Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial.

OBJECTIVE: To determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects. DESIGN: A 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement. SUBJECTS: Sixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months. EFFICACY: changes in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices. SAFETY: blood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms. RESULTS: Forty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality. CONCLUSION: A dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.

Quantitative determination of ginsenosides by high-performance liquid chromatography-tandem mass spectrometry.

An HPLC-MS/MS method was developed for the quantitative determination of ginsenosides, which are the marker compounds for herbal products containing Panax ginseng (Korean or Chinese ginseng) and P. quinquefolius (American ginseng). Samples were extracted with BondElut C18 HF extraction columns and the concentrations of seven major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) were determined by reversed-phase HPLC-MS/MS employing a quadrupole-ion trap mass spectrometer. Both positive and negative electrospray ionisation techniques were evaluated. Positive ionisation spectra of these compounds gave strong sodium adduct molecular and sodium adduct dimer ions. Negative ionisation yielded the molecular ion primarily and was, therefore, used for analysis: quantitative determination was based on the most abundant product ions for each ginsenoside. The method was used to extract and analyse commercial samples of P. ginseng and P. quinquefolius.

Variability in commercial ginseng products: an analysis of 25 preparations.

BACKGROUND: Because dietary supplements are not subject to the same regulations that pharmaceuticals are, there is concern among medical professionals that these products may lack purity or potency. OBJECTIVE: To determine the variability in a range of ginseng herbal products available in the United States, we identified and measured the concentration of marker compounds by using HPLC and liquid chromatography-tandem mass spectrometry. DESIGN: Twenty-five commercial ginseng preparations from the genera Panax or Eleutherococcus were obtained from a local health food store and analyzed for 7 ginsenosides (marker compounds for Panax species, which include Asian and American ginseng) and 2 eleutherosides (marker compounds for Eleutherococcus senticosus, also known as Siberian ginseng). RESULTS: All plant products were correctly identified by botanical plant species (ie, Panax species or E. senticosus); however, concentrations of marker compounds differed significantly from labeled amounts. There was also significant product-to-product variability: concentrations of ginsenosides varied by 15- and 36-fold in capsules and liquids, respectively, and concentrations of eleutherosides varied by 43- and 200-fold in capsules and liquids, respectively. Although a systematic search for adulterants was not conducted, review of the HPLC and liquid chromatography-tandem mass spectrometry data suggest that no substances other than ginsenosides or eleutherosides were extracted from the plant material. CONCLUSION: Our data suggest that US ginseng products are correctly labeled as to plant genus; however, variability in concentrations of marker compounds suggests that standardization may be necessary for quality assurance and that characterization of herbal products should be considered in the design and evaluation of studies on herbal products.

Hypnosis and asthma: a critical review.

Asthma is among the most common chronic diseases of the western world and has significant effects on patients' health and quality of life. Asthma is typically treated with pharmaceutical products, but there is interest in finding nonpharmaceutical therapies for this condition. Hypnosis has been used clinically to treat a variety of disorders that are refractive to pharmaceutical-based therapies, including asthma, but relatively little attention has been given recently to the use of clinical hypnosis as a standard treatment for asthma. Significant data suggest that hypnosis may be an effective treatment for asthma, but it is premature to conclude that hypnosis is unequivocally effective. Studies conducted to date have consistently demonstrated an effect of hypnosis with asthma. More and larger randomized, controlled studies are needed. Existing data suggest that hypnosis efficacy is enhanced in subjects who are susceptible to the treatment modality, with experienced investigators, when administered over several sessions, and when reinforced by patient autohypnosis. Children in particular appear to respond well to hypnosis as a tool for improving asthma symptoms.

Effects of ginseng components on c-DNA-expressed cytochrome P450 enzyme catalytic activity.

