Herein, we determined if a multi-ingredient supplement (NAD3; 312 mg of combined Wasabia japonica extract, theacrine, and copper (I)niacin chelate) versus a placebo (CTL) affected peripheral blood mononuclear (PMBC) transcriptomic, DNA methylation, and sirtuin activity profiles in middle-aged adults after 12 weeks of supplementation. Several mRNAs demonstrated interactions (n = 148 at ±1.5-fold change, p < 0.01), and more stringent filtering indicated that 25 mRNAs were upregulated and 29 were downregulated in the NAD3 versus CTL group. Bioinformatics on these 64 mRNAs suggested that DNA conformational alterations may have been promoted with NAD3 supplementation, and this was corroborated with more CpG sites being hypermethylated (p < 0.001) in the CTL versus the NAD3 group when examining pre- to post-intervention changes (369 versus 35). PBMC SIRT activity decreased in CTL participants (p < 0.001), but not in NAD3 participants (p = 0.289), and values at 12 weeks trended higher in NAD3 participants (p = 0.057). Interestingly, the pre- to post- changes in SIRT activity values significantly correlated with changes in PBMC NAD+: NADH values obtained from a previous investigation in these participants (r = 0.534, p = 0.015). In conclusion, the current mRNA and DNA methylation data indirectly suggest that NAD3 supplementation may affect PBMC DNA conformation, while other direct assays suggest that NAD3 supplementation maintains SIRT activity through the potential maintenance of NAD+: NADH levels. However, these results are preliminary due to limited n-sizes and the study being performed in middle-aged adults.

Although several resistance exercise studies have used bioinformatics platforms to identify the biological relevance of gene expression changes, these platforms seldom provide in-depth information on genes that have been mechanistically linked to skeletal muscle hypertrophy. Thus, we sought to perform a secondary analysis on a muscle transcriptomic dataset we previously collected involving two different bouts of resistance exercise. Previously trained college-aged males (n=11, training experience: 4±3 years) performed two resistance exercise bouts separated by one week. The higher-load bout (80fail) consisted of 4 sets of back squats and 4 sets of leg extensions to failure using 80% of their estimated one-repetition maximum. The lower-load bout (30fail) consisted of this same paradigm using 30% of their one-repetition maximum. Vastus lateralis muscle biopsies were collected before (PRE), 3 hours (3h), and 6 hours (6h) after each exercise bout, and bouts were separated by a one-week washout. Muscle mRNA was analyzed for genome-wide mRNA expression patterns using the Clariom S mRNA array. Based on an extensive literature search performed by us and others, the mRNA expression profile of gene candidates mechanistically associated with skeletal muscle hypertrophy (58 genes) was interrogated between 30fail and 80fail training. Select targets were further interrogated for associated protein expression and phospho-signaling events. Although none of the 58 skeletal muscle hypertrophy-associated gene targets demonstrated significant bout✕time point interactions, ~57% showed a significant time-only effect from PRE to 3h (15↑ and 18↓, p<0.01) and ~26% showed significant time-only effect from PRE to 6h (8↑ and 9↓, p<0.01). Genes related to myostatin signaling (9 genes) and mTORC1 signaling (9 genes) were well represented on the gene list. Compared to mTORC1 signaling mRNAs, a greater percentage of myostatin signaling-related mRNAs were dynamically altered post-exercise (i.e., significant time-only effects). There were increases in phospho (Thr389)/pan p70S6K (p=0.001; PRE to 3h) and follistatin protein levels (p=0.021; PRE to 6h) regardless of bout. No significant time effects or interactions were observed for phospho (Ser2448)/pan mTOR, phospho (Thr389)/pan AKT, phospho (Ser235/236)/pan rpS6, or myostatin protein levels. The data have multiple implications. First, performing lighter load and heavier load resistance exercise to failure elicits similar alterations in the mRNA responses of genes mechanistically associated with skeletal muscle hypertrophy and mTORC1 signaling. Second, acute resistance exercise predominantly affects the myostatin signaling pathway via transcriptional mechanisms and genes involved with mTORC1 signaling are less affected in this regard. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise.

