Adriane Fugh-Berman

Herb-drug interactions

Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St Johns wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St Johns wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

Complementary and Alternative Medicine for Menopausal Symptoms: A Review of Randomized, Controlled Trials

Women are frequent users of complementary and alternative medicine (CAM) therapies in many countries (1-5), including the United States, where women use CAM therapies more often than men (48.9% vs. 37.8%) (6). Many women report using these therapies for menopausal symptoms (7, 8). A national magazine received more than 15 000 responses to a survey of alternative treatments for menopausal women (7). Primary symptoms included hot flashes, joint pain, sleep problems, forgetfulness, and fatigue; hot flashes (the most common menopausal symptom for women in the United States) (9) were most commonly treated. Therapies of choice were herbal remedies, chiropractic, and meditation. Recently, dietary supplements and foods containing phytoestrogens have become increasingly popular, despite the lack of data from clinical trials. The science of CAM therapies is still inadequate to sufficiently inform clinicians and the public of the benefits or potential risks of CAM therapies. To provide information for clinicians, we reviewed randomized, controlled clinical trials of CAM therapies for menopausal symptoms. Methods Study Selection We searched MEDLINE from January 1966 to December 2002, the Alternative and Complementary Database (AMED) of the British Library from January 1985 to December 2000, and our own extensive files. Databases were searched under the terms hot flash/flush, menopause, and climacteric, combined with phytoestrogens, alternative medicine, herbal medicine, traditional medicine, Traditional Chinese Medicine (TCM), Ayurveda, naturopathy, chiropractic, osteopathy, massage, yoga, relaxation therapy, homeopathy, aromatherapy, and therapeutic touch. We did not limit the search to English-language literature. Studies that examined single symptoms or conditions that are not clearly associated with menopause (for example, anxiety and lipids) were excluded. All other randomized, controlled trials, regardless of their quality, were included. A total of 29 studies were identified. Each author extracted information on the number of patients, study design, outcome measures, and results for half the studies; the other author then checked results. Role of the Funding Source The funding source had no role in the design, conduct, analyses, or reporting of the study or the decision to submit the manuscript for publication. CAM Therapies Herbal Remedies Herbs used in the United States for menopausal problems include black cohosh (Cimicifuga racemosa), chaste tree berry (Vitex agnus-castus), dong quai (Angelica sinensis), ginseng (Panax ginseng and other Panax species), evening primrose oil (Oenethera biennis), motherwort (Leonurus cardiaca), red clover (Trifolium pratense), and licorice (Glycyrrhiza glabra). We identified 10 trials of herbs (Table 1) (10-19). Most studies found no significant changes in primary outcome measures. However, these studies were small, of short duration, and far from sufficient to yield definitive conclusions. Table 1. Herbs for Menopausal Symptoms The most studied and perhaps most popular herb is black cohosh, traditionally used by Native Americans for gynecologic and other conditions. Almost all clinical studies of black cohosh have used the standardized product Remifemin (GlaxoSmithKline, Pittsburgh, Pennsylvania); however, the formulation and the dosage have changed over time. One of four randomized, controlled trials of black cohosh for hot flashes was placebo controlled (10), one used both a treatment and placebo control (12), and two were treatment controlled (11, 13). Three of the four trials found black cohosh to be beneficial for treating hot flashes. Neither the identity of active compounds nor the mechanism of action of black cohosh is known. Although formononetin, an estrogenic isoflavone, was reported to have been isolated from black cohosh extract (20), another study found no formononetin in black cohosh extract (21). In addition, a recent systematic examination of extracts of black cohosh collected from 13 locations in the eastern United States as well as Remifemin also found no formononetin in any sample (22). Thus, other compounds must be responsible for its biological activity. Small amounts of biochanin, another isoflavone, have been isolated from C. racemosa roots (23). Other candidates for the biological activity of black cohosh include triterpene glycosides, organic acids, and esters. Black cohosh is not usually used on a long-term basis, and no clinical trials have lasted for more than 6 months. This is of concern because women using this product for natural hormone replacement therapy may take it for years. There are no published data from human trials about long-term safety, particularly regarding endometrial or breast stimulation. Effects on vaginal epithelium are inconclusive; two of five randomized, controlled