American Ginseng (Panax quinquefolius)

Human immunodeficiency virus (HIV)-infected patients often take herbal medicines, which may interact with antiretrovirals. American ginseng induces phase 2 and antioxidant enzymes in vitro and might increase the clearance of zidovudine and/or enhance antioxidant activity. Ten healthy volunteers received 300 mg of zidovudine orally before and after 2 weeks of treatment with a ginsenoside-enriched American ginseng extract 200 mg twice daily. This ginseng extract induced the phase 2 enzyme quinone reductase with an average concentration of doubling of enzyme activity of 190 microg/mL. Total ginsenoside content was 8.5 +/- 0.5%. Pharmacokinetic profiles of zidovudine and oxidative stress marker concentrations were measured post-zidovudine dose. American ginseng does not significantly affect the formation clearance of zidovudine to its glucuronide (ratio post- to pre-American ginseng = 1.17; 90% confidence interval: 0.95-1.45; P = .21), total clearance (ratio = 0.97; 0.82-1.14; P = .70), or plasma zidovudine AUC0-8 (ratio = 1.03; 0.87-1.21; P = .77). Oxidative stress biomarkers are reduced post-American ginseng (F2-isoprostane ratio = 0.79; 0.72-0.86; P < .001; 8-hydroxy-deoxyguanosine ratio = 0.74; 0.59-0.92; P = .02). Two weeks of American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative stress markers.

BACKGROUND AND OBJECTIVES: American ginseng (Panax quinquefolius L.) purportedly alleviates menopause symptoms because of putative estrogenicity. METHODS: Using a standardized American ginseng (AG) extract in MCF-7 breast cancer cells, the objectives were to evaluate the ability of AG to induce the estrogen- regulated gene pS2 by Northern blot analysis, determine the effect on cell growth using the MTT assay, and evaluate the cell cycle effects by flow cytometry. RESULTS: AG and estradiol equivalently induced RNA expression of pS2. AG, in contrast to estradiol, caused a dose-dependent decrease in cell proliferation (P < 0.005). AG had no adverse effect on the cell cycle while estradiol significantly increased the proliferative phase (percent S-phase) and decreased the resting phase (G(0)-G(1) phase) (P < 0.005). Concurrent use of AG and breast cancer therapeutic agents resulted in a significant (P < 0.005) suppression of cell growth for most drugs evaluated. CONCLUSIONS: In vitro use of AG and breast cancer therapeutics synergistically inhibited cancer cell growth. Copyright 1999 Wiley-Liss, Inc.

Compared with Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng) has received relatively little research attention. Nevertheless, across several clinical trials a common finding is that P. quinquefolius extracts improve aspects of mood, mental fatigue, and cognitive function. This review details the findings from double-blind, randomized, controlled clinical trials which included assessment of cognitive performance, fatigue, or mood, individually or in combination. Limited fatigue benefits were observed in cancer patients at high doses (2000mg). The most notable effects at lower doses (100mg-400 mg) included enhancement of attentional and working memory performance in healthy adults and in Schizophrenia patients. Several studies also highlighted potential mechanisms underlying the cognitive effects of P. quinquefolius. These include increased activation of frontoparietal neural circuits and, in the context of the gut-brain axis, alterations of the human gut microbiome composition. The effects are also consistent with cholinergic modulation. Such effects suggest that P. quinquefolius extract may have benefits to everyday cognitive function.

