Orlistat-associated adverse effects and drug interactions: a critical review.

Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

Effect of rosuvastatin treatment on plasma visfatin levels in patients with primary hyperlipidemia.

Visfatin is a novel adipokine involved in the process of atherosclerosis. We assessed the effect of rosuvastatin on plasma visfatin levels in patients with primary hyperlipidemia. Eighty hyperlipidemic patients without evidence of cardiovascular disease were randomized to receive either rosuvastatin 10 mg/day or therapeutic lifestyle changes intervention. Plasma visfatin levels were determined at baseline and after 12-weeks post-randomization. Rosuvastatin induced a significant decrease in plasma visfatin levels (17.1+/-2.1 versus 15.5+/-2.0 ng/ml, P=0.03). This effect correlated with baseline visfatin levels (r=0.51, P<0.01) and was independent of any lipid-lowering actions of rosuvastatin.

Glycemic index, glycemic control and beyond.

It is currently estimated that over 370 million individuals have diabetes, making diabetes a major public health issue contributing significantly to global morbidity and mortality. The steep rise in diabetes prevalence over the past decades is attributable, in a large part, to lifestyle changes, with dietary habits and behaviour as significant contributors. Despite the relatively wide availability of antidiabetic medicine, it is lifestyle approaches that still remain the cornerstone of diabetes prevention and treatment. Glycemic index (GI) is a nutritional tool which represents the glycemic response to carbohydrate ingestion. In light of the major impact of nutrition on diabetes pathophysiology, with the rising need to combat the escalating diabetes epidemic, this review will focus on the role of GI in glycemic control, the primary target of diabetic treatment and beyond. The review will present the evidence relating GI and diabetes treatment and prevention, as well as weight loss, weight maintenance and cardiovascular disease risk factors.

Effect of Plant Polyphenols on Adipokine Secretion from Human SGBS Adipocytes.

Introduction. Adipose tissue contributes to atherosclerosis with mechanisms related to adipokine secretion. Polyphenols may exhibit antiatherogenic properties. The aim of the study was to investigate the effects of three polyphenols, namely, quercetin, epigallocatechin gallate (EGCG), and resveratrol on adipokine secretion from cultured human adipocytes. Methods. Human SGBS adipocytes were treated with quercetin, EGCG, and resveratrol for 24 and 48 hours. Visfatin, leptin, and adiponectin were measured in the supernatant. Results. Visfatin secretion was inhibited by quercetin 10 µM by 16% and 24% at 24 and 48 hours respectively. The corresponding changes for quercetin 25 µM were 47% and 48%. Resveratrol 25 µM reduced visfatin by 28% and 38% at 24 and 48 hours. EGCG did not have an effect on visfatin. None of tested polyphenols influenced leptin and adiponectin secretion. Conclusion. Quercetin and resveratrol significantly decreased visfatin secretion from SGBS adipocytes. This effect may contribute to their overall antiatherogenic properties.

Review article: effects of plant sterols and stanols beyond low-density lipoprotein cholesterol lowering.

Consumption of foods and supplements enriched with plant sterols/stanols (PS) may help reduce low-density lipoprotein cholesterol (LDL-C) levels. In this review, we consider the effects of PS beyond LDL-C lowering. Plant sterols/stanols exert beneficial effects on other lipid variables, such as apolipoprotein (apo) B/apoAI ratio and, in some studies, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Plant sterols/stanols may also affect inflammatory markers, coagulation parameters, as well as platelet and endothelial function. Evidence also exists about a beneficial effect on oxidative stress, but this does not seem to be of greater degree than that expected from the LDL-C lowering. Many of these effects have been demonstrated in vitro and animal models. Some in vitro effects cannot be seen in vivo or in humans at usual doses. The epidemiological studies that evaluated the association of plasma PS concentration with cardiovascular disease (CVD) risk do not provide a definitive answer. Long-term randomized placebo-controlled studies are required to clarify the effects of supplementation with PS on CVD risk and progression of atherosclerosis.

Visfatin/PBEF and atherosclerosis-related diseases.

Visfatin is highly expressed in adipose tissue (mainly by the stromal cells), but it is also ubiquitously present in most tissues. Visfatin, which plays a role in nicotinamide adenine dinucleotide (NAD) biosynthesis, has been implicated in inflammatory states. Controversial results exist about the expression, circulating levels and the role of visfatin in atherosclerosis-related diseases. Most studies showed increased levels of visfatin in diabetes mellitus, obesity, hypertension, renal and cardiovascular disease. However, other studies reported lower levels of visfatin in these diseases. The discrepancies in clinical studies may be attributed to the multifactorial regulation of visfatin. There is evidence that visfatin expression and circulating levels are influenced by fat area and distribution, inflammatory state, renal function, iron metabolism, hormones as well as several other factors. Furthermore, discrepancies and lack of correlation between commercially available visfatin assays have been reported. More research is needed to better understand the factors that control its synthesis/release and to evaluate the role of visfatin in atherosclerosis-related disease. Large studies with homogeneous populations will probably be needed to answer these questions. Whether visfatin will eventually become a therapeutic target remains to be established.

Effects of rimonabant, as monotherapy and in combination with fenofibrate or ezetimibe, on plasma adipokine levels: a pilot study.

Weight loss and hypolipidemic drugs can improve lipid and adipokine levels. We assessed the effects of rimonabant, alone and in combination with fenofibrate or ezetimibe, on adipokine levels in obese/overweight patients with dyslipidemia. Overweight/obese patients (n = 60, body mass index = 27-40 kg/m(2)) with mixed dyslipidemia were recruited. Patients received a hypocaloric diet and were randomized to rimonabant 20 mg/d (group R, n = 20), rimonabant 20 mg/d plus fenofibrate 200 mg/d (group RF, n = 20), or rimonabant 20 mg/d plus ezetimibe 10 mg/d (group RE, n = 20). After 3 months, leptin concentration was significantly reduced in all groups (-38%, P < .005; -40%, P < .005; and -44%, P < .001 in the R, RF, and RE groups, respectively). Total adiponectin remained unaltered. Visfatin concentration decreased significantly only in the RE and RF groups (-18% and -38%, respectively; P < .047). Treatment with rimonabant may improve adipokine levels in overweight/obese patients with dyslipidemia. The addition of fenofibrate or ezetimibe may reinforce this effect.

Effects of a 6-month infliximab treatment on plasma levels of leptin and adiponectin in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) appear to have increased plasma levels of leptin and adiponectin. These adipokines may be implicated in the pathophysiology of RA. Tumour necrosis factor alpha (TNF-alpha) is a potential modulator of adipokines. The effects of long-term anti-TNF treatment on plasma levels of leptin and adiponectin are not clear. The aim of this study was to assess the effects of 6-month anti-TNF treatment (infliximab) on leptin and adiponectin plasma levels in RA patients. Thirty women with RA were included in the study. Patients with diabetes mellitus, any endocrine disorder or receiving any hypolipidemic or antidiabetic medication were not included. Thirty healthy age- and body mass index-matched women served as controls. Plasma levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. Mean age and disease duration of patients were 51.8 +/- 14.4 and 12.2 +/- 6.7 years, respectively. Body weight did not change significantly over the 6-month period. Plasma levels of leptin and adiponectin were higher in patients than controls and did not change significantly after 6-month treatment. Interestingly, in the tertile of patients with the highest baseline adiponectin concentrations, adiponectin levels were significantly reduced (P < 0.05). Infliximab treatment did not change plasma levels of leptin and adiponectin after 6-month treatment in the whole study population. However, a reduction of adiponectin levels was observed in patients with higher baseline adiponectin levels.