Flavonoid-drug interactions: effects of flavonoids on ABC transporters

Flavonoids are present in fruits, vegetables and beverages derived from plants (tea, red wine), and in many dietary supplements or herbal remedies including Ginkgo Biloba, Soy Isoflavones, and Milk Thistle. Flavonoids have been described as health-promoting, disease-preventing dietary supplements, and a high intake of flavonoids has been associated with a reduced risk of cancer, cardiovascular diseases, osteoporosis and other age-related degenerative diseases. Due to an increased public interest in alternative medicine and disease prevention, the use of herbal preparations containing high doses of flavonoids for health maintenance has become very popular, raising the potential for interactions with conventional drug therapies. This review will summarize the current literature regarding the interactions of flavonoids with ATP-binding cassette (ABC) efflux transporters, mainly P-glycoprotein, MRP1, MRP2 and BCRP and discuss the potential consequences for flavonoid-drug transport interactions.     

Botanicals authentication in food,food supplements and herbal medicinal products

Nowadays, there is a constant increase of health products (food supplements, medical devices and so on), in the market, despite the crisis that involves a lot of nations at the international level. The plants and their derivatives are present in high percentage in these products and moreover people usually have great trust in plants and in natural products in general. The above-mentioned products are available in the market in the form of tablets, pills, lozenges, syrups and other forms that supplement our diet (food or dietary supplements) or act with a therapeutic effect (herbal medicines). In Italy, about 50% of the sold products contain plants and/or plant extracts, better known as botanicals according to the European Food Safety Authority settlement. It is therefore understandable how the botanicals adulteration and/or the sophistication can heavily weigh on the quality of the finished products, not only from an economic point of view but also in guaranteeing the safety of consumers.     

Risk Associated with the Use of Selected Ingredients in Food Supplements

This review focuses on four new product categories of food supplements: pre-workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to ‘camouflage’ stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti-Doping Agency.     

Proposed rule: current good manufacturing practice in manufacturing, packing, or holding dietary ingredients and dietary supplements

The Dietary Supplement Health and Education Act (DSHEA) was enacted in October 1994 to promote the health of Americans by ensuring easier access to safe dietary supplements. Many supplements such as vitamins, minerals, herbs and amino acids have been reported to be helpful in chronic conditions (i.e., heart disease, cancer and osteoporosis). Under DSHEA, dietary supplements can be marketed without prior FDA approval; the burden is on this agency to show that a marketed dietary supplement is unsafe. However, DSHEA retained the FDA's authority to issue regulations that require the manufacture of dietary supplements be in compliance with current good manufacturing practice (cGMP) standards, which are needed to ensure their quality. Several quality-related concerns of marketed dietary supplements that came to light since the passage of DSHEA prompted the FDA in 2003 to propose rules for cGMP for the manufacture, packaging and holding (storage) of dietary supplements. This review will present the highlights of these proposed rules, focusing on the legislative history of DSHEA, rationale for proposing cGMPs along with a general discussion of the specific requirements. Given the voluminous nature of the specific details, the reader is directed to the pertinent FDA publications for details. In this analysis, selected scientific and legal issues are also discussed to promote a better understanding and implications of these rules.     

Environmental Contaminants in the Botanical Dietary Supplement Ginseng and Potential Human Risk

Botanical dietary supplements have a long history of use in Europe and Asia, but the use of these products is becoming increasing popular in the United States. Because these products are classified as dietary supplements, the U.S. Food and Drug Administration does not routinely monitor them for environmental contaminants. Ginseng served as a model botanical dietary supplement and was purchased from suppliers in the United States, Europe, and Asia. Samples were analyzed for metals (e.g., cadmium, nickel) and chlorinated pesticides (e.g., PCNB, DDT, and metabolites). Flame and furnace atomic absorption spectrophotometry were utilized for analysis of metals, while gas chromatography (GC) and GC-mass spectrophotometry were utilized for analysis of chlorinated pesticides. Because no formalized guidelines exist to determine risk of botanical dietary supplements, U.S. Environmental Protection Agency guidelines for protection of human health were used. Metals and chlorinated organics were found in Ginseng samples, but the concentrations posed no noncarcinogenic hazard; however, a 1000?mg/d dose for 350?d/yr resulted in 1 × 10^?6 carcinogenic risk in 19% of the Ginseng samples analyzed. At a lower usage rate (42?d/yr), no samples exceeded 1 × 10^?6 risk. Chlorinated organics, such as aldrin and heptachlor epoxide, accounted for the carcinogenic risk (1 X 10-6) in the Ginseng samples.     