BACKGROUND: Diabetes mellitus and hypertension often occur together, amplifying cardiovascular disease (CVD) risk and emphasizing the need for a multitargeted treatment approach. American ginseng (AG) and Korean Red Ginseng (KRG) species could improve glycemic control via complementary mechanisms. Additionally, a KRG-inherent component, ginsenoside Rg3, may moderate blood pressure (BP). Our objective was to investigate the therapeutic potential of coadministration of Rg3-enriched Korean Red Ginseng (Rg3-KRG) and AG, added to standard of care therapy, in the management of hypertension and cardiometabolic risk factors in type-2 diabetes. METHODS: Within a randomized controlled, parallel design of 80 participants with type-2 diabetes (HbA1c: 6.5-8%) and hypertension (systolic BP: 140-160 mmHg or treated), supplementation with either 2.25 g/day of combined Rg3-KRG + AG or wheat-bran control was assessed over a 12-wk intervention period. The primary endpoint was ambulatory 24-h systolic BP. Additional endpoints included further hemodynamic assessment, glycemic control, plasma lipids and safety monitoring. RESULTS: Combined ginseng intervention generated a mean ± SE decrease in primary endpoint of 24-h systolic BP (-3.98 ± 2.0 mmHg, p = 0.04). Additionally, there was a greater reduction in HbA1c (-0.35 ± 0.1% [-3.8 ± 1.1 mmol/mol], p = 0.02), and change in blood lipids: total cholesterol (-0.50 ± 0.2 mmol/l, p = 0.01), non-HDL-C (-0.54 ± 0.2 mmol/l, p = 0.01), triglycerides (-0.40 ± 0.2 mmol/l, p = 0.02) and LDL-C (-0.35 ± 0.2 mmol/l, p = 0.06) at 12 wks, relative to control. No adverse safety outcomes were observed. CONCLUSION: Coadministration of Rg3-KRG + AG is an effective addon for improving BP along with attaining favorable cardiometabolic outcomes in individuals with type 2 diabetes. Ginseng derivatives may offer clinical utility when included in the polypharmacy and lifestyle treatment of diabetes. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01578837. © 2020 The Korean Society of Ginseng, Published by Elsevier Korea LLC.

BACKGROUND: Type 2 diabetes is known to abrogate the vascular response. Combination of two commonly consumed ginseng species, American ginseng (AG) and a Korean Red ginseng (KRG), enriched with ginsensoide Rg3, was shown to concomitantly improve glucemic control and blood pressure. We evaluated the hypothesis that improvements in central hemodynamics, vascular function and stiffness markers are involved in observed benefits of co-administration. METHODS: In this randomized, placebo controlled, two-center trial, patients with type 2 diabetes and hypertension were assigned to either 2.25 g ginsenoside Rg3-enriched KRG&AG co-administration or a control 3 times daily for 12-weeks, treated by standard of care. The effects on central hemodynamics, pulse wave velocity (PWV) and endothelial function over the 12-week administration were analyzed. RESULTS: In intent-to-treat analysis of 80 individuals, a reduction in central systolic BP (-4.69 ± 2.24 mmHg, p = 0.04) was observed with co-administration of Rg3-KRG + AG relative to control at 12-weeks, which was characterized by a decrease in end-systolic pressure (-6.60 ± 2.5 mmHg, p = 0.01) and area under the systolic/diastolic BP curve (-132.80 ± 65.1, p = 0.04, 220.90 ± 91.1, p = 0.02, respectively). There was no significant change in reactive hyperemia index (0.09 ± 0.11, p = 0.44), PWV (-0.40 ± 0.28 %, p = 0.17), and other related pulse wave analysis components. CONCLUSION: Co-administration of complementary ginseng species improved central systolic BP and components of pulse waveform without a direct effect on endothelial function, when added to background pharmacotherapy in individuals with diabetes. These data support potential utility of ginseng for modest blood pressure benefit to broaden its role in diabetes management.

