An overview of the efficacy of inhaled curcumin: a new mode of administration for an old molecule.

INTRODUCTION: Curcumin is a polyphenol with a variety of pharmacological actions. Despite its therapeutic effects and well-known safety profile, the utility of curcumin has been limited due to its deprived physical, chemical, and pharmacokinetic profile resulting from limited solubility, durability, prompt deterioration and pitiable systemic availability. Employment of an amalgamated framework integrating the potential advantages of a nanoscaffold alongside the beneficial traits of inhalational drug delivery system beautifully bringing down the restricting attributes of intended curative interventions and further assures its clinical success. AREAS COVERED: Current review discussed different application of inhalable nanocurcumin in different medical conditions. Lung diseases have been the prime field in which inhalable nanocurcumin had resulted in significant beneficial effects. Apart from this several lung protective potentials of the inhaled nanocurcumin have been discussed against severe pulmonary disorders such as pulmonary fibrosis, radiation pneumonitis and IUGR induced bronchopulmonary dysplasia. Also, application of the disclosed intervention in the clinical management of COVID-19 and Alzheimer's Disease has been discussed. EXPERT OPINION: In this portion, the potential of inhalable nanocurcumin in addressing various medical conditions along with ongoing advancements in nanoencapsulation techniques and the existing challenges in transitioning from pre-clinical models to clinical practice has been summarized.

Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction.

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.

Efficacy and safety of N-acetyl-L-leucine in patients with ataxia telangiectasia: A randomized, double-blind, placebo-controlled, crossover clinical trial.

BACKGROUND: Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder. Most patients have progressive cerebellar ataxia, oculocutaneous telangiectasia, frequent pulmonary infection, and an increased risk of malignancies. Although N-acetyl-dl-leucine (ADLL) has shown some efficacy in patients with AT, its more pharmacologically active enantiomer, N-acetyl-l-leucine (NALL), has just recently been investigated in ataxic individuals. The current study assessed the efficacy of NALL in patients with AT. METHODS: This 2 × 2 crossover, double-blind, randomized clinical trial was conducted on 20 patients with AT. After excluding four patients, 16 subjects (eight females, eight males; mean age 9.8 ± 3.5 years) with a definitive genetic diagnosis of AT were randomly assigned to one of two study groups, with one group receiving 1-4 g/day NALL or a placebo for six weeks. Subjects then had a 4-week washout before crossing over to the other treatment for an additional six weeks. The Spinocerebellar Ataxia Functional Index (SCAFI) and the Scale for Assessment and Rating of Ataxia (SARA) score assessed patients' motor function. Quality of life (QOL) was evaluated by a specialist using the PedsQL questionnaire. Fasting blood samples were taken from all subjects before and after each intervention to determine potential side effects. RESULTS: Although patients' nausea and constipation were improved, the results failed to reveal any significant benefits of NALL treatment on ataxia symptoms. NALL treatment had no significant effects on SARA, SCAFI-9HPT (9-hole peg test) nondominant, SCAFI-9HPT dominant, or SCAFI-8WMT (8 m walking time) (p > 0.05). Our patient's Physical Health score in Child self-report and Parent proxy-report did not significantly change in the treatment group compared to the placebo (p > 0.05). Furthermore, there were no significant changes in energy and macronutrient intake after NALL treatment. None of the volunteers reported serious or moderate side effects. CONCLUSIONS: To the best of our knowledge, this was the first placebo-controlled, randomized clinical trial exploring NALL's potential effects for treating AT. Despite improvements in some symptomss, NALL intervention failed to improve motor function significantly. However, patients' nausea and constipation were improved by NALL, which can be a relevant benefit clinically.

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer.

Hypoxia can lead to different responses from cancer cells, including cell death or survival, partially depending on how long it is exposed. Patients with cancer and under hypoxic tumour conditions have a poorer prognosis and are at greater risk of metastasis. Physiological response to low oxygen levels is controlled by hypoxia-inducible factor (HIF)-1. Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF). In addition, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia. One of the most compelling features that drive continued interest in curcumin is the molecules' modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours. In this review, we discuss the role of curcumin in modulating hypoxia and investigate the mechanisms and regulatory factors of hypoxia in tumour tissues.

Effects of an Unripe Avocado Extract on Glycaemic Control in Individuals with Obesity: A Double-Blinded, Parallel, Randomised Clinical Trial.

