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 Effect of long-term allopurinol administration on serial GFR in normotensive and hypertensive hyperuricemic subjects. Diet and medication in the treatment of hyperuricemia in hypertensive patients. Fructose-rich beverages and risk of gout in women. Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus Serum Uric Acid Level and Risk for Peripheral Arterial Disease: Analysis of Data From the Multiple Risk Factor Intervention Trial Is hyperuricemia a risk factor of stroke and coronary heart disease among Africans? Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study A controlled study of the effect of long term allopurinol treatment on renal function in gout. Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. 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. The determinants and prognostic significance of serum uric acid in elderly patients of the European Working Party on High Blood Pressure in the Elderly trial. Hyperuricemia and Incident Heart Failure Consumption of sucrose-sweetened soft drinks increases plasma levels of uric acid in overweight and obese subjects: a 6-month randomised controlled trial Uric acid and chronic kidney disease: new understanding of an old problem. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.
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 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 OBJECTIVE To evaluate the effects of diet and medication , either isolated or associated , on serum levels of uric acid in patients with hyperuricemia . METHODS We studied patients from the Hypertension Unit of the University of Goias who had hyperuricemia ( men > or = 8.5 mg/dL and women > or = 7.5 mg/dL ) . We divided the patients into three groups : G1 ( low purine diet ) , G2 ( low purine diet + medication ) , and G3 ( medication only ) . Patients received allopurinol , 150 mg/day titrated up to 300 mg/dL when necessary . Patients were evaluated with regards to their lifestyles ( diet , smoking , physical , activity , alcohol consumption ) , uric acid , blood pressure , use of medication , body mass index , cholesterol , and triglyceride . Follow-up took place in weeks 0 ( M1 ) , 6 ( M2 ) , 12 ( M3 ) during the intervention and in week 36 ( M4 ) after the study was completed . RESULTS Fifty-five patients participated in the study , 31 women , mean age 54.4+/-10.6 years , body mass index 28.6+/-3.9 kg/m2 . A similar reduction ( p<0.001 ) in uric acid levels occurred in the three intervention groups . In week 36 ( M4 ) , after 24 weeks without intervention , a tendency toward elevation of uricemia was noted in G2 and G3 , and a continuous drop in uricemia was noted in G1 . No significant modifications were observed in the other variables analyzed . CONCLUSION Considering the cost x benefit relationship , a diet low in purine should be the 1st therapeutic option for controlling hyperuricemia in patients with similar characteristic to the ones presented in this study 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 Hyperuricaemia is associated with an increased risk of gout , kidney stones and cardiovascular disease . The present post hoc analysis of pooled data from four placebo‐controlled phase III studies assessed the effect of canagliflozin , a sodium‐glucose co‐transporter 2 inhibitor , on serum uric acid levels in patients with type 2 diabetes mellitus ( T2DM ) and in a subset of patients with hyperuricaemia [ defined as baseline serum uric acid ≥475 µmol/l ( ∼8 mg/dl ) ] . At week 26 , canagliflozin 100 and 300 mg were associated with a ∼13 % reduction in serum uric acid compared with placebo . In the subset of patients with hyperuricaemia , placebo‐subtracted percent reductions in serum uric acid were similar to those in the overall cohort . More patients in the hyperuricaemic group achieved a serum uric acid level of < 360 µmol/l ( ∼6 mg/dl ) with both canagliflozin 100 mg ( 23.5 % ) and 300 mg ( 32.4 % ) compared with placebo ( 3.1 % ) . Incidences of gout and kidney stones were low and similar across groups . In conclusion , canagliflozin  treatment decreased serum uric acid in patients with T2DM , including those with baseline hyperuricaemia 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 Uric acid stabilizes platelet aggregation and enhances thrombotic tendency . OBJECTIVE To examine the relationship between raised serum uric acid and subsequent  cardiovascular events ( mortality , myocardial infa rct ion , stroke ) . METHODS This is a longitudinal study in a small r and om number ( 418 ) of patients in Kinshasa , Congo . In this hospital-based study , uricemia was determined with respect to gender , obesity and hypertension as well correlated with traditional cardiovascular risk factors . A univariate regression model was used to investigate the association of serum uric acid with the incidence of mortality , stroke and myocardial infa rct ion . RESULTS Serum uric acid was higher ( P<0.05 ) in obese women and men as well in hypertensives , than in their controls . The significant ( P<0.05 and 0.001 ) highest frequency of hyperuricemia was observed in both diabetic and hypertensive patients . Blood pressure ( BP ) was higher ( P<0.001 ) in patients with hyperuricemia than in those with normal serum uric acid . Serum uric acid was significantly correlated with body weight , BP , glucose , fibrinogen , urea , creatinin and total cholesterol . In men , hyperuricemia was significantly ( P<0.01 ) associated with a twofold increased risk of both myocardial infa rct ion and stroke incidence . However , hyperuricemia was significantly related to a double risk of all mortality and stroke onset . CONCLUSION Our results indicate that hyperuricemia among african patients is a strong predictor of myocardial infa rct ion  in men , stroke in both sexes and all causes of mortality in women Objective To examine the relation between intake of sugar sweetened soft drinks and fructose and the  risk of incident gout in men . Design Prospect i ve cohort over 12 years . Setting Health professionals follow-up study . Participants 46 393 men with no history of gout at baseline who provided information on intake of soft drinks and fructose through vali date d food frequency question naires . Main outcome measure Incident cases of gout meeting the American College of Rheumatology survey criteria for gout . Results During the 12 years of follow-up 755 confirmed incident cases of gout were reported . Increasing intake of sugar sweetened soft drinks was associated with an increasing risk of gout . Compared with consumption of less than one serving of sugar sweetened soft drinks a month the multivariate relative risk of gout for 5 - 6 servings a week was 1.29 ( 95 % confidence interval 1.00 to 1.68 ) , for one serving a day was 1.45 ( 1.02 to 2.08 ) , and for two or more servings a day was 1.85 ( 1.08 to 3.16 ; P for trend=0.002 ) . Diet soft drinks were not associated with risk of gout ( P for trend=0.99 ) . The multivariate relative risk of gout according to increasing fifths of fructose intake were 1.00 , 1.29 , 1.41 , 1.84 , and 2.02 ( 1.49 to 2.75 ; P for trend < 0.001 ) . Other major contributors to fructose intake such as total fruit juice or fructose rich fruits ( apples and oranges ) were also associated with a higher risk of gout ( P values for trend < 0.05 ) . Conclusions Prospect i ve data suggest that consumption of sugar sweetened soft drinks and fructose is strongly associated with an increased  risk of gout in men . Furthermore , fructose rich fruits and fruit juices may also increase the risk .  