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.