Evaluation of Microwave-Assisted Extraction Method for Preparation and Assessment of Thai Herbal Medicine Oral Tablets With Enriched Phytochemical Compounds.

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 µg/mL and 4.02 ± 0.24 µg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.

Critical evaluation of causality assessment of herb-drug interactions in patients.

The aim of this review was to assess the severity of adverse drug reactions (ADRs) due to herb-drug interactions (HDI) in patients taking herbs and prescribed medications based on published evidence. Electronic databases of PubMed, the Cochrane Library, Medline and Scopus were searched for randomized or nonrandomized clinical studies, case-control and case reports of HDI. The data were extracted and the causal relationship of ADRs as consequences of HDI assessed using Horn's drug interaction probability scale or Roussel Uclaf Causality Assessment Method scoring systems. The mechanism of interaction was ascertained using Stockley's herbal medicine interaction companion. Forty-nine case reports and two observational studies with 15 cases of ADRs were recorded. The majority of the patients were diagnosed with cardiovascular diseases (30.60%), cancer (22.45%) and renal transplants (16.32%) receiving mostly warfarin, alkylating agents and cyclosporine, respectively. HDI occurred in patients resulting in clinical ADRs with different severity. Patients may poorly respond to therapeutic agents or develop toxicity due to severe HDI, which in either scenario may increase the cost of treatment and/or lead to or prolong patient hospitalization. It is warranted to increase patient awareness of the potential interaction between herbs and prescribed medicines and their consequences to curb HDI as a potential health problem.

Incorporation of Herbal Supplements into a Pharmacogenomic Medication Therapy Management Practice.

Personalized medicine, including direct-to-consumer (DTC) testing, is becoming a more common patient-centered approach to pharmacotherapy. However, DTC testing companies may not provide adequate information and follow-up to patients after genetic testing is done. This article is the first report describing a medication therapy management pharmacotherapy service that specializes in pharmacogenomic counseling, specifically geared toward identifying implications of dietary and herbal supplements. A pharmacist provides a comprehensive review of pharmacokinetic and pharmacodynamic consequences of a patient's herbal substances, and counseling is provided on subsequent drug therapy effects. If properly implemented, offering a pharmacogenomic medication therapy management service that specializes in the use of herbal supplements provides patients with education on the safe use of these substances based on their genetic factors.

Demographic, Lifestyle Factors, and Reasons for Use of Dietary Supplements by Air Force Personnel.

BACKGROUND: Dietary supplement (DS) use is common among U.S. Army personnel to purportedly improve health, provide energy, and increase strength. However, a comprehensive analysis of DS use among U.S. Air Force (USAF) personnel has not been conducted using the same survey instrument, which would permit direct comparisons to DS use by Army personnel. METHODS: A standardized questionnaire was used to assess DS use, demographic factors, and reasons for use of DS by USAF personnel (N = 1750). Logistic regression models adjusted for age, sex, and rank were used to determine relationships among categories of DS (multivitamin and multimineral, individual vitamins and minerals, protein/amino acid supplements, combination products, herbal supplements, purported steroid analogs, and other) and demographic factors. Findings were compared to reports from other military services and civilian populations. RESULTS: DS were used by 68% of USAF personnel: 35% used 1-2 DS ≥ 1 time/wk, 13% 3-4 DS ≥ 1 time/wk, and 20% ≥ 5 DS ≥ 1 time/wk. There were 45% of personnel who used a multivitamin and mineral, 33% protein supplements, 22% individual vitamins/minerals, 22% combination products, and 7% herbals. Logistic regression demonstrated aerobic exercise duration and strength training were associated with increased DS use. Individuals who previously deployed were more likely to use DS. CONCLUSIONS: Like Army personnel, college students and athletes, USAF personnel use more DS than the general population and are more likely to use purported performance enhancing DS, such as protein supplements, and concurrently consume multiple DS. Austin KG, Price LL, McGraw SM, Leahy G, Lieberman HR. Demographic, lifestyle factors, and reasons for use of dietary supplements by Air Force personnel. Aerosp Med Hum Perform. 2016; 87(7):628-637.

Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14).

OBJECTIVE: To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available. METHODS: Data for this population-based case-control study were collected from drivers of 'case' vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and 'control' vehicles representative of 'driving time' in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk. FINDINGS: Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90-11.63). The related population attributable risk was 18.37% (95% CI: 13.77-22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use. CONCLUSION: In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common.

Possible Parkinson's Disease Induced by Chronic Manganese Supplement Ingestion.

OBJECTIVE: The objective is to report a case of possible neurotoxicity resulting from an incorrect dietary supplement for osteoporosis taken at a toxic dose. SUMMARY: The case study examined here is a 37-year-old African-American female who consumed excessive manganese over a period of years, resulting in Parkinson's disease (PD). This patient was referred to the pharmacist pharmacotherapy service by a neurology physician. PD has been shown in the medical literature to be caused by chronic exposure to high levels of manganese. It may be concluded that daily doses of manganese well above the upper limit of 9 mg per day were taken by this patient for an extended period of time, possibly causing PD via manganism. CONCLUSION: This case illustrates the unknown risks taken by patients who use excessive amounts of over-the-counter herbals and supplements and how pharmacists can assist patients and physicians in the proper use of these popular products. ABBREVIATIONS: AI = Adequate intake, EMS = Eosinophilia myalgia syndrome, MTM = Medication therapy management, UL = Tolerable upper limit.

Assessment of the environmental risk factors for a gastric ulcer in northern Ghana.

Numerous risk factors have been implicated in the development of a gastric ulcer. Common risk factors are Helicobacter pylori infection, chronic non-steroidal anti-inflammatory intake, and alcohol consumption. The aim of the current study was to identify environmental risk factors for a gastric ulcer in northern Ghana. The data for this retrospective study were obtained from 2035 patient records from the Minimal Access Therapy and Operative Endoscopy unit of the Tamale Teaching Hospital in Tamale, Ghana from 2010 to 2014. A separate questionnaire was administered to assess the environmental risk factors. The rapid urease test was used to determine the presence of H. pylori. The Statistical Package for Social Sciences version 20.0 was used to analyse the data. Univariate and bivariate analyses were performed, and the results were presented in tables provided. The Chi-square values of the bivariate analysis were considered statistically significant when P < 0.05. Bivariate analysis revealed a strong association between gastric ulcer and various risk factors such as smoking (P = 0.001, χ2 = 27.3), fasting (P = 0.001, χ2 = 42.6), H. pylori infection (P = 0.01, χ2 = 19.9), and alcohol consumption (P = 0.001, χ2 = 30.6). There was no association between the traditional herbal preparation usage (P = 0.251, χ2 = 1.8) and the gastric ulcer. Environmental risk factors responsible for the development of a gastric ulcer in people of the northern part of Ghana show a similar pattern to other geographical regions of the world.

Toxic metal content in 52 frequently prescribed herbal medicines on the Korean market.

This study was conducted to investigate the toxic metal content (Pb, As, Cd and Hg) of 52 frequently prescribed herbal medicines and to identify herbal medicines that exceed the Korea Food and Drug Administration (KFDA) maximum limits. A total of 3534 samples, including 1966 domestic samples and 1568 imported samples, were analysed using an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Total amounts of Pb, As, Cd and Hg were significantly different between domestic (0.63 mg kg(-1)) and imported (0.81 mg kg(-1)) medicines (p < 0.05). Among the 52 kinds of samples, 4 kinds of herbs required quality control for Pb and 12 kinds of herbs required quality control for Cd. No sample contained As and Hg above the limits.

Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy.