Because little is known about the interactions between herbal products and standard medications, the effects of seven ginsenosides and two eleutherosides (active components of the ginseng root) on the catalytic activity of c-DNA expressed cytochrome P450 isoforms were studied in in vitro experiments. Increasing concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 and eleutherosides B and E were incubated with a panel of recombinant human CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and their effects on the conversion of specific surrogate substrates measured fluorometrically in a 96-well plate format. For each test substance, the IC50 (the concentration required to inhibit the metabolism of the surrogate substrates by 50%) was estimated and this value compared with that obtained for positive control inhibitory drugs furafylline, sulfaphenazole, tryanylcypromine, quinidine, and ketoconizole. Of the components tested, three ginsenosides (Rd, Rc, and Rf) modified the activity of the recombinant enzymes. Ginsenoside Rd produced weak inhibitory activity against the surrogate substrates for CYP3A4 and CYP2D6 and even weaker inhibitory activity against the surrogate substrates for CYP2C19 and CYP2C9. The IC50 values of 58 and 74 uM for the two substrates for CYP3A4 are orders of magnitude higher than that for the potent inhibitor ketoconazole used as a positive control. Ginsenoside Rc produced an increase in the activity of CYP2C9 (70% at 200 uM) and ginsenoside Rf produced an increase in the activity of CYP3A4 (54% at 200 uM). The biological significance of this is unclear at this time. Enzyme "activation", the process by which direct addition of one compound to an enzyme enhances the rate of reaction of the substrate, has been observed in a number of cases with P450 enzymes; however, a matrix effect caused by the test compound fluorescing at the same wavelength as the metabolite of the marker substrate cannot be ruled out. In summary, these studies suggest that the ginsenosides and eleutherosides tested are not likely to inhibit the metabolism of coadministered medications in which the primary route of elimination is via cytochrome P450; the potential of ginsenosides to enhance the catalysis of certain substrates requires further investigation.

Mushrooms, tumors, and immunity.

Medicinal properties have been attributed to mushrooms for thousands of years. Mushroom extracts are widely sold as nutritional supplements and touted as beneficial for health. Yet, there has not been a critical review attempting to integrate their nutraceutical potential with basic science. Relatively few studies are available on the biologic effects of mushroom consumption, and those have been performed exclusively in murine models. In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects. We believe that the antitumor mechanisms of several species of whole mushrooms as well as of polysaccharides isolated from Lentinus edodes, Schizophyllum commune, Grifola frondosa, and Sclerotinia sclerotiorum are mediated largely by T cells and macrophages. Despite the structural and functional similarities of these glucans, they differ in their effectiveness against specific tumors and in their ability to elicit various cellular responses, particularly cytokine expression and production. Unfortunately, our data base on the involvement of these important mediators is still rather limited, as are studies concerning the molecular mechanisms of the interactions of glucans with their target cells. As long as it remains unclear what receptors are involved in, and what downstream events are triggered by, the binding of these glucans to their target cells, it will be difficult to make further progress in understanding not only their antitumor mechanisms but also their other biological activities.

The use of complementary/alternative medicine for the treatment of asthma in the United States.

Despite our advances in the diagnosis and treatment of asthma, the incidence of mortality is increasing in developed countries. As patients and health care providers seek new options for the treatment and prevention of asthma, various complementary and alternative medical therapies are being used. With funding from the Office of Alternative Medicine, National Institutes of Health, our goal was to identify the type and prevalence of complementary and alternative treatments for asthma in use in the United States in order to establish a research agenda for the study of the most promising therapies. A survey was developed by an expert panel. After undergoing a preliminary round of testing and improvement, the survey was then sent along with a postage-paid return envelope as inserts in the May 1996 issue of Alternative Therapies in Health and Medicine, a peer-reviewed periodical of complementary and alternative medical research and scholarly activity; 10,000 surveys were distributed. We asked that only those who treated asthma respond. The surveys were designed to identify characteristics of the respondent, their particular practice type, use of complementary and alternative medicine, or conventional medicine in general, patient characteristics and numbers, and their use of 20 specific potential therapies to treat asthma. A total of 564 surveys were returned. The 5.64% response rate was low but was reflective of the demographics of the readership of this journal of complementary and alternative medicine. The survey population was 46% male and 43% female; 11% did not specify gender. They ranged in age from under 31 years old to over 70. The largest group (37%) of respondents held degrees as medical doctors, 27% held doctorates in complementary and alternative medicine related disciplines, 11% had registered nursing degrees, 4% were acupuncturists and 18% did not specify their training. Practice characteristics between MD and non-MD asthma care providers did not differ. The majority had general practices (75%) seeing all ages of patients. MDs were less likely to employ complementary and alternative medicine techniques for asthma compared to non-MDs. Both groups identified dietary and nutritional approaches as their most prevalent and useful asthma treatment option. Use of botanicals, meditation and homeopathy were frequently cited; statistically significant differences appeared in the rankings of treatment usefulness and prevalence between MD and non-MDs. Non-MD asthma care providers were more likely to ask patients about their use of complementary and alternative treatments for asthma than MDs (92% vs. 70%), while both groups showed statistically significant increases in their levels of patient inquiries compared to 2 years previously (up 9% and 8% for MDs and non-MDs respectively). The predominance of diet and nutrition supplementation used by MDs and non-MDs suggests that further attention and research efforts should be directed toward this area of complementary and alternative practice. Other complementary and alternative medicine practices such as botanicals, meditation and homeopathy appear to warrant research efforts. Differences between MDs and non-MDs in their use of such therapies may reflect different philosophies as well as training.