trials that examined estrogenic effect on vaginal epithelium reported a stimulatory effect (11, 12). In vitro and in vivo studies are not consistent or sufficient. Although black cohosh may be useful for menopausal symptoms, long-term use cannot be presumed to be safe until appropriate safety studies are conducted. Red clover contains the phytoestrogens formononetin, biochanin A, daidzein, and genistein (24). Two small, 3-month clinical trials conducted in Australia reported no significant benefit of red clover extract for hot flashes (14, 15) (Table 1). Several larger trials are in progress. Red clover, a Native American herb, has not been traditionally used on a long-term basis for hot flashes, and it is unknown whether long-term use would have an estrogenic effect on the breast or endometrium. Dong quai, a Chinese herb traditionally prescribed as a tonic for women, is most commonly used as part of a mixture. It is sold in the United States for use alone or as part of newly formulated, nontraditional herbal combinations. One trial of dong quai found no benefit for hot flashes (16) (Table 1). It would be valuable to study Traditional Chinese Medicine (TCM) formulas, prescribed in accordance with TCM diagnostic methods. Dong quai does not contain the typically reported phytoestrogens, and the data on stimulation of estrogen receptorpositive breast cancer cells or binding to estrogen receptors (25, 26) are conflicting. Dong quai contains coumarins and can cause bleeding when administered concurrently with warfarin (27); the furocoumarins contained in dong quai can cause photosensitization (24). Oil of evening primrose, a good source of the prostaglandin E1 precursor -linolenic acid, was evaluated for hot flashes in one trial; no differences were found between a group of patients using evening primrose oil and a placebo group (17). Single-dose studies are difficult to evaluate when optimum dose and duration of treatments are unknown. Evening primrose oil is a benign treatment. Ginseng has been used as a tonic for centuries in Asia. One trial found no benefit of ginseng over placebo for menopausal symptoms and quality-of-life measures, although there were positive effects on mood (18). Case reports link ingestion of ginseng with postmenopausal bleeding (28, 29); one case of postmenopausal bleeding occurred after topical use of a ginseng-containing face cream (30). Ginseng also reduced the international normalized ratio in one patient receiving warfarin therapy (27). In summary, of the herbs that have been tested for hot flashes, only black cohosh has shown a beneficial effect. Questions remain about the long-term safety of most herbs. Dietary Phytoestrogens Many food plants contain phytoestrogens, primarily phenolic (rather than steroidal) compounds that include isoflavones, lignans, and coumestans. Isoflavone precursors are found in soy and other types of beans, clover, and alfalfa. Lignan precursors are found in whole grains, seeds (especially flaxseed [linseed]), fruits, vegetables, rye, millet, and legumes (31). Intestinal bacteria convert plant lignans to mammalian lignans (enterolactone and enterodiol) and convert conjugated isoflavones to unconjugated active isoflavones (genistein, daidzein, and equol). Phytoestrogens are estrogenic, and, thus, diet may modulate endocrine actions in the body. High dietary intake of soy products in Japan, China, and Korea has been proposed as one reason for the lower prevalence of menopausal symptoms reported in those countries (32, 33). Soy foods have become popular in the United States for treating hot flashes, despite few strong supporting clinical studies. We identified 11 clinical trials that examined soy or isoflavone supplementation for hot flashes (Table 2) (34-44); one additional study of soy for menopausal women examined vaginal epithelium rather than hot flashes (45). Products studied ranged from soy foods to purified isoflavone preparations. Only 3 of 8 studies with treatment phases that lasted for more than 6 weeks showed significant improvement in hot flashes at the end of the study (35, 41, 43). The longest study to date showed no benefit for hot flashes (or other symptoms) at 24 weeks (36). Comparisons are difficult because of variations in product, dosage, scoring systems for symptoms of hot flashes, and the menopausal status of patients. Published data show only modest effects (primarily on the severity of hot flashes), and most benefits disappeared after 6 weeks (for hot flashes, even 3 months is barely adequate to appropriately assess efficacy). It is of interest that in most of these studies, symptoms decreased in all groupsoften as much as 50% to 60% in placebo as well as treatment groups. Studies of longer duration must be done to determine whether this placebo effect would have declined over time in any or all groups. Additional studies of menopausal symptoms are warranted to differentiate among whole foods, soy protein, and isoflavone extracts. Soy foods have been a staple in Asian cuisine for thousands of years and are presumed safe. Supplementing the diet with beans or bean products is a benign interve