Improved screening of microcystin genes and toxins in blue-green algal dietary supplements with PCR and a surface plasmon resonance biosensor

Microcystins (MCs) comprise a group of cyclic heptapeptide toxins that share a common backbone and have two variable l-amino acids that yield at least 21 known analogs of varying potency. These hepatotoxins and potential tumor promoters are produced by certain cyanobacteria, including Microcystis aeruginosa. The cyanobacterium M. aeruginosa blooms in freshwater lakes and can potentially co-occur with other species such as Aphanizomenon flos-aquae, which is targeted and harvested for the production of dietary supplements known as blue-green algae (BGA). BGA supplements are currently marketed in the U.S. and internationally as a product that may elevate mood, increase energy, and alleviate attention deficit hyperactivity disorder. However, the potential for BGA dietary supplements to be contaminated with MCs is of concern, and there are currently no validated methods for detection of MCs in these products. This research focused on establishing screening methods for toxic Microcystis and MCs in BGA supplements. A DNA-based method employing polymerase chain reaction (PCR) was used as a prescreening tool to evaluate the dietary supplements and to detect the presence of toxin genes (i.e., presence of toxic Microcystis). A rapid, sensitive surface plasmon resonance (SPR) biosensor, directed towards recognition of all MC forms, was also developed and validated. This improved SPR biosensor incorporates a commercial Adda-group antibody (Ab) that has the capacity for broader recognition of MCs than previously developed sensors for BGA supplements that rely solely on an arginine-reactive Ab and can quantitate MC levels down to 0.24 ng/mL (equivalent to 0.24 μg per gram of BGA supplement) in less than 10 min. Such a rapid, quantitative screening method may allow for further surveillance of BGA products to assist risk assessment efforts, establishment of regulatory guidance levels, and response to potential consumer complaints related to BGA products. The PCR technique and SPR biosensor may be used in concert as prescreening and screening tools, respectively or individually, thereby limiting the number of samples that must be evaluated with confirmatory methods.     

Applications of LC-MS in the study of the uptake, distribution, metabolism and excretion of bioactive polyphenols from dietary supplements

Specific and quantitative analyses of the bioactive components and their metabolites in body fluids are essential to assess the interaction between groups of compounds in dietary supplements and preparations of psychoactives. Reverse-phase LC separations combined with tandem mass spectrometry provide the necessary specificity and sensitivity. In this paper, applications of these methods are described for the analysis of isoflavones, salvinorin A, synephrine isomers and their metabolites in serum, urine and aqueous humor.     

Regulatory issues concerning the safety, efficacy and quality of herbal remedies

Herbal remedies and alternative medicines are used throughout the world, and in the past herbs were often the original sources of most drugs. Today we are witnessing an increase in herbal remedy use throughout the Western world raising the question as to how safe are these preparations for the unborn fetus? Many women use herbal products during pregnancy. The dilemma facing most regulatory authorities is that the public considers these products as either traditional medicines or natural food supplements. The user sees no reason for regulation. Most countries have laws concerning foods, drugs, and cosmetics, the details of which seldom clearly define to what section of the law and regulations alternative remedies belong. In most countries alternative remedies are regulated as foods, provided that no medicinal claim is made on the label. The global regulatory sector, however, is changing rapidly. The Therapeutic Goods Administration (TGA) in Australia created a Complimentary Medicines Evaluation Committee in late 1997 to address this issue, and Canada has created a new Natural Health Products Directorate in the realigned Therapeutic Products and Foods Branch in 2000. In parallel, the European Agency for the Evaluation of Medicinal Products has drafted test procedures and acceptance criteria for herbal drug preparations and herbal medicinal products. In the US, the Food and Drug Administration classifies these natural products as dietary supplements. Manufacturers must label a dietary supplement thus: “this statement has not been evaluated by the FDA [, and] this product is not intended to diagnose, treat, cure or prevent any disease.” Whether these products are foods or drugs is undecided. To add complexity to this issue, most of the potential deleterious effects of natural products on the unborn may be related to hormonal effects (e.g., phytoestrogens) and nutriceutical drug interactions (e.g., St. John's Wort and antidepressants), rather than direct embryotoxicity per se. We suggest that ensuring quality of herbal products should receive immediate attention by regulatory authorities, before embarking on the more arduous tasks of safety and efficacy. Birth Defects Res B 68:505–510, 2003. © 2003 Wiley‐Liss, Inc.     

