Effects of dietary supplementation with a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) on joint mobility, comfort, and functional capacity in healthy overweight subjects: a randomized placebo-controlled clinical trial.

BACKGROUND: Joint and connective tissue integrity, comfort and function are paramount to optimal performance in exercise, recreational and occupational activities. The fruit of Terminalia chebula has been used extensively in various traditional health systems for different ailments, with additional preclinical and clinical data demonstrating antioxidant and anti-inflammatory potential. The aim of this study was to evaluate the effects of a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) dietary supplementation on joint mobility, comfort, and functional capacity in healthy overweight subjects. METHODS: One-hundred and five (105) overweight, apparently healthy male and female subjects (35-70 years of age) were pre-screened and randomized to one of three groups for 84 days: placebo, AyuFlex1 (250 mg twice daily) or AyuFlex2 (500 mg twice daily) in a randomized, double-blind, placebo-controlled design. A two-week placebo lead-in period was used to improve data quality/validity. All subjects had no knee joint discomfort at rest, but experienced knee joint discomfort only with activity/exercise of at least 30 on 100 mm Visual Analog Scale (VAS). Primary outcome measures included symptoms of joint health and function as measured by modified-Knee Injury & Osteoarthritis Outcomes Score (mKOOS) global & modified-Western Ontario and McMaster Universities Arthritis Index (mWOMAC) subscales (discomfort, stiffness and function). Secondary outcomes included VAS questionnaires on overall/whole-body joint health, low back health, knee mobility, willingness and ability to exercise, 6-min walk test for distance and range of motion (ROM) of pain-free knee flexion/extension. Tertiary outcome measures included inflammatory (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α) and extracellular matrix (ECM)/Connective Tissue (COMP) biomarkers, and safety (vital signs and blood markers) & tolerability (Adverse Event (AE)/ side effect profiles). RESULTS: Compared to placebo, at day 84 AyuFlex® treatment significantly: 1) improved mKOOS global scores in AyuFlex1 + AyuFlex2 (P = 0.023), and improved total and physical function subscale of mWOMAC relative to baseline, 2) improved VAS scores for Knee Discomfort with activity/exercise in AyuFlex1 + AyuFlex2 (P = 0.001) relative to baseline, 3) improved VAS scores for whole-body joint function in AyuFlex1 + AyuFlex2 (P < 0.029) relative to baseline, 4) improved VAS score for decreased knee joint soreness following leg extension challenge for AyuFlex1 (P = 0.022) and AyuFlex2 (P = 0.043) relative to baseline, 5) improved 6-min walk performance distance covered (P = 0.047) and VAS discomfort (P = 0.026) post-6 min walk in AyuFlex1 + AyuFlex2 relative to baseline, 6) and tended to decrease COMP levels in AyuFlex1 + AyuFLex2 (P = 0.104) relative to baseline. All biomarkers of safety remained within normative limits during the study. Low back health tended to improve in the AyuFlex1 and AyuFlex2 group, but failed to reach significance relative to placebo group. CONCLUSIONS: AyuFlex® improved mKOOS global scores, knee joint discomfort with activity/exercise, 6-min walk test distance covered and discomfort post-6 min walk test, overall whole-body joint function, knee soreness following leg extension resistance exercise in a healthy, overweight population, without AE. Differences between 250 mg/BID and 500 mg/BID were non-significant for most of the outcome measures, validating the efficacy of the lower dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02589249 ; October 26, 2015.

Efficacy of chemically characterized Foeniculum vulgare Mill seed essential oil in protection of raw tobacco leaves during storage against fungal and aflatoxin contamination.

AIMS: To report fungal and aflatoxin contamination in stored tobacco leaves and the potential of Foeniculum vulgare (fennel) seed essential oil (EO) as a plant-based preservative in protection of tobacco during storage. METHODS AND RESULTS: Mycological analysis of tobacco samples was done by surface sterilization and serial dilution tests. The Aspergillus flavus isolates were screened for their toxigenicity. Both in vivo and in vitro tests were done to evaluate antifungal and antiaflatoxigenic efficacy of chemically characterized EO. The mycoflora analysis revealed 108 fungal colonies belonging to five genera and nine species. All A. flavus isolates were found aflatoxigenic during screening. Gas chromatography and mass spectrometry analysis of EO identified 19 components (99·66%); estragole being the major component (47·49%). The EO showed broad fungitoxicity at 1·25 µl ml(-1) and 100% inhibition to AFB1 production as well as ergosterol synthesis at 1·0 µl ml(-1) concentration. EO showed 100% protection of stored tobacco samples from aflatoxin B1 contamination. CONCLUSIONS: The fennel EO can thus be formulated as a plant-based preservative for food items. SIGNIFICANCE AND IMPACT OF THE STUDY: The present investigation comprises the first report on antiaflatoxin efficacy of fennel oil and its potency in the protection of tobacco leaves from fungal and aflatoxin contamination during storage.

