Dietary Purine Intake Research Articles

Assessment of the temporal trend and daily profiles of the dietary purine intake among Chinese residents during 2014 to 2021.

The incidence of hyperuricemia is on the rise in China, primarily due to dietary habits. However, limited data exists regarding dietary purine intake in the country. This study aimed to estimate the daily dietary purine intake among Chinese residents from 2014 to 2021 and evaluate the temporal trend using joinpoint regression analysis. The analysis revealed an annual percentage change (APC) of 0.8% (95% CI: 0.1-1.5%) in dietary purine intake prior to the joinpoint (2014-2019). Following the joinpoint (2019-2021), the APC significantly increased to 6.5% (95% CI: 3.3-9.8%), indicating a noteworthy upward trend (p = 0.045). Furthermore, the average daily purine intake varied significantly among different regions of China, with the southern region showing the highest dietary intake of purines. Considering the diverse contributions of various food sources to dietary purine intake, it was observed that meat consumption had the greatest impact, accounting for 36.2% of purine intake, followed by cereals consumption (25.3%) and vegetables and edible fungi (24.2%). These findings hold significance for dietary intervention and management strategies aimed at reducing purine intake among the population.

Anaerobic purinolytic enzymes enable dietary purine clearance by engineered gut bacteria

Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.

The Association between Dietary Purine Intake and Mortality: Evidence from the CHNS Cohort Study.

Objectives: To investigate the association between dietary purine intake and mortality among Chinese adults. Methods: Based on data from the 2004–2015 China Health and Nutrition Survey (CHNS) and the corresponding edition of China Food Composition, the average purine intake per day (mg/day) from 2004 to 2011 was calculated, and the surveyed population was divided into five groups by quintiles. The outcome event and timepoint of concern were defined as death and time, respectively, as reported by family members, recorded until the 2015 survey. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for death. The possibly nonlinear relationship between purine intake and mortality was examined with restricted cubic splines. Results: We included 17,755 subjects, and the average purine intake among them was 355.07 ± 145.32 mg/day. Purine intake was inversely associated with mortality (Ptrend < 0.001). Compared with the lowest quintiles of purine intake, the highest quintiles (HR = 0.60; 95% CI: 0.46, 0.77) showed a significant association with lower mortality. The negative association with mortality was mainly found in plant-derived purine (Ptrend = 0.001) and, weakly, in animal-derived purine (Ptrend = 0.052). In addition, a U-shaped relationship between purine intake and mortality was observed in males; however, there was no statistically significant dose–response relationship in females. Conclusion: Considering the low-purine-intake levels of the Chinese population, we observed a U-shaped relationship between purine intake and mortality in males, but purine intake may not relate to mortality in females. Future studies should investigate the causal relationship between purine intake and disease burden in China.

Inulin-type prebiotics reduce serum uric acid levels via gut microbiota modulation: a randomized, controlled crossover trial in peritoneal dialysis patients.

Increased levels of uric acid (UA), which is mainly excreted through the kidneys, are independently associated with higher mortality in end-stage renal disease (ESRD) patients. The uricolysis of gut microbiota plays an important role in extrarenal excretion of UA. This study aimed to examine the effect of inulin-type prebiotics (a type of fermentable dietary fiber) on intestinal microbiota modulation and serum UA levels in ESRD patients. Continuous ambulatory peritoneal dialysis (CAPD) patients were recruited to a randomized, double-blind, placebo-controlled crossover trial of 12-week inulin-type prebiotics. Participants were visited before and after treatment with prebiotics or placebo. Serum UA levels, dietary purine intake, serum xanthine oxidase (XO) activity, daily "renal excretion" of UA, and fecal UA degradation capability were measured at each visit. Fecal metagenomic analysis was conducted to assess microbial composition and function. Sixteen participants (mean age = 37 y; 10 men and 6 women) completed the trial, and 64 specimens were analyzed. The average concentration of serum UA decreased by approximately 10% in the prebiotic intervention group in comparison to the placebo group (p = 0.047) without an increase in daily "renal excretion" of UA via urine and dialysate. There were no significant changes in purine intake or activity of XO. Notably, enhanced fecal UA degradation was observed after prebiotic intervention (p = 0.041), and the ratio of Firmicutes/Bacteroidetes, which was positively associated with fecal UA degradation, increased in the prebiotic period (p = 0.032). Furthermore, prebiotics enriched purine-degrading species in the gut microbiota, including unclassified_o_Clostridiales, Clostridium sp. CAG:7, Clostridium sp. FS41, Clostridium citroniae, Anaerostipes caccae, and Clostridium botulinum. Inulin-type prebiotics is a promising therapeutic candidate to reduce serum UA levels in renal failure patients, and this urate-lowering effect could possibly be attributed to intestinal microbial degradation of UA. This study was registered at the Chinese Clinical Trials Registry ( http://www.chictr.org.cn/ ), registration ID: ChiCTR-INR-17013739, registration date: 6th Dec 2017.