Acupuncture in the treatment of asthma: a critical review.

BACKGROUND: Increasingly, patients are turning to treatments and drugs that are considered "alternative" or "complementary" as part of their healthcare. In response, the National Institutes of Health (NIH) established an Office of Alternative Medicine (OAM) in 1992 to facilitate identification and evaluation of alternative and complementary therapies. Acupuncture, a therapy that has been used to treat disease in China for approximately 2,500 years has attracted considerable attention. NIH in a consensus statement derived from a Fall of 1997 consensus conference to assess acupuncture has indicated that acupuncture was useful in pain control and maybe a useful adjunct treatment for the management of asthma. Further, the US Food and Drug Administration has removed acupuncture from the "experimental medical devices" category. METHODS: We have extensively searched the literature for reports addressing the use of acupuncture in asthma treatment. We sought these using the National Library of Medicine, the Office of Alternative Medicine's database as well as other databases both English language based as well as other languages that catalog literature pertaining to alternative and complementary therapies. We then reviewed these reports and weighted the validity of the conclusions reached in the reports based on assessment of study design, number of subjects studied, duration of studies, types and number of controls, and statistical analyses used. RESULTS: Data presently in the literature do not provide sufficient support for a useful role for acupuncture in asthma management. CONCLUSIONS: Further properly designed clinical studies examining the use of acupuncture in asthma are extremely important and urgently needed.

Complementary medicine: a review of immunomodulatory effects of Chinese herbal medicines.

Popular demand for and scientific interest in complementary or alternative medicine, particularly medicinal botanicals, has increased considerably in recent years. The medicinal botanicals with the longest tradition, and for which extensive data are available, are Chinese herbal medicines and their Japanese counterparts--Kampo medicines. This review focuses on some representative examples of studies examining the effects of some traditional Chinese medicines on various aspects of the immune response. In vitro as well as in vivo studies are cited, the latter including not only animal experiments but also clinical trials. Although by no means exhaustive, this review attempts to show that much research has focused on the specific beneficial effects of Chinese herbal medicines. Studies examining the mechanisms by which they exert their immunomodulatory actions, however, are found much less frequently. Nonetheless, even the limited number of mechanistic experiments presented here reveal that numerous mechanisms are likely involved in the various actions of even a single medicine. It will be the elucidation of such mechanisms that will provide the scientific basis for establishing the efficacy and safety of not only Chinese herbal medicines but all forms of medicinal botanicals.

Phosphorus magnetic resonance spectra and changes in body composition during weight loss.

OBJECTIVE: The use of magnetic resonance spectroscopy (MRS) to monitor cellular bioenergetics during weight loss may provide novel insights regarding metabolic functioning. METHODS: Changes were noted in 18 sedentary, moderately overweight women following a 7-week program consisting of a low-fat, 422-428 MJ/day (1010-1025 kcal/day) diet, a progressive walking program, a vitamin-mineral-fortified, isolated-protein meal supplement drink and a weekly group meeting. Mitochondrial energy production and utilization were assessed by measuring the concentrations of inorganic phosphate (Pi) and phosphocreatine (PCr) through magnetic resonance spectroscopy. Anthropometric changes were also monitored. RESULTS: Dietary analysis of subjects' pre-intervention food records showed intakes of numerous vitamins and minerals below 100% of the Recommended Dietary Allowances (RDA), most commonly for folic acid, vitamin E, magnesium, iron and zinc. Relative to pre-intervention levels, final measurements showed that all women lost body weight, ranging from 2.6 to 10.0 kg. Body mass index declined in all subjects, from 0.55 to 3.86 kg/m2. All subjects lost fat mass, ranging from 0.9 to 10.4 kg. Seventeen of 18 women showed a decline in their percentage of body fat, ranging from 2.3 to 10.1%. Twelve of 18 subjects showed an increase of 0.1-3.5 kg of fat-free mass, with half of these values increasing by > 1.0 kg. No changes from baseline levels were found in the Pi/PCr ratio over 7 weeks under resting, exercise or recovery conditions, suggesting a preservation in muscle energy function over the course of the study while the subjects were losing fat mass and total body weight. CONCLUSIONS: The possible metabolic advantage associated with a program that employs moderate energy restriction, repletion of vitamin and mineral intakes to RDA levels, and a regular aerobic exercise program is proposed.