The present study was designed to investigate if exposure to dried ginger during pregnancy would increase the risk of adverse fetal and neonatal outcomes. Participants consisted of 159 singleton pregnant women who received dried ginger as a herbal medication. We also included a control group of 306 pregnant women who had not been exposed to any herbal medication or any known teratogen. No increased risk of major malformations was detected in exposed women (OR = 4.9; 95% CI 0.9-25.5; p = 0.051). The incidence of stillbirths in the exposed group was marginally higher than in the controls (OR = 7.8; 95% CI 0.9-70.3; p = 0.05). The risk was more evident when the exposed group was compared with the general population in the Republic of Korea (OR = 7.9; 95% CI 2.9-21.4; p < 0.0001). Other fetal and neonatal study outcomes investigated in the exposed group were similar (p > 0.05) to the controls. In conclusion, dried ginger does not appear to be a major teratogen. However, due to the limitations of the study, e.g. the large variability in the dose of dried ginger in the exposed group, as well as the concomitant exposure to other herbal medications, the increased incidence of stillbirths requires confirmation in larger cohort studies.

Initial clinical assessment of a novel multifunctional topical ointment for difficult-to-heal wounds: a case series.

Chronic wounds are characterized by prolonged inflammation, bacterial bioburden, and ischemia. These factors represent the barriers to wound healing that need to be addressed in order to achieve wound closure. The authors performed the initial clinical testing of WinVivo Wound Ointment ("WinVivo"), a novel topical ointment containing several botanicals that have been previously shown to promote favorable wound environment and advance wound healing. In this series of 13 patients with difficult-to-heal lower-extremity wounds, WinVivo was well tolerated and demonstrated the ability to simultaneously support granulation tissue formation; decrease the amount of exudate, edema, and malodor; and reduce pain. The ulcers included in this study have been present for a minimum of 3 weeks and a maximum of 5 years prior to the start of treatment with WinVivo. Eight of 13 wounds have previously been treated with at least 1 type of advanced wound healing modality, such as dermal substitutes or negative-pressure wound therapy. Treatment with WinVivo lasted for 3 to 12 weeks and resulted in a mean 88% wound closure, with 4 wounds healing completely. In addition to significant reduction in wound size, all patients have exhibited other clinical benefits, suggesting overall improvement in wound conditions. Future studies in a larger population, as well as case-control studies comparing WinVivo with a standard of care, are therefore warranted to further evaluate the efficacy of this new treatment.

Running economy and maximal oxygen consumption after 4 weeks of oral Echinacea supplementation.

The purpose of this investigation was to determine the effects of 4 weeks of oral Echinacea (ECH) supplementation on erythropoietin (EPO), red blood cell (RBC) count, running economy (RE), and VO2max. Twenty-four men aged 24.9 ± 4.2 years, height 178.9 ± 7.9 cm, weight 87.9 ± 14.6 kg, body fat 19.3 ± 6.5% were grouped using a double-blind design and self-administered an 8,000-mg·d(-1) dosage of either ECH or placebo (PLA) in 5 × 400 mg × 4 times per day for 28 days. Blood samples were collected and analyzed for RBCs and EPO using automated flow cytometery and enzyme-linked immunosorbent assay. Maximal graded exercise tests (GXTs) were administered to measure VO2max, RE, and heart-rate responses. Analysis of variance was used to determine statistically significant differences (P ≤ 0.05). The EPO increased significantly in ECH at 7 days (ECH: 15.75 ± 0.64, PLA: 10.01 ± 0.73 mU·ml(-1)), 14 days (ECH: 18.88 ± 0.71, PLA: 11.02 ± 0.69 mU·ml(-1)), and 21 days (ECH: 16.06 ± 0.55, PLA: 9.20 ± 0.55 mU·ml(-1)). VO2max increased significantly in ECH (ECH: 1.47 ± 1.28, PLA: -0.13 ± 0.52%). Running economy improved significantly in ECH as indicated by a decrease in submaximal VO2max during the first 2 stages of the GXT (stage 1: ECH -1.50 ± 1.21, PLA 0.60 ± 1.95%; stage 2: ECH -1.67 ± 1.43, PLA 0.01 ± 1.03%). These data suggest that ECH supplementation results in significant increases in EPO, VO2max, and running economy.

Impact of orange juice consumption on macronutrient and energy intakes and body composition in the US population.