The Association Between Dietary Purine Intake and Mortality: Evidence From the CHNS Cohort Study

ObjectivesTo investigate the association between dietary purine intake and mortality among Chinese adults. MethodsBased on data from the 2004–2015 China Health and Nutrition Survey (CHNS) and the corresponding edition of China Food Composition, the average purine intake per day from 2004 to 2011 was calculated and divided into five groups by quintiles. The outcome event and time we concerned were defined as self-reported death and time in 2015 survey. Cox proportional hazards regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for death. The possibly non-linear relation between purine intake and mortality was examined with restricted cubic splines. ResultsWe included 17,751 subjects and the average purine intake among them was 329.14 ± 142.74 mg/day. Purine intake was inversely associated with mortality (P = 0.002). Compared with the lowest quintiles, the HRs (95% CI) of the highest quintiles were 0.60 (0.46, 0.77) for purine (P < 0.001). Besides, a U-shaped relationship between purine intake and mortality was observed in males; however, there is no dose-response relationship in females. ConclusionsUnder the low purine intake levels of the Chinese population, purine intake showed a protective effect. We observed a U-shaped relationship between purine intake and mortality in men but not found in women. Funding SourcesNational Key R&D Program of China (2017YFC0907200,2017YFC0907201).

Effect of body mass index on serum urate and renal uric acid handling responses to an oral inosine load: experimental intervention study in healthy volunteers

BackgroundHigh body mass index (BMI) is strongly associated with hyperuricaemia. It is unknown whether overweight and obesity influences serum urate primarily through increased urate production or reduced renal clearance of uric acid. The aim of this study was to determine the influence of BMI on the response to inosine, a purine nucleoside that functions as an intermediate in the purine salvage and degradation pathways.MethodsFollowing an overnight fast, 100 healthy participants without gout attended a study visit. Blood and urine samples were taken prior to and over 180 min after 1.5 g oral inosine. Serum urate and fractional excretion of uric acid (FEUA) were analysed according to high BMI (≥ 25 kg/m2) and low/normal BMI (< 25 kg/m2) groups, and according to BMI as a continuous variable.ResultsParticipants in the high BMI group (n = 52, mean BMI 30.8 kg/m2) had higher serum urate concentrations at baseline (P = 0.002) compared to those with low/normal BMI (mean BMI 21.8 kg/m2). However, the high BMI group had a smaller increase in serum urate following the inosine load (P = 0.0012). The two BMI groups had a similar FEUA at baseline (P = 0.995), but those in the high BMI group had a smaller increase in FEUA following the inosine (P = 0.0003). Similar findings were observed when analysing BMI as a continuous variable. Those with high BMI had a smaller increase in FEUA per increase in serum urate, compared to those with low BMI (P = 0.005).ConclusionsIn a fasting state, people with high BMI have elevated serum urate levels but similar FEUA values compared with those with low/normal BMI. Following a purine load, those with high BMI have an attenuated renal excretion of uric acid. These data, using an experimental method to dynamically assess human urate handling, suggest that people with high BMI have a higher renal capacity for uric acid reabsorption when fasted and following a dietary purine intake have reduced renal clearance.Trial registrationAustralia and New Zealand Clinical Trials Registry, ACTRN12615001302549, date of registration 30 November 2015.

A Targeted Metabolomics Assay to Measure Eight Purines in the Diet of Common Bottlenose Dolphins, Tursiops truncatus.

Bottlenose dolphins managed under human care, human beings and Dalmatian dogs are prone to forming urate uroliths. Limiting dietary purine intake limits urate urolith formation in people and dogs because purines are metabolized to uric acid, which is excreted in urine. Managed dolphins develop ammonium urate nephroliths, whereas free-ranging dolphins do not. Free-ranging dolphins consume live fish, whereas managed dolphins consume different species that have been stored frozen and thawed. Differences in the purine content of fish consumed by dolphins under human care versus in the wild may be responsible for the difference in urolith prevalence. Commercially available purine assays measure only four purines, but reported changes in purines during frozen storage suggest that a wider range of metabolites should be measured when comparing fresh and stored fish. A method using high performance liquid chromatography with tandem mass spectrometry was developed to quantify eight purine metabolites in whole fish and squid commonly consumed by dolphins. The coefficient of variation within and among days was sometimes high for purines present in small amounts but was acceptable (≤ 25%) for guanine, hypoxanthine, and inosine, which were present in high concentrations. This expanded assay identified a total purine content up to 2.5 times greater than the total that would be quantified if only four purines were measured. Assuming additional purines are absorbed, these results suggest that additional purine metabolites should be measured to better understand the associated risk when fish or other purine-rich foods are consumed by people or animals prone to developing uroliths.

