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1.
Nutrients ; 11(9)2019 Sep 17.
Article in English | MEDLINE | ID: mdl-31533291

ABSTRACT

The prevalence of obesity is increasing worldwide. Bioactive phytochemicals in food supplements are a trending approach to facilitate dieting and to improve patients' adherence to reducing food and caloric intake. The aim of this systematic review was to assess efficacy and safety of the most commonly used bioactive phytochemicals with appetite/hunger-suppressing and/or satiety/fullness-increasing properties. To be eligible, studies needed to have included at least 10 patients per group aged 18 years or older with no serious health problems except for overweight or obesity. Of those studies, 32 met the inclusion criteria, in which 27 different plants were tested alone or as a combination, regarding their efficacy in suppressing appetite/hunger and/or increasing satiety/fullness. The plant extracts most tested were derived from Camellia sinensis (green tea), Capsicum annuum, and Coffea species. None of the plant extracts tested in several trials showed a consistent positive treatment effect. Furthermore, only a few adverse events were reported, but none serious. The findings revealed mostly inconclusive evidence that the tested bioactive phytochemicals are effective in suppressing appetite/hunger and/or increasing satiety/fullness. More systematic and high quality clinical studies are necessary to determine the benefits and safety of phytochemical complementary remedies for dampening the feeling of hunger during dieting.


Subject(s)
Appetite Depressants/therapeutic use , Appetite Regulation/drug effects , Feeding Behavior/drug effects , Obesity/drug therapy , Phytochemicals/therapeutic use , Satiety Response/drug effects , Weight Loss/drug effects , Appetite Depressants/adverse effects , Female , Humans , Male , Obesity/epidemiology , Obesity/physiopathology , Obesity/psychology , Phytochemicals/adverse effects , Randomized Controlled Trials as Topic , Treatment Outcome
2.
Med Princ Pract ; 28(2): 167-177, 2019.
Article in English | MEDLINE | ID: mdl-30517949

ABSTRACT

OBJECTIVES: Nutraceuticals are advertised and sold with the label claim of being natural and safe herbal products. Due to the absence of clear regulations and guidelines for safety assessments of these products, nutraceuticals are commonly adulterated in order to increase sales. The objective of the current study was to design a comprehensive evaluation system to assess the safety, efficacy, authenticity according to label claim, and pharmaceutical quality of herbal slimming products in between 2015 and 2017. METHODS: We designed a comprehensive assessment system to evaluate the safety, authenticity according to label claim, and pharmaceutical quality of slimming nutraceuticals. Six different popular products were evaluated (Zotreem Plus®, Zotreem Extra®, Malaysian Super Slim®, AB Slim®, Chinese Super Slim®, and Metabolites®). The pharmaceutical evaluation included analyzing the samples via high-performance liquid chromatography to determine any possible adulterants. Additionally, the products' physical properties were assessed via pharmacopeial tests. Finally, a microbial evaluation and a cross-sectional observational retrospective prevalence study were conducted to assess the products' safety and efficacy. -Results: The tested products were found to be adulterated with unreported active pharmaceutical ingredients such as sibutramine, sildenafil, phenolphthalein, and orlistat. Furthermore, they contained heterogeneous amounts of adulterants and exhibited an unsatisfactory pharmaceutical and microbial quality. Finally, the observational survey conducted on users showed that high percentages of participants suffered from common side effects such as depression, diarrhea, and hypertension. CONCLUSIONS: These products threaten the health of consumers. There is a need to raise awareness of the lethal consequences of illegal nutraceuticals.


Subject(s)
Anti-Obesity Agents/analysis , Appetite Depressants/analysis , Dietary Supplements/analysis , Drugs, Chinese Herbal/analysis , Nonprescription Drugs/analysis , Anti-Obesity Agents/adverse effects , Appetite Depressants/adverse effects , Cross-Sectional Studies , Dietary Supplements/adverse effects , Drugs, Chinese Herbal/adverse effects , Egypt , Humans , Nonprescription Drugs/adverse effects , Weight Loss
3.
Arch Physiol Biochem ; 124(2): 156-166, 2018 May.
Article in English | MEDLINE | ID: mdl-28857634