Ginseng, a traditional medical herb, has been reported having beneficial effects in fatigue, heart diseases, diabetes, immune function and erectile dysfunction. In recent years, increasing investigations have been conducted on ginseng in preventing and treating of obesity, one of the major worldwide escalating public health concerns. However, the effect and the relevant mechanisms behind how ginseng works as an antiobesity treatment are still controversial. In this review, we briefly discussed the chemical structures, metabolism and pharmacokinetics of ginseng and its major bioactive components ginsenosides. The major focus is on the antiobesity effects and the physiological, cellular and molecular mechanisms of ginseng and its ginsenosides in cultured cells, animal models and humans. We particularly compared the ginsenosides profiles, the antiobesity effects and the mechanisms between Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius), the two major ginseng species having opposite medical effects in traditional Chinese medicine. Our unpublished data on the ginseng antiobesity in cultured cells and mice were also included. We further addressed the current problems and future directions of the ginseng antiobesity research.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenosides are the proposed bioactive constituent of ginseng, especially for the attenuation of postprandial glycemia (PPG). The efficacious proportion of total and specific ginsenosides, remains unknown. Alcohol extraction of whole ginseng root can be used to selectively manipulate the ginsenoside profile with increasing alcohol concentrations producing high yields of total ginsenosides and varying their individual proportions. AIM OF THE STUDY: We aimed to compare the acute efficacy of different ethanol-extraction preparations of American ginseng (AG) and Korean red ginseng (KRG), with their whole-root origins, on PPG and insulin parameters in healthy adults. MATERIALS AND METHODS: Following an overnight fast, 13 healthy individuals (Gender: 5M:8F, with mean ± SD, age: 28.9 ± 9.2 years, BMI: 26.3 ± 2.7 kg/m(2) and fasting plasma glucose: 4.21 ± 0.04 mmol/L) randomly received 3g of each of the following 10 different ginseng treatments on separate visits: whole root KRG and AG; 30%, 50% or 70% ethanol extracts of KRG and AG and 2 cornstarch placebos. Treatments were consumed 40 min prior to a 50 g oral glucose challenge test with capillary blood samples collected at baseline, 15, 30, 45, 60, 90 and 120 min. Insulin samples were collected at 0, 30, 60 and 120 min. RESULTS: There was no difference in attenuation of PPG among the tested ginseng preparations. Measures of Insulin Sensitivity Index (ISI) showed increased insulin sensitivity (IS) with KRG-30% and AG-50% extracts compared to placebo (p<0.05). CONCLUSIONS: The insulin sensitizing effects of KRG-30% and AG-50% extracts suggest that other root parts, including other ginsenosides not typically measured, may influence PPG and insulin parameters. There is potential for AG and KRG extracts to modulate IS, an independent predictor of type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Substantial pre-clinical and some clinical data are available showing that Asian ginseng (Panax ginseng C.A. Meyer) varieties or its particular ginsenosides exert a vasodilatating effect, thus may modulate vascular function. However, the clinical evidence for American ginseng (Panax quinquefolius L.) is scarce. Therefore, this study evaluates the effect of American ginseng (AG) on arterial stiffness, as measured by augmentation index (AI), and blood pressure (BP), in type 2 diabetes patients with concomitant hypertension. MATERIALS AND METHODS: Using a double-blind, placebo-controlled, parallel design, each participant was randomized to either the selected AG extract or placebo at daily dose of 3g for 12 weeks as an adjunct to their usual antihypertensive and anti-diabetic therapy (diet and/or medications). AI and BP were measured by applanation tonometry at baseline and after 12 weeks of treatment. RESULTS: A total of 64 individuals with well-controlled essential hypertension and type 2 diabetes (gender: 22 M:42 F, age:63 ± 9.3 years, BP: 145 ± 10.8/84 ± 8.0 mmHg, HbA1c: 7.0 ± 1.3%, fasting blood glucose (FBG): 8.1 ± 2.3 mmol/L) completed the study. Compared to placebo, 3g of AG significantly lowered radial AI by 5.3% (P=0.041) and systolic BP by 11.7% (P<0.001) at 12 weeks. No effect was observed with diastolic BP. CONCLUSIONS: Addition of AG extract to conventional therapy in diabetes with concomitant hypertension improved arterial stiffness and attenuated systolic BP, thus warrants further investigation on long-term endothelial parameters before recommended as an adjunct treatment. © 2013 Elsevier Ireland Ltd. All rights reserved.

