United States Pharmacopeia Safety Review of Willow Bark.

Willow bark (Salix spp.) is an ingredient in some dietary supplements. No serious adverse effects were reported from trials of willow bark extracts delivering 120 - 240 mg salicin (the purported active constituent) daily for up to 8 weeks. All studies involved adults only; none involved special subpopulations such as pregnant or breastfeeding women, or children. The most common adverse effects associated with willow bark are gastrointestinal; a few allergic reactions were also reported. Some publications advise caution when taking willow bark. There is a risk of increased bleeding in vulnerable individuals, salicylates cross the placenta and are eliminated slowly in newborns, some persons are sensitive or allergic to aspirin, and children are at risk of Reye syndrome. Concurrent use with other salicylate-containing medicines increases these risks. Metabolism of 240 mg salicin from willow bark could yield 113 mg of salicylic acid, yet dietary supplement products are not required to be labeled with warnings. In contrast, over-the-counter low-dose aspirin (81 mg strength), which delivers 62 mg salicylic acid, is required by law to include cautions, warnings, and contraindications related to its use in pregnant and nursing women, children, and other vulnerable subpopulations, e.g., those using anticoagulants. In the interest of protecting public health, the United States Pharmacopeia has included a cautionary labeling statement in the United States Pharmacopeia Salix Species monograph as follows: "Dosage forms prepared with this article should bear the following statement: 'Not for use in children, women who are pregnant or nursing, or by persons with known sensitivity to aspirin.'".

Complementary, holistic, and integrative medicine: advice for clinicians on herbs and breastfeeding.

The use of herbal remedies is a tradition held in many cultures throughout the world, and women may use herbal remedies during lactation. Because of the limitations of the current literature, it is difficult to develop accurate information on the safety and efficacy of specific herbs used during breastfeeding. It is critical that more research is conducted in this area, including national prevalence studies and safety and efficacy studies.

Contemplative medicine: A practical approach to "Well-Being 2.0" in medicine.

OBJECTIVE: To examine the relationship between Contemplative Medicine training and clinician burnout. METHODS: Clinicians underwent a 12 month training program in Contemplative Medicine, which addresses several of the "Well-being 2.0" framework elements. An uncontrolled pre and post test study design was used with the validated Maslach Burnout Inventory (MBI) as the study tool to evaluate efficacy of the program. RESULTS: Participants demonstrated improvement in burnout levels after the intervention. There were significant differences at the 0.05 significance level or better on all three scales of the MBI instrument when comparing baseline to follow-up responses, including emotional exhaustion, depersonalization, and sense of personal accomplishment. Particular improvement was noted in the "personal accomplishment" domain, with p < 0.01 when comparing baseline and follow-up responses. CONCLUSION: The results of this study suggest that Contemplative Medicine training is a viable approach for improving clinician burnout and concretely implementing the "Well-being 2.0" framework.

United States pharmacopeia safety evaluation of spirulina.

The Dietary Supplements Information Expert Committee (DSI-EC) of the United States Pharmacopeial Convention (USP) reviews the safety of dietary supplements and dietary supplement ingredients for the purpose of determining whether they should be admitted as quality monographs into the United States Pharmacopeia and National Formulary (USP-NF). The United States Food and Drug Administration (FDA) has enforcement authority to pursue a misbranding action in those instances where a dietary supplement product indicates that it conforms to USP standards but fails to so conform. Recently DSI-EC undertook a safety evaluation of spirulina, a widely used dietary ingredient. DSI-EC reviewed information from human clinical trials, animal studies, and regulatory and pharmacopeial sources and analyzed 31 adverse event reports regarding spirulina to assess potential health concerns. At the conclusion of this review, DSI-EC assigned a Class A safety rating for Spirulina maxima and S. platensis, thereby permitting the admission of quality monographs for these dietary supplement ingredients in USP-NF. DSI-EC continually monitors reports concerning the safety of dietary supplements and dietary supplement ingredients for which USP dietary supplement monographs are developed. The DSI-EC may revisit the safety classification of spirulina as new information on this dietary ingredient becomes available.

