Search

Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems. 1 While current models of pharmacovigilance, with their tools and methodologies, were developed for prescription drugs, safety surveillance is just as important for over-the-counter health products such as dietary supplements. The practice of pharmacovigilance is challenging in itself; however, there are unique challenges associated with dietary supplements. 2 ., (© 2018 Her Majesty the Queen in Right of Canada. Clinical Pharmacology & Therapeutics © 2018 ASCPT Reproduced with the permission of the Minister of Health.)

The National Toxicology Program's (NTP) mission is "to evaluate agents of public health concern, by developing and applying the tools of modern toxicology and molecular biology." Botanical dietary supplements (BDS) represent agents of public health concern due to widespread exposure to high doses, a lack of safety data for most products, variable quality, and reports of adverse events. This commentary will address lessons learned in NTP testing activities with BDS and recommendations for moving forward., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

Exposure to botanicals in dietary supplements is increasing across many geographies; with increased expectations from consumers, regulators, and industry stewards centered on quality and safety of these products. We present a tiered approach to assess the safety of botanicals, and an in silico decision tree to address toxicity data gaps. Tier 1 describes a Threshold of Toxicologic Concern (TTC) approach that can be used to assess the safety of conceptual levels of botanicals. Tier 2 is an approach to document a history of safe human use for botanical exposures higher than the TTC. An assessment of botanical-drug interaction (BDI) may also be necessary at this stage. Tier 3 involves botanical chemical constituent identification and safety assessment and the in silico approach as needed. Our novel approaches to identify potential hazards and establish safe human use levels for botanicals is cost and time efficient and minimizes reliance on animal testing., (© 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: We describe the purpose of the Dietary Supplement Ingredient Database (DSID), the statistical methodology underlying online calculators of analytically verified supplement content estimates, and the application and significance of DSID label adjustments in nutritional epidemiology., Background and History: During dietary supplement (DS) manufacturing, many ingredients are added at higher than declared label amounts, but overages are not standardized among manufacturers. As a result, researchers may underestimate nutrient intakes from DSs. The DSID provides statistical tools on the basis of the results of chemical analysis to convert label claims into analytically predicted ingredient amounts. These adjustments to labels are linked to DS products reported in NHANES., Rationale: Tables summarizing the numbers of NHANES DS products with ingredient overages and below label content show the importance of DSID adjustments to labels for accurate intake calculations., Recent Developments: We show the differences between analytically based estimates and labeled content for vitamin D, calcium, iodine, caffeine, and omega-3 (n-3) fatty acids and their potential impact on the accuracy of intake assessments in large surveys. Analytical overages >20% of label levels are predicted for several nutrients in 50-99% of multivitamin-mineral products (MVMs) reported in NHANES: for iodine and selenium in adult MVMs, for iodine and vitamins D and E in children's MVMs, and for iodine, chromium, and potassium in nonprescription prenatal MVMs. Predicted overages of 10-20% for calcium can be applied to most MVMs and overages >10% for folic acid in the vast majority of adult and children's MVMs., Future Directions: DSID studies are currently evaluating ingredient levels in prescription prenatal MVMs and levels of constituents in botanical DSs., Conclusions: We estimate that the majority of MVM products reported in NHANES have significant overages for several ingredients. It is important to account for nonlabeled additional nutrient exposure from DSs to better evaluate nutritional status in the United States., (© Crown copyright 2018.)

Until a decade ago, no dietary supplement (DS) databases with open access for public use existed in the United States. They were needed by researchers, since half of American adults use dietary DSs and, without information on supplement use and composition, exposures could not be estimated. These articles on Challenges and Future Directions for Dietary Supplement Databases describe subsequent progress. They begin by describing why information on DSs is needed by the government and how it is used to ensure the health of the public. Current developments include: application of DS information to meet public health needs; research efforts on DS quality, efficacy, and safety (as conducted by the Office of Dietary Supplements and other federal agencies); enhanced regulatory activities implemented by the FDA Office of Dietary Supplement Programs, the FDA Office of Enforcement, and the Federal Trade Commission; and initiatives for broader development and dissemination of DS databases for commercial and public use. Other contributions in this journal supplement describe the challenges of working with DSs and the progress that has been made. Additional articles describe surveys of DS use among the general US population and also among special groups such as high supplement users, illustrating why there is a need in the United States for information on supplements. Likely directions for the future of DS science are summarized., (© Crown copyright 2018.)

