ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium.

BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.

Efficacy and tolerability of a novel herbal formulation for weight management.

OBJECTIVE: To evaluate the efficacy of an herbal blend. DESIGN AND METHODS: A randomized, double-blind, clinical trial in 60 subjects with body mass index (BMI) between 30 and 40 kg/m(2) . Participants were randomized into two groups receiving either 400 mg herbal capsules or 400 mg placebo capsules twice daily. The herbal blend comprises of extracts from Sphaeranthus indicus and Garcinia mangostana. Participants received a standard diet (2,000 kcal per day) and walked 30 min 5 days per week. RESULTS: After 8 weeks, significant net reductions in body weight (3.74 kg; P < 0.0001), BMI (1.61 kg/m(2) ; P < 0.0001), and waist circumference (5.44 cm; P < 0.05) were observed in the herbal group compared with placebo. Additionally, a significant increase in serum adiponectin concentration was found in the herbal group versus placebo (P = 0.001). Adverse events were mild and were equally distributed between the two groups. In vitro studies in the 3T3-L1 adipocyte cell line showed that the herbal extract markedly downregulated the expression of peroxisome proliferator-activated receptor gamma, adipocyte-differentiation related protein, and cluster of differentiation 36 but increased adiponectin expression. The herbal extract also reduced the expression and the recruitment of perilipin onto the membrane of lipid droplets. CONCLUSION: Supplementation with the herbal blend resulted in a greater degree of weight loss than placebo over 8 weeks.

Gilles de la Tourette syndrome in pregnancy: a retrospective series.

Tourette syndrome is a neuropsychiatric syndrome characterized by motor and vocal tics with further co-morbidities, e.g. obsessive-compulsive disorder and attention deficit hyperactivity disorder. There is only a single prior case report in pregnancy in addition to a postal questionnaire study including 10 pregnancies. In a series of 11 pregnancies in patients assessed by the authors, there were no adverse effects on the pregnancy, although some obstetricians were unduly concerned. There was no consistent effect on the severity of the tics, although in some women there seemed to be a significant improvement during pregnancy.

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.

Distributed neural actions of anti-parkinsonian therapies as revealed by PET.

There is a limited understanding of how different anti-parkinsonian treatments act at the neuronal systems level. Using positron emission tomography we examined the effects of levodopa and deep brain stimulation of the subthalamic nucleus on patterns of regional cerebral blood flow in patients with Parkinson's disease during a homogenous cognitive-behavioural state rather than during an unspecified resting state. We found that when medicated precuneus, frontal, parietal, cerebellar and midbrain areas were relatively more activated than when stimulated, whereas when stimulated the precentral gyrus, caudate and thalamus were relatively more activated than when medicated. Areas that were activated by both treatments included the temporal gyri, anterior thalamus, and midbrain. Regions of prefrontal cortex showed relatively greater activation in the "off treatment" conditions of both the medicated and stimulated groups. Our findings suggest that the two treatment methods may lead to symptomatic relief via both common and different sites of action.

Gilles de la Tourette's syndrome and its impact in the UK.

Gilles de la Tourette's syndrome of chronic multiple motor and vocal tics is now acknowledged to be far more common than once thought, affecting up to 1% of schoolchildren with a wide range of severity. At the milder end of the spectrum the associated psychopathologies can in themselves impair social and educational functioning, in particular obsessive compulsive disorder and attention deficit hyperactivity disorder. Many patients with this condition are not being adequately served by health and education services in the UK. The epidemiology, clinical features, aetiological factors, and management of the syndrome are reviewed.

Low bone mass in premenopausal chronic dieting obese women.

BACKGROUND: Obese premenopausal women are thought to be at low risk for osteoporosis due to increased body weight and effects of estrogen on weight-bearing bone. OBJECTIVE: To examine the effect of restrained eating on obese women, we examined bone mineral density (BMD) and content (BMC) of the spine and femur in obese women who were restrained eaters, with emphasis on the relationship between BMC and determinants of bone mass, and current eating behaviors, dietary intake, physical activity, and indices of calcium regulation, bone metabolism, stress and inflammation. DESIGN: A total of 78 obese, Caucasian, female, restrained eaters, ages 30-45 y, were enrolled in a weight lose program. Height, weight, bone turnover markers, serum parathyroid hormone (PTH), cortisol, c-reactive protein (CRP), dietary intake, eating behaviors, physical activity, and BMD and BMC were measured. SETTING: This study was conducted at the University of California, in Davis, CA, USA. RESULTS: In all, 31% of women had osteopenia or osteoporosis (OSTEO). In the OSTEO group, 87.5% of women had osteoporosis or osteopenia of the lumbar spine and 12.5% of the women had osteoporosis or osteopenia in femur. A significant positive correlation between BMC and energy expenditure (r=0.256), and a significant negative correlation between BMC and number of times on a weight loss diet (r=-0.250) and cognitive restraint (r=-0.239) were observed. No significant differences were observed between OSTEO women and nonosteoporotic women for current eating behaviors, dietary intake, physical activity habits, bone turnover, calcium regulation, stress, or inflammation. CONCLUSIONS: Obese restrained eaters are at risk for low bone mass. Prior dieting may be responsible. Chronic dieters should be encouraged to decrease their dietary restraint, develop healthy eating habits and increase physical activity.

