Consumers’ attitude towards the use and safety of herbal medicines and herbal dietary supplements in Serbia

Background The use of herbal medicines and herbal dietary supplements in Serbia is very common and many patients consume herbal preparations with conventional drug therapy. Objective The aim of this survey was to evaluate the consumers’ awareness of herbal remedies and the safety of herbal dietary supplements, their attitude towards combining herbals and drugs, and the source of recommendations for their use. Setting The study included all consumers who bought herbal remedies and herbal dietary supplements in 15 pharmacies on the territory of Novi Sad during 2011 and who accepted to be interviewed. Methods Structured interviews using questionnaire, conducted by pharmacists. The questionnaire included 4 parts: socio-demographic characteristics of consumers, source of recommendations for the use of herbal products, attitude towards safety of herbal remedies and herbal dietary supplements use and their combination with regular drugs, as well as the question of purchased herbal products. Main outcome measure Consumers’ attitude towards the safety and use of herbal medicines and herbal dietary supplements measured by 9 items. Results The majority of interviewed participants were highly educated, aged 41–60 and they consumed herbal remedies on their own initiative or on recommendation of nonmedically educated person, without previous consultation with medical doctor or pharmacist. Out of all participants: 88.9 % did not consider it important to inform their physician or pharmacist about use of herbal remedies and herbal dietary supplements; 73.3 % found the use of herbal remedies harmless (where 9.4 % did not have any attitude towards that issue), while 40.3 % of participants regarded the combining of herbal and regular drugs unsafe. Conclusion There is a need for consumers’ education on reliable use of herbal medicines and herbal dietary supplements, in order to improve their awareness of the limits of herbal remedies safety and potential risks of their combination with drugs.     

New drug information resources for pharmacists at the National Library of Medicine

ObjectiveTo provide an overview of selected drug information-related databases of the National Library of Medicine (NLM), with a focus on newer resources that support the professional information needs of pharmacists and other health care providers.SummaryNLM, which is the world's largest medical library, provides an array of bibliographic, factual, and evidence-based drug, herbal remedy, and dietary supplement information resources. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies.ConclusionNLM provides several clinical–scientific drug information resources that are particularly useful in meeting the professional information needs of pharmacists.     

植物药-化学药药代动力学相互作用及机制研究进展

植物药用于疾病治疗和保健的历史悠久。近年来,随着植物药与化学药联合应用的增多,二者相互作用和不良反应的报道逐渐增多。已知植物药中多种成分是P-糖蛋白和细胞色素P450的底物,同时也可诱导或抑制二者活性,是导致植物药-化学药相互作用的重要原因之一。本文就植物药-化学药药代动力学相互作用及可能机制进行综述。     

Consumption of herbal remedies and dietary supplements amongst patients hospitalized in medical wards

AIMS: Herbal remedies may have adverse effects and potentially serious interactions with some commonly prescribed conventional medications. Little is known about consumption of herbal remedies and dietary supplements by hospitalized patients. The aim was to evaluate the rate of consumption and characterize the patients hospitalized in internal medicine departments who consume herbal remedies and dietary supplements. Also, to assess the medical teams' awareness and assess the percentage of patients with possible drug-herb interactions. METHODS: Patients hospitalized in the medical wards of two hospitals in Israel were interviewed about their use of herbal remedies or dietary supplements. The medical records were searched for evidence that the medical team had knowledge of the use of herbal remedies or dietary supplements. RESULTS: Two hundred and ninety-nine hospitalized medical patients were interviewed. Of the participants, 26.8% were herbal or dietary supplement consumers (HC). On multivariate analysis the only variates associated with herbal or dietary supplement consumption were the hospital [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.29, 6.52], income (OR 0.39, 95% CI 0.15, 1.05), smoking habits (OR 0.17, 95% CI 0.05, 0.55) and benign prostatic hypertrophy (OR 4.64, 95% CI 1.3, 16.5). Ninety-four percent of the patients had not been asked specifically of herbal consumption by the medical team. Only 23% of the hospital's medical files of the HC patients had any record of the use of herbal or dietary supplements. Seven possible drug-herbal interactions were encountered (7.1%). The most serious was an interaction between camomile tea and ciclosporin. CONCLUSIONS: Herbal remedy consumption is common amongst patients hospitalized in internal medicine wards and is often overlooked by the medical team. Patients and doctors should be more aware of the possible adverse effects and of the potential of herb-drug interactions.     