RATIONALE: Over the last decade, Asian ginseng (Panax ginseng) has been shown to improve aspects of human cognitive function. American ginseng (Panax quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising cognitive enhancing properties in preclinical studies and benefits processes linked to human cognition. OBJECTIVES: The availability of a highly standardised extract of P. quinquefolius (Cereboost™) led us to evaluate its neurocognitive properties in humans for the first time. METHODS: This randomised, double-blind, placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg) of Cereboost™ (P. quinquefolius standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6 h following administration. RESULTS: There was a significant improvement of working memory (WM) performance associated with P. quinquefolius. Corsi block performance was improved by all doses at all testing times. There were differential effects of all doses on other WM tasks which were maintained across the testing day. Choice reaction time accuracy and 'calmness' were significantly improved by 100 mg. There were no changes in blood glucose levels. CONCLUSIONS: This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile.

INTRODUCTION: Functional beverages are increasingly popular but it is important to validate their purported effects through research. The aim of the current study was to investigate the effects of a new functional energy shot on cognitive performance and mood states in healthy adults, with a focus on measuring mental energy enhancement and attenuation of negative effects associated with extended performance of mentally demanding tasks. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial. Thirty-seven healthy males and females, aged 18-30 years, consumed a functional energy shot (Ryde: Energize) or placebo on separate testing occasions one-week apart. Participants completed cognitive and mood assessments pre-dose, and then 30 minutes post-dose over the course of approximately 2 hours. The functional energy shot contained caffeine, ginseng, vitamins and taurine, while the placebo shot was matched for flavor but did not contain these additional ingredients. RESULTS: Use of the functional energy shot was associated with significant improvements over placebo in cognitive performance, as measured by the Cognitive Demand Battery, with enhanced global performance, task-specific accuracy and speed across repeated assessments. Additionally, the shot mitigated negative effects associated with extended cognitive tasks, reducing perceived mental fatigue and increasing perceived alertness and energy. Working memory tasks showed faster performance post-consumption, and mood assessments revealed positive effects on vigor, fatigue and overall mood disturbance. DISCUSSION: These results indicate wide cognitive and mood effects of this functional energy shot, potentially attributable to synergistic combination of active ingredients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT06384586.

PURPOSE: To update the ASCO guideline on the management of cancer-related fatigue (CRF) in adult survivors of cancer. METHODS: A multidisciplinary panel of medical oncology, geriatric oncology, internal medicine, psychology, psychiatry, exercise oncology, integrative medicine, behavioral oncology, nursing, and advocacy experts was convened. Guideline development involved a systematic literature review of randomized controlled trials (RCTs) published in 2013-2023. RESULTS: The evidence base consisted of 113 RCTs. Exercise, cognitive behavioral therapy (CBT), and mindfulness-based programs led to improvements in CRF both during and after the completion of cancer treatment. Tai chi, qigong, and American ginseng showed benefits during treatment, whereas yoga, acupressure, and moxibustion helped to manage CRF after completion of treatment. Use of other dietary supplements did not improve CRF during or after cancer treatment. In patients at the end of life, CBT and corticosteroids showed benefits. Certainty and quality of evidence were low to moderate for CRF management interventions. RECOMMENDATIONS: Clinicians should recommend exercise, CBT, mindfulness-based programs, and tai chi or qigong to reduce the severity of fatigue during cancer treatment. Psychoeducation and American ginseng may be recommended in adults undergoing cancer treatment. For survivors after completion of treatment, clinicians should recommend exercise, CBT, and mindfulness-based programs; in particular, CBT and mindfulness-based programs have shown efficacy for managing moderate to severe fatigue after treatment. Yoga, acupressure, and moxibustion may also be recommended. Patients at the end of life may be offered CBT and corticosteroids. Clinicians should not recommend L-carnitine, antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of CRF. There is insufficient evidence to make recommendations for or against other psychosocial, integrative, or pharmacological interventions for the management of fatigue.Additional information is available at www.asco.org/survivorship-guidelines.