A randomised, placebo-controlled, double-blind, parallel clinical study was performed to examine the effects of a probiotic-amylase (PRO) blend on gastrointestinal (GI) symptoms. Sixty men and women (44.4 +/- 8.9 yr; 82.0 +/- 18.4 kg; 170.3 +/- 11.5 cm; 28.1 +/- 4.6 kg/m(2)) were randomised into PRO (n = 29) or placebo (PLA: n = 31) groups. Participants exhibited mild to moderate GI symptoms and severity [via Gastrointestinal Symptom Rating Scale (GSRS)] to be eligible for participation. Participants were tested before (Baseline) and after (POST) 6 weeks of supplementation on various gastrointestinal indices, the GSRS (to assess GI symptoms, frequency, and severity), an anxiety questionnaire (GAD-7), and an overall well-being questionnaire (SF-36). Two (PRO vs PLA) x 2 (Baseline vs POST) mixed factorial ANOVAs were completed to assess group, time, and (group x time) interaction effects. Fiftytwo subjects who completed the entire study were analysed (PRO: n = 25, PLA: n = 27). There were statistically significant (P <= 0.05) interactions for bloating, GSRS score, and abdominal discomfort but time effects for flatulence, constipation, stool regularity, and GAD-7 total score. PRO significantly reduced GSRS score (similar to 60 vs 25%, d = 0.72), bloating (similar to 49% vs 25%, d = -0.63) and abdominal discomfort (59% vs 32%, d = -0.66) to a greater degree than PLA. PRO significantly reduced subjective feelings of irritability, pain, and overall health interference. Oral supplementation of the probiotic-amylase blend was very well tolerated. Our study showed that the probioticamylase blend reduced the GSRS score and other GI symptoms to a greater degree than PLA.

We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to "Focal adhesion," "MAPK signaling," and "PI3K-Akt signaling" were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

With this study we expand our understanding of how the manipulation of RT variables affect epigenetic modifications in skeletal muscle.

Introduction: Many consumers use dietary supplements in the hopes of increasing energy and burning more calories, which if sustained over time may help accelerate weight loss. The purpose of this clinical trial was to investigate the effects of an over-the-counter thermogenic supplement called Burn-XT™ (BXT) on metabolic rate, substrate oxidation, and various psychometric indices of affect that impact weight management. Methods: Using a double-blind, placebo-controlled, cross-over design, 16 women and 10 men (29.3 ± 7.3 yr, 169.4 ± 8.6 cm, 75.5 ± 14.3 kg) underwent two testing sessions: placebo (PL) and BXT. Seated metabolic rate and substrate oxidation, vital signs, and anchored visual analogue scale (VAS) assessments of energy, mood, motivation, focus, fatigue, concentration, and appetite were made before supplementation and hourly for three hours post-ingestion. Two-factor (2x4) factorial ANOVAs and paired sample t-tests (corrected for multiple comparisons) were used for analyses. Results: Significant increases in metabolic rate (oxygen consumption) were noted at 60 minutes in BXT (+11.9 mL O2/min) vs. PL (-2.5 mL O2/min), p = 0.004, d = -0.74. Only BXT increased metabolic rate compared to baseline at 60 minutes (+11.9 mL O2/min, p = 0.021, d = -0.53) and 120 minutes (+12.1 mL O2/min, p = 0.019, d = -0.54). The AUC for resting energy expenditure increased more in BXT vs. PL (p = 0.007, d = -0.57). VAS detected significant improvements in energy, mood, focus, and concentration for BXT vs. PL at 120 and 180 minutes (all p < 0.05, d = -0.58 to -0.68). In all cases, within-group changes from baseline for these VAS parameters were significant (all p < 0.05, d = -0.76 to -1.38) in BXT but not in PL. No within or between group differences in appetite, substrate oxidation, or heart rate were noted. Small (~3-4 mm Hg), but statistically significant (p < 0.05, d = -0.51 to -0.69) increases in diastolic blood pressure were noted in BXT at 60, 120, and 180 min vs. PL; and in systolic blood pressure at 60 min vs. PL. In all cases, values remained within normal clinical hemodynamic ranges. Conclusions: A single dose of BXT safely increased metabolic rate, energy, mood, focus, and concentration. Given that these factors are known to favorably impact weight management, future studies should determine whether daily supplementation with BXT reduces body weight and improves body composition.