Dietary supplement use among adolescent athletes in central Nebraska and their sources of information

The purpose of this study was to investigate the prevalence of dietary supplement use among adolescent athletes. The project was also directed at identifying the sources these student-athletes used for acquiring information about dietary supplements. One hundred thirty nine high school athletes (99 males; 34 females; mean age = 15.8 +/- 1.19 years) volunteered to participate in this study. A 16-question anonymous survey instrument examined use of dietary supplements, reasons for use, type of sport participation, and sources of information regarding dietary supplements. Of the participants in this study, 22.3% (N = 31) reported currently taking dietary supplements. There was no relationship found between dietary supplement use and age. There were a significantly higher number of males reporting current dietary supplement use. Of those who reported to be currently taking dietary supplements, sports performance (N = 25) was the most reported reason for use. There were no significant differences found in reported dietary supplement use between any of the sports. Of the participants, 38.1% (N = 53) listed their coach as their best source of information on dietary supplements. The results of this study offer the current literature some additional insight into trends in supplement use among high school student athletes. Practical implications suggest that it may be necessary to ensure coaches have sufficient knowledge about dietary supplements so that adolescent athletes are receiving accurate information.     

Dietary supplement Standard Reference Materials

A new category of Standard Reference Materials (SRMs) based on dietary supplements is under development by the National Institute of Standards and Technology (NIST), with certified values for organic constituents and selected trace elements. These materials are provided primarily for use in method development and as control materials. The SRMs will assist manufacturers of dietary supplements in characterizing raw materials for potency, authenticity, and contamination or adulteration. In addition, the SRMs will assist in assessment of consistency and quality in finished products. The goal of this ongoing effort is to provide tools to the dietary supplement industry and measurement communities that will lead to improved quality of dietary supplements, and ultimately reduce public health risks that could potentially be associated with these products.     

Quality Control and Assurance: crucial for the sustainability of the applied phycology industry

The chemical and nutritional properties of microalgae are well known, which has led to an ever expanding industry for foods and dietary supplements both in terms of quantity and products. Little has been done to regulate or control quality and assurance in the applied phycology industry and it is known that it varies considerably. Nutritional aspects of produced biomass and consumption as dietary supplements have become issues of concern, especially since the industry is lucrative and fast growing. Various claims are made regarding dietary and food supplements that include health, nutrition, structure and functioning, many often unsubstantiated. Although quality is a subjective term many organisations are involved in testing, controlling and determining criteria. Today quality is more than just standards where it is an "integrated quality management approach" involving amongst others "hazard analyses and critical control points" (HACCP) practices. Microalgae are not recognised as a food or food supplement and they are also not categorised under herbals or botanicals, but as "other supplements". Produced microalgal biomass is subject to contamination from the entire range of contaminants and pathogens. Contamination of products by algal toxins in mixed culture populations also occurs. The industry has largely regulated itself, but there is considerable scope for improvement. There is a need for support and dissemination of information in the industry.     

Detection of microcystin producing cyanobacteria in Spirulina dietary supplements using multiplex HRM quantitative PCR

Arthrospira species, under the name ‘Spirulina’, are used as food supplement for its protein, vitamins, and minerals which have several health benefits. Cyanobacterial toxins including microcystins can possibly contaminate these dietary supplements causing hepatotoxicity, tumour formation, and other disorders. The safe use of dietary supplements necessitates the need to assess such toxins in the algal food supplement. The methods which evaluate these dietary supplements should be highly sensitive, cost-effective, and rapid. In this study, multiplex HRM qPCR analysis was used to detect microcystin (MC)-producing cyanobacteria in Spirulina dietary supplements. The multiplex HRM qPCR detection limit was found to be 25 ag of mcyB spiked in a standard concentration of pcb (25 pg). Two distinct melt curves characteristic of pcb (Tm 82.8 ± 0.07 °C) and mcyB (Tm 77.9 ± 0.05 °C) were observed. Microcystin contamination was detected only in the fish food supplements and not in human dietary supplements of Spirulina. Liquid chromatography–high-resolution mass spectrometry analysis further confirmed the presence of the congeners of microcystin in the identified positive samples.     

Development of a comprehensive detection method for medicinal and toxic plant species

Pharmacologically active ingredients in plants can cause significant morbidity through their increasingly common use in herbal alternative medicines and dietary supplements. Monitoring consumer products for the presence of toxic plants is encumbered by the lack of rapid and specific assays. To create a sensitive, reliable, fast, and broad-spectrum assay for medicinal or toxic plant species, we tested multiplexed ligation-dependent probe amplification (MLPA), which requires partial genomic DNA sequences from species of plants that are not well represented in currently available genetic databases. Genomic DNA was obtained from 21 species of medicinal and/or toxic plants. The PCR products were amplified from these plants and cloned for sequencing. The MLPA method was successful with DNA samples from many different species. The use of a microarray to facilitate screening of potentially thousands of plants in a single assay also was successful. The combination of the specificity of the MLPA assay with the broad-scale capabilities of microarray technology should make this an especially useful tool in screening in foods and commercial herbal preparations to identify the plant compounds actually present. Other applications could potentially extend to the identification of any plant species in samples for academic botanical studies and for biodefense and forensics applications.     

Estimation of Potential Availability of Essential Oil in Some Brands of Herbal Teas and Herbal Dietary Supplements

Introduction

The aim of the study was to estimate potential availability of essential oil in some brands of herbal products.