Ginseng is a very commonly used natural product in the world, and its two main species are Asian ginseng and American ginseng. Ginseng is an adaptogenic botanical that reportedly protects the body against stress, stabilizes physiological processes, and restores homeostasis. Previously, different animal models and contemporary research methodologies have been used to reveal ginseng's biomedical activities in different body systems and the linked mechanisms of actions. However, human clinical observation data on ginseng effects have attracted more attention from the general public and medical community. In this paper, after an introduction of the phytochemistry of ginseng species, we review positive ginseng clinical studies, mainly conducted in developed countries, performed over the past 20 years. The reported effects of ginseng are presented in several sections, and conditions impacted by ginseng include diabetes; cardiovascular disorders; cognition, memory, and mood; the common cold and flu; cancer fatigue and well-being; quality of life and social functioning, etc. Administration of ginseng demonstrated a good safety record in humans. Although encouraging beneficial effects obtained from clinical data, using the study treatment regimen, the reported ginseng effects in general only ranged from mild to moderate. Nonetheless, these beneficial effects of ginseng could be a valuable add-on therapy for patients receiving standard drug treatments. Additionally, as a dietary supplement, ginseng possesses an important role in maintaining and promoting human health. We believe that the quality of future ginseng trials should be improved, particularly by providing detailed herbal phytochemistry and quality control information. With solid effectiveness data obtained from a well-designed, carefully executed ginseng clinical trial, this meritoriously herbal medicine will be widely used by consumers and patients.

IMPORTANCE: Effective strategies for preventing type 2 diabetes are needed. Many people turn to complementary medicines, but there is little well-conducted scientific evidence to support their use. OBJECTIVE: To assess the efficacy of α-cyclodextrin for cholesterol control and that of hydrolyzed ginseng for glycemic control in people with prediabetes and overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: This 6-month double-blind, placebo-controlled, randomized clinical trial, with a 2 × 2 factorial design, was conducted between July 2015 and October 2018 at 2 locations in Sydney, Australia. Eligible participants were aged 18 years or older, had a body mass index (weight in kilograms divided by height in meters squared) of 25 or higher, and had prediabetes within 6 months of study entry according to the American Diabetes Association guidelines. Data analysis was performed from May to August 2019. INTERVENTIONS: Participants were randomized to 1 of 4 groups to take active or placebo versions of each supplement (α-cyclodextrin plus hydrolyzed ginseng, α-cyclodextrin plus placebo, placebo plus hydrolyzed ginseng, or placebo plus placebo) for 6 months. All participants received dietetic advice for weight loss. MAIN OUTCOMES AND MEASURES: The primary outcomes were the differences in total cholesterol and fasting plasma glucose between groups after 6 months. The primary analysis used the intention-to-treat principle. Multiple predetermined subsample analyses were conducted. RESULTS: A total of 401 participants were eligible for the study (248 women [62%]; mean [SD] age, 53.5 [10.2] years; mean [SD] body mass index, 34.6 [6.2]). One hundred one patients were randomized to receive α-cyclodextrin plus hydrolyzed ginseng, 99 were randomized to receive α-cyclodextrin plus placebo, 101 were randomized to receive placebo plus hydrolyzed ginseng, and 100 were randomized to receive placebo plus placebo. For 200 participants taking α-cyclodextrin compared with 201 participants taking placebo, there was no difference in total cholesterol after 6 months (-1.5 mg/dL; 95% CI, -6.6 to 3.5 mg/dL; P = .51). For 202 participants taking hydrolyzed ginseng compared with 199 partic

Objective: This study assessed whether a multi-ingredient herbal supplement containing Bacopa monniera (BM), Panax quinquefolius ginseng (PQ) and whole coffee fruit extract (WCFE) could enhance cognitive performance and cerebral-cortical activation during tasks of working memory and attention.Method: In a randomised, double-blind, placebo-controlled, between-group study, 40 healthy adults between 18-60 years (M = 34.46 SD = 12.95) completed tasks of working memory and attention at baseline and 45 min post active or placebo supplement consumption. During the cognitive testing, changes in hemodynamic response in the prefrontal cortex (PFC) were continuously measured using functional near-infrared spectroscopy (fNIRS).Results: Working memory task performance on the N-back task was significantly improved following active supplement consumption compared to placebo in terms of accuracy (p < .01) and response time (p < .05). Improved performance was associated with a reduction of PFC activation (p < .001) related to effortful mental demand, reflecting increased neural efficiency concomitant with improved cognitive performance. The effects were independent of background demographics variables and changes in blood glucose response and mood.Discussion: This is the first report of acute effects on cognitive performance in healthy adults following intake of a combined, multi-ingredient herbal supplement with concomitant changes in cerebral haemodynamic response. The potential synergistic effects of polyphenolic compounds on neurocognitive function and fNIRS use in nutritional intervention studies, poses a significant increase in the capacity to understand the effects of dietary compounds on the brain.