Interactions between herbal remedies and antirheumatic drugs

Many patients with rheumatological conditions use herbal remedies as an adjunct to their conventional antirheumatic medication, often without seeking advice. Herbal remedies are exempt from the usual drug safety requirements and may be a cause of both adverse effects and drug interactions. Data on interactions between herbal remedies and conventional antirheumatic medication is scarce. Reasons include a perception that herbal remedies are safe, a lack of reporting by patients and healthcare professionals and a lack of knowledge about the pharmacology and composition of herbal remedies, as well as adulteration. Interactions are likely between herbal remedies with antiplatelet or nephrotoxic effects and NSAIDs, hepatotoxic herbal remedies and disease-modifying antirheumatic medication, and between St. John's Wort and cyclosporin.     

Herbal remedies for asthma treatment: between myth and reality

Asthma is one of the most common chronic diseases worldwide. To treat this widespread disease there is a high prevalence of usage of herbal medicine. The use of plants is as old as humankind and it has been steadily increasing over the past 10 years. Plant-based remedies are now one of the most popular complementary treatments. Herbal supplements are receiving increasing exposure through media, including the Internet, in lay journals and more recently in the scientific press. Interest in herbal medicine has been facilitated by multiple factors, including the perception that pharmaceutical medications are expensive, overprescribed and may often be dangerous. Alternatively, herbal medicine is often perceived as being "natural" and therefore is considered safe. However, the scientific literature supporting the efficacy of herbal therapies is incomplete. There are few well-controlled studies that support the efficacy of herbal remedies in the treatment and clinical improvement of patients with asthma. Available scientific evidence has not yet confirmed the validity of their popular role in the treatment of asthma. The present review evaluates herbs and their efficacy in asthma to provide a balanced and objective view for the reader seeking information on herbal therapy     

Herbal products: behaviors and beliefs among Italian women

PURPOSE: The use of phytotherapy is growing worldwide, but the popular perception is that this kind of approach is natural and therefore safer than traditional medicine; for this reason the use is frequently not communicated to the doctor. Instead, even if many herbal remedies are benign in nature, some of these therapies have potentially harmful side effects or adverse interactions with other medications. So, the purpose of our study was to analyze the behavior patterns and decision-making modalities about herbal remedy use among a sample of Italian women. METHODS: During a 5-month period, interviews to women attending the outpatient ambulatory of an urban university general hospital were made on the basis of a pre-structured 25-item questionnaire. RESULTS: Among a random study population of 1,044 subsequent patients, 491 women (47.03%) reported to have been taking one or more herbal products in the last year, sometimes used during pregnancy or given to their children (35.23%). The 10 most frequently used herbal products reported were propolis, aloe, valerian root, blueberry, fennel, dandelion, mallow, arnica, thyme, and Echinacea. The major purposes for using these products were to stimulate the immune system and to cure respiratory problems. 47/491 (9.57%) women reported side effects, but only 36% referred to the doctor. In most of the cases, herbal products were taken in combination with drugs (44.61%) or homeopathic treatments (11.81%). The majority of our women did not obtain information about this kind of therapy from a health care provider (72.71%). CONCLUSIONS: The present survey highlights the general use of phytomedicines by a sample of Italian women, the potential risk of their confidence with the 'natural world,' and the lack of discussion on this argument with doctors and pharmacists. This suggests the importance of training for health care providers and the need of informational programs for consumers.     