Current evidence shows that cholesterol management either reduces the likelihood of cardiovascular disease (CVD) or slows down its progression. Hence, it is important that all health professionals make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and positive lifestyle changes to the use of functional foods, food supplements, and drugs. This review examines the effect of the most frequently occurring cholesterol-lowering substances in functional foods or in supplements across Europe, namely plant sterols and stanols, monacolin K found in red yeast rice, berberine and beta-glucans. We conclude that currently available supplements and functional foods can effectively reduce plasma LDL cholesterol levels by about 5 to 25%, either alone or in combination. Suitable candidates for these products are mainly individuals at low absolute cardiovascular risk at a young age or according to classic algorithms. Of note, despite being freely available for purchase, these products should be used following shared agreement between the physician and the patient ("concordance")., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The Dietary Supplement Label Database (DSLD) is sponsored by the Office of Dietary Supplements (ODS) and the National Library of Medicine (NLM). It provides a searchable, free database of the contents of ∼65,000 supplement labels. A companion database of analytically verified product labels [the Dietary Supplement Ingredient Database (DSID)] was created by ODS, NLM, and the USDA. There are considerable challenges to populating both databases, but the DSID faces unique analytic chemistry challenges. This article describes the challenges to creating analytically verified marketplace surveys of dietary supplement (DS) product content claims for inclusion in public databases. Nutritionists and public health scientists require information on actual exposures to DS constituents because labeled content may not match labeled product content. Analytic verification of composition of DSs provides a link to actual exposure. A public database of analytically derived DS content was developed to provide more accurate estimates of dietary intake in population-based epidemiologic studies. The DSID has conducted surveys of several types of vitamin- and mineral-containing DSs. Results showing label content claims as analytically derived values are available in the current DSID. A recent pilot project explored the feasibility of adding botanical DS products to the DSID. Candidates for future botanical DSID studies will be based on sales volume, potential public health impacts, and the availability of validated analytic methods and reference materials. Databases like DSID and the DSLD are essential for researchers and clinicians to evaluate dietary ingredient intakes in population-based epidemiologic studies. Together, these databases provide a picture of the DS marketplace. The DSID provides an analytic survey of marketed DSs. However, selection of future botanical supplements for DSID evaluation involves analytic challenges. Even when appropriate resources are available, method selection and data evaluation are resource- and time-consuming., (© Crown copyright 2018.)

Background: Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In the year 2017 alone, 2082 articles were published under the key words 'sport nutrition'. Consequently, staying current with the relevant literature is often difficult., Methods: This paper is an ongoing update of the sports nutrition review article originally published as the lead paper to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a well-referenced overview of the current state of the science related to optimization of training and performance enhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy and performance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements are legally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value of various dietary and supplemental approaches., Conclusions: This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.

This work aims at giving an updated picture of the strict interaction between main plant biologically active compounds and botanicals. The main features of the emerging class of dietary supplements, the botanicals, are highlighted. Focus is also on the definition of actual possibilities of study approach and research strategies. Examples of innovative directions are given: assessment of interaction of bioactive compounds, chemometrics and the new goal of biorefineries. Current models of existing databases, such as plant metabolic pathways, food composition, bioactive compounds, dietary supplements, and dietary markers, are described as usable tools for health research. The need for categorization of botanicals as well as for the implementation of specific and dedicated databases emerged, based on both analytical data and collected data taken from literature throughout a harmonized and standardized approach for the evaluation of an adequate dietary intake., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Nutraceuticals containing collagen peptides, vitamins, minerals and antioxidants are innovative functional food supplements that have been clinically shown to have positive effects on skin hydration and elasticity in vivo. In this study, we investigated the interactions between collagen peptides (0.3-8 kDa) and other constituents present in liquid collagen-based nutraceuticals on normal primary dermal fibroblast function in a novel, physiologically relevant, cell culture model crowded with macromolecular dextran sulphate. Collagen peptides significantly increased fibroblast elastin synthesis, while significantly inhibiting release of MMP-1 and MMP-3 and elastin degradation. The positive effects of the collagen peptides on these responses and on fibroblast proliferation were enhanced in the presence of the antioxidant constituents of the products. These data provide a scientific, cell-based, rationale for the positive effects of these collagen-based nutraceutical supplements on skin properties, suggesting that enhanced formation of stable dermal fibroblast-derived extracellular matrices may follow their oral consumption.

Dietary supplements in many countries such as the USA do not require registration prior to commercialization. The Agência Nacional de Vigilância Sanitária (ANVISA) registers substances with functional properties as foods. Lutein is a carotenoid with antioxidant activity available on the market. However, no regulatory mandates exist to govern the design of quality control tests, which are necessary to ensure formulation effectiveness. Therefore, in the present study, tablet and dosage formulations from different manufacturers were tested following general methods outlined in the Brazilian and American Pharmacopeias. The averageweight, disintegration, content and dose uniformity assays were performed for all tablets and capsules, whereas hardness assays were only performed on tablets. None of the 10 formulations studied were found to be of satisfactory quality. Of all tablets tested, two had no-significant available lutein content, which may indicate adulteration. The capsules displayed adequate amounts of lutein, however had alarmingly negative disintegration and dissolution test results, which may contribute to non-bioavailability of lutein. All formulations analyzed are currently being marketed in the Brazilian and American markets. The low physicochemical performance in these formulations can be explained by the lack of specific regulations, which are necessary to ensure the quality of lutein-containing products on the market.

The objective of the study was to develop a self-microemulsifying drug delivery system (SMEDDS), also known as microemulsion preconcentrate, for oral delivery of five poorly water-soluble nutraceuticals or bioactive agents, namely, vitamin A, vitamin K2, coenzyme Q 10 , quercetin and trans-resveratrol. The SMEDDS contained a 1:1 mixture (w/w) of Capmul MCM NF (a medium chain monoglyceride) and Captex 355 EP/NF (a medium chain triglyceride) as the hydrophobic lipid and Tween 80 (polysorbate 80) as the hydrophilic surfactant. The lipid and surfactant were mixed at 50:50 w/w ratio. All three of the SMEDDS components have GRAS or safe food additive status. The solubility of nutraceuticals was determined in Capmul MCM, Captex 355, Tween 80, and the SMEDDS (microemulsion preconcentrate mixture). The solubility values of vitamin A palmitate, vitamin K2, coenzyme Q 10 , quercetin, and trans-resveratrol per g of SMEDDS were, respectively, 500, 12, 8, 56, and 87 mg. Appropriate formulations of nutraceuticals were prepared and filled into hard gelatin capsules. They were then subjected to in vitro dispersion testing using 250 mL of 0.01 N HCl in USP dissolution apparatus II. The dispersion test showed that all SMEDDS containing nutraceuticals dispersed spontaneously to form microemulsions after disintegration of capsule shells with globule size in the range of 25 to 200 nm. From all formulations, except that of vitamin K2, >80-90% nutraceuticals dispersed in 5-10 min and there was no precipitation of compounds during the test period of 120 min. Some variation in dispersion of vitamin K2 was observed due to the nature of the material used (vitamin K2 pre-adsorbed onto calcium phosphate). The present report provides a simple and organic cosolvent-free lipid-based SMEDDS for the oral delivery of poorly water-soluble nutraceuticals. Although a 50:50 w/w mixture of lipid to surfactant was used, the lipid content may be increased to 70:30 without compromising the formation of microemulsion.

