A multi-analytical strategy for evaluation of quality and authenticity of artichoke food supplements for overweight control.

Despite the widespread use of artichoke-based food supplements for obesity control (FSOC), studies on evaluation of the quality/authenticity of these commercial products are scarce. To that aim, a new multi-analytical strategy, based on the use of gas chromatography coupled to mass spectrometry (GC-MS) and high performance liquid chromatography coupled to ultraviolet and mass spectrometry detection (HPLC-UV-MS), in combination with chemometrics, has been developed. Twenty-one artichoke FSOC and different bract and leaf extracts (used as reference samples) were analysed. Sugars, inositols, caffeoylquinic acids, dicaffeoylquinic acids, flavonoids and their glycosides were detected in reference samples and in most artichoke FSOC. Low concentrations of bioactives, and the presence of other compounds probably related to heat treatment during manufacturing (difructosyl anhydrides, 3-deoxyglucosone), or to the addition of caloric additives (maltose, maltotriose) or non-declared plants (e.g. pinitol, disaccharides, silybin derivatives) were also detected in some FSOC by either GC-MS or HPLC-UV-MS. Application of Principal Component Analysis to the combined GC-MS + HPLC-UV data matrix, proved that this multi-analytical strategy provides advantages over single analytical techniques for the detection of the wide variety of fraudulent practices affecting authenticity of artichoke FSOC and for assessment of their quality.

Extraction and UHPLC-DAD detection of undeclared substances in market-available dietary supplements and slimming products in Eastern region, Saudi Arabia: An application of principal component analysis.

BACKGROUND: Dietary supplements (DS) containing undeclared substances may pose serious risk to s public health. The consumers of DS should be aware of such products in order to avoid the risk of fatal outcomes. AIM OF THE STUDY: The study is based on the determination and identification of undeclared substances - theobromine (TB), theophylline (TH), pseudoephedrine (PE), caffeine (C), hydrochlorothiazide (HTZ) and yohimbine (Y) - in market-available DS. MATERIAL AND METHODS: Ultra-high-performance liquid chromatography with diode array detection (UHPLC-DAD) was utilized to identify and quantify the presence of undeclared substances, in 52 different DS collected from the market. RESULTS: A fast and reliable UHPLC-DAD method was developed and validated for simultaneous determination of the analyte where an efficient separation was achieved within 7 min runtime (TB 1.47, TH 1.79, PE 2.08, C 2.26, HTZ 3.78, Y 6.50) with resolution >1.5. The method validation produced r2 values ranging from 0.975 to 0.999 within a linearity range of 1-300 ppm. The UHPLC method revealed the presence of undeclared substances in 11 samples (HD3, HD4, HD9, HD13, HD14, HD15, HD21, HD24, HD27, HD38 and HD40), where the most widely distributed analyte was PE and C. The analyte found to have the highes concentrations (mg) in these DS were PE (11) and C (2.01). Among the 52 DS products tested, the product HD3 revealed a greater number and amount (mg) of undeclared substances, i.e. TH (0.05), C (2.01), HTZ (0.37) and Y (0.05), followed by HD14, i.e. PE (9.31), C (0.40), HTZ (0.01) and HD9 PE (11.00), C (0.41). CONCLUSION: The abundance of undeclared substances in these DS products was PE > C > Y > HTZ. None of the DS contained TB whereas TH was present in only one sample.

Principal component analysis of synthetic adulterants in herbal supplements advertised as weight loss drugs.

OBJECTIVE: Obesity is one of the major problems in many countries. Herbal drugs are widely used to treat obesity. Unfortunately the majority of herbal weight loss drugs are adulterated with active pharmaceutical ingredients. The purpose of the present study was to analyse herbal weight loss drugs for the general search for pharmaceuticals. METHODS: sixty one herbal weight loss drugs that were collected from herb shops and internet in Kermanshah, Iran were analysed qualitatively using gas chromatography/mass spectrometry. RESULTS: Of the 61 weight loss products sampled, 72% were found to be adulterated with tramadol, caffeine, fluoxetine, rizatriptan, venlafaxine and methadone. CONCLUSION: Herbal weight loss products were adulterated with controlled and legitimate drugs. Patients should be aware of the danger of using adulterated supplements.

Yellow Oleander Seed, or "Codo de Fraile" (Thevetia spp.): A Review of Its Potential Toxicity as a Purported Weight-Loss Supplement.