ABSTRACT

The current study aimed to investigate the effect of Citrullus colocynthis (C. colocynthis) hydro-alcoholic extract on blood haemostasis in control and high-fat diet (HFD) induced obese rats. In control rats, the extract significantly enhanced bleeding time and plasma levels of tPA and significantly decreased plasma levels PAI-1 and serum levels of thromboxane B2 leading to inhibition of platelets aggregation. In HFD induced obese rats, similar effects were seen and the extract was also able to reverse HFD induced increases in fibrinogen and VWF. Searching for the mechanism, C. colocynthis acts by (1) inhibiting of food intake, (2) inhibiting the activity of pancreatic lipase, (3) decreasing levels of TNF-α and IL-6 and (4) decreasing circulatory levels of the prothrombotic adipokine, leptin and enhanced circulatory levels of the antithrombic adipokines and adiopnectin. In conclusion, C. colocynthis has antiplatelets and profibrinolytic activity in both control and HFD induced obese rats.


Subject(s)
Anti-Obesity Agents/therapeutic use , Antifibrinolytic Agents/therapeutic use , Citrullus colocynthis/chemistry , Dietary Supplements , Obesity/prevention & control , Plant Extracts/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Animals , Anti-Obesity Agents/adverse effects , Anti-Obesity Agents/metabolism , Antifibrinolytic Agents/adverse effects , Antifibrinolytic Agents/metabolism , Appetite Depressants/adverse effects , Appetite Depressants/metabolism , Appetite Depressants/therapeutic use , Biomarkers/analysis , Biomarkers/blood , Biomarkers/urine , Bleeding Time , Diet, High-Fat/adverse effects , Dietary Supplements/adverse effects , Feces/chemistry , Fibrinolysis , Fruit/chemistry , Lipid Metabolism , Male , Obesity/blood , Obesity/etiology , Obesity/metabolism , Plant Extracts/adverse effects , Plant Extracts/metabolism , Plasminogen Activator Inhibitor 1/blood , Platelet Aggregation , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/metabolism , Rats, Sprague-Dawley , Thromboxane B2/blood , Tissue Plasminogen Activator/blood
4.
Nutr Neurosci ; 21(8): 546-555, 2018 Oct.
Article in English | MEDLINE | ID: mdl-28511588

ABSTRACT

STUDY OBJECTIVES: Sleep is important for memory consolidation in children. This study intended to find out whether an evening milk-based drink could influence sleep efficiency and memory recall in a group of Indonesian children (5-6 years old) with sleep deprivation. METHODS: Children were randomly allocated to one of three interventions: Reference product, satiety-stimulating product, and a relaxing product. The intervention lasted for 6 weeks and children consumed two servings per day of each 200 ml, the serving in the morning being the same for all children. All measurements took place at baseline and at the end of the intervention. Sleep parameters were studied using actigraphy and a sleep diary during three consecutive days. Memory consolidation was tested using a 20 word-pair list, which was memorized the evening before being recalled the next morning at home-base. Anthropometry was measured using standard equipment. RESULTS: The Satiety group showed a significant decrease in word recall, and a significant increase in nocturnal awakenings that was inversely associated with sleep efficiency at the end of the intervention. Sleep efficiency did not differ between the three groups being 75.5 ± 8.6% and 75.7 ± 6.3% at baseline and end of the intervention, respectively. Despite the lower energy intake in the Standard (reference) group, this condition showed the highest increase in weight. DISCUSSION: Evening growing-up milks can affect memory recall, sleep characteristics, and growth. However, to correct sleep efficiency and sleep duration, improvement of parental behavior may be the most important factor with nutrition providing a supplementary effect.


Subject(s)
Child Nutritional Physiological Phenomena , Dietary Supplements , Hypnotics and Sedatives/therapeutic use , Milk , Sleep Disorders, Intrinsic/therapy , Actigraphy , Animals , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Child , Child, Preschool , Dietary Supplements/adverse effects , Double-Blind Method , Female , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Indonesia , Male , Memory Consolidation , Memory Disorders/etiology , Memory Disorders/prevention & control , Mental Recall , Milk/adverse effects , Severity of Illness Index , Sleep Deprivation/etiology , Sleep Deprivation/prevention & control , Sleep Disorders, Intrinsic/physiopathology , Snacks , Weight Gain
5.
Mol Nutr Food Res ; 61(11)2017 11.
Article in English | MEDLINE | ID: mdl-28730743