Complementary and Alternative Medicine in the Management of Pain, Dyspnea, and Nausea and Vomiting Near the End of Life: A Systematic Review

To review the evidence for efficacy of complementary and alternative medicine (CAM) modalities in treating pain, dyspnea, and nausea and vomiting in patients near the end of life, original articles were evaluated following a search through MEDLINE, CancerLIT, AIDSLINE, PsycLIT, CINAHL, and Social Work Abstracts databases. Search terms included alternative medicine, palliative care, pain, dyspnea, and nausea. Two independent reviewers extracted data, including study design, subjects, sample size, age, response rate, CAM modality, and outcomes. The efficacy of a CAM modality was evaluated in 21 studies of symptomatic adult patients with incurable conditions. Of these, only 12 were directly accessed via literature searching. Eleven were randomized controlled trials, two were non-randomized controlled trials, and eight were case series. Acupuncture, transcutaneous electrical nerve stimulation, supportive group therapy, self-hypnosis, and massage therapy may provide pain relief in cancer pain or in dying patients. Relaxation/imagery can improve oral mucositis pain. Patients with severe chronic obstructive pulmonary disease may benefit from the use of acupuncture, acupressure, and muscle relaxation with breathing retraining to relieve dyspnea. Because of publication bias, trials on CAM modalities may not be found on routine literature searches. Despite the paucity of controlled trials, there are data to support the use of some CAM modalities in terminally ill patients. This review generated evidence-based recommendations and identified areas for future research.

Citrus aurantium, an Ingredient of Dietary Supplements Marketed for Weight Loss: Current Status of Clinical and Basic Research

Seville orange (Citrus aurantium) extracts are being marketed as a safe alternative to ephedra in herbal weight-loss products, but C. aurantium may also have the potential to cause adverse health effects. C. aurantium contains synephrine (oxedrine), which is structurally similar to epinephrine. Although no adverse events have been associated with ingestion of C. aurantium products thus far, synephrine increases blood pressure in humans and other species, and has the potential to increase cardiovascular events. Additionally, C. aurantium contains 6′,7′-dihydroxybergamottin and bergapten, both of which inhibit cytochrome P450-3A, and would be expected to increase serum levels of many drugs. There is little evidence that products containing C. aurantium are an effective aid to weight loss. Synephrine has lipolytic effects in human fat cells only at high doses, and octopamine does not have lipolytic effects in human adipocytes.

Medicinal plants used by Latino healers for women's health conditions in New York City

This paper examines the use of medicinal plants by Latino healers in New York City to treat various women’s illnesses. Eight Latino healers collaborated on the study through consultations with female patients who had one of the following conditions as diagnosed by biomedically trained physicians: uterine fibroids, hot flashes, menorrhagia, or endometriosis. The study identified a total of 67 plant species prescribed by the healers in the form of mixtures or as individual plants. Voucher specimens were collected from local botánicas and identified by specialists at The New York Botanical Garden. Studies of immigrant traditional healers and the plants they use in an urban setting can provide interesting ethnobotanical data and information to assist in diagnosing conditions and contributing to treatment of patients from Latino as well as non-Latino communities.ResumenEste documento examina el uso de plantas medicinales por curanderos Latinos en la ciudad de Nueva York en el tratamiento de varias enfermedades en mujeres. Ocho curanderos Latinos colaboraron en el estudio a través de consultas con pacientes mujeres que tenían una de las siguentes condiciones de salud diagnosticadas por médicos: fibroma del útero, incrementos de temperatura repentinos, menorrea o endometriosis. El estudio identificó un total de 67 especies de plantas presentas por los curanderos ya sea en mezclas o individualmente. Muestras de los especímenes fueron colectadas en botánicas locales e identificadas por especialistas en El Jardín Botánico de Nueva York. Estudios de curanderos tradicionales inmigrantes y sus plantas en un área urbana pueden proveer datos etnobotánicos interesantes e información que asista en el diagnóstico del estado de salud y contribuya al tratamiento de pacientes tanto de comunidades Latinos, como no Latinos.

Dietary Supplements and Natural Products as Psychotherapeutic Agents

Alternative therapies are widely used by consumers. A number of herbs and dietary supplements have demonstrable effects on mood, memory, and insomnia. There is a significant amount of evidence supporting the use of Hypericum perforatum (St. Johns wort) for depression and Ginkgo biloba for dementia. Results of randomized, controlled trials also support the use of kava for anxiety and valerian for insomnia. Although evidence for the use of vitamins and amino acids as sole agents for psychiatric symptoms is not strong, there is intriguing preliminary evidence for the use of folate, tryptophan, and phenylalanine as adjuncts to enhance the effectiveness of conventional antidepressants. S-adenosylmethionine seems to have antidepressant effects, and omega-3 polyunsaturated fatty acids, particularly docosahexaenoic acid, may have mood-stabilizing effects. More research should be conducted on these and other natural products for the prevention and treatment of various psychiatric disorders.