Chronic kidney disease (CKD) is a very common disorder in elderly cats. A proper renal diet represents the most efficient therapeutic intervention to improve survival and life quality in feline patients with 3 and 4 International Renal Interest Society (IRIS) stages. Twenty cats were selected in this study. Ten were administered the dietary supplementation for 360 days and the other ten, whose owners did not give consent for any supplemental therapies apart from the renal diet, were selected from a clinical database and used as control group. The present study is a long term study (360 days) aiming to evaluate the efficacy and palatability of a dietary supplementation containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in cats diagnosed with 3 and 4 IRIS stages of CKD. The owners were asked to fill in questionnaires to get information on the cat's appetite, the palatability of the given supplement, the presence of vomit and/or diarrhoea, general health and vitality. Hematochemical, biochemical and urinary analyses were performed on day 0, 30, 60, 90, 120, 150,180 and 360. GraphPad Prism® software was used to perform statistical analysis. Our study shows that the given dietary supplement reduced serum phosphorus and increased serum bicarbonate values in cats with CKD. In turn, this supplement could be used as a support therapy in cats with advanced CKD improving their clinical conditions without any adverse reaction. Finally, it is important to underline that all the animals completed the study and the owners reported a good palatability of the feed supplement.

Background: Malnutrition is a significant problem in those undergoing peritoneal dialysis (PD). Factors such as gastrointestinal (GI) symptoms and the need for a fluid reduced diet can limit tolerance and thereby the efficacy of oral nutritional supplements to treat malnutrition., Objectives: To evaluate the acceptability and impact of two different forms of oral nutrition supplementation for 16 weeks on nutritional markers and quality of life of malnourished patients undergoing PD., Design: A randomised, within-subject cross-over study. Patients assessed as malnourished or with serum albumin <35 g/l were recruited. Participants were randomised to receive either 200 ml of a 1.25 kcal/ml nutrition supplement or a high protein nutrition supplement bar, for eight weeks. Each group then crossed over to receive the alternative supplement for eight weeks. Total intervention time was 16 weeks. Serum albumin, serum transthyretin and food intake were evaluated at baseline, at 8 and 16 weeks. Subjective Global Assessment, the presence of GI symptoms and quality of life were evaluated at baseline and 16 weeks., Results: Sixteen weeks of nutritional support was associated with statistically significant improvements in weight and a reduction in the proportion of patients who were malnourished. There was no difference in the impact of bars compared with liquid oral nutrition supplementation. Patients preferred the fluid supplement to the bars., Conclusion: Sixteen weeks of nutritional support improved nutritional status in malnourished patients on PD., (© 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Background: In order to define appropriate quality of botanical dietary supplements, botanical drugs, and herbal medicines, the United States Pharmacopeia (USP) and the Herbal Medicines Compendium (HMC) contain science-based quality standards that include multiple interrelated tests to provide a full quality characterization for each article in terms of its identity, purity, and content., Purpose: To provide a comprehensive description of the pharmacopeial tests and requirements for articles of botanical origin in the aforementioned compendia. Selective chromatographic procedures, such as high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC), are used as Identification tests in pharmacopeial monographs to detect species substitution or other confounders. HPLC quantitative tests are typically used to determine the content of key constituents, i.e., the total or individual amount of plant secondary metabolites that are considered bioactive constituents or analytical marker compounds. Purity specifications are typically set to limit the content of contaminants such as toxic elements, pesticides, and fungal toxins. Additional requirements highlight the importance of naming, definition, use of reference materials, and packaging/storage conditions., Methods: Technical requirements for each section of the monographs were illustrated with specific examples. Tests were performed on authentic samples using pharmacopeial reference standards. The chromatographic analytical procedures were validated to provide characteristic profiles for the identity and/or accurate determination of the content of quality markers., Results: The multiple tests included in each monograph complement each other to provide an appropriate pharmacopeial quality characterization for the botanicals used as herbal medicines and dietary supplements. The monographs provide detailed specifications for identity, content of bioactive constituents or quality markers, and limits of contaminants, adulterants, and potentially toxic substances. Additional requirements such as labeling and packaging further contribute to preserve the quality of these products., Conclusion: Compliance with pharmacopeial specifications should be required to ensure the reliability of botanical articles used for health care purposes., (Copyright © 2018. Published by Elsevier GmbH.)

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.