Evaluating a 'non-diet' wellness intervention for improvement of metabolic fitness, psychological well-being and eating and activity behaviors.

CONTEXT: Current public health policy recommends weight loss for obese individuals, and encourages energy-restricted diets. Others advocate an alternative, 'non-diet' approach which emphasizes eating in response to physiological cues (eg hunger and satiety) and enhancing body acceptance. OBJECTIVE: To evaluate the effects of a 'health-centered' non-diet wellness program, and to compare this program to a traditional 'weight loss-centered' diet program. DESIGN: Six-month, randomized clinical trial. SETTING: Free-living, general community. PARTICIPANTS: Obese, Caucasian, female, chronic dieters, ages 30-45 y (n=78). INTERVENTIONS: Six months of weekly group intervention in a non-diet wellness program or a traditional diet program, followed by 6 months of monthly after-care group support. OUTCOME MEASURES: Anthropometry (weight, body mass index); metabolic fitness (blood pressure, blood lipids); energy expenditure; eating behavior (restraint, eating disorder pathology); psychology (self-esteem, depression, body image); attrition and attendance; and participant evaluations of treatment helpfulness. Measures obtained at baseline, 3 months, 6 months and 1 y. RESULTS: (1 y after program initiation): Cognitive restraint increased in the diet group and decreased in the non-diet group. Both groups demonstrated significant improvement in many metabolic fitness, psychological and eating behavior variables. There was high attrition in the diet group (41%), compared to 8% in the non-diet group. Weight significantly decreased in the diet group (5.9+/-6.3 kg) while there was no significant change in the non-diet group (-0.1+/-4.8 kg). CONCLUSIONS: Over a 1 y period, a diet approach results in weight loss for those who complete the intervention, while a non-diet approach does not. However, a non-diet approach can produce similar improvements in metabolic fitness, psychology and eating behavior, while at the same time effectively minimizing the attrition common in diet programs.

Chitosan supplementation does not affect fat absorption in healthy males fed a high-fat diet, a pilot study.

BACKGROUND: The use of dietary supplements, especially those for weight control, is increasing. Advertising claims for some of these supplements may give consumers unrealistic expectations. For example, it is claimed that the supplement chitosan can block the absorption of up to 120 g of dietary fat per day. OBJECTIVE: To test the effect of a chitosan supplement used as directed, on the absorption of dietary fat. DESIGN: Seven healthy male volunteers with average age 28, range 23-30, average body mass index (BMI) 26, range 23-31, maintained a high fat intake (>120 g/day) for 12 days. On days 6-9, chitosan was taken as directed by the manufacturer prior to meals and snacks and totaled 15 capsules or 5.25 g of chitosan daily. A charcoal marker was consumed on days 2, 6 and 10 to mark the baseline and supplement periods. All feces were collected on days 2-12, and were divided based on the appearance of charcoal in the feces. Fecal fat content corresponding to the four baseline and four chitosan-supplemented days was measured. RESULTS: Average dietary fat intake did not differ between baseline (135+/-5 g), and chitosan (135+/-3 g) periods. Fecal fat excretion did not differ between the two periods (6.9+/-1.0 g/day baseline; 6.8+/-0.4 g/day chitosan). The fecal fat content as a percentage of fat consumed did not differ (5.1+/-0.7% baseline, 5.0+/-0.3% chitosan). Fecal mass did not differ (176+/-26 g/day baseline, 182+/-14 g/day chitosan). CONCLUSION: Consumption of this chitosan supplement did not increase fecal fat content and therefore did not block fat absorption.

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.

Hyperphagia as a mediator of renal disease initiation in obese Zucker rats.

