Effect of long-term allopurinol administration on serial GFR in normotensive and hypertensive hyperuricemic subjects. Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup Hyperuricemia after renal transplantation. Placebo-controlled double-blind dose-response study of the non-purine-selective xanthine oxidase inhibitor febuxostat (TMX-67) in patients with hyperuricemia (including gout patients) in japan: late phase 2 clinical study. Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study Hyperuricemia and Incident Heart Failure Serum Uric Acid Level and Risk for Peripheral Arterial Disease: Analysis of Data From the Multiple Risk Factor Intervention Trial Hyperuricemia induces endothelial dysfunction. An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 2 exploratory clinical study. Effects of dietary fructose on plasma lipids in healthy subjects. Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Fructose-rich beverages and risk of gout in women. A pilot study on the impact of a low fructose diet and allopurinol on clinic blood pressure among overweight and prehypertensive subjects: a randomized placebo controlled trial. A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. Hyperuricemia as a risk factor on cardiovascular events in Taiwan: The Chin-Shan Community Cardiovascular Cohort Study. The relationships among serum uric acid, plasma insulin, and serum lipoprotein levels in subjects with spinal cord injury. Febuxostat in Gout: Serum Urate Response in Uric Acid Overproducers and Underexcretors Epidemiology of gout and hyperuricemia. A long-term population study. Long-term cardiovascular mortality among middle-aged men with gout.
Acute experiments of uric acid infusion in animals and the clinical observation that in patients with gout there is an increased incidence of renal lesions , suggested that high levels of plasma uric acid may be detrimental to the kidney and cause a decrease in renal function . It is not known , however , whether hyperuricemia , not clinical ly associated with gout , causes kidney damage , nor is it known whether therapeutic reduction of serum uric acid levels slows the rate of the deterioration of renal function in such patients . To establish whether maintenance of normal plasma uric acid concentration in patients with hyperuricemia associated with various diseases has any effect on serial determination of GFR or slows the rate of kidney deterioration , this study was planned Background Prospect i ve studies in humans examining the effects of fructose consumption on biological markers associated with the development of metabolic syndrome are lacking . Therefore we investigated the relative effects of 10 wks of fructose or glucose consumption on plasma uric acid and RBP-4 concentrations , as well as liver enzyme ( AST , ALT , and GGT ) activities in men and women . Methods As part of a parallel arm study , older ( age 40–72 ) , overweight and obese male and female subjects ( BMI 25–35 kg/m2 ) consumed glucose- or fructose-sweetened beverages providing 25 % of energy requirements for 10 wks . Fasting and 24-h blood collection s were performed at baseline and following 10 wks of intervention and plasma concentrations of uric acid , RBP-4 and liver enzyme activities were measured . Results Consumption of fructose , but not glucose , led to significant increases of 24-h uric acid profiles ( P < 0.0001 ) and RBP-4 concentrations ( P = 0.012 ) , as well as plasma GGT activity ( P = 0.04 ) . Fasting plasma uric acid concentrations increased in both groups ; however , the response was significantly greater in subjects consuming fructose ( P = 0.002 for effect of sugar ) . Within the fructose group male subjects exhibited larger increases of RBP-4 levels than women ( P = 0.024 ) . Conclusions These findings suggest that consumption of fructose at 25 % of energy requirements for 10 wks , compared with isocaloric consumption of glucose , may contribute to the development of components of the metabolic syndrome by increasing circulating uric acid , GGT activity , suggesting alteration of hepatic function , and the production of RBP-4 Objective : The dietary intake of fructose-rich sugar-sweetened beverages ( SSB ) may have a significant role in raising serum uric acid ( SUA ) levels as well as the risk of contracting gout and cardiovascular risk factors . Our objective was to investigate the impact of SSB intake on SUA , body mass index ( BMI ) and systolic blood pressure ( SBP ) among adolescents in Taiwan . Methods : We evaluated data from 2727 representative adolescents who were multistage sample d from 36 Junior High schools in Taiwan . We cross-sectionally collected demographic , physical , dietary and anthropometric variables , and prospect ively measured clinical outcomes . Data were analyzed using multiple regression and logistic models adjusted for covariates . Results : We found that 87.7 % of adolescents were SSB drinkers , with 25.1 % drinking > 500 ml per day of such beverages . Increased SSB intake was associated with increased waist and hip circumferences , body fat , BMI , SBP and SUA . As compared with non-drinkers , SSB drinkers had a 3.2–4.9 elevated risk of obesity . The prevalence of hyperuricemia in heavy SSB  users ( 40.2–49.4 % ) was appreciably greater than that for non-users ( 24.2 % ) . Adolescents who consumed > 500 ml per day of heavy high-fructose corn syrup ( HFCS ) containing beverages had a 0.42 mg dl−1 higher SUA level and a 2.0–2.1 increased risk of developing hyperuricemia than non-drinkers . The consumption of HFCS-rich beverages was also found to interact with obesity in determining higher levels of SUA ( 2.2–2.4 mg dl−1 increases ) . Conclusion : High SSB consumption has a notable effect on increased levels of BMI and SUA . The intake of HFCS-rich beverages and BMI were likely to interactively strengthen SUA levels among obese adolescents Hyperuricemia is common in  cyclosporine-treated renal allograft recipients . An increased incidence of gout in patients receiving both diuretics and cyclosporine  has been reported , but the effect of hyperuricemia on renal allograft function has not been studied . In a prospect i ve , r and omized trial of cyclosporine and prednisone versus azathioprine , prednisone , and antilymphocyte globulin for immunosuppression in renal allograft recipients , 105 of 131 cyclosporine and prednisone-treated patients ( 80 percent ) experienced hyperuricemia ( serum uric acid level above 8 mg/dl ) and 13 of 131 ( 10 percent ) were severely hyperuricemic ( serum uric acid level above 14 mg/dl ) . In contrast , hyperuricemia developed in 63 of 115 patients ( 55 percent ) treated with azathioprine , prednisone , and antilymphocyte globulin ( p less than 0.002 ) . Despite the frequent occurrence of hyperuricemia , gout was rare . Clinical gout developed in six patients in the cyclosporine and prednisone group and in 0 patients in the azathioprine , prednisone , and antilymphocyte globulin group between 1 and 43 months ( median 22.5 months ) after transplantation . Neither severe hyperuricemia nor diuretic therapy were associated with a significantly increased incidence of gout . The mean serum creatinine concentration of severely hyperuricemic patients ( all on cyclosporine and prednisone ) was similar to that of normouricemic cyclosporine and prednisone patients ( 1.8 mg/dl versus 1.6 mg/dl , p greater than 0.2 ) , and the severely hyperuricemic patients had a 4-year graft survival rate of 90 percent . Asymptomatic hyperuricemia after renal transplantation does not adversely affect allograft function , requires no specific therapy , and is not a contraindication to use of diuretics BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES A multicenter study with r and omized , placebo-controlled , double-blind , parallel , intergroup comparison was carried out to evaluate the dose-response relationship , efficacy , and safety of febuxostat in 202 patients with hyperuricemia ( including patients with gout ) in Japan . METHODS The subjects were treated with febuxostat at fixed maintenance doses ( 20 - 80 mg/d ) or a placebo for 16 weeks . The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated . RESULTS The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8 % in the 80-mg/d dose group , 83.3 % in the 60-mg/d group , 82.9 % in the 40-mg/d group , 46.5 % in the 20-mg/d group , and 2.6 % in the placebo group ( P < 0.001 , Mantel-Haenszel test ) . A statistically significant dose-response relationship was found . The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d . No deaths , events posing a clinical problem , or serious adverse reactions attributable to febuxostat were noted . Similar results were obtained regardless of gout history . CONCLUSIONS Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80 % or more of patients with hyperuricemia ( including gout ) at doses of 40 mg/d or higher Background : Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common hepatic diseases in the general adult population . Dyslipidemia , hyperuricemia , and insulin resistance are common risk factors and accompanying features of NAFLD . Curcumin is a dietary natural product with beneficial metabolic effects relevant to the treatment of NAFLD . Aim : To assess the effects of curcumin on metabolic profile in subjects with NAFLD . Methods : Patients diagnosed with NAFLD ( grade s 1–3 ; according to liver sonography ) were r and omly assigned to curcumin ( 1000 mg/d in 2 divided doses ) ( n = 50 ) or control ( n = 52 ) group for a period of 8 weeks . All patients received dietary and lifestyle advises before the start of trial . Anthropometric measurements , lipid profile , glucose , insulin , glycated