Randomized Trial to Assess the Safety and Tolerability of Daily Intake of an Allulose Amino Acid-Based Hydration Beverage in Men and Women.

BACKGROUND: Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance. METHODS: We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects (n = 40; four groups, n = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake. RESULTS: Statistical analyses displayed ten significant main effects (p < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group (p < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level. CONCLUSIONS: Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.

The Effect of Short-Term NAD3® Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 Years.

Objective This study aimed to assess the impact of acute and short-term supplementation with NAD3®, a theacrine-containing supplement, on circulating adult stem cell numbers in a healthy male and female population aged 40-70 years. Methods This was a double-blind, placebo-controlled crossover study with 12 participants randomized to receive either NAD3® or a placebo for seven days. Blood samples were collected after an overnight fast, before and after the seven-day supplementation period, and one and two hours after the final supplement dose. Using flow cytometry, circulating stem cells, including lymphocytoid CD34+ stem cells (CD45dimCD34+), stem cells associated with vascular maintenance and repair (CD45dimCD34+CD309+), CD34+ stem cells linked to a progenitor phenotype (CD45dimCD34+CD309neg), circulating endothelial stem cells (CD45negCD31+CD309+), and mesenchymal stem cells (CD45negCD90+) were quantified. Results Acute NAD3® supplementation did not result in the mobilization of stem cells from the bone marrow. However, seven days of daily NAD3® supplementation resulted in selective changes in circulating stem cell numbers. A significant time*treatment interaction was observed for CD45dimCD34+ cells (p=0.04) and CD45dimCD34+CD309neg cells (p=0.04), indicating a decrease in cell numbers with supplementation. There was also a trend toward an increase in circulating endothelial cells (p=0.08) with seven days of NAD3®supplementation. Conclusion Short-term NAD3® supplementation demonstrated an effect on the quantity of bone marrow-derived stem cells in circulation. The study suggests that this theacrine-containing supplement may play a role in modulating adult stem cell populations, emphasizing the potential impact of NAD3® on regenerative processes. Further research with extended supplementation periods and larger sample sizes is warranted to elucidate the functional consequences of these changes and explore the therapeutic implications for age-related declines in stem cell function.

Safety and efficacy of a probiotic cocktail containing P. acidilactici and L. plantarum for gastrointestinal discomfort in endurance runners: randomized double-blinded crossover clinical trial.

Probiotics are increasingly used to treat conditions associated with gastrointestinal injury and permeability, including exercise-induced gastrointestinal discomfort. This study assessed safety and efficacy of a probiotic in altering the intestinal milieu and mitigating gastrointestinal symptoms (GIS) in endurance runners. In a double blind, crossover study, 16 runners were randomized to 4 weeks of daily supplementation with a probiotic cocktail containing Pediococcus acidilactici bacteria and Lactobacillus plantarum or placebo. Fasting blood and stool samples were collected for measurement of gut permeability markers, immune parameters, and microbiome analyses. Treadmill run tests were performed before and after treatment; participants ran at 65%-70% of VO2max at 27 °C for a maximum of 90 min or until fatigue/GIS developed. A blood sample was collected after the treadmill run test. In healthy individuals, 4 weeks of probiotic supplementation did not alter health parameters, although a marginal reduction in aspartate aminotransferase levels was observed with probiotic treatment only (p = 0.05). GIS, gut permeability-associated parameters (intestinal fatty acid binding protein, lipopolysaccharide binding protein, zonulin, and cytokines), and intestinal microbial content were not altered by the probiotic supplementation. Post-run measurements of GIS and gut-associated parameters did not differ between groups; however, the observed lack of differences is confounded by an absence of measurable functional outcome as GIS was not sufficiently induced during the run. Under the current study conditions, the probiotic was safe to use, and did not affect gut- or immune-associated parameters, or intestinal symptoms in a healthy population. The probiotic might reduce tissue damage, but more studies are warranted.

The dietary supplement Cyplexinol® alleviates joint pain in men and women.