Effect of diet, body mass index, and proton pump inhibitors on antitubercular therapy-induced hyperuricemia in patients of tuberculosis

Background: Risk factors for developing hyperuricemia other than inherited abnormalities are obesity, moderate to heavy alcohol intake, high blood pressure, and abnormal kidney function. Factors that increase urate formation are excess dietary purine intake, increased nucleic acid turnover, obesity, and exercise. Factors that decrease urate excretion are kidney disease, diabetic ketoacidosis, hypertension, drugs, and trisomy 21. Aims and Objectives: To see the effect of diet, body mass index (BMI), and proton pump inhibitors (PPIs) in antitubercular therapy (ATT)–induced hyperuricemic tubercular patients. Materials and Methods: This prospective study was conducted at a tertiary care teaching hospital of Rajasthan in tubercular patients aged 18–65 years of either sex. Serum uric acid level was estimated at weekly interval after starting ATT for 2 months along with baseline value. Patients developing hyperuricemia were finally included in the study. Patients were divided into vegetarian and nonvegetarian groups. BMI of all the patients was calculated. All the patients were grouped into two categories on the basis of those receiving or not receiving PPI. Appropriate statistical tests were used to compare the data. Results: Out of the total 123 hyperuricemic patients, 71 patients were on vegetarian diet while 52 patients were on nonvegetarian diet. Difference between the serum uric acid levels of vegetarian and nonvegetarian groups was found to be insignificant. Out of the total, 90 patients were underweight, 28 were having normal weight while 5 were overweight. Pearson’s correlation test showed no correlation between BMI and serum uric acid levels. PPIs were taken by 72 patients. Difference between serum uric acid levels of patients receiving PPIs and those not receiving PPIs was found to be insignificant. Conclusion: The serum uric acid level was not found to be affected by diet, BMI, and use of PPI in ATT-treated tubercular patients probably due to some altered physiology in these patients.

Low-Level Lead Exposure and the Prevalence of Gout

Blood lead levels (BLLs) less than 1.21 µmol/L (<25 µg/dL) among adults are considered acceptable by current national standards. Lead toxicity can lead to gouty arthritis (gout), but whether the low lead exposure in the contemporary general population confers risk for gout is not known. To determine whether BLLs within the range currently considered acceptable are associated with gout. Population-based cross-sectional study. The National Health and Nutrition Examination Survey for 2005 through 2008. 6153 civilians aged 40 years or older with an estimated glomerular filtration rate greater than 10 mL/min per 1.73 m2. Outcome variables were self-reported physician diagnosis of gout and serum urate level. Blood lead level was the principal exposure variable. Additional data collected were anthropometric measures, blood pressure, dietary purine intake, medication use, medical history, and serum creatinine concentration. The prevalence of gout was 6.05% (95% CI, 4.49% to 7.62%) among patients in the highest BLL quartile (mean, 0.19 µmol/L [3.95 µg/dL]) compared with 1.76% (CI, 1.10% to 2.42%) among those in the lowest quartile (mean, 0.04 µmol/L [0.89 µg/dL]). Each doubling of BLL was associated with an unadjusted odds ratio of 1.74 (CI, 1.47 to 2.05) for gout and 1.25 (CI, 1.12 to 1.40) for hyperuricemia. After adjustment for renal function, diabetes, diuretic use, hypertension, race, body mass index, income, and education level, the highest BLL quartile was associated with a 3.6-fold higher risk for gout and a 1.9-fold higher risk for hyperuricemia compared with the lowest quartile. Blood lead level does not necessarily reflect the total body lead burden. Blood lead levels in the range currently considered acceptable are associated with increased prevalence of gout and hyperuricemia.

Studies on the purine-pyrimidine metabolism (2)--Effects of sample preparation and diet on the concentrations of oxypurines in blood and urine.