The role of nutrition in mental health.

A truly integrative approach to mental health includes a thorough assessment of dietary habits, level of exercise/physical activity, environmental exposures, medications, comorbid conditions, life stressors, level of social support, and family history. A complete physical exam and appropriate laboratory and imaging studies should be utilized to rule out underlying causes of depressed or anxious mood. Many patients will benefit from the use of specific dietary supplements, such as a multivitamin-mineral high in B-vitamins and omega-3 fatty acid. And no matter what the underlying cause of the mood disorder, patients should be counseled about the relationship between food and mood, for the evidence now substantiates what laypeople and medical professionals have long known intuitively: the way we eat affects the way we feel. The Western diet consumed in a growing number of countries is devoid of many of the key nutrients critical for the proper functioning of the central nervous system. When making dietary recommendations, clinicians should consider a low-glycemic, modified Mediterranean diet rich in fruits, vegetables, whole grains, and seafood (if not vegetarian) and low in processed, refined foods for optimizing mental health. A future article on the topic of nutrition and mental health will address the role of nutraceuticals and herbal medicines in mental health.

United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts.

As part of the United States Pharmacopeia's ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)."

The use of botanicals during pregnancy and lactation.

Women are the largest consumers of healthcare, and this extends to their utilization of complementary and alternative medicine (CAM). Researchers have attempted to uncover the reasons why women turn to CAM in general and to botanical medicine in particular. Desire to have personal control over their health has been cited as the strongest motive for women to use herbal medicine. Second was dissatisfaction with conventional treatment and its disregard for a holistic approach, as well as concerns about the side effects of medications.' These concerns may explain, in part, the fact that many women use herbal remedies during pregnancy. A survey of 578 pregnant women in the eastern United States reported that 45% of respondents had used herbal medicines, and a survey of 588 women in Australia revealed that 36% had used at least 1 herbal product during pregnancy. Women probably feel comfortable using herbal remedies because of their perceived safety, easy access, and the widespread availability of information about them (ie, Internet, magazines, books). While it is true that many botanicals are mild in both treatment effects and side effects, the data regarding safety during pregnancy are very limited. Given the small sample sizes in clinical trials studying botanicals in pregnant women, only large differences in measures of pregnancy outcomes would likely be detected. For example, if an herb were thought to increase the rate of spontaneous abortion from 6% to 7%, a sample size of more than 19000 women would be needed. It is highly unlikely that there will be any studies of a botanical (or drug) with this large a sample size. So when addressing the safety of an herb during pregnancy, we must look at the totality of the evidence, which includes traditional and contemporary use, animal studies, pharmacological studies, and clinical trial data, when available. Survey data tell us that women often do not share their use of herbal remedies with their healthcare providers due to fear of offending providers or to the belief that clinicians will be ignorant about their use. Practitioners should maintain an open and respectful demeanor when counseling pregnant and nursing women about the use of botanical medicines, and they should know how to access unbiased and authoritative information sources, so they may reliably answer questions on inadvertent exposures and provide guidance on herbal products that might be beneficial.

United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity.

OBJECTIVE: Black cohosh [Actaea racemosa L., formerly Cimicifuga racemosa (L.) Nutt.] is a botanical used mainly for the management of menopausal symptoms. Recently, regulatory agencies in Australia, Canada, and the European Union have released statements regarding the "potential association" between black cohosh and hepatotoxicity. In response, the Dietary Supplement Information Expert Committee of the US Pharmacopeia's Council of Experts reviewed safety information for black cohosh products. DESIGN: The Expert Committee analyzed information from human clinical case reports, adverse event reports, animal pharmacological and toxicological data, historical use, regulatory status, and contemporaneous extent of use. Reports were obtained from diverse sources, including the European Medicines Agency, Health Canada, the Australian Therapeutic Goods Administration, and the US Food and Drug Administration. Case reports pertaining to liver damage were evaluated according to the Naranjo causality algorithm scale. RESULTS: Thirty nonduplicate reports on use of black cohosh products concerning liver damage were analyzed. All the reports of liver damage were assigned possible causality, and none were probable or certain causality. The clinical pharmacokinetic and animal toxicological information did not reveal unfavorable information about black cohosh. CONCLUSIONS: Based on this safety review, the Dietary Supplement Information Expert Committee determined that black cohosh products should be labeled to include a cautionary statement. This is a change from the Expert Committee's decision of 2002, which required no such statement. With this decision, the US Pharmacopeia's Botanical Expert Committee may develop monographs for black cohosh, and the US Pharmacopeia may offer its verification programs to dietary supplement ingredient and product manufacturers.

