Effect of a Euglena gracilis Fermentate on Immune Function in Healthy, Active Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

Euglena gracilis produce high amounts of algal ß-1,3-glucan, which evoke an immune response when consumed. This study investigated the effect of supplementation with a proprietary Euglena gracilis fermentate (BG), containing greater than 50% ß-1,3-glucan, on immune function as measured by self-reported changes in upper respiratory tract infection (URTI) symptoms. Thirty-four healthy, endurance-trained participants were randomized and received either 367 mg of BG or placebo (PLA) for 90 days. Symptoms were assessed by the 24-item Wisconsin Upper Respiratory Symptom Survey and safety via clinical chemistry, hematology, vitals, and adverse event reporting. Participants supplemented with BG over 90 days reported fewer sick days (BG: 1.46 ± 1.01; PLA: 4.79 ± 1.47 days; p = 0.041), fewer URTI symptoms (BG: 12.62 ± 5.92; PLA: 42.29 ± 13.17; p = 0.029), fewer symptom days (BG: 5.46 ± 1.89; PLA: 15.43 ± 4.59 days; p = 0.019), fewer episodes (BG: 2.62 ± 0.67; PLA: 4.79 ± 0.67; p = 0.032), and lower global severity measured as area under curve for URTI symptoms (BG: 17.50 ± 8.41; PLA: 89.79 ± 38.92; p = 0.0499) per person compared to placebo. Sick days, symptoms, and global severity were significantly (p < 0.05) fewer over 30 days in the BG group compared to PLA. All safety outcomes were within clinically normal ranges. The study provides evidence that supplementation with a proprietary Euglena gracilis fermentate containing greater than 50% ß-1,3-glucan may reduce and prevent URTI symptoms, providing immune support and protecting overall health.

The attention-enhancing effects of spearmint extract supplementation in healthy men and women: a randomized, double-blind, placebo-controlled, parallel trial.

Previous studies have demonstrated that chronic supplementation with a proprietary spearmint extract (PSE) can improve cognitive performance in individuals 50-70 years of age with age-related memory issues. In the present study, our hypothesis was that chronic supplementation of PSE would improve cognitive performance in young, active individuals. Using a randomized, double-blind, placebo-controlled, parallel design, healthy, recreationally active men and women (N = 142) received 900 mg of PSE or placebo (PLA) daily for 90 days. Cognition was assessed via cognitive test battery (CNS Vital Signs) that resulted in 10 cognitive domains. Sleep, mood, and quality of life were assessed via validated questionnaires. Measurements were evaluated on days 0, 7, 30, and 90 of supplementation. Significant (P < .05) treatment effects were observed for sustained attention, wherein PSE improved sustained attention vs PLA at day 30 (PSE: 33.3 ±â€¯0.54 vs PLA: 31.2 ±â€¯0.98; P = .001) and day 90 (PSE: 34.0 ±â€¯0.44 vs PLA: 32.7 ±â€¯0.75; P = .007). Significant (P < .05) treatment × visit interactions were observed for complex attention, wherein PSE improved complex attention compared to PLA at day 7 (PSE: 8.0 ±â€¯2.22 vs PLA: 7.6 ±â€¯0.57; P = .016). Significant (P < .05) improvements were observed in 2 individual tests: the shifting attention test and the 4-part continuous performance test. No significant differences were observed in mood, sleep, or quality of life. The current study demonstrates that chronic supplementation with 900 mg of PSE improves cognitive performance in a young, active population, further supporting PSE as an efficacious nootropic.

Efficacy of a nootropic spearmint extract on reactive agility: a randomized, double-blind, placebo-controlled, parallel trial.