黄酮类化合物对细胞色素P450 CYP1，2E1，3A4和19的影响

黄酮类化合物广泛存在于蔬菜、坚果、水果和饮料及中草药中，可诱导或抑制多种细胞色素P450的活性。本篇综述主要集中回顾黄酮类化合物对于细胞色素P450 CYP1，2E1，3A4和19的影响。归纳总结了该类物质抑制和诱导细胞色素P450的多种机制，如刺激特定的受体、稳定相关mRNA等。并总结了该类物质对细胞色素P450的影响体内和体外水平的研究结果并非总是一致的原因，如体内外的浓度的差异、基因和其他环境因素的影响。由于黄酮类化合物可通过影响细胞色素P450的活性影响药物代谢从而导致药物不良反应和药物相互作用，因此在将该类物质与其他药物合用时应高度重视。     

How natural are 'natural herbal remedies'? A Saudi perspective

OBJECTIVE: There is a rapidly growing trend in the consumption of herbal remedies in industrialised and developing countries. Users of herbal remedies are at risk of toxicity and adverse interactions of herbal preparations due to their frequent contamination with metals and adulteration with synthetic drugs. The purpose of this study was to assess the quality of herbal remedies present on the market in Saudi Arabia in recent years. METHODOLOGY: 247 herbal remedies and related preparations were examined from 2000-2001 at the Toxicology Laboratory, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Herbal powder samples were the most common sample type examined (n = 80), followed by complete, packed preparations (n = 59), single undescribed capsules or pills (n = 46), loose plant leaves or seeds (n = 28), creams (n = 18) and liquid or jelly samples (n = 16). All samples were subjected to toxicological screening for organic substances using gas chromatographic-mass spectrometric analysis, screening for heavy metals (arsenic, mercury, and lead) using inductive coupled plasma-mass spectrometry and microbiological examination. RESULTS: The preparations analysed were used to treat the following indications: leukaemia and other forms of cancer (n = 22); obesity (n = 18); diabetes mellitus (n = 14); rheumatic disorders (n = 14); skin pigmentation problems (n = 11); or to enhance male sexual activity (n = 9). In 123 cases, the indication of use was not known. 39 samples contained high concentrations of heavy metals. This was particularly striking in remedies used to treat leukaemia (arsenic content of 522-161,600 ppm) and in creams for whitening skin (mercury content of 5,700-126,000 ppm). Eight preparations contained synthetic drugs (e.g. benzodiazepines and tricyclic antidepressants in sedative preparations, cyproheptadine in a remedy to gain bodyweight, ibuprofen and dipyrone in herbal capsules used to treat rheumatism). 18 samples were contaminated with micro-organisms. 14 samples contained toxic substances of natural origin. Of the 247 examined preparations, 77 (i.e. over 30%) were disqualified due to high heavy metals content, bacterial contamination or presence of toxic organic substances. CONCLUSION: The study shows an urgent need to control the production, importing and selling of herbal preparations.     

ADME properties of herbal medicines in humans: evidence, challenges and strategies

Herbal medicines, an important group of multicomponent therapeutics, are widely and increasignly used worldwide. Despite the popularitiy of herbal medicines, the clinical evidence that support the use of most herbal medicines is weak. Pharmacokinetic and absorption, distribution, metabolism and excretion (ADME) studies have been integrated into modern drug development, but ADME studies are generally not needed for herbal remedy discovery and development. For the majority of herbal medicines, data on their ADME and pharmacokinetic properties in humans are lacking or scant. An extensive literature search indicates that there are limited data on ADME properties of herbal medicines in humans. Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein (P-gp/MDR1/ABCB1) which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are critical determining factors for the in vivo ADME processes of herbal remedies. There are increasing ADME studies of herbal remedies, but these studies are mainly focused on a small number of herbal medicines including St John's wort, milk thistle, curcumin, echinacea, ginseng, ginkgo, and ginger. For an herbal medicine, the pharmacological activity is gained when the active agents or the active metabolites reach and sustain proper levels at their sites of action. Both the dose levels and ADME processes of active herbal components in the body govern their target-site concentrations and thus the therapeutic responses. In this regard, a safe and optimal use of herbal medicines requires a full understanding of their ADME profiles. To optimize the use of herbal remedies, further studies to explore their ADME properties in humans are certainly warranted.     