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.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Food supplements in Europe are subject to food safety legislation. They should not be confused with pharmaceuticals. Rather, they are foods, whose purpose is to supplement the normal diet, and represent concentrated sources of nutrients (i. e. vitamins and minerals, including trace elements) or other substances with a nutritional or physiological effect. Nevertheless, it should be kept in mind that consumers may in some cases use food supplements for the purpose of self-medication. In the context of anamnesis, physicians should specifically question their patients about the use of food supplements. This can be of significant relevance for evaluation of possible undesirable or adverse effects, influences on laboratory parameters, or interactions with pharmaceuticals, which may be due to consumption of certain products that are marketed as food supplements. Furthermore, education of patients with respect to the possible benefits and risks related to the use of vitamins, minerals and other constituents of food supplements should be intensified., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

OA is a chronic and disabling joint disease with limited evidence-based pharmacological treatment options available that improve outcomes for patients safely. Faced with few effective pharmacological treatments, the use has grown of dietary supplements and complementary medicines for symptomatic relief among people living with OA. The aim of this review is to provide a summary of existing evidence and recommendations supporting the use of supplements for OA. Systematic reviews and randomized controlled trials investigating oral supplements for treating OA were identified. Limited research evidence supports recommendations for the oral use of Boswellia serrata extract and Pycnogenol, curcumin and methylsulfonylmethane in people with OA despite the poor quality of the available studies. Few studies adequately reported possible adverse effects related to supplementation, although the products were generally recognized as safe. Further high quality trials are needed to improve the strength of evidence to support this recommendation and better guide optimal treatment of people living with OA.

A growing population and concern over the sufficiency of natural resources for feeding this population have motivated researchers and industries to search for alternative and complementary sources of food ingredients and additives. Numerous plant species and parts of plants are explored as raw materials for food production. An interesting example is wood; to date, only a few wood-based additives or ingredients are authorized for food use. Wood hemicelluloses, such as softwood galactoglucomannans (GGM), constitute an abundant bioresource that shows a high potential functionality in edible materials. Spruce GGM acts as a multi-functional emulsion stabilizer, and it could be used in various processed food products, replacing less effective, conventional emulsifiers. Before new materials can be released into the food market, their safety must be evaluated, according to the Novel Food regulation. This review focuses on the safety aspects that must be considered before polysaccharide- and phenolic-rich plant extracts can be awarded the status of authorized food ingredients. In this review, GGM is presented as a case study and examples are given of plant-based polysaccharides that are already authorized for food purposes. The legislation regarding Novel Food ingredients in Europe is also briefly reviewed.

Dietary supplements are a global business worth more than US$100 billion annually. These supplements are taken by up to 50% of adults and perhaps one-third of children in economically advanced economies. Definitions of dietary supplements differ from country to country, and regulation is generally lax and often seems to be directed more toward promoting commerce than protecting public health. Supplements may directly cause toxic reactions or may interact with other supplements or pharmaceuticals. Some supplements are found to have been contaminated with heavy metals, and others do not contain the expected quantities of active ingredients. In general, supplements are not needed except in cases of established deficiencies, and excess of some nutrients can increase cancer rates. There are important public health reasons for taking some supplements, including folate and iodine in pregnancy. This review discusses the public health concerns associated with dietary supplements and suggests directions for further regulation.

Currently, nutraceuticals do not have a specific definition distinct from those of other food-derived categories, such as food supplements, herbal products, pre- and probiotics, functional foods, and fortified foods. Many studies have led to an understanding of the potential mechanisms of action of pharmaceutically active components contained in food that may improve health and reduce the risk of pathological conditions while enhancing overall well-being. Nevertheless, there is a lack of clear information and, often, the claimed health benefits may not be properly substantiated by safety and efficacy information or in vitro and in vivo data, which can induce false expectations and miss the target for a product to be effective, as claimed. An officially shared and accepted definition of nutraceuticals is still missing, as nutraceuticals are mostly referred to as pharma-foods, a powerful toolbox to be used beyond the diet but before the drugs to prevent and treat pathological conditions, such as in subjects who may not yet be eligible for conventional pharmaceutical therapy. Hence, it is of utmost importance to have a proper and unequivocal definition of nutraceuticals and shared regulations. It also seems wise to assess the safety, mechanism of action and efficacy of nutraceuticals with clinical data. A growing demand exists for nutraceuticals, which seem to reside in the grey area between pharmaceuticals and food. Nonetheless, given specific legislation from different countries, nutraceuticals are experiencing challenges with safety and health claim substantiation., (© 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Given the expanding market of plant food supplements (PFSs) not undergoing any pre-marketing authorization, the overall quality, safety and efficacy of PFSs were subjected to a critical examination. Although many high-quality PFSs exist on the legal market, quality concerns are in general justified. Besides economic adulteration, active ingredients dramatically differing from label claims and among products were reported in several studies. In addition, PFSs sold via the Internet may be intentionally adulterated with undeclared prescription drugs. Compared to PFSs with only one single herb, PFSs containing herbal mixtures were more involved in moderate and severe clinical courses. Although prohibited by regulation, misleading labels on PFSs are common. Above all, only vague evidence for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and insufficient safety assessment, PFSs represent a relevant source for consumers to get access to herbal preparations in the United States and meanwhile also in Europe, as launching of licensed/registered European herbal medicinal products (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products, PFSs are neither food nor drugs. In terms of protecting public health and providing the consumer with high-quality, effective, and safe PFSs, possibilities are shown how to deal with the many challenges of PFSs. Last but not least, suggestions are made for assigning PFSs a separate regulatory category being less regulated compared to HMPs but more strictly regulated compared to food laws including implementation of good manufacturing practices and a scientific pre-marketing review process by an expert commission., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