BACKGROUND: Unripe avocados (Persea americana) are naturally enriched in mannoheptulose (MH), which is a candidate caloric restriction mimetic. OBJECTIVES: To evaluate the effects of a diet supplement made from unripe avocado on glucose tolerance, and cardiometabolic risk factors in free-living nondiabetic adults with obesity. METHODS: In a double-blinded, randomised controlled trial, 60 adults (female n = 47, age 48 ± 13 years, BMI 34.0 ± 2.6 kg/m2) were stratified by sex and randomised to avocado extract (AvX, 10 g finely ground, freeze-dried unripe avocado) or placebo (10 g finely ground cornmeal plus 5% spinach powder) daily, for 12 weeks. The primary outcome was a change in glucose area under the curve (AUC) in response to a 75 g oral glucose tolerance test. A post-hoc analysis was subsequently performed in a subgroup with insulin AUC above the median of baseline values after removal of participants >2 SD from the mean. RESULTS: There were no between-group differences in glucose AUC (p = 0.678), insulin AUC (p = 0.091), or cardiovascular outcomes. In the subgroup analysis, insulin AUC was lower in AxV versus placebo (p = 0.024). CONCLUSIONS: Daily consumption of unripe avocado extract enriched in MH did not alter glucose tolerance or insulin sensitivity in nondiabetic adults with obesity, but the data provided preliminary evidence for a benefit in insulin AUC in a subgroup of participants with elevated baseline postprandial insulin levels.

The effect of intravenous trehalose administration in a patient with multiple sulfatase deficiency.

Introduction: We describe the case of a female child with multiple sulfatase deficiency (MSD) who received intravenous (IV) trehalose (15 g/week) for 3 months. Methods: The efficacy of trehalose was evaluated by comparing serum biomarkers, a quality-of-life questionnaire (HRQoL), and imaging (brain MRI and ultrasonography of liver and spleen) at weeks 0 (W0) and 12 (W12). Results: The improvement in quality of life assessments along with a slight decrease in the spleen dimensions were observed after 3-month intervention. Conclusions: Future research with a larger MSD population and a longer-term follow-up is warranted to determine whether trehalose can improve MSD patient health and clinical outcomes.

The Beneficial Effects of Curcumin on Lipids: Possible Effects on Dyslipidemia-Induced Cardiovascular Complications.

Dyslipidemia and altered lipid metabolism are closely involved in the pathogenesis and clinical manifestation of many metabolic and non-metabolic diseases. Therefore, mitigation of pharmacological and nutritional factors together with lifestyle modifications is paramount. One potential nutraceutical exhibiting cell signaling and lipid-modulating properties implicated in dyslipidemias is curcumin. Specifically, recent evidence suggest that curcumin may improve lipid metabolism and prevent dyslipidemia-induced cardiovascular complications via several pathways. Although the exact molecular mechanisms involved are not well understood, the evidence presented in this review suggests that curcumin can provide significant lipid benefits via modulation of adipogenesis and lipolysis, and prevention or reduction of lipid peroxidation and lipotoxicity via different molecular pathways. Curcumin can also improve the lipid profile and reduce dyslipidemia-dependent cardiovascular problems by impacting important mechanisms of fatty acid oxidation, lipid absorption, and cholesterol metabolism. Although only limited direct supporting evidence is available, in this review we assess the available knowledge regarding the possible nutraceutical effects of curcumin on lipid homeostasis and its possible impacts on dyslipidemic cardiovascular events from a mechanistic viewpoint.

Polyphenolic Nano-formulations: A New Avenue against Bacterial Infection.

The gradual emergence of new bacterial strains impervious to one or more antibiotics necessitates discovering and applying natural alternatives. Among natural products, various polyphenols exhibit antibacterial activity. However, polyphenols with biocompatible and potent antibacterial characteristics are limited due to low aqueous solubility and bioavailability; therefore, recent studies are considering new polyphenol formulations. Nanoformulations of polyphenols, especially metal nanoparticles, are currently being investigated for their potential antibacterial activity. Nanonization of such products increases their solubility and helps attain a high surface-to-volume ratio and, therefore, a higher reactivity of the nanonized products with better remedial potential than non-nanonized products. Polyphenolic compounds with catechol and pyrogallol moieties efficiently bond with many metal ions, especially Au and Ag. These synergistic effects exhibit antibacterial pro-oxidant ROS generation, membrane damage, and biofilm eradication. This review discusses various nano-delivery systems for considering polyphenols as antibacterial agents.