BACKGROUND: Proprietary spearmint extract (PSE) containing a minimum 14.5% rosmarinic acid and 24% total phenolic content, has evinced positive effects on cognition in individuals aged 50-70 with memory impairment after chronic supplementation. To address the growing interest in connecting mental and physical performance, the present study examined whether the nootropic effects of PSE translate into changes in reactive agility following daily supplementation with PSE. METHODS: Utilizing a randomized, double-blind, placebo-controlled, parallel design, healthy, recreationally-active men and women (n = 142) received 900 mg of PSE or placebo (PLA) daily for 90 days. Reactive agility, our primary outcome, was determined by measuring the number of hits and average reaction time (ART) on a Makoto Arena II, a 3600 audio-visual device that measures stationary, lateral, and multi-directional active choice reaction performance. Safety was evaluated using complete blood count, comprehensive metabolic panel, and blood lipids. Measurements were evaluated on days 7, 30, and 90 of supplementation. RESULTS: An overall treatment effect (p = 0.019) was evident for increased hits with PSE on the stationary test with footplates, with between group differences at Day 30 (PSE vs. PLA: 28.96 ± 2.08 vs. 28.09 ± 1.92 hits; p = 0.040) and Day 90 (PSE vs. PLA: 28.42 ± 2.54 vs. 27.02 ± 3.55 hits; p = 0.002). On the same task, ART improved (treatment effect, p = 0.036) with PSE at Day 7 (PSE vs. PLA: 0.5896 ± 0.060 vs. 0.6141 ± 0.073 s; p = 0.049) and Day 30 (PSE vs. PLA: 0.5811 ± 0.068 vs. 0.6033 ± 0.055 s; p = 0.049). PSE also significantly increased hits (treatment effect, p = 0.020) at Day 30 (PSE vs. PLA: 19.25 ± 1.84 vs. 18.45 ± 1.48 hits; p = 0.007) and Day 90 (PSE vs. PLA: 19.39 ± 1.90 vs. 18.66 ± 1.64 hits; p = 0.026) for the multi-directional test with footplates. Significant differences were not observed in the remaining Makoto tests. PSE was well tolerated as evidenced by no effects observed in the blood safety panels. CONCLUSIONS: The findings of the current study demonstrate that consumption of 900 mg of PSE improved specific measures of reactive agility in a young, active population. TRIAL REGISTRATION: clinicaltrials.gov, NCT02518165 . Registered August 7, 2015 - retrospectively registered.

Resistance Exercise Selectively Mobilizes Monocyte Subsets: Role of Polyphenols.

PURPOSE: To examine the impact of polyphenol supplementation on the recruitment, mobilization, and activation of monocyte subsets after resistance exercise. METHODS: Thirty-eight recreationally active males (22.1 ± 3.1 yr; 173.9 ± 7.9 cm; 77.8 ± 14.5 kg) were assigned to 28 d of polyphenol blend (PPB) supplementation, placebo (PL), or control (CON). Blood samples were obtained before (PRE) postresistance exercise, immediately (IP) postresistance exercise, 1 h (1H) postresistance exercise, 5 h (5H) postresistance exercise, 24 h (24H) postresistance exercise, and 48 h (48H) postresistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and 48H. Circulating concentrations of macrophage chemoattractant protein-1 (MCP-1) and fractalkine, as well as intramuscular MCP-1 were analyzed via multiplex assay. Changes in the proportions and expression of CD11b on monocyte subsets were assessed via flow cytometry. RESULTS: Circulating MCP-1 increased in PPB and PL at IP with further increases at 5H. Intramuscular MCP-1 was increased at 1H, 5H, and 48H in all groups. Classical monocyte proportions were reduced in PPB and PL at IP, and increased at 1H. Nonclassical monocytes were increased in PPB and PL at IP, whereas intermediate monocytes were increased at IP, and reduced at 1H. Intermediate monocytes were increased in PPB at 24H and 48H. CD11b expression was reduced on PPB compared with PL and CON at PRE on intermediate and nonclassical monocytes. CONCLUSIONS: Resistance exercise may elicit selective mobilization of intermediate monocytes at 24H and 48H, which may be mediated by tissue damage. Additionally, polyphenol supplementation may suppress CD11b expression on monocyte subsets at rest.

Spearmint Extract Improves Working Memory in Men and Women with Age-Associated Memory Impairment.

OBJECTIVE: The purpose of this study was to investigate the effects of supplementation with a spearmint (Mentha spicata L.) extract, high in polyphenols including rosmarinic acid, on cognitive performance, sleep, and mood in individuals with age-associated memory impairment (AAMI). DESIGN: Subjects with AAMI (N = 90; 67% female; age = 59.4 ± 0.6 years) were randomly assigned (n = 30/group) to consume 900, 600, or 0 mg/day (two capsules, once daily) spearmint extract for 90 days, in this double-blind, placebo-controlled trial. Assessments were completed for cognition (days 0, 45, and 90), sleep (days 0 and 90), and mood (days 0 and 90) by using the Cognitive Drug Research (CDR) System™, Leeds Sleep Evaluation Questionnaire (LSEQ), and Profile of Mood States (POMS™), respectively. RESULTS: Quality of working memory and spatial working memory accuracy improved after supplementation with 900 mg/day spearmint extract by 15% (p = 0.0469) and 9% (p = 0.0456), respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo (p = 0.0046). Overall treatment effects were evident for vigor-activity (p = 0.0399), total mood disturbance (p = 0.0374), and alertness and behavior following wakefulness (p = 0.0415), with trends observed for improvements after spearmint supplementation relative to placebo. CONCLUSIONS: These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI.

