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Theanine, Uric acid, Mood, and Sinus health

March 2016

By Life Extension

Uric acid

Epidemiology of hyperuricemia and gout.

Gout is an increasingly common medical problem. The traditional risk factors of male sex and high red meat or alcohol consumption have been joined by a wave of newer risk factors, such as increased longevity, the metabolic syndrome (hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular disease risk), use of diuretics, low-dose aspirin, or cyclosporine, and end-stage renal disease. Atypical presentations of gout in the elderly can mimic osteoarthritis and rheumatoid arthritis. There is a resurgence of interest in hyperuricemia as an independent and potentially modifiable cardiovascular risk factor. The pharmacologic management of gout in general practice suffers from a number of quality-control issues. This article reviews these and other new epidemiologic data on this ancient disease.

Am J Manag Care. 2005 Nov;11(15 Suppl):S435-42; quiz S465-8

Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008.

OBJECTIVE: To estimate the prevalence of gout and hyperuricemia based on the latest nationally representative sample of US men and women (National Health and Nutrition Examination Survey [NHANES] 2007-2008). METHODS: Using data from 5,707 participants in NHANES 2007-2008, we estimated the prevalence of gout and hyperuricemia. During home interviews for NHANES 2007-2008, all participants were asked about a history of health professional- or physician-diagnosed gout. Our primary definition of hyperuricemia was a serum urate level of >7.0 mg/dl for men and >5.7 mg/dl for women. We explored potential secular trends in these estimates and their possible explanations by comparing them with estimates based on 18,825 participants in NHANES-III (1988-1994). RESULTS: The prevalence of gout among US adults in 2007-2008 was 3.9% (8.3 million individuals). The prevalence among men was 5.9% (6.1 million), and the prevalence among women was 2.0% (2.2 million). The mean serum urate levels were 6.14 mg/dl among men and 4.87 mg/dl among women, corresponding to hyperuricemia prevalences of 21.2% and 21.6%, respectively. These estimates were higher than those in NHANES-III, with differences of 1.2% in the prevalence of gout (95% confidence interval [95% CI] 0.6, 1.9), 0.15 mg/dl in the serum urate level (95% CI 0.07, 0.24), and 3.2% in the prevalence of hyperuricemia (95% CI 1.2, 5.2). These differences were substantially attenuated after adjusting for body mass index and/or hypertension. CONCLUSION: These findings from nationally representative samples of US adults suggest that the prevalence of both gout and hyperuricemia remains substantial and may have increased over the past 2 decades, which is likely related to increasing frequencies of adiposity and hypertension.

Arthritis Rheum . 2011 Oct;63(10):3136-41

Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population.

OBJECTIVE: To determine whether the prevalence of gout and/or clinically significant hyperuricemia increased in a managed care population over 10 years. METHODS: The study was a descriptive analysis utilizing an administrative claims database to ascertain 10-year trends in prevalence of gout and/or hyperuricemia. Prevalence rates were calculated cross-sectionally for each year (1990-99) and expressed/compared as rates per 1,000 enrollees. RESULTS: The prevalence of gout and/or hyperuricemia in the overall population increased by about 2 cases per 1000 enrollees over 10 years. In the > 75 year age group, rates increased from 21 per 1,000 persons in 1990 to 41 per 1,000 in 1999. In the 65-74 year age group, prevalence increased from between 21 and 24 per 1,000 persons in the years 1990-92 to over 31 per 1000 during the years 1997-99. Prevalence rates in younger age groups (< 65 years) stayed consistently low during the years under study. There were sex differences in most age groups, with men having the greater burden of disease at every time point. CONCLUSION: Prevalence of gout and/or hyperuricemia in the overall study population increased during the 10-year period. When stratified by age, there were increases in prevalence among groups over age 65 in both sexes. Although gout prevalence increased in both sexes over the 10-year period, men still had most of the burden of disease. In ages younger than 65, men had 4 times higher prevalence than women (4:1 ratio), but in the older age groups (> 65), the gender gap narrowed to 1 woman to every 3 men with gout and/or hyperuricemia (3:1 ratio).

J Rheumatol . 2004 Aug;31(8):1582-7

Uric acid, hyperuricemia,and vascular diseases.

Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation.

Front Biosci (Landmark Ed) . 2012 Jan 1;17:656-69

Gout and hyperuricemia.

Gout is a condition characterized by the deposition of monosodium urate crystals in the joints or soft tissue. The four phases of gout include asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout and chronic tophaceous gout. The peak incidence occurs in patients 30 to 50 years old, and the condition is much more common in men than in women. Patients with asymptomatic hyperuricemia do not require treatment, but efforts should be made to lower their urate levels by encouraging them to make changes in diet or lifestyle. Acute gout most commonly affects the first metatarsal joint of the foot, but other joints are also commonly involved. Definitive diagnosis requires joint aspiration with demonstration of birefringent crystals in the synovial fluid under a polarized light microscope. Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroids and analgesics. In patients without complications, NSAID therapy is preferred.

Am Fam Physician . 1999 Feb 15;59(4):925-34

An open-label, 6-month study of allopurinol safety in gout: the LASSO study.

OBJECTIVES: Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses. METHODS: Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0mg/dL. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency. RESULTS: Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the < 300-, 300-, and > 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA < 6.0mg/dL at month 6 was achieved by 35.9% of patients overall: 22.4%, 35.0%, and 48.3% in dosing categories < 300, 300, and > 300 mg, respectively. CONCLUSIONS: This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.

Semin Arthritis Rheum. 2015 Oct;45(2):174-83

Serum urate during acute gout.

OBJECTIVE: To study the frequency of normal serum urate (SU) levels during acute gout in the largest studies of acute gout treatment to date. METHODS: Data collected from 2 randomized controlled clinical trials assessing the efficacy of etoricoxib or indomethacin for 7 days in acute gout were used to assess SU levels during acute gouty attacks. Efficacy was similar with both agents, so both groups were combined for analysis. RESULTS: A total of 339 patients were enrolled in the 2 studies; 94% were male; mean age was 50.5 years. At baseline, 14% of patients had a "true" normal SU (<or=6 mg/dl) and 32% had SU<or=8 mg/dl during acute gout. Baseline mean SU was 7.1 versus 8.5 mg/dl (p<0.001) in those taking allopurinol versus nonusers. Patients taking chronic allopurinol were more likely to have lower SU at baseline compared to those not taking chronic allopurinol (p<0.001) during the acute attack. CONCLUSION: A normal SU level at presentation does not exclude an acute gouty attack. In the largest studies of acute gout to date, attacks still occurred despite SU levels being below 6.8 mg/dl, the saturation level for urate. This may be attributed to persistence of tophi and an increased body uric acid pool. Additional studies are needed to determine the correlation between SU and the body uric acid pool as well as the relationship to timing of changes during acute gout.

J Rheumatol. 2009 Jun;36(6):1287-9