This study continues to display how different modalities of resistance training affect the skeletal muscle molecular milieu and furthers our scientific understanding of factors that contribute to training adaptations.

Limited pre-clinical and clinical data suggest theacrine or theacrine-based supplements modulate biological processes associated with lipid metabolism and aging. Herein, we sought to examine if 12 weeks of daily supplementation with a theacrine-based supplement (termed NAD3®; 312 mg of combined Wasabia japonica freeze-dried rhizome standardized for isothicyantes, theacrine, and copper (I)niacin chelate) altered serum lipids as well as select nicotinamide adenine dinucleotide (NAD+)-associated metabolites in peripheral blood mononuclear cells (PBMCs). Twenty-eight participants (12 males, 16 females) were randomly assigned to receive either NAD3 (n = 13; age: 52 ± 7 years old, body mass index: 29.0 ± 5.0 kg/m2) or a cellulose placebo (n = 15; age: 51 ± 5 years old, body mass index: 28.3 ± 3.9 kg/m2). Blood samples were obtained in mornings following overnight fasts prior to supplementation (Pre) and following the 12-week intervention (Post). PBMCs were freshly isolated and prepared for targeted NAD+ metabolomics, and serum as well as whole blood was assayed for blood lipids and other safety markers through a commercial laboratory. Significant interactions (p < 0.05) were observed for total cholesterol, LDL cholesterol, and LDL: HDL ratio and post hoc analyses indicated these biomarkers significantly decreased with NAD3 supplementation (Pre-to-Post percent decreases were 11.1, 15.2, and −18.9%, respectively). A significant interaction was also observed for PBMC NAD+: NADH values, where levels trended downward from Pre to Post in the CTL group (p = 0.081) and values at Post were greater in NAD3 versus CTL (p = 0.023). No interactions were observed for systolic/diastolic blood pressure, body mass, or blood markers indicative of clinical safety. Although participant numbers were limited, these first-in-human data demonstrate a theacrine-based NAD3 supplement can favorably alter biomarkers of lipid metabolism and cellular NAD+ status. However, the latter data are limited to targeted NAD+ metabolites, and the effects of supplementation on other cellular metabolites or mechanisms related to the observed outcomes need to be further explored.

Background: Previously we reported that acute supplementation with an amylopectin- chromium complex combined with a six-gram dose of whey protein increased rates of muscle protein synthesis. The purpose of this study was to examine if chronic supplementation with the same amylopectin-chromium complex plus a higher dose of protein could impact resistance training adaptations, recovery, and biomarkers of safety.Methods: Using a randomized, active-controlled, double-blind design, 35 recreationally active men (mean ± age, height, weight: 40.9 ± 7.6 y, 180.2 ± 6.1 cm, 95.8 ± 14.5 kg) were matched according to HOMA-IR and resistance-training experience and then randomly allocated to one of three groups: an active group consisting of 2 g amylopectin-chromium complex + 15 g whey protein isolate (V15P), an equivalent dose of whey protein isolate (15 g of whey protein, 15P), or a 30 gram dose of whey protein isolate (30P). Subjects consumed their respective supplement immediately following resistance exercise on days when training occurred and at the same time of day on non-training days. At 0, 4, and 8 weeks of training, body composition (4C via DXA, Bod Pod, Bioimpedance), whole-body protein balance (oral 15N-alanine), upper body and lower body performance (bench press, squat, jump power), and visual analog scale (VAS) scores for recovery, sleep quality, energy, willingness to train, and muscle soreness were assessed. Safety assessments included systemic hemodynamics, complete blood count, and comprehensive metabolic panels. Results: All groups gained strength, increased fat-free mass, and improved muscle size. Similarly, all groups increased squat repetitions to failure (RTF), with V15P experiencing a greater increase (+25.3 reps, p = 0.02) when compared to 15P (+12.0 reps) and 30P (+13.9 reps). After normalizing data to body mass, vertical jump power increased (p = 0.03) more for V15P (+2.1 Watts/kg) than either 15P (+0.4 Watts/kg) or 30P (+0.3 Watts/kg). Vertical jump height calculated from power output increased more in V15P (+8.7 cm, p = 0.04) than 15P (+1.6 cm) and 30P (+0.9 cm). Net protein balance was greater (p = 0.04) in V15P compared to 15W and 30W at four weeks (p < 0.05), but this difference was not observed after eight weeks (p = 0.51). No changes in VAS were identified between groups. Diastolic blood pressure decreased in V15P (p = 0.002) compared to the other groups, and outside of an interaction for creatinine and aspartate aminotransferase (which still remained well within clinical limits), all blood- based markers of safety demonstrated no differences between groups.