Impact of Polyphenol Supplementation on Acute and Chronic Response to Resistance Training.

Beyer, KS, Stout, JR, Fukuda, DH, Jajtner, AR, Townsend, JR, Church, DD, Wang, R, Riffe, JJ, Muddle, TWD, Herrlinger, KA, and Hoffman, JR. Impact of polyphenol supplementation on acute and chronic response to resistance training. J Strength Cond Res 31(11): 2945-2954, 2017-This study investigated the effect of a proprietary polyphenol blend (PPB) on acute and chronic adaptations to resistance exercise. Forty untrained men were assigned to control, PPB, or placebo. Participants in PPB or placebo groups completed a 4-week supplementation period (phase I), an acute high-volume exercise bout (phase II), and a 6-week resistance training program (phase III); whereas control completed only testing during phase II. Blood draws were completed during phases I and II. Maximal strength in squat, leg press, and leg extension were assessed before and after phase III. The exercise protocol during phase II consisted of squat, leg press, and leg extension exercises using 70% of the participant's strength. The resistance training program consisted of full-body exercises performed 3 d·wk. After phase I, PPB (1.56 ± 0.48 mM) had greater total antioxidant capacity than placebo (1.00 ± 0.90 mM). Changes in strength from phase III were similar between PPB and placebo. Polyphenol blend supplementation may be an effective strategy to increase antioxidant capacity without limiting strength gains from training.

Safety and tolerability of a dried aqueous spearmint extract.

Spearmint (Mentha spicata L.) and spearmint extracts are Generally Recognized as Safe (GRAS) for use as flavoring in beverages, pharmaceuticals, and confectionaries. Studies of spearmint extracts in humans and animals have reported conflicting results with respect to toxicity. Since the chemical composition of these extracts was not reported and the spearmint source material was different, the relevance of these existing data to evaluating the risks associated with ingestion of a dried aqueous spearmint extract standardized to rosmarinic acid is not clear. Hence, the safety and tolerability of the dried aqueous spearmint extract was evaluated as part of a double-blind, randomized, placebo-controlled trial in healthy adults with age-associated memory impairment. Ingestion of both 600 and 900 mg/day for 90 days had no effect on plasma levels of follicular stimulating hormone, luteinizing hormone, or thyroid stimulating hormone, or other safety parameters including vital signs, plasma chemistry or whole blood hematology values. Additionally, there were no reported severe adverse events, no significant between-group differences in the number of subjects reporting adverse effects and the adverse events reported could not be attributed to ingestion of the extract. These results therefore show that ingestion of the aqueous dried spearmint extract is safe and well-tolerated.

Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile Fraction of a Rosemary (Rosmarinus officinalis L.) Extract.

This paper presents a comprehensive analysis of the phytochemical profile of a proprietary rosemary (Rosmarinus officinalis L.) extract rich in carnosic acid. A characterization of the (poly)phenolic and volatile fractions of the extract was carried out using mass spectrometric techniques. The (poly)phenolic composition was assessed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MSn) and a total of 57 compounds were tentatively identified and quantified, 14 of these being detected in rosemary extract for the first time. The rosemary extract contained 24 flavonoids (mainly flavones, although flavonols and flavanones were also detected), 5 phenolic acids, 24 diterpenoids (carnosic acid, carnosol, and rosmanol derivatives), 1 triterpenoid (betulinic acid), and 3 lignans (medioresinol derivatives). Carnosic acid was the predominant phenolic compound. The volatile profile of the rosemary extract was evaluated by head space solid-phase microextraction (HS-SPME) linked to gas chromatography-mass spectrometry (GC-MS). Sixty-three volatile molecules (mainly terpenes, alcohols, esters, aldehydes, and ketones) were identified. This characterization extends the current knowledge on the phytochemistry of Rosmarinus officinalis and is, to our knowledge, the broadest profiling of its secondary metabolites to date. It can assist in the authentication of rosemary extracts or rosemary-containing products or in testing its bioactivity. Moreover, this methodological approach could be applied to the study of other plant-based food ingredients.

Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice.

