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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 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.

Background: The gut microbiome contributes to numerous physiological processes in humans, and diet and exercise are known to alter both microbial composition and mood. We sought to explore the effect of a 10-week resistance training (RT) regimen with or without peanut protein supplementation (PPS) in untrained young adults on fecal microbiota and mood disturbance (MD). Methods: Participants were randomized into PPS (n = 25) and control (CTL [no supplement]; n = 24) groups and engaged in supervised, full-body RT twice a week. Measures included body composition, fecal microbe relative abundance, alpha- and beta-diversity from 16 s rRNA gene sequencing with QIIME2 processing, dietary intake at baseline and following the 10-week intervention, and post-intervention MD via the profile of mood states (POMS) questionnaire. Independent samples t-tests were used to determine differences between PPS and CTL groups. Paired samples t-tests investigated differences within groups. Results: Our sample was mostly female (69.4%), white (87.8%), normal weight (body mass index 24.6 ± 4.2 kg/m2), and 21 ± 2.0 years old. Shannon index significantly increased from baseline in all participants (p = 0.040), with no between-group differences or pre-post beta-diversity dissimilarities. Changes in Blautia abundance were associated with the positive POMS subscales, Vigor and self-esteem-related-affect (SERA) (rho = −0.451, p = 0.04; rho = −0.487, p = 0.025, respectively). Whole tree phylogeny changes were negatively correlated with SERA and Vigor (rho = −0.475, p = 0.046; rho = −0.582, p = 0.011, respectively) as well as change in bodyfat percentage (rho = −0.608, p = 0.007). Mediation analysis results indicate changes in PD Whole Tree Phylogeny was not a significant mediator of the relationship between change in fat-free mass and total MD. Conclusions: Mood state subscales are associated with changes in microbial taxa and body composition. PD Whole Tree Phylogeny increased following the 10-week RT regimen; further research is warranted to explore how RT-induced changes in microbial diversity are related to changes in body composition and mood disturbance.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p &lt, 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl−-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]−. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.

There is evidence in rodents to suggest that theacrine-based supplements modulate tissue sirtuin activity as well as other biological processes associated with aging. Herein, we examined if a theacrine-based supplement (termed NAD3) altered sirtuin activity in vitro while also affecting markers of mitochondrial biogenesis. The murine C2C12 myoblast cell line was used for experimentation. Following 7 days of differentiation, myotubes were treated with 0.45 mg/mL of NAD3 (containing ~2 mM theacrine) for 3 and 24 h (n = 6 treatment wells per time point). Relative to control (CTL)-treated cells, NAD3 treatments increased (p < 0.05) Sirt1 mRNA levels at 3 h, as well as global sirtuin activity at 3 and 24 h. Follow-up experiments comparing 24 h NAD3 or CTL treatments indicated that NAD3 increased nicotinamide phosphoribosyltransferase (NAMPT) and SIRT1 protein levels (p < 0.05). Cellular nicotinamide adenine dinucleotide (NAD+) levels were also elevated nearly two-fold after 24 h of NAD3 versus CTL treatments (p < 0.001). Markers of mitochondrial biogenesis were minimally affected. Although these data are limited to select biomarkers in vitro, these preliminary findings suggest that a theacrine-based supplement can modulate select biomarkers related to NAD+ biogenesis and sirtuin activity. However, these changes did not drive increases in mitochondrial biogenesis. While promising, these data are limited to a rodent cell line and human muscle biopsy studies are needed to validate and elucidate the significance of these findings.