ABSTRACT

SCOPE: Independently, prebiotics and dietary protein have been shown to improve weight loss and/or alter appetite. Our objective was to determine the effect of combined prebiotic and whey protein on appetite, body composition and gut microbiota in adults with overweight/obesity. METHODS AND RESULTS: In a 12 week, placebo-controlled, double-blind study, 125 adults with overweight/obesity were randomly assigned to receive isocaloric snack bars of: (1) Control; (2) Inulin-type fructans (ITF); (3) Whey protein; (4) ITF + Whey protein. Appetite, body composition and gut microbiota composition/genetic potential were assessed. Compared to Control, body fat was significantly reduced in the Whey protein group at 12 wks. Hunger, desire to eat and prospective food consumption were all lower with ITF, Whey protein and ITF + Whey protein compared to Control at 12 wks. Microbial community structure differed from 0 to 12 wks in the ITF and ITF +Whey Protein groups (i.e. increased Bifidobacterium) but not Whey Protein or Control. Changes in microbial genetic potential were seen between Control and ITF-containing treatments. CONCLUSION: Adding ITF, whey protein or both to snack bars improved several aspects of appetite control. Changes in gut microbiota may explain in part the effects of ITF but likely not whey protein.


Subject(s)
Appetite Depressants/therapeutic use , Dietary Carbohydrates/therapeutic use , Dietary Supplements , Dysbiosis/diet therapy , Fructans/therapeutic use , Overweight/diet therapy , Whey Proteins/therapeutic use , Adiposity , Adult , Appetite Depressants/adverse effects , Bifidobacterium/classification , Bifidobacterium/growth & development , Bifidobacterium/isolation & purification , Body Mass Index , Dietary Carbohydrates/adverse effects , Dietary Supplements/adverse effects , Double-Blind Method , Dysbiosis/microbiology , Energy Intake , Feces/microbiology , Female , Fructans/adverse effects , Gastrointestinal Microbiome , Humans , Lost to Follow-Up , Male , Middle Aged , Molecular Typing , Obesity/diet therapy , Obesity/microbiology , Overweight/microbiology , Patient Dropouts , Prebiotics , Principal Component Analysis , Whey Proteins/adverse effects
6.
Diabetes Obes Metab ; 19(12): 1751-1761, 2017 12.
Article in English | MEDLINE | ID: mdl-28556449

ABSTRACT

AIMS: There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib. MATERIALS AND METHODS: Participants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co-primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ-CT); possible score 0-36] and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151. RESULTS: One-hundred and seven participants were included in the intention-to-treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference -6.3, 95% CI -9.6 to -3.0; P = .0003) and 2.4 mg beloranib groups (-7.0, 95% CI -10.5 to -3.6; P = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference - 8.2%, 95% CI -10.8 to -5.6; P < .0001) and 2.4 mg beloranib (-9.5%, 95% CI -12.1 to -6.8; P < .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo. CONCLUSIONS: MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.


Subject(s)
Aminopeptidases/antagonists & inhibitors , Appetite Depressants/therapeutic use , Cinnamates/therapeutic use , Cyclohexanes/therapeutic use , Epoxy Compounds/therapeutic use , Glycoproteins/antagonists & inhibitors , Hyperphagia/prevention & control , Obesity/prevention & control , Prader-Willi Syndrome/drug therapy , Protease Inhibitors/therapeutic use , Sesquiterpenes/therapeutic use , Adolescent , Adult , Aminopeptidases/metabolism , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Body Mass Index , Cinnamates/administration & dosage , Cinnamates/adverse effects , Cyclohexanes/administration & dosage , Cyclohexanes/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Epoxy Compounds/administration & dosage , Epoxy Compounds/adverse effects , Female , Glycoproteins/metabolism , Humans , Hyperphagia/etiology , Hyperphagia/physiopathology , Intention to Treat Analysis , Male , Methionyl Aminopeptidases , Obesity/etiology , Prader-Willi Syndrome/physiopathology , Protease Inhibitors/administration & dosage , Protease Inhibitors/adverse effects , Sesquiterpenes/administration & dosage , Sesquiterpenes/adverse effects , Severity of Illness Index , Venous Thrombosis/chemically induced , Venous Thrombosis/physiopathology , Weight Loss/drug effects , Young Adult
7.
Diabetes Obes Metab ; 19(8): 1165-1170, 2017 08.
Article in English | MEDLINE | ID: mdl-28261955