Methods

A comparison was performed on the basis of the essential oil yield in the unprocessed raw materials such as leaves of peppermint and lemon balm and inflorescence of chamomile as well as herbal tea bags and in dietary supplements. The yield of essential oil was determined by distillation. Essential oil was analyzed by GC-FID and GC-MS.

Results

It was found that the average potential availability of essential oils in the products such as dietary supplements for the doses recommended by the producers is lower than in the corresponding tea infusions: for peppermint formulations approximately 6-fold lower, for the formulations with lemon balm about 4-fold lower, and for the chamomile preparations about 3-fold lower. It was found that essential oils extracted from herbal teas have a similar chemical profile with characteristic deviations in the amount of individual components, which arise from the origin of the raw material.

Discussion

In contrast to homogenous pharmaceutical herbal mixtures consistent with, the Pharmacopoeia requirements, herbal teas (available in grocery stores) and dietary supplements are often out of control in terms of the yield and composition of the essential oil, which is primarily responsible for the health benefits and aromatic qualities of these products. Analysis of the composition of the dietary supplements showed that they contain on average significantly lower amounts of plant material compared to the herbal teas.     

Dietary Supplement Use and Colorectal Adenoma Risk in Individuals with Lynch Syndrome: The GEOLynch Cohort Study

Background and Aims

Individuals with Lynch syndrome have a high lifetime risk of developing colorectal tumors. In this prospective cohort study of individuals with Lynch syndrome, we examined associations between use of dietary supplements and occurrence of colorectal adenomas.

Materials and Methods

Using data of 470 individuals with Lynch syndrome in a prospective cohort study, associations between dietary supplement use and colorectal adenoma risk were evaluated by calculating hazard ratios (HR) and 95% confidence intervals (CI) using cox regression models adjusted for age, sex, and number of colonoscopies during person time. Robust sandwich covariance estimation was used to account for dependency within families.

Results

Of the 470 mismatch repair gene mutation carriers, 122 (26.0%) developed a colorectal adenoma during an overall median person time of 39.1 months. 40% of the study population used a dietary supplement. Use of any dietary supplement was not statistically significantly associated with colorectal adenoma risk (HR = 1.18; 95%CI 0.80–1.73). Multivitamin supplement use (HR = 1.15; 95%CI 0.72–1.84), vitamin C supplement use (HR = 1.57; 95%CI 0.93–2.63), calcium supplement use (HR = 0.69; 95%CI 0.25–1.92), and supplements containing fish oil (HR = 1.60; 95%CI 0.79–3.23) were also not associated with occurrence of colorectal adenomas.

Conclusion

This prospective cohort study does not show inverse associations between dietary supplement use and occurrence of colorectal adenomas among individuals with Lynch syndrome. Further research is warranted to determine whether or not dietary supplement use is associated to colorectal adenoma and colorectal cancer risk in MMR gene mutation carriers.     

Potential benefits and harms: a review of poisonous mushrooms in the world

Mushrooms have long been considered as delicacies as well as used as important dietary supplements and food. However, there are major concerns with poisonous mushrooms as these pose threats to public health and safety. In this paper, we provide a review focusing on poisonous mushrooms, their toxins, symptoms and utilizations. In addition, this paper establishes a poisonous mushroom list which includes 643 species from two phyla, 16 orders, 51 families and 148 genera. The toxicity of all these species was verified and 332 species were ranked as P1 signifying that these species have toxic studies and or clinical poisoning case records and 311 species were P2 meaning they had previously been recorded as poisonous in other studies. Furthermore, we discuss advances in technology including how genomic studies could be used as a breakthrough tool in the field of toxic mushrooms. With this comprehensive review, we aim to promote public awareness of poisonous mushrooms, including how to avoid mushroom poisoning, and how to better utilize poisonous mushroom resources.     

Probiotic Formulations: Application and Status as Pharmaceuticals—A Review

The use of probiotics is a new way to control and treat infections in this modern era. Application of beneficial bacteria to protect against detrimental bacteria in the gastrointestinal tract and thus reap a positive health benefit is the basis of probiotic therapy. Probiotics have a long global history of traditional use. They are normally consumed through fermented foods and are currently sold mostly as ingredients in foods or nutritional supplements. They are also supplied as pharma products. Recent research has highlighted the probiotic potential in the treatment or prevention of disease conditions, maintenance of health, improving immunity and in the reduction in the risk of future diseases. But their position in the pharmaceutical industry is still not very clear. Clinical practitioners use probiotic pharma products mostly as supplements. Their status as drugs is still unclear. This review is aimed to analyze probiotics as pharmaceuticals, their current status as dietary supplements and drugs, existing probiotic preparations and future research needs.