Background and Aim: Joint pain afflicts millions of adults worldwide. The effect of a bone morphogenetic protein complex on joint pain is assessed in this study. Methods: We compared the impact of a dietary supplement protein complex (Cyplexinol®) and placebo in 18 men and women (aged 43 ± 10 years) with self-reported joint pain. Subjects were randomly assigned to each condition, consumed twice daily for 14 days (900 mg/day). Subjects completed questionnaires (e.g., Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective pain using a visual analog scale [VAS]) at the start and end of each treatment phase. Blood samples were analyzed for bone morphogenic protein (BMP), alkaline phosphatase, and cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-10, IL-1ß, and TGF-ß). Blood was also collected on days 1 and 15 to determine the acute impact of treatment on these measures. Results: Pain and discomfort scores improved (P ≤ 0.05) for subjects following use of Cyplexinol® but not placebo. Improvements were noted for WOMAC pain (P = 0.05), stiffness (P = 0.039), and total pain (P = 0.026), as well as VAS pain (P = 0.015), recreational activity interference (P = 0.023), mood interference (P = 0.012), and total pain (P = 0.024). A trend was noted for WOMAC physical function (P = 0.052). An approximate 50% increase in BMP5 was noted following Cyplexinol® (P = 0.01), with a similar increase noted for placebo (P = 0.022). A near doubling in TGF-ß (P = 0.001) was noted for Cyplexinol®. No other changes of significance were noted across time, nor were any differences noted in cytokines following acute intake of the conditions (P > 0.05). Conclusions: Cyplexinol® can alleviate joint pain in middle-aged men and women, while elevating BMP5 and TGF-ß. Cyplexinol® does not influence cytokines, at least within a short 2-week supplementation period or within the 2-h post-ingestion period. Relevance for Patients: Individuals suffering with joint pain in the knee and/or hip may benefit from daily use of Cyplexinol®, as we observed decreased pain and stiffness following treatment.

Fasting Protocols Do Not Improve Intestinal Architecture and Immune Parameters in C57BL/6 Male Mice Fed a High Fat Diet.

BACKGROUND: The intestinal ecosystem, including epithelium, immune cells, and microbiota, are influenced by diet and timing of food consumption. The purpose of this study was to evaluate various dietary protocols after ad libitum high fat diet (HFD) consumption on intestinal morphology and mucosal immunity. METHODS: C57BL/6 male mice were fed a 45% high fat diet (HFD) for 6 weeks and then randomized to the following protocols; (1) chow, (2) a purified high fiber diet known as the Daniel Fast (DF), HFD consumed (3) ad libitum or in a restricted manner; (4) caloric-restricted, (5) time-restricted (six hours of fasting in each 24 h), or (6) alternate-day fasting (24 h fasting every other day). Intestinal morphology and gut-associated immune parameters were investigated after 2 months on respective protocols. RESULTS: Consuming a HFD resulted in shortening of the intestine and reduction in villi and crypt size. Fasting, while consuming the HFD, did not restore these parameters to the extent seen with the chow and DF diet. Goblet cell number and regulatory T cells had improved recovery with high fiber diets, not seen with the HFD irrespective of fasting. CONCLUSION: Nutritional content is a critical determinant of intestinal parameters associated with gut health.

Risk Factors for Cardiometabolic Disease in Professional Firefighters.

OBJECTIVE: Firefighters are plagued with cardiometabolic disease (CMD). Obesity, poor cardiorespiratory and muscular fitness, and blood lipids (low-density lipoprotein cholesterol, triglycerides, low high-density lipoprotein cholesterol) are risk factors for CMD. However, markers of oxidative stress, inflammation, and insulin resistance can provide further insight regarding CMD risk. METHODS: This study investigated the relationships between fitness metrics (cardiorespiratory and muscular fitness, percent body fat, waist circumference), blood lipids, blood pressure, and years of experience as a firefighter to blood markers of insulin resistance: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), oxidative stress: advanced oxidation protein products (AOPPs), and inflammation: C-reactive protein. RESULTS: Waist circumference and blood concentrations of triglycerides were significantly related to AOPPs and HOMA-IR. Cardiorespiratory fitness was inversely related to AOPPs, HOMA-IR and C-reactive protein. CONCLUSION: These findings demonstrate the importance of high cardiorespiratory fitness and low waist circumference to reduce markers of CMD.

A Topical Botanical Ointment for Self-Reported Hip and/or Knee Pain: A Randomized Placebo-Controlled Clinical Trial.