Recent advances in curcumin-based nanoformulations in diabetes.

Diabetes is predicted to affect 700 million people by the year 2045. Despite the potential benefits for diabetics, curcumin's low bioavailability significantly reduces its utility. However, newer formulation methods of decreasing particle size, such as through nanotechnological advances, may improve curcumin's bioavailability and cell-absorption properties. Various curcumin nanoformulations such as nanofibers, nanoparticles-like nanostructured lipid carriers (NLCs), Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) and nanohydrogels have been evaluated. These studies reported increased bioavailability of nanoformulated curcumin compared to free curcumin. Here, we provide a detailed review of the antidiabetic effects of nanocurcumin compounds and subsequent effects on diabetic complications. Overall, various nanocurcumin formulations highly increase curcumin water-solubility and bioavailability and these safe formulations can positively affect managing some diabetes-related manifestations and complications. Moreover, nanocurcumin efficacy in various diabetes complications is discussed. These complications included inflammation, neuropathy, depression, anxiety, keratopathy, cataract, cardiomyopathy, myocardial infarction (MI), nephropathy, erectile dysfunction and diabetic wound. Moreover, several nanocurcumin formulations improved wound healing in the diabetic. However, few studies have been performed in humans, and most results have been reported from cellular and animal studies. Therefore, more human studies are needed to prove the antidiabetic effects of nanocurcumin.

The Effect of N-Acetyl-DL-Leucine on Neurological Symptoms in a Patient with Ataxia-Telangiectasia: a Case Study.

Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder with no available curative treatment. Although the positive effects of N-acetyl-DL-leucine on cerebellar ataxia have been reported previously, there is little evidence of N-acetyl-DL-leucine's effects in patients with AT. This study assessed the effect of 16 weeks N-acetyl-DL-leucine supplementation on ataxia symptoms in a 9-year-old female with AT. The subject consumed 4 g/day N-acetyl-DL-leucine (2 g in the morning and 2 g in the evening) for 16 weeks. Safety was assessed via clinical blood chemistry prior to the intervention and after 6 and 16 weeks. Additionally, The Scale for the Assessment and Rating of Ataxia (SARA) score was used to assess the drug's effects on ataxia symptoms at baseline, 6, 12, and 16 weeks. Quality of life has also been evaluated by a specialist using the PedsQL questionnaire.Despite some initial (first week only) nausea and constipation, supplementation with N-acetyl-DL-leucine was well tolerated and safe according to blood chemistry measures. The SARA score progressively improved, and by week 16 had improved by 11.0 points (48.88%). Parent and self-reported quality of life assessments indicated physical, emotional, social, and school functions all improved by 16 weeks. Supplementation with N-acetyl-DL-leucine at a dose of 4 g/day for 16 weeks was well tolerated and significantly improved ataxia symptoms and quality of life measures in a young child with AT.

Is Curcumin a Safe and Effective Therapeutic in the Treatment against Oral Lichen Planus?

Oral lichen planus (OLP) is a chronic mucocutaneous, immunological disease that occurs more frequently in the buccal mucosa of middle-aged female patients. OLP's standard treatment is topical or systemic corticosteroids. Due to corticosteroids' numerous potential side effects, there is an effort to find an alternative treatment. One alternative treatment is curcumin. Several studies have investigated the effectiveness and safety of curcumin in OLP patients. In this review, we summarized the literature focusing on the effectiveness and safety of curcumin in OLP patients. Our review of clinical trials revealed that either 6000 mg/day curcumin, 80 mg/day nano-curcumin, or 1% curcumin oral gel 6 times/day offered benefits in the treatment of OLP.

Intermittent fasting and protein pacing are superior to caloric restriction for weight and visceral fat loss.