The levels of pseudouridine (psi rd), uridine (Urd), hypoxanthine (Hyp), xanthine (Xan) and uric acid (UA) in both blood and urine samples were assayed by a reversed-phase high performance liquid chromatographic (HPLC) method. The evaluation of the sampling procedures showed that the levels of plasma oxypurines were overestimated by more than 15% for Hyp and 35% for Xan when heparinized plasma separation was delayed for 5 minutes after sampling. The fact that oxypurines levels of serum were significantly higher than those of plasma was also documented. Hence, for the accurate measurement of plasma oxypurines, plasma should be immediately separated from the blood with anticoagulants after it is collected. Physiological variation under a suitable sample preparation was also studied in 6 healthy male volunteers after their usual and a low purine diet for 4 days. The mean plasma levels for 6 male volunteers on a usual diet were 2.52 +/- 0.19 mumol/l for psi rd, 290.1 +/- 88.8 for UA, 49.4 +/- 1.24 for Urd, 0.82 +/- 0.30 for Hyp and 0.49 +/- 0.12 for Xan. On a low purine diet, the declines in the plasma oxypurine concentrations and the renal excretions of UA as well as oxypurine were demonstrated. When a dietary purine intake was restricted, the reference range of the Hyp level in plasma wa 0.48 +/- 0.26, and Xan was 0.36 +/- 0.17 mumol/l. Dietary influences on purine-pyrimidine metabolites should also be considered for the accurate measurement of their concentrations in blood and urine.

The contribution of dietary purine over-consumption to hyperuricosuria in calcium oxalate stone formers

Excessive urine uric acid excretion appears to play a causal role in calcium oxalate stone formation and excessive purine intake is a major factor producing hyperuricosuria. We have studied spontaneous dietary purine intake in 10 hyperuricosuric men with recurrent calcium oxalate renal stones in order to define the basis for their purine over-consumption and the precise relationship that exists between purine intake and urine uric acid excretion. Diet diaries, kept by patients, were used to assess purine intake. The stone patients consumed more purine than five matched control subjects eating isocaloric diets. Steak, poultry and roast beef were the main sources of surplus purine. Urine uric acid excretion was linearly related to purine intake in both normal subjects and patients, and uric acid excretion on a purine-free diet predicted by the linear regression equation derived from diet diaries corresponded well with measured values, an observation confirming the accuracy of the dietary measurements employed. Stone patients who excreted normal amounts of uric acid on a purine-free diet displayed a relationship between uric acid excretion and dietary purine intake indistinguishable from normal.

Dietary-induced variation of hypoxanthine-guanine phosphoribosyl transferase activity in patients with the Lesch-Nyhan syndrome.

We have studied three patients with the Lesch-Nyhan syndrome to assess the effect of dietary purines on erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. During dietary purine restriction HGPRT activity rose in all three patients; resumption of normal dietary purine intake or the addition of adenine (10 mg/kg per day) to a purinefree diet resulted in a fall in HGPRT activity. These changes in enzyme activity appeared to be due to an activation or inactivation of the mutant enzyme without a change in the half-life or absolute amount of HGPRT enzyme protein.

A Second Enzyme Defect in Acquired Lactase Deficiency: Lack of Small-Intestinal Phlorizin-Hydrolase

To differentiate between extrarenal and renal causes of hyperuricaemia and gout, clearances of urate and creatinine were monitored for 31/2 days in fifty-two individuals (seven with a history of gout) with no gross impairment of renal function (creatinine clearance 52–137 ml/min). Dietary purine intake was kept constant. Monophasic circadian fluctuations of fractional urate excretion (= urate clearance over creatinine clearance) were observed with peak values in the afternoon, about 50% higher than during the night. Circadian fluctuations of urinary flow rate were almost identical. However, enhancement of urinary flow rate due to water diuresis had no effect on urate clearance. Despite wide variation of plasma urate concentrations among different individuals (±30% SD), daily urate excretion varied little (± 4% SD) and did not correlate with plasma urate (r= 0–03). Thus extrarenal factors appear not to account for the occurrence of hyperuricaemia in these patients. In contrast, a clearcut negative correlation was apparent between plasma urate concentration and fractional urate clearance (r= -0 72), which could fully account for the variations of plasma urate concentration. To elucidate further the mechanism responsible for antiuricosuria in hyperuricaemic patients, the effects of the uricosuric agents benzbromarone and probenecid were tested. A clearcut correlation was apparent between control fractional urate excretion and uricosuric effect of both benzbromarone and probenecid (r= 0–83 and 0–88, respectively), suggesting that anti-uricosuria was due to defective secretion. In an additional series, the uricosuric effect of probenecid was tested in ten patients with renal insufficiency. In these patients the uricosuric effect was clearly blunted, indicating that urate reab-sorption is reduced in renal insufficiency.