Joint pain is a common ailment among adults worldwide. Six men and 14 women (aged 51 ± 10 years) with self-reported joint pain were randomly assigned, using a cross-over design, to a botanical ointment (Yeahhh Baby!®) or placebo, twice daily for 14 days. Subjects completed questionnaires regarding their joint pain and discomfort (eg, WOMAC and subjective pain using a visual analog scale [VAS]) each evening and underwent a washout period of two weeks before crossing into the other condition. Pain and discomfort scores improved for subjects when using Yeahhh Baby!® ointment from day 1 to the average of days 2-15. For certain measures, similar, albeit insignificant, improvements were noted when subjects used the placebo-demonstrating the powerful placebo effect. Specifically, with Yeahhh Baby!® ointment, effects were noted for WOMAC pain (P = .008), WOMAC physical function (P = .024), WOMAC total (P = .019), and VAS mood interference (P = .042). The most pronounced improvement was noted for WOMAC pain (P = .048), with a 25% reduction observed with Yeahhh Baby!®, with a 10% reduction noted for placebo. These findings indicate that, as compared to a placebo, Yeahhh Baby!® ointment may provide relief to individuals suffering from joint pain in their knees and/or hips.

Firefighters With Higher Cardiorespiratory Fitness Demonstrate Lower Markers of Cardiovascular Disease Risk.

OBJECTIVE: High cardiorespiratory fitness (CRF) is associated with reduced markers of oxidative stress and cardiovascular disease (CVD) risk factors; however, this relationship has not been elucidated in firefighters. The purpose of this study was to examine differences in markers of CVD risk between firefighters who have either high or low levels of CRF. METHODS: Forty-six firefighters participated in a maximal graded exercise test and a dual-energy x-ray absorptiometry scan and provided a fasted blood sample. V˙O 2max values were categorized based on American College of Sports Medicine guidelines to establish high- and low-fitness groups. RESULTS: High fitness firefighters demonstrated significantly higher high-density lipoprotein cholesterol and lower markers of CVD risk: cholesterol, triglycerides, low-density lipoprotein cholesterol, insulin, homeostatic model assessment for insulin resistance, C-reactive protein, and advanced oxidation protein products concentrations. CONCLUSION: Firefighters are encouraged to maintain high CRF to reduce risk of CVD.

Impact of AmaTea® Max on physiological measures and gaming performance in active gamers: A placebo-controlled, double-blind, randomized study.

Background and Aim: The activity of "gaming" has increased greatly in popularity in recent years, with many gamers using nutritional supplements to aid mood and gaming performance. We evaluated the impact of AmaTea® Max (referred to as AmaTea® throughout; a patented dietary supplement consisting of a blend of caffeine and polyphenol antioxidants), compared to both caffeine and a placebo, on gaming and cognitive performance in active gamers. Methods: Subjects reported to the lab on three occasions, separated by approximately 1 week. On each day, they had baseline measurements taken and then played the game Fortnite for four 1-h periods. Measures of cognitive performance, gaming performance, heart rate and blood pressure (BP), and blood cortisol were measured before and at selected times following gameplay. Results: Neither caffeine nor AmaTea® impacted gaming or cognitive performance in a statistically significant manner. However, a trend (P=0.075) was noted for the condition effect for kills/match, with values 21% higher for AmaTea® (1.84) compared to placebo (1.51), and 12% higher for AmaTea® compared to caffeine (1.63). Subjective mood was relatively unaffected, although a condition effect was noted for jittery (P=0.05), with values lower for placebo than for caffeine (P=0.02). BP was minimally elevated with both AmaTea® and caffeine, while cortisol followed the normal diurnal variation and was lower for placebo than AmaTea® and caffeine. Conclusion: AmaTea® modestly increased kills/match during gameplay. It is possible that a different gaming stimulus, varied time of gameplay, or different dosage of the supplement may have yielded different results. Relevance for Subjects: Active gamers who seek to use a dietary supplement for purposes of gaming performance may benefit slightly from ingestion of AmaTea® before gameplay while experiencing greater vigor and lower fatigue as compared to placebo.

Early Time-Restricted Feeding Amends Circadian Clock Function and Improves Metabolic Health in Male and Female Nile Grass Rats.

