PURPOSE OF REVIEW: This review summarizes the recent data on lifestyle factors that influence serum uric acid levels and the risk of gout and attempts to provide holistic recommendations, considering both their impact on gout as well as on other health implications. RECENT FINDINGS: Large-scale studies have clarified a number of long-suspected relations between lifestyle factors, hyperuricemia, and gout, including purine-rich foods, dairy foods, various beverages, fructose, and vitamin C supplementation. Furthermore, recent studies have identified the substantial burden of comorbidities among patients with hyperuricemia and gout. SUMMARY: Lifestyle and dietary recommendations for gout patients should consider overall health benefits and risk, since gout is often associated with the metabolic syndrome and an increased future risk of cardiovascular disease (CVD) and mortality. Weight reduction with daily exercise and limiting intake of red meat and sugary beverages would help reduce uric acid levels, the risk of gout, insulin resistance, and comorbidities. Heavy drinking should be avoided, whereas moderate drinking, sweet fruits, and seafood intake, particularly oily fish, should be tailored to the individual, considering their anticipated health benefits against CVD. Dairy products, vegetables, nuts, legumes, fruits (less sugary ones), and whole grains are healthy choices for the comorbidities of gout and may also help prevent gout by reducing insulin resistance. Coffee and vitamin C supplementation could be considered as preventive measures as these can lower urate levels, as well as the risk of gout and some of its comorbidities.

The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73-line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

The red cell glutathione levels of 10 healthy volunteers who are accustomed to winter-swimming were measured before and after this short-term whole body exposition to hypothermic environment. From the increases of the erythrocytic level of oxidized glutathione (GSSG) and of GSSG: total glutathione ratio an extensive formation of oxygen free radicals during and following the exposition to the intensive cold stimulus was concluded. That is in accordance with the finding on the drastic decrease of the concentration of uric acid as an important radical scavenger of the human blood plasma. Furthermore, the initial erythrocytic concentrations of reduced glutathione (GSH) and GSSG of subjects accustomed to winter-swimming were compared with those of healthy control persons who are not accustomed to regular winter-swimming. The markedly increased concentration of GSH and the reduced GSSG:total glutathione ratio in the erythrocytes of winter-swimmers reflect the adaptation to a regular oxidative stress. This antioxidative adaptation is postulated as a new basic mechanism of the hardening by exposition to an intensive short-term cold stimulus often applied within the hydrotherapy.

The objective of the study was to determine the efficacy of vitamin C in reducing serum uric acid (UA). This study was a double-blind placebo-controlled randomized trial conducted in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh from July 2007 and August 2008. Study participants were included from out patient department (OPD) of Rheumatology of BSMMU suffering from various Rheumatological problems other than gouty arthritis. All of the participants were non-smokers, non-alcoholics, and randomized to take either placebo or vitamin C (500 mg/day) for 12 weeks. A total of 98 subjects were enrolled in the study; 71 completed the trial, with 34 in the placebo group and 37 receiving vitamin C. Serum uric acid levels were not significantly reduced in the experimental group and they increased in the placebo group. In the vitamin C group, the mean change was -0.32mg/dl [95% confidence interval -0.73, 0.77], whereas in the placebo group, the mean change was +0.12mg/dl [95% confidence interval was -0.22, 0.47]. Subgroups were defined by sex, body mass index, and quartiles of baseline serum uric acid levels. In a subgroup analysis, vitamin C lowered serum uric acid significantly in those who had comparatively higher baseline uric acid levels. Although vitamin C did not lower serum uric acid significantly, participants with higher baseline serum uric acid levels experienced a significant uric acid lowering effect, but as the sample size was very small, it is difficult to draw any definitive conclusion.

Ten healthy subjects who swim regularly in ice-cold water during the winter (winter swimming), were evaluated before and after this short-term whole body exposure. A drastic decrease in plasma uric acid concentration was observed during and following the exposure to the cold stimulus. We hypothesize that the uric acid decrease can be caused by its consumption after formation of oxygen radicals. In addition, the erythrocytic level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione also increased following cold exposure, which supports this hypothesis. Furthermore, the baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of nonwinter swimmers. This can be viewed as an adaptation to repeated oxidative stress, and is postulated as mechanism for body hardening. Hardening is the exposure to a natural, e.g., thermal stimulus, resulting in an increased tolerance to stress, e.g., diseases. Exposure to repeated intensive short-term cold stimuli is often applied in hydrotherapy, which is used in physical medicine for hardening.

OBJECTIVE: We examined associations between vitamin C intake and serum uric acid in men in a population-based study. METHODS: We included 1387 men without hypertension and with body mass index (BMI) < 30 kg/m(2) in the Health Professional Follow-up Study. Dietary intake was assessed with a semiquantitative food frequency questionnaire validated for use in this population. Serum uric acid concentrations were measured. RESULTS: Greater intakes of total vitamin C were significantly associated with lower serum uric acid concentrations, after adjustment for smoking, BMI, ethnicity, blood pressure, presence of gout, use of aspirin, and intake of energy, alcohol, dairy protein, fructose, meat, seafood and coffee. An inverse dose-response association was observed through vitamin C intake of 400-500 mg/day, and then reached a plateau. Adjusted mean uric acid concentrations across total vitamin C intake categories (< 90, 90-249, 250-499, 500-999, or >/= 1000 mg/day) were 6.4, 6.1, 6.0, 5.7, and 5.7 mg/dl, respectively (p for trend < 0.001). Greater vitamin C intake was associated with lower prevalence of hyperuricemia (serum uric acid > 6 mg/dl). Multivariate odds ratios for hyperuricemia across total vitamin C intake categories were 1 (reference), 0.58, 0.57, 0.38, and 0.34 (95% CI 0.20-0.58; P for trend < 0.001). When we used dietary data, which were assessed 4-8 years before blood collection, as predictors, we observed similar inverse associations between vitamin C intake and uric acid. CONCLUSION: These population-based data indicate that vitamin C intake in men is inversely associated with serum uric acid concentrations. These findings support a potential role of vitamin C in the prevention of hyperuricemia and gout.