ABSTRACT

AIMS: Hypothalamic injury-associated obesity (HIAO) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumours in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO. We aimed to assess efficacy, safety and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO. MATERIALS AND METHODS: This Phase 2a, double-blind, placebo-controlled study included 14 patients with HIAO, randomized to receive beloranib 1.8 mg or placebo subcutaneously twice weekly for 4 weeks with an optional 4-week open-label extension in which all patients received beloranib. The primary endpoint was change in weight from baseline to Week 4. RESULTS: Participants were 64% female, with a mean (SD) age of 32 (9) years, BMI of 43 (7) kg/m2 and weight of 126 (22) kg. Compared with placebo (N = 4), beloranib 1.8 mg (N = 8) resulted in a mean (95% CI) difference in weight of -3.2 (-5.4, -0.9) kg after 4 weeks. Weight loss continued through the 8 weeks in patients randomized to beloranib (mean -6.2 [-8.2, -4.1] kg). Beloranib treatment was associated with improvements in high-sensitivity CRP. Adverse events were mild to moderate. No patients who received beloranib discontinued treatment. CONCLUSION: Beloranib treatment resulted in progressive weight loss in patients with HIAO that was comparable to that observed with beloranib in patients with exogenous obesity. These findings indicate a novel mechanism for treating obesity in patients with HIAO.


Subject(s)
Aminopeptidases/antagonists & inhibitors , Appetite Depressants/therapeutic use , Cardiovascular Diseases/prevention & control , Cinnamates/therapeutic use , Cyclohexanes/therapeutic use , Epoxy Compounds/therapeutic use , Glycoproteins/antagonists & inhibitors , Hypothalamus/injuries , Metabolic Syndrome/prevention & control , Obesity, Morbid/drug therapy , Sesquiterpenes/therapeutic use , Adult , Aminopeptidases/metabolism , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Biomarkers/blood , Body Mass Index , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cinnamates/administration & dosage , Cinnamates/adverse effects , Cohort Studies , Cyclohexanes/administration & dosage , Cyclohexanes/adverse effects , Double-Blind Method , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Epoxy Compounds/administration & dosage , Epoxy Compounds/adverse effects , Female , Follow-Up Studies , Glycoproteins/metabolism , Humans , Injections, Subcutaneous , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Methionyl Aminopeptidases , Obesity, Morbid/blood , Obesity, Morbid/etiology , Obesity, Morbid/physiopathology , Proof of Concept Study , Risk , Sesquiterpenes/administration & dosage , Sesquiterpenes/adverse effects , Weight Loss/drug effects , Young Adult
8.
Ann Hepatol ; 15(6): 932-938, 2016.
Article in English | MEDLINE | ID: mdl-27740529

ABSTRACT

 Introduction and aim. Non-cirrhotic idiopathic portal hypertension (NCIPH), also known as hepatoportal sclerosis (HPS) is a disease of uncertain etiology. However, various pathophysiological mechanisms has been postulated, including chronic or recurrent infections and exposure to drugs or toxins. In this context, it appears to be of multifactorial etiology or resulting from a portal vascular endothelium aggression. It is important to consider whether the use of dietary supplements and herbs can trigger or contribute to the occurance of HPS. We report a possible association of HPS with the consumption of herbals and / or dietary supplements. MATERIAL AND METHODS: We describe two cases of HPS in patients without known etiology causes associated with this disease. RESULTS: Both patients were females who were diagnosed with HPS following the consumption of Herbalife® products and putative anorexigenic agents in the form herbals infusions. Image-based analysis and the assessment of the histopathological alterations found in the livers confirmed the diagnosis. The histopatological analysis of liver samples from both patients showed portal tracts enlarged by fibrosis with disappearance or reduction in the diameter of the portal vein branches. In many portal tracts, portal veins branches were replaced by aberrant thin-walled fendiforme vessels. The bile ducts and branches of the hepatic artery show normal aspects. CONCLUSION: After the exclusion of other etiologic factors and a comprehensive analysis of clinical history, consumption of Herbalife® products and anorexigenic agents was pointed-out as a puttative predisposing factor for the development of the disease.