Vitamin D and calcium supplementation have been posited to improve body composition and different formulations of calcium may impact bioavailability. However, data are lacking regarding the combinatorial effects of exercise, diet, and calcium and/or vitamin D supplementation on body composition changes in post-menopausal women. Herein, 128 post-menopausal women (51.3 &plusmn, 4.5 years, 36.4 &plusmn, 5.7 kg/m2, 46.2 &plusmn, 4.5% fat) were assigned to diet and supplement groups while participating in a supervised circuit-style resistance-training program (3 d/week) over a 14-week period. Diet groups included: (1) normal diet (CTL), (2) a low-calorie, higher protein diet (LCHP, 1600 kcal/day, 15% carbohydrates, 55% protein, 30% fat), and (3) a low-calorie, higher carbohydrate diet (LCHC, 1600 kcal/day, 55% carbohydrates, 15% protein, 30% fat). Supplement groups consisted of: (1) maltodextrin (PLA), (2) 800 mg/day of calcium carbonate (Ca), and (3) 800 mg/day of calcium citrate and malate and 400 IU/day of vitamin D (Ca+D). Fasting blood samples, body composition, resting energy expenditure, aerobic capacity, muscular strength and endurance measures were assessed. Data were analyzed by mixed factorial ANOVA with repeated measures and presented as mean change from baseline [95% CI]. Exercise training promoted significant improvements in strength, peak aerobic capacity, and blood lipids. Dieting resulted in greater losses of body mass (CTL &minus, 0.4 &plusmn, 2.4, LCHC &minus, 5.1 &plusmn, 4.2, LCHP &minus, 3.8 &plusmn, 4.2 kg) and fat mass (CTL &minus, 1.4 &plusmn, 1.8, 3.7 &plusmn, 3.7, 3.4 &plusmn, 3.4 kg). When compared to LCHC-PLA, the LCHC + Ca combination led to greater losses in body mass (PLA &minus, 4.1 [&minus, 6.1, &minus, 2.1], Ca &minus, 6.4 [&minus, 8.1, &minus, 4.7], Ca+D &minus, 4.4 [&minus, 6.4, &minus, 2.5] kg). In comparison to LCHC-Ca, the LCHC-Ca+D led to an improved maintenance of fat-free mass (PLA &minus, 0.3 [&minus, 1.4, 0.7], Ca &minus, 1.4 [&minus, 2.3, &minus, 0.5], Ca+D 0.4 [&minus, 0.6, 1.5] kg) and a greater loss of body fat (PLA &minus, 2.3 [&minus, 3.4, &minus, 1.1], Ca &minus, 1.3 [&minus, 0.3], Ca+D &minus, 3.6 [&minus, 4.8, &minus, 2.5]%). Alternatively, no significant differences in weight loss or body composition resulted when adding Ca or Ca+D to the LCHP regimen in comparison to when PLA was added to the LCHP diet. When combined with an energy-restricted, higher carbohydrate diet, adding 800 mg of Ca carbonate stimulated greater body mass loss compared to when a PLA was added. Alternatively, adding Ca+D to the LCHC diet promoted greater% fat changes and attenuation of fat-free mass loss. Our results expand upon current literature regarding the impact of calcium supplementation with dieting and regular exercise. This data highlights that different forms of calcium in combination with an energy restricted, higher carbohydrate diet may trigger changes in body mass or body composition while no impact of calcium supplementation was observed when participants followed an energy restricted, higher protein diet.

High-intensity interval training (HIIT) involves short bursts of intense activity interspersed by periods of low-intensity exercise or rest. HIIT is a viable alternative to traditional continuous moderate-intensity endurance training to enhance maximal oxygen uptake and endurance performance. Combining nutritional strategies with HIIT may result in more favorable outcomes. The purpose of this narrative review is to highlight key dietary interventions that may augment adaptations to HIIT, including creatine monohydrate, caffeine, nitrate, sodium bicarbonate, beta-alanine, protein, and essential amino acids, as well as manipulating carbohydrate availability. Nutrient timing and potential sex differences are also discussed. Overall, sodium bicarbonate and nitrates show promise for enhancing HIIT adaptations and performance. Beta-alanine has the potential to increase training volume and intensity and improve HIIT adaptations. Caffeine and creatine have potential benefits, however, longer-term studies are lacking. Presently, there is a lack of evidence supporting high protein diets to augment HIIT. Low carbohydrate training enhances the upregulation of mitochondrial enzymes, however, there does not seem to be a performance advantage, and a periodized approach may be warranted. Lastly, potential sex differences suggest the need for future research to examine sex-specific nutritional strategies in response to HIIT.

Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5–7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.