OBJECTIVE: The present study evaluated the contribution of 100 % orange juice (OJ) consumption to the intakes of macronutrients and energy and its impact on body composition. DESIGN: A cross-sectional study was conducted. The main exposure was OJ consumption based on two non-consecutive 24 h diet recalls. Macronutrient and energy intakes and body composition parameters were outcome measures. All statistical analyses were carried out using SAS and SUDAAN statistical software packages to allow for multistage sample designs. SETTING: The US population and its subgroups. SUBJECTS: The US population aged ≥4 years (n 13 971) from the National Health and Nutrition Examination Survey 2003-2006, conducted by the National Center for Health Statistics. RESULTS: In this US population, OJ consumers had lower BMI and healthier lifestyle behaviours (including lower alcohol consumption and smoking as well as higher exercise level) than non-consumers (P < 0.05). After adjusting for covariates, OJ consumers had higher daily intakes of carbohydrate, total sugar, total fat and energy than non-consumers (P < 0.01). However, these linear trends still remained even after OJ was removed from the food list of items consumed. Adult OJ consumers had lower BMI, waist circumference and percentage body fat than non-consumers (P < 0.01), as well as lower odds ratio for overweight and obesity (P < 0.01). These effects were not seen in children and adolescents, where there was no significant difference in BMI, waist circumference and percentage body fat in OJ consumers compared with non-consumers. CONCLUSIONS: OJ consumption was associated with healthier body composition in adults; while there were no significant associations between OJ consumption and body composition in children and adolescents.

Plant food supplement (PFS) market structure in EC Member States, methods and techniques for the assessment of individual PFS intake.

The popularity of herbal products, especially plant food supplements (PFS) and herbal medicine is on the rise in Europe and other parts of the world, with increased use in the general population as well as among specific subgroups encompassing children, women or those suffering from diseases such as cancer. The aim of this paper is to examine the PFS market structures in European Community (EC) Member States as well as to examine issues addressing methodologies and consumption data relating to PFS use in Europe. A revision of recent reports on market data, trends and main distribution channels, in addition an example of the consumption of PFS in Spain, is presented. An overview of the methods and administration techniques used to assess individual food consumption as a starting point, including their uses and limitations, as well as some examples of studies that collect Food Supplement (FS) information, including herbal/botanical/plant-derived products are also discussed. Additionally, the intake estimation process of food nutrients is described and used to propose the PFS ingredients intake estimation process. Nationally representative PFS consumption data is scarce in Europe. The majority of studies have been conducted in Scandinavia and the UK. However the heterogeneity of definitions, study design and objectives make it difficult to compare results and extrapolate conclusions.

Control of tungiasis through intermittent application of a plant-based repellent: an intervention study in a resource-poor community in Brazil.

BACKGROUND: Tungiasis, an ectoparasitosis caused by the female sand flea Tunga penetrans, is an important health problem in many impoverished communities in the tropics. Sand flea disease is associated with a broad spectrum of clinical pathology and severe sequels are frequent. Treatment options are limited. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the effectiveness of the intermittent application of the plant-based repellent Zanzarin to reduce infestation intensity and tungiasis-associated morbidity in a resource-poor community in Brazil, characterized by a very high attack rate. The study population was randomized into three cohorts. Initially, during a period of four weeks, the repellent was applied twice daily to the feet of all cohort members. This reduced the number of embedded sandfleas to 0 in 98% of the participants. Thereafter members of cohort A applied the repellent every second week twice daily for one week, members of cohort B every fourth week for one week, and members of cohort C served as controls. Infestation intensity and tungiasis-associated morbidity were monitored during five months. The intermittent application of Zanzarin for one week every second week significantly reduced infestation intensity from a median 4 lesions (IQR 1-9) during the whole transmission season. In contrast, in cohort B (application of the repellent every fourth week) the infestation intensity remained twice as high (median 8 lesions, IQR 9-16; p = 0.0035), and in the control cohort C 3.5 times as high (median 14 lesions; IQR 7-26; p = 0.004 during the transmission season). Tungiasis-related acute pathology remained very low in cohort A (median severity score 2; IQR 1-4) as compared to cohort B (median severity score 5; IQR 3-7; p<0.001), and control cohort C (median severity score 6.5; IQR 4-8; p<0.001). CONCLUSIONS/SIGNIFICANCE: Our study shows that in a setting with intense transmission, tungiasis-associated morbidity can be minimized through the intermittent application of a plant-based repellent.