BACKGROUND: Prediabetes describes a state of hyperglycemia outside of normal limits that does not meet the criteria for diabetes diagnosis, is generally symptomless, and affects an estimated 38% of adults in the United States. Prediabetes typically precedes the diagnosis of type 2 diabetes, which accounts for increased morbidity and mortality. Although the use of dietary and herbal supplements is popular worldwide, and a variety of single herbal medicines have been examined for glycemic management, the potential of increasingly common polyherbal formulations to return glycemic parameters to normal ranges among adults with prediabetes remains largely unexplored. The purpose of this study is to evaluate the efficacy of a commercially available, polyherbal dietary supplement on glycemic and lipid parameters in prediabetic individuals. METHODS: In this multi-site, double-blinded, randomized controlled clinical trial, 40 participants with prediabetes will be randomized to either a daily oral polyherbal dietary supplement (GlucoSupreme™ Herbal; Designs for Health®, Suffield, CT, USA; containing cinnamon bark (Cinnamomum cassia), banaba leaf (Lagerstroemia speciosa standardized to 1% corosolic acid), kudzu root (Pueraria lobata standardized to 40% isoflavones), fenugreek seed (Trigonella foenum-graceum standardized to 60% saponins), gymnema leaf (Gymnema sylvestre standardized to 25% gymnemic acid), American ginseng root (Panax quinquefolius standardized to 5% ginsenosides), and berberine HCl derived from bark (Berberis aristata)) or placebo for 12 weeks. Short-, medium-, and comparatively long-term markers of glycemic control (blood glucose and fasting insulin, fructosamine, and glycated hemoglobin/A1c, respectively), and other glycemic parameters (GlycoMark, β-cell function, and insulin sensitivity/resistance) will be obtained. Lipid profile (total cholesterol, LDL, HDL, and triglycerides), inflammation (hs-CRP), progression to type 2 diabetes mellitus, as well as safety indices (ALT, AST) will be obtained. An intention-to-treat analysis will be used to assess changes in study outcomes. DISCUSSION: Treatment options for adults with prediabetes are currently limited.

OBJECTIVE: To determine whether American ginseng (Panax Quinquefolium) confers antioxidant protection to postmenopausal women at rest and after a mild aerobic exercise session. METHODS: In this double-blinded parallel study, 12 female subjects (age range 55-75) consumed two capsules, containing 500 mg of dry American ginseng whole-root powder, everyday for 4 months, whereas 13 female control subjects of the same age range consumed two placebo capsules. Before and after the supplementation regimen each subject performed 30 minutes of treadmill walking on a 5% grade incline at an estimated 60% of VO(2)max. RESULTS: Ginseng supplementation had no effect on heart rate, blood pressure, plasma blood glucose, or lactate concentration at rest or immediately after exercise tests. The ginseng supplemented group displayed a higher resting plasma glutathione disulfide (GSSG) concentration and lower glutathione (GSH):GSSG ratio, as well as a lower resting total antioxidant content (TAC). Plasma GSSG concentration decreased, whereas the GSH:GSSG ratio and TAC increased after exercise in all subjects. Furthermore, plasma malondialdehyde and urine 8-hydroxydeoxyguanosine concentrations were elevated in the ginseng-supplemented group. Erythrocyte superoxide dismutase and GSH reductase activities were increased after ginseng supplementation. The 30-minute treadmill walking, however, did not alter these changes. CONCLUSIONS: These data suggest that chronic American ginseng supplementation at the given dose can cause an oxidative stress in postmenopausal women, as reflected by the elevated oxidative damage markers and the increased erythrocyte antioxidant enzyme activity.