Subject(s)
Appetite Depressants/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Hypertension, Portal/chemically induced , Liver Cirrhosis/chemically induced , Liver/drug effects , Pancytopenia/chemically induced , Plant Preparations/adverse effects , Portal Vein/drug effects , Splenomegaly/chemically induced , Adult , Biopsy , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/pathology , Female , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/pathology , Liver/blood supply , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Middle Aged , Pancytopenia/diagnosis , Pancytopenia/pathology , Portal Vein/pathology , Predictive Value of Tests , Risk Factors , Sclerosis , Splenomegaly/diagnosis , Splenomegaly/pathology , Idiopathic Noncirrhotic Portal Hypertension
9.
Appetite ; 105: 27-36, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27166077

ABSTRACT

Controlling hunger between meals is a challenge for many individuals. This manuscript comprises 2 sequential clinical trials investigating the effects of psyllium (Metamucil) on satiety, both using a randomized, double-blind, placebo-controlled cross-over design. The first study determined the effects of 3.4 g, 6.8 g, and 10.2 g of psyllium taken before breakfast and lunch for 3 days. The second study determined the effects of 6.8 g (taken before breakfast and lunch on Days 1 and 2 and before breakfast on Day 3) on the satiety of participants receiving an energy restricted meal in the morning (breakfast) for 3 days. Efficacy endpoints were mean inter-meal hunger, desire to eat, and Satiety Labeled Intensity Magnitude Visual Analog Scale scores. In Study 1, all 3 psyllium doses resulted in directional or statistically significant mean reductions in hunger and desire to eat, and increased fullness between meals compared to placebo, with both higher doses better than placebo or 3.4 g. The 6.8 g dose provided more consistent (p ≤ 0.013) satiety benefits versus placebo. In Study 2, satiety was assessed similarly to Study 1. A significant (p ≤ 0.004) decrease in the 3-day mean hunger and desire to eat, as well as an increase in fullness for psyllium relative to placebo was observed. Most adverse events were mild gastrointestinal symptoms and were similar for psyllium compared to placebo. These results indicate that psyllium supplementation contributes to greater fullness and less hunger between meals.


Subject(s)
Appetite Depressants/administration & dosage , Energy Intake , Overweight/prevention & control , Prebiotics , Psyllium/administration & dosage , Satiety Response , Adult , Appetite Depressants/adverse effects , Appetite Depressants/therapeutic use , Body Mass Index , Breakfast , Cross-Over Studies , Double-Blind Method , Female , Humans , Hunger , Intention to Treat Analysis , Lunch , Male , Middle Aged , Nausea/etiology , Overweight/diet therapy , Patient Dropouts , Prebiotics/adverse effects , Psyllium/adverse effects , Psyllium/therapeutic use , Reproducibility of Results , Young Adult
11.
Article in English | MEDLINE | ID: mdl-27092588

ABSTRACT

In 2013 the Dutch authorities issued a warning against a dietary supplement that was linked to 11 reported adverse reactions, including heart problems and in one case even a cardiac arrest. In the UK a 20-year-old woman, said to have overdosed on this supplement, died. Since according to the label the product was a herbal mixture, initial LC-MS/MS analysis focused on the detection of plant toxins. Yohimbe alkaloids, which are not allowed to be present in herbal preparations according to Dutch legislation, were found at relatively high levels (400-900 mg kg(-1)). However, their presence did not explain the adverse health effects reported. Based on these effects the supplement was screened for the presence of a ß-agonist, using three different biosensor assays, i.e. the validated competitive radioligand ß2-adrenergic receptor binding assay, a validated ß-agonists ELISA and a newly developed multiplex microsphere (bead)-based ß-agonist assay with imaging detection (MAGPIX(®)). The high responses obtained in these three biosensors suggested strongly the presence of a ß-agonist. Inspection of the label indicated the presence of N-isopropyloctopamine. A pure standard of this compound was bought and shown to have a strong activity in the three biosensor assays. Analysis by LC-full-scan high-resolution MS confirmed the presence of this 'unknown known' ß3-agonist N-isopropyloctopamine, reported to lead to heart problems at high doses. A confirmatory quantitative analysis revealed that one dose of the preparation resulted in an intake of 40-60 mg, which is within the therapeutic range of this compound. The case shows the strength of combining bioassays with chemical analytical techniques for identification of illegal pharmacologically active substances in food supplements.