OBJECTIVE: This study compared intermittent fasting and protein pacing (IF-P) versus a heart-healthy caloric restriction (CR) diet, matched for energy intake and physical activity energy expenditure, on body weight, total and visceral fat mass, and cardiometabolic health outcomes in adults with obesity. METHODS: IF-P (n = 21) and CR (n = 20) were assessed pre- (week 0), mid- (week 5), and post- (week 9) intervention. RESULTS: Both groups reduced (p < 0.05) weight, total and visceral fat mass, blood pressure and lipids, and desire to eat food and increased proportion of fat-free mass. IF-P resulted in greater (p < 0.05) reductions in weight (-9% vs. -5%), total (-16% vs. -9%) and visceral (-33% vs. -14%) fat mass, and desire to eat (-17% vs. 1%) and increased fat-free mass percent (6% vs. 3%) compared with CR. These improvements were despite similar weekly total energy intake (IF-P, 9470 ± 550 vs. CR, 9095 ± 608 kcal/wk; p = 0.90) and physical activity energy expenditure (IF-P, 300 ± 150 vs. CR, 350 ± 200 kcal/d; p = 0.79). CONCLUSIONS: IF-P and CR optimize weight loss, body composition, cardiometabolic health, and hunger management, with IF-P providing greater benefits.

Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity.

Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.

Protective effects of curcumin against traumatic brain injury.

Neuroinflammation is a key pathophysiological mechanism implicated in the neurodegenerative condition. One such condition implicating neuroinflammation is traumatic brain injury (TBI). Over the past decades, various alternative natural compounds, such as curcumin, have been investigated as novel therapeutic options to mitigate the pathophysiological pathways and clinical sequelae involved in TBI. As the main component of turmeric (Curcuma longa), curcumin has a broad range of clinical properties due to its considerable antioxidative and anti-inflammatory actions. This review discusses the pleiotropic mechanisms, the side effects, curcumin's delivery to the central nervous system (CNS), and its immunomodulatory and protective effects on TBI. Clinical trials, in vivo, and in vitro studies were extracted from different scientific databases, including PubMed, Scopus, and Google Scholar, to assess the effects of curcumin or its derivatives in TBI. Findings reveal that curcumin exhibited some protective effects on TBI via modulation of cell signaling pathways including toll-like receptor-4 (TLR-4), nuclear factor kappa B (NF-κB), and Nod-like receptor family proteins (NLRPs). Moreover, curcumin upregulates the brain-derived Neurotrophic Factor/Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), nuclear factor erythroid 2-related factor 2 (Nrf2), which have crucial functions in modulation of TBI pathophysiological-mediated pathways. Curcumin displays beneficial immunomodulatory functions and protective capacities in different TBI models, although more clinical experiments are required to clarify curcumin's precise mechanisms and function in TBI.

Intermittent fasting two days versus one day per week, matched for total energy intake and expenditure, increases weight loss in overweight/obese men and women.

BACKGROUND: Intermittent fasting (IF), consisting of either a one-day (IF1) or two consecutive days (IF2) per week, is commonly used for optimal body weight loss. Our laboratory has previously shown an IF1 diet combined with 6d/week of protein pacing (P; 4-5 meals/day evenly spaced, ~ 30% protein/day) significantly enhances weight loss, body composition, and cardiometabolic health in obese men and women. Whether an IF1-P or IF2-P, matched for weekly energy intake (EI) and expenditure (EE), is superior for weight loss, body composition, and cardiometabolic health is unknown. METHODS: This randomized control study directly compared an IF1-P (n = 10) versus an IF2-P (n = 10) diet on weight loss and body composition, cardiovascular (blood pressure and lipids), hormone, and hunger responses in 20 overweight men and women during a 4-week weight loss period. Participants received weekly dietary counseling and monitoring of compliance from a registered dietitian. All outcome variables were assessed pre (week 0) and post (week 5). RESULTS: Both groups significantly reduced body weight, waist circumference, percent body fat, fat mass, hunger, blood pressure, lipids, glucose, and increased percent fat-free mass (p < 0.05). However, IF2-P resulted in significantly greater reductions in body weight (-29%) and waist circumference (-38%) compared to IF1-P (p < 0.05), and showed a strong tendency for greater reductions in fat mass, glucose, and hunger levels (p < 0.10) despite similar weekly total EI (IF1-P, 9058 ± 692 vs. IF2-P, 8389 ± 438 kcals/week; p = 0.90), EE (~ 300 kcals/day; p = 0.79), and hormone responses (p > 0.10). CONCLUSIONS: These findings support short-term IF1-P and IF2-P to optimize weight loss and improve body composition, cardiometabolic health, and hunger management, with IF2-P providing enhanced benefits in overweight women and men. TRIAL REGISTRATION: This trial was registered March 03, 2020 at www. CLINICALTRIALS: gov as NCT04327141 .