OBJECTIVE: To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms. METHODS: A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography. RESULTS: The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group. CONCLUSION: Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.

AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance. METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo) and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk. They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover, the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise, immediately after exercise, and 20, 40, 60, and 120 min after exercise. RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen. CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.

BACKGROUND: People using prescription medication often concurrently take herbal supplements. In a case report, the anticoagulant effect of warfarin decreased after patients consumed ginseng. OBJECTIVE: To evaluate the interactions between American ginseng and warfarin. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General Clinical Research Center, University of Chicago, Chicago, Illinois. PARTICIPANTS: 20 healthy patients. INTERVENTION: In this 4-week study, 20 patients received warfarin for 3 days during weeks 1 and 4. Beginning in week 2, patients were assigned to receive either American ginseng or placebo. MEASUREMENTS: International normalized ratio (INR) and plasma warfarin level. RESULTS: The peak INR statistically significantly decreased after 2 weeks of ginseng administration compared with placebo (difference between ginseng and placebo, -0.19 [95% CI, -0.36 to -0.07]; P = 0.0012). The INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC were also statistically significantly reduced in the ginseng group as compared with the placebo group. Peak INR and peak plasma warfarin level were positively correlated. LIMITATIONS: The study sample consisted of young, healthy volunteers in a research setting rather than patients taking therapeutic doses of warfarin. CONCLUSIONS: American ginseng reduces warfarin's anticoagulant effect. When prescribing warfarin, physicians should ask patients about ginseng use.

OBJECTIVE: To create an evidence-based position statement regarding the treatment of vasomotor symptoms associated with menopause. DESIGN: The North American Menopause Society (NAMS) enlisted clinicians and researchers acknowledged to be experts in the field of menopause-associated vasomotor symptoms to review the evidence obtained from the medical literature and develop a document for final approval by the NAMS Board of Trustees. RESULTS: For mild hot flashes, lifestyle-related strategies such as keeping the core body temperature cool, participating in regular exercise, and using paced respiration have shown some efficacy without adverse effects. Among nonprescription remedies, clinical trial results are insufficient to either support or refute efficacy for soy foods and isoflavone supplements (from either soy or red clover), black cohosh, or vitamin E; however, no serious side effects have been associated with short-term use of these therapies. Single clinical trials have found no benefit for dong quai, evening primrose oil, ginseng, a Chinese herbal mixture, acupuncture, or magnet therapy. Few data support the efficacy of topical progesterone cream; safety concerns should be the same as for other progestogen preparations. No clinical trials have been conducted on the use of licorice for hot flashes. Among nonhormonal prescription options, the antidepressants venlafaxine, paroxetine, and fluoxetine and the anticonvulsant gabapentin have demonstrated some efficacy for treating hot flashes and were well tolerated. Two antihypertensive agents, clonidine and methyldopa, have shown modest efficacy but with a relatively high rate of adverse effects. For moderate to severe hot flashes, systemic estrogen therapy, either alone (ET) or combined with progestogen (EPT) or in the form of estrogen-progestin oral contraceptives, has been shown to significantly reduce hot flash frequency and severity. Clinical trials have associated ET/EPT with adverse effects, including breast cancer, stroke, and thromboembolism. Several progestogens (both oral and intramuscular formulations) have shown efficacy in treating hot flashes, including women with a history of breast cancer, althou