Oxidative damage is one of the hallmarks of the aging process. The current study evaluated effects of two proprietary antioxidant-based ingredients, rosemary extract and spearmint extract containing carnosic acid and rosmarinic acid, respectively, on learning and memory in the SAMP8 mouse model of accelerated aging. The two rosemary extracts contained carnosic acid (60% or 10% carnosic acid) and one spearmint extract contained 5% rosmarinic acid. Three doses of actives in each extract were tested: 32, 16, 1.6 or 0mg/kg. After 90days of treatment mice were tested in T-maze foot shock avoidance, object recognition and lever press. Rosemary extract containing 60% carnosic acid improved acquisition and retention in T-maze foot shock, object recognition and lever press. Rosemary extract with 10% carnosic acid improved retention in T-maze foot shock avoidance and lever press. Spearmint with 5% rosmarinic acid improved acquisition and retention in T-maze foot shock avoidance and object recognition. 4-hydroxynonenal (HNE) was reduced in the brain cortex after treatment with all three extracts (P<0.001) compared to the vehicle treated SAMP8. Protein carbonyls were reduced in the hippocampus after administration of rosemary with 10% carnosic acid (P<0.05) and spearmint containing 5% rosmarinic acid (P<0.001). The current results indicate that the extracts from spearmint and rosemary have beneficial effects on learning and memory and brain tissue markers of oxidation that occur with age in SAMP8 mice.

Phenolic and Volatile Composition of a Dry Spearmint (Mentha spicata L.) Extract.

The present paper reports a complete mass spectrometric characterization of both the phenolic and volatile fractions of a dried spearmint extract. Phenolic compounds were analysed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MS(n)) and a total of 66 compounds were tentatively identified, being the widest phenolic characterisation of spearmint to date. The analysis suggests that the extract is composed of rosmarinic acid and its derivatives (230.5 ± 13.5 mg/g) with smaller amounts of salvianolic acids, caffeoylquinic acids, hydroxybenzoic acids, hydroxycinnamic acids, flavones, and flavanones. Head space solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) technique, that was applied to characterize the volatile fraction of spearmint, identified molecules belonging to different chemical classes, such as p-cymene, isopiperitone, and piperitone, dihydroedulan II, menthone, p-cymen-8-ol, and ß-linalool. This comprehensive phytochemical analysis can be useful to test the authenticity of this product rich in rosmarinic acid and other phenolics, and when assessing its biological properties. It may also be applied to other plant-derived food extracts and beverages containing a broad range of phytochemical compounds.

The effect of polyphenols on cytokine and granulocyte response to resistance exercise.

This study examined the effect of resistance exercise on the production, recruitment, percentage, and adhesion characteristics of granulocytes with and without polyphenol (PPB) supplementation. Thirty-eight untrained men were randomized into three groups: PPB (n = 13, 21.8 ± 2.5 years, 171.2 ± 5.5 cm, 71.2 ± 8.2 kg), placebo (PL; n = 15, 21.6 ± 2.5 years, 176.5 ± 4.9 cm, 84.0 ± 15.7 kg), or control (CON; n = 10, 23.3 ± 4.3 years, 173.7 ± 12.6 cm, 77.3 ± 16.3 kg). Blood samples were obtained pre (PRE), immediately (IP), 1 h (1H), 5 h (5H), 24 h (24H), 48 h (48H), and 96 h (96H) postresistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and 48H. Plasma concentrations and intramuscular content of interleukin-8 (IL-8), granulocyte (G-CSF), and granulocyte-macrophage colony stimulating factor (GM-CSF) were analyzed via multiplex assays. Changes in relative number of circulating granulocytes and adhesion receptor (CD11b) were assessed using flow cytometry. Intramuscular IL-8 was significantly elevated at 1H, 5H, and 48H (P < 0.001). Area under the curve analysis indicated a greater intramuscular IL-8 content in PL than PPB (P = 0.011). Across groups, circulating G-CSF was elevated from PRE at IP (P < 0.001), 1H (P = 0.011), and 5H (P = 0.025), while GM-CSF was elevated at IP (P < 0.001) and 1H (P = 0.007). Relative number of granulocytes was elevated at 1H (P < 0.001), 5H (P < 0.001), and 24H (P = 0.005, P = 0.006) in PPB and PL, respectively. Across groups, granulocyte CD11b expression was upregulated from PRE to IP (P < 0.001) and 1H (P = 0.015). Results indicated an increase in circulating CD11b on granulocytes, and IL-8 within the muscle following intense resistance exercise. Polyphenol supplementation may attenuate the IL-8 response, however, did not affect granulocyte percentage and adhesion molecule expression in peripheral blood following resistance exercise.

Supplementation with a polyphenolic blend improves post-exercise strength recovery and muscle soreness.