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/m(2)) ingested either Hemp Oil Extract [Hemp, 60 mg/d PlusCBD(TM)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.

We examined if resistance training affected muscle NAD+ and NADH concentrations as well as nicotinamide phosphoribosyltransferase (NAMPT) protein levels and sirtuin (SIRT) activity markers in middle-aged, untrained (MA) individuals. MA participants (59±4 years old; n=16) completed 10 weeks of full-body resistance training (2 d/wk). Body composition, knee extensor strength, and vastus lateralis muscle biopsies were obtained prior to training (Pre) and 72 hours following the last training bout (Post). Data from trained college-aged men (22±3 years old, training age: 6±2 years old; n=15) were also obtained for comparative purposes. Muscle NAD+ (+127%, p<0.001), NADH (+99%, p=0.002), global SIRT activity (+13%, p=0.036), and NAMPT protein (+15%, p=0.014) increased from Pre to Post in MA participants. Additionally, Pre muscle NAD+ and NADH in MA participants were lower than college-aged participants (p<0.05), whereas Post values were similar between cohorts (p>0.10). Interestingly, muscle citrate synthase activity levels (i.e., mitochondrial density) increased in MA participants from Pre to Post (+183%, p<0.001), and this increase was significantly associated with increases in muscle NAD+ (r2=0.592, p=0.001). In summary, muscle NAD+, NADH, and global SIRT activity are positively affected by resistance training in middle-aged, untrained individuals. Whether these adaptations facilitated mitochondrial biogenesis remains to be determined.

Introduction: Purple tea exhibits a unique composition of chemical constituents that may exert favorable outcomes related to recovery from muscle damage, improvements in blood flow, perfusion, and recovery. The purpose of this study was to examine the impact of a brief oral dosing period of purple tea in exercising humans after stressful, damaging exercise.Methods: Using a randomized, placebo-controlled, double-blind, crossover study design, 30 healthy men (33.5 ± 11.4 years, 178.4 ± 7.6 cm, 92.5 ± 13.3 kg) completed an eight day supplementation regimen consisting of either a maltodextrin placebo or 100 mg of purple tea extract (PurpleForceTM, Oryza Oil & Fat, Ltd.) interspersed with a two week washout period. After five and eight days of supplementation, changes in muscle oxygenation, body composition, reactive hyperemia, visual analog responses, exercise performance, and muscle damage markers were assessed. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES).Results: Lactate dehydrogenase was significantly reduced (p = 0.04) in PT in comparison to PLA after eight days of supplementation and exercise performance challenge. In comparison to PT, arm circumference increased in PLA after five days of supplementation (p=0.04) and tended to be greater after eight days (p=0.06). Significantly greater decreases in impedance were observed in PT (p=0.02) while between-group differences in oxygen saturation post-leg extension exercise were greater in PT 30s into recovery (p=0.04) and tended to be greater 60s after recovery (p=0.06). Total bench press repetitions completed were greater in purple tea than PLA (p = 0.001). Total leg extension repetitions completed tended to be different between groups (p=0.09) while the total number of repetitions completed in purple tea increased from day five to day eight (p<0.001) with no change in PLA (p=0.37). No between-group changes were observed in the visual analog scales; however, only the PT condition experienced a significant improvement in Willingness to Exercise (p=0.02).Conclusions: Acute supplementation of PT decreased lactate dehydrogenase, a marker of muscle damage, while also improving lower body muscle endurance performance.