This study examined the effect of zinc supplementation on the sleep quality (SQ) of intensive care unit (ICU) nurses. In a double-blind, randomized controlled trial, 54 ICU nurses were randomly assigned to the intervention group ( n = 27) that received 220 mg zinc sulfate capsules every 72 hours for 1 month and the control group ( n = 26) that received placebo. Sleep quality of ICU nurses was measured by calculating the total quality sleep score using the Pittsburgh Sleep Quality Index (PSQI). The serum zinc level was a secondary outcome. All measurements were calculated at both baseline and 1 month after intervention. The total PSQI, subjective SQ, and sleep latency scores for the intervention group were significantly lower than the control group, which means that the SQ of ICU nurses in the intervention group improved from baseline. The serum zinc level of the intervention group at the end of the study was significantly higher than the control group, which means that zinc supplementation improved participants' serum zinc level. Based on these findings, the researcher suggested that zinc supplementation could be associated with better SQ, subjective SQ, and sleep latency in this group of workers.

As the population in the industrialized world develops preference for what is perceived as a natural and holistic way of disease treatment, the popularity and the number of food supplements on the market, including herbal ones, is experiencing an unprecedented rise. However, unlike herbal medicinal products, intended for treating or preventing disease, current legislation classifies food supplements as products intended for achieving nutritional or physiological effect and to supplement the normal diet. Accordingly, most food supplements are not to be associated with specific health claims. However, either due to the subtle suggestions by the producers or the wishful thinking of the consumers, certain pharmacological effects from food supplements are often expected. Medicinal plants included in food supplements usually do not produce dramatic and instant pharmacological effects. Therefore, in order to meet the expectation of their customers, some producers have turned to the illicit and dangerous practice of adulterating their products with synthetic adulterants, including naturally occurring molecules, having the desired activity. Such practice is prevalent in, although not limited to, food supplements intended for use as weight-loss aids, as well as for sport performance and libido enhancement. The review is focusing on naturally occurring alkaloids, phenylethanolamines, and their semi-synthetic derivatives in food supplements in the European Union as reported by the Rapid Alert System for Food and Feed. Their desired and undesired pharmacological effects, as well as the methods for their detection and quantification in food supplements, will be reviewed., Competing Interests: The author has no conflict of interest to declare., (Georg Thieme Verlag KG Stuttgart · New York.)

Background The use of oral complementary and alternative medicines, including herbal supplements, has been increasing in pregnant women worldwide despite limited safety data. The decision of healthcare professionals to recommend these products to pregnant patients is controversial and not well documented. Objective To explore the recommendations and information sources that healthcare professionals use to determine the safety of oral non-prescribed supplements during pregnancy. Setting An Australian metropolitan maternity hospital. Method An electronic survey was distributed to doctors, midwives, pharmacists, dietitians, lactation consultants and physiotherapists. Main outcome measure The nature of recommendations and information sources that healthcare professionals use to determine the safety of oral non-prescribed supplements during pregnancy. Results Responses were received from 54 healthcare professionals. Forty of 54 (74.1%) were concerned about the safety of their patients' supplements, while 35 of 54 (64.8%) felt that they had access to trustworthy safety information. Supplements most commonly recommended as safe to use were ginger (40.7%), probiotics (29.6%) and raspberry leaf (22.2%). Participants specifically requested further safety information for raspberry leaf, evening primrose oil, fish oil, probiotics, ginger, vitamin C, valerian, turmeric, blue cohosh and colloidal silver. Written resources most frequently consulted included MIMS ® (61.1%) and 'Google Searches' (29.6%), and healthcare professionals most referred to were pharmacists (74.1%), doctors (22.2%), and naturopaths or herbalists (3.7%). Conclusion The recommendations of maternity heath care professionals and quality of information sources used varied. Further education and access to unbiased safety information is required to empower healthcare professionals to provide informed recommendations to pregnant patients.

The aim of this study was to prove whether Ginkgo biloba food supplements on the European market comply with pharmaceutical quality, and whether their composition satisfies the European Pharmacopoeia criteria. Medicinal products containing a standardised Ginkgo leaf extract are used for the improvement of cognitive impairment and quality of life in mild dementia. Further, Ginkgonis folium is used for the treatment of peripheral circulation disorders. Pharmacopoeial Ginkgo dry extract contains 22.0 - 27.0% flavonoids and 5.4 - 6.6% terpene lactones (ginkgolides, bilobalide). In addition to its widespread use as an herbal medicine (herbal medicinal product), the same extract can be an ingredient in food supplements. The content of active secondary metabolites was quantified in a number of European food supplements containing Ginkgo dry extract or Ginkgo leaf. Flavonoids were quantified using a modified pharmacopoeial HPLC-UV method, and terpene lactones (ginkgolides A, B, C, and bilobalide) using LC-MS/MS. Some Ginkgo leaf supplement samples were also analysed by microscopy. The quality of food supplements on the European market is dubious. In this paper, we present selected examples of several methods of adulteration and falsification, including higher/lower doses of Ginkgo dry extract or Ginkgo leaf than declared and the addition of undeclared extraneous materials. These examples reveal several patterns in the manufacturing of adulterated products., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Nowadays herbal products used in traditional medicine are sold in processed forms and thus morphological authentication is almost impossible. With herbal industry rapidly growing size, consumer safety becomes an important issue that requires special attention. Identification of herbal species in the products is therefore needed., Methods: Sequences from the selected regions (matK, rbcL, trnL and ITS1) were retrieved and analysed. Then the most suitable barcode was assessed for discrimination of T. crispa from closely related species by HRM analysis and used in authentication of commercial products., Results: The ITS1 barcode was found to be the suitable primer as melting data from the HRM assay proved to be capable of distinguishing T. crispa from its related species. The developed protocol was then employed to authenticate medicinal products in powdered form. HRM analysis of all tested samples here revealed that five out of eight products contained not only the indicated species T. crispa but also other Tinospora, that have a high level of morphological similarity., Conclusion: Misrepresentation, poor packaging and inappropriate labeling of the tested medicinal herbal products are thought to be the reason of the results here. Using Bar-HRM with the ITS marker lead to success in authenticating the tested herbal products.