The Athletic Trainer's Role in Modifying Nutritional Behaviors of Adolescent Athletes: Putting Theory into Practice.

Nutritional practices influence athletic performance and recovery from injury. The athletic trainer is ideally positioned to effect dietary changes with adolescent athletes-a group at high-risk for nutritional imbalances. Research shows that young adults generally do not change dietary practices when given factual nutrition and health information. This article provides a variety of behavior change strategies, based on models derived from health education and health psychology, which are likely to influence dietary choices. Promoting self-efficacy by enhancing perception of choice and control, peer modeling, cooperative support networks, goal-setting techniques, and behavioral self-monitoring may provide the motivational framework necessary to enhance dietary compliance. Dietary behavior change techniques are a valuable part of an athletic trainer's resources.

The significance of receptor physiology for corticosterone-induced cleft palate in A/J mice.

Mean plasma corticosterone levels of A/J mice rise from nonpregnant levels of 20.4 micrograms % to 40.6 micrograms % on day 11 and 167.11 micrograms % on day 14 of pregnancy. These changes in mean steroid levels are associated with proportionally increased diurnal swings. This suggests that the control mechanisms for diurnal swings respond in a proportional, rather than an absolute, way in regulating plasma hormone levels. Large diurnal hormone swings may be teratogenic or facilitate teratogenesis. The rules of receptor physiology may have wide application to the understanding of teratogenic risk.

Interactions of salicylate, dietary zinc, and genetic strain in teratogenesis in rats.

The influence of dietary zinc concentration on salicylate teratogenesis was studied in Wistar and Sprague-Dawley rats. Females were fed purified diets containing 0.4, 4.5, 9, 100, or 1,000 micrograms zinc/gm diet, or a stock diet (Purina Rat Chow) from day zero to day 21 of gestation, when they were killed and the fetuses were examined. On day 9, rats were given saline or 250, 500, or 750 mg sodium salicylate/kg body weight by gavage. Increasing drug dose caused increased frequency of malformed or resorbed fetuses, while increasing dietary zinc reduced the teratogenic effects of salicylate, but in different patterns in the two strains. The teratogenic effect of zinc deficiency also varied by strain. Statistical analysis showed that the frequency of malformed fetuses was significantly affected by levels of dietary zinc or salicylate dose, and interactions of zinc X salicylate and genetic strain X zinc. Frequency of resorption was affected by strain, zinc, salicylate, and interactions of strain X salicylate, zinc X salicylate, and strain X zinc X salicylate. Frequency of abnormal sites (malformed or resorbed) was affected by strain, zinc, salicylate, and interactions of strain X salicylate, zinc X salicylate, and strain X zinc X salicylate. The results suggest that marginal zinc deficiency in certain pregnant women might increase the possibility of salicylate teratogenicity.

Interaction of dietary zinc, genetic strain, and acetazolamide in teratogenesis in mice.

The effect of dietary zinc and genetic strain on acetazolamide-induced malformations was assessed. CBA (sensitive) and SWV (resistant) mice were fed purified diets containing five different levels of zinc throughout gestation and were given acetazolamide orally for a limited period during organogenesis. Controls received either no treatment or the drug vehicle. Litters were assessed for resorptions and malformations at term. The significance for influencing litter outcome was tested for the three main treatments: strain, dietary zinc level, and acetazolamide dose, plus their interactions. The magnitude of the litter response was strongly influenced by strain. The incidence of forelimb ectrodactyly, a characteristic malformation caused by acetazolamide, was much greater in CBA than in SWV fetuses. SWV fetuses had no ectrodactyly when dams were fed at least 9 micrograms/g zinc, but 5-8% showed ectrodactyly when dams received a zinc-deficient (0.4 or 4.5 micrograms/g) diet. The incidence of ectrodactyly in the CBA strain decreased as dietary zinc increased, but was still present when dams were fed a high (1,000 micrograms/g) zinc diet. The incidence of resorptions and total abnormal sites from litters of dams receiving acetazolamide decreased as dietary zinc increased, with the magnitude of the response being influenced by the strain. A significant (dietary zinc X acetazolamide) and (strain X acetazolamide) interaction was found for the ectrodactyly response. The results demonstrate the importance of considering interactions among genetic strain, diet, and drugs, as well as single factors as determinants of fetal risk.