The market for products featuring hemp extracts is large and growing larger. However, safety concerns have been raised by medical and regulatory agencies. Post marketing surveillance of full spectrum hemp extract (FSHE) products manufactured and distributed by CV Sciences (CVSI) and traded under the brand PlusCBD™ was conducted over a 2-year period (2018-2019). The safety of these products was assessed by analyzing adverse events reports. From a total of approximately five million product units sold during the 2-year period, 1,429 (0.03%) adverse events (AE) were reported in 1,151 unique customers. Of those, only two were classified as serious AEs. For orally ingested products, the most common types of AEs reported were gastrointestinal (e.g. abdominal discomfort), while for topically applied products, the most reports mentioned dermatological symptoms (e.g. rashes). There has been no evidence of liver toxicity associated with CVSI products. Based on this longitudinal dataset, the products manufactured using CVSI's proprietary processes are safe and well tolerated at the recommended doses.

Dietary supplement marketers assure the safety of their products by complying with current good manufacturing practices and a host of federal regulations, including those enforced by the Food and Drug Administration (FDA). Post-market surveillance is a key part of identifying safety problems associated with dietary supplement products. FDA requires dietary supplement marketers to provide a domestic address or phone number on product labels for consumers, family members, or health care professionals to report adverse events (AEs) associated with product use and to report all serious adverse events (SAEs) to the agency within 15 business days of receipt. We aimed to evaluate the characteristics of AEs reported with dietary supplement use, including dietary supplement type and Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) that occur with reported SAEs. A total of 41,121 unique adverse event cases reported to two large, U.S.-based dietary supplement marketers in a 2.5-year period (March 1, 2014-August 31, 2016) were assessed for seriousness using established criteria. Each SAE was assigned one or more MedDRA preferred terms and system organ classes (SOC). The types of supplements most responsible for SAEs were assessed. Of the 41,121 AE cases reported, 203 (0.48%) were SAEs. SAEs tended to occur with products marketed for weight loss (69.0%) and glycemic control (19.2%). SAEs occurred most commonly in the cardiovascular, gastrointestinal, and nervous system disorder SOCs. The percentage of SAEs reported to dietary supplement marketers is low, predominantly among consumers of two types of supplements. Further study is needed among a larger cohort of supplement users to determine causal associations between types of supplement products and serious adverse events.

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 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 a proprietary milk protein concentrate (MP) 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 MP versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of MP improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, MP 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 proprietary milk protein concentrate 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.

Background: Very few weight and fat loss supplements undergo finished-product research to examine efficacy. The purpose of this study was to determine the effects of an 8-week diet and exercise program on body composition, hip and waist girth, and adipokines and evaluate whether a dietary supplement containing raspberry ketone, capsaicin, caffeine, garlic, and Citrus aurantium enhanced outcomes. Methods: Overweight men and women completed this randomized, placebo-controlled, double-blind study. Participants consumed 4 capsules/d of supplement (EXP; n = 18) or placebo (PLA; n = 18). Participants underwent 8 weeks of daily supplementation, calorie restriction (500 kcal < RMR [resting metabolic rate] x 1.2), and supervised progressive exercise training 3 times a week. Body composition, girth, and adipokines were assessed at baseline and postintervention (T1 and T2). Results: Significant decreases in weight (-2.6 +/- 0.57 kg, p < 0.001), fat mass (-1.8 +/- 0.20 kg; p < 0.001), and percentage body fat (-3.7% +/- 0.29%, p < 0.001) and a significant increase in lean body mass (LBM; 1.5 +/- 0.26 kg; p < 0.001) were seen from T1 to T2 in both groups. For men, only those in the EXP group increased LBM from T1 to T2 (1.3 +/- 0.38 kg; p < 0.05). Hip girth was also reduced, with the women in the EXP group (-10.7 +/- 2.15 cm, p < 0.001) having a greater reduction. There was a time by group interaction, with significant decreases in leptin (p < 0.001) and significant increases in adiponectin (p < 0.05) in the EXP group. Conclusions: Significant improvements in adipokines and leptin support the utility of exercise, diet, and fat loss for impacting inflammatory biomarkers. The improvement in adiponectin with EXP may suggest a unique health mechanism.