Background: People undergoing haemodialysis (HD) often have poor nutrition, which in turn can contribute to worse outcomes. Inadequate nutrition has a particularly deleterious effect on growth and neurocognitive development, as well as mortality, in children and adolescents. Nutritional supplementation can improve outcomes but can be difficult to administer., Objective: Determine the tolerability of intradialytic oral nutrition in children and adolescents., Design: A cross-sectional quality improvement study in an outpatient paediatric HD unit. Intervention was intradialytic oral nutritional supplementation provided as protein bars and/or meals., Subjects: Children and adolescents undergoing outpatient HD who were able to participate in surveys and eat by mouth., Measurements: Adverse effects and symptoms on nurse- and patient-reported surveys, respectively. Relationships between the predictor variables and the outcomes were assessed using generalised estimating equations., Results: The majority of children felt better after eating on dialysis (72%) with no adverse effects (80%). On unadjusted analyses and confirmed with generalised estimating equation modelling, children who reported being hungry felt better after eating on dialysis, despite being more likely to have adverse effects., Conclusion: The study demonstrates that our children and adolescents feel better after eating on HD with minimal adverse effects. The finding that hungry patients are more likely to feel better despite having a higher likelihood of an adverse effect demonstrates the tolerability of eating on HD. Intradialytic oral nutrition could be a safe and well-tolerated opportunity to provide supplemental nutrition to paediatric HD patients and improve outcomes., (© 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these foods/food components have been the object of a request of authorization for use of health claims under Articles 13(5) or 14 of the Regulation (EC) 1924/2006. Most of these requests have received a negative opinion from the European Food Safety Authority (EFSA) due to the choice of inappropriate outcome variables (OVs) and/or methods of measurement (MMs) applied in the studies used to substantiate the claims. This manuscript refers to the collection, collation and critical analysis of OVs and MMs related to vision. Guidance document and requests for authorization of health claims were used to collect OVs and MMs related to vision. A literature review was performed to critically analyse OVs and MMs, with the aim of defining their appropriateness in the context of a specific claimed effect related to vision. The results highlight the importance of adequate choices of OVs and MMs for an effective substantiation of claims related to visual function., Competing Interests: The authors declare no conflict of interest.

Siberian ginseng (Eleutherococcus senticosus, Araliaceae) and roseroot (Rhodiola rosea, Rosaceae) are popular herbal supplements which have been shown to improve resilience to conditions such as stress and exhaustion. Using DNA barcoding methods we tested 25 Siberian ginseng and 14 roseroot products which are widely available to UK customers to test whether the herbal ingredient stated on the label is also in the product. All Siberian ginseng supplements contained E. senticosus, however, 36% also contained an Eleutherococcus species other than E. senticosus. In three out of the 13 roseroot products which produced amplifiable DNA, we could only retrieve sequences matching alfalfa (declared on the product label) and fenugreek (not declared). In the other 10 supplements Rhodiola was detected but only five matched the target species R. rosea. As DNA can get severely degraded during the manufacturing process we did not take the absence of Rhodiola DNA as proof for a compromised product. Contamination could explain the presence of non-target species such as fenugreek but is unlikely to be account for the detection of congeneric Rhodiola species in roseroot preparations. Our results therefore suggest that the substitution or mixing of the target medicinal ingredient in these two popular supplements with other species is common., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background The purchase of dietary supplements (DS) via the Internet is increasing worldwide as well as in the Czech Republic. Objective The aim of the study is to evaluate the quality of information on DS available on the Internet. Setting Czech websites related to dietary supplements. Methods A cross-sectional study was carried out involving the analysis of information placed on the websites related to the 100 top-selling DS in the Czech Republic in 2014, according to IMS Health data. Main outcome measure The following criteria were evaluated: contact for the manufacturer, recommended dosage, information on active substances as well as overall composition, permitted health claims, % of the daily reference intake value (DRIV) for vitamins and minerals, link for online counseling, pregnancy/breastfeeding, allergy information, contraindications, adverse reactions, and supplement-drug interactions (some criteria were evaluated from both points of view). Results A total of 199 web domains and 850 websites were evaluated. From the regulatory point of view, all the criteria were fulfilled by 11.3% of websites. Almost 9% of the websites reported information referring to the treatment, cure, or prevention of a disease. From the clinical point of view, all the criteria were only met by one website. Conclusions The quality of information related to DS available on the Internet in the Czech Republic is quite low. The consumers should consult a specialist when using DS purchased online.