Aerobic exercise and thermal stress instigate robust challenges to the immune system. Various attempts to modify or supplement the diet have been proposed to bolster the immune system responses. The purpose of this study was to identify the impact of yeast beta-glucan (Saccharomyces cerevisiae) supplementation on exercise-induced muscle damage and inflammation. Healthy, active men (29.6 &plusmn, 6.7 years, 178.1 &plusmn, 7.2 cm, 83.2 &plusmn, 11.2 kg, 49.6 &plusmn, 5.1 mL/kg/min, n = 16) and women (30.1 &plusmn, 8.9 years, 165.6 &plusmn, 4.1 cm, 66.7 &plusmn, 10.0 kg, 38.7 &plusmn, 5.8 mL/kg/min, n = 15) were randomly assigned in a double-blind and cross-over fashion to supplement for 13 days with either 250 mg/day of yeast beta-glucan (YBG) or a maltodextrin placebo (PLA). Participants arrived fasted and completed a bout of treadmill exercise at 55% peak aerobic capacity (VO2Peak) in a hot (37.2 &plusmn, 1.8 &deg, C) and humid (45.2 &plusmn, 8.8%) environment. Prior to and 0, 2, and 72 h after completing exercise, changes in white blood cell counts, pro- and anti-inflammatory cytokines, markers of muscle damage, markers of muscle function, soreness, and profile of mood states (POMS) were assessed. In response to exercise and heat, both groups experienced significant increases in white blood cell counts, plasma creatine kinase and myoglobin, and soreness along with reductions in peak torque and total work with no between-group differences. Concentrations of serum pro-inflammatory cytokines in YBG were lower than PLA for macrophage inflammatory protein 1&beta, (MIP-1&beta, ) (p = 0.044) and tended to be lower for interleukin 8 (IL-8) (p = 0.079), monocyte chemoattractment protein 1 (MCP-1) (p = 0.095), and tumor necrosis factor &alpha, (TNF-&alpha, ) (p = 0.085). Paired samples t-tests using delta values between baseline and 72 h post-exercise revealed significant differences between groups for IL-8 (p = 0.044, 95% Confidence Interval (CI): (0.013, 0.938, d = &minus, 0.34), MCP-1 (p = 0.038, 95% CI: 0.087, 2.942, d = &minus, 0.33), and MIP-1&beta, (p = 0.010, 95% CI: 0.13, 0.85, d = &minus, 0.33). POMS outcomes changed across time with anger scores in PLA exhibiting a sharper decline than YBG (p = 0.04). Vigor scores (p = 0.04) in YBG remained stable while scores in PLA were significantly reduced 72 h after exercise. In conclusion, a 13-day prophylactic period of supplementation with 250 mg of yeast-derived beta-glucans invoked favorable changes in cytokine markers of inflammation after completing a prolonged bout of heated treadmill exercise.

The aim of this study was to determine if adults in Central Queensland have accurate self-perceptions of health. Data were collected as part of the 2010 Central Queensland Social Survey (N = 1289). Overweight/obesity is considered a health disorder and was determined using body mass index. Disease states were determined by asking respondents if they have: heart disease, high/low blood pressure, high cholesterol, high triglycerides, thyroid disorder, diabetes, and osteopenia/osteoporosis. Self-perceptions of health were assessed by asking, “Would you say that in general your health is” poor, fair, good, very good, excellent, don’t know, and no response. An accurate health perception occurred if: (1) A respondent with a disease/health disorder reported that their health was poor/fair or (2) A respondent without a disease/health disorder reported that their health was good/very good/excellent. The proportions of people with an accurate health perception by disease/health disorder were compared using a χ2 test. A proportion ratio (PR) with a 95% confidence interval (CI) was calculated for each disease/health disorder. A logistic regression analysis was performed to examine the association between each disease/health disorder and health perception using gender, age, education, physical activity level, and smoking status as covariates. More than 50% of residents with each disease/health disorder reported their health to be good/very good/excellent. Residents with each disease/health disorder were less likely to have an accurate health perception than those without the corresponding disease/health disorder prior to (p < 0.001) and following adjustment of the covariates (p < 0.001). Our results suggest that overweight/obesity and prevalence of disease are not being recognized as unhealthy, which contradicts established definitions of health.

Aging is associated with an increase in fat mass which increases the risk for disease, morbidity and premature mortality. Creatine supplementation in combination with resistance training has been shown to increase lean tissue mass in adults ≥50 years of age; however, the synergetic effects of creatine and resistance training on fat mass in this population are unclear. Creatine metabolism plays an important role in adipose tissue bioenergetics and energy expenditure. Thus, the combination of creatine supplementation and resistance training may decrease fat mass more than resistance training alone. The purpose of this review is two-fold: (1) to perform meta-analyses on studies involving creatine supplementation during resistance training on fat mass in adults ≥50 years of age, and (2) to discuss possible mechanistic actions of creatine on reducing fat mass. Nineteen studies were included in our meta-analysis with 609 participants. Results from the meta-analyses showed that adults ≥50 years of age who supplemented with creatine during resistance training experienced a greater reduction in body fat percentage (0.55%, p = 0.04) compared to those on placebo during resistance training. Despite no statistical difference (p = 0.13), adults supplementing with creatine lost ~0.5 kg more fat mass compared to those on placebo. Interestingly, there are studies which have linked mechanism(s) explaining how creatine may influence fat mass, and these data are also discussed.

We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the other two groups. In conclusion, short- and long-term KD improves select markers of liver oxidative stress compared to SC feeding, although long-term KD feeding may negatively affect skeletal muscle mitochondrial physiology.