hemoglobin , and uric acid concentrations were measured at baseline and after 8 weeks of follow-up . Results : Eighty-seven subjects ( n = 44 and 43 in the curcumin and control group , respectively ) completed the trial . Supplementation with curcumin was associated with a reduction in serum levels of total cholesterol ( P < 0.001 ) , low-density lipoprotein cholesterol ( P < 0.001 ) , triglycerides ( P < 0.001 ) , non – high-density lipoprotein cholesterol ( P < 0.001 ) , and uric acid ( P < 0.001 ) , whereas serum levels of high-density lipoprotein cholesterol and glucose control parameters remained unaltered . Curcumin was safe and well tolerated during this study . Conclusion : Results of the present trial suggest that curcumin supplementation reduces serum lipids and uric acid concentrations in patients with NAFLD Objective To prospect ively 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 Prospect i ve cohort study . Setting The Health Professionals Follow-up Study . Participants 44 444 men with no history of gout at baseline . Using vali date d food frequency question naires , 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 Background —Hyperuricemia , a known correlate of oxidative stress , is a marker for adverse prognosis among individuals with heart failure . However , the relationship between hyperuricemia and the risk for incidence of heart failure in a community-based population has not been studied . Methods and Results —We prospect ively analyzed the relationship between serum uric acid concentration at baseline and subsequent heart failure among the participants of the Framingham Offspring cohort ( n=4912 ; mean baseline age , 36 years ; 52 % women ) . By using Cox regressions , we calculated the risk of heart failure with increasing serum uric acid after adjusting for sex , age , smoking , body mass index , renal dysfunction , diuretics , systolic blood pressure , valvular heart disease , diabetes , alcohol , and use of antihypertensive medications . The incidence rates of heart failure were ≈6-fold higher among those at the highest quartile of serum uric acid ( > 6.3 mg/dL ) compared with those at the lowest quartile ( < 3.4 mg/dL ) . The adjusted hazard ratio for the highest quartile of serum uric acid compared with the lowest was 2.1 ( 1.04 to 4.22 ) . The relationship between hyperuricemia and heart failure was found in participants without metabolic syndrome and other subgroups as well . Conclusions —Hyperuricemia is a novel , independent risk factor for heart failure in a group of young general community dwellers . This has implication s for development of preventive strategies for heart failure Although several studies report an association between hyperuricemia and coronary artery disease , little is known about the effect of hyperuricemia and gout on the risk of peripheral arterial disease ( PAD ) . Data on 283 incident clinical cases of PAD during a r and omized controlled trial of multiple cardiovascular risk factor intervention  are evaluated . The  serum uric acid levels  among these individuals are compared with those of individuals who did not develop PAD during the study period . Multivariate logistic regression analyses measure the risk of developing PAD associated with higher levels of serum uric acid after adjusting for the effect of traditional vascular risk factors . Age and smoking are independently associated with development of PAD , with odds ratios of 1.08 ( 95 % confidence interval [ CI ] , 1.06 - 1.09 ) and 3.83 ( 95 % CI , 2.49 - 5.91 ) per year , respectively . Hyperuricemia ( serum uric acid level , > 7.0 mg/dL ) is an independent risk factor , with an odds ratio of 1.23 , but the confidence interval of the estimate is wide ( 95 % CI , 0.98 - 1.54 ) . In this multivariate model , a history of gout was associated with an odds ratio of 1.33 ( 95 % CI , 1.07 - 1.66 ) . Serum uric acid level is independently associated with a higher ( but statistically nonsignificant ) risk of PAD . A history of gouty arthritis is an independent and statistically significant predictor of incidence of PAD even after adjustment for the effect of underlying hyperuricemia BACKGROUND Hyperuricemia has been linked to cardiovascular and renal diseases , possibly through the generation of reactive oxygen species ( ROS ) and subsequent endothelial dysfunction . The enzymatic effect of xanthine oxidase is the production of ROS and uric acid . Studies have shown that inhibiting xanthine oxidase with allopurinol can reverse endothelial dysfunction . Furthermore , rat studies have shown that hyperuricemia-induced hypertension and vascular disease is at least partially reversed by the supplementation of the nitric oxide synthase ( NOS ) substrate , L-arginine . Therefore , we hypothesized that uric acid induces endothelial dysfunction by inhibiting nitric oxide production . METHODS Hyperuricemia was induced in male Sprague-Dawley rats with an uricase inhibitor , oxonic acid , by gavage ; control rats received vehicle . Allopurinol was placed in drinking water to block hyperuricemia . Rats were r and omly divided into four groups : ( 1 ) control , ( 2 ) allopurinol only , ( 3 ) oxonic acid only , and ( 4 ) oxonic acid + allopurinol .  