Drug interactions in African herbal remedies

Herbal usage remains popular as an alternative or complementary form of treatment, especially in Africa. However, the misconception that herbal remedies are safe due to their "natural" origins jeopardizes human safety, as many different interactions can occur with concomitant use with other pharmaceuticals on top of potential inherent toxicity. Cytochrome P450 enzymes are highly polymorphic, and pose a problem for pharmaceutical drug tailoring to meet an individual's specific metabolic activity. The influence of herbal remedies further complicates this. The plants included in this review have been mainly researched for determining their effect on cytochrome P450 enzymes and P-glycoprotein drug transporters. Usage of herbal remedies, such as Hypoxis hemerocallidea, Sutherlandia frutescens and Harpagophytum procumbensis popular in Africa. The literature suggests that there is a potential for drug-herb interactions, which could occur through alterations in metabolism and transportation of drugs. Research has primarily been conducted in vitro, whereas in vivo data are lacking. Research concerning the effect of African herbals on drug metabolism should also be approached, as specific plants are especially popular in conjunction with certain treatments. Although these interactions can be beneficial, the harm they pose is just as great.     

Plants traditionally used in age-related brain disorders (dementia): an ethanopharmacological survey

Context: Epidemiological studies have shown that despite mortality due to communicable diseases, poverty and human conflicts, the incidence of dementia increases in the developing world in tandem with the ageing population. Although some FDA approved drugs are available for the treatment of dementia, the outcomes are often unsatisfactory. In traditional practices of medicine, numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases such as Alzheimer’s disease (AD) and other memory-related disorders. In western medicine most of the drugs used for the treatment of neurodegenerative disorders are derived from plant sources.

Objective: This article reviews plants and their active constituents that have been used for their reputed cognitive-enhancing and antidementia effects.

Methods: A literature survey in Science Direct, Pubmed, and Google Scholar was performed to gather information regarding drug discovery from plants sources for the treatment of congnitive disorders and dementia.

Results: More than forty herbal remedies were identified with cholinesterase inhibitory, anti-inflammatory, or antioxidant activities. Bioactive compounds include alkaloids, flavonoids, steroids, saponins, terpenoids, and essential oils. About eleven herbal plants with multipotent activity against AD are discussed.

Conclusion: Literature surveys show that most of the research has been conducted on herbal remedies effect on cholinesterase inhibitory and antioxidant activities. Studies regarding the effect of herbal drugs on β-secretase inhibitory activity and antiaggregation property are lacking. This review provides leads for identifying potential new drugs from plant sources for the treatment of neurodegenerative disorders.     

Application of LC-ESI-MS-MS for detection of synthetic adulterants in herbal remedies

Adulteration of allegedly "natural herbal medicines" with undeclared synthetic drugs is a common and dangerous phenomenon of alternative medicine. The purpose of the study was to develop a procedure for detection of most common synthetic adulterants in herbal remedies, using high-pressure liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS-MS). Eighty drugs belonging to various pharmacological classes were included in the study. For most drugs two transitions were monitored, using protonated or deprotonated molecules as precursor ions. The drugs were isolated from herbal remedies using simple methanol extraction. Chromatographic separation was done in gradient of acetonitrile-10 mM ammonium formate buffer (pH 3.0). Drugs tested were grouped in suites, comprising analgesic drugs, antibiotics, antidiabetic drugs, antiepileptic drugs, aphrodisiacs, hormones and anabolic drugs, psychotropic drugs, and weight reducing compounds. These suites were used according to the declared benefits of examined preparations. Limits of detection ranged from 5 pg to 1 ng per injected sample. Drug-free herbal remedy spiked with eight various pharmaceuticals occurring in adulterated herbal preparations was used for internal proficiency testing. The recoveries of spiked drugs ranged from 63 to 100%. The procedure was applied in everyday casework. Several undeclared drugs were identified in "herbal" remedies, like e.g. sildenafil, tadalafil, testosterone, or glibenclamide. Pharmacological properties of detected drugs always corresponded with the claims of the "natural" remedies. The method presents a valuable extension of standard GC-MS screening used for this purpose.     

Herb-drug interactions: Focus on metabolic enzymes and transporters

As the uses of herbal medicines from traditional natural products are increased, the need for pharmacokinetic studies and relevant data are also increased for safe pharmacotherapy. The market entry for the traditional herbal medicine is easier compared with that for synthetic drugs because of a lower regulatory barrier. Thus, the exact mechanisms for the absorption, distribution, metabolism and excretion of active components in herbal medicines and the potential herb-drug interactions are not always fully understood. Recently, there has been an increasing interest in pharmacokinetic studies of herbal remedies and relevant data of commonly used herbal remedies are accumulating in this field. In this review, the effects of nine botanicals (ginkgo, green tea, grapes, licorice, saw palmetto, garlic milk thistle, ginseng and St. John’s wort) on metabolic enzymes and transporters affecting absorption and disposition of herbal products are summarized. The source of samples (extracts and individual components), the species (human and animal) and in vivo and in vitro systems were separately reviewed for a better understanding of herb-drug interactions.     