Safety of green tea extracts : a systematic review by the US Pharmacopeia.

Green tea [Camellia sinensis (L.) Kuntze] is the fourth most commonly used dietary supplement in the US. Recently, regulatory agencies in France and Spain suspended market authorization of a weight-loss product containing green tea extract because of hepatotoxicity concerns. This was followed by publication of adverse event case reports involving green tea products. In response, the US Pharmacopeia (USP) Dietary Supplement Information Expert Committee (DSI EC) systematically reviewed the safety information for green tea products in order to re-evaluate the current safety class to which these products are assigned. DSI EC searched PubMed (January 1966-June 2007) and EMBASE (January 1988-June 2007) for clinical case reports and animal pharmacological or toxicological information. Reports were also obtained from a diverse range of other sources, including published reviews, the US FDA MedWatch programme, USP's MEDMARX adverse event reporting system, the Australian Therapeutic Goods Administration, the UK Medicines and Healthcare products Regulatory Agency, and Health Canada's Canadian Adverse Drug Reaction Monitoring Program. Case reports pertaining to liver damage were evaluated according to the Naranjo causality algorithm scale. In addition, the Committee analysed information concerning historical use, regulatory status, and current extent of use of green tea products. A total of 216 case reports on green tea products were analysed, including 34 reports concerning liver damage. Twenty-seven reports pertaining to liver damage were categorized as possible causality and seven as probable causality. Clinical pharmacokinetic and animal toxicological information indicated that consumption of green tea concentrated extracts on an empty stomach is more likely to lead to adverse effects than consumption in the fed state. Based on this safety review, the DSI EC determined that when dietary supplement products containing green tea extracts are used and formulated appropriately the Committee is unaware of significant safety issues that would prohibit monograph development, provided a caution statement is included in the labelling section. Following this decision, USP's DSI ECs may develop monographs for green tea extracts, and USP may offer its verification programmes related to that dietary ingredient.

The state of dietary supplement adverse event reporting in the United States.

PURPOSE: The Dietary Supplements Information Expert Committee (DSI-EC; the Committee) of the United States Pharmacopeial Convention (USP) reviews safety profiles of dietary supplements before development of USP-National Formulary (USP-NF) quality monographs. Because the veracity of dietary supplement adverse event reports (DS AERs) directly affects DSI-EC safety reviews, the Committee reviewed the current status of DS AER reporting in the US. METHODS: DSI-EC reviewed PubMed searches, information from the US Food and Drug Administration's (FDA) MedWatch program, the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers (AAPCC), and reports from US and other agencies. DSI-EC analyzed this information to identify key factors that affect the quality of DS AERs. RESULTS: The overall incidence of DS AERs appears generally to be low. However, the primary reporting portal (FDA MedWatch) receives fewer AERs than do poison control centers (PCCs), and limited coordination exists among national and international surveillance programs for evaluating signals that may indicate potential public health risks. Both inadequate and poor-quality reporting of DS AERs are major limitations of DS safety monitoring in the US. CONCLUSIONS: Based on its assessments, the Committee advances recommendations to improve the quality of reporting, monitoring, and assessing DS AERs. These include (1) enhanced data collection approaches, (2) improved coordination of AER surveillance programs, (3) strengthening of educational programs for public and health care sectors, and (4) conduct of research concerning the safety of DS. If taken, these approaches are expected to improve the health and well-being of DS users.