Effects of a pre-workout supplement on lean mass, muscular performance, subjective workout experience and biomarkers of safety.

In this prospective, randomized, double-blind, trial conducted in two parts, we examined the effects of a multi-ingredient pre-exercise workout supplement blend of creatine, betaine and a dendrobium extract (MMP) on safety, performance, and body composition in healthy men and women undergoing a supervised program of resistance exercise. Part 1 was an acute hemodynamic safety study wherein forty young, healthy men and women (26.2 ± 5.3 years, 70.4 ± 3.3 inches, 83.7 ± 14.9 kg, 26.0 ± 3.2 kg●m(-2)) ingest one dose of either the MMP or comparator in a randomized, double-blind, comparator controlled, crossover fashion before having their resting heart rate, blood, ECG and comprehensive blood chemistry and blood counts completed. Systolic (SBP) and diastolic (DBP) blood pressures were generally raised (3.0-5.4 mm Hg, p<0.01) following supplementation with MPP whereas in the comparator group SBP was marginally reduced by 0.3 to 1.2 mm Hg, p>0.05 at all time points) and DBP was increased (3.0 - 3.9 mm Hg, p<0.05 at all time points). No changes in EKG-corrected QT interval were observed, and no serious adverse events were reported. Part 2 was a six-week training study wherein forty-three young, healthy men and women (24.3 ± 2.9 years, 70.5 ± 3.1 inches, 83.8 ± 9.6 kg, 26.1 ± 2.7 kg●m(-2)) supplemented with daily pre-workout doses of either the MPP or a comparator in a randomized, double-blind, comparator-controlled fashion while following a standardized resistance training program for six weeks. MPP and the comparator were isocaloric and delivered the same amount of caffeine. Significant improvements in visual analog scale (VAS) scores for energy (p<0.024) and concentration (p<0.041) were found along with consistently higher levels of focus accompanied by less fatigue when MPP was consumed in comparison to comparator during upper body muscular strength-endurance tests at weeks 3 and 6. MPP supplementation for 6 weeks did not improve dual-energy x-ray absorptiometry (DEXA) measures of body composition or objective assessments of exercise performance. Overall, MPP use and administration was well tolerated. Self-reported scores for energy and concentration were significantly greater. Over a six-week training and supplementation period, MPP use was not associated with improvements in performance or body composition. Future studies should confirm these effects over a more prolonged training period.

Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects.

We determined the effects of a commercially available, GRAS (Generally Recognized As Safe) by independent conclusion, CBD-containing hemp oil extract on stress resilience, perceived recovery, mood, affect, body composition, and clinical safety markers in healthy human subjects.Methods: Using a randomized, placebo-controlled, double-blind design, 65 overweight, but otherwise healthy men and women (35.2 ± 11.4 years, 28.5 ± 3.3 kg/m2) ingested either Hemp Oil Extract [Hemp, 60 mg/d PlusCBDTM Extra Strength Hemp Extract Oil (15 mg hemp-derived CBD)] or a placebo (PLA) every day for six weeks while continuing to follow their normal diet and physical activity patterns. Outcome variables included changes in stress resilience, a 14-item panel of various psychometric parameters, heart-rate variability, plasma chromogranin A, body composition, and general markers of health. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES).Results: HDL cholesterol significantly improved in the Hemp group (p = 0.004; ES = 0.75). No other statistically significant group x time interaction effects were observed. Statistical tendencies for between-group differences were found for 'I Get Pleasure From Life' (p = 0.06, ES = 0.48) and 'Ability to Cope with Stress' (p = 0.07, ES = 0.46). Sleep quality (Hemp, p = 0.005, ES = 0.54) and sleep quantity (Hemp, p = 0.01, ES = 0.58) exhibited significant within-group changes. All values for hepato-renal function, cardiovascular health, fasting blood lipids, and whole blood cell counts remained within normal clinical limits with no between-group differences over time being identified.Conclusions: Hemp supplementation improved HDL cholesterol, tended to support psychometric measures of perceived sleep, stress response, and perceived life pleasure and was well tolerated with no clinically relevant safety concerns. Registered at clinicaltrials.gov: NCT04294706.

Proprietary Milk Protein Concentrate Reduces Joint Discomfort While Improving Exercise Performance in Non-Osteoarthritic Individuals.