Lengthening the daily eating period contributes to the onset of obesity and metabolic syndrome. Dietary approaches, including energy restriction and time-restricted feeding, are promising methods to combat metabolic disorders. This study explored the effect of early and late time-restricted feeding (TRF) on weight and adiposity, food consumption, glycemic control, clock gene expression, and liver metabolite composition in diurnal Nile grass rats (NGRs). Adult male and female Nile grass rats were randomly assigned to one of three groups: (1) access to a 60% high-fat (HF) diet ad-libitum (HF-AD), (2) time-restricted access to the HF diet for the first 6 h of the 12 h light/active phase (HF-AM) or (3) the second 6 h of the 12 h light/active phase (HF-PM). Animals remained on their respective protocols for six weeks. TRF reduced total energy consumption and weight gain, and early TRF (HF-AM) reduced fasting blood glucose, restored Per1 expression, and reduced liver lipid levels. Although sex-dependent differences were observed for fat storage and lipid composition, TRF improved metabolic parameters in both male and female NGRs. In conclusion, this study demonstrated that early TRF protocol benefits weight management, improves lipid and glycemic control, and restores clock gene expression in NGRs.

Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain.

As a redox-sensitive coenzyme, nicotinamide adenine dinucleotide (NAD+) plays a central role in cellular energy metabolism and homeostasis. Low NAD+ levels are linked to multiple disease states, including age-related diseases, such as metabolic and neurodegenerative diseases. Consequently, restoring/increasing NAD+ levels in vivo has emerged as an important intervention targeting age-related neurodegenerative diseases. One of the widely studied approaches to increase NAD+ levels in vivo is accomplished by using NAD+ precursors, such as nicotinamide mononucleotide (NMN). Oral administration of NMN has been shown to successfully increase NAD+ levels in a variety of tissues; however, it remains unclear whether NMN can cross the blood-brain barrier to increase brain NAD+ levels. This study evaluated the effects of oral NMN administration on NAD+ levels in C57/B6J mice brain tissues. Our results demonstrate that oral gavage of 400 mg/kg NMN successfully increases brain NAD+ levels in mice after 45 min. These findings provide evidence that NMN may be used as an intervention to increase NAD+ levels in the brain.

Working memory and hippocampal expression of BDNF, ARC, and P-STAT3 in rats: effects of diet and exercise.

OBJECTIVES: Mounting evidence suggests diet and exercise influence learning and memory (LM). We compared a high-fat, high-sucrose Western diet (WD) to a plant-based, amylose/amylopectin blend, lower-fat diet known as the Daniel Fast (DF) in rats with and without regular aerobic exercise on a task of spatial working memory (WM). METHODS: Rats were randomly assigned to the WD or DF at 6 weeks of age. Exercised rats (WD-E, DF-E) ran on a treadmill 3 times/week for 30 min while the sedentary rats did not (WD-S, DF-S). Rats adhered to these assignments for 12 weeks, inclusive of ab libitum food intake, after which mild food restriction was implemented to encourage responding during WM testing. For nine months, WM performance was assessed once daily, six days per week, after which hippocampal sections were collected for subsequent analysis of brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeletal protein (ARC), and signal transducer and activator of transcription 3 (P-STAT3, Tyr705). RESULTS: DF-E rats exhibited the best DSA performance. Surprisingly, the WD-S group outperformed the WD-E group, but had significantly lower BDNF and ARC relative to the DF-S group, with a similar trend from the WD-E group. P-STAT3 expression was also significantly elevated in the WD-S group compared to both the DF-S and WD-E groups. DISCUSSION: These results support previous research demonstrating negative effects of the WD on spatial LM, demonstrate the plant-based DF regimen combined with chronic aerobic exercise produces measurable WM and neuroprotective benefits, and suggest the need to carefully design exercise prescriptions to avoid over-stressing individuals making concurrent dietary changes.

Acute Resistance Exercise Reduces Postprandial Lipemia and Oxidative Stress in Resistance-Trained Men.

