Introduction
Uric acid is the end product of purine metabolism and is secreted by the kidney[1]. Elevated levels of serum uric acid level (SUA) can result from decreased renal clearance[1]. Hyperuricemia is an abnormal condition with higher level of uric acid in the blood [2]. Hyperuricemia is due to an imbalance of increased production of uric acid or/and decreased excretion of uric acid, which may result in serious complications including gout, tophi, kidney stones, or urate nephropathy even kidney failure[1, 2] . In human, if the concentration of SUA reaches to 357 μmol/l (6 mg/dl) for women and 416 μmol/l (7.0 mg/dl) for men, hyperuricemia could be diagnosed [2]. Hyperuricemia increases the risk of gout, but it is also a risk factor for cardiovascular diseases (CVD)[3]. Uric acid seems to be involved in the pathogenesis of both coronary and carotid atherosclerosis [4]. Pro inflammatory properties of uric acid, accounting for this atherogenic potential, include a positive correlation of its concentration with increased levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor α (TNF α) as well as of chemoattractant and adhesion molecules[4]. High levels of SUA will lead to sequelae including hypertension hypertriglyceridemia, and hypercholesterolemia[1]. Also, hyperuricemia has been associated with an increased risk for early death in patients with an acute stroke[1]. Hyperuricemia spans CVD and CKD; increased SUA level can enhance the risk for both these morbidities [2]. As a cardiovascular risk factor, SUA often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia and obesity [2].
Obesity and dyslipidemia increase the risk of hyperuricemia [2]. Adults with increasing Body Mass Index (BMI) over time show increased SUA and hs-CRP. Serum uric acid has also been shown to correlate with liver dysfunction and increased inflammatory markers[1]. In developed countries, hyperuricemia was proved to be related to obesity-induced metabolic dysfunction and body weight control can improved lifestyle, dyslipidemia and hyperuricemia and ameliorate metabolic risk factors Obesity in women and hypertriglyceridemia in men may aggravate hyperuricemia to develop gout [2]. Also have found a significant correlation between nonalcoholic fatty liver disease (NAFLD) and hyperuricemia. The higher SUA level accompanied the risk of NAFLD [5]. In developing countries, for example, an Indian study reported that the prevalence of hyperuricemia increased significantly in population with obesity [2].
Orlistat (tetrahydrolipstatin) which is β-lactone is the only Food and Drug Administration (FDA) approved PL inhibitor. Orlistat is marketed as weight loss drug at a therapeutic oral dose of 120mg, three times a day[6]. Orlistat has been used for decades with no serious side-effects. It reversibly inhibits dietary lipid digestion in the gastrointestinal (GI) lumen, which leads to a modest weight loss [7]. Orlistat treatment in the conventional oral dosage forms is associated with frequent (~20% of patients) GI side-effects, such as liquid and oily stools [7]. Weight loss (>5 kg) achieved by therapeutic lifestyle changes or bariatric surgery has been reported to decrease urate levels by 8.0 to 10.0 μmol/dl[8].
A study showed that, there is no changes in plasma uric acid among children with obesity in one trial[9]. Also a short study showed that statistically significant drop of plasma uric acid levels [10]. The last meta-analysis is the first study to consider the effect of antiobesity drugs (orlistat) on serum uric acid focused its attention on patients with obesity and other metabolic disease only and not on a specific drugs. On the contrary, we aimed to carry out a meta-analysis of randomized controlled trials to specifically investigate if orlistat therapy is associated to decreased uric acid in adults and to assess the magnitude of the decrease in serum uric acid levels. Our study incorporate a sufficient number of RCTs but include articles only in English language.