OBJECTIVE: We sought to determine whether prevention of overeating would block the very earliest manifestations of renal injury in young obese Zucker rats (OZRs). RESEARCH METHODS AND PROCEDURES: Three groups of rats were studied, obese (fa/fa) Zucker rats and lean (Fa/Fa). Zucker controls were allowed to feed ad libitum, whereas a group of obese (fa/fa) Zucker rats was pair-fed to the lean group. Urine albumin and serum lipids were studied weekly from 6 to 10 weeks of age. Renal pathology and renal glomerular gene expression were examined when the rats were killed at 10 weeks of age. RESULTS: Obese rats fed ad libitum developed significant albuminuria by 6 weeks of age, increasing at each subsequent time-point. This increase was completely blocked by pair-feeding. Serum triglycerides were significantly increased in obese rats fed ad libitum vs. the other groups. Urine albumin correlated significantly with both body weight and serum triglyceride level. Renal histopathology was normal in all groups. Analysis of gene expression of glomerular proteins by reverse transcriptase-polymerase chain reaction revealed that pair-feeding attenuated the increased expression of glomerular desmin, fibronectin, and the 92-kDa collagenase that was seen in obese animals fed ad libitum. DISCUSSION: Prevention of overeating in young OZR normalizes albuminuria and attenuates the pathogenic alterations in glomerular gene expression seen at the initiation of renal disease in obese animals allowed to feed ad libitum. This model may be relevant for studying the early end-organ effects of obesity.

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.

Calorie restriction in obesity: prevention of kidney disease in rodents.

The incidence of end-stage renal disease (ESRD) has risen considerably in the past two decades. This trend is partly due to the alarming rise in the incidence of type 2 diabetes over the same period, which in turn might be linked to the staggering increase in overweight and obesity. If these trends continue, ESRD can be expected not only to cause suffering of ever growing numbers of patients, but also to become an increasing financial as well as logistical burden on the health care system. Therefore, it is imperative not only to gain a better understanding of the molecular, cellular and metabolic mechanisms involved in renal pathology, but also to uncover treatment modalities, including lifestyle changes, that can help prevent and/or slow the progression of kidney pathogenesis. Insights into both of these aspects are provided by animal models of obesity and diabetes. It has long been known that food restriction, more so than restriction of any particular dietary component, can greatly enhance longevity in laboratory rodents. These findings are being extended into a variety of other mammals, including nonhuman primates. These studies have indicated that caloric restriction in nonobese laboratory animals does not primarily affect specific disease processes but rather nonspecifically slows the aging process. In contrast, a growing body of evidence suggests that in genetically obese animals, food restriction can prevent or greatly delay the onset of specific degenerative lesions, in particular glomerulonephritis associated with obesity and diabetes.

Shosaiko-to and other Kampo (Japanese herbal) medicines: a review of their immunomodulatory activities.

The use of alternative medicine, including consumption of herbal products and dietary supplements, has been increasing substantially both in the United States and in Western Europe. One area that is garnering increased attention is the use of Oriental Medicine including Kampo, or Japanese herbal medicine. Herein, we review representative examples of research available on the most common use of Kampo medicinals, namely to improve the immune response. We also provide an extensive background on the history of Kampo. There are more than 210 different Kampo formulae used in Japan and most uses of Kampo are to modulate the immune response, i.e. to improve immunity. We have extracted data on seven common Kampo medicinals, and the data are reviewed with respect to in vitro and in vivo activities for both humans and experimental animals; the ingredients as well as the problems with classification of these materials are presented. Research suggests that Kampo herbals are biologically active and may have therapeutic potential. While it is believed that Kampo medicines have few side effects, there is a paucity of data on their toxicity as well as a relative lack of knowledge of the bioactive constituents and potential drug interactions of these agents.

Augmented insulinotropic action of arachidonic acid through the lipoxygenase pathway in the obese Zucker rat.

OBJECTIVE: The metabolism of arachidonic acid (AA) has been shown to be altered in severe insulin resistance that is present in obese (fa/fa) Zucker rats. We examined the effects and mechanism of action of AA on basal and glucose-stimulated insulin secretion in pancreatic islets isolated from obese (fa/fa) Zucker rats and their homozygous lean (Fa/Fa) littermates. RESEARCH METHODS AND PROCEDURES: Islets were isolated from 10- to 12-week-old rats and incubated for 45 minutes in glucose concentrations ranging from 3.3 to 16.7 mM with or without inhibitors of the cyclooxygenase or lipoxygenase pathways. Medium insulin concentrations were measured by radioimmunoassay, and islet production of the 12-lipoxygenase metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), was measured by enzyme immunoassay. RESULTS: In islets from lean animals, AA stimulated insulin secretion at submaximally stimulatory glucose levels (<11.1 mM) but not at 16.7 mM glucose. In contrast, in islets derived from obese rats, AA potentiated insulin secretion at all glucose concentrations. AA-induced insulin secretion was augmented in islets from obese compared with lean rats at high concentrations of AA in the presence of 3.3 mM glucose. Furthermore, the inhibitor of 12-lipoxygenase, esculetin (0.5 microM), inhibited AA-stimulated insulin secretion in islets from obese but not lean rats. Finally, the islet production of the 12-HETE was markedly enhanced in islets from obese rats, both in response to 16.7 mM glucose and to AA. DISCUSSION: The insulin secretory response to AA is augmented in islets from obese Zucker rats by a mechanism related to enhanced activity of the 12-lipoxygenase pathway. Therefore, augmented action of AA may be a mechanism underlying the adaptation of insulin secretion to the increased demand caused by insulin resistance in these animals.