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats.

Background: Doxorubicin as an anti-cancer drug causes cardiotoxicity, limiting its tolerability and use. The mechanism of toxicity is due to free radical production and cardiomyocytes injury. This research evaluated Rheum turkestanicum (R.turkestanicum) extract against doxorubicin cardiotoxicity due to its considerable in vitro antioxidant activity. Methods: Male Wistar rats received 2.5 mg/kg doxorubicin intraperitoneally every other day for 2 weeks to create an accumulative dose. R. turkestanicum was administrated at a dose of 100 and 300 mg/kg intraperitoneally from the second week for 7 days. On the 15th day, the animals were anesthetized and blood was collected from cardiac tissue for evaluation of alanine aminotransferase (ALT), cardiac muscle creatinine kinase (CK-MB), troponin T (cTn-T), lactate dehydrogenase (LDH), and B-type natriuretic peptide brain natriuretic peptide. A cardiac homogenate was also collected to determine superoxide dismutase (SOD), catalase Catalase Activity, malondialdehyde (MDA), and thiols. Histopathology was also performed. Results: Doxorubicin increased all cardiac enzymes and malondialdehyde, correlating with a reduction in SOD, catalase, and thiols. Histopathology revealed extracellular edema, moderate congestion, and hemorrhage of foci. In contrast, administration of R. turkestanicum ameliorated these doxorubicin-induced pathophysiological changes. Conclusion: This study revealed that the extract ameliorated doxorubicin-induced cardiac toxicity via modulation of oxidative stress-related pathways. Liquid chromatography-mass spectrometry analysis of R. turkestanicum indicated several components with potent pharmacological properties.

Recent advances and health implications of dietary fasting regimens on the gut microbiome.

Calorie restriction is a primary dietary intervention demonstrated over many decades in cellular and animal models to modulate aging pathways, positively affect age-associated diseases and, in clinical studies, to promote beneficial health outcomes. Because long-term compliance with daily calorie restriction has proven problematic in humans several intermittent fasting regimens, including alternate day fasting and time-restricted feeding, have evolved revealing similar clinical benefits as calorie restriction. Despite significant research on the cellular and physiological mechanisms contributing to, and responsible for, these observed benefits, relatively little research has investigated the impact of these various fasting protocols on the gut microbiome (GM). Reduced external nutrient supply to the gut may beneficially alter the composition and function of a "fed" gut microflora. Indeed, the prevalent, obesogenic Western diet can promote deleterious changes in the GM, signaling intermediates involved in lipid and glucose metabolism, and immune responses in the gastrointestinal tract. This review describes recent preclinical and clinical effects of varying fasting regimens on GM composition and associated physiology. Although the number of preclinical and clinical interventions are limited, significant data thus far suggest fasting interventions impact GM composition and physiology. However, there are considerable heterogeneities of study design, methodological considerations, and practical implications. Ongoing research on the health impact of fasting regimens on GM modulation is warranted.

Caffeine-Containing, Adaptogenic-Rich Drink Modulates the Effects of Caffeine on Mental Performance and Cognitive Parameters: A Double-Blinded, Placebo-Controlled, Randomized Trial.

Using a placebo-controlled, double-blinded, within-participants, randomized, cross-over design, we examined the neurocognitive effects of a: (a) caffeine-containing, adaptogenic herbal-rich natural energy shot (e+ shot), (b) a matched caffeine-containing shot (caffeine), and, (c) a placebo. Participants (n = 30) were low consumers of caffeine without elevated feelings of energy. Before and three times after beverage consumption, a 27-min battery was used to assess motivation to perform cognitive tasks, mood, attention ((serial subtractions of 3 (SS3) and 7 (SS7), the continuous performance task (CPT), and the rapid visual input processing tasks)), heart rate (HR), blood pressure (BP), and motor coordination (nine-hole peg test) with a 10-min break between each post-consumption battery. The procedure was repeated for each beverage for each participant at least 48 h apart and within 30 min the same time of day using a random group assignment with blinding of researchers and subjects. To evaluate for changes in outcomes, a Treatment × Time analysis of covariance controlling for hours of prior night's sleep was used. Analysis of all outcomes and all treatment comparisons indicated that compared to placebo, both e+ shot ( Δ ¯   = 2.60; η2 = 0.098) and caffeine ( Δ ¯   = 5.30, η2 = 0.098) increased systolic BP 30 min post consumption (still within normal healthy ranges). The caffeine beverage also led to an improvement in most cognitive measures and moods 30-min post-consumption with improvements tapering at 69 and 108 min, while e+ shot noted more steady improvements with no significant differences between beverages on most cognitive and mood measures at 69 and 108 min. However, compared to caffeine, e+ shot noted a significant increase in reaction time at 108 min, while caffeine noted a small change in the opposite direction. No side-effects were reported by any intervention. These results suggest that the specific blend of adaptogens in e+ shot may modulate the neurocognitive effects of caffeine on mood, and cognition.