Use and Factors Associated With Herbal/Botanical and Nonvitamin/Nonmineral Dietary Supplements Among Women of Reproductive Age: An Analysis of the Infant Feeding Practices Study II.

INTRODUCTION: Little is known about the changes in prevalence of dietary supplement use in pregnancy, postpartum, and in a comparison group of nonpregnant women. METHODS: We conducted a secondary analysis of the Infant Feeding Practices II study. The purpose of this study is to report the prevalence of herbal or botanical and nonvitamin, nonmineral dietary supplement use by US women with respect to demographic, behavioral, and health factors. We compared pregnant and postpartum women to a comparison group of nonpregnant women who had not given birth in the past 12 months. Our main outcome was the prevalence of dietary supplements. Multiple logistic regression models were used to examine factors associated with herbal or botanical and nonvitamin, nonmineral dietary supplement use during reproductive age, pregnancy, and postpartum. RESULTS: The total sample included 1444 women assessed during the prenatal period, 1422 from the postpartum period, and 1517 women in a comparison group. In terms of herb or botanical use, 15% of the prenatal group, 16% of the postpartum group, and 22% of the comparison group reported using herbs or botanicals. The most frequently used nonvitamin, nonmineral supplement was omega-3 fatty acid. Among the total prenatal group and comparison group, women eating 5 or more servings of fruits or vegetables were less likely to report using herbs or botanicals. Women in the comparison group self-identifying as black were 4 times as likely to report using herbs or botanicals compared to participants self-identifying as white. In addition, women identifying as a race other than white were almost twice as likely to report herb or botanical use across all study groups. DISCUSSION: This is one of the rare studies that shows the changing prevalence of herbs or botanicals and nonvitamin, nonmineral dietary supplement use in women in the reproductive stage of their lives.

Safety and performance benefits of arginine supplements for military personnel: a systematic review.

CONTEXT: Dietary supplements are widely used by military personnel and civilians for promotion of health. OBJECTIVE: The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel. DATA SOURCES: Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals. STUDY SELECTION: Studies and reports were included if they evaluated the safety and the putative outcomes of enhanced performance or improved recovery from exhaustion associated with the intake of arginine alone or in combination with caffeine and/or creatine in healthy adults aged 19 to 50 years. DATA EXTRACTION: Information related to population, intervention, comparator, and outcomes was abstracted. Of the 2687 articles screened, 62 articles meeting the inclusion criteria were analyzed. Strength of evidence was assessed in terms of risk of bias, consistency, directness, and precision. RESULTS: Most studies had few participants and suggested risk of bias that could negatively affect the results. l-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery. Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects. No information about the effects of arginine on the performance of military personnel was available. CONCLUSIONS: The available information does not support the use of l-arginine, either alone or in combination with caffeine, creatine, or both, to enhance athletic performance or improve recovery from exhaustion. Given the information gaps, an evidence-based review to assess the safety or effectiveness of multi-ingredient dietary supplements was not feasible, and therefore the development of a computational model-based approach to predict the safety of multi-ingredient dietary supplements is recommended.

Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief.

OBJECTIVE: This comprehensive review examines the safety of Cimicifuga racemosa for the treatment of menopause symptoms, particularly in populations in which conventional menopause treatment regimens, including estrogen replacement, are contraindicated. DESIGN: An extensive database of information on Cimicifuga, which included all published literature pertaining to preclinical and clinical safety of various forms of Cimicifuga, the FDA and World Health Organization adverse-event reporting systems, monographs, compendia, internal unpublished data from a major manufacturer, foreign literature, and historical anecdotal reports, was reviewed, and findings pertaining to the safety of Cimicifuga use for menopause treatment were reported. RESULTS: Uncontrolled reports, postmarketing surveillance, and human clinical trials of more than 2,800 patients demonstrate a low incidence of adverse events (5.4%). Of the reported adverse events, 97% were minor and did not result in discontinuation of therapy, and the only severe events were not attributed to Cimicifuga treatment. CONCLUSIONS: Although the effects of Cimicifuga may be dependent on the specific extract preparation, this review clearly supports the safety of specific Cimicifuga extracts, particularly isopropanolic preparations, for use in women experiencing menopausal symptoms and as a safe alternative for women in whom estrogen therapy is contraindicated.