The Dietary Supplements and Health Education Act (DSHEA), passed by the United States Congress in October of 1994, defines herbal products as nutritional supplements, not medications. This opened the market for diverse products made from plants, including teas, extracts, essential oils, and syrups. Mexico and the United States share an extensive border, where diverse herbal products are available to the public without a medical prescription. Research undertaken in the neighboring cities of Ciudad Juarez, Mexico, and El Paso, Texas, USA, shows the use of herbs is higher in this border area compared to the rest of the United States. A portion of the population is still under the erroneous impression that "natural" products are completely safe to use and therefore lack side effects. We review the dangers of ingesting the toxic seed of Thevetia spp. (family Apocynaceae), commonly known as "yellow oleander" or "codo de fraile," misleadingly advertised on the Internet as an effective and safe dietary supplement for weight loss. Lack of proper quality control regarding herbs generates a great variability in the quantity and quality of the products' content. Herb-drug interactions occur between some herbal products and certain prescription pharmaceuticals. Certain herbs recently introduced into the U.S. market may not have been previously tested adequately for purity, safety, and efficacy. Due to the lack of reliable clinical data regarding the safe use of various herbal products currently available, the public should be made aware regarding the possible health hazards of using certain herbs for therapeutic purposes. The potentially fatal toxicity of yellow oleander seed is confirmed by cases reported from various countries, while the purported benefits of using it for weight loss have not been evaluated by any known clinical trials. For this reason, the use of yellow oleander seed as a dietary supplement should be avoided.

Banned and discouraged-use ingredients found in weight loss supplements.

OBJECTIVES: To identify banned and discouraged-use ingredients, such as ephedra, 1,3-dimethylamylamine, and beta-methyl-phenylethylamine, in readily available weight loss dietary supplements within a 10-mile radius of Regis University. METHODS: A list of banned and discouraged-use ingredients was compiled with the use of the Food and Drug Administration (FDA) dietary supplement website which provides information on supplement ingredients that are no longer legal or are advised against owing to adverse event reporting. Investigators visited all retail outlet stores within a 10-mile radius of Regis University in Denver, Colorado. Retail chains were not duplicated and only one of each chain was evaluated. RESULTS: A total of 51 weight loss supplement products from retail stores were found with banned or discouraged-use substances listed on their labels. At least one banned ingredient was found to be listed on the product labels in 17 of the 51 studied supplements (33%). At least one discouraged-use ingredient was found in 46 of the 51 products (90%). Retail outlet stores dedicated to supplements and sports nutrition alone were found to have the greatest number of weight loss supplements that included banned and discouraged-use ingredients. CONCLUSION: The FDA has taken action to remove some weight loss supplements from the market that contain banned ingredients. Unfortunately, based on the findings of this study, it is evident that products containing these ingredients remain on the market today.

Study on health hazards through medicines purchased on the Internet: a cross-sectional investigation of the quality of anti-obesity medicines containing crude drugs as active ingredients.

BACKGROUND: Weight-loss medicines, including crude drugs and herbal supplements disguised as diet-aid products, are readily obtainable and distributed widely, especially in Southeast Asia. Even if such products are unapproved or prescription-only medicines, consumers can purchase them through an agency or directly on the Internet. We evaluated the quality and safety of herbal products purchased on the Internet to reveal their influence on public health. METHODS: Diet-aid products containing Bukuryo (Poria sclerotium), Bakumondo (Ophiopogonis tuber), or Daio (rhubarb rhizome) were purchased through websites that did not provide physical addresses or which advertised misleading medicines (e.g., unapproved Cialis 100 mg tablets, Viagra 100 mg tablets) on websites. We carefully noted details in the descriptions on package inserts or accompanying product characteristics and analyzed the ingredients using qualitative and quantitative methods, namely high-performance liquid chromatography equipped with a photodiode array detector. We requested the respective manufacturers to authenticate their products through a structured questionnaire. RESULTS: We purchased 15 items from 15 Internet sites and imported all 15 items to Japan. One item stated to contain rhubarb rhizome was identified as a prescription medicine; the others were dietary supplements and not medicines. Even though we did not analyze the constituents of all crude drugs, we found some active ingredients in the items. Sibutramine was detected in items confirmed to be supplements, including those containing Poria sclerotium and Ophiopogonis tuber. Each capsule contained ≈ 12 mg of sibutramine, which is the daily dose for anti-obesity medicines. Sibutramine is not approved for use in Japan and its sale has been suspended in Europe and the USA owing to serious adverse effects on the circulatory system. CONCLUSIONS: Our findings indicate that dietary supplements containing injurious ingredients are distributed to Japanese consumers and potentially to a broader international audience, and that purchasing them through unreliable websites bears potential health risks. To avoid potential adverse events, there should be adequate alerts about the risks of taking products without appropriate indications.

Optimization of co-agonism at GLP-1 and glucagon receptors to safely maximize weight reduction in DIO-rodents.

