recommend further investigation of such diets for the treatment of gout.

How Would You Manage This Patient With Gout?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Gout is the most common form of inflammatory arthritis. In 2012, the American College of Rheumatology (ACR) issued a guideline, which was followed in 2017 by one from the American College of Physicians (ACP). The guidelines agree on treating acute gout with a corticosteroid, nonsteroidal anti-inflammatory drug, or colchicine and on not initiating long-term urate-lowering therapy (ULT) for most patients after a first gout attack and in those whose attacks are infrequent (<2 per year). However, they differ on treatment of both recurrent gout and problematic gout. The ACR advocates a "treat-to-target" approach, and the ACP did not find enough evidence to support this approach and offered an alternative strategy that bases intensity of ULT on the goal of avoiding recurrent gout attacks ("treat-to-avoid-symptoms") with no monitoring of urate levels. They also disagree on the role of a gout-specific diet. Here, a general internist and a rheumatologist discuss these guidelines; they debate how they would manage an acute attack of gout, if and when to initiate ULT, and the goals for ULT. Lastly, they offer specific advice for a patient who is uncertain about whether to begin this therapy.

Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts.

OBJECTIVE: To systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels. DESIGN: Meta-analysis of cross sectional data from the United States. DATA SOURCES: Five cohort studies. REVIEW METHODS: 16 760 individuals of European ancestry (8414 men and 8346 women) from the US were included in analyses. Eligible individuals were aged over 18, without kidney disease or gout, and not taking urate lowering or diuretic drugs. All participants had serum urate measurements, dietary survey data, information on potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome wide genotypes. The main outcome measures were average serum urate levels and variance in serum urate levels. ß values (95% confidence intervals) and Bonferroni corrected P values from multivariable linear regression analyses, along with regression partial R2 values, were used to quantitate associations. RESULTS: Seven foods were associated with raised serum urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb)) and eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits) in the male, female, or full cohorts. Three diet scores, constructed on the basis of healthy diet guidelines, were inversely associated with serum urate levels and a fourth, data driven diet pattern positively associated with raised serum urate levels, but each explained ≤0.3% of variance in serum urate. In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation. CONCLUSION: In contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population.

Effects of breeds, tissues and genders on purine contents in pork and the relationships between purine content and other meat quality traits.

The purine contents of animal foods are becoming widely concerned because excess intake of purine increases the risk of hyperuricemia and gout. In this study, we investigated the impacts of breed, tissue and sex on pork purine content and its correlations with multiple meat quality traits. Among six pig breeds, the average value of total purine contents (TP) in longissimus lumborum muscle was lowest in Chinese Laiwu pigs (114.2 mg/100 g) while highest in Chinese Bamaxiang mini pigs (139.3 mg/100 g). Considerable variations in TP were observed within most breeds, as well as among twelve pork organs with the range from 7 to 245 mg/100 g. However, no significant differences in TP were found between barrows and gilts. Intriguingly, lower purine content in meat was significantly associated with higher ultimate pH, better meat color and more abundant intramuscular fat content and marbling. The results thus suggest that the selection of low-purine pig species is available, which may simultaneously improve other meat quality traits.

Low-Purine Diet Is More Effective Than Normal-Purine Diet in Reducing the Risk of Gouty Attacks After Sleeve Gastrectomy in Patients Suffering of Gout Before Surgery: a Retrospective Study.

BACKGROUND: Obese patients with preoperative gout often suffer of gouty attacks after bariatric surgery (BS), probably due to the lack of an adequate postoperative diet. OBJECTIVES: The objectives of the study are to assess whether sleeve gastrectomy (SG) is effective in reducing the frequency of gouty attacks and also whether a postoperative low-purine diet (LPD) may further reduce these attacks as compared to a normal-purine diet (NPD) in a series of patients suffering of gout before SG. METHODS: In this retrospective study, we measured and compared total body weight (TBW), body mass index (BMI), uric acid levels (UAL), anti-gout medication (allopurinol) requirements, and frequency in gouty attacks in 40 patients that underwent SG and who received either a LPD (n = 24) or NPD (n = 16). Compliance in following the prescribed diet was assessed in both groups study. RESULTS: Before surgery, LPD and NPD patients had hyperuricemia and were receiving allopurinol. One year after SG, LPD and NPD groups showed a significant decrease in serum UAL (p < 0.001 and p = 0.00175, respectively). However, serum UAL decreased more significantly with the LPD compared to the NPD (p < 0.001). Furthermore, while NPD group showed a significant decrease in allopurinol requirements (p = 0.00130) and on the frequency in gouty attacks (p < 0.001), LPD group were off allopurinol therapy and had no gouty attacks 12 months after SG. Both groups showed high compliance in following the prescribed diets. CONCLUSION: LPD is more effective in reducing the frequency of gouty attacks after SG compared with NPD in patients suffering of gout before surgery.