OBJECTIVE: To review the evidence of herbs commonly used by women. DATA SOURCES: Articles were located by searching Medline, Cochrane Database of Systemic Reviews, and the Combined Health Information Database and by hand searching the reference lists of recent systematic reviews. The databases were searched in January 2000 and October 2000 by using the Latin and common name of each herb. METHODS OF STUDY SELECTION: Preference was given to randomized, placebo-controlled trials. When available, English language studies were reviewed. If not, data are presented from review articles that summarize the foreign study. RESULTS: Many women use herbal therapies. In the United States, herbs are considered dietary supplements. The Food and Drug Administration (FDA) cannot remove them from the market unless they are proven unsafe. The herb industry plans to improve monitoring. Many prospective randomized controlled trials are being funded. Gingko biloba seems to slow the progression of dementia but increases the risk of bleeding. St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Ginseng seems to improve well being in perimenopausal women, but it is often impure and has side effects and drug interactions. Garlic slightly lowers blood pressure and lipids. Echinacea slightly decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia, but there is no long-term safety data. Black cohosh may help the symptoms of perimenopause, and chasteberry may improve premenstrual syndrome. More study is needed on both herbs. CONCLUSION: Some herbs are medically useful, but the American public would benefit from increased regulation. Manufacturers should be able to ensure that herbs contain pure ingredients. Side effects and drug interactions should be listed. Well-designed studies are being conducted. The results will be helpful to physicians and patients when the clinical evidence becomes available.

OBJECTIVE: To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. RESULTS: A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. CONCLUSIONS: There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.

OBJECTIVE: To review the evidence of herbs commonly used by women. DATA SOURCES: Articles were located by searching Medline, Cochrane Database of Systemic Reviews, and the Combined Health Information Database and by hand searching the reference lists of recent systematic reviews. The databases were searched in January 2000 and October 2000 by using the Latin and common name of each herb. METHODS OF STUDY SELECTION: Preference was given to randomized, placebo-controlled trials. When available, English language studies were reviewed. If not, data are presented from review articles that summarize the foreign study. RESULTS: Many women use herbal therapies. In the United States, herbs are considered dietary supplements. The Food and Drug Administration (FDA) cannot remove them from the market unless they are proven unsafe. The herb industry plans to improve monitoring. Many prospective randomized controlled trials are being funded. Gingko biloba seems to slow the progression of dementia but increases the risk of bleeding. St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Ginseng seems to improve well being in perimenopausal women, but it is often impure and has side effects and drug interactions. Garlic slightly lowers blood pressure and lipids. Echinacea slightly decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia, but there is no long-term safety data. Black cohosh may help the symptoms of perimenopause, and chasteberry may improve premenstrual syndrome. More study is needed on both herbs. CONCLUSION: Some herbs are medically useful, but the American public would benefit from increased regulation. Manufacturers should be able to ensure that herbs contain pure ingredients. Side effects and drug interactions should be listed. Well-designed studies are being conducted. The results will be helpful to physicians and patients when the clinical evidence becomes available.

OBJECTIVES: To review use of alternative pharmacotherapy (AP) in patients with cardiovascular disease (CVD) and significant drug interactions between AP and traditional CVD medications. STUDY DESIGN: A literature search of MEDLINE and the National Complementary and Alternative Medicine database was done using these search terms: supplements, vitamins, garlic, fish oil, L-arginine, soy, coenzyme Q10, herbs, phytosterols, chelation therapy, alternative medicine, and CVD. PATIENTS AND METHODS: English human clinical trials measuring surrogate and clinical end points. RESULTS: Antioxidants have not been consistently proven beneficial in reducing cardiovascular mortality. Fish oils may be beneficial in patients with hypertension and hypercholesterolemia, but therapeutic doses need to be defined. Use of coenzyme Q10 in patients with heart failure has not demonstrated consistent benefits. Garlic may lower blood pressure and cholesterol levels, but also may increase bleeding, so its use in CVD patients should be monitored. Clinical studies with small sample sizes have demonstrated that L-arginine may be useful to prevent and treat CVD. The Food and Drug Administration recommends 25 g/day of soy protein as part of a diet low in saturated fats for cholesterol reduction. Plant sterols are recommended by the American Heart Association and the National Cholesterol Education Program Expert Panel as adjunct therapy to reduce low-density lipoprotein. No data support use of chelation therapy. Some APs interact with common prescription CVD medications (eg, gingko and ginseng with warfarin, St. John's Wort with digoxin). CONCLUSIONS: The benefits of APs as part of the treatment for CVD are controversial. Routine use is not recommended.