Ocular side effects associated with dietary supplements and herbal medicines

Dietary supplements are prevalent worldwide and play a significant role in the treatment of human disease. In the United States, allopathic physicians are at the early stage of learning how to treat patients with natural remedies and other forms of alternative medicine. Elsewhere, however, alternative remedies have been embraced more fully. In Germany, for example, the German Federal Health Agency created Commission E, which has allowed for a more sophisticated approach to assessing the efficacy and safety of dietary supplements and herbal medicines. Health insurance in Germany frequently covers costs for doctor-prescribed herbal remedies. While there is strong evidence that many herbal products have therapeutic effects, there are also a large number of cases of severe adverse reactions due to some of the many thousands of herbal products. One of the first signs of potential toxicity is in the visual system, as in many cases patients notice loss of vision more than systemic side effects. In addition, ophthalmologists are able to detect objective findings through external eye exams and dilated fundus exams. Presented here are some of the more common ocular side effects from frequently prescribed dietary supplements. In most instances, stopping the treatment or decreasing the dose allows for full resolution of symptoms. In addition, comment is made on the regulatory confusion that exists for this industry, especially in the United States.     

Nephrotoxicity associated with exposure to plant toxins, with particular reference to Africa

Acute renal failure is a frequent cause of morbidity and mortality in the hospitalized population worldwide. In Africa, apart from hemodynamic causes and infections, herbal remedies contribute to both morbidity and mortality, although these causes often go unrecognized. This paper reviews reports of herbal remedies that have been shown to result in nephrotoxicity. The indications for use of the remedies, signs and symptoms in poisoned patients, and the methods used to detect toxic compounds in plant specimens or in biological fluids are covered.     

The influence of ethnicity on use of herbal remedies in elderly Hispanics and non-Hispanic whites

OBJECTIVE: To compare the use of herbal remedies between elderly, self-identified Hispanics and non-Hispanic whites (NHW). DESIGN: Cross-sectional, interviewer-administered survey. PATIENTS/SETTING: 186 patients, 65 years and older, at a university-based, ambulatory, senior health center. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Differences in herbal use patterns between Hispanic and NHW participants. Main outcome measures were participants' use of herbal remedies, types of remedies used, medical reason for use, age, sex, Hispanic or NHW ethnicity, income, and education. RESULTS: Overall, 61% of patients had used an herbal remedy at some time in their lives. A larger proportion of Hispanic subjects used herbal remedies than did NHW subjects (77% versus 47%, respectively). Hispanic subjects preferred to use the raw herb in a tea, whereas NHW subjects preferred processed herbs in a capsule or tablet form. Significantly more Hispanic subjects grew or gathered their own herbs and received their information about herbs from a family member than did NHW subjects. Few subjects in either ethnic group received their information about herbal remedies from an allopathic provider. For both groups, the herbs most often used were yerba buena, manzanilla, poleo, osha, and alhucema. The top perceived medical problems that herbs were used for were health care maintenance, dyspepsia, upper respiratory infection, skin problems, and anxiety/nerves/insomnia. CONCLUSION: Ethnicity was related to the frequency of herbal use, the choice and preferred form of herb, and the source of knowledge of herbal remedies. Hispanic culture may account for the observed differences.     

Disposition pathways and pharmacokinetics of herbal medicines in humans

Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. To retrieve relevant data, the authors have searched through computer-based literatures by full text search in Medline (via Pubmed), ScienceDirect, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO), CrossRef Search and Embase (all from inception to May 2010). Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein (P-gp) which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger. The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action. Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a full understanding of their pharmacokinetic profiles. To optimize the use of herbal remedies, further clinical studies to explore their biological fate including the disposition pathways and kinetics in the human body are certainly needed.