Use of herbal medicine by elderly Hispanic and non-Hispanic white patients.

STUDY OBJECTIVES: To determine the types and prevalence of herbal medicines used by Hispanic and non-Hispanic white individuals aged 65 years and older. Secondary objectives were to compare herbal medicine use according to ethnicity, sex, age, socioeconomic status, and education level, and to determine patients' beliefs about herbal medicines. Use of nonphysician health care providers such as acupuncturists and chiropractors also was assessed. METHODS: Data for a cross-sectional, interviewer-administered survey were collected at the University of New Mexico Senior Health Center, an ambulatory health care clinic, in Albuquerque, New Mexico, from February 1996-January 1997. To participate in the study, patients had to be at least 65 years of age, established patients at the clinic, and live independently in a community dwelling. They were excluded if they had dementia, lived in an institution, or belonged to any ethnic group other than Hispanic or non-Hispanic white. Ethnicity was determined by asking the patients in which ethnic group they identified themselves. RESULTS: A total of 186 patients were surveyed: 84 Hispanic (34 men, 50 women) and 102 non-Hispanic white (47 men, 55 women). Of the 186 patients, 91 (49%) admitted to having taken herbal medicines in the previous year. The most common were spearmint, chamomile, aloe vera, garlic, brook-mint, osha, lavender, ginger, ginseng, and camphor. Most of the patients who used herbal medicines were 65-74 years of age and took them primarily for health care maintenance or self-perceived problems. CONCLUSION: As approximately half of the elderly patients stated that they used herbal medicines, health care providers should be knowledgeable about herbal remedies and provide reliable information to their patients about them in a nonjudgmental manner.

Developing and implementing core competencies for integrative medicine fellowships.

The Consortium of Academic Health Centers for Integrative Medicine defines integrative medicine as "the practice of medicine that reaffirms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, health care professionals, and disciplines to achieve optimal health and healing." Over the past three decades, the U.S. public increasingly has sought integrative medicine approaches. In an effort to train medical professionals to adequately counsel patients on the safe and appropriate use of these approaches, medical schools and residencies have developed curricula on integrative medicine for their trainees. In addition, integrative medicine clinical fellowships for postresidency physicians have emerged to provide training for practitioners interested in gaining greater expertise in this emerging field. Currently, 13 clinical fellowships in integrative medicine exist in the United States, and they are predominantly connected to academic medical centers or teaching affiliate hospitals. In 2010, the Consortium of Academic Health Centers for Integrative Medicine, represented by 56 member academic health care institutions with a shared commitment to advance the principles and practices of integrative medicine, convened a two-year task force to draft integrative medicine fellowship core competencies. These competencies would guide fellowship curriculum development and ensure that graduates possessed a common body of knowledge, skills, and attitudes. In this article, the authors discuss the competencies and the task force's process to develop them, as well as associated teaching and assessment methods, faculty development, potential barriers, and future directions.

Evidence-based evaluation of potential benefits and safety of beta-alanine supplementation for military personnel.

This Department of Defense-sponsored evidence-based review evaluates the safety and putative outcomes of enhancement of athletic performance or improved recovery from exhaustion in studies involving beta-alanine alone or in combination with other ingredients. Beta-alanine intervention studies and review articles were collected from 13 databases, and safety information was collected from adverse event reporting portals. Due to the lack of systematic studies involving military populations, all the available literature was assessed with a subgroup analysis of studies on athletes to determine if beta-alanine would be suitable for the military. Available literature provided only limited evidence concerning the benefits of beta-alanine use, and a majority of the studies were not designed to address safety. Overall, the strength of evidence in terms of the potential for risk of bias in the quality of the available literature, consistency, directness, and precision did not support the use of beta-alanine by military personnel. The strength of evidence for a causal relation between beta-alanine and paresthesia was moderate.