Withania somnifera (Ashwagandha) is an Ayurvedic herb categorized as having “rasayana” (rejuvenator), longevity, and revitalizing properties. Sensoril® is a standardized aqueous extract of the roots and leaves of Withania somnifera. Purpose: To examine the impact of Sensoril® supplementation on strength training adaptations. Methods: Recreationally active men (26.5 ± 6.4 years, 181 ± 6.8 cm, 86.9 ± 12.5 kg, 24.5 ± 6.6% fat) were randomized in a double-blind fashion to placebo (PLA, n = 19) or 500 mg/d Sensoril® (S500, n = 19). Body composition (DEXA), muscular strength, power, and endurance, 7.5 km cycling time trial, and clinical blood chemistries were measured at baseline and after 12 weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and to follow a specific, progressive overload resistance-training program (4-day/week, upper body/lower body split). 2 × 2 mixed factorial ANOVA was used for analysis and statistical significance was set a priori at p ≤ 0.05. Results: Gains in 1-RM squat (S500: +19.1 ± 13.0 kg vs. PLA +10.0 ± 6.2 kg, p = 0.009) and bench press (S500: +12.8 ± 8.2 kg vs. PLA: +8.0 ± 6.0 kg, p = 0.048) were significantly greater in S500. Changes in DEXA-derived android/gynoid ratio (S500: +0.0 ± 0.14 vs. PLA: +0.09 ± 0.1, p = 0.03) also favored S500. No other between-group differences were found for body composition, visual analog scales for recovery and affect, or systemic hemodynamics, however, only the S500 group experienced statistically significant improvements in average squat power, peak bench press power, 7.5 km time trial performance, and perceived recovery scores. Clinical chemistry analysis indicated a slight polycythemia effect in PLA, with no other statistical or clinically relevant changes being noted. Conclusions: A 500 mg dose of an aqueous extract of Ashwagandha improves upper and lower-body strength, supports a favorable distribution of body mass, and was well tolerated clinically in recreationally active men over a 12-week resistance training and supplementation period.