Complementary and alternative medicine (CAM) in reproductive-age women: a review of randomized controlled trials

PURPOSEnComplementary and alternative medicine (CAM) therapies are widely used in the general population. This paper reviews randomized controlled trials of CAM therapies for obstetrical and gynecologic conditions and presents therapies that are likely to be used by women of reproductive age and by pregnant women.nnnDATA SOURCESnSources included English-language papers in MEDLINE 1966-2002 and AMED (1985-2000) and the authors extensive holdings.nnnSTUDY SELECTIONnRandomized controlled clinical trials of CAM therapies for obstetric and gynecologic conditions.nnnDATA EXTRACTIONnClinical information was extracted from the articles and summarized in tabular form or in the text.nnnDATA SYNTHESISnNinety-three trials were identified, 45 of which were for pregnancy-related conditions, 33 of which were for premenstrual syndrome, and 13 of which were for dysmenorrhea. Data support the use of acupressure for nausea of pregnancy and calcium for PMS. Preliminary studies indicate a role for further research on Vitamin B6 or ginger for nausea and vomiting of pregnancy; calcium, magnesium, Vitamin B6, or chaste-tree berry extract for PMS; and a low-fat diet, exercise, or fish oil supplementation for dysmenorrhea.nnnCONCLUSIONSnLimited evidence supports the efficacy of some CAM therapies. Exposure of women of reproductive age to these therapies can be expected.

Ethnobotanical literature survey of medicinal plants in the Dominican Republic used for women's health conditions.

This ethnobotanical literature survey is part of an on-going study in New York City investigating Dominican and Chinese healing systems and the herbal treatments used for the following womens conditions: uterine fibroids (benign tumors of uterine smooth muscle); menorrhagia (excessive uterine bleeding); endometriosis (growth of endometrial tissue outside of the uterus); and hot flashes (sudden brief sensations of heat commonly experienced during menopause). The objectives of this survey were: (1) to search literature on medicinal plants used in the Dominican Republic and identify those used for the above listed conditions and their symptoms; (2) to compare the use between herbal treatments reported in the literature with those prescribed by Dominican healers in New York City; and (3) to evaluate the extent to which healers may have changed their use of plants in order to adapt to availability in the New York City environment. A total of 87 plant species were reported in the Dominican literature for these conditions and symptoms. Nineteen species overlapped from the literature survey and the fieldwork with Dominican healers in New York City, representing 29% (n=65) of the plants prescribed by healers in New York City. This study offers a model to investigate changes in plant use as people migrate to urban centers where they are surrounded by diverse cultures, healing systems, and new environments.

Severity of menopausal symptoms and use of both conventional and complementary/alternative therapies

Objective To describe the prevalence and correlates of using conventional therapies, complementary and alternative therapies, or a combination of both types of therapies for menopausal symptoms and to examine the association between severity of symptoms and type of therapy use. Design Data on 2,602 women aged 45 years or older were gathered through a cross-sectional telephone survey conducted in Florida, Minnesota, and Tennessee during 1997 and 1998 using the Behavioral Risk Factor Surveillance System. Participants were asked a series of questions about their menopausal status, menopausal symptoms, healthcare provider selection in relation to menopause, and therapies used for menopausal symptoms. Results Of the eight menopausal symptoms assessed, the highest prevalence estimates were reported for hot flashes (62.9%), night sweats (48.3%), and trouble sleeping (41.1%). The average number of symptoms (range 0–8) was 3.10 (SD ± 2.25) and, for women reporting symptoms, the average symptom severity score (range 1–24) was 6.78 (SD ±4.63). About 45% of the women had not consulted with a healthcare provider for treatment of menopausal symptoms or for medical conditions related to menopause even though only 16.3% did not report any of the symptoms included in the survey. Forty-six percent of the women used complementary/alternative therapy either alone or in combination with conventional therapies. Age-adjusted average symptom severity scores were significantly higher among women who had undergone a hysterectomy, with removal of the ovaries (7.73; 95% CI 7.33,8.12) or without (7.60; 95% CI 7.16,8.05), than among women who experienced a natural menopause (6.42; 95% CI 6.14,6.71). Average severity scores were significantly higher among women who used both conventional and complementary/alternative therapies in relation to menopause (8.61; 95% CI 8.26,8.96) than among women who used only conventional therapies (7.09; 95% CI 6.67,7.50). This statistically significant association persisted when adjusted for age, education, income, race/ethnicity, state of residence, and menopausal category. Conclusions In this sample, 46% of the women used complementary/alternative therapy either alone or in combination with conventional therapies, whereas a third of the women did not use any therapy in relation to menopause. Although causal inferences cannot be made, the menopausal symptom severity score was significantly higher among women who reported using a combination of conventional and complementary/alternative therapies than among women who used only conventional therapy, only complementary/alternative, or no therapy.

The Haunting of Medical Journals: How Ghostwriting Sold “HRT”

Adriane Fugh-Berman examines documents unsealed in recent litigation to investigate how pharmaceutical companies promoted hormone therapy drugs, including the use of medical writing companies to produce ghostwritten manuscripts and place them into medical journals.