Subject(s)
Adrenergic beta-3 Receptor Agonists/poisoning , Antipyrine/analogs & derivatives , Appetite Depressants/adverse effects , Dietary Supplements/adverse effects , Food Contamination , Heart Diseases/etiology , Plant Preparations/adverse effects , Adrenergic beta-3 Receptor Agonists/analysis , Alkaloids/analysis , Alkaloids/toxicity , Anabolic Agents/adverse effects , Anabolic Agents/chemistry , Anabolic Agents/poisoning , Anabolic Agents/standards , Antipyrine/analysis , Antipyrine/poisoning , Appetite Depressants/chemistry , Appetite Depressants/poisoning , Appetite Depressants/standards , Biosensing Techniques , Dietary Supplements/analysis , Dietary Supplements/poisoning , Dietary Supplements/standards , Food Inspection , Food Labeling , Foodborne Diseases/etiology , Foodborne Diseases/mortality , Foodborne Diseases/therapy , Heart Diseases/mortality , Heart Diseases/therapy , Hospitalization , Humans , Internet , Netherlands , Nootropic Agents/adverse effects , Nootropic Agents/chemistry , Nootropic Agents/poisoning , Nootropic Agents/standards , Pausinystalia/adverse effects , Pausinystalia/chemistry , Performance-Enhancing Substances/adverse effects , Performance-Enhancing Substances/chemistry , Performance-Enhancing Substances/poisoning , Performance-Enhancing Substances/standards , Plant Preparations/chemistry , Plant Preparations/poisoning , Plant Preparations/standards
12.
Am J Cardiol ; 117(10): 1691-1696, 2016 05 15.
Article in English | MEDLINE | ID: mdl-27018933

ABSTRACT

Obesity is pandemic in the Western Hemisphere, especially in the United States (US) and is associated with morbidity and mortality. Recent data show that a large proportion of the US population is at least overweight and almost 2 in 5 Americans are obese. This ongoing trend of increasing obesity rates has led to a thriving market for anorexigens. Despite the health benefits of weight loss, several anorexigens had devastating side effects including pulmonary vascular disease which manifests as the clinical syndrome of pulmonary arterial hypertension (PAH). PAH is an incurable and fatal disease and is characterized by vascular constriction, hypertrophy, and proliferation that over time lead to right-sided cardiac failure. Over the past few decades, several weight loss medications have been associated with the development of PAH, possibly caused by an increase in systemic serotonin levels, resulting in vasoconstriction of the pulmonary arteries and initiating a cascade of pathologic vascular remodeling leading to vascular fibrosis. Once sufficient evidence for the association of these drugs with PAH or other related pathologies was found, many were removed from the market. However, there are other appetite suppressants still currently on the market (whether Food and Drug Administration-approved or "dietary supplements") that have to some extent similar mechanisms of action to those associated with PAH but lack robust enough data to prove or disprove an association. The serotonin pathway seems to be repeatedly implicated. In conclusion, given that PAH is a progressive and debilitating disease, it is important to highlight possible risk factors that could be avoided.


Subject(s)
Appetite Depressants/adverse effects , Hypertension, Pulmonary/etiology , Obesity/drug therapy , Pulmonary Artery/physiopathology , Pulmonary Circulation , Serotonin/blood , Vasoconstriction/physiology , Humans , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/epidemiology , Obesity/blood , Obesity/complications
13.
Diabetes Obes Metab ; 18(5): 508-18, 2016 May.
Article in English | MEDLINE | ID: mdl-26863991

ABSTRACT

AIMS: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. METHODS: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. RESULTS: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. CONCLUSIONS: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.


Subject(s)
Appetite Depressants/therapeutic use , Arginine/therapeutic use , Dietary Supplements , Gastrointestinal Agents/therapeutic use , Glucagon-Like Peptide 1/agonists , Obesity/diet therapy , Peptide YY/agonists , Animals , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Appetite Depressants/pharmacology , Arginine/administration & dosage , Arginine/adverse effects , Cells, Cultured , Dietary Supplements/adverse effects , Energy Intake/drug effects , Energy Metabolism/drug effects , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/adverse effects , Gastrointestinal Agents/pharmacology , Glucagon-Like Peptide 1/blood , Glucagon-Like Peptide 1/metabolism , In Vitro Techniques , Injections, Intraperitoneal , Injections, Intraventricular , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Mice, Inbred C57BL , Mice, Knockout , Obesity/drug therapy , Obesity/metabolism , Obesity/pathology , Peptide YY/blood , Peptide YY/metabolism , Random Allocation , Rats, Wistar , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Weight Loss/drug effects
14.
Am J Clin Nutr ; 103(2): 305-13, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26718419