BACKGROUND: Exercise can initiate a cascade of inflammatory and oxidative stress-related events leading to delayed onset muscle soreness. Polyphenols possess antioxidant and anti-inflammatory properties. OBJECTIVE: The current study examined the effects of a proprietary polyphenolic blend (PB), containing catechins and theaflavins, on exercise performance and recovery following an eccentric exercise challenge. DESIGN: Male participants (18-35 years of age) received placebo or PB at a low dose (PB-L, 1,000 mg/d) or high dose (PB-H, 2,000 mg/d) for 13 weeks. During the 13th week of supplementation, participants completed an eccentric exercise (40 min downhill treadmill run) followed by a strength assessment (peak torque on isokinetic leg extensions) pre-exercise, and 24, 48, and 96 h post-exercise. Muscle soreness (subjective questionnaire), markers of muscle stress (cortisol and creatine phosphokinase [CK]), and antioxidant capacity (ferric reducing ability of plasma [FRAP]) were also assessed. RESULTS: PB-H attenuated the decrease in peak torque observed in the placebo group from pre-exercise to 48 h (p=0.012) and 96 h (p=0.003) post-exercise. At 48 h post-exercise, PB-H reduced whole body and hamstring soreness (p=0.029) versus placebo. Chronic consumption of PB improved serum FRAP (p=0.039). As expected, serum cortisol and CK increased from pre- to post-exercise in all groups; however, by 96 h, cortisol and CK levels returned to pre-exercise levels following PB supplementation. At 96 h, the change in cortisol from pre- to post-exercise was significantly greater in placebo versus PB-H (p=0.039). CONCLUSION: These findings show that chronic consumption of PB improved antioxidant status, reduced markers of muscle stress, and promoted strength recovery post-exercise.

The safety of a dry spearmint extract in vitro and in vivo.

A proprietary dry spearmint extract containing 15.4% rosmarinic acid was assessed in a 90-day study with Sprague-Dawley rats that were gavaged at 0, 422 (low), 844 (mid), or 1948 (high) mg dry spearmint extract/kg bw/day, (equivalent to 0, 65, 130, or 300 mg rosmarinic acid/kg bw/day, respectively). No treatment-related clinical signs or adverse effects were observed in body weight, feed consumption, neurological parameters, hematology, clinical chemistry, gross pathology, and histopathology. However, there were statistically significant increases in the absolute and relative weight of the pituitary gland in mid- and high-dose males, absolute and relative weight of the thyroid gland in the high-dose groups of both sexes and in mid-dose males, and absolute and relative weight of the salivary glands in high-dose females compared to vehicle control group. These changes were considered non-adverse since no corresponding microscopic changes were seen. Based on these findings, the no-observed-adverse-effect level (NOAEL) for the dry spearmint extract was 1948 mg extract/kg bw/day, the highest dose tested, in Sprague-Dawley rats. In addition, the extract showed no mutagenic activity in the Ames assay using Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) and did not induce chromosomal aberrations when tested with human peripheral blood lymphocytes.

Antihypertensive effect of passion fruit peel extract and its major bioactive components following acute supplementation in spontaneously hypertensive rats.

Extracts from leaves, peels or flowers of Passiflora are noted for their medicinal effects. Passiflora edulis peel extract (PFPE) has been proposed to lower blood pressure (BP); however, only indirect measurement techniques have been employed. To more accurately measure the effect of PFPE on hemodynamic parameters and determine the minimal effective dose, hemodynamic parameters were directly measured in spontaneously hypertensive rats (SHR) implanted with radiotelemeters. PFPE was given orally at 0, 2.5, 50 or 200 mg/kg body weight (BW) to determine the minimal effective dose. Once this dose was determined, the potential active components, edulilic acid (EA), anthocyanin fraction (AF) or γ-aminobutyric acid (GABA), were tested to determine which may contribute to the reductions in BP. The 50 mg PFPE/kg BW dose was the lowest dose that significantly reduced all hemodynamic parameters from baseline when compared to control. When the potential actives were provided at equivalent doses to those found in 50 mg PFPE/kg BW, the EA and AF significantly reduced all measured hemodynamic parameters from baseline when compared to control. GABA did not significantly affect any hemodynamic parameters compared to control and significantly increased heart rate. These direct measurements indicate that PFPE can decrease hemodynamic parameters in SHR and indicate that EA and AF are active compounds that contribute to the antihypertensive effects of PFPE supplementation. While these results are encouraging, detailed mechanistic studies are needed to determine the putative value of PFPE for blood pressure control in humans.