ABSTRACT: McAllister, MJ, Steadman, KS, Renteria, LI, Case, MJ, Butawan, MB, Bloomer, RJ, and McCurdy, KW. Acute resistance exercise reduces postprandial lipemia and oxidative stress in resistance-trained men. J Strength Cond Res 36(8): 2139-2146, 2022-Acute ingestion of a high-fat meal (HFM) results in significant increases in postprandial triacylglycerols (TAG) and markers of oxidative stress (OS). Combined aerobic and resistance exercise can attenuate postprandial lipemia; however, it is not clear if acute resistance exercise alone can reduce postprandial OS. The purpose of this study was to determine if acute resistance exercise can attenuate postprandial OS and to compare the effects of moderate versus high-intensity resistance exercise in this regard. Nine ( n = 9) moderately resistance-trained individuals completed 3 testing conditions in a randomized order as follows: (a) rest (no exercise), (b) moderate intensity (3 sets of 10 repetitions at 68% 1 repetition maximum [RM]), and (c) high-intensity resistance exercise (4 sets of 6 repetitions at 85% 1RM). Exercises included barbell back squat, bench press, straight leg deadlift, lat pull-down, upright row, and sit-ups. A HFM was ingested 12 hours after each condition. Blood samples were collected immediately before as well as 2 and 4 hours after ingestion and analyzed for TAG, cholesterol (CHOL), insulin, malondialdehyde (MDA), total nitrate/nitrite (NOx), glutathione (GSH), and advanced oxidation protein products (AOPP). When comparing 4 hour area under curve (AUC) data between conditions, AOPP demonstrated a significantly lower AUC after the moderate-intensity condition compared with resting condition. In addition, resistance exercise resulted in significantly higher plasma NOx concentrations as well as lower TAG and CHOL concentrations after HFM ingestion. Resistance exercise also prevented a decline in GSH that was induced by the HFM. These results demonstrate that acute resistance exercise can attenuate postprandial OS.

Astaxanthin Supplementation Increases Glutathione Concentrations but Does Not Impact Fat Oxidation During Exercise in Active Young Men.

This study investigated the effects of 6 mg/day of astaxanthin supplementation on markers of oxidative stress and substrate metabolism during a graded exercise test in active young men. A double-blind, randomized, counterbalanced, cross-over design was used. Fourteen men (age = 23 ± 2 years) supplemented with 6 mg/day of astaxanthin and a placebo for 4 weeks, with a 1 week washout period between treatments. Following each supplementation period, a fasting blood sample was obtained to measure markers of oxidative stress: glutathione, hydrogen peroxide, advanced oxidation protein products, and malondialdehyde. Participants also completed a graded exercise test after each treatment to determine substrate utilization during exercise at increasing levels of intensity. Glutathione was ∼7% higher following astaxanthin compared with placebo (1,233 ± 133 vs. 1,156 ± 185 µM, respectively; p = .02, d = 0.48). Plasma hydrogen peroxide and malondialdehyde were not different between treatments (p > .05). Although not statistically significant (p = .45), advanced oxidation protein products were reduced by ∼28%. During the graded exercise test, mean fat oxidation rates were not different between treatments (p > .05); however, fat oxidation decreased from 50 to 120 W (p < .001) and from 85 to 120 W (p = .004) in both conditions. Astaxanthin supplementation of 6 mg/day for 4 weeks increased whole blood levels of the antioxidant glutathione in active young men but did not affect oxidative stress markers or substrate utilization during exercise. Astaxanthin appears to be an effective agent to increase endogenous antioxidant status.

Effects of Feeding Time on Markers of Muscle Metabolic Flexibility Following Acute Aerobic Exercise in Trained Mice Undergoing Time Restricted Feeding.

Time-restricted feeding (TRF) is becoming a popular way of eating in physically active populations, despite a lack of research on metabolic and performance outcomes as they relate to the timing of food consumption in relation to the time of exercise. The purpose of this study was to determine if the timing of feeding/fasting after exercise training differently affects muscle metabolic flexibility and response to an acute bout of exercise. Male C57BL/6 mice were randomized to one of three groups for 8 weeks. The control had ad libitum access to food before and after exercise training. TRF-immediate had immediate access to food for 6 h following exercise training and the TRF-delayed group had access to food 5-h post exercise for 6 h. The timing of fasting did not impact performance in a run to fatigue despite TRF groups having lower hindlimb muscle mass. TRF-delayed had lower levels of muscle HSL mRNA expression and lower levels of PGC-1α expression but displayed no changes in electron transport chain enzymes. These results suggest that in young populations consuming a healthy diet and exercising, the timing of fasting may not substantially impact metabolic flexibility and running performance.

The Impact of a Dried Fruit and Vegetable Supplement and Fiber Rich Shake on Gut and Health Parameters in Female Healthcare Workers: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial.