Diet soft drinks were not associated with the risk of gout An association between gout and kidney dysfunction has been long recognised . It is a reasonable presumption that gout might be the cause of the renal disease.1 Hypertension , urolithiasis and urinary infection may contribute to this association but it is far from certain whether hyperuricaemia itself may exert a deleterious effect . The available data have been variously interpreted as showing that hyperuricaemia is detrimental2 or of no Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes , but whether it has a causal role in insulin resistance remains controversial . Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance . Methods Subjects with asymptomatic hyperuricemia ( n = 73 ) were prospect ively placed on allopurinol ( n = 40 ) or control ( n = 33 ) for 3 months . An additional control group consisted of 48 normouricemic subjects .  Serum uric acid , fasting glucose , fasting insulin , HOMA-IR ( homeostatic model assessment of insulin resistance ) , and high-sensitivity C-reactive protein were measured at baseline and at 3 months . Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose , fasting insulin , and HOMA-IR index , as well as a reduction in serum high-sensitivity C-reactive protein . The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline ( n = 8 [ 20 % ] vs n = 30 [ 75 % ] , 3 months vs baseline , P < 0.001 ) . In the hyperuricemic control group , only glucose decreased significantly and , in the normouricemic control , no end point changed . Conclusions Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia . Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes 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 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 Determinants and risks associated with serum uric acid were investigated in 822 elderly hypertensive patients treated with hydrochlorothiazide and triamterene or placebo .  Pretreatment serum uric acid levels were significantly higher in men than in women and had positive correlation with serum creatinine . After adjustment for serum creatinine , positive correlations of serum uric acid with body weight and fasting blood glucose in women and with serum cholesterol in men were significant . During follow-up , serum uric acid increased significantly in the treated patients , but remained unchanged in the placebo group . Total , cardiovascular , and noncardiovascular mortality were unrelated to initial serum uric acid levels . One placebo patient and seven treated patients developed gout . Of those seven , most were male patients and had significantly higher serum levels of uric acid and creatinine than the other patients . Gender and renal function were the major determinants of serum uric acid in elderly hypertensive patients 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 Background / Objectives : Sucrose-sweetened soft drinks ( SSSDs ) are associated with the development of metabolic disorders . Fructose is a major component of SSSDs and is demonstrated to induce uric acid ( UA ) production and stimulate fat accumulation independent of excess caloric intake . UA induce insulin resistance and low- grade inflammation , suggesting that UA may have a causal role in the development of metabolic complications . The objective of this study is to investigate the long-term effects of consuming SSSDs on circulating levels of UA in overweight and obese subjects . Subjects/ Methods : Using a previously published study , circulating UA levels were assessed at baseline and after 6 months using chromogenic enzymatic absorptiometry . The study included 47 overweight and obese subjects without diabetes , r and omised to consume 1 l daily of either SSSD ( regular cola ) , isocaloric semi-skimmed milk , diet cola or water for 6 months . Results : Circulating UA levels increased ~15 % ( P=0.02 ) after the 6-month intervention in the SSSD group with no change in the other groups . In the SSSD  group , circulating UA levels increased significantly after the intervention in both absolute ( P=0.005 ) and relative values ( P=0.004 ) . The change in UA after the intervention correlated with changes in liver fat ( P=0.005 ) , triglycerides ( P=0.02 ) and insulin ( P=0.002 ) . Conclusions : In this secondary analysis daily intake of 1 l SSSD for 6 months was found to increase circulating UA levels compared with isocaloric milk , diet cola and water . Thus , a high daily intake of SSSDs in overweight and obese subjects without overt diabetes may increase the risk of developing metabolic complications through the elevation of UA . This trial is registered at Clinical Trials.gov as NCT00777647 Although an elevation of serum uric acid level is often associated with chronic kidney disease ( CKD ) , it remains controversial whether hyperuricemia per se is a true risk factor for the development or aggravation of CKD . Recent epidemiologic studies in healthy population s or in subjects with established kidney disease have reported the independent role of uric acid in lowering glomerular filtration rate and increasing the risk for new-onset kidney disease . Furthermore , lowering uric acid in patients with established renal disease has been reported to stabilize renal function independent of other confounders , suggesting a causative role of elevated uric acid in progression of CKD , rather than as an incidental finding related to CKD severity . In this manuscript we will discuss the potential role of uric acid in the development and aggravation of CKD based on epidemiologic , clinical and experimental studies . Given the worldwide epidemic of CKD , the importance of identifying modifiable risk factors of CKD , and the clinical implication of hyperuricemia in CKD , we propose large r and omized clinical trials to investigate whether uric acid-lowering therapy can slow the progression of CKD 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
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 .