ABSTRACT

BACKGROUND: Capsaicin, which is the major pungent principle in chili peppers, is able to induce satiety and reduce caloric intake. The exact mechanism behind this satiating effect is still unknown. We hypothesized that capsaicin induces satiety through the release of gastrointestinal peptides, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), from enteroendocrine cells in the small intestine. OBJECTIVE: We investigate the effects of an intraduodenal capsaicin infusion (1.5 mg pure capsaicin) in healthy volunteers on hunger, satiety, and gastrointestinal symptoms and the release of GLP-1 and PYY. DESIGN: Thirteen participants (7 women) [mean ± SEM age: 21.5 ± 0.6 y; body mass index (in kg/m(2)): 22.8 ± 0.6] participated in this single-blind, randomized, placebo-controlled crossover study with 2 different treatments. During test days, an intraduodenal infusion of either capsaicin or a placebo (physiologic saline) was performed with the use of a nasoduodenal catheter over a period of 30 min. Visual analog scale scores were used to measure hunger, satiety, and gastrointestinal symptoms. Blood samples were drawn at regular intervals for GLP-1 and PYY. Gallbladder volumes were measured with the use of real-time ultrasonography. RESULTS: The intraduodenal capsaicin infusion significantly increased satiety (P-treatment effect < 0.05) but also resulted in an increase in the gastrointestinal symptoms pain (P-treatment × time interaction < 0.0005), burning sensation (P-treatment × time interaction < 0.0001), nausea (P-treatment × time interaction < 0.05), and bloating (P-treatment × time interaction < 0.001) compared with the effects of the placebo infusion. Satiety scores had a positive correlation with all gastrointestinal symptoms. No differences in GLP-1 and PYY concentrations and gallbladder volumes were observed after the capsaicin infusion compared with after the placebo infusion. CONCLUSIONS: An intraduodenal infusion of capsaicin significantly increases satiety but does not affect plasma concentrations of GLP-1 and PYY. Rather, the effect on satiety seems related to gastrointestinal stress as shown by the associations with pain, burning sensation, nausea, and bloating scores. This trial was registered at clinicaltrials.gov as NCT01667523.


Subject(s)
Appetite Depressants/adverse effects , Capsaicin/adverse effects , Dietary Supplements/adverse effects , Enteritis/etiology , Glucagon-Like Peptide 1/metabolism , Peptide YY/metabolism , Satiety Response , Abdominal Pain/etiology , Adult , Appetite Depressants/administration & dosage , Biomarkers , Capsaicin/administration & dosage , Cross-Over Studies , Enteritis/metabolism , Enteritis/pathology , Enteritis/physiopathology , Female , Gallbladder/diagnostic imaging , Gallbladder/metabolism , Gallbladder/pathology , Glucagon-Like Peptide 1/blood , Humans , Intubation, Gastrointestinal , Nausea/etiology , Organ Size , Pain Measurement , Peptide YY/blood , Single-Blind Method , Ultrasonography , Young Adult
15.
Endocrinology ; 157(1): 233-44, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26492472

ABSTRACT

Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements.


Subject(s)
Appetite Depressants/therapeutic use , Energy Metabolism/drug effects , Leptin/analogs & derivatives , Obesity/drug therapy , Recombinant Fusion Proteins/therapeutic use , Satiety Response/drug effects , Amino Acid Motifs , Animals , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Appetite Depressants/chemistry , Dose-Response Relationship, Drug , Energy Intake/drug effects , Female , Hypothalamus/drug effects , Hypothalamus/metabolism , Hypothalamus/pathology , Injections, Subcutaneous , Leptin/administration & dosage , Leptin/genetics , Leptin/therapeutic use , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mice, Mutant Strains , Molecular Weight , Motor Activity/drug effects , Obesity/metabolism , Obesity/pathology , Peptides/metabolism , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/chemistry , Specific Pathogen-Free Organisms , Thermogenesis/drug effects , Weight Loss/drug effects
16.
J Ethnopharmacol ; 155(2): 987-91, 2014 Sep 11.
Article in English | MEDLINE | ID: mdl-24955559