Rats were sacrificed at 1 and 7 days , and their serum analyzed for serum uric acid and nitrites/nitrates concentrations . The effect of uric acid on nitric oxide production was also determined in bovine aortic endothelial cells . RESULTS Oxonic acid induced mild hyperuricemia at both 1 and 7 days ( P < 0.05 ) . Allopurinol reversed the hyperuricemia at 7 days ( P < .001 ) . Serum nitrites and nitrates ( NO(X ) ) were reduced in hyperuricemic rats at both 1 and 7 days ( P < .001 ) . Allopurinol slightly reversed the decrease in NO(X ) at 1 day and completely at 7 days ( P < .001 ) . There was a direct linear correlation between serum uric acid and NO(X ) ( R(2)= 0.56 ) and a trend toward higher systolic blood pressure in hyperuricemic rats ( P= NS ) . Uric acid was also found to inhibit both basal and vascular endothelial growth factor (VEGF)-induced nitric oxide production in bovine aortic endothelial cells . CONCLUSION Hyperuricemic rats have a decrease in serum nitric oxide which is reversed by lowering uric acid levels . Soluble uric acid also impairs nitric oxide generation in cultured endothelial cells . Thus , hyperuricemia induces endothelial dysfunction ; this may provide insight into a pathogenic mechanism by which uric acid may induce hypertension and vascular disease BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol . METHODS The starting dose of febuxostat and allopurinol was 10 and 100 mg/d , respectively , and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks . RESULTS : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96 % ± 13.33 % and -52.47 % ± 9.79 % for the febuxostat 40- and 60-mg/d groups , respectively , and -36.55 % ± 18.59 % for the allopurinol group , indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol ( P = 0.0239 , 2- sample t test ) . The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9 % and 100 % for the febuxostat 40- and 60-mg/d groups , respectively , and 68.8 % for the allopurinol group , showing higher achievements for the febuxostat groups compared with the allopurinol group . All adverse drug reactions were mild to moderate in severity , and there were no severe symptoms or reactions leading to drug discontinuation . CONCLUSIONS These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol BACKGROUND About 9 % of average dietary energy intake in the United States comes from fructose . Such a high consumption raises concern about the metabolic effects of this sugar . OBJECTIVE The objective of this study was to determine the effect of dietary fructose on plasma lipids . DESIGN The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center . The participants were 24 healthy adult volunteers ( 12 men and 12 women ; 6 of each sex were aged < 40 y and 6 of each sex were aged > /=40 y ) . All subjects received 2 isoenergetic study diets assigned by using a r and omized , balanced crossover design . One diet provided 17 % of energy as fructose . The other diet was sweetened with glucose and was nearly devoid of fructose . Each diet was fed for 6 wk . Both diets were composed of common foods and contained nearly identical amounts of carbohydrate , protein , fat , fiber , cholesterol , and saturated , monounsaturated , and polyunsaturated fatty acids . All meals were prepared in the metabolic kitchen of the General Clinical Research Center . RESULTS The responses to the study diets differed by sex . In men , the fructose diet produced significantly higher fasting , postpr and ial , and daylong plasma triacylglycerol concentrations than did the glucose diet . The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32 % greater in men than the corresponding concentration during the glucose diet ( P : < 0.001 ) . The fructose diet had no significant effect on fasting or postpr and ial plasma triacylglycerol concentrations in women . The fructose diet also had no persistent effect on fasting plasma cholesterol , HDL cholesterol , or LDL cholesterol in either men or women . CONCLUSIONS Dietary fructose was associated with increased fasting and postpr and ial plasma triacylglycerol concentrations in men . Diets high in added fructose may be undesirable , particularly for men . Glucose may be a suitable replacement sugar OBJECTIVE Gout affects a large fraction of persons with advanced chronic kidney disease , and hyperuricemia may increase the risk of cardiovascular disease . Several hypouricemic agents are contraindicated in patients with end-stage renal disease .  Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract . Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid , another organic anion . We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term , r and omized , clinical trial comparing sevelamer with calcium-based phosphate binders . METHODS Two hundred subjects undergoing maintenance hemodialysis were r and omly assigned to receive either sevelamer or calcium-based phosphorus binders in an international , multicenter , clinical trial . Data on baseline and end-of- study uric acid concentrations were available in 169 subjects ( 85 % ) ; the change in uric acid concentration from baseline to the end of the study was the outcome of interest . RESULTS Baseline clinical characteristics , including mean uric acid concentrations , were similar in subjects r and omly assigned to receive sevelamer and calcium-based phosphate binders . The mean change in uric acid concentration ( from baseline to the end of the study ) was significantly larger in sevelamer-treated subjects ( -0.64 mg/dl versus -0.26 mg/dl ; P = 0.03 ) . The adjusted mean change in uric acid concentration was more pronounced when the effects of age , sex , diabetes , vintage ( time since initiation of dialysis ) , dialysis dose , and changes in blood urea nitrogen and bicarbonate concentrations were considered ( -0.72 mg/dl versus -0.15 mg/dl ; P = 0.001 ) . Twenty-three percent of sevelamer-treated subjects experienced a study -related reduction in the concentration of uric acid equal to -1.5 mg/dl or more , compared with 10 % of calcium-treated subjects ( P = 0.02 ) . CONCLUSION In a r and omized clinical trial comparing sevelamer and calcium-based phosphate binders , treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations BACKGROUND Despite abundant epidemiologic evidence , the role of elevated serum uric acid level as a cardiovascular risk factor is controversial . We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality . METHODS A population -based prospect i ve cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease , cancer , or diabetes . The main outcome measure was death from cardiovascular disease and any cause . RESULTS The mean follow-up was 11.9 years . There were 157 deaths during follow-up , of which 55 were cardiovascular . In age-adjusted analyses , serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third . Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73 . Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77 . Excluding the 53 men using diuretics did not alter the results . In age-adjusted analyses , men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third . Adjustment for further risk factors strengthened the association somewhat . CONCLUSIONS Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men , independent of variables commonly associated with gout or the metabolic syndrome . Serum uric acid measurement is an easily available and inexpensive risk marker , but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered CONTEXT Fructose-rich beverages such as sugar-sweetened soda and orange juice can increase serum uric acid levels and , thus , the risk of gout , but prospect i ve data on the relationship are limited . OBJECTIVE To examine the relationship between intake of fructose-rich beverages and fructose and the risk of incident gout among women . DESIGN , SETTING , AND PARTICIPANTS In the Nurses ' Health Study , a US prospect i ve cohort study spanning 22 years ( 1984 - 2006 ) , we analyzed data from 78,906 women with no history of gout at baseline who provided information on intake of beverages and fructose through vali date d food frequency question naires . MAIN OUTCOME MEASURE Incident cases that met the American College of Rheumatology survey criteria for gout . RESULTS During 22 years of follow-up , we documented 778 confirmed incident cases of gout . Increasing intake of sugar-sweetened soda was independently associated with increasing risk of gout . Compared with consumption of less than 1 serving per month of sugar-sweetened soda , the multivariate relative risk of gout for 1 serving per day was 1.74 ( 95 % confidence interval [ CI ] , 1.19 - 2.55 ) and for 2 or more servings per day was 2.39 ( 95 % CI , 1.34 - 4.26 ) ( P<.001 for trend ) . The corresponding relative risks for orange juice were 1.41 ( 95 % CI , 1.03 - 1.93 ) and 2.42 ( 95 % CI , 1.27 - 4.63 ) ( P = .02 for trend ) . The absolute risk differences corresponding to these relative risks were 36 and 68 cases per 100,000 person-years for sugar-sweetened soda and 14 and 47 cases per 100,000 person-years for orange juice , respectively . Diet soft drinks were not associated with the risk of gout ( P = .27 for trend ) . Compared with the lowest quintile of fructose intake , the multivariate relative risk of gout in the top quintile was 1.62 ( 95 % CI , 1.20 - 2.19 ; P = .004 