Objective: to increase understanding of psychosocial factors (behavioural, normative and control beliefs) motivating vitamin and mineral supplement use during pregnancy., Design: ten focus group discussions and two in-depth interviews were conducted using a script comprising questions based on study objectives. All discussions were recorded, transcribed verbatim and analysed using a framework approach., Setting: South Australia, Australia., Subjects: 40 women aged 21-45 years who were either pregnant or<12 months postpartum. Groups were stratified by education level (secondary education only vs. post-secondary) and gravidity (first vs. subsequent pregnancy)., Results: all women, except one, used dietary supplements during pregnancy. Most women took supplements to achieve peace of mind knowing that nutrient requirements were 'definitely' being met. Other common factors motivating supplement use were the beliefs that supplementation: benefits maternal and fetal health; corrects known nutritional deficiencies; and is a more efficient method of obtaining required nutrients relative to food. Advice received from healthcare providers and marketing of supplements also motivated supplementation, while forgetting to take supplements was the most common barrier to use. Cost was only a barrier when considering whether or not to continue supplementation post-birth., Key Conclusions and Implications for Practice: women believe that supplements are an easier and more reliable source of nutrients than food intake alone, and rely on dietary supplementation as an insurance policy during pregnancy. Further studies are needed in larger and more representative samples to validate these findings and to test the effectiveness of information and intervention strategies targeting appropriate supplement use during pregnancy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them., Competing Interests: Johanna T. Dwyer holds stock in several food and drug companies, and serves on the scientific advisory boards of Conagra Foods, McCormick Spices, and as a consultant for Gerber/Nestle. She accepted partial travel and per diem expenses to speak at a symposium on dietary supplements sponsored by the International Association of Dietary/Food Supplement Associations at the International Congress of Nutrition in Buenos Aires, Argentina in October 2017. Michael J. Smith holds stock in several food and drug companies as well as acting as a consultant with clients in both the private and public sector including companies in dietary supplement and natural health products sector. He sits on the scientific advisory board of ISURA and the advisory board of the American Botanical Council. Paul M. Coates reports no conflicts of interest.

Background and Objective: Extra virgin olive oil (EVOO) is the common element among the Mediterranean countries. It can be considered a nutraceutical and functional food, thanks to its bioactive compounds. It can act and modulate different processes linked to ageing and age-related diseases related to a common chronic low grade inflammation. Depending on the cultivar, the growth conditions, the period of harvesting, the productive process and time of product storage, EVOO could contain different amount of vegetal components. Of course, the same is for table olives., Methods: The aim of our review is to summarize the effects of EVOO and table olives on the immunemediated inflammatory response, focusing our attention on human studies., Results: Our report highlights the effect of specific molecules obtained from EVOO on the modulation of specific cytokines and anti-oxidants suggesting the importance of the daily consumption of both EVOO and table olives in the context of a Mediterranean dietary pattern. In addition, the different action on immune-inflammatory biomarkers, are depending on the olive tree cultivar., Conclusion: Thanks to their bioactive compounds, EVOO and table olive can be considered as nutraceutical and functional foods. The beneficial effects analysed in this review will help to understand the potential application of specific olive components as therapeutic adjuvant, supplements or drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To evaluate the effectiveness of vitamin D supplementation as protection factor against infection of patients with chronic kidney disease on conservative treatment., Method: Retrospective cohort study carried out between 2013 and 2016 in the Conservative Treatment Outpatient Clinics (Ambulatório de Tratamento Conservador) of the Hypertension and Kidney Hospital (Hospital do Rim e Hipertensão) of the Universidade Federal de São Paulo. Data on sociodemographic factors, comorbidity, infection episodes and use or nonuse of vitamin D supplementation for at least 6 months were collected from medical records. The primary outcomes considered in both groups were: presence or absence of infection anywhere on the body (bloodstream, urinary, respiratory and surgical sites)., Results: A total of 263 patients were included and those who received (n=43) vitamin D had 59% less chance of developing infections (OR=0.41; 95%CI; 0.15-0.99), when compared to those who did not receive., Conclusion: Vitamin D supplementation was a protective factor against infections of all causes.

Context: With the increasing use of unregulated dietary supplements, athletes are at continued risk from adverse medical events and inadvertent doping., Evidence Acquisition: A review of Clinical Key, MEDLINE, and PubMed databases from 2012 to 2017 was performed using search terms, including dietary supplement, contamination, doping in athletes, inadvertent doping, and prohibited substances. The references of pertinent articles were reviewed for other relevant sources., Study Design: Clinical review., Level of Evidence: Level 3., Results: Poor manufacturing processes and intentional contamination with many banned substances continue to occur in dietary supplements sold in the United States. Certain sectors, such as weight loss and muscle-building supplements, pose a greater threat because they are more likely to be contaminated., Conclusion: Athletes will continue to be at risk for adverse events and failed doping tests due to contaminated dietary supplements until legislation changes how they are regulated. In the interim, there are several steps that can be taken to mitigate this risk, including improved education of medical staff and athletes and use of third party-certified products.