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Hoodia gordonii (family Apocynaceae) has become known globally for its claimed effect of appetite suppression. Despite a relatively large body of evidence of the plant׳s chemical make-up, peer-reviewed studies to provide scientific information on physiological effects of Hoodia gordonii are relatively sparse. The role of the pregnane glycoside P57-commonly accepted to be responsible for appetite suppression-has been questioned recently. Furthermore, a variety of physiological side-effects associated with consumption of the plant in extracted form questions its suitability for consumption. Although adverse effects have been described before, the relative abundance of non-peer-reviewed data originating from patent documents and lay publication for advertising, which specifically only focus on beneficial outcomes, skews the view of the risk-benefit-balance. Here we provide a review of peer-reviewed studies on the plant׳s physiological effects. Novel data from an in vivo rodent study further elucidate the benefit-to-risk ratio associated with consumption. CONCLUSIONS: we conclude that although Hoodia gordonii seems to have a desired effect on appetite and weight loss, this effect may at least in part be a secondary symptom of the serious adverse effects that are associated with consumption of the high doses required to achieve therapeutic clinical effect.


Subject(s)
Apocynaceae/chemistry , Appetite Depressants/isolation & purification , Plant Extracts/pharmacology , Animals , Appetite/drug effects , Appetite Depressants/adverse effects , Appetite Depressants/pharmacology , Ethnopharmacology , Humans , Plant Extracts/adverse effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Weight Loss/drug effects
17.
Endocrinology ; 155(5): 1679-89, 2014 May.
Article in English | MEDLINE | ID: mdl-24517227

ABSTRACT

Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.


Subject(s)
Appetite Depressants/therapeutic use , Appetite Regulation/drug effects , Endoplasmic Reticulum Stress/drug effects , Fatty Liver/prevention & control , Nicotine/therapeutic use , Nicotinic Agonists/therapeutic use , Obesity/drug therapy , AMP-Activated Protein Kinases/antagonists & inhibitors , AMP-Activated Protein Kinases/metabolism , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Diet, Fat-Restricted , Diet, High-Fat/adverse effects , Dyslipidemias/etiology , Dyslipidemias/prevention & control , Fatty Liver/etiology , Hyperinsulinism/etiology , Hyperinsulinism/prevention & control , Hypothalamus/drug effects , Hypothalamus/enzymology , Hypothalamus/metabolism , Injections, Subcutaneous , Liver/drug effects , Liver/enzymology , Liver/metabolism , Liver/pathology , Male , Nicotine/administration & dosage , Nicotine/adverse effects , Nicotinic Agonists/administration & dosage , Nicotinic Agonists/adverse effects , Non-alcoholic Fatty Liver Disease , Obesity/diet therapy , Obesity/etiology , Obesity/metabolism , Rats , Rats, Sprague-Dawley , Thermogenesis/drug effects , Weight Loss/drug effects
18.
Ned Tijdschr Geneeskd ; 157(51): A6676, 2013.
Article in Dutch | MEDLINE | ID: mdl-24345358

ABSTRACT

BACKGROUND: Weight-loss products, which are freely available in some other countries and on the Internet, may be contaminated with ingredients not mentioned on the label. CASE DESCRIPTION: We describe a 43-year-old woman who presented to the emergency ward of our hospital after stabbing herself in the stomach with a knife, because of severe psychosis. A few days after admission her symptoms were completely gone and there were no longer signs of psychosis. The most likely explanation for the psychosis was the use of sibutramine-contaminated weight-loss coffee (Brazil Potent Slimming Coffee). CONCLUSION: Brazil Potent Slimming Coffee and possibly also other weight-loss products may be contaminated with sibutramine and as a result cause severe adverse reactions. It is always important to consider intoxication due to the use of herbal supplements and other OTC products in the differential diagnosis.


Subject(s)
Appetite Depressants/adverse effects , Coffee/chemistry , Cyclobutanes/adverse effects , Psychotic Disorders/etiology , Adult , Brazil , Coffee/adverse effects , Cyclobutanes/administration & dosage , Female , Food Contamination , Humans , Internet , Weight Loss
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