for trend ) ( risk difference of 28 cases per 100,000 person-years ) . CONCLUSION Among this cohort of women , consumption of fructose-rich beverages is associated with an increased risk of incident gout , although the contribution of these beverages to the risk of gout in the population is likely modest given the low incidence rate among women Fructose and sodium intake have been associated with hypertension and metabolic syndrome . Although various mechanisms are involved , fructose causes hypertension partly through rising intracellular and serum uric acid . To date , there are no studies in adults that have evaluated the impact of low fructose diets and allopurinol on prehypertensive and overweight subjects . The objective of this study was to compare the effect of low fructose diet and allopurinol or placebo on blood pressure ( BP ) and metabolic syndrome components The study was a controlled clinical trial and consisted of two phases ; in the first phase of intervention ( 4 weeks ) , patients were r and omized to either low fructose diet ( 34 patients ) or control diet ( 38 patients ) . In the second phase of intervention ( weeks 4 - 8 ) , the same groups continued with the same diet prescriptions but were further r and omized to receive placebo or allopurinol ( 300 mg/d ) . Clinic and 24-hour ambulatory BP , anthropometric measures , and laboratory data were determined at baseline , weeks 4 and 8 . Seventy-two patients were included in the trial . At the end of the dietary phase , both diet groups significantly reduced their BP , but there were no between-group differences . Compared to placebo , at the end of follow-up , subjects in the allopurinol group had a lower clinic systolic blood pressure and this was significant within- and between-group comparisons . The percentage of dippers was higher in the allopurinol group , and weight was reduced significantly despite the absence of caloric restriction Allopurinol was associated with a significant reduction in clinic BP , an increase in the percentage of dippers , and significant weight loss . Larger studies with longer follow-up are needed to confirm our findings BACKGROUND AND OBJECTIVES Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease . Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease . We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol  might improve endothelial dysfunction , BP , estimated GFR ( eGFR ) , and inflammatory markers . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month r and omized prospect i ve study . Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups .  Flow-mediated dilation ( FMD ) , eGFR , ambulatory BP monitoring , spot urine protein-creatine ratio , and highly sensitive C-reactive protein were measured at baseline and at 4 months . RESULTS Age , gender , lipid profile , eGFR , hemoglobin , glucose , and level of proteinuria were similar in hyperuricemic subjects and controls at baseline . As expected , hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients . Allopurinol treatment result ed in a decrease in serum uric acid , a decrease in systolic BP , an increase in FMD , and an increase in eGFR compared with baseline . No significant difference was observed in the control hyperuricemic and normouricemic groups . In a multiple regression analysis , FMD levels were independently related to uric acid both before ( beta = -0.55 ) and after ( beta = -0.40 ) treatment . CONCLUSIONS Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia A positive association between hyperuricemia and cardiovascular disease has been reported , but no study has evidence d yet the precise role of serum uric acid in the development of cardiovascular disease . In addition , no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia , even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage . The present prospect i ve cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population . The subjects were 49,413 Japanese male railroad workers , aged 25 - 60 years at enrollment .  Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982 . The vital status of the subjects was traced until the end of 1985 for those who remained alive . During an average 5.4-year study period , 984 deaths were recorded . Those with serum uric acid over 8.5 mg/dl showed elevated relative risks ( RRs ) of death in all causes ( RR 1.62 , p<0.01 ) , coronary heart disease ( RR 1.52 ) , stroke ( RR 2.33 , p<0.01 ) , hepatic disease ( RR 3.58 , p<0.01 ) , and renal failure ( RR 8.52 , p<0.01 ) , as compared with those with serum uric acid levels of 5.0 - 6.4mg/dl . The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol ( 2.00 , p<0.01 ) , age and alcohol intake ( 1.85 , p<0.001 ) , age and smoking ( 1.69 , p<0.001 ) , age and gout treatment ( 1.61 , p<0.05 ) , and also age and BMI ( 1.50 , p < 0.05 ) . On the other h and , the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose ( 1.62 ) , age and systolic blood pressure ( 1.32 ) , age and GOT ( 1.23 ) , and also age and history of cardiovascular disease ( 1.17 ) . These results showed that hyperuricemia has a strong association with the RRs of death in all causes , coronary heart disease , stroke , hepatic disease and renal failure , and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy Little is known about uric acid role for cardiovascular events in the Asian-Pacific countries with relatively low coronary heart disease ( CHD ) but high stroke events . Also , there is scanty evidence for repeated measures of uric acid levels among population . We examined associations of basic and repeated measures of uric acid level with  CHD and stroke events in one Taiwanese adult community prospect ively .  Cox proportional hazards models , treating uric acid as baseline and time-dependent covariates , were used to assess the 11-year risk of CHD and stroke events . Among 3602 adult subjects older than 35 years , 86 incident CHD and 155 incident stroke cases were identified . The rate ratios of hyperuricemia ranged between 2.00 and 3.96 , with higher risk ratios in women than in men . The rate differences and population attributable fractions were also higher in women than in men , implying that women had high risk of uric acid on cardiovascular events . After adjustment for age effect , time-dependent uric acid was associated with significant CHD risk in both genders ( hazard risk [ HR ] 1.43 , 95 % CI : 1.10 - 1.87 in men and HR 1.22 , 95 % CI : 1.03 - 1.44 in women ) . But the magnitude of hazard risks decreased after adjusting more atherosclerotic risk factors for CHD . For stroke event , the age-adjusted hazard risk of time-dependent continuous uric acid level was 1.23 ( 95 % CI : 1.00 - 1.54 ) in men and 1.36 ( 95 % CI : 1.05 - 1.75 ) in women . Multiple adjustment by risk factors demonstrated that uric acid was still a significant predictor for stroke in women ( HR 1.32 , 95 % CI : 1.00 - 1.73 ) . The similar hazard risk patterns existed for binary categories of hyperuricemia . Subgroup analyses demonstrated uric acid had significant risk only in hypertension and metabolic syndrome subgroups , not in their counterparts . We concluded that uric acid , in the baseline and time-dependent variables , could predict cardiovascular events in the community of relatively low CHD but high stroke risk in Taiwan Relationships were investigated among  serum uric acid ( UA )  , the insulin response to a st and ard oral glucose load ( 75 g ) , and  serum lipoprotein levels  in 197 individuals with chronic spinal cord injury ( SCI ) . All subjects had normal liver and renal function . None had a prior history of diabetes mellitus or gout . The mean age of subjects was 50 + /- 1 years , duration of injury ( DOI ) , 18 + /- 1 years , and body mass index ( BMI ) , 25 + /- 0.4 kg/m2 . No significant differences were found between those with paraplegia or quadriplegia for any of the parameters measured . The mean serum UA values were not significantly different among the subgroups of subjects with normal glucose tolerance , impaired glucose tolerance , or diabetes mellitus ( 5.6 + /- 0.2 mg/dl , 5.6 + /- 0.2 and 5.7 + /- 0.3 , respectively ) . Approximately one-half of the subjects had an abnormality in oral glucose tolerance . The levels of serum UA ( p < 0.001 ) and serum triglycerides ( TG ) ( p < 0.01 ) in the subgroup with hyperinsulinemia were significantly higher than in the subgroup with normal insulin levels . By linear regression analyses , the serum UA concentration was positively correlated with peak plasma insulin level ( r = 0.31 , p < 0.001 ) , and BMI ( r = 0.20 , p < 0.01 ) , but not with age , DOI , or peak glucose . The data suggest that in subjects with chronic SCI , as in the healthy able-bodied population , hyperuricemia is associated with hyperinsulinemia , obesity and abnormal lipoprotein metabolism Objective . Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid . Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease . The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate ( sUA ) levels in gouty patients who were either overproducers or underexcretors . Methods . Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2 , 28-day , multicenter , r and omized , double-blind , placebo-controlled trial and r and omized to receive febuxostat 40 mg , 80 mg , or 120 mg daily , or placebo . The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28 . Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid ( uUA ) from baseline to Day 28 . Results . Of the 153 subjects , 118 ( 77 % ) were underexcretors ( uUA ≤ 800 mg/24 h ) and 32 ( 21 % ) were overproducers ( uUA > 800 mg/24 h ) ; baseline uUA data were missing for 3 subjects . Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28 . Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group , for both underexcretors and overproducers . Conclusion . Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status T HE characteristics of a disease as it appears in the general population are likely to be quite different from its characteristics in a hospital population , since only patients who are severely afflicted or in whom complications have developed are likely to be found in the hospital population . Analysis of a hospital population , therefore , will give an exaggerated idea of the usual severity of the disease and of the frequency with which complications occur . A similar bias may be introduced when patients coming to the hospital with other complaints are used as controls , and an even greater bias introduced when autopsy series are used . This paper presents some observations of a forward-going study of an adult population sample in respect to the characteristics of hyperuricemia and gouty arthritis . The characteristics investigated include ( 1 ) the prevalence of hyperuricemia and its relationship to age ; ( 2 ) the prevalence of secondary hyperuricemia ; ( 3 ) the prevalence of gouty arthritis ; ( 4 ) the incidence of gouty arthritis and its relationship to age ; ( 5 ) the relationship of gouty arthritis to hyperuricemia and the risk of developing gouty arthritis for each uric acid level ; ( 6 ) the clinical features of gouty arthritis in this population ; and ( 7 ) the prevalence of complications related to gouty arthritis and to hyperuricemia . In the Town of Framingham , Massachusetts , a population was selected by r and om sampling for the studp of coronaryartery disease and hJ , pertension . This population has been described in detail elsewhere [ /--31 . A total of 5,127 subjects ( 2,283 men and 2,844 women ) , age thirtythrough fifty-nine , free of evidence of coronary heart disease on initial examination , were included in the sample ( hereinafter referred to as the population ) . The mean age on admission was forty-four . Biennial examination included history , physical examination , electrocardiogram , roentgenograms and various laboratory tests . The results of these examinations , transcripts of admission to the community hospital , and information obtained from physicians and hospitals outside the community formed the record of each subject . At the time of this report the population had been examined an average of seven times for a follow-up period of twelve years . A few subjects have died , moved away or have missed one or two examinations for various reasons . Some have had eight examinations . The current health status of approxiluately 95 per cent of the original 5,127 subjects is known and only 0.7 per cent are considered lost to follow-up [ J ] BACKGROUND There are limited data available on the association of gouty arthritis ( gout ) in middle age with long-term cardiovascular disease ( CVD ) mortality . METHODS We performed a 17-year follow-up study of 9105 men , aged 41 to 63 years and at above-average risk for coronary heart disease , who were r and omized to the Multiple Risk Factor Intervention Trial and who did not die or have clinical or electrocardiographic evidence of coronary artery disease during the 6-year trial .  Risk of CVD death and other causes subsequent to the sixth annual examination associated with gout was assessed by means of Cox proportional hazards regressions . RESULTS The unadjusted mortality rates from CVD among those with and without gout were 10.3 per 1000 person-years and 8.0 per 1000 person-years , respectively , representing an approximately 30 % greater risk . After adjustment for traditional risk factors , use of diuretics and aspirin , and serum creatinine level , the hazard ratio ( gout vs no gout ) for coronary heart disease mortality was 1.35 ( 95 % confidence interval [ CI ] , 1.06 - 1.72 ) . The hazard ratio for death from myocardial infa rct ion was 1.35 ( 95 % CI , 0.94 - 1.93 ) ; for death from CVD overall , 1.21 ( 95 % CI , 0.99 - 1.49 ) ; and for death from any cause , 1.09 ( 95 % CI , 1.00 - 1.19 ) ( P = .04 ) . The association between hyperuricemia and CVD was weak and did not persist when analysis was limited to men with hyperuricemia without a diagnosis of gout . CONCLUSION Among middle-aged men , a diagnosis of gout accompanied by an elevated uric acid level imparts significant independent CVD mortality risk . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000487
These analyses do not support a uric acid-increasing effect  of isocaloric fructose intake in nondiabetic and diabetic participants .
Hypercaloric fructose intake may , however , increase uric acid concentrations .
Hyperuricemia is linked to gout and features of metabolic syndrome .
There is concern that dietary fructose may increase uric acid concentrations .