Adherence to gout management recommendations of Chinese patients.

Though efficacious and affordable treatments for gout are widely available, gout is still not well controlled in many countries of the world including China.To investigate patient adherence to gout management recommendations and potential barriers in Chinese male gout patients, a survey was carried out by telephone interview in male patients registered in the gout clinic at Peking Union Medical College Hospital. Adherence to dietary and medication recommendations was measured by a food frequency questionnaire and proportion of cumulative time adherent to chemical urate-lowering therapy (ULT), respectively. Dietary adherence was defined as consumption of alcohol, seafood and animal organs less than once per month, and reduced red meat after dietary counseling. Medication adherence was defined as ULT ≥80% of time in the past 12 months for patients with indications. Logistic regression models were used to identify patient characteristics associated with management adherence. Reasons for nonadherence were also sought by open-end questions.Dietary and medication adherence were 44.2% and 21.9%, respectively. Older age (odds ratio [OR] 7.90, 95% confidence interval [CI] 2.49-25.04 for age ≥60), higher serum uric acid (sUA) levels (OR 3.53, 95% CI 1.42-8.75 for the highest quartile), and tophi (OR 2.31, 95% CI 1.12-4.77) were associated with dietary adherence independently, while tophi (OR 14.05, 95% CI 2.67-74.08) and chronic kidney disease (OR 16.66, 95% CI 2.63-105.37) were associated with medication adherence independently. Reasons that patients reported for nonadherence to medication included remission after treatment (35.3%), concerns for potential side effects (22.7%), insufficient patient education (8.7%), and adverse events (8.2%).Patient adherence to gout management recommendations is poor in China. Older age, increased disease burden, and specific comorbidities were associated with management adherence.

The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study.

Objective To prospectively examine the relation between the Dietary Approaches to Stop Hypertension (DASH) and Western diets and risk of gout (ie, the clinical endpoint of hyperuricemia) in men.Design Prospective cohort study.Setting The Health Professionals Follow-up Study.Participants 44 444 men with no history of gout at baseline. Using validated food frequency questionnaires, each participant was assigned a DASH dietary pattern score (based on high intake of fruits, vegetables, nuts and legumes, low fat dairy products, and whole grains, and low intake of sodium, sweetened beverages, and red and processed meats) and a Western dietary pattern score (based on high intake of red and processed meats, French fries, refined grains, sweets, and desserts).Main outcome measure Risk of incident gout meeting the preliminary American College of Rheumatology survey criteria for gout, adjusting for potential confounders, including age, body mass index, hypertension, diuretic use, and alcohol intake.Results During 26 years of follow-up, 1731 confirmed cases of incident gout were documented. A higher DASH dietary pattern score was associated with a lower risk for gout (adjusted relative risk for extreme fifths 0.68, 95% confidence interval 0.57 to 0.80, P value for trend <0.001). In contrast, a higher Western dietary pattern score was associated with an increased risk for gout (1.42, 1.16 to 1.74, P=0.005).Conclusion The DASH diet is associated with a lower risk of gout, suggesting that its effect of lowering uric acid levels in individuals with hyperuricemia translates to a lower risk of gout. Conversely, the Western diet is associated with a higher risk of gout. The DASH diet may provide an attractive preventive dietary approach for men at risk of gout.

Sex differences in gout characteristics: tailoring care for women and men.

BACKGROUND: To characterize the differences between women and men with gout. METHODS: We analyzed a US national cohort of gout patients cared for by rheumatologists. RESULTS: Compared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05). CONCLUSIONS: The profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians.

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. Methods: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. Target Audience and Patient Population: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. Recommendation 1: ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). Recommendation 2: ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence). Recommendation 3: ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence). Recommendation 4: ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. METHODS: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. RECOMMENDATION 1: ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 3: ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 4: ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).