Does a perioperative belladonna and opium suppository improve postoperative pain following robotic assisted laparoscopic radical prostatectomy? Results of a single institution randomized study.

INTRODUCTION: Robotic assisted laparoscopic radical prostatectomy (RALP) is a common treatment for localized prostate cancer. Despite a primary advantage of improved postoperative pain, patients undergoing RALP still experience discomfort. Belladonna, containing the muscarinic receptor antagonists atropine and scopolamine, in combination with opium as a rectal suppository (B & O) may improve post-RALP pain. This study evaluates whether a single preoperative B & O results in decreased postoperative patient-reported pain and analgesic requirements. MATERIALS AND METHODS: Patients undergoing RALP at Virginia Mason Medical Center between November 2008 and July 2009 were offered the opportunity to enter a randomized, double-blind, placebo-controlled trial. Exclusion criteria included: glaucoma, bronchial asthma, convulsive disorders, chronic pain, chronic use of analgesics, or a history of alcohol or opioid dependency. Surgeons were blinded to suppository placement which was administered after induction of anesthesia. All patients underwent a standardized anesthesia regimen. Postoperative pain was assessed by a visual analog scale (VAS) and postoperative narcotic use was calculated in intravenous morphine equivalents. RESULTS: Ninety-nine patients were included in the analysis. The B & O and control groups were not significantly different in terms of age, body mass index, operative time, nerve sparing status or prostatic volume. Postoperative pain was significantly improved during the first two postoperative hours in the B & O group. Similarly, 24-hour morphine consumption was significantly lower in patients who received a B & O. No adverse effects secondary to suppository placement were identified. CONCLUSION: Preoperative administration of B & O suppository results in significantly decreased postoperative pain and 24-hour morphine consumption in patients undergoing RALP.

The pituri story: a review of the historical literature surrounding traditional Australian Aboriginal use of nicotine in Central Australia.

The harmful outcomes of nicotine self administration have been the focus of sustained global health education campaigns that have targeted tobacco smoking and to a lesser extent, smokeless tobacco use. 'Smokeless tobacco' infers that the nicotine is not burnt, and administration can be through a range of methods including chewing.The chewing of wild tobacco plants (Nicotiana spp.) is practiced across a broad inland area of Central Australia by traditional Aboriginal groups. Collectively these plants are known by a variety of names - one common name being 'pituri'. This is the first paper to examine the historical literature and consider the linkage between pituri use and health outcomes. Using a narrative approach, this paper reviews the literature generated since 1770 surrounding the term pituri and the behaviours associated with its use. The review examines the scientific literature, as well as the diaries and journals of nineteenth century explorers, expedition notes, and early Australian novels to expound the scientific evidence and broaden the sense of understanding related to pituri, particularly the behavioural elements. The evaluation considers the complexities of ethnobotany pertaining to language and distance and the ethnopharmacology of indigenous plant usage. The review compares the use of burnt and smokeless tobacco to pituri and establishes the foundation for research into the clinical significance and health outcomes of pituri use. Additionally, this review provides contemporary information for clinicians providing care for patients who chew pituri.

Long-term sustainability of a worksite canteen intervention of serving more fruit and vegetables.

OBJECTIVE: To analyse the 5-year sustainability of a worksite canteen intervention of serving more fruit and vegetables (F&V). DESIGN: Average F&V consumption per customer per meal per day was assessed in five worksite canteens by weighing F&V served and subtracting waste. Data were collected by the canteen staff during a 3-week continuous period and compared to data from the same five canteens measured at baseline, at end point and at 1-year follow-up. The intervention used a participatory and empowering approach, self-monitoring and networking among the canteen staff, management and a consultant. The method focused on providing ideas for increased F&V for lunch, making environmental changes in the canteens by giving access to tasteful and healthy food choices and reducing the availability of unhealthy options. SETTING: Five Danish worksites serving from 50 to 500 meals a day: a military base, an electronic component distributor, a bank, a town hall and a waste-handling facility. SUBJECTS: Worksite canteen managers, canteen staff. RESULTS: Four of the five worksite canteens were able to either maintain the intervention or even increase the consumption of F&V. The average increase from baseline to 5-year follow-up was 95 g per customer per meal per day (18, 144, 66, 105 and 141 g, respectively). On average, the five canteens at the long-term follow-up had an F&V consumption of 208 g/meal per customer. CONCLUSIONS: The present study indicates that sustainability of F&V is possible in worksites where the participatory and empowering approach, self-monitoring, environmental change, dialogue with suppliers and networking among worksite canteens are applied.