A novel organic mineral complex prevented high fat diet-induced hyperglycemia, endotoxemia, liver injury and endothelial dysfunction in young male Sprague-Dawley rats.

The prevalence of metabolic syndrome (MetSyn) has risen 35% since 2012 and over two-thirds of Americans exhibit features characterizing this condition (obesity, dyslipidemia, hyperglycemia, insulin resistance and/or endothelial dysfunction). The aim of this study was to evaluate the effects of a novel dietary supplemental organic mineral complex (OMC) on these risk factors in a rodent model of MetSyn. Six-week old male Sprague-Dawley rats were fed either standard chow or a high-fat diet (HFD) composed of 60% kcal from fat for 10 weeks. Rats were also treated with OMC in their drinking water at either 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL. The HFD-treated rats exhibited significantly increased body mass (p<0.05), epididymal fat pad mass (p<0.001), waist circumference (p = 0.010), in addition to elevations in plasma endotoxins (p<0.001), ALT activity (p<0.001), fasting serum glucose (p = 0.025) and insulin concentrations (p = 0.009). OMC did not affect body weight or adiposity induced by the HFD. At the higher dose OMC significantly blunted HFD-induced hyperglycemia (p = 0.021), whereas both low and high doses of OMC prevented HFD-induced endotoxemia (p = 0.002 and <0.001, respectively) and hepatocyte injury (ALT activity, p<0.01). Despite evidence of oxidative stress (elevated urinary H2O2 p = 0.032) in HFD-fed rats, OMC exhibited no demonstrable antioxidative effect. Consistent with prior studies, mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) in addition to impaired endothelium-dependent vasodilation that was abrogated by the high dose of OMC (p<0.05). This effect of OMC may be attributed to the high nitrate content of the supplement. These findings suggest that the OMC supplement, particularly at the higher dose, ameliorated several risk factors associated with MetSyn via a non-antioxidant-dependent mechanism.

Nitrate-Rich Fruit and Vegetable Supplement Reduces Blood Pressure in Normotensive Healthy Young Males without Significantly Altering Flow-Mediated Vasodilation: A Randomized, Double-Blinded, Controlled Trial.

Nitric oxide (NO) is a primary vasodilatory factor released from endothelial cells of the peripheral vasculature. NO production is stimulated through enzymatic-dependent mechanisms via NO synthase and from dietary intake of nitrate-containing foods or supplements. We evaluated the efficacy of a nitrate-rich fruit and vegetable liquid supplement (FVS, AMPED NOx, Isagenix International LLC) versus a juice low in nitrates (prune juice, PRU) on circulating nitrates/nitrites as well as cardiovascular parameters in 45 healthy normotensive men (18-40 y). Blood pressure, flow-mediated dilation (FMD), and plasma nitrates and nitrites were measured at baseline and after two weeks of supplementation (2 oz/d). Subjects also completed questionnaires on sleep quality and mood since these measures have been associated with endothelial function. In contrast to PRU, FVS significantly increased plasma nitrates and nitrites (+67%, p < 0.001) and decreased diastolic blood pressure (-9%, p=0.029) after two weeks. The change in FMD for FVS supplementation versus PRU supplementation was not significant (+2% vs. -9%, respectively, p=0.145). Changes in sleep quality or total mood state did not differ between groups after the 2-week study. Thus, the nitrate-rich FVS supplement increased plasma NO and reduced diastolic blood pressure in young normotensive men, but increased plasma NO was not associated with improvements in FMD, mood, or sleep. This trial is registered with ClinicalTrials.gov NCT03486145.