Background and Objective: Atherosclerosis is characterized by a chronic low-grade inflammatory process which can result in atherothrombosis and a number of cardiovascular diseases (CVD). It is believed to be caused by multiple processes that involve inflammation and immunity. Mediterranean Diet (MedD) has been discovered to possess anti-inflammatory properties and associated with a reduction in the CVD risk and mortality. Its main component, extra-virgin olive oil (EVOO), is believed to be largely responsible for these effects and therefore, has been investigated in various studies. The present review article aims to summarize the available literature on the antiinflammatory and cardio-protective effects of EVOO., Methods: A search based on the key concepts "olive oil", "atherosclerosis", "inflammation" and "cardiovascular disease" was performed to retrieve relevant studies and articles on the association between the consumption of EVOO and the levels of inflammatory biomarkers as well as CVD incidence and mortality from online databases; Pubmed, Embase and Cochrane Library., Results: Consumption of EVOO is associated with a reduction in inflammatory biomarkers and molecules implicated in atherosclerosis as well as CVD incidence and mortality as well as other complications such as heart failure and atrial fibrillation. Moreover, these anti-inflammatory and cardioprotective effects of EVOO are mostly attributable to its high content of polyphenol molecules., Conclusion: Currently available evidence supports the anti-inflammatory and cardio-protective roles of EVOO. However, there is limited amount of available randomized controlled trials especially lacking those investigating the use of EVOO as secondary prevention, heterogeneity of study design, limited generalization to wide population groups, and inability to determine the minimum intake of EVOO required to clinically achieve the anti-inflammatory and cardioprotective effects. Therefore, more highquality randomized controlled trials still need to be carried out to overcome these challenges to further assess the health benefits of EVOO consumption and potentially translate it into clinical practice as primary or secondary prevention of atherosclerosis-related conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Interest in vegetarian diets is growing in Italy and elsewhere, as government agencies and health/nutrition organizations are emphasizing that regular consumption of plant foods may provide health benefits and help prevent certain diseases., Methods and Results: We conducted a Pubmed search, up to September, 2015, for studies on key nutrients (proteins, vitamin B12, iron, zinc, calcium, vitamin D, and n-3 fatty acids) in vegetarian diets. From 295 eligible publications the following emerged: Vegetarians should be encouraged to supplement their diets with a reliable source of vitamin B12 (vitamin-fortified foods or supplements). Since the plant protein digestibility is lower than that of animal proteins it may be appropriate for vegetarians to consume more proteins than recommended for the general population. Vegetarians should also be encouraged to habitually consume good sources of calcium, iron and zinc - particularly vegetables that are low in oxalate and phytate (e.g. Brassicaceae), nuts and seeds, and calcium-rich mineral water. Calcium, iron, and zinc bioavailability can be improved by soaking, germination, and sour-dough leavening that lower the phytate content of pulses and cereals. Vegetarians can ensure good n-3 fatty acid status by habitually consuming good sources of a-linolenic acid (walnuts, flaxseeds, chia seeds, and their oils) and limiting linoleic acid intake (corn and sunflower oils)., Conclusions: Well-planned vegetarian diets that include a wide variety of plant foods, and a reliable source of vitamin B12, provide adequate nutrient intake. Government agencies and health/nutrition organizations should provide more educational resources to help Italians consume nutritionally adequate vegetarian diets., (Copyright © 2017. Published by Elsevier B.V.)

Background and Purpose: Despite achievement of optimal low-density lipoprotein cholesterol (LDL-C) control with statin therapy, patients with elevated triglycerides (TGs) and residual cardiovascular risk are commonly encountered in clinical practice., Methods: We present information from completed and ongoing clinical trials examining Rx omega-3s for TG-lowering and omega-3 dietary supplements to highlight important differences affecting patient management for nurse practitioners., Conclusions: Rx omega-3s demonstrate robust reductions in TGs and may have a role in reducing residual cardiovascular risk. Products containing docosahexaenoic acid (DHA) may raise LDL-C and should not be substituted for Rx eicosapentaenoic acid (EPA)-only icosapent ethyl, which does not raise LDL-C. Omega-3 dietary supplements (e.g., fish oils containing EPA and DHA) may be used for general health promotion; however, they are not regulated as medications and concerns regarding quality, purity, safety, and variability of content exist. It is important to advise patients that omega-3 dietary supplements are not medications and should not be substituted for Rx omega-3s. Large-scale cardiovascular outcomes studies are underway for Rx omega-3s in statin-treated patients., Implications for Practice: Nurse practitioners can take an active role in reducing residual cardiovascular risk and educating patients about important differences between Rx omega-3s and fish oil supplements., (©2017 American Association of Nurse Practitioners.)

The consumption of nutritional ergogenic aids is conditioned by laws/regulations, but standards/regulations vary between countries. The aim of this review is to explore legislative documents that regulate the use of nutritional ergogenic aids intended for sportspeople in a Spanish/European framework. A narrative review has been developed from official websites of Spanish (Spanish Agency of the Consumer, Food Safety, and Nutrition) and European (European Commission and European Food Safety Authority) bodies. A descriptive analysis of documents was performed. Eighteen legislative documents have been compiled in three sections: (1) Advertising of any type of food and/or product; (2) Composition, labeling, and advertising of foods; (3) Nutritional ergogenic aids. In spite of the existence of these legal documents, the regulation lacks guidance on the use/application of nutritional ergogenic aids for sportspeople. It is essential to prevent the introduction or dissemination of false, ambiguous, or inexact information and contents that induce an error in the receivers of the information. In this field, it is worth highlighting the roles of the European Food Safety Authority and the World Anti-Doping Agency, which provide information about consumer guidelines, prescribing practices, and recommendations for the prudent use of nutritional ergogenic aids., Competing Interests: The authors declare no conflict of interest.