Herbal medicine: affecting factors and prevalence of use among Thai population in Bangkok.

BACKGROUND: Remarkable growth in use of herbal medicines has recently been noted. In Thailand, eight items of herbal medicines with single composition are currently placed on the National List of Essential Medicines (EM). This study was to clarify the actual state of factors affecting the usage and knowledge of these herbal medicines, as the study concerning with these aspects was infrequently performed. MATERIAL AND METHOD: A descriptive and cross-sectional research was conducted by using self-administered questionnaires. Six hundred and thirty-one subjects were randomly sampling and the data were analyzed by the Statistic Package for the Social Sciences software program. RESULTS: The finding revealed that 28.6% of total subjects had experienced on herbal medicine treatment, especially eight items listed in EM. The elderly and government officers usually purchased the drugs from hospital and drugstore, while housewife purchased them from supermarket. Subjects with positive attitude towards herbal medicine use usually were government officers. Almost all of herbal medicines were well-known about their indications by less than 55% of total subjects. Among all well-known indications, the relief of gastric distress by Zingiber officinale was the most well-known one (73.2%). On the other hand, high percentage of media exposure (55-70%) was found in majority of the subjects which indicated that media was more likely to influence consumer's knowledge and behavior. CONCLUSION: Only 28.6% of total subjects had experienced on herbal medicines listed in EM, despite of high percentage of media exposure. Therefore, the providing proper information of herbal medicines on various medias and integrated education about herbal medicine in medical curricula could effectively help increase appropriate drug use and consumers' safety.

Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans.

Pharmacological sodium nitrate supplementation has been reported to reduce the O2 cost of submaximal exercise in humans. In this study, we hypothesized that dietary supplementation with inorganic nitrate in the form of beetroot juice (BR) would reduce the O2 cost of submaximal exercise and enhance the tolerance to high-intensity exercise. In a double-blind, placebo (PL)-controlled, crossover study, eight men (aged 19-38 yr) consumed 500 ml/day of either BR (containing 11.2 +/- 0.6 mM of nitrate) or blackcurrant cordial (as a PL, with negligible nitrate content) for 6 consecutive days and completed a series of "step" moderate-intensity and severe-intensity exercise tests on the last 3 days. On days 4-6, plasma nitrite concentration was significantly greater following dietary nitrate supplementation compared with PL (BR: 273 +/- 44 vs. PL: 140 +/- 50 nM; P < 0.05), and systolic blood pressure was significantly reduced (BR: 124 +/- 2 vs. PL: 132 +/- 5 mmHg; P < 0.01). During moderate exercise, nitrate supplementation reduced muscle fractional O2 extraction (as estimated using near-infrared spectroscopy). The gain of the increase in pulmonary O2 uptake following the onset of moderate exercise was reduced by 19% in the BR condition (BR: 8.6 +/- 0.7 vs. PL: 10.8 +/- 1.6 ml.min(-1).W(-1); P < 0.05). During severe exercise, the O2 uptake slow component was reduced (BR: 0.57 +/- 0.20 vs. PL: 0.74 +/- 0.24 l/min; P < 0.05), and the time-to-exhaustion was extended (BR: 675 +/- 203 vs. PL: 583 +/- 145 s; P < 0.05). The reduced O2 cost of exercise following increased dietary nitrate intake has important implications for our understanding of the factors that regulate mitochondrial respiration and muscle contractile energetics in humans.