BackgroundMany commercial diet plans are readily available to the weight conscious consumer; however, evidence on their effectiveness for promoting weight loss is often lacking. In three previous short term (one‐ and two‐week) studies examining the effects of Nutrisystem® weight loss plans on changes in body weight and other anthropometric indices, subjects observed an average weight loss of ~5 lb after one week with an aggressive 1000 kcal/d diet (Nutrisystem Fast Five™), and similar weight loss when subjects followed varying combinations of less aggressive Nutrisystem® plans (1200 – 1500 kcal/d) for two weeks. These findings are of interest because previous research has shown that initial weight loss during the first few weeks of treatment is associated with better long‐term weight loss outcomes (Handjieva‐Darlenska, 2010; Fabricatore, 2009; Craighead, 1981; Dubbert, 1984; Finer, 2006; Wadden, 1992; Dhurandhar, 1999; Hansen, 2001; Hollis, 2008).ObjectiveThe primary purpose of this randomized, parallel group study was to determine changes in body weight and body circumferences when generally healthy overweight and obese adults followed the Nutrisystem® program vs. a self‐directed diet (i.e. Dietary Approaches to Stop Hypertension, DASH) for 4 weeks.Methods84 overweight/obese adults (n = 57 women, n = 27 men) with a mean (± standard error of the mean) age of 40.5 ± 12.1 y, body weight of 95.0 ± 17.1 kg (~210 pounds), and body mass index (BMI) of 34.1 ± 4.9 kg/m2 were stratified by age and BMI prior to being randomized into the Nutrisystem® program or DASH program. Targets for daily energy intake for each program were 1200 kcal/day for women and 1500 kcal/day for men, except for the first week of the intervention where all groups consumed 1000 kcal/day. Subjects with BMI > 40 added 200 additional kcal to their diet each day through grocery food options. Subjects were required to maintain their current activities of daily living and were encouraged to engage in three, 10‐minute exercise sessions per day. Changes in body weight and body circumferences (chest, arm, waist, hip, thigh) were examined in a Per Protocol sample (N=75) using repeated measures analysis of covariance. Statistical significance was accepted at p<0.05.ResultsBoth programs resulted in significant reductions in body weight and body circumference parameters. Subjects on the Nutrisystem® program lost approximately twice as much weight during weeks 1–4 than subjects on the DASH diet (all values p<0.0005). Subjects on the Nutrisystem® program lost significantly more total body circumference (i.e. sum of chest, arm, waist, hip, thigh) than subjects on the DASH diet during weeks 2, 3 and 4 (all values p≤0.002). Across all four weeks and both genders combined, subjects on the Nutrisystem® program lost significantly more waist circumference than subjects on the DASH diet (p<0.05). Subjects on the Nutrisystem® program lost significantly more hip and chest circumference than subjects on the DASH diet during weeks 2, 3 and 4 (all values p<0.05).ConclusionsWithin the framework of the current experimental design, the Nutrisystem® program is superior to the self‐directed DASH diet for weight loss and reductions in waist, hip, chest, and total body (i.e. sum of chest, arm, waist, hip, thigh) circumferences over a 4‐week period.Support or Funding InformationThis study was sponsored by Nutrisystem Inc and conducted by an independent contract research organization (The Center for Applied Health Sciences, Stow, OH). Statistical analyses were completed by an independent 3rd party statistician (Omega Statistics, Murrieta, CA). Week 1 Week 2 Week 3 Week 4 Body Weight (lb) NS −5.50 ± 0.4* −7.57 ± 0.5* −9.75 ± 0.6* −11.63 ± 0.7* 95% CI (−6.25, −4.75) (−8.51, −6.62) (−11.00, −8.49) (−13.11, −10.19) DASH −2.73 ± 0.4 −4.38 ± 0.5 −5.37 ± 0.7 −5.94 ± 0.8 95% CI (−3.52, −1.92) (−5.39, −3.37) (−6.71, −4.05) (−7.50, −4.38) Total Body Circumference (inches) NS −3.31 ± 0.6 −5.60 ± 0.6* −6.38 ± 0.6* −8.00 ± 0.7* 95% CI (−4.55, −2.09) (−6.72, −4.49) (−7.67, −5.09) (−9.33, −6.68) DASH −2.05 ± 0.7 −2.61 ± 0.6 −3.26 ± 0.7 −3.75 ± 0.7 95% CI (−3.37, −0.73) (−3.80, −1.41) (−4.64, −1.89) (−5.07, −2.23) Waist (inches) NS −1.10 ± 1.5 −1.59 ± 1.9 −1.82 ± 1.8 −2.40 ± 1.9^ 95% CI (−1.68, −0.53) (−2.18, −1.00) (−2.41, −1.23) (−3.00, −1.80) DASH −0.48 ± 1.5 −0.79 ± 1.2 −1.12 ± 1.8 −1.68 ± 2.0 95% CI (−1.00, 0.03) (−1.24, −0.35) (−1.76, −0.49) (−2.38, −0.99) Values reported are change from baseline ± standard error of the mean. statistically significant difference between groups at corresponding weekly time point. statistically significant main effect over time (i.e. group difference). 95% CI = 95% confidence intervals for change from baseline.

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.