The ratio of GLP-1/glucagon receptor (GLP1R/GCGR) co-agonism that achieves maximal weight loss without evidence of hyperglycemia was determined in diet-induced obese (DIO) mice chronically treated with GLP1R/GCGR co-agonist peptides differing in their relative receptor agonism. Using glucagon-based peptides, a spectrum of receptor selectivity was achieved by a combination of selective incorporation of GLP-1 sequences, C-terminal modification, backbone lactam stapling to stabilize helical structure, and unnatural amino acid substitutions at the N-terminal dipeptide. In addition to α-amino-isobutyric acid (Aib) substitution at position two, we show that α,α'-dimethyl imidazole acetic acid (Dmia) can serve as a potent replacement for the highly conserved histidine at position one. Selective site-specific pegylation was used to further minimize enzymatic degradation and provide uniform, extended in vivo duration of action. Maximal weight loss devoid of any sign of hyperglycemia was achieved with a co-agonist comparably balanced for in vitro potency at murine GLP1R and GCGR. This peptide exhibited superior weight loss and glucose lowering compared to a structurally matched pure GLP1R agonist, and to co-agonists of relatively reduced GCGR tone. Any further enhancement of the relative GCGR agonist potency yielded increased weight loss but at the expense of elevated blood glucose. We conclude that GCGR agonism concomitant with GLP1R agonism constitutes a promising approach to treatment of the metabolic syndrome. However, the relative ratio of GLP1R/GCGR co-agonism needs to be carefully chosen for each species to maximize weight loss efficacy and minimize hyperglycemia.

The development of pharmacological treatment of obesity in children. A European regulatory perspective.

Childhood obesity is recognized by the World Health Organization as one of the most serious public health challenges of the 21st century. Current treatment recommendations consider the role of pharmacotherapy in the treatment of childhood obesity, as an adjunct to lifestyle modifications. This article focuses on key requirements for paediatric development of medicines for obesity in Europe with reference to the European Medicines Agency guideline and a review of Paediatric Investigation Plans (PIP) submitted for this condition, under Regulation (EC) No. 1901/2006 on medicines for paediatric use. To date the European Medicines Agency (EMA) received four paediatric investigation plans for childhood obesity. Issues encountered during the assessment of paediatric investigation plans were all related to the characteristics of the patient population, trial design, choice of endpoints, and safety aspects. Although the number of paediatric investigation plans submitted to the European Medicines Agency thus far is limited, current experience highlights the need for clinical trial protocols that are in line with the specific European guideline. Divergent approaches should be discussed with regulatory authorities before paediatric trials are initiated and included in paediatric investigation plans.

Pharmaceutical quality of nine generic orlistat products compared with Xenical(r).

OBJECTIVE: To compare the pharmaceutical quality of Xenical (chemically produced orlistat) with nine generic products, each produced by fermentation processes. METHODS: Xenical 120 mg capsules (Roche, Basel, Switzerland) were used as reference material. Generic products were from India, Malaysia, Argentina, Philippines, Uruguay, and Taiwan. Colour, melting temperature, crystalline form, particle size, capsule fill mass, active pharmaceutical ingredient content, amount of impurities, and dissolution were compared. Standard physical and chemical laboratory tests were those developed by Roche for Xenical. RESULTS: All nine generic products failed the Xenical specifications in four or more tests, and two generic products failed in seven tests. A failure common to all generic products was the amount of impurities present, mostly due to different by-products, including side-chain homologues not present in Xenical. Some impurities were unidentified. Two generic products tested failed the dissolution test, one product formed a capsule-shaped agglomerate on storage and resulted in poor (

Sibutramine--a review of clinical efficacy.

Controlled studies have shown that sibutramine produces dose-related weight loss when given in the range 5-30 mg per day, with optimal doses of 10 and 15 mg per day. Weight loss with sibutramine is 3-5 kg better than placebo at 24 weeks, and weight loss is maintained to 52 weeks at doses of 10 and 15 mg. By six months, 69% of patients treated with sibutramine 15 mg achieve a 5% or greater reduction in their baseline weight. The weight loss achieved with sibutramine was similar to that achieved with dexfenfluramine over 12 weeks (4.5 kg compared with 3.2 kg). Sibutramine-induced weight loss has been found to be accompanied by a significant reduction in waist/hip ratio, and decreases in plasma triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol. There were also increases in high density lipoprotein (HDL) cholesterol. In patients with type II diabetes, sibutramine-induced weight loss was accompanied by a shift towards improved glycaemic control. In controlled studies, 84% of sibutramine-treated patients reported adverse events, compared with 71% of patients receiving placebo. The most frequently reported adverse events are related to pharmacological actions of sibutramine, and include dry mouth, decreased appetite, constipation and insomnia.