Aim: Phytochemicals from fruits and vegetables are known to reduce inflammation and improve overall health. The objective of this study was to determine the effect of a fruit and vegetable concentrate (FVC) and high fiber component on the gut microbiome in an overweight/obese, female population. Methods: The study was a randomized, double blind, placebo-controlled trial with 57 asymptomatic, pre-menopausal, overweight/obese females between 25-50 years of age working in healthcare. Blood and fecal samples were collected before and after two, four and five months of daily supplementation. Metabolic parameters were measured, and the gut microbiome analyzed. Results: No effect was observed with FVC supplementation for blood lipids, glucose and immune parameters. There was an improvement in glucose clearance. The FVC supplement did not result in taxonomic alterations at phyla level, or changes in α or ß diversity, but reduced Bacteroides abundance and increased fecal butyrate. An additional high fiber component improved levels of health associated bacteria. Conclusion: The results suggest that a dried fruit and vegetable supplement, with a high fiber meal replacement can alter the intestinal microbiota and improve glucose clearance, suggesting that this combination of supplements can improve glucose metabolism and possibly reduce the risk of insulin resistance.

Impact of Nuun Electrolyte Tablets on Fluid Balance in Active Men and Women.

BACKGROUND: Maintaining adequate hydration is important for overall health and has major implications for athletes involved in physically demanding tasks. While water is viewed as an effective means to rehydrate, and is inexpensive and readily available, electrolyte beverages appear to be more beneficial, in particular for athletes who routinely lose electrolytes through sweating. Nuun tablets contain a mix of electrolytes and are quickly dissolved in water to create an electrolyte-rich beverage. We determined the impact of Nuun tablets on the fluid balance of healthy, exercise-trained men and women at rest. METHODS: Eight men (25.9 ± 4.5 yrs) and 10 women (28.2 ± 9.4 yrs) ingested either water only or water with Nuun electrolyte tablets, at both a single and double strength concentration, in random order, on three separate occasions separated by approximately one week, in a fasted and euhydrated state. A total of 1 liter of fluid was ingested at each visit over a 30 minute period. Urine was collected from each subject at 0, 1, 2, 3, and 4 hours post-ingestion. Urine mass values were used to calculate fluid balance and the beverage hydration index (BHI; i.e., the volume of urine produced after drinking the Nuun beverages, relative to that of water only-control condition). Heart rate and blood pressure were measured throughout the four-hour period, while body weight was measured at the start and end of the experiment. RESULTS: Neither heart rate nor blood pressure were impacted by beverage consumption. Nuun tablets resulted in a lower urine output compared to water, with fluid balances for both concentrations more favorable compared to water (p < 0.05), beginning at 2 h post-ingestion and continuing at the 3 h and 4 h times. Body weight loss was less with Nuun at the single dose (0.38 kg; p = 0.02) and double dose (0.43 kg; p = 0.08), compared to water (0.57 kg). The BHI was higher for Nuun (single dose in particular) compared to water at both 2 h (p = 0.05) and 4 h (p = 0.02). CONCLUSION: The addition of Nuun electrolyte tablets to water improves the fluid balance and BHI in healthy men and women. Results were similar for both concentrations, suggesting that additional electrolytes are not necessary when in a rested state. Future studies should determine the impact of various concentrations of the Nuun beverage during physical exercise-in particular, exercise in the heat, when sweat loss may be highest.

Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for characterizing caffeine, methylliberine, and theacrine pharmacokinetics in humans.

Coffea liberica possesses stimulant properties without accumulating the methylxanthine caffeine. The basis for this peculiar observation is that methylurates (e.g., theacrine and methylliberine) have replaced caffeine. The stimulant properties of methylurates, alone and in combination with caffeine, have recently been investigated. However, human pharmacokinetics and LC-MS/MS methods for simultaneous measurement of methylxanthines and methylurates are lacking. To address this deficiency, we conducted a pharmacokinetic study in which subjects (n = 12) were orally administered caffeine (150 mg), methylliberine (Dynamine™, 100 mg), and theacrine (TeaCrine®, 50 mg) followed by blood sampling over 24 h. Liquid-liquid extraction of plasma samples containing purine alkaloids and internal standard (13C-Caffeine) were analyzed using a C18 reversed-phase column and gradient elution (acetonitrile and water, both containing 0.1% formic acid). A Waters Xevo TQ-S tandem mass spectrometer (positive mode) was used to detect caffeine, methylliberine, theacrine, and IS transitions of m/z 195.11 â†’ 138.01, 225.12 â†’ 168.02, 225.12 â†’ 167.95, and 198.1 â†’ 140.07, respectively. The method was validated for precision, accuracy, selectivity, and linearity and was successfully applied to characterize the oral pharmacokinetics of caffeine, methylliberine, and theacrine in human plasma. Successful development and application of LC-MS/MS-based methods such as ours for the simultaneous measurement of methylxanthines and methylurates are essential for the characterization of potential pharmacokinetic and pharmacodynamic interactions.