Factors affecting blood pressure responses to diet: the Vanguard study.

To study physiologic factors affecting the blood pressure (BP) response to nonpharmacologic maneuvers, fasting blood glucose, insulin, lipid and mineral levels, urinary mineral excretion, and the calcium regulating hormones parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D (1,25 (OH)2D) were measured in 71 unmedicated hypertensive (26 hypertensive only [HT], 45 hypertensive hyperlipidemic [HTHL]), and 87 normotensive hyperlipidemic (NTHL) control subjects before and during a 10-week multicenter, randomized controlled trial comparing a prepared meal plan (CCNW) with a self-selected diet (SSD) based on nutritionist counseling. Blood pressure fell to a greater extent in hypertensive versus normotensive subjects (-8+/-1/-5+/-1 v -2+/-1/-2+/-1 mm Hg, P < .0001/P < .0001), and on CCNW versus SSD diets (delta systolic BP [SBP]/delta diastolic BP [DBP], P = .033/P = .002). Diet-induced weight change was the strongest correlate of changes in BP (SBP: r = 0.360, P < .0001; DBP: r = 0.414, P < .0001), which, on multivariate analysis for deltaSBP, could partly be accounted for by diet-induced changes in fasting glucose (r = 0.215, P = .009) and cholesterol (r = 0.219, P = .006) levels. Independently of weight, diet-induced changes in SBP also were significantly related to concomitant changes in urinary excretion of potassium (r = -0.285, P = .001), magnesium (r = -0.254, P = .003), and calcium relative to sodium (r = -0.200, P = .021), but not to sodium per se; and to changes in serum potassium (r = -0.249, P = .002), phosphorus (r = -0.279, P = .001), PTH (r = 0.288, P = .0006), and 1,25 D (r = 0.202, P = .017). We conclude that the ability of diet to lower BP successfully may result from the additive contributions of multiple components. Independently of weight loss and the associated changes in circulating glucose and cholesterol, BP is influenced by the increasing provision of minerals such as potassium, magnesium, and calcium, perhaps by virtue of their suppressive effects on circulating vasoactive calcium regulating hormones.

Effects of increased consumption of fluid milk on energy and nutrient intake, body weight, and cardiovascular risk factors in healthy older adults.

OBJECTIVE: To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers. DESIGN: Randomized, controlled open trial. INTERVENTION: Advice to increase skim or 1% milk intake by 3 cups per day (n = 101) or to maintain usual diet (n = 103) for 12 weeks after a 4-week baseline period. MAIN OUTCOME MEASURES: Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels. STATISTICAL ANALYSES PERFORMED: Group-by-time analysis of variance with repeated-measures, chi 2 test. RESULTS: Compliance with the intervention was good. Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothenate, calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% at baseline vs 13% at 12 weeks, P < .001) and vitamin B-12 (6% vs 0%, P < .05) and tended to decrease (P < .10) for protein and thiamin (women) and magnesium and vitamin B-6 (men). The milk group gained 0.6 kg more than control group (P < .01); however, weight gain was less than predicted, which suggests some compensation for the added energy from milk. Blood pressure decreased similarly over time in both groups. Total and low-density lipoprotein cholesterol levels, and the ratio of total cholesterol to high-density lipoprotein cholesterol, were unchanged. Triglyceride levels increased within the normal range in the milk group (P = .002). Quality of life scores were high at baseline and remained high throughout. APPLICATIONS/CONCLUSIONS: Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes. Dietitians can play a key role in disseminating this advice.

Inflammation and Native American medicine: the role of botanicals.

There is a growing interest in medicinal botanicals as part of complementary medicine in the United States. In particular, both physicians and consumers are becoming aware of the use of herbals by Native American societies; many botanicals sold today as dietary supplements in the United States were used by Native Americans for similar purposes. Yet, these supplements represent only a small number of the >2500 different plant species from vascular taxa, and >2800 species from all taxa, known to have been prized for their medicinal properties by the indigenous inhabitants of the North American continent. We review some of the studies of the immunomodulatory activities of botanicals used by native peoples of North America, the bioactive constituents responsible for those activities, and the mechanisms by which these constituents might modulate the immune system. We focus particularly on 3 species of purple coneflower (ECHINACEA:) because of the widespread use of purple coneflower in the United States to boost immunity and prevent upper respiratory infections. Seven of the 10 most common botanicals sold in the United States were used extensively by Native Americans. However, there are very few data to support such use and even less information about drug toxicity or interactions.