Milk and dairy products are known to contain various bioactives with potential anti-inflammatory and immune modulating effects. Previous research has indicated that milk produced from hyperimmunized cows provided meaningful health benefits to individuals suffering from varying degrees of osteoarthritis and rheumatoid arthritis. PURPOSE: To examine the impact of MicroLactin®, a proprietary milk protein concentrate, on joint discomfort and physical function, exercise performance, quality of life and various measures of affect. METHODS: Non-osteoarthritic men (42.5 ± 8.9 years, 176.7 ± 6.7 cm, 89.9 ± 11.5 kg, 28.8 ± 3.5 kg/m², n = 30) and women (46.4 ± 9.6 years, 163.1 ± 8.2 cm, 72.2 ± 13.1 kg, 27.2 ± 5.3 kg/m², n = 28) with mild to moderate knee pain during physical activity were randomized in a double-blind, placebo-controlled fashion to consume daily either a placebo (PLA) or MicroLactin® (ML) for a period of 8 weeks. Participants completed a functional capacity test pre and post-supplementation and completed visual analog scales (VAS), a 6-min walking test, WOMAC and profile of mood states (POMS) to assess changes in joint health, discomfort, physical function, exercise performance and affect. Mixed factorial ANOVA was used for all statistical analysis and significance was set a priori at p ≤ 0.05. RESULTS: Distance covered in the 6-min walking significantly improved 9% in ML versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of ML improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, ML also improved overall perceptions of neck and back health compared to PLA. Serum and whole blood indicators of clinical safety remained within normal ranges throughout the study. CONCLUSIONS: In comparison to placebo, daily doses of MicroLactin® yielded improvements in several components of the WOMAC, multiple visual analog scales indicative of joint health and stability, discomfort and pain, as well as significant improvements in distance covered during a 6-min walking test. Supplementation was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.

A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters.

Theacrine (1,3,7,9-tetramethyluric acid) is a naturally occurring purine alkaloid, present in Camellia assamica variety kucha tea. Using a two-part approach in humans, the impact of theacrine (TeaCrine®, TC) was used to examine subjective dose-response, daily changes in cognitive and psychometric parameters, and changes in gas exchange and vital signs. All indicators were chosen to better ascertain the previously reported animal and human outcomes involving theacrine administration. Part 1 was a randomized, open-label, dose-response investigation in nine healthy participants whereby three participants ingested 400 mg TC per day and six participants ingested 200 mg/day. Participants recorded subjective changes in cognitive, psychometric, and exercise attributes using 150-mm anchored visual analog scale (VAS) before, and 1, 4, and 6 hours after ingestion every day for 7 consecutive days. Part 2 was a randomized, double-blind, placebo-controlled, crossover investigation in 15 healthy subjects in which all participants ingested a single 200 mg dose of TC or Placebo (PLA). Anchored VAS questionnaires were used to detect subjective changes in various aspects of physical and mental energy along with changes in gas exchange and hemodynamic parameters before, and 1, 2, and 3 hours after acute ingestion. Energy, focus, and concentration increased from baseline values in both doses with no dose-response effect. VAS responses in the 200 mg for willingness to exercise, anxiety, motivation to train and libido increased across the measurement period while no such change was seen with the 400 mg dose. After consuming a single 200 mg dose, significant group × time interaction effects were seen for energy, fatigue, and concentration. No changes in resting heart rate, gas exchange, systemic hemodynamics or side effect profiles were noted.

Effect of a Multi-Nutrient Over-the-Counter Supplement on Changes in Metabolic Rate and Markers of Lipolysis.

Using a prospective, randomized, double-blind, crossover study design, fifteen healthy male (n = 8) and female (n = 7) participants (mean ± standard deviation (SD): 28.3 ± 6.1 yr, 176.3 ± 11.4 cm, 89.8 ± 21.7 kg, 28.5 ± 4.8 kg/m2) completed this study. Two testing sessions occurred after an overnight fast and refraining from physical exercise. Prior to and 60, 120, and 180 minutes after single dose ingestion of placebo (PLA) or a Thermogenic Supplement (TS), visual analog scales (VAS), resting metabolic rate (VO2), and venous blood were collected. Resting heart rate and blood pressures were collected before, and 30, 60, 90, 120, 150 and 180 minutes after PLA or TS ingestion. Significant group × time interactions were found for VO2 with TS experiencing significant (p < 0.05) increases 60 and 120 minutes after ingestion. Respiratory quotient values tended to be lower 180 minutes (p = 0.07) after TS ingestion. TS group reported increased energy 60 minutes (p < 0.05) after ingestion. No interactions were reported for resting heart rate or blood pressure. Significant within-group reductions in systolic blood pressure were noted for PLA, while resting heart rates were significantly lower in TS 30 and 60 minutes after ingestion. An interaction for epinephrine (p = 0.02) was found, while no changes were reported for norepinephrine and dopamine. Dependent t-tests using area under the curve calculations revealed higher AUC values for epinephrine in TS compared to PLA (p = 0.001). In conclusion, ingestion of a single dose of TS increased oxygen consumption, epinephrine and energy levels, while substrate oxidation tended to change in comparison to a placebo. No adverse responses were reported.

Effects of an amylopectin and chromium complex on the anabolic response to a suboptimal dose of whey protein.

BACKGROUND: Previous research has demonstrated the permissive effect of insulin on muscle protein kinetics, and the enhanced insulin sensitizing effect of chromium. In the presence of adequate whole protein and/or essential amino acids (EAA), insulin has a stimulatory effect on muscle protein synthesis, whereas in conditions of lower blood EAA concentrations, insulin has an inhibitory effect on protein breakdown. In this study, we determined the effect of an amylopectin/chromium (ACr) complex on changes in plasma concentrations of EAA, insulin, glucose, and the fractional rate of muscle protein synthesis (FSR). METHODS: Using a double-blind, cross-over design, ten subjects (six men, four women) consumed 6 g whey protein + 2 g of the amylopectin-chromium complex (WPACr) or 6 g whey protein (WP) after an overnight fast. FSR was measured using a primed, continuous infusion of ring-d5-phenylalanine with serial muscle biopsies performed at 2, 4, and 8 h. Plasma EAA and insulin were assayed by ion-exchange chromatography and ELISA, respectively. After the biopsy at 4 h, subjects ingested their respective supplement, completed eight sets of bilateral isotonic leg extensions at 80% of their estimated 1-RM, and a final biopsy was obtained 4 h later. RESULTS: Both trials increased EAA similarly, with peak levels noted 30 min after ingestion. Insulin tended (p = 0.09) to be higher in the WPACr trial. Paired samples t-tests using baseline and 4-h post-ingestion FSR data separately for each group revealed significant increases in the WPACr group (+0.0197%/h, p = 0.0004) and no difference in the WP group (+0.01215%/hr, p = 0.23). Independent t-tests confirmed significant (p = 0.045) differences in post-treatment FSR between trials. CONCLUSIONS: These data indicate that the addition of ACr to a 6 g dose of whey protein (WPACr) increases the FSR response beyond what is seen with a suboptimal dose of whey protein alone.

Effects of a dietary supplement on golf drive distance and functional indices of golf performance.

BACKGROUND: Limited research exists examining the impact of nutrition on golfing performance. This study's purpose was to determine the impact of daily supplementation with an over-the-counter dietary supplement on golf performance. METHODS: Healthy men (30.3 ± 6.9 y, 183.1 ± 5.6 cm, 86.7 ± 11.9 kg), with a 5-15 handicap were assigned in a double-blind, placebo-controlled manner to ingest for 30 days either a placebo (PLA, n = 13) or a dietary supplement containing creatine monohydrate, coffea arabica fruit extract, calcium fructoborate and vitamin D (Strong Drive™, SD, n = 14). Subjects ingested two daily doses for the first two weeks and one daily dose for the remaining two weeks. Participants followed their normal dietary habits and did not change their physical activity patterns. Two identical testing sessions in a pre/post fashion were completed consisting of a fasting blood sample, anthropometric measurements, 1-RM bench press, upper body power and golf swing performance using their driver and 7-iron. Data were analyzed using two-way mixed factorial ANOVAs and ANCOVA when baseline differences were present. Statistical significance was established a priori at p ≤ 0.05. RESULTS: ANCOVA revealed significantly greater (post-test) best drive distance (p = 0.04) for SD (+5.0% [+13.6 yards], ES = 0.75) as well as a tendency (p = 0.07) for average drive distance to increase (+8.4% [+19.6 yards], ES = 0.65), while no such changes were found with PLA (-0.5% [-1.2 yards], ES = 0.04 and +1.3% [+2.8 yards], ES = 0.08, respectively). Both groups experienced significant increases in body mass and 1-RM bench press (p < 0.001). No other significant group × time interactions were found. For the SD group only, within-group analysis confirmed significant improvements in set 1 average (+8.9%, p = 0.001) and peak velocity (+6.8%, p < =0.01). No changes were noted for reported adverse events, pain inventories, quality of life or any measured blood parameter. CONCLUSIONS: SD supplementation for 30 days significantly improved best drive distance more than placebo. Supplementation was well tolerated and did not result in any clinically significant changes in markers of health or adverse events/side effect profiles.

Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra).

OBJECTIVES: To determine whether the response to the new oral medication, sildenafil citrate (Viagra), was influenced by the presence or absence of the neurovascular bundles, as recent reports on its success did not specify the efficacy of the drug in patients with erectile dysfunction after radical prostatectomy. METHODS: Baseline and follow-up data from 28 healthy patients presenting with erectile dysfunction after radical prostatectomy were obtained. Patients receiving any neoadjuvant/adjuvant hormones or adjuvant radiation therapy were excluded. Patients reported what their erectile status was before surgery, before sildenafil therapy, and after using a minimum of four doses of sildenafil. Both the patients and their spouses were interviewed using the Cleveland Clinic post-prostatectomy questionnaire, which includes questions about response to therapy, duration of intercourse, spousal satisfaction, side effects, and related topics. The patients were compared on the basis of the type of surgical procedure they had undergone-nerve sparing or non-nerve sparing. A positive response to sildenafil was defined as erection sufficient for vaginal penetration. RESULTS: Of the 15 patients who had bilateral nerve-sparing procedures, 12 (80%) had a positive response to sildenafil, with a mean duration of 6.92 minutes of vaginal intercourse. These 12 patients also reported a spousal satisfaction rate of 80%. All 12 of the responders had a positive response within the first three doses, and 10 of the 12 responded with the first or second dose. None of the 3 patients who had undergone a unilateral nerve-sparing procedure responded, nor did any of the 10 patients who had undergone a non-nerve-sparing procedure. The two most common side effects of the drug were transient headaches (39%) and abnormal color vision (11%). No patients discontinued the medication because of side effects. CONCLUSIONS: Successful treatment of erectile dysfunction in a patient after prostatectomy with sildenafil citrate may depend on the presence of bilateral neurovascular bundles. No patient who had undergone a non-nerve-sparing procedure responded. Whether patients who undergo unilateral nerve-sparing procedures will respond to sildenafil is still unclear because of the small number of patients in our study. These findings should encourage urologists to continue to perform and perfect the nerve-sparing approach. The ability to restore potency with an oral medication after radical prostatectomy will impact our discussion with the patient on the surgical morbidity of radical prostatectomy.

Role of Viagra after radical prostatectomy.

OBJECTIVES: To determine whether the response to sildenafil citrate (Viagra) in patients with erectile dysfunction after radical prostatectomy was influenced by the presence or absence of neurovascular bundles, the interval from surgery to the initiation of drug therapy, and the dose of the drug. METHODS: Baseline and follow-up data from 91 patients presenting with erectile dysfunction after radical prostatectomy were obtained. The patients were stratified according to the type of nerve-sparing (NS) procedure: bilateral NS, unilateral NS, and non-NS. They were interviewed using the Cleveland Clinic Post Prostatectomy (CCPP) questionnaire and the International Index of Erectile Function (IIEF) questionnaire. RESULTS: The presence or absence of the neurovascular bundles influenced the ability to achieve vaginal intercourse. In the patients who had undergone bilateral NS, 71.7% (38 of 53) responded; in those with unilateral NS, 50% (6 of 12) responded; and in those with non-NS, 15.4% (4 of 26) responded. The IIEF questionnaire confirmed the quality of the positive responses, with significant improvements in response to question 3 (frequency of penetration), question 4 (frequency of maintenance of erection), and question 7 (satisfaction with intercourse). The magnitude of improvement in responses was higher in the bilateral NS group than in the unilateral NS and non-NS groups (P <0.05). When the data of the 48 positive responders were analyzed, no difference in the response rate was found when the interval from surgery to drug therapy was stratified by the following three intervals: 0 to 6 months (44%), 6 to 12 months (55%), and greater than 12 months (53%). Of the positive responders, 14 (29.1%) required the 50-mg dose, and 34 (70.9%) required the 100-mg dose. The most common side effects were transient headaches (28.6%), flushing (21.9%), dizziness (8.8%), dyspepsia (6.5%), and nasal congestion (5.4%), with an increase in the incidence of headaches seen at the higher dose (P = 0.04). CONCLUSIONS: Successful treatment of erectile dysfunction with sildenafil citrate after radical prostatectomy depends on the presence of the neurovascular bundles. Our data suggest that the response to sildenafil is not related to the interval between the surgery and initiation of drug therapy but is related to the dose.