A 28-Day Carbohydrate-Restricted Diet Improves Markers of Cardiovascular Disease in Professional Firefighters.

Waldman, HS, Smith, JW, Lamberth, J, Fountain, BJ, Bloomer, RJ, Butawan, MB, and McAllister, MJ. A 28-day carbohydrate-restricted diet improves markers of cardiovascular disease in professional firefighters. J Strength Cond Res 34(10): 2785-2792, 2020-This study compared the effects of a 4-week, nonketogenic, carbohydrate-restricted (<25% of calories) diet (CRD) on markers of inflammation and oxidative stress in professional firefighters (FF). Subjects (n = 15) reported to the laboratory for 2 sessions (i.e., baseline and post-CRD) where blood was drawn from an antecubital vein after a 10-hour overnight fast. Dependent variables measured at baseline and post-CRD included adiponectin, insulin, human growth hormone, cortisol, C-reactive protein, albumin, lipids, glucose, amylase, creatine kinase, malondialdehyde (MDA), advance oxidation protein products (AOPP), total nitrate + nitrite, and soluble intracellular adhesion molecule-1. Compared with baseline, the CRD resulted in dramatic improvements to subjects' cardiometabolic profiles, including decreases in AOPP (51.3 ± 27.3 vs. 32.9 ± 7.9 ng·ml), MDA (1.6 ± 0.6 vs. 1.1 ± 0.5 µmol·L), and triglycerides (84.4 ± 34.4 vs. 64.2 ± 14.4 mg·dl), respectively. In addition, the CRD increased total cholesterol (151.5 ± 23.0 vs. 167.7 ± 38.2 mg·dl) and high-density lipoprotein cholesterol (46.3 ± 12.7 vs. 50.6 ± 15.5 mg·dl), but no differences were found with low-density lipoprotein cholesterol. Overall, our results show a 4-week CRD can favorably improve some markers of cardiovascular health in male FF.

An Assessment of the Glyconutrient Ambrotose™ on Immunity, Gut Health, and Safety in Men and Women: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial.

BACKGROUND: Certain dietary fibers have been reported to improve gut health and cellular immunity. Ambrotose is a glyconutrient supplement that contains mannose-rich polysaccharides (acemannan), reported to improve immune function. A more nutrient-dense version of this dietary supplement has been developed recently, with added aloe leaf gel powder (acemannan). The purpose of this study was to evaluate the impact of the traditional and newly developed Ambrotose products on immunity, gut health, and psychological well-being in healthy men and women. METHODS: Seventy-five men and women were randomly assigned in double-blind manner to one of five treatments, as follows: Ambrotose Advanced (AA) at 2 or 4 g daily, Ambrotose LIFE (AL) at 2 or 4 g daily, or placebo. Subjects ingested their assigned treatment daily for eight weeks. Resting heart rate, blood pressure, and measures of psychological well-being were analyzed before and after four and eight weeks of supplementation. Blood samples were collected at the same times and analyzed for zonulin, hematology measures, and cytokines-IL-6, IL-10, IL-1ß, and TNF-α (analyzed both with and without stimulation via lipopolysaccharide [LPS]). RESULTS: All Ambrotose treatments were well-tolerated. There were no differences among treatments in heart rate or blood pressure across time. Self-reported well-being scores were generally higher for the Ambrotose treatments but there were no changes of statistical significance across time (p > 0.05). Differences of statistical significance were noted for select biochemical variables, the most notable being a dramatic decrease in monocytes in the Ambrotose groups. No change was noted in the cytokine response to LPS stimulation in all groups, indicating a maintenance of a healthy immune response. Conclusion: Regular supplementation with Ambrotose is safe and can improve subclinical cellular adversity (as evidenced